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Background The metabolic effect of fructose in sugar-sweetened beverages (SSB) has been linked to de novo lipogenesis and uric acid (UA) production. Objectives This study investigated the biological effects of SSB consumption on serum lipid profiles and retinol-binding protein 4 (RBP4) among Taiwanese adolescents. Methods We evaluated the anthropometric parameters and biochemical outcomes of 200 representative adolescents (98 boys and 102 girls) who were randomly selected from a large-scale cross-sectional study. Data were analyzed using multiple regression models adjusted for covariates. Results Increased SSB consumption was associated with increased waist and hip circumferences, body mass index (BMI) values and serum UA, triglyceride (TG) and RBP4 levels. Adolescents who consumed >500 ml/day of beverages half-to-heavily sweetened with high-fructose corn syrup (HFCS) exhibited TG and RBP4 levels 22.7 mg/dl and 13.92 ng/ml higher than non-drinkers, respectively. HFCS drinkers with hyperuricemia had higher TG levels than HFCS drinkers with normal UA levels (98.6 vs. 81.6 mg/dl). The intake of HFCS-rich SSBs and high value of BMI (?24) interactively reinforced RBP4 levels among overweight/obese adolescents. Circulating RBP4 levels were significantly correlated with weight-related outcomes and TG and UA concentration among HFCS drinkers (r?=?0.253 to 0.404), but not among non-drinkers. Conclusions High-quantity HFCS-rich beverage consumption is associated with higher TG and RBP4 levels. Hyperuricemia is likely to intensify the influence of HFCS-rich SSB intake on elevated TG levels, and in overweight and obese adolescents, high BMI may modify the action of fructose on higher circulating levels of RBP4. PMID:24475021
Chan, Te-Fu; Lin, Wei-Ting; Chen, Yi-Ling; Huang, Hsiao-Ling; Yang, Wei-Zeng; Lee, Chun-Ying; Chen, Meng-Hsueh; Wang, Tsu-Nai; Huang, Meng-Chuan; Chiu, Yu-Wen; Huang, Chun-Chi; Tsai, Sharon; Lin, Chih-Lung; Lee, Chien-Hung
Background The association of genetic polymorphisms of Tanis with triglyceride concentration in human has not been thoroughly examined. We aimed to investigate the relationship between triglyceride concentrations and Tanis genetic polymorphisms. Methods All participants (n=1497) selected from subjects participating in the Cardiovascular Risk Survey (CRS) study were divided into two groups according to ethnicity (Han: n=1059; Uygur: n= 438). Four tagging SNPs (rs12910524, rs1384565, rs2101171, rs4965814) of Tanis gene were genotyped using TaqMan� assays from Applied Biosystems following the manufacturer�s suggestions and analyzed in an ABI 7900HT Fast Real-Time PCR System. Results We found that the SNP rs12910524 was associated with triglyceride levels by analyses of a dominant model (P<0.001), recessive model (P <0.001) and additive model (P < 0.001) not only in Han ethnic but also in Uygur ethnic group, and the difference remained significant after the adjustment of sex, age, alcohol intake, smoking, BMI and plasma glucose (GLU) level (All P < 0.001). However, this relationship was not observed in rs1384565, rs2101171, and rs4965814 before and after multivariate adjustment (All P > 0.05). Furthermore, there were significant interactions between rs12910524 and GLU on TG both in Han (P=0.001) and Uygur population (P=2.60�10-4). Conclusion Our results indicated that the rs12910524 in the Tanis gene was associated with triglyceride concentrations in subjects without diabetes in China. PMID:23829426
CYP2E1-dependent elevation of serum cholesterol, triglycerides, and hepatic bile acids by isoniazid
Isoniazid is the first-line medication in the prevention and treatment of tuberculosis. Isoniazid is known to have a biphasic effect on the inhibition�induction of CYP2E1 and is also considered to be involved in isoniazid-induced hepatotoxicity. However, the full extent and mechanism of involvement of CYP2E1 in isoniazid-induced hepatotoxicity remain to be thoroughly investigated. In the current study, isoniazid was administered to wild-type and Cyp2e1-null mice to investigate the potential toxicity of isoniazid in vivo. The results revealed that isoniazid caused no hepatotoxicity in wild-type and Cyp2e1-null mice, but produced elevated serum cholesterol and triglycerides, and hepatic bile acids in wild-type mice, as well as decreased abundance of free fatty acids in wild-type mice and not in Cyp2e1-null mice. Metabolomic analysis demonstrated that production of isoniazid metabolites was elevated in wild-type mice along with a higher abundance of bile acids, bile acid metabolites, carnitine and carnitine derivatives; these were not observed in Cyp2e1-null mice. In addition, the enzymes responsible for bile acid synthesis were decreased and proteins involved in bile acid transport were significantly increased in wild-type mice. Lastly, treatment of targeted isoniazid metabolites to wild-type mice led to similar changes in cholesterol, triglycerides and free fatty acids. These findings suggest that while CYP2E1 is not involved in isoniazid-induced hepatotoxicity, while an isoniazid metabolite might play a role in isoniazid-induced cholestasis through enhancement of bile acid accumulation and mitochondria ?-oxidation. -- Highlights: ? Isoniazid metabolites were elevated only in wild-type mice. ? Isoniazid caused no hepatotoxicity in wild-type and Cyp2e1-null mice. ? Isoniazid elevated serum cholesterol and triglycerides, and hepatic bile acids. ? Bile acid transporters were significantly decreased in isoniazid-treated mice.
Cheng, Jie; Krausz, Kristopher W. [Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States)] [Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States); Li, Feng; Ma, Xiaochao [Department of Pharmacology, Toxicology and Therapeutics, The University of Kansas Medical Center, 4089 KLSIC, MS 1018, 3901 Rainbow Boulevard, Kansas City, KS 66160 (United States)] [Department of Pharmacology, Toxicology and Therapeutics, The University of Kansas Medical Center, 4089 KLSIC, MS 1018, 3901 Rainbow Boulevard, Kansas City, KS 66160 (United States); Gonzalez, Frank J., E-mail: firstname.lastname@example.com [Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States)
This study determined the role of intramuscular triglyceride (IMTG) and adipose lipolysis in the elevated fat oxidation during exercise caused by a high-fat diet. In four separate trials, six endurance-trained cyclists exercised at 50% peak O2 consumption for 1 h after a two-day control diet (22% fat, CON) or an isocaloric high-fat diet (60% fat, HF) with or without the ingestion of acipimox, an adipose lipolysis inhibitor, before exercise. During exercise, HF elevated fat oxidation by 72% and whole body lipolysis [i.e., the appearance rate of glycerol in plasma (Ra glycerol)] by 79% compared with CON (P < 0.05), and this was associated with a 36% increase (P < 0.05) in preexercise IMTG concentration. Although acipimox lowered plasma free fatty acid (FFA) availability, HF still increased fat oxidation and Ra glycerol to the same magnitude above control as the increase caused by HF without acipimox (i.e., both increased fat oxidation 13-14 micromol.kg(-1).min(-1)). In conclusion, the marked increase in fat oxidation after a HF diet is associated with elevated IMTG concentration and whole body lipolysis and does not require increased adipose tissue lipolysis and plasma FFA concentration during exercise. This suggests that altered substrate storage in skeletal muscle is responsible for increased fat oxidation during exercise after 2 days of an HF diet. PMID:14559721
Zderic, Theodore W; Davidson, Christopher J; Schenk, Simon; Byerley, Lauri O; Coyle, Edward F
Background Schisandrin B (Sch B), a dibenzocyclooctadiene compound, is isolated from schisandrae fructus (SF). This study was conducted to compare the time- and dose-response between Sch B- and SF oil (SFO)-induced changes in hepatic and serum parameters in mice. Methods Institute of Cancer Research (ICR) mice were given a single oral dose of Sch B (0.125�2 g/kg) or SFO (0.3�5 g/kg). Serum alanine aminotransferase (ALT) activity, hepatic malondialdehyde, and triglyceride (TG) levels were measured at increasing time intervals within 6�120 hours postdosing. Results Serum ALT activity was elevated by 60%, with maximum effect (Emax) =45.77 U/L and affinity (KD) =1.25 g/kg at 48�96 hours following Sch B, but not SFO, treatment. Sch B and SFO treatments increased hepatic malondialdehyde level by 70% (Emax =2.30 nmol/mg protein and KD =0.41 g/kg) and 22% (Emax =1.42 nmol/mg protein and KD =2.56 g/kg) at 72 hours postdosing, respectively. Hepatic index was increased by 16%�60% (Emax =11.01, KD =0.68 g/kg) and 8%�32% (Emax =9.88, KD =4.47 g/kg) at 12�120 hours and 24�120 hours after the administration of Sch B and SFO, respectively. Hepatic TG level was increased by 40%�158% and 35%�85%, respectively, at 12�96 hours and 6�48 hours after Sch B and SFO treatment, respectively. The values of Emax and KD for Sch B/SFO-induced increase in hepatic TG were estimated to be 22.94/15.02 ?mol/g and 0.78/3.03 g/kg, respectively. Both Sch B and SFO increased serum TG (up to 427% and 123%, respectively), with the values of Emax =5.50/4.60 mmol/L and KD =0.43/2.84 g/kg, respectively. Conclusion The findings indicated that Sch B/SFO-induced increases in serum/hepatic parameters occurred in a time-dependent manner, with the time of onset being serum TG level < hepatic TG level < hepatic index < serum ALT activity. However, the time of recovery of these parameters to normal values varied as follow: serum TG level < hepatic TG level and liver injury < hepatic index. The Emax and affinity of Sch B on tissue/enzyme/receptor were larger than those of SFO. PMID:25278745
Zhang, Yi; Pan, Si-Yuan; Zhou, Shu-Feng; Wang, Xiao-Yan; Sun, Nan; Zhu, Pei-Li; Chu, Zhu-Sheng; Yu, Zhi-Ling; Ko, Kam-Ming
Elevated intramyocellular triglyceride (IMTG) is strongly associated with insulin resistance, though a cause and effect relationship has not been fully described. Insulin sensitivity and IMTG content are both dynamic and can alter rapidly in response to dietary variation, physical activity and thermoregulatory response. Physically active humans (athletes) display elevated IMTG content, but in contrast to obese persons, are insulin sensitive. This paradox has created confusion surrounding the role of IMTG in the development of insulin resistance. In this review we consider the modern athlete as the physiological archetype of the Late Palaeolithic hunter�gatherer to whom the selection pressures of food availability, predation and fluctuating environmental conditions applied and to whom the genotype of modern man is virtually identical. As food procurement by the hunter�gatherer required physical activity, �thrifty� genes that encouraged immediate energy storage upon refeeding after food deprivation (Neel, 1962) must have been of secondary importance in survival to genes that preserved physical capacity during food deprivation. Similarly genes that enabled survival during cold exposure whilst starved would be of primary importance. In this context, we discuss the advantage afforded by an elevated IMTG content, and how under these conditions, a concomitant muscle resistance to insulin-mediated glucose uptake would also be advantageous. In sedentary modern man, adiposity is high and skeletal muscle appears to respond as if a state of starvation exists. In this situation, elevated plasma lipids serve to accrue lipid and induce insulin resistance in skeletal muscle. Reversal of this physiological state is primarily dependant on adequate contractile activity, however, in modern Western society, physical inactivity combined with abundant food and warmth has rendered IMTG a redundant muscle substrate. PMID:14608009
Stannard, S R; Johnson, N A
3xTgAD mice exhibit altered behavior and elevated A? after chronic mild social stress
Chronic stress may be a risk factor for developing Alzheimer�s disease (AD), but most studies of the effects of stress in models of AD utilize acute adverse stressors of questionable clinical relevance. The goal of this work was to determine how chronic psychosocial stress affects behavioral and pathological outcomes in an animal model of AD, and to elucidate underlying mechanisms. A triple-transgenic mouse model of AD (3xTgAD mice) and nontransgenic control mice were used to test for an affect of chronic mild social stress on blood glucose, plasma glucocorticoids, plasma insulin, anxiety and hippocampal A?, ptau and BDNF levels. Despite the fact that both control and 3xTgAD mice experienced rises in corticosterone during episodes of mild social stress, at the end of the 6 week stress period 3xTgAD mice displayed increased anxiety, elevated levels of A? oligomers and intraneuronal A?, and decreased BDNF levels, whereas control mice did not. Findings suggest 3xTgAD mice are more vulnerable than control mice to chronic psychosocial stress, and that such chronic stress exacerbates A? accumulation and impairs neurotrophic signaling. PMID:21855175
Rothman, Sarah M.; Herdener, Nathan; Camandola, Simonetta; Texel, Sarah J.; Mughal, Mohamed R.; Cong, Wei-Na; Martin, Bronwen; Mattson, Mark P
Male, Sprague-Dawley rats (154{plus minus}1 g) were fed diets containing 2% corn oil (CO) + 14% butterfat (BF), beef tallow (BT), olive oil (OO) or coconut oil (CN) vs a 16% CO control diet for 5 weeks. Changes in plasma TG specific activity (dpm/mg TG) were determined in individual unanesthetized rats after injection of 100 {mu}Ci (2-{sup 3}H)-glycerol via a carotid cannula. Fractional rate constants were obtained using a 2-compartment model and nonlinear regression analysis. Results demonstrated no difference in the fractional rate constants among dietary groups; but, differences in the rates of hepatic TG secretion were noted. Rats fed BT showed a higher rate of hepatic TG secretion than rats fed CO. Rats fed BF, OO or CN showed somewhat higher rates of hepatic TG secretion than CO. VLDL TG, phospholipid, and apolipoprotein B and E levels were higher with saturated fats vs CO. The data suggest that the higher plasma TG levels noted in response to feeding saturated fats vs corn oil can be explained, in part, by an increased flux of hepatic TG secretion.
Lai, H.C.; Yang, H.; Lasekan, J.; Clayton, M.; Ney, D.M. (Univ. of Wisconsin, Madison (United States))
Olanzapine induced a marked elevation in triglyceride and cholesterol levels and in liver transaminase enzymes after 12 weeks of treatment in a patient with schizophrenia. These changes were not seen in an earlier 10-week course of treatment with risperidone, and improved substantially 1 week after the patient stopped olanzapine and began treatment with aripiprazole. The patient did not exhibit weight gain or hyperglycemia with any of the medications. This case and a review of the literature suggest that olanzapine may have unique properties that affect hepatic enzyme pathways, independent of any effects on weight and glucose, that may lead to hyperlipidemia and transaminitis in some patients. PMID:25036587
Pawelczyk, Tomasz; Pawelczyk, Agnieszka; Rabe-Jablonska, Jolanta
Hepatic ABCA1 and VLDL triglyceride production
Elevated plasma triglyceride (TG) and reduced high density lipoprotein (HDL) concentrations are prominent features of metabolic syndrome (MS) and type 2 diabetes (T2D). Individuals with Tangier disease also have elevated plasma TG concentrations and a near absence of HDL, resulting from mutations in ATP binding cassette transporter A1 (ABCA1), which facilitates the efflux of cellular phospholipid and free cholesterol to assemble with apolipoprotein A-I (apoA-I), forming nascent HDL particles. In this review, we summarize studies focused on the regulation of hepatic very low density lipoprotein (VLDL) TG production, with particular attention on recent evidence connecting hepatic ABCA1 expression to VLDL, LDL, and HDL metabolism. Silencing ABCA1 in McArdle rat hepatoma cells results in diminished assembly of large (>10nm) nascent HDL particles, diminished PI3 kinase activation, and increased secretion of large, TG-enriched VLDL1 particles. Hepatocyte-specific ABCA1 knockout (HSKO) mice have a similar plasma lipid phenotype as Tangier disease subjects, with a twofold elevation of plasma VLDL TG, 50% lower LDL, and 80% reduction in HDL concentrations. This lipid phenotype arises from increased hepatic secretion of VLDL1 particles, increased hepatic uptake of plasma LDL by the LDL receptor, elimination of nascent HDL particle assembly by the liver, and hypercatabolism of apoA-I by the kidney. These studies highlight a novel role for hepatic ABCA1 in the metabolism of all three major classes of plasma lipoproteins and provide a metabolic link between elevated TG and reduced HDL levels that are a common feature of Tangier disease, MS, and T2D. PMID:22001232
Liu, Mingxia; Chung, Soonkyu; Shelness, Gregory S.
... such as type 2 diabetes or kidney disease Hypothyroidism Genetic factors When triglycerides are very high (greater ... these conditions, the strategy is to treat the primary cause. When high triglycerides are not caused by ...
Interruption of the enterohepatic circulation of bile acids increases cholesterol catabolism, thereby stimulating hepatic cholesterol synthesis from acetate. We hypothesized that such treatment should lower the hepatic acetate pool which may alter triglyceride and glucose metabolism. We explored this using mice deficient of the ileal sodium-dependent BA transporter (Slc10a2) and ob/ob mice treated with a specific inhibitor of Slc10a2. Plasma TG levels were reduced in Slc10a2-deficient mice, and when challenged with a sucrose-rich diet, they displayed a reduced response in hepatic TG production as observed from the mRNA levels of several key enzymes in fatty acid synthesis. This effect was paralleled by a diminished induction of mature sterol regulatory element-binding protein 1c (Srebp1c). Unexpectedly, the SR-diet induced intestinal fibroblast growth factor (FGF) 15 mRNA and normalized bile acid synthesis in Slc10a2-/- mice. Pharmacologic inhibition of Slc10a2 in diabetic ob/ob mice reduced serum glucose, insulin and TGs, as well as hepatic mRNA levels of Srebp1c and its target genes. These responses are contrary to those reported following treatment of mice with a bile acid binding resin. Moreover, when key metabolic signal transduction pathways in the liver were investigated, those of Mek1/2-Erk1/2 and Akt were blunted after treatment of ob/ob mice with the Slc10a2 inhibitor. It is concluded that abrogation of Slc10a2 reduces hepatic Srebp1c activity and serum TGs, and in the diabetic ob/ob model it also reduces glucose and insulin levels. Hence, targeting of Slc10a2 may be a promising strategy to treat hypertriglyceridemia and diabetes. PMID:22662222
Lund�sen, Thomas; Andersson, Eva-Marie; Snaith, Michael; Lindmark, Helena; Lundberg, Johanna; �stlund-Lindqvist, Ann-Margret; Angelin, Bo; Rudling, Mats
Central Nervous System Neuropeptide Y Signaling Modulates VLDL Triglyceride Secretion
OBJECTIVE Elevated triglyceride (TG) is the major plasma lipid abnormality in obese and diabetic patients and contributes to cardiovascular morbidity in these disorders. We sought to identify novel mechanisms leading to hypertriglyceridemia. Resistance to negative feedback signals from adipose tissue in key central nervous system (CNS) energy homeostatic circuits contributes to the development of obesity. Because triglycerides both represent the largest energy depot in the body and are elevated in both the plasma and adipose in obesity and diabetes, we hypothesized that the same neural circuits that regulate energy balance also regulate the secretion of TGs into plasma. RESEARCH DESIGN AND METHODS In normal fasting rats, the TG secretion rate was estimated by serial blood sampling after intravascular tyloxapol pretreatment. Neuropeptide Y (NPY) signaling in the CNS was modulated by intracerebroventricular injection of NPY, receptor antagonist, and receptor agonist. RESULTS A single intracerebroventricular injection of NPY increased TG secretion by 2.5-fold in the absence of food intake, and this was determined to be VLDL by fast performance liquid chromatography (FPLC). This effect was recapitulated by activating NPY signaling in downstream neurons with an NPY-Y5 receptor agonist. An NPY-Y1 receptor antagonist decreased the elevated TGs in the form of VLDL secretion rate by 50% compared with vehicle. Increased TG secretion was due to increased secretion of VLDL particles, rather than secretion of larger particles, because apolipoprotein B100 was elevated in FPLC fractions corresponding to VLDL. CONCLUSIONS We find that a key neuropeptide system involved in energy homeostasis in the CNS exerts control over VLDL-TG secretion into the bloodstream. PMID:18332095
Stafford, John M.; Yu, Fang; Printz, Richard; Hasty, Alyssa H.; Swift, Larry L.; Niswender, Kevin D.
Triglyceride kinetics, tissue lipoprotein lipase, and liver lipogenesis in septic rats
The mechanism for the development of hypertriglyceridemia during gram-negative sepsis was studied by examining liver production and clearance of very-low-density lipoprotein (VLDL) triglyceride (TG). To assess liver output and peripheral clearance the kinetics of VLDL-TG were determined by a constant iv infusion of (2-3H)glycerol-labeled VLDL. Clearance of VLDL-TG was also evaluated by measuring activities of lipoprotein lipase (LPL) in heart, soleus muscle, and adipose tissue from fasted control, fasted E. coli-treated, fed control, and fed E. coli-treated rats. Lewis inbred rats, 275-300 g, were made septic with 8 x 10(7) live E. coli colonies per 100 g body wt. Twenty-four hours after E. coli injection, serum TG, free fatty acids (FFA), and cholesterol of fasted E. coli-treated rats were elevated by 170, 76, and 16%, respectively. The elevation of serum TG may be attributed to the 67% decrease in clearance rate of VLDL-TG in fasted E. coli-treated rats compared with their fasted controls. The suppressed activities of LPL in adipose tissue, skeletal muscle, and heart were consistent with reduced clearance of TG. Secretion of VLDL-TG declined by 31% in livers of fasted E. coli-treated rats, which was accompanied by a twofold increase in the composition of liver TG. Rates of in vivo TG synthesis in livers of the fasted E. coli-treated rats were twofold higher than in those of fasted control rats. Decreased rate of TG appearance along with the increase in liver synthesis of TG contributed to the elevation of liver lipids in the fasted E. coli-treated rats.
Lanza-Jacoby, S.; Tabares, A. (Jefferson Medical College, Philadelphia, PA (USA))
Genetic determinants of plasma triglycerides
Plasma triglyceride (TG) concentration is reemerging as an important cardiovascular disease risk factor. More complete understanding of the genes and variants that modulate plasma TG should enable development of markers for risk prediction, diagnosis, prognosis, and response to therapies and might help specify new directions for therapeutic interventions. Recent genome-wide association studies (GWAS) have identified both known and novel loci associated with plasma TG concentration. However, genetic variation at these loci explains only ?10% of overall TG variation within the population. As the GWAS approach may be reaching its limit for discovering genetic determinants of TG, alternative genetic strategies, such as rare variant sequencing studies and evaluation of animal models, may provide complementary information to flesh out knowledge of clinically and biologically important pathways in TG metabolism. Herein, we review genes recently implicated in TG metabolism and describe how some of these genes likely modulate plasma TG concentration. We also discuss lessons regarding plasma TG metabolism learned from various genomic and genetic experimental approaches. Treatment of patients with moderate to severe hypertriglyceridemia with existing therapies is often challenging; thus, gene products and pathways found in recent genetic research studies provide hope for development of more effective clinical strategies. PMID:21041806
Johansen, Christopher T.; Kathiresan, Sekar; Hegele, Robert A.
Objective The goal of this study was to compare the effectiveness of fish oil, fenofibrate, gemfibrozil, and atorvastatin on reducing triglyceride (TG) levels among a large cohort of HIV-infected patients in clinical care. Design Retrospective observational cohort study Methods The primary endpoint was absolute change in TG levels measured using the last TG value pre-treatment and the first TG value post-treatment. A pre-post quasi-experimental design was used to estimate the change in TG due to initiating fish oil. Linear regression models examined the comparative effectiveness of treatment with fish oil versus gemfibrozil, fenofibrate, or atorvastatin for TG reduction. Models were adjusted for baseline differences in age, sex, race, CD4+ cell count, diabetes, body mass index, protease inhibitor use, and time between TG measures. Results A total of 493 patients (mean age 46 years; 95% male) were included (46 receiving gemfibrozil, 80 fenofibrate, 291 atorvastatin, 76 fish oil) with a mean baseline TG of 347 mg/dL. New use of fish oil decreased TG (?TG -45 mg/dL 95% Confidence interval (CI):-80 to -11) in the pre-post study. Compared with fish oil (reference), fibrates were more effective (?TG -66; 95% CI:-120 to -12) in reducing TG levels, whereas atorvastatin was not (?TG -39; 95% CI:-86 to 9). Conclusion In HIV-infected patients in routine clinical care, fish oil is less effective than fibrates (but not atorvastatin) at lowering triglyceride values. Fish oil may still represent an attractive alternative for patients with moderately elevated triglycerides particularly among patients who may not want or tolerate fibrates. PMID:23892238
Mu�oz, Monica A; Liu, Wei; Delaney, Joseph AC; Brown, Elizabeth; Mugavero, Michael J; Mathews, W Chris; Napravnik, Sonia; Willig, James H; Eron, Joseph J; Hunt, Peter W; Kahn, James O; Saag, Michael S; Kitahata, Mari M; Crane, Heidi M
Although fasting induces hepatic triglyceride (TG) accumulation in both rodents and humans, little is known about the underlying mechanism. Because parasympathetic nervous system activity tends to attenuate the secretion of very-low-density-lipoprotein-triglyceride (VLDL-TG) and increase TG stores in the liver, and serum cholinesterase activity is elevated in fatty liver disease, the inhibition of the parasympathetic neurotransmitter acetylcholinesterase (AChE) may have some influence on hepatic lipid metabolism. To assess the influence of AChE inhibition on lipid metabolism, the effect of physostigmine, an AChE inhibitor, on fasting-induced increase in liver TG was investigated in mice. In comparison with ad libitum-fed mice, 30�h fasting increased liver TG accumulation accompanied by a downregulation of sterol regulatory element-binding protein 1 (SREBP-1) and liver-fatty acid binding-protein (L-FABP). Physostigmine promoted the 30�h fasting-induced increase in liver TG levels in a dose-dependent manner, accompanied by a significant fall in plasma insulin levels, without a fall in plasma TG. Furthermore, physostigmine significantly attenuated the fasting-induced decrease of both mRNA and protein levels of SREBP-1 and L-FABP, and increased IRS-2 protein levels in the liver. The muscarinic receptor antagonist atropine blocked these effects of physostigmine on liver TG, serum insulin, and hepatic protein levels of SREBP-1 and L-FABP. These results demonstrate that AChE inhibition facilitated fasting-induced TG accumulation with up regulation of the hepatic L-FABP and SREBP-1 in mice, at least in part via the activation of muscarinic acetylcholine receptors. Our studies highlight the crucial role of parasympathetic regulation in fasting-induced TG accumulation, and may be an important source of information on the mechanism of hepatic disorders of lipid metabolism. PMID:25383314
Yokota, Shin-Ichi; Nakamura, Kaai; Ando, Midori; Kamei, Hiroyasu; Hakuno, Fumihiko; Takahashi, Shin-Ichiro; Shibata, Shigenobu
Acute hypoxia induces hypertriglyceridemia by decreasing plasma triglyceride clearance in mice
Obstructive sleep apnea (OSA) induces intermittent hypoxia (IH) during sleep and is associated with elevated triglycerides (TG). We previously demonstrated that mice exposed to chronic IH develop elevated TG. We now hypothesize that a single exposure to acute hypoxia also increases TG due to the stimulation of free fatty acid (FFA) mobilization from white adipose tissue (WAT), resulting in increased hepatic TG synthesis and secretion. Male C57BL6/J mice were exposed to FiO2 = 0.21, 0.17, 0.14, 0.10, or 0.07 for 6 h followed by assessment of plasma and liver TG, glucose, FFA, ketones, glycerol, and catecholamines. Hypoxia dose-dependently increased plasma TG, with levels peaking at FiO2 = 0.07. Hepatic TG levels also increased with hypoxia, peaking at FiO2 = 0.10. Plasma catecholamines also increased inversely with FiO2. Plasma ketones, glycerol, and FFA levels were more variable, with different degrees of hypoxia inducing WAT lipolysis and ketosis. FiO2 = 0.10 exposure stimulated WAT lipolysis but decreased the rate of hepatic TG secretion. This degree of hypoxia rapidly and reversibly delayed TG clearance while decreasing [3H]triolein-labeled Intralipid uptake in brown adipose tissue and WAT. Hypoxia decreased adipose tissue lipoprotein lipase (LPL) activity in brown adipose tissue and WAT. In addition, hypoxia decreased the transcription of LPL, peroxisome proliferator-activated receptor-?, and fatty acid transporter CD36. We conclude that acute hypoxia increases plasma TG due to decreased tissue uptake, not increased hepatic TG secretion. PMID:22621867
Shin, Mi-Kyung; Yao, Qiaoling; Bevans-Fonti, Shannon; Poole, James; Drager, Luciano F.; Polotsky, Vsevolod Y.
Background Single nucleotide polymorphisms in the APOA5-A4-C3-A1 gene complex are associated with elevated plasma triglycerides and elevated vascular risk in healthy populations. In patients with clinically manifest vascular disease, hypertriglyceridemia and metabolic syndrome are frequently present, but the contribution of these single nucleotide polymorphisms to plasma triglycerides, effect modification by obesity and risk of recurrent vascular events is unknown in these patients. Methods Prospective cohort study of 5547 patients with vascular disease. Rs964184 (APOA5-A4-C3-A1 gene complex) was genotyped, and we evaluated the relation with plasma lipid levels, presence of metabolic syndrome and the risk for new vascular events. Results The minor allele of rs964184 was strongly associated with log plasma triglycerides (? 0.12; 95%CI 0.10-0.15, p?=?1.1*10?19), and was also associated with 0.03 mmol/L lower high-density lipoprotein-cholesterol (95%CI 0.01�0.04), and 0.14 mmol/L higher non-high-density lipoprotein-cholesterol (95%CI 0.09�0.20). The minor allele frequency increased from 10.9% in patients with plasma triglycerides <1 mmol/L to 24.6% in patients with plasma triglycerides between 4 and 10 mmol/L. The relation between rs964184 and plasma triglycerides was modified by body mass index in patients with one minor allele (? 0.02; (95%CI ?0.04�0.09) if body mass index <24 kg/m2, ? 0.17 (95%CI 0.12�0.22) if body mass index >27 kg/m2, p for interaction?=?0.02). The prevalence of the metabolic syndrome increased from 52% for patients with two copies of the major allele to 62% for patients with two copies of the minor allele (p?=?0.01). Rs964184 was not related with recurrent vascular events (HR 0.99; 95%CI 0.86�1.13). Conclusion The single nucleotide polymorphism rs964184 (APOA5-A4-C3-A1) is associated with elevated plasma triglycerides concentrations in patients with clinically manifest vascular disease. In carriers of one minor allele, the effect on plasma triglycerides was modified by body mass index. There is no relation between rs964184 and recurrent vascular events in these patients. PMID:24979386
van de Woestijne, Anton P.; van der Graaf, Yolanda; de Bakker, Paul I. W.; Asselbergs, Folkert W.; Spiering, Wilko; Visseren, Frank L. J.
Objective States of insulin resistance, hyperinsulinemia, and hepatic steatosis are associated with increased secretion of triglycerides (TG) and apolipoprotein B (apoB), even though insulin targets apoB for degradation. We used hepatic-specific (h) Pten knockout (ko) mice, with increased hepatic insulin signaling, to determine the relative roles of insulin signaling and hepatic TG in regulating apoB secretion. Results/Methods TG and apoB secretion were elevated in hPten-ko mice. When hepatic TG was reduced by inhibition of DGAT1/DGAT2 or SREBP-1c, both TG and apoB secretion fell without changes in hepatic insulin signaling. Acute reconstitution of hPten reduced hepatic TG content and both TG and apoB secretion fell within 4 days despite decreased hepatic insulin signaling. Acute depletion of hepatic Pten by adenoviral introduction of Cre into Pten Floxed mice caused steatosis within 4 days, and secretion of TG and apoB both increased despite increased hepatic insulin signaling. Even when steatosis after acute Pten depletion was prevented by pre-treatment with SREBP-1c ASO, apoB secretion was not reduced after 4 days. Ex vivo results were in primary hepatocytes were similar. Conclusion Either hepatic TG is the dominant regulator of apoB secretion or any inhibitory effects of hepatic insulin signaling on apoB secretion is very short-lived. PMID:22155452
Moon, Byoung C.; Hernandez-Ono, Antonio; Stiles, Bangyan; Wu, Hong; Ginsberg, Henry N.
Background/Objectives: Individually, genetic variants only moderately influence cardiometabolic (CM) traits, such as lipid and inflammatory markers. In this study we generated genetic risk scores from a combination of previously reported variants influencing CM traits, and used these scores to explore how adiposity levels could mediate genetic contributions to CM traits. Subjects/Methods: Participants included 1649 women from the 2005 Cebu Longitudinal Health and Nutrition Survey. Three genetic risk scores were constructed for C-reactive protein (CRP), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TGs). We used linear regression models to assess the association between each genetic risk score and its related trait. We also tested for interactions between each score and measures of adiposity. Results: Each genetic risk score explained a greater proportion of variance in trait levels than any individual genetic variant. We found an interaction between the TG genetic risk score (2.29�14.34 risk alleles) and waist circumference (WC) (Pinteraction=1.66 � 10?2). Based on model predictions, for individuals with a higher TG genetic risk score (75th percentile=12), having an elevated WC (?80?cm) increased TG levels from 1.32 to 1.71?mmol?l?1. However, for individuals with a lower score (25th percentile=7), having an elevated WC did not significantly change TG levels. Conclusions: The TG genetic risk score interacted with adiposity to synergistically influence TG levels. For individuals with a genetic predisposition to elevated TG levels, our results suggest that reducing adiposity could possibly prevent further increases in TG levels and thereby lessen the likelihood of adverse health outcomes such as cardiovascular disease. PMID:24932782
Zubair, N; Mayer-Davis, E J; Mendez, M A; Mohlke, K L; North, K E; Adair, L S
Impact of body composition on very-low-density lipoprotein-triglycerides kinetics.
Upper body obese (UBO) subjects have greater cardiovascular disease risk than lower body obese (LBO) or lean subjects. Obesity is also associated with hypertriglyceridemia that may involve greater production and impaired removal of very-low-density lipoprotein (VLDL)-triglycerides (TG). In these studies, we assessed the impact of body composition on basal VLDL-TG production, VLDL-TG oxidation, and VLDL-TG storage. VLDL-TG kinetics were assessed in 10 UBO, 10 LBO, and 10 lean women using a bolus injection of [1-(14)C]VLDL-TG. VLDL-TG oxidation was measured by (14)CO(2) production (hyamine trapping) and VLDL-TG adipose tissue storage by fat biopsies. Insulin sensititvity was assessed by the hyperinsulinemic-euglycemic clamp technique and body composition by dual X-ray absorptiometry in combination with computed tomography. Hepatic VLDL-TG production was significantly greater in UBO than in lean women [(mumol/min) UBO: 64.8 (SD 40.0) vs. LBO: 42.5 (SD 25.6) vs. lean: 31.8 (SD 13.3), P = 0.04], whereas VLDL-TG oxidation was similar in the three groups and averaged 20% of resting energy expenditure [(mumol/min) UBO: 38.3 (SD 26.5) vs. LBO: 23.5 (SD 13.5) vs. lean: 21.1 (SD 9.7), P = 0.09]. In UBO women, more VLDL-TG was deposited in upper body subcutaneous fat [VLDL-TG redeposition in abdominal adipose tissue (mumol/min): UBO: 5.0 (SD 2.9) vs. LBO: 4.0 (SD 3.2) vs. lean: 1.3 (SD 1.0), ANOVA P = 0.01]; in LBO women, more VLDL-TG was deposited in femoral fat [VLDL-TG redeposition in femoral adipose tissue (mumol/min): UBO: 5.1 (SD 3.1) vs. LBO: 5.8 (SD 4.3) vs. lean: 2.3 (SD 1.5), ANOVA P = 0.04]. Only a small proportion of VLDL-TG (8-16%) was partitioned into redeposition in either group. We found that elevated VLDL-TG production without concomitant increased clearance via oxidation and adipose tissue redeposition contributes to hypertriglyceridemia in UBO women. PMID:18984851
Gormsen, Lars C; Nellemann, Birgitte; S�rensen, Lars P; Jensen, Michael D; Christiansen, Jens S; Nielsen, S�ren
Direct Antidiabetic Effect of Leptin through Triglyceride Depletion of Tissues
Leptin is currently believed to control body composition largely, if not entirely, via hypothalamic receptors that regulate food intake and thermogenesis. Here we demonstrate direct extraneural effects of leptin to deplete fat content of both adipocytes and nonadipocytes to levels far below those of pairfed controls. In cultured pancreatic islets, leptin lowered triglyceride (TG) content by preventing TG formation from
Michio Shimabukuro; Kazunori Koyama; Guoxun Chen; May-Yun Wang; Falguni Trieu; Young Lee; Christopher B. Newgard; Roger H. Unger
The oxysterol-activated liver X receptor (LXR) provides a link between sterol and fatty acid metabolism; activation of LXR induces transcription of lipogenic genes. This study shows that induction of the lipogenic genes Srebp-1c, Fas, and Acc1 upon administration of the synthetic LXR agonist T0901317 to C57BL/6J mice (10 mg/kg/day, 4 days) is associated with massive hepatic steatosis along the entire liver lobule and a 2.5-fold increase in very low density lipoprotein-triglyceride (VLDL-TG) secretion. The increased VLDL-TG secretion was fully accounted for by formation of larger (129 +/- 9 nm versus 94 +/- 12 nm, a 2.5-fold increase of particle volume) TG-rich particles. Stimulation of VLDL-TG secretion did not lead to elevated plasma TG levels in C57BL/6J mice, indicating efficient particle metabolism and clearance. However, T0901317 treatment did lead to severe hypertriglyceridemia in mouse models of defective TG-rich lipoprotein clearance, i.e. APOE*3-Leiden transgenic mice (3.2-fold increase) and apoE-/- LDLr-/- double knockouts (12-fold increase). Incubation of rat hepatoma McA-RH7777 cells with T0901317 also resulted in intracellular TG accumulation and enhanced TG secretion. We conclude that, in addition to raising high density lipoprotein cholesterol concentrations, pharmacological LXR activation in mice leads to development of hepatic steatosis and secretion of atherogenic, large TG-rich VLDL particles. PMID:12097330
Grefhorst, Aldo; Elzinga, Baukje M; Voshol, Peter J; Pl�sch, Torsten; Kok, Tineke; Bloks, Vincent W; van der Sluijs, Fjodor H; Havekes, Louis M; Romijn, Johannes A; Verkade, Henkjan J; Kuipers, Folkert
CD36 deficiency in mice impairs lipoprotein lipase-mediated triglyceride clearance
CD36 is involved in high-affinity peripheral FFA uptake. CD36-deficient ( cd36 ? \\/ ? ) mice exhibit increased plasma FFA and triglyceride (TG) levels. The aim of the present study was to elucidate the cause of the increased plasma TG levels in cd36 ? \\/ ? mice. cd36 ? \\/ ? mice showed no differences in hepatic VLDL-TG production or
Jeltje R. Goudriaan; Marion A. M. den Boer; Patrick C. N. Rensen; Maria Febbraio; Folkert Kuipers; Johannes A. Romijn; Louis M. Havekes; Peter J. Voshol
Stereospecific analysis of triglycerides
Stereospecific analysis determines how the fatty acids of triglycerides are distributed over the three different positions\\u000a of the glycerol. The special problem is the differentiation of position I-1 and L-3 of glycerol. In the presently known methods,\\u000a triglycerides are first degraded to mixtures of diglycerides, either by the action of a lipase or by degradation with a Grignard\\u000a reagent. The
H. Brockerhoff
Water's Tg-endotherm, sub-Tg peak of glasses and Tg of water
NASA Astrophysics Data System (ADS)
In our studies of Tg of amorphous forms of water, it had been ascertained that the observed endotherm had the characteristics of glass softening and not those of a sub-Tg peak, but an explicit discussion was not provided. To prevent this Tg-endotherm from being mistaken as part of a sub-Tg peak, we use our earlier data to explain why the endotherm corresponds to water's Tg of 136 K, and not to a sub-Tg peak.
Johari, G. P.
Intracellular triglyceride (TG) is an important energy source for skeletal muscle. However, recent evidence suggests that if muscle contains abnormally high TG stores its sensitivity to insulin may be reduced, and this could predispose to type II diabetes. To test this hypothesis, we measured muscle lipid content in 27 women aged 47 to 55 years (mean, 52) and related it
D. I. W. Phillips; S. Caddy; V. Ilic; B. A. Fielding; K. N. Frayn; A. C. Borthwick; R. Taylor
Triglycerides and gallstone formation
Changes in bile acid (BA) metabolism and gallbladder function are critical factors in the pathogenesis of gallstones. Patients with hypertriglyceridemia (HTG) � often overweight and insulin resistant � are at risk for gallstone disease. The question arises whether HTG itself contributes to gallstone formation or whether gallstone disease only associates with this disorder.Triglycerides are formed in response to fluxes of
A. H. M. Smelt
Recent preclinical and clinical evidence suggests that the stearoyl-CoA desaturase-1 (Scd1) enzyme plays a key role in the regulation of triglyceride (TG) biosynthesis and insulin sensitivity, and in vitro studies have found that antipsychotic medications up-regulate Scd1 mRNA expression. To investigate these effects in vivo, rats were treated with risperidone (1.5, 3, and 6mg/kg/d), paliperidone (1.5, 3, and 6mg/kg/d), olanzapine (2.5, 5, and 10mg/kg/d), quetiapine (5, 10, and 20mg/kg/d), haloperidol (1, and 3mg/kg/d) or vehicle through their drinking water for 40days. Effects on liver Scd1 mRNA expression and an index of Scd1 activity (the plasma 18:1/18:0 ratio, 'desaturation index') were determined, as were postprandial plasma triglyceride (TG), glucose, insulin, and polyunsaturated fatty acid (PUFA) levels. All atypical antipsychotics increased the plasma 18:1/18:0 ratio, but not liver Scd1 mRNA expression, at doses found to also increase plasma TG levels. Among all rats (n=122), the plasma 18:1/18:0 ratio accounted for 56% of the variance in TG concentrations. The plasma 18:1/18:0 ratio was also positively associated with erythrocyte and heart membrane phospholipid 18:1n-9 composition. All antipsychotics except risperidone increased glucose levels at specific doses, and none of the antipsychotics significantly altered insulin levels. The plasma 18:1/18:0 ratio accounted for 20% of the variance in glucose levels. Plasma omega-3 and omega-6 PUFA levels were inversely correlated with the plasma 18:1/18:0 ratio and TG and glucose levels. These in vivo data demonstrate that different atypical antipsychotic medications increase the plasma 18:1/18:0 ratio in association with elevations in postprandial TG and glucose levels, and that concomitant elevations in PUFA biosynthesis oppose these effects. PMID:21474290
McNamara, Robert K; Jandacek, Ronald; Rider, Therese; Tso, Patrick; Cole-Strauss, Allyson; Lipton, Jack W
Dependence of plasma alpha-tocopherol flux on very low-density triglyceride clearance in humans.
To evaluate the effect of dietary fat-induced alterations in triglyceride (TG) metabolism on plasma and very low-density lipoprotein (VLDL)-alpha-tocopherol, nine healthy males (mean +/- SEM, age: 36 +/- 3 years, BMI: 24.7 +/- 1.1) consumed a 35%-fat diet (control) for one week followed by a 15% low-fat, high-carbohydrate diet for 5 weeks. After each dietary phase, the subjects ingested an evening meal along with a 50 mg capsule of (2)H(6)-RRR-alpha-tocopheryl acetate; blood samples were drawn over a 24 h period while the subjects remained fasted. Low-fat feeding increased fasting plasma TG concentrations by 53% (116 +/- 27 to 178 +/- 32, mg/dl, p < 0.0001) primarily by reducing VLDL-TG clearance. Total plasma alpha-tocopherol concentrations (labeled + unlabeled) were unchanged (25.8 +/- 2.3 vs. 26.4 +/- 3.0 nmol/ml plasma) and no differences between the diets were observed for plasma (2)H(6)-alpha-tocopherol concentration (4.8 +/- 0.6 nmol/ml, for both diets) or enrichments (18.1 +/- 1.8% average for both diets). However, low-fat feeding significantly increased the amount of alpha-tocopherol in the VLDL fraction (43%, p = 0.04) in concert with elevations in VLDL-apoB and TG. The alpha-tocopherol and TG content of VLDL varied in parallel in individual subjects and fractional replacement rates and clearance of alpha-tocopherol and TG in VLDL were closely correlated. Kinetic parameters were decreased by 32-39% from high-fat to low-fat. These data suggest that vitamin E bioavailability is similar between a 15 and 35% fat diet, with a redistribution of alpha-tocopherol in lipoproteins occurring during low-fat feeding (increased in the VLDL fraction, reduced in the other lipoproteins), and transfer of alpha-tocopherol from VLDL depends upon TG removal from the particle, consistent with previous observations in vitro and in animal studies. PMID:11121723
Parks, E J; Dare, D; Frazier, K B; Hellerstein, M K; Neese, R A; Hughes, E; Traber, M G
Triglycerides: how much credit do they deserve?
In the modern era of statin therapy, major advances have been made in treating coronary heart disease. However, despite intensive treatment with statin therapy, residual cardiovascular risk persists and has been attributed to the persistence of atherogenic dyslipidemia and, in part, elevated triglycerides (TGs). In this review, the authors focus on the mechanism of elevated TGs and provide a discussion of the challenges of measuring TGs as a biomarker, its role in the pathogenesis of atherosclerotic heart disease, and results of several recent studies that have elucidated the relationship between TGs and cardiovascular morbidity and mortality. PMID:22391250
Kohli, Payal; Cannon, Christopher P
Synthesis of triglyceride estolides from lesquerella and castor oils
Triglyceride (TG) estolides were synthesized from the hydroxy moieties of lesquerella and castor oils with oleic acid. Complete\\u000a esterification of the hydroxy oils was possible when a slight excess of oleic acid was employed (1 to 1.5 mole equivalents).\\u000a The estolides could be formed in the absence of catalyst at 175 to 250C under vacuum or a nitrogen atmosphere. The
Terry A. Isbell; Steven C. Cermak
Glucocorticoids play important roles in the regulation of distinct aspects of adipocyte biology. Excess glucocorticoids in adipocytes are associated with metabolic disorders, including central obesity, insulin resistance and dyslipidemia. To understand the mechanisms underlying the glucocorticoid action in adipocytes, we used chromatin immunoprecipitation sequencing to isolate genome-wide glucocorticoid receptor (GR) binding regions (GBRs) in 3T3-L1 adipocytes. Furthermore, gene expression analyses were used to identify genes that were regulated by glucocorticoids. Overall, 274 glucocorticoid-regulated genes contain or locate nearby GBR. We found that many GBRs were located in or nearby genes involved in triglyceride (TG) synthesis (Scd-1, 2, 3, GPAT3, GPAT4, Agpat2, Lpin1), lipolysis (Lipe, Mgll), lipid transport (Cd36, Lrp-1, Vldlr, Slc27a2) and storage (S3-12). Gene expression analysis showed that except for Scd-3, the other 13 genes were induced in mouse inguinal fat upon 4-day glucocorticoid treatment. Reporter gene assays showed that except Agpat2, the other 12 glucocorticoid-regulated genes contain at least one GBR that can mediate hormone response. In agreement with the fact that glucocorticoids activated genes in both TG biosynthetic and lipolytic pathways, we confirmed that 4-day glucocorticoid treatment increased TG synthesis and lipolysis concomitantly in inguinal fat. Notably, we found that 9 of these 12 genes were induced in transgenic mice that have constant elevated plasma glucocorticoid levels. These results suggested that a similar mechanism was used to regulate TG homeostasis during chronic glucocorticoid treatment. In summary, our studies have identified molecular components in a glucocorticoid-controlled gene network involved in the regulation of TG homeostasis in adipocytes. Understanding the regulation of this gene network should provide important insight for future therapeutic developments for metabolic diseases. PMID:21187916
Yu, Chi-Yi; Mayba, Oleg; Lee, Joyce V.; Tran, Joanna; Harris, Charlie; Speed, Terence P.; Wang, Jen-Chywan
Apolipoprotein A5 (APOA5) gene plays a key role in plasma triglyceride (TG) metabolism, and shows the involvement in coronary artery disease (CAD). A set of single nucleotide polymorphisms around the APOA5 gene was identified to be associated with plasma TG levels. It is of biological and clinical importance to discern the genuine genetic determinants. A polymorphism in 3' untranslated region of the APOA5 gene, rs2266788, is deserving of investigation for suggestive clues from the association in multiple independent studies. In this study, rs2266788 was genotyped in 3222 unrelated subjects consisting of 2062 CAD cases and 1160 controls. The statistical analyses indicated that the minor C allele of rs2266788 was significantly associated with elevated plasma TG levels and higher CAD risk. In normal human liver tissues, comparison of global APOA5 mRNA levels among genotypes and allelic expression imbalance analysis showed the decreased gene expression for the C allele. Luciferase assays confirmed a concordant result that transcriptional activity was lowered for the C allele compared with the T allele in four cell lines. Multiple lines of evidence in our study supported that rs2266788 was causally associated with plasma TG levels conferring CAD risk in Han Chinese population owing to a cis-acting effect to the APOA5 gene expression. PMID:25151233
Shou, Weihua; Wang, Ying; Xie, Fang; Wang, Beilan; Yang, Lin; Wu, Hong; Wang, Yi; Wang, Zhimin; Shi, Jinxiu; Huang, Wei
The adipose triglyceride lipase (PNPLA2, also known as ATGL) is a novel triacylglycerol (TG) lipase which specifically removes\\u000a the first fatty acid from the triglyceride molecule generating free fatty acid and diglyceride (DG) in mammalian cells. Here\\u000a we describe the molecular characterization of the porcine ATGL gene. The full-length cDNA sequence contains a 1,461�bp open reading frame encoding a protein
Li He Dai; Yuan Zhu Xiong; Si Wen Jiang; Jun Feng Chen
Causes of the triglyceride-lowering effect of exercise training in rats
NASA Technical Reports Server (NTRS)
Studies conducted with human subjects and laboratory animals have consistently shown a reduction in serum triglyceride (TG) in exercise-trained subjects. The obtained data have suggested that this decrease was due to a reduction in hepatic TG secretion. The present investigation, which was conducted with rats trained to attain a high level of spontaneous running activity, provides support for the earlier results. In addition, insights are obtained regarding the mechanism by which exercise lowers TG levels. Since the liver accounts for the vast majority of endogenous very low density lipoprotein (VLDL)-TG secretion, the fall in TG secretion rate seen in exercise-trained (ET) rats must be due to a reduction in hepatic TG secretion.
Mondon, C. E.; Dolkas, C. B.; Tobey, T.; Reaven, G. M.
Postabsorptive VLDL-TG fatty acid storage in adipose tissue in lean and obese women.
Adipose tissue lipoprotein lipase (LPL) is a necessary enzyme for storage of very-low-density lipoprotein-triglyceride (VLDL-TG), but whether it is a rate-determining step is unknown. To test this hypothesis we included 10 upper-body obese (UBO), 11 lower-body obese (LBO), and 8 lean women. We infused ex vivo-labeled VLDL-(14)C-TG and then performed adipose tissue biopsies to understand the relationship between VLDL-TG storage and LPL activity in femoral and upper-body subcutaneous fat. Both fractional tracer storage and rate of storage of the VLDL-TG tracer were evaluated. VLDL-TG storage was also examined as a function of regional adipose tissue blood flow (ATBF), insulin, VLDL-TG turnover, regional fat mass, fat-free mass (FFM), and fat cell size. LPL activity per adipocyte was significantly greater in obese than lean women but not significantly different per gram lipid. Both VLDL-TG fractional tracer storage per kg lipid and VLDL-TG storage rate per kg lipid were similar in abdominal and femoral fat in all three groups and were not significantly different between groups. Multiple regression analysis identified FFM and femoral fat mass as significant independent predictors of VLDL-TG fractional tracer storage and insulin as a significant predictor of VLDL-TG fatty acid storage rate. LPL activity, ATBF, and VLDL-TG turnover did not predict VLDL-TG storage. We conclude that lower FFM and greater plasma insulin are associated with greater VLDL-TG deposition in abdominal subcutaneous and femoral fat. Greater femoral fat mass signals greater femoral VLDL-TG storage. We suggest that the differences in VLDL-TG storage in abdominal and femoral fat that occur with progressive obesity are regulated through mechanisms other than LPL activity. PMID:19875996
Nellemann, Birgitte; Gormsen, Lars C; Christiansen, Jens S; Jensen, Michael D; Nielsen, S�ren
Triglycerides and Cardiovascular Disease: FAQ
... their physicians, dietitians and nutritionists. 5. Do high-carbohydrate diets increase triglycerides and risk for cardiovascular disease? ... ATP III), suggests that very high intakes of carbohydrates (CHO) (greater than 60 percent of total calories) ...
Alkaline pH stress resulted in triglyceride (TG) accumulation in Chlorella CHLOR1 and was independent of medium nitrogen or carbon levels. Based on morphological observations, alkaline pH inhibited autospore release, thus increasing the time for cell cycle completion. Autospore release has been postulated to coincide with TG utilization within the microalgal cell division cycle. The alkaline pH stress affected lipid accumulation by inhibiting the cell division cycle prior to autospore release and, therefore, prior to TG utilization. Cells inhibited in this manner showed an increase in TG accumulation but a decrease in both membrane lipid classes (glycolipid and polar lipid). Unlike TG fatty acid profiles, membrane lipid fatty acid profiles were not stable during TG accumulation. The membrane profiles became similar to the TG, i.e. less unsaturated than in the membrane lipids of unstressed control cells.
Guckert, J.B.; Cooksey, K.E. (Montana State Univ., Bozeman (USA))
The ability of growth hormone (GH) to stimulate lipolysis and cause insulin resistance in skeletal muscle may be causally linked, but the mechanisms remain obscure. We investigated the impact of GH on the turnover of FFA and VLDL-TG, intramuscular triglyceride content (IMTG), and insulin sensitivity (euglycemic clamp) in nine healthy men in a randomized double-blind placebo-controlled crossover study after 8 days treatment with (A) Placebo+Placebo, (B) GH (2 mg daily)+Placebo, and (C) GH (2 mg daily)+Acipimox (250 mgx3 daily). In the basal state, GH (B) increased FFA levels (P<0.05), palmitate turnover (P<0.05), and lipid oxidation (P=0.05), but VLDL-TG kinetics were unaffected. Administration of acipimox (C) suppressed basal lipolysis but did not influence VLDL-TG kinetics. In the basal state, IMTG content increased after GH (B; P=0.03). Insulin resistance was induced by GH irrespective of concomitant acipimox (P<0.001). The turnover of FFA and VLDL-TG was suppressed by hyperinsulinemia during placebo and GH, whereas coadministration of acipimox induced a rebound increase FFA turnover and VLDL-TG clearance. We conclude that these results show that GH-induced insulin resistance is associated with increased IMTG and unaltered VLDL-TG kinetics; we hypothesize that fat oxidation in muscle tissue is an important primary effect of GH and that circulating FFA rather than VLDL-TG constitute the major source for this process; and the role of IMTG in the development of GH-induced insulin resistance merits future research. PMID:17132823
Krag, Morten B; Gormsen, Lars C; Guo, Zengkui; Christiansen, Jens S; Jensen, Michael D; Nielsen, S�ren; J�rgensen, Jens O L
Important players in triglyceride (TG) metabolism include the liver (production), white adipose tissue (WAT) (storage), heart and skeletal muscle (combustion to generate ATP), and brown adipose tissue (BAT) (combustion toward heat), the collective action of which determine plasma TG levels. Interestingly, recent evidence points to a prominent role of the hypothalamus in TG metabolism through innervating the liver, WAT, and BAT mainly via sympathetic branches of the autonomic nervous system. Here, we review the recent findings in the area of sympathetic control of TG metabolism. Various neuronal populations, such as neuropeptide Y (NPY)-expressing neurons and melanocortin-expressing neurons, as well as peripherally produced hormones (i.e., GLP-1, leptin, and insulin), modulate sympathetic outflow from the hypothalamus toward target organs and thereby influence peripheral TG metabolism. We conclude that sympathetic stimulation in general increases lipolysis in WAT, enhances VLDL-TG production by the liver, and increases the activity of BAT with respect to lipolysis of TG, followed by combustion of fatty acids toward heat. Moreover, the increased knowledge about the involvement of the neuroendocrine system in TG metabolism presented in this review offers new therapeutic options to fight hypertriglyceridemia by specifically modulating sympathetic nervous system outflow toward liver, BAT, or WAT. PMID:24285857
Geerling, Janine J; Boon, Mari�tte R; Kooijman, Sander; Parlevliet, Edwin T; Havekes, Louis M; Romijn, Johannes A; Meurs, Illiana M; Rensen, Patrick C N
Triglycerides-based diesel fuels
Efforts are under way in many countries, including India, to search for suitable alternative diesel fuels that are environment friendly. The need to search for these fuels arises mainly from the standpoint of preserving the global environment and the concern about long-term supplies of conventional hydrocarbon-based diesel fuels. Among the different possible sources, diesel fuels derived from triglycerides (vegetable oils\\/animal
Anjana Srivastava; Ram Prasad
Adipose triglyceride lipase (ATGL, also known as PNPLA2) is an essential molecule for hydrolysis of intracellular triglyceride (TG). Genetic ATGL deficiency is a rare multi-systemic neutral lipid storage disease. Information regarding its clinical profile and pathophysiology, particularly for cardiac involvement, is still very limited. A previous middle-aged ATGL-deficient patient in our institute (Case 1) with severe heart failure required cardiac transplantation (CTx) and exhibited a novel phenotype, "Triglyceride deposit cardiomyovasculopathy (TGCV)". Here, we tried to elucidate molecular mechanism underlying TGCV. The subjects were two cases with TGCV, including our second case who was a 33-year-old male patient (Case 2) with congestive heart failure requiring CTx. Case 2 was homozygous for a point mutation in the 5' splice donor site of intron 5 in the ATGL, which results in at least two types of mRNAs due to splicing defects. The myocardium of both patients (Cases 1 and 2) showed up-regulation of peroxisome proliferated activated receptors (PPARs), key transcription factors for metabolism of long chain fatty acids (LCFAs), which was in contrast to these molecules' lower expression in ATGL-targeted mice. We investigated the intracellular metabolism of LCFAs under human ATGL-deficient conditions using patients' passaged skin fibroblasts as a model. ATGL-deficient cells showed higher uptake and abnormal intracellular transport of LCFA, resulting in massive TG accumulation. We used these findings from cardiac specimens and cell-biological experiments to construct a hypothetical model to clarify the pathophysiology of the human disorder. In patients with TGCV, even when hydrolysis of intracellular TG is defective, the marked up-regulation of PPAR? and related genes may lead to increased uptake of LCFAs, the substrates for TG synthesis. This potentially vicious cycle of LCFAs could explain the massive accumulation of TG and severe clinical course for this rare disease. PMID:24332944
Hirano, Ken-ichi; Tanaka, Tatsuya; Ikeda, Yoshihiko; Yamaguchi, Satoshi; Zaima, Nobuhiro; Kobayashi, Kazuhiro; Suzuki, Akira; Sakata, Yasuhiko; Sakata, Yasushi; Kobayashi, Kunihisa; Toda, Tatsushi; Fukushima, Norihide; Ishibashi-Ueda, Hatsue; Tavian, Daniela; Nagasaka, Hironori; Hui, Shu-Ping; Chiba, Hitoshi; Sawa, Yoshiki; Hori, Masatsugu
Basal and Insulin Mediated VLDL-Triglyceride Kinetics in Type 2 Diabetic Men
OBJECTIVE Increased very-low-density lipoprotein triglycerides (VLDL-TG) concentration is a central feature of diabetic dyslipidemia. The objective was to compare basal and insulin mediated VLDL-TG kinetics, oxidation, and adipose tissue storage in type 2 diabetic and healthy (nondiabetic) men. RESEARCH DESIGN AND METHODS Eleven type 2 diabetic and 11 healthy men, matched for BMI and age, were included. Ex vivo-labeled VLDL-TG tracers, blood and breath samples, fat biopsies, indirect calorimetry, and body composition measures were applied to determine VLDL-TG kinetics, VLDL-TG fatty acids (FA) oxidation, and storage in regional adipose tissue before and during a hyperinsulinemic euglycaemic clamp. RESULTS VLDL-TG secretion was significantly greater in diabetic compared with healthy men (basal: 86.9 [31.0] vs. 61.9 [30.0] ?mol/min, P = 0.03; clamp: 60.0 [26.2] vs. 34.2 [17.9] ?mol � min?1, P = 0.01). The insulin mediated suppression of VLDL-TG secretion was significant in both groups. VLDL-TG clearance was lower in diabetic men (basal: 84.6 [32.7] vs. 115.4 [44.3] ml � min?1, P = 0.08; clamp: 76.3 [30.6] vs. 119.0 [50.2] ml � min?1, P = 0.03). During hyperinsulinemia fractional VLDL-TG FA oxidation was comparable, but in percentage of energy expenditure (EE), significantly higher in diabetic men. Basal VLDL-TG storage was similar, but significantly greater in abdominal compared with leg fat. CONCLUSIONS Increased VLDL-TG in type 2 diabetic men is caused by greater VLDL-TG secretion and less so by lower VLDL-TG clearance. The ability of hyperinsulinemia to suppress VLDL-TG secretion appears preserved. During hyperinsulinemia VLDL-TG FA oxidation is significantly increased in proportion of EE in type 2 diabetic men. Greater basal abdominal VLDL-TG storage may help explain the accumulation of upper-body fat in insulin-resistant individuals. PMID:20858686
S?rensen, Lars P.; Andersen, Iben R.; S?ndergaard, Esben; Gormsen, Lars C.; Schmitz, Ole; Christiansen, Jens S.; Nielsen, S?ren
Current methods for the authentication of cocoa butter (CB) are mainly based on a knowledge of its triglyceride (TG) composition. The performances of capillary GLC and nonaqueous HPLC with an evaporative light-scattering detector (ELSD) for the quantification of TG of CB of different geographical origins were compared. Use of capillary columns coated with a polarizable stationary phase or two reversed-phase HPLC columns coupled in series efficiently separated the major TG species contained in CB. The velocity of the GLC carrier gas influenced the FID response factors of TG standard compounds, which were linearly related to the retention times of the analytes studied. Within a certain mass range the ELSD response of standard TG solutions did not deviate from unity to a greater extent, independent of the molecular structure of the TG species. The quantities of individual TG as obtained by both methods were in close agreement, and the precisions of the methods were also of comparable magnitude, so that either method can be applied to assess the purity of CB. Capillary GLC has the advantage of higher sample throughput due to a shorter run time and because the consumption of chemicals is negligible. PMID:10956116
Buchgraber, M; Ulberth, F; Anklam, E
Studies in mature adults suggest that the plasma concentration ratio of triglyceride (TG)/HDL-cholesterol (HDL-C) provides a simple way to identify apparently healthy individuals who are insulin resistant (IR) and at increased cardiometabolic risk. This study extends these observations by examining the clinical utility of the TG/HDL-C ratio and the metabolic syndrome (MetS) in 2,244 healthy college students (17�24 years old) of Mexican Mestizo ancestry. The TG/HDL-C ratio separating the 25% with the highest value was used to identify IR and increased cardiometabolic risk. Cardiometabolic risk factors were more adverse in men and women whose TG/HDL-C ratios exceeded 3.5 and 2.5, respectively, and approximately one third were identified as being IR. The MetS identified fewer individuals as being IR, but their risk profile was accentuated. In conclusion, both a higher TG/HDL-C ratio and a diagnosis of the MetS identify young IR individuals with an increased cardiometabolic risk profile. The TG/HDL-C ratio identified a somewhat greater number of �high risk� subjects, whereas the MetS found a group whose risk profile was somewhat magnified. These findings suggest that the TG/HDL-C ratio may serve as a simple and clinically useful approach to identify apparently healthy, young individuals who are IR and at increased cardiometabolic risk. PMID:23863983
Murgu�a-Romero, Miguel; Jim�nez-Flores, J. Rafael; Sigrist-Flores, Santiago C.; Espinoza-Camacho, Miguel A.; Jim�nez-Morales, Mayra; Pi�a, Enrique; M�ndez-Cruz, A. Ren�; Villalobos-Molina, Rafael; Reaven, Gerald M.
Mitochondrial cytopathy has been associated with modifications of lipid metabolism in various situations, such as the acquisition of an abnormal adipocyte phenotype ob- served in multiple symmetrical lipomatosis or triglyceride (TG) accumulation in muscles associated with the myoclonic epilepsy with ragged red fibers syndrome. However, the mo- lecular signaling leading to fat metabolism dysregulation in cells with impaired mitochondrial activity
S�bastien Vankoningsloo; Marie Piens; Christophe Lecocq; Audrey Gilson; Aur�lia De Pauw; Patricia Renard; Catherine Demazy; Andr�e Houbion; Martine Raes; Thierry Arnould
Elevated plasma levels of triglyceride-rich lipoproteins, a decreased high-density lipoprotein (HDL) cholesterol concentration, hyperinsulinemia, and impaired fibrinolytic function frequently aggregate in patients with premature coronary heart disease (CHD). Experimetnal studies suggest that the cytokine tumor necrosis factor ? (TNF?) produced by adipocytes plays a part in the regulation of triglyceride and glucose metabolism. The present study examined whether TNF? is
Stefan Jovinge; Anders Hamsten; Per Tornvall; Anthony Proudler; Peter B�venholm; Carl-G�ran Ericsson; Ian Godsland; Ulf de Faire; Jan Nilsson
Our previous results showed that kisspeptin-10 (Kp-10) injections via intraperitoneal (i.p.) once daily for three weeks notably promoted the egg laying rate in quails. In order to investigate the mechanism behind the effects of Kp-10 on enhancing the egg laying rate in birds, this study focused on the alternations of lipids synthesis in liver after Kp-10 injections. 75 female quails (22 d of age) were allocated to three groups randomly, and subjected to 0 (control, Con), 10 nmol (low dosage, L) and 100 nmol (high dosage, H) Kp-10 injections via i.p. once daily for three weeks, respectively. At d 52, quails were sacrificed and sampled for further analyses. Serum E2 concentration was increased by Kp-10 injections, and reached statistical significance in H group. Serum triglyceride (TG) concentrations were increased by 46.7% in L group and 36.8% in H group, respectively, but did not reach statistical significance, and TG contents in liver were significantly elevated by Kp-10 injections in a dose-dependent manner. Serum total cholesterol (Tch) concentrations significantly decreased in H group, while in H group the hepatic Tch content was markedly increased. The level of non-esterified fatty acid (NEFA), apolipoprotein A1 and B (apoA1 and apoB) were not altered by Kp-10 injections. The genes expression of sterol regulatory element binding protein-1 (SREBP-1), fatty acid synthetase (FAS), apolipoprotein VLDL-II (apoVLDL-II), cholesterol 7?-hydroxylase (CYP7A1) and vitellogenin II (VTG-II) were significantly up-regulated by high but not low dosage of Kp-10 injection compared to the control group. However, the expression of SREBP-2, acetyl-CoA carboxylase (ACC?), malic enzyme (ME), stearoyl-CoA (?9) desaturase 1 (SCD1), apolipoprotein A1 (apoA1), fatty acid binding protein 2 (FABP2), 3-hydroxyl-3-methyl glutaryl-coenzyme A reductases (HMGCR), estrogen receptor ?, ? (ER? and ?) mRNA were not affected by Kp-10 treatment. In line with hepatic mRNA abundance, hepatic SREBP1 protein content was significantly higher in H group. Although the mRNA expression was not altered, the content of ER? protein in liver was also significantly increased in H group. However, SREBP-2 protein content in liver was not changed by Kp-10 treatment. In conclusion, exogenous Kp-10 consecutive injections during juvenile stage significantly advanced the tempo of egg laying in quails, which was associated with the significant elevation in hepatic lipids synthesis and transport. PMID:25049888
Wu, J.; Fu, W.; Huang, Y.; Ni, Y.; Zhao, R.
The objective of this experiment was to determine whether there is a dose of slow-release insulin (SRI) that decreases concentrations of plasma nonesterified fatty acids (NEFA) and liver triglyceride (TG) without decreasing plasma glucose concentration, dry matter intake (DMI), and milk yield. Forty-three Holsteins weighing 765 � 70 kg with body condition score of 3.29 � 0.25 (mean � SD)
A. Hayirli; S. J. Bertics; R. R. Grummer
The use of stable isotopes in conjunction with compartmental modeling analysis has greatly facilitated stud- ies of the metabolism of the apolipoprotein B (apoB)-con- taining lipoproteins in humans. The aim of this study was to develop a multicompartment model that allows us to simul- taneously determine the kinetics of apoB and triglyceride (TG) in VLDL 1 and VLDL 2 after
Martin Adiels; Chris Packard; Muriel J. Caslake; Philip Stewart; Aino Soro; Jukka Westerbacka; Bernt Wennberg; Sven-Olof Olofsson; Marja-Riitta Taskinen; Jan Bor�n
Estimation of heat of combustion of triglycerides and fatty acid methyl esters
Equations were developed for the estimation of gross heat of combustion (HG) of triglycerides (TGs) and fatty acid methyl\\u000a esters (FAMEs) from their saponification number (SN) and iodine value (IV). HG of TG=1,896,000\\/SN ? 0.6 IV � 1600 and HG of\\u000a FAME=618,000\\/SN ? 0.08 IV � 430. When these equations were tested on cottonseed oil, soybean oil, partially hydrogenated soybean
Kanit Krisnangkura
Pathophysiology of triglyceride-rich lipoproteins in atherothrombosis: cellular aspects.
Elevated plasma levels of triglyceride-rich lipoproteins (TGRLP), including very low-density lipoproteins (VLDL), chylomicrons, and their remnants, are now acknowledged as risk factors for cardiovascular disease. Interactions of TGRLP with lipoprotein receptors on monocytes, macrophages, and endothelial cells may be mechanistically linked to this risk. Triglyceride-rich lipoproteins from hypertriglyceridemic (HTG) subjects have the abnormal ability to bind to low-denisty lipoprotein receptors via apoE, and plasma chylomicrons from all subjects bind to a new, distinct receptor for apoB48 that is expressed specifically by monocytes, macrophages, and endothelial cells. Receptor binding and uptake of TGRLP by these cells are likely mechanisms involved in the formation of lipid-filled, macrophage-derived "foam cells" of atherosclerotic lesions and for defective fibrinolysis due to endothelial dysfunction. Recognition of the atherothrombogenic potential of TGRLP may lead to improved interventions to lessen or prevent the often fatal sequelae of coronary atherosclerosis and thrombosis associated with elevated plasma triglyceride levels. PMID:10376191
Gianturco, S H; Bradley, W A
Packaged bulk micromachined triglyceride biosensor
NASA Astrophysics Data System (ADS)
Estimation of triglyceride concentration is important for the health and food industries. Use of solid state biosensors like Electrolyte Insulator Semiconductor Capacitors (EISCAP) ensures ease in operation with good accuracy and sensitivity when compared to conventional sensors. In this paper we report on packaging of miniaturized EISCAP sensors on silicon. The packaging involves glass to silicon bonding using adhesive. Since this kind of packaging is done at room temperature, it cannot damage the thin dielectric layers on the silicon wafer unlike the high temperature anodic bonding technique and can be used for sensors with immobilized enzyme without denaturing the enzyme. The packaging also involves a teflon capping arrangement which helps in easy handling of the bio-analyte solutions. The capping solves two problems. Firstly, it helps in the immobilization process where it ensures the enzyme immobilization happens only on one pit and secondly it helps with easy transport of the bio-analyte into the sensor pit for measurements.
Mohanasundaram, S. V.; Mercy, S.; Harikrishna, P. V.; Rani, Kailash; Bhattacharya, Enakshi; Chadha, Anju
Systemic Free Fatty Acid Disposal Into Very Low-Density Lipoprotein Triglycerides
We measured the incorporation of systemic free fatty acids (FFA) into circulating very low-density lipoprotein triglycerides (VLDL-TGs) under postabsorptive, postprandial, and walking conditions in humans. Fifty-five men and 85 premenopausal women with BMI 18�24 (lean) and 27�36 kg/m2 (overweight/obese) received an intravenous bolus injection of [1,1,2,3,3-2H5]glycerol (to measure VLDL-TG kinetics) and either [1-14C]palmitate or [9,10-3H]palmitate to determine the proportion of systemic FFA that is converted to VLDL-TG. Experiments started at 0630 h after a 12-h overnight fast. In the postabsorptive protocol, participants rested and remained fasted until 1330 h. In the postprandial protocol, volunteers ingested frequent portions of a fat-free smoothie. In the walking protocol, participants walked on a treadmill for 5.5 h at ?3� resting energy expenditure. Approximately 7% of circulating FFA was converted into VLDL-TG. VLDL-TG secretion rates (SRs) were not statistically different among protocols. Visceral fat mass was the only independent predictor of VLDL-TG secretion, explaining 33�57% of the variance. The small proportion of systemic FFA that is converted to VLDL-TG can confound the expected relationship between plasma FFA concentration and VLDL-TG SRs. Regulation of VLDL-TG secretion is complex in that, despite a broad spectrum of physiological FFA concentrations, VLDL-TG SRs did not vary based on different acute substrate availability. PMID:23434937
Koutsari, Christina; Mundi, Manpreet S.; Ali, Asem H.; Patterson, Bruce W.; Jensen, Michael D.
Circulating triglycerides (TGs) normally increase after a meal but are altered in pathophysiological conditions, such as obesity. Although TG metabolism in the brain remains poorly understood, several brain structures express enzymes that process TG-enriched particles, including mesolimbic structures. For this reason, and because consumption of high-fat diet alters dopamine signaling, we tested the hypothesis that TG might directly target mesolimbic reward circuits to control reward-seeking behaviors. We found that the delivery of small amounts of TG to the brain through the carotid artery rapidly reduced both spontaneous and amphetamine-induced locomotion, abolished preference for palatable food�and reduced the motivation to engage in food-seeking behavior. Conversely, targeted disruption of the TG-hydrolyzing enzyme lipoprotein lipase specifically in the nucleus accumbens increased palatable food preference and food-seeking behavior. Finally, prolonged TG perfusion resulted in a return to normal palatable food preference despite continued locomotor suppression, suggesting that adaptive mechanisms occur. These findings reveal new mechanisms by which dietary fat may alter mesolimbic circuit function and reward seeking. PMID:24732670
Cansell, C; Castel, J; Denis, R G P; Rouch, C; Delbes, A-S; Martinez, S; Mestivier, D; Finan, B; Maldonado-Aviles, J G; Rijnsburger, M; Tsch�p, M H; DiLeone, R J; Eckel, R H; la Fleur, S E; Magnan, C; Hnasko, T S; Luquet, S
Overexpression of apolipoprotein C-III decreases secretion of dietary triglyceride into lymph
Abstract Apolipoprotein C?III (apoC?III) is not only predominantly synthesized by the liver but also by the small intestine. Because apoC?III is secreted from the intestine on the chylomicron along with lipid absorption, we questioned whether apoC?III might play a role in intestinal lipid absorption and/or transport. Using both wild?type (WT) and apoC?III transgenic (apoC?III Tg) mice, we showed that apoC?III Tg mice have decreased lymphatic lipid transport compared with WT mice in response to an intraduodenal infusion of radiolabeled lipid. This is associated with accumulation of radiolabeled lipids in the luminal compartment of the apoC?III Tg mice, indicating delayed lipid uptake from the lumen. The total amount of radioactive lipids in the mucosal compartment did not differ between apoC?III Tg and WT mice, but the lipid distribution analysis indicated a predominance of free fatty acids and monoacylglycerol in the mucosa of apoC?III Tg mice, implying impaired esterification capacity. Thus, the mechanisms underlying the reduced lymphatic lipid transport in apoC?III Tg mice involve both a delayed lipid uptake into enterocytes, as well as impaired esterification to form triglyceride in the mucosa. These data document a novel role for apoC?III in the uptake, re?esterification, and lymphatic transport of dietary lipids in the intestine. PMID:24760506
Wang, Fei; Kohan, Alison B.; Dong, H. Henry; Yang, Qing; Xu, Min; Huesman, Sarah; Lou, Danwen; Hui, David Y.; Tso, Patrick
Progesterone-specific stimulation of triglyceride biosynthesis in a breast cancer cell line (T-47D)
The purpose of this study was to examine the lactogenic response of human mammary cancer cell lines to hormones in vitro. Progesterone was found to stimulate the incorporation of 14C from (14C)acetate into triglycerides (TG) and to promote accumulation of TG with a fatty acid composition similar to that of human milk fat in T-47D cells. Lipid droplets were observed in larger numbers without concomitant accumulation of casein granules in cells incubated with progesterone, but secretion of lipid into the medium did not occur. An effect of progesterone on TG accumulation was detectable after 12 hr and was maximal at 72 hr. Increasing doses of progesterone (10(-9) to 10(-5) M) caused a progressive increase in TG accumulation. The presence of cortisol and/or prolactin did not alter TG formation nor the dose response of the cells to progesterone. The growth rate of T-47D cells was not altered by the presence of progesterone in the medium. Neither of the human mammary cancer cell lines, MCF-7 and HBL-100, nor the human fibroblast cell lines, 28 and 857, responded to progesterone. The data indicate that, while the normally lactogenic hormones do not stimulate milk product biosynthesis in the cell lines tested, progesterone specifically stimulated synthesis and accumulation of TG in the T-47D cells.
Judge, S.M.; Chatterton, R.T. Jr.
Dog Age and Breeds Associated with High Plasma Cholesterol and Triglyceride Concentrations
ABSTRACT The objectives of this study were to set specific dog breed and sex standards for total cholesterol (T-Cho) and total triglyceride (T-TG) concentrations in dogs and to quantify the associations between dog age and concentrations of both lipids for different breeds. Increased age was associated with higher T-Cho and T-TG concentrations in all five breed groups (P<0.05); T-Cho concentrations increased by 62.5 mg/dl between 9 and 16 years of age, and T-TG concentrations increased by 4.8 mg/dl per year of age (P<0.05). Miniature Schnauzers had the highest T-Cho concentrations of the studied breeds, while Miniature Dachshunds had the lowest concentrations (P<0.05). Veterinarians should consider dog age and breed when they use the lipid concentrations for diagnostic purposes. PMID:24107429
USUI, Shiho; MIZOGUCHI, Yasushi; YASUDA, Hidemi; ARAI, Nobuaki; KOKETSU, Yuzo
Reassessing triglyceride synthesis in adipose tissue
The synthesis and breakdown of triglycerides in adipose tissue and muscle is a crucial element of energy metab- olism because it ensures that adequate fuel is available during starvation. Triglyceride turnover determines the availability of fatty acids for utilization by mammalian tissues, and any dysfunction in this process can lead to alterationsinglucosemetabolism,insulinresistanceand type 2 diabetes. Our understanding of the reactions
Colleen Nye; Jaeyeon Kim; Satish C. Kalhan; Richard W. Hanson
Non-Alcoholic fatty liver disease (NAFLD) is characterized by accumulation of triglycerides (TG) in hepatocytes, which may also trigger cirrhosis. The mechanisms of NAFLD are not fully understood, but insulin resistance has been proposed as a key determinant.AimsTo determine the TG content and long chain fatty acyl CoA composition profile in liver from obese non-diabetic insulin resistant (IR) and lean insulin
Subhash Kamath; Alberto O. Chavez; Amalia Gastaldelli; Francesca Casiraghi; Glenn A. Halff; Gregory A. Abrahamian; Alberto M. Davalli; Raul A. Bastarrachea; Anthony G. Comuzzie; Rodolfo Guardado-Mendoza; Lilia M. Jimenez-Ceja; Vicki Mattern; Ana Maria Paez; Andrea Ricotti; Mary E. Tejero; Paul B. Higgins; Iram Pablo Rodriguez-Sanchez; Devjit Tripathy; Ralph A. DeFronzo; Edward J. Dick; Gary W. Cline; Franco Folli
Background: The ratio of triglycerides (TG, mg\\/dl) to high-density lipoprotein cholesterol (HDL-C, mg\\/dl) is a reliable indicator of insulin resistance and atherosclerotic diseases. The purpose of this study was to examine the association between TG\\/HDL-C and chronic kidney disease (CKD) in a nationally representative sample of Korean adults. Methods: This cross-sectional study included 5,503 subjects (?19 years of age) who
Hee-Taik Kang; Jae-Yong Shim; Yong-Jae Lee; Jung-Eun Lee; John A. Linton; Jong-Koo Kim; Hye-Ree Lee
NASA Astrophysics Data System (ADS)
The basis for the conjecture that water's Tg may be 165�5 K [Velikov, Borick, and Angell, Science 294, 2335 (2001)] has been examined. It is shown that (i) differential scanning calorimetry (DSC) scans provided by Hallbrucker and Mayer [J. Phys. Chem. 91, 503 (1987)], and used as a basis for the conjecture, do not represent the heat capacity of the assumed, slow-cooled glassy water or of hyperquenched glassy water, and (ii) there is no fundamental requirement that the excess heat capacity show a peak at T<Tg�instead the peak may appear at T<Tg, at Tg, or at T>Tg. On heating, the enthalpy of glasses produced by hyperquenching or rapid cooling begins to decrease at a much lower T than that of the glasses obtained by slow cooling. Annealing increases this temperature toward Tg, and the enthalpy decrease continues at T above Tg. In the enthalpy relaxation region, the diffusion coefficient of the hyperquenched glassy state is higher than that of a slow-cooled glassy state at a given T, and a local minimum in the DSC scan does not appear at T<Tg in several glasses. These findings remove the basis for the conjecture that water's Tg may be �165 K. Several analyses confirm that the known sigmoid-shape endotherm of glassy water represents the glass-softening range with onset temperature of 136 K. The DSC scans of a glassy state similar to that of water have been simulated by using a nonlinear, nonexponential enthalpy relaxation formalism. These show that a peak in the difference scan of the simulated glass appears above its Tg of 136 K.
Johari, G. P.
Background Acute reduction in dietary energy intake reduces very low-density lipoprotein triglyceride (VLDL-TG) concentration. Although chronic dietary energy surplus and obesity are associated with hypertriglyceridemia, the effect of acute overfeeding on VLDL-TG metabolism is not known. Objective The aim of the present study was to investigate the effects of acute negative and positive energy balance on VLDL-TG metabolism in healthy women. Design Ten healthy women (age: 22.0�2.9 years, BMI: 21.2�1.3 kg/m2) underwent a stable isotopically labeled tracer infusion study to determine basal VLDL-TG kinetics after performing, in random order, three experimental trials on the previous day: i) isocaloric feeding (control) ii) hypocaloric feeding with a dietary energy restriction of 2.89�0.42 MJ and iii) hypercaloric feeding with a dietary energy surplus of 2.91�0.32 MJ. The three diets had the same macronutrient composition. Results Fasting plasma VLDL-TG concentrations decreased by ?26% after hypocaloric feeding relative to the control trial (P?=?0.037), owing to decreased hepatic VLDL-TG secretion rate (by 21%, P?=?0.023) and increased VLDL-TG plasma clearance rate (by ?12%, P?=?0.016). Hypercaloric feeding increased plasma glucose concentration (P?=?0.042) but had no effect on VLDL-TG concentration and kinetics compared to the control trial. Conclusion Acute dietary energy deficit (?3MJ) leads to hypotriglyceridemia via a combination of decreased hepatic VLDL-TG secretion and increased VLDL-TG clearance. On the other hand, acute dietary energy surplus (?3MJ) does not affect basal VLDL-TG metabolism but disrupts glucose homeostasis in healthy women. PMID:23533676
Bellou, Elena; Maraki, Maria; Magkos, Faidon; Botonaki, Helena; Panagiotakos, Demosthenes B.; Kavouras, Stavros A.; Sidossis, Labros S.
Obesity results in abnormally high levels of triglyceride (TG) storage in tissues such as liver, heart, and muscle, which disrupts their normal functions. Recently, we found that lean mice challenged with high levels of dietary fat store TGs in cytoplasmic lipid droplets in the absorptive cells of the intestine, enterocytes, and that this storage increases and then decreases over time after an acute dietary fat challenge. The goal of this study was to investigate the effects of obesity on intestinal TG metabolism. More specifically we asked whether TG storage in and secretion from the intestine are altered in obesity. We investigated these questions in diet-induced obese (DIO) and leptin-deficient (ob/ob) mice. We found greater levels of TG storage in the intestine of DIO mice compared to lean mice in the fed state, but similar levels of TG storage after a 6-h fast. In addition, we found similar TG storage in the intestine of lean and DIO mice at multiple time points after an acute dietary fat challenge. Surprisingly, we found remarkably lower TG secretion from both DIO and ob/ob mice compared to lean controls in response to an acute dietary fat challenge. Furthermore, we found altered mRNA levels for genes involved in regulation of intestinal TG metabolism in lean and DIO mice at 6?h fasting and in response to an acute dietary fat challenge. More specifically, we found that many of the genes related to TG synthesis, chylomicron synthesis, TG storage, and lipolysis were induced in response to an acute dietary fat challenge in lean mice, but this induction was not observed in DIO mice. In fact, we found a significant decrease in intestinal mRNA levels of genes related to lipolysis and fatty acid oxidation in DIO mice in response to an acute dietary fat challenge. Our findings demonstrate altered TG handling by the small intestine of obese compared to lean mice. PMID:22375122
Uchida, Aki; Whitsitt, Mary C.; Eustaquio, Trisha; Slipchenko, Mikhail N.; Leary, James F.; Cheng, Ji-Xin; Buhman, Kimberly K.
Triglycerides with acrylate functionality were prepared from various oils and model triglycerides. The triglyceride-acrylates were homopolymerized and copolymerized with styrene. The cross-link densities of the resulting polymer networks were predicted utilizing the F...
Quantitative gas-liquid chromatography of triglycerides
To determine optimum operating conditions, an extensive study was made of the variables affecting quantitative recovery and\\u000a resolution of model triglyceride mixtures. Parameters investigated included: flash heater temperature, carrier gas flow rate,\\u000a type of carrier gas, column length, glass and metal columns, temperature program rate, linearity of detector response, physical\\u000a design of gas chromatograph, and molecular species of triglyceride.\\u000a \\u000a Results
Carter Litchfield; R. D. Harlow; Raymond Reiser
Background Non-fasting triglyceride-rich lipoproteins cholesterol (TRL-C) contributes to cardiovascular risk, in that it includes remnant cholesterol (RC). TRL-C is computed as total C - [LDL-C?+?HDL-C]. Such calculation applies only if LDL-C is directly measured, or obtained from a non-Friedewald�s formula, a method as yet never benchmarked against independent markers of TRL burden. Methods The Discriminant Ratio (DR) methodology was used in 120 type 2 diabetic patients in order: (i) to compute TRL-C from non-fasting lipids; (ii) to establish the performance of TRL-C and TRL-C/apoA-I (vs. TG-based markers) to grade TRLs and atherogenic dyslipidemia (AD); and (iii) to relate TRL-C with non-fasting TG. Results Depending on apoB100 availability, TRL-C (mg/dL) can be derived from non-fasting lipids in two ways: (a) total cholesterol (TC) - [(0.0106 * TC - 0.0036 * TG?+?0.017 * apoB100 - 0.27) * 38.6] - HDL-C; and (b) TC - [(0.0106 * TC - 0.0036 * TG?+?0.017 * [0.65 * (TC - HDL-C)?+?6.3] - 0.27) * 38.6] - HDL-C. Discrimination between log[TG] and TRL-C was similar (DR 0.94 and 0.84, respectively), whereas that of log[TG]/HDL-C was better than TRL-C/apoA-I (DR 1.01 vs. 0.65; p 0.0482). All Pearson�s correlations between pairs reached unity, allowing formulation of two unbiased equivalence equations: (a) TRL-C?=?97.8 * log[TG] - 181.9; and (b) TRL-C/apoA-I?=?8.15 * (log[TG]/HDL-C) - 0.18. Conclusions TRL-C and log[TG] are as effective and interchangeable for assessing remnant atherogenic particles. For grading TRL-AD, it is best to use log[TG]/HDL-C, inherently superior to TRL-C/apoA-I, while measuring the same underlying variable. PMID:24612479
Background: Some reports suggest that atorvastatin is more effective than other statins in decreasing serum triglyceride (TG) levels in patients with hypercholesterolemia.Objective: The aim of this study is to compare the hypotriglyceridemic activity of atorvastatin and simvastatin at doses that elicit similar hypocholesterolemic effects.Methods: Outpatients with primary hypercholesterolemia that was not adequately controlled with a stable low-fat, low-cholesterol diet were
Adriana Branchi; Anna Maria Fiorenza; Adriana Torri; Fulvio Muzio; Angelo Rovellini; Cristina Berra; Domenico Sommariva
The main triglycerides (TG) found in the Cornicabra virgin olive oil variety samples analyzed (n=224, from 1995\\/96 to 1999\\/2000 crop seasons) were OOO, SOL+POO, OLO+LnPP and OLA+SOO, as expected from the high oleic acid and low linoleic and linolenic acid contents observed for both the total and sn-2 position fatty acids (FA); these accounted for more than 85% of the
F Aranda; S G�mez-Alonso; R. M Rivera del �lamo; M. D Salvador; G Fregapane
Epidemiologic and clinical trials show that elevated triglycerides and low levels of high-density lipoprotein cholesterol (HDL-C) are independent risk factors for coronary heart disease (CHD). However, adjustment for covariates frequently weakens or abolishes the predictive significance of triglycerides, whereas the evidence for HDL-C is more consistently strong. Data indicate that there is a 2% to 3% decrease in coronary risk
Antonio M. Gotto
We know that upper body obesity is associated with metabolic complications, but we don't know how regional body fat distribution influences postprandial lipemia in obese adults. Thus, this study explored the respective effects of android or gynoid types of obesity and fasting triglyceridemia on postprandial lipid metabolism and especially triglyceride-rich lipoproteins. Twenty-four obese and 6 lean normotriglyceridemic women (control), age 24-57 yr, were enrolled. Among obese women with an android phenotype, 9 exhibited normal plasma triglyceride levels (mean: 1.38 mmol/L) (NTAO), and 7 displayed a frank hypertriglyceridemia (mean: 2.40 mmol/L) (HTAO). The 8 patients with a gynoid phenotype had normal triglyceride levels (mean: 1.00 mmol/L) (GO). All were given a mixed test meal providing 40 g triglycerides. Serum and incremental chylomicron triglycerides 0-7 h areas under the curve (AUCs) as well as triglyceride levels in apoB-48-containing triglyceride-rich lipoprotein (TRLs) or chylomicrons were significantly higher in HTAOs and NTAOs than in GOs and controls postprandially. The size of chylomicron particles was bigger in controls and GOs than in HTAOs and NTAOs postprandially. Android obese subjects showed abnormally elevated fasting apoB-48 and apoB-100 triglyceride-rich lipoprotein (TRL) levels. Most abnormalities that were found correlated to plasma levels of insulin and apoC-III. In conclusion, an abnormal postprandial lipid pattern is a trait of abdominal obesity even without fasting hypertriglyceridemia. PMID:9920081
Mekki, N; Christofilis, M A; Charbonnier, M; Atlan-Gepner, C; Defoort, C; Juhel, C; Borel, P; Portugal, H; Pauli, A M; Vialettes, B; Lairon, D
Pleiotropic regulation of mitochondrial function by adipose triglyceride lipase-mediated lipolysis?
Lipolysis is defined as the catabolism of triacylglycerols (TGs) stored in cellular lipid droplets. Recent discoveries of essential lipolytic enzymes and characterization of numerous regulatory proteins and mechanisms have fundamentally changed our perception of lipolysis and its impact on cellular metabolism. Adipose triglyceride lipase (ATGL) is the rate-limiting enzyme for TG catabolism in most cells and tissues. This review focuses on recent advances in understanding the (patho)physiological impact due to defective lipolysis by ATGL deficiency on mitochondrial (dys)function. Depending on the type of cells and tissues investigated, absence of ATGL has pleiotropic roles in mitochondrial function. PMID:23827855
Kratky, Dagmar; Obrowsky, Sascha; Kolb, Dagmar; Radovic, Branislav
Long-chain fatty acids (FA) supply 70-80% of the energy needs for normal cardiac muscle. To determine the sources of FA that supply the heart, [(14)C]palmitate complexed to bovine serum albumin and [(3)H]triolein [triglyceride (TG)] incorporated into Intralipid were simultaneously injected into fasted male C57BL/6 mice. The ratio of TG to FA uptake was much greater for hearts than livers. Using double-labeled Intralipid with [(3)H]cholesteryl oleoyl ether (CE) and [(14)C]TG, we observed that hearts also internalize intact core lipid. Inhibition of lipoprotein lipase (LPL) with tetrahydrolipstatin or dissociation of LPL from the heart with heparin reduced cardiac uptake of TG by 82 and 64%, respectively (P < 0.01). Palmitate uptake by the heart was not changed by either treatment. Uptake of TG was 88% less in hearts from LPL knockout mice that were rescued via LPL expression in the liver. Our data suggest that the heart is especially effective in removal of circulating TG and core lipids and that this is due to LPL hydrolysis and not its bridging function. PMID:12388125
Augustus, Ayanna S; Kako, Yuko; Yagyu, Hiroaki; Goldberg, Ira J
Tg in Polymer/Oligomer Athermal Blends
NASA Astrophysics Data System (ADS)
The glass transition behavior of poly(?-methyl styrene), its tridecamer, and athermal blends with its hexamer is investigated using differential scanning calorimetry. The blends are prepared to exhibit approximately the same Tg as the tridecamer but with varying molecular weight distributions. The glass transition of the blends is found to become broader than that of the pure materials. However, the absolute heat capacity of the blends maintains unchanged from its components indicating that the blends are athermal mixtures. The broadening of the Tg is evaluated in the context of recent models describing this behavior. In addition, we examine the ability of the TNM model to describe the rate dependence of Tg and aging effects.
Zheng, Wei; Simon, Sindee
Cosmological applications of F (T ,TG) gravity
NASA Astrophysics Data System (ADS)
We investigate the cosmological applications of F (T ,TG) gravity, which is a novel modified gravitational theory based on the torsion invariant T and the teleparallel equivalent of the Gauss-Bonnet term TG. F (T ,TG) gravity differs from both F (T ) theories as well as from F (R ,G ) class of curvature modified gravity, and thus its corresponding cosmology proves to be very interesting. In particular, it provides a unified description of the cosmological history from early-times inflation to late-times self-acceleration, without the inclusion of a cosmological constant. Moreover, the dark energy equation-of-state parameter can be quintessence or phantomlike, or experience the phantom-divide crossing, depending on the parameters of the model.
Kofinas, Georgios; Saridakis, Emmanuel N.
Biogenesis of apolipoprotein A-V and its impact on VLDL triglyceride secretion[S
Apolipoprotein A-V (apoA-V) is a potent regulator of intravascular triglyceride (TG) metabolism, yet its plasma concentration is very low compared with that of other apolipoproteins. To examine the basis for its low plasma concentration, the secretion efficiency of apoA-V was measured in stably transfected McA-RH7777 rat hepatoma cells. Pulse-chase experiments revealed that only ?20% of newly synthesized apoA-V is secreted into culture medium within 3 h postsynthesis and that ?65% undergoes presecretory turnover; similar results were obtained with transfected nonhepatic Chinese hamster ovary cells. ApoA-V secreted by McA-RH7777 cells was not associated with cell surface heparin-competable binding sites. When stably transfected McA-RH7777 cells were treated with oleic acid, the resulting increase in TG synthesis caused a reduction in apoA-V secretion, a reciprocal increase in cell-associated apoA-V, and movement of apoA-V onto cytosolic lipid droplets. In a stably transfected doxycycline-inducible McA-RH7777 cell line, apoA-V expression inhibited TG secretion by ?50%, increased cellular TG, and reduced Z-average VLDL1 particle diameter from 81 to 67 nm; however, no impact on apoB secretion was observed. These data demonstrate that apoA-V inefficiently traffics within the secretory pathway, that its intracellular itinerary can be regulated by changes in cellular TG accumulation, and that apoA-V synthesis can modulate VLDL TG mobilization and secretion. PMID:21115968
Blade, Anna M.; Fabritius, Melissa A.; Hou, Li; Weinberg, Richard B.; Shelness, Gregory S.
Influences of APOA5 Variants on Plasma Triglyceride Levels in Uyghur Population
Objective Single nucleotide polymorphisms (SNPs) in apolipoprotein A5 (APOA5) gene are associated with triglyceride (TG) levels. However, the minor allele frequencies and linkage disequilibriums (LDs) of the SNPs in addition to their effects on TG levels vary greatly between Caucasians and East Asians. The distributions of the SNPs/haplotypes and their associations with TG levels in Uyghur population, an admixture population of Caucasians and East Asians, have not been reported to date. Here, we performed a cross-sectional study to address these. Methods Genotyping of four SNPs in APOA5 (rs662799, rs3135506, rs2075291, and rs2266788) was performed in 1174 unrelated Uyghur subjects. SNP/haplotype and TG association analyses were conducted. Results The frequencies of the SNPs in Uyghurs were in between those in Caucasians and East Asians. The LD between rs662799 and rs2266788 in Uyghurs was stronger than that in East Asians but weaker than that in Caucasians, and the four SNPs resulted in four haplotypes (TGGT, CGGC, TCGT, and CGTT arranged in the order of rs662799, rs3135506, rs2075291, and rs2266788) representing 99.2% of the population. All the four SNPs were significantly associated with TG levels. Compared with non-carriers, carriers of rs662799-C, rs3135506-C, rs2075291-T, and rs2266788-C alleles had 16.0%, 15.1%, 17.1%, and 12.4% higher TG levels, respectively. When haplotype TGGT was defined as the reference, the haplotypes CGGC, TCGT, and CGTT resulted in 16.1%, 19.0%, and 19.8% higher TG levels, respectively. The proportions of variance in TG explained by APOA5 locus were 2.5%, 0.3%, 0.4%, and 1.9% for single SNP rs662799, rs3135506, rs2075291, and rs2266788, respectively, and 3.0% for the haplotypes constructed by them. Conclusions The association profiles between the SNPs and haplotypes at APOA5 locus and TG levels in this admixture population differed from those in Caucasians and East Asians. The functions of these SNPs and haplotypes need to be elucidated comprehensively. PMID:25313938
Wang, Yi; Wu, Di; Jin, Li; Wang, Xiaofeng
We investigated the fat metabolic characteristics in non-obese and diabetic Goto-Kakizaki (GK) rat and the effects of dietary egg white hydrolysate (EWH) on glucose and fat metabolism. Wistar (W) and GK (G) rats were placed into dietary casein (WC and GC) or EWH (WE and GE) group, and fed their respective diet for six weeks. Triglyceride (TG) content and stearoyl-CoA desaturase (SCD) indices in the soleus muscle were higher in the GC group than WC group in parallel with worsening serum glucose metabolic parameters. The glucose metabolic parameters were significantly improved in the GE group. The TG accumulation and SCD indices in the soleus muscle were also significantly lower in the GE group than in the GC group. In conclusion, dietary EWH not only improved glucose metabolism but also reduced both TG accumulation and SCD indices in the soleus muscle of GK rat. PMID:24467567
Ochiai, Masaru; Kuroda, Takashi; Matsuo, Tatsuhiro
Background Both low and high serum phosphate levels may be associated with morbidity and mortality from cardiovascular disease. As smoking increases risk for type 2 diabetes (as shown by dyslipidemia and hyperglycemia), we wanted to study whether smoking and type 2 diabetes were associated with serum phosphate and triglyceride levels independently from other CVD risk factors. Methods Upon admittance to the Vindeln Health Education Centre (VHE-centre) for a four-week comprehensive lifestyle intervention, the participants (1408 women and 1096 men) completed a questionnaire that included their smoking habits � current smoker or non-smoker. We used multiple linear regression analyses to investigate the association between smoking and other CVD risk factors with S-P and S-TG levels. Results In the non-type 2 diabetes populations, the smokers, compared to the non-smokers, had higher S-P and higher serum triglycerides (S-TG). In women, serum-TG in smokers with type 2 diabetes was higher than in smokers with non-type 2 diabetes. Non-type 2 diabetes patients exhibited an inverse relation between S-Glucose (S-Glu) and S-P and a positive association with S-TG. For men only, an association was seen between age (-) and S-Crea (-) and S-P. For women only, an association was seen between BMI (-) and S-Cholesterol (+) (S-Chol) and S-P. Conclusions Compared to non-smokers, smoking women with non-type 2 diabetes and smoking men with type 2 diabetes had a higher level of S-P and S-TG. The association between smoking and S-P and S-TG levels still existed after adjusting for age and CVD risk factors in the multiple linear regression analyses. Trial registration The study has been registered as a sub-study to the Lifestyle Intervention Trial no. ISRCTN79355192. PMID:24636522
Hepatic diseases related to triglyceride metabolism.
Triglycerides participate in key metabolic functions such as energy storage, thermal insulation and as deposit for essential and non-essential fatty acids that can be used as precursors for the synthesis of structural and functional phospholipids. The liver is a central organ in the regulation of triglyceride metabolism, and it participates in triglyceride synthesis, export, uptake and oxidation. The metabolic syndrome and associated diseases are among the main concerns of public health worldwide. One of the metabolic syndrome components is impaired triglyceride metabolism. Diseases associated with the metabolic syndrome promote the appearance of hepatic alterations e.g., non-alcoholic steatosis, steatohepatitis, fibrosis, cirrhosis and cancer. In this article, we review the molecular actions involved in impaired triglyceride metabolism and its association with hepatic diseases. We discuss mechanisms that reconcile the chronic inflammation and insulin resistance, and new concepts on the role of intestinal micro-flora permeability and proliferation in fatty liver etiology. We also describe the participation of oxidative stress in the progression of events leading from steatosis to steatohepatitis and fibrosis. Finally, we provide information regarding the mechanisms that link fatty acid accumulation during steatosis with changes in growth factors and cytokines that lead to the development of neoplastic cells. One of the main medical concerns vis-a-vis hepatic diseases is the lack of symptoms at the onset of the illness and, as result, its late diagnosis. The understandings of the molecular mechanisms that underlie hepatic diseases could help design strategies towards establishing markers for their accurate and timely diagnosis. PMID:24059726
Aguilera-M�ndez, Asdrubal; �lvarez-Delgado, Carolina; Hern�ndez-Godinez, Daniel; Fernandez-Mejia, Cristina
Echium oil (EO), which is enriched in SDA (18:4 n-3), reduces plasma triglyceride (TG) concentrations in humans and mice. We compared mechanisms by which EO and fish oil (FO) reduce plasma TG concentrations in mildly hypertriglyceridemic male apoB100-only LDLrKO mice. Mice were fed one of three atherogenic diets containing 0.2% cholesterol and palm oil (PO; 20%), EO (10% EO + 10% PO), or FO (10% FO + 10% PO). Livers from PO- and EO-fed mice had similar TG and cholesteryl ester (CE) content, which was significantly higher than in FO-fed mice. Plasma TG secretion was reduced in FO vs. EO-fed mice. Plasma very low density lipoprotein (VLDL) particle size was ordered: PO (63 � 4 nm) > EO (55 � 3 nm) > FO (40 � 2 nm). Post-heparin lipolytic activity was similar among groups, but TG hydrolysis by purified lipoprotein lipase was significantly greater for EO and FO VLDL compared to PO VLDL. Removal of VLDL tracer from plasma was marginally faster in EO vs. PO fed mice. Our results suggest that EO reduces plasma TG primarily through increased intravascular lipolysis of TG and VLDL clearance. Finally, EO may substitute for FO to reduce plasma TG concentrations, but not hepatic steatosis in this mouse model. PMID:23857172
Forrest, Lolita M; Lough, Christopher M; Chung, Soonkyu; Boudyguina, Elena Y; Gebre, Abraham K; Smith, Thomas L; Colvin, Perry L; Parks, John S
Mutations in microsomal triglyceride transfer protein (MTP) cause abetalipoproteinemia (ABL), characterized by the absence of plasma apoB-containing lipoproteins. In this study, we characterized the effects of various MTP missense mutations found in ABL patients with respect to their expression, subcellular location, and interaction with protein disulfide isomerase (PDI). In addition, we characterized functional properties by analyzing phospholipid and triglyceride transfer activities and studied their ability to support apoB secretion. All the mutants colocalized with calnexin and interacted with PDI. We found that R540H and N780Y, known to be deficient in triglyceride transfer activity, also lacked phospholipid transfer activity. Novel mutants S590I and G746E did not transfer triglycerides and phospholipids and did not assist in apoB secretion. In contrast, D384A displayed both triglyceride and phospholipid transfer activities and supported apoB secretion. These studies point out that ABL is associated with the absence of both triglyceride and phospholipid transfer activities in MTP. PMID:23475612
Khatun, Irani; Walsh, Meghan T.; Hussain, M. Mahmood
De novo lipogenesis is activated in most cancers and several lipogenic enzymes have been implicated as therapeutic targets. Here, we demonstrate a novel function of the lipogenic enzyme, ATP citrate lyase (ACLY), in lipid metabolism in cancer cells. ACLY depletion by small interfering RNAs caused growth suppression and/or apoptosis in a subset of cancer cell lines. To investigate the effect of ACLY inhibition on lipid metabolism, metabolome and transcriptome analysis was performed. ACLY depletion blocks the fatty acid chain elongation from C16 to C18 in triglyceride (TG), but not in other lipid classes. Meanwhile, wild-type ACLY overexpression enhanced fatty acid elongation of TG, whereas an inactive mutant ACLY did not change it. ACLY depletion-mediated blockade of fatty acid elongation was coincident with downregulation of long-chain fatty acid elongase ELOVL6, which resides in endoplasmic reticulum (ER). Paradoxically, ACLY depletion-mediated growth suppression was associated with TG accumulation. ACLY depletion downregulated the expression of carnitine palmitoyltransferase 1A, which is a mitochondrial fatty acid transporter. Consistent with this finding, metabolome analysis revealed that ACLY positively regulates the carnitine system, which plays as an essential cofactor for fatty acid transport across mitochondrial membrane. AICAR, an activator of mitochondrial fatty acid oxidation (FAO), significantly reduced ACLY depletion-mediated TG accumulation. These data indicate that inhibition of ACLY might affect both fatty acid elongation in ER and FAO in mitochondria, thereby explaining the TG accumulation with altered fatty acid composition. This phenotype may be a hallmark of growth suppression mediated by ACLY inhibition. PMID:24310723
Migita, Toshiro; Okabe, Sachiko; Ikeda, Kazutaka; Igarashi, Saori; Sugawara, Shoko; Tomida, Akihiro; Soga, Tomoyoshi; Taguchi, Ryo; Seimiya, Hiroyuki
Analysis of the Triglycerides of Some Vegetable Oils.
ERIC Educational Resources Information Center
Explains that triglycerides consist of a mixture of different compounds, depending on the total number of fatty acid constituents. Details the method and instrumentation necessary for students to analyze a vegetable oil for its triglyceride content. Describes sample results. (CW)
Farines, Marie; And Others
Medium chain triglycerides and structured lipids
Lipids are an essential component of our body composition and necessary in our daily food intake. Conventional fats and oils\\u000a are composed of glycerides of long chain fatty acids and are designated as long chain triglycerides (LCT). Body fat as well\\u000a as the fats and oils in our daily intake fall into this category. In enteral and parenteral hyperalimentation, we
Vigen K. Babayan
Nucleation kinetics of emulsified triglyceride mixtures
The purpose of this study is to determine character istic nucleation parameters such as the surface free energy for nucleus\\u000a formation in mixtures of fully hydrogenated palm oil (HP) in sunflower oil (SF). These parameters will be used to model the\\u000a bulk crystallization kinetics of the same mixtures. This was achieved by determining the crystallization kinetics in emulsified\\u000a triglyceride mixtures
William Kloek; Pieter Walstra; Ton van Vliet
Triglycerides (TG) are synthesized in the liver principally from two sources of fatty acids (FA): FA synthesized de novo in the liver and preformed FA. We have measured the rate of secretion of de novo synthesized FA and total secretion of FA bound to VLDL-TG in healthy men (n = 5) in the basal state, and after 1 (day 1) and 4 d (day 4) of a hypercaloric carbohydrate diet (approximately 2.5 times energy expenditure) that generated a moderate endogenous hyperinsulinemia (plasma insulin approximately 60 microU/ml). Prolonged carbohydrate hyperalimentation/hyperinsulinemia increased plasma VLDL-TG approximately 10-fold in part due to a 3.4-fold increase in total VLDL-TG secretion rate (basal state = 72+/-23, day 4 = 242+/-78 micromol TG/kg/d). Although the secretion of de novo synthesized FA increased throughout the study (basal state = 1.1+/-0.4, day 1 = 15.9+/-7.9, day 4 = 50.0+/-18.8 micromol TG/ kg/d), the 2.7-fold increase in secretion rate of preformed FA (basal state = 70+/-23, day 4 = 191+/-57 micromol TG/kg/d) quantitatively contributed the most to total VLDL-TG secretion rate. Decreased catabolism of VLDL-TG also contributed to the hypertriglyceridemia as reflected by an approximately fourfold decrease in both fractional turnover rate (basal state = 9.2+/-3.8, day 1 = 2.1+/-0.2, day 4 = 2.1+/-0.3 pools/d) and rate of clearance (basal state = 0.35+/-0.08, day 1 = 0.11+/-0.01, day 4 = 0.09+/-0.01 liter/kg/d) of VLDL-TG. Thus, the primary difference between 1 and 4 d of hyperinsulinemia in conjunction with carbohydrate hyperalimentation is the increase in hepatic secretion of preformed FA into VLDL-TG. PMID:8903319
Aarsland, A; Chinkes, D; Wolfe, R R
Supercritical Fluid Extraction of the Triglycerides Present in Vegetable Oils
The use of supercritical carbon dioxide to extract the triglycerides present in vegetable oils was studied over a temperature range of 40 to 80�C and at pressures of 100 to 300 bar. The solubility of the triglycerides was found to be dependent upon the solvent density and the solute volatility. Minimal selectivity for the different molecular weight triglycerides was observed
K. D. Tilly; R. P. Chaplin; N. R. Foster
A carotenoid-rich salad meal with varying amounts and types of triglycerides (TG) was digested using simulated gastric and small intestinal conditions. Xanthophylls (lutein and zeaxanthin) and carotenes (alpha-carotene, beta-carotene, and lycopene) in chyme and micelle fraction were quantified to determine digestive stability and efficiency of micellarization (bioaccessibility). Micellarization of lutein (+zeaxanthin) exceeded that of alpha- and beta-carotenes, which was greater than that of lycopene for all test conditions. Micellarization of carotenes, but not lutein (+zeaxanthin), was enhanced (P < 0.05) by addition of TG (2.5% v/w) to the meal and was dependent on fatty acyl chain length in structured TG (c18:1 > c8:0 > c4:0). The degree of unsaturation of c18 fatty acyl chains in TG added to the salad pur�e did not significantly alter the efficiency of micellarization of carotenoids. Relatively low amounts of triolein and canola oil (0.5-1%) were required for maximum micellarization of carotenes, but more oil (approximately 2.5%) was required when TG with medium chain saturated fatty acyl groups (e.g., trioctanoin and coconut oil) was added to the salad. Uptake of lutein and beta-carotene by Caco-2 cells also was examined by exposing cells to micelles generated during the simulated digestion of salad pur�e with either triolein or trioctanoin. Cell accumulation of beta-carotene was independent of fatty acyl composition of micelles, whereas lutein uptake was slightly, but significantly, increased from samples with digested triolein compared to trioctanoin. The results show that the in vitro transfer of alpha-carotene, beta-carotene, and lycopene from chyme to mixed micelles during digestion requires minimal (0.5-1%) lipid content in the meal and is affected by the length of fatty acyl chains but not the degree of unsaturation in TG. In contrast, fatty acyl chain length has limited if any impact on carotenoid uptake by small intestinal epithelial cells. These data suggest that the amount of TG in a typical meal does not limit the bioaccessibility of carotenoids. PMID:17927194
Huo, Tianyao; Ferruzzi, Mario G; Schwartz, Steven J; Failla, Mark L
Enhanced glycogen metabolism in adipose tissue decreases triglyceride mobilization.
Adipose tissue is a primary site for lipid storage containing trace amounts of glycogen. However, refeeding after a prolonged partial fast produces a marked transient spike in adipose glycogen, which dissipates in coordination with the initiation of lipid resynthesis. To further study the potential interplay between glycogen and lipid metabolism in adipose tissue, the aP2-PTG transgenic mouse line was utilized since it contains a 100- to 400-fold elevation of adipocyte glycogen levels that are mobilized upon fasting. To determine the fate of the released glucose 1-phosphate, a series of metabolic measurements were made. Basal and isoproterenol-stimulated lactate production in vitro was significantly increased in adipose tissue from transgenic animals. In parallel, basal and isoproterenol-induced release of nonesterified fatty acids (NEFAs) was significantly reduced in transgenic adipose tissue vs. control. Interestingly, glycerol release was unchanged between the genotypes, suggesting that enhanced triglyceride resynthesis was occurring in the transgenic tissue. Qualitatively similar results for NEFA and glycerol levels between wild-type and transgenic animals were obtained in vivo during fasting. Additionally, the physiological upregulation of the phosphoenolpyruvate carboxykinase cytosolic isoform (PEPCK-C) expression in adipose upon fasting was significantly blunted in transgenic mice. No changes in whole body metabolism were detected through indirect calorimetry. Yet weight loss following a weight gain/loss protocol was significantly impeded in the transgenic animals, indicating a further impairment in triglyceride mobilization. Cumulatively, these results support the notion that the adipocyte possesses a set point for glycogen, which is altered in response to nutritional cues, enabling the coordination of adipose glycogen turnover with lipid metabolism. PMID:20424138
Markan, Kathleen R; Jurczak, Michael J; Allison, Margaret B; Ye, Honggang; Sutanto, Maria M; Cohen, Ronald N; Brady, Matthew J
Short-term caloric restriction increases plasma levels of nonesterified fatty acids (NEFAs) and is associated with increased myocardial triglyceride (TG) content and decreased myocardial function in healthy subjects. Whether this flexibility of myocardial TG stores and myocardial function is also present in patients with type 2 diabetes mellitus (T2DM) is yet unknown. Myocardial TG content and left ventricular (LV) ratio between the early (E) and atrial (A) diastolic filling phase (E/A) were determined using magnetic resonance (MR) spectroscopy and MR imaging, respectively, before and after a 3-day very low-calorie diet (VLCD) in 11 patients with T2DM. In addition, we studied patients after a 3-day VLCD combined with the antilipolytic drug acipimox. The VLCD induced myocardial TG accumulation [from 0.66 +/- 0.09% (mean +/- SE, baseline) to 0.98 +/- 0.16%, P = 0.028] and a decrease in E/A ratio [from 1.00 +/- 0.05 (baseline) to 0.90 +/- 0.06, P = 0.002]. This was associated with increased plasma NEFA levels (from 0.57 +/- 0.08 mmol/l at baseline to 0.92 +/- 0.12, P = 0.019). After the VLCD with acipimox, myocardial TG content, diastolic function, and plasma NEFA levels were similar to baseline values. In conclusion, in patients with T2DM, a VLCD increases myocardial TG content and is associated with a decrease in LV diastolic function. These effects were not observed when a VLCD was combined with acipimox, illustrating the physiological flexibility of myocardial TG stores and myocardial function in patients with T2DM. PMID:18628354
Hammer, Sebastiaan; van der Meer, Rutger W; Lamb, Hildo J; de Boer, Hans H; Bax, Jeroen J; de Roos, Albert; Romijn, Johannes A; Smit, Johannes W A
Objectives: To evaluate if logarithm of the ratio of plasma concentration of triglycerides to HDL-cholesterol (Log[TG\\/HDL-C]) correlates with cholesterol esterification rates in apoB-lipoprotein-depleted plasma (FERHDL) and lipoprotein particle size.Design and methods: We analyzed previous data dealing with the parameters related to the FERHDL (an indirect measure of lipoprotein particle size). In a total of 1433 subjects from 35 cohorts with
Jiri Frohlich
OBJECTIVE To assess basal and insulin-mediated VLDL-triglyceride (TG) kinetics and the relationship between VLDL-TG secretion and hepatic insulin resistance assessed by endogenous glucose production (EGP) in obese and lean men. RESEARCH DESIGN AND METHODS A total of 12 normoglycemic, obese (waist-to-hip ratio >0.9, BMI >30 kg/m2) and 12 lean (BMI 20�25 kg/m2) age-matched men were included. Ex vivo�labeled [1-14C]VLDL-TGs and [3-3H]glucose were infused postabsorptively and during a hyperinsulinemic-euglycemic clamp to determine VLDL-TG kinetics and EGP. Body composition was determined by dual X-ray absorptiometry and computed tomography scanning. Energy expenditure and substrate oxidation rates were measured by indirect calorimetry. RESULTS Basal VLDL-TG secretion rates were increased in obese compared with lean men (1.25 � 0.34 vs. 0.86 � 0.34 ?mol/kg fat-free mass [FFM]/min; P = 0.011), whereas there was no difference in clearance rates (150 � 56 vs. 162 � 77 mL/min; P = NS), resulting in greater VLDL-TG concentrations (0.74 � 0.40 vs. 0.38 � 0.20 mmol/L; P = 0.011). The absolute insulin-mediated suppression of VLDL-TG secretion was similar in the groups. However, the percentage reduction (?36 � 18 vs. ?54 � 10%; P = 0.008) and achieved VLDL-TG secretion rates (0.76 � 0.20 vs. 0.41 � 0.19 ?mol/kg FFM/min; P < 0.001) were impaired in obese men. Furthermore, clearance rates decreased significantly in obese men, but there was no significant change in lean men (?17 � 18 vs. 7 � 20%; P = 0.007), resulting in less percentage reduction of VLDL-TG concentrations in obese men (?22 � 20 vs. ?56 � 11%; P < 0.001). Insulin-suppressed EGP was similar (0.4 [0.0-0.8] vs. 0.1 [0.0-1.2] mg/kg FFM/min (median [range]); P = NS), and the percentage reduction was equivalent (?80% [57�98] vs. ?98% [49�100], P = NS). Insulin-mediated glucose disposal was significantly reduced in obese men. CONCLUSIONS Basal VLDL-TG secretion rates are increased in normoglycemic but insulin-resistant, obese men, resulting in hypertriglyceridemia. Insulin-mediated suppression of EGP is preserved in obese men, whereas suppression of VLDL-TG secretion is less pronounced in obese men. Compared with EGP, the inability to achieve suppression of VLDL-TG secretions to a level similar to control subjects during hyperinsulinemia seems to be an early manifestation in male obesity. PMID:21810597
S?rensen, Lars P.; S?ndergaard, Esben; Nellemann, Birgitte; Christiansen, Jens S.; Gormsen, Lars C.; Nielsen, S?ren
Elevated plasma triglyceride levels represent a risk factor for premature atherosclerosis. In mice, accumulation of triglyceride-rich lipoproteins can occur if sulfation of heparan sulfate in hepatocytes is diminished, as this alters hepatic lipoprotein clearance via heparan sulfate proteoglycans (HSPGs). However, the relevant HSPG has not been determined. In this study, we found by RT-PCR analysis that mouse hepatocytes expressed the membrane proteoglycans syndecan-1, -2, and -4 and glypican-1 and -4. Analysis of available proteoglycan-deficient mice showed that only syndecan-1 mutants (Sdc1�/� mice) accumulated plasma triglycerides. Sdc1�/� mice also exhibited prolonged circulation of injected human VLDL and intestinally derived chylomicrons. We found that mice lacking both syndecan-1 and hepatocyte heparan sulfate did not display accentuated triglyceride accumulation compared with single mutants, suggesting that syndecan-1 is the primary HSPG mediating hepatic triglyceride clearance. Immunoelectron microscopy showed that syndecan-1 was expressed specifically on the microvilli of hepatocyte basal membranes, facing the space of Disse, where lipoprotein uptake occurs. Abundant syndecan-1 on wild-type murine hepatocytes exhibited saturable binding of VLDL and inhibition by heparin and facilitated degradation of VLDL. Furthermore, adenovirus-encoded syndecan-1 restored binding, uptake, and degradation of VLDL in isolated Sdc1�/� hepatocytes and the lipoprotein clearance defect in Sdc1�/� mice. These findings provide the first in vivo genetic evidence that syndecan-1 is the primary hepatocyte HSPG receptor mediating the clearance of both hepatic and intestinally derived triglyceride-rich lipoproteins. PMID:19805913
Stanford, Kristin I.; Bishop, Joseph R.; Foley, Erin M.; Gonzales, Jon C.; Niesman, Ingrid R.; Witztum, Joseph L.; Esko, Jeffrey D.
The plasma profile of major lipoprotein classes and its subdivision into particular fractions plays a crucial role in the pathogenesis of atherosclerosis and is a major predictor of coronary artery disease. Our aim was to identify genomic determinants of triglyceride and cholesterol distribution into lipoprotein fractions and lipoprotein particle sizes in the recombinant inbred rat set PXO, in which alleles of two rat models of the metabolic syndrome (SHR and PD inbred strains) segregate together with those from Brown Norway rat strain. Adult male rats of 15 PXO strains (n?=?8-13/strain) and two progenitor strains SHR-Lx (n?=?13) and BXH2/Cub (n?=?18) were subjected to one-week of high-sucrose diet feeding. We performed association analyses of triglyceride (TG) and cholesterol (C) concentrations in 20 lipoprotein fractions and the size of major classes of lipoprotein particles utilizing 704 polymorphic microsatellite markers, the genome-wide significance was validated by 2,000 permutations per trait. Subsequent in silico focusing of the identified quantitative trait loci was completed using a map of over 20,000 single nucleotide polymorphisms. In most of the phenotypes we identified substantial gradient among the strains (e.g. VLDL-TG from 5.6 to 66.7 mg/dl). We have identified 14 loci (encompassing 1 to 65 genes) on rat chromosomes 3, 4, 7, 8, 11 and 12 showing suggestive or significant association to one or more of the studied traits. PXO strains carrying the SHR allele displayed significantly higher values of the linked traits except for LDL-TG and adiposity index. Cholesterol concentrations in large, medium and very small LDL particles were significantly associated to a haplotype block spanning part of a single gene, low density lipoprotein receptor-related protein 1B (Lrp1b). Using genome-wide association we have identified new genetic determinants of triglyceride and cholesterol distribution into lipoprotein fractions in the recombinant inbred panel of rat model strains. PMID:25296178
Hod�lov�, Miloslava; Sedov�, Lucie; K?enov�, Drahom�ra; Li�ka, Franti�ek; Krupkov�, Michaela; Kazdov�, Ludmila; Tremblay, Johanne; Hamet, Pavel; K?en, Vladim�r; Seda, Ond?ej
The plasma profile of major lipoprotein classes and its subdivision into particular fractions plays a crucial role in the pathogenesis of atherosclerosis and is a major predictor of coronary artery disease. Our aim was to identify genomic determinants of triglyceride and cholesterol distribution into lipoprotein fractions and lipoprotein particle sizes in the recombinant inbred rat set PXO, in which alleles of two rat models of the metabolic syndrome (SHR and PD inbred strains) segregate together with those from Brown Norway rat strain. Adult male rats of 15 PXO strains (n?=?8�13/strain) and two progenitor strains SHR-Lx (n?=?13) and BXH2/Cub (n?=?18) were subjected to one-week of high-sucrose diet feeding. We performed association analyses of triglyceride (TG) and cholesterol (C) concentrations in 20 lipoprotein fractions and the size of major classes of lipoprotein particles utilizing 704 polymorphic microsatellite markers, the genome-wide significance was validated by 2,000 permutations per trait. Subsequent in silico focusing of the identified quantitative trait loci was completed using a map of over 20,000 single nucleotide polymorphisms. In most of the phenotypes we identified substantial gradient among the strains (e.g. VLDL-TG from 5.6 to 66.7 mg/dl). We have identified 14 loci (encompassing 1 to 65 genes) on rat chromosomes 3, 4, 7, 8, 11 and 12 showing suggestive or significant association to one or more of the studied traits. PXO strains carrying the SHR allele displayed significantly higher values of the linked traits except for LDL-TG and adiposity index. Cholesterol concentrations in large, medium and very small LDL particles were significantly associated to a haplotype block spanning part of a single gene, low density lipoprotein receptor-related protein 1B (Lrp1b). Using genome-wide association we have identified new genetic determinants of triglyceride and cholesterol distribution into lipoprotein fractions in the recombinant inbred panel of rat model strains. PMID:25296178
Hodulova, Miloslava; Sedova, Lucie; Krenova, Drahomira; Liska, Frantisek; Krupkova, Michaela; Kazdova, Ludmila; Tremblay, Johanne; Hamet, Pavel; Kren, Vladimir; Seda, Ondrej
Failure simulations of triglyceride-based adhesives
NASA Astrophysics Data System (ADS)
The use of natural plant oils in the production of adhesives has been the focus of a large amount of research because the natural oils are a renewable resource which have environmental and economic advantages over the petroleum-derived chemicals used in traditional adhesives. An off-lattice Monte Carlo simulation was used to model the formation of networks consisting of the triglycerides found in soybean, linseed and olive oils and networks made from other `theoretical' natural oils. Each of these networks has a different number of carbon-carbon double bonds n present in a given triglyceride molecule. The stress-strain behavior of these networks is studied using large-scale molecular dynamics simulations. Tensile strains are applied to the networks and it is observed that with increasing n the failure stress increases but the failure strain decreases. Also, at low values of n, the systems have large voids form while the system is strained and then the system fails cohesively. However for large n, no significant voiding is observed and the system fails close to the interface. The simulation results are shown to be consistent with vector percolation theoretical predictions for how the failure stress and the crosslink density relate to n.
Lorenz, Christian D.; Stevens, Mark J.; Wool, Richard P.
The present study aimed to compare the associations of postprandial glucose (ppGL) and postprandial triglycerides (ppTG) with carotid intima media thickness (cIMT) in women with normal glucose metabolism (NGM) and type 2 diabetes (DM2).Post-menopausal women (76 with NGM, 78 with DM2), received two consecutive fat-rich and two consecutive carbohydrate-rich meals on separate occasions. Blood samples were taken before and 1,
M. Alssema; R. K. Schindhelm; J. M. Dekker; M. Diamant; P. J. Kostense; T. Teerlink; P. G. Scheffer; G. Nijpels; R. J. Heine
The immobilized 1,3-regiospecific lipase, Mucor miehei, was employed to catalyze the trans-esterification reaction to enrich n-3 polyunsaturated fatty acid (n-3 PUFA) content of triglycerides (TG) in Menhaden oil under supercritical carbon dioxide (SCCO2). A supercritical reacting system with a syringe pump to pressurize CO2 to supercritical condition and a high-pressure liquid pump to transfer the substrate into the reactor is
Tsao-Jen Lin; Shin-Wan Chen; An-Chan Chang
[Staged oncological screening with TG test].
The authors present their analysis of screening methods used for early diagnostics of cancer of various localization and for detection of high-risk individuals. They offer a program of step-by-step screening that makes it possible to cover more population with prophylactic examination and to reduce the need for special examination methods. TG-test is a universal and the most informative blastomatous process indicator at any stage, including the preclinical one. The practical screening results double the revealing rate of oncopathology and allow for three-fold reduction in the diagnostic costs compared with standard methods of cancer diagnostics. The medical efficiency of the oncological screening is high; in one third of the examined patients a tumor is diagnosed at the preclinical stage. PMID:17243615
Bakhlaev, I E; Ageenko, A I; Rolik, I S
Insulin therapy in burn patients does not contribute to hepatic triglyceride production.
Lipid kinetics were studied in six severely burned patients who were treated with a high dose of exogenous insulin plus glucose to promote protein metabolism. The patients were 20+/-2-yr-old (SD) with 63+/-8% total body surface area burned. They were studied in a randomized order (a) in the fed state on the seventh day of a control period (C) of continuous high-carbohydrate enteral feeding alone, and (b) on the seventh day of enteral feeding plus exogenous insulin (200 pmol/h = 28 U/h) with extra glucose given as needed to avoid hypoglycemia (I+G). Despite a glucose delivery rate approximately 100% in excess of energy requirements, the following lipid parameters were unchanged: (a) total hepatic VLDL triglyceride (TG) secretion rate (0.165+/-0.138 [C] vs. 0.154+/- 0.138 mmol/kg . d-1 [I+G]), (b) plasma TG concentration (1.58+/-0.66 [C] vs. 1. 36+/-0.41 mmol/liter [I+G]), and (c) plasma VLDL TG concentration (0. 68+/-0.79 [C] vs. 0.67+/- 0.63 mmol/liter [I+G]). Instead, the high-carbohydrate delivery in conjunction with insulin therapy increased the proportion of de novo-synthesized palmitate in VLDL TG from 13+/-5% (C) to 34+/-14% (I+G), with a corresponding decreased amount of palmitate from lipolysis. In association with the doubling of the secretion rate of de novo-synthesized fatty acid (FA) in VLDL TG during insulin therapy (P > 0.5), the relative amount of palmitate and stearate increased from 35+/-5 to 44+/-8% and 4+/-1 to 7+/-2%, respectively, in VLDL TG, while the relative concentration of oleate and linoleate decreased from 43+/-5 to 37+/-6% and 8+/-4% to 2+/-2%, respectively. A 15-fold increase in plasma insulin concentration did not change the rate of release of FA into plasma (8.22+/-2.86 [C] vs. 8.72+/-6.68 mmol/kg.d-1 [I+G]. The peripheral release of FA represents a far greater potential for hepatic lipid accumulation in burn patients than the endogenous hepatic fat synthesis, even during excessive carbohydrate intake in conjunction with insulin therapy. PMID:9593779
Aarsland, A; Chinkes, D L; Sakurai, Y; Nguyen, T T; Herndon, D N; Wolfe, R R
Pituitary dependent hyperadrenocorticism (PDH) shows a high morbidity and blindness is one of its complications. Compression of the optic chiasm (OC) by the hypophysis adenoma is one of the causes. Another cause could be due to vascular and metabolic alterations of the PDH. Out of a total of 70 dogs with confirmed diagnosis of PDH, 12/70 showed blindness. In only 2/12 the OC was compromised. Electroretinography in dogs without the OC being compromised showed altered A and B wave patterns. Ophthalmological Doppler showed an alteration of the blood flow only in blind dogs without OC compression. Cortisol concentrations (Co), triglycerides (Tg) and glycaemia (G) were greater in 10 dogs with non-compressive blindness vs. dogs with conserved vision. Loss of vision correlated with the increase in these variables. Blindness in dogs with PDH would be related to changes in retinal blood flow, associated to higher Co, Tg and G concentrations. PMID:21575979
Cabrera Blatter, M F; del Prado, A; Gallelli, M F; D'Anna, E; Ivanic, J; Esarte, M; Miceli, D D; G�mez, N V; Castillo, V A
Pancreatic lipase hydrolysis of triglycerides by a semimicro technique
Procedures are described for rapid lipase hydrolysis of triglycerides, isolation of the hydrolytic products by TLC and their\\u000a conversion to methyl esters and fatty acid analysis by GLC. The techniques are applicable to a few mg of triglycerides or\\u000a fats. Examples of data obtained with purified triglycerides indicate that the specific action of pancreatic lipase for the\\u000a 1,3 ester groups
F. E. Luddy; R. A. Barford; S. F. Herb; P. Magidman; R. W. Riemenschneider
The microsomal triglyceride (TG) transfer protein (MTP) is a heterodimeric lipid transfer protein that catalyzes the transport of triglyceride, cholesteryl ester, and phosphatidylcholine between membranes. Previous studies showing that the proximal cause of abetalipoproteinemia is an absence of MTP indicate that MTP function is required for the assembly of the apolipoprotein B (apoB) containing plasma lipoproteins, i.e., very low density lipoproteins and chylomicrons. However, the precise role of MTP in lipoprotein assembly is not known. In this study, the role of MTP in lipoprotein assembly is investigated using an inhibitor of MTP-mediated lipid transport, 2-[1-(3, 3-diphenylpropyl)-4-piperidinyl]-2,3-dihydro-1H-isoindol-1-o ne (BMS-200150). The similarity of the IC50 for inhibition of bovine MTP-mediated TG transfer (0.6 microM) to the Kd for binding of BMS-200150 to bovine MTP (1.3 microM) strongly supports that the inhibition of TG transfer is the result of a direct effect of the compound on MTP. BMS-200150 also inhibits the transfer of phosphatidylcholine, however to a lesser extent (30% at a concentration that almost completely inhibits TG and cholesteryl ester transfer). When BMS-200150 is added to cultured HepG2 cells, a human liver-derived cell line that secretes apoB containing lipoproteins, it inhibits apoB secretion in a concentration dependent manner. These results support the hypothesis that transport of lipid, and in particular, the transport of neutral lipid by MTP, plays a critical role in the assembly of apoB containing lipoproteins. PMID:8876250
Jamil, H; Gordon, D A; Eustice, D C; Brooks, C M; Dickson, J K; Chen, Y; Ricci, B; Chu, C H; Harrity, T W; Ciosek, C P; Biller, S A; Gregg, R E; Wetterau, J R
siRNA screening reveals JNK2 as an evolutionary conserved regulator of triglyceride homeostasis.
Lipid homeostasis is essential for proper function of cells and organisms. To unravel new regulators of this system, we developed a screening procedure, combining RNA interference in HeLa cells and TLC, which enabled us to monitor modifications of lipid composition resulting from short, interfering RNA knock-downs. We applied this technique to the analysis of 600 human kinases. Despite the occurrence of off-target effects, we identified JNK2 as a new player in triglyceride (TG) homeostasis and lipid droplet metabolism and, more specifically, in the regulation of lipolysis. Similar control of the level of TGs and lipid droplets was observed for its Schizosaccharomyces pombe homolog, Sty1, suggesting an evolutionary conserved function of mitogen-activated protein kinases in the regulation of lipid storage in eukaryotic cells. PMID:18612143
Grimard, Vinciane; Massier, Julia; Richter, Doris; Schwudke, Dominik; Kalaidzidis, Yannis; Fava, Eugenio; Hermetter, Albin; Thiele, Christoph
Bioconversion of Xylan to Triglycerides by Oil-Rich Yeasts
A series of lipid-accumulating yeasts was examined for their potential to saccharify xylan and accumulate triglyceride. Of the genera tested, including Candida, Cryptococcus, Lipomyces, Rhodosporidium, Rhodotorula, and Trichosporon, only Cryptococcus and Trichosporon isolates saccharified xylan. All of the strains could assimilate xylose and accumuate triglyceride under nitrogen-limiting conditions. Strains of Cryptococcus albidus were found to be especially useful for a one-step saccharification of xylan coupled to triglyceride synthesis. Cryptococcus terricolus, a strain constitutive for lipid accumulation, lacked extracellular xylanase, but did assimilate xylose and xylobiose and was able to continuously convert xylan to triglyceride if the culture medium was supplemented with xylanase. PMID:16346541
Fall, Ray; Phelps, Patricia; Spindler, Diane
21 CFR 862.1705 - Triglyceride test system.
Code of Federal Regulations, 2013 CFR
...ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems � 862.1705 Triglyceride test system. (a)...
Microsomal triglyceride transfer protein (MTP) catalyzes the assembly of triglyceride (TG)-rich apolipoprotein B-containing liver (e.g., VLDL) and intestinal (e.g., chylomicron) lipoproteins. The human MTP gene promoter is reported here to associate in vivo with endogenous hepatocyte nuclear factor-4alpha (HNF-4alpha) and to be transactivated or transsuppressed by overexpressed or by dominant negative HNF-4alpha, respectively. Human MTP (hMTP) transactivation by HNF-4alpha is accounted for by the concerted activity of distal (-83/-70) and proximal (-50/-38) direct repeat 1 elements of the hMTP promoter that bind HNF-4alpha. Transactivation by HNF-4alpha is specifically antagonized by chicken ovalbumin upstream promoter. Transcriptional activation of hMTP by HNF-4alpha is mediated by HNF-4alpha domains engaged in ligand binding and ligand-driven transactivation and is further complemented by HNF-4alpha/HNF-1alpha synergism that involves the HNF-4alpha activation function 1 (AF-1) domain. hMTP transactivation by HNF-4alpha is specifically inhibited by beta,beta-tetramethyl-hexadecanedioic acid acting as an HNF-4alpha antagonist ligand. hMTP transactivation by HNF-4alpha may account for the activation or inhibition of MTP expression and the production of TG-rich lipoproteins by agonist (e.g., saturated fatty acids) or antagonist [e.g., (n-3) PUFA, hypolipidemic fibrates, or Methyl-substituted dicarboxylic acid (Medica) compounds] HNF-4alpha ligands. PMID:15547294
Sheena, Vered; Hertz, Rachel; Nousbeck, Janna; Berman, Ina; Magenheim, Judith; Bar-Tana, Jacob
The adipose triglyceride lipase (PNPLA2, also known as ATGL) is a novel triacylglycerol (TG) lipase which specifically removes the first fatty acid from the triglyceride molecule generating free fatty acid and diglyceride (DG) in mammalian cells. Here we describe the molecular characterization of the porcine ATGL gene. The full-length cDNA sequence contains a 1,461 bp open reading frame encoding a protein of 486 amino acids with a calculated molecular mass of 53.2 kDa and an isoelectric point of 7.90. The porcine ATGL protein shares high identity with other mammalian ATGL. The ATGL gene contains 9 coding exons, spans approximately 6 kb. The porcine ATGL mRNA was expressed predominantly in backfat, mildly in muscle, small intestine and heart, and almost absent in liver, spleen, lung, stomach, kidney and ovary. Statistical analysis showed the ATGL gene polymorphism (G/A(392)) was different between Chinese indigenous and introduced commercial western pig breeds, and was highly associated with almost all the fat deposition and carcass traits, including subcutaneous fat thickness, viscera adipose tissue, lean percentage, loin eye traits and even rib numbers. PMID:20480242
Dai, Li He; Xiong, Yuan Zhu; Jiang, Si Wen; Chen, Jun Feng
Adipose triglyceride lipase activity is inhibited by long-chain acyl-coenzyme A
Adipose triglyceride lipase (ATGL) is required for efficient mobilization of triglyceride (TG) stores in adipose tissue and non-adipose tissues. Therefore, ATGL strongly determines the availability of fatty acids for metabolic reactions. ATGL activity is regulated by a complex network of lipolytic and anti-lipolytic hormones. These signals control enzyme expression and the interaction of ATGL with the regulatory proteins CGI-58 and G0S2. Up to date, it was unknown whether ATGL activity is also controlled by lipid intermediates generated during lipolysis. Here we show that ATGL activity is inhibited by long-chain acyl-CoAs in a non-competitive manner, similar as previously shown for hormone-sensitive lipase (HSL), the rate-limiting enzyme for diglyceride breakdown in adipose tissue. ATGL activity is only marginally inhibited by medium-chain acyl-CoAs, diglycerides, monoglycerides, and free fatty acids. Immunoprecipitation assays revealed that acyl-CoAs do not disrupt the protein�protein interaction of ATGL and its co-activator CGI-58. Furthermore, inhibition of ATGL is independent of the presence of CGI-58 and occurs directly at the N-terminal patatin-like phospholipase domain of the enzyme. In conclusion, our results suggest that inhibition of the major lipolytic enzymes ATGL and HSL by long-chain acyl-CoAs could represent an effective feedback mechanism controlling lipolysis and protecting cells from lipotoxic concentrations of fatty acids and fatty acid-derived lipid metabolites. PMID:24440819
Nagy, Harald M.; Paar, Margret; Heier, Christoph; Moustafa, Tarek; Hofer, Peter; Haemmerle, Guenter; Lass, Achim; Zechner, Rudolf; Oberer, Monika; Zimmermann, Robert
Objective To investigate the relationship between lipid profiles [including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C)] and a mild decline in the estimated glomerular filtration rate (eGFR) in subjects with normal serum lipid levels. Design and Methods In this study, we included 2647 participants who were ?40 years old and had normal serum lipid levels. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation was used to estimate the GFR. A mildly reduced eGFR was defined as 60�90 mL/min/1.73 m2. First, multiple linear regression analysis was used to estimate the association of lipid profiles with the eGFR. Then, the levels of each lipid component were divided into four groups, using the 25th, 50th and 75th percentiles as cut-off points. Finally, multiple logistic regression analysis was used to investigate the association of different lipid components with the risk of mildly reduced eGFR. Results In the group with a mildly reduced eGFR, TG and LDL-C levels were significantly increased, but HDL-C levels were significantly decreased. After adjusting for age, gender, body mass index (BMI), systolic blood pressure (SBP), glycated hemoglobin (HbA1c), smoking and drinking, only TC and TG were independently related to the eGFR. Additionally, only TG showed a linear relationship with an increased risk of a mildly reduced eGFR, with the highest quartile group (TG: 108�150 mg/dl [1.22�1.70 mmol/L]) having a significantly increased risk after adjusting for the above factors. Conclusions Triglyceride levels are closely associated with a mildly reduced eGFR in subjects with normal serum lipid levels. Dyslipidemia with lower TG levels could be used as new diagnostic criteria for subjects with mildly reduced renal function. PMID:25275610
Zhang, Xiuping; Zhao, Xiangmin; Wang, Yulian; Li, Chengqiao; Li, Mei; Wang, Shaoyuan; Yang, Weifang; Ma, Zeqiang; Ma, Aixia; Zheng, Huizhen; Wu, Jiahui; Sun, Yu; Song, Jun; Lin, Peng; Liang, Kai; Gong, Lei; Wang, Meijian; Liu, Fuqiang; Li, Wenjuan; Xiao, Juan; Yan, Fei; Yang, Junpeng; Wang, Lingshu; Tian, Meng; Liu, Jidong; Zhao, Ruxing; Chen, Shihong; Chen, Li
Dicarboxylic aciduria and medium chain triglyceride supplemented milk.
Pronounced dicarboxylic aciduria was observed in preterm infants fed a medium chain triglyceride supplemented milk formula. As many special formulas contain a medium chain triglyceride oil attention needs to be drawn to its metabolic effects, regarding the diagnosis of inborn errors of metabolism and that dicarboxylic acids might be harmful. PMID:3729533
Henderson, M J; Dear, P R
Physical properties of triglyceride estolides from lesquerella and castor oils
Lesquerella is a developing hydroxy oilseed crop suitable for rotation in the arid Southwestern United States. The hydroxy oil of lesquerella makes it suitable for esterification into triglyceride estolides. The estolide functionality imparts unique physical properties that make this class of materials suitable for functional fluid applications. Lesquerella and castor hydroxy triglycerides were converted to their corresponding estolides by reacting
Terry A. Isbell; Benjamin A. Lowery; Stephanie S. DeKeyser; Melissa L. Winchell; Steven C. Cermak
Construction of a triglyceride amperometric biosensor based on chitosan-ZnO nanocomposite film.
A method is described for construction of a novel amperometric triglyceride (TG) biosensor based on covalent co-immobilization of lipase, glycerol kinase (GK) and glycerol-3-phosphate oxidase (GPO) onto chitosan (CHIT) and zinc oxide nanoparticles (ZnONPs) composite film deposited on the surface of Pt electrode. The enzymes-ZnONPs-CHIT composite was characterized by X-ray diffraction (XRD), scanning electron microscope (SEM), cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). The sensor showed optimum response within 6s at pH 7.5 and temperature of 35�C. The sensor measures current due to electrons generated at 0.4V against Ag/AgCl from H(2)O(2), which is produced from triolein by co-immobilized enzymes. A linear relationship was obtained between a wide triolein concentration range (50-650 mg/dl) and current (mA) under optimum conditions. The biosensor showed high sensitivity, low detection limit (20 mg/dl) and good storage stability (half-life of 7 months at 4�C). The biosensor was unaffected modified by a number of serum substances at their physiological concentrations. The biosensor was evaluated and employed for determination of TG in sera in apparently healthy subjects and persons suffering from hypertriglyceridemia. PMID:21763341
Narang, Jagriti; Pundir, C S
The map asymptotics constant tg Edward A. Bender
The map asymptotics constant tg Edward A. Bender Department of Mathematics University of California vertex of the edge and a side of the edge. With Mn,g the number of rooted maps on g with n edges, Bender interesting families of maps also satisfy asymptotic for- mulas of the form tg(n)5(g-1)/2 n (2) and presented
Bender, Ed
Nonalcoholic fatty liver disease (NAFLD) and alterations in hepatic lipoprotein kinetics are common metabolic complications associated with obesity. Lifestyle modification involving diet-induced weight loss and regular exercise decreases intrahepatic triglyceride (IHTG) content and very low density lipoprotein (VLDL) triglyceride (TG) secretion rate. The aim of this study was to evaluate the weight loss-independent effect of following the physical activity guidelines recommended by the Department of Health and Human Services on IHTG content and VLDL kinetics in obese persons with NAFLD. Eighteen obese people (BMI: 38.1 � 4.6 kg/m2) with NAFLD were randomized to 16 weeks of exercise training (45-55% V?O2peak, 30-60 min � 5 days/week; n = 12) or observation (control; n = 6). Magnetic resonance spectroscopy and stable isotope tracer infusions in conjunction with compartmental modeling were used to evaluate IHTG content and hepatic VLDL-TG and apolipoprotein B-100 (apoB-100) secretion rates. Exercise training resulted in a 10.3 � 4.6 % decrease in IHTG content (p<0.05), but did not change total body weight (103.1 � 4.2 kg before and 102.9 � 4.2 kg after training) or percent body fat (38.9 � 2.1 % before and 39.2 � 2.1 % after training). Exercise training did not change the hepatic VLDL-TG secretion rate (17.7 � 3.9 ?mol/min before and 16.8 � 5.4 ?mol/min after training) or VLDL-apoB-100 secretion rate (1.5 � 0.5 nmol/min before and 1.6 � 0.6 nmol/min after training). Conclusions: Following the Department of Health and Human Services recommended physical activity guidelines has small but beneficial effects on IHTG content, but does not improve hepatic lipoprotein kinetics, in obese persons with NAFLD. PMID:22213436
Sullivan, Shelby; Kirk, Erik P.; Mittendorfer, Bettina; Patterson, Bruce W.; Klein, Samuel
High triglycerides (TG) and low high density lipoprotein cholesterol (HDL-C) are important cardiovascular risk factors in women. The prognostic utility of the TG/HDL-C ratio, a marker for insulin resistance and small dense low density lipoprotein particles, is unknown among high risk women. Methods We studied 544 women without prior myocardial infarction or coronary revascularization, referred for clinically indicated coronary angiography and enrolled in the Women�s Ischemia Syndrome Evaluation (WISE). Fasting lipid profiles and detailed demographic and clinical data were obtained at baseline. Multi-variate Cox-proportional hazards models for all cause mortality and cardiovascular events (death, myocardial infarction, heart failure, stroke) over a median follow-up of 6 years were constructed using log TG/HDL-C ratio as a predictor variable and accounting for traditional cardiovascular risk factors. Results Mean age was 57�11 years, 84% were white, 55% hypertensive, 20% diabetic, 50% current or prior smokers. TG/HDL-C ranged from 0.3 to 18.4 (median 2.2, first quartile 0.35 to <1.4, fourth quartile 3.66�18.4). Deaths (n=33) and CV events (n=83) increased across TG/HDL-C quartiles (both p<0.05 for trend). TG/HDL-C was a strong independent predictor of mortality in models adjusted for age, race, smoking, hypertension, diabetes, and angiographic coronary disease severity (HR 1.95, 95% CI 1.05, 3.64, p=0.04). For cardiovascular events, the multivariate HR was 1.54 (95% CI 1.05, 2.22, p=0.03) when adjusted for demographic and clinical variables, but became non-significant when angiographic results were included. Conclusion Among women with suspected ischemia, the TG/HDL-C ratio is a powerful independent predictor of all cause mortality and cardiovascular events. PMID:19249427
Bittner, Vera; Johnson, B. Delia; Zineh, Issam; Rogers, William J.; Vido, Diane; Marroquin, Oscar C.; Bairey-Merz, C. Noel; Sopko, George
Medium Chain Triglycerides in Paediatric Practice
Medium chain triglycerides (MCT) bypass the steps necessary for the absorption of long chain fats (LCT), and so have theoretical grounds for their use in various disease states, particularly malabsorptive disorders. In childhood, MCT have particular advantages since they allow restriction of dietary long chain fats without limiting the intake of protein necessary for growth while providing adequate calories. In malabsorptive states, MCT have been used mostly in cystic fibrosis, where they may reduce steatorrhoea. However, the long-term growth patterns of these children are dependent on the extent and severity of their chest disease. MCT may be a useful source of calories for those with anorexia due to infection or liver disease and in babies recovering from meconium ileus. The decrease in offensive stools, flatus, and abdominal discomfort improves well-being and social acceptability which is important for many schoolchildren and adolescents. Rectal prolapse may be helped. Where there is loss of the small intestinal absorptive surface, particularly after massive small bowel resection, MCT can help to maintain weight and nutrition. They may also be a useful supplementary nutritional measure in patients severely affected with coeliac disease while awaiting response to a gluten-free diet, and in patients with regional enteritis. In children with liver disease, MCT provide a ready source of calories while avoiding the loss of fat in their stools. Infants with neonatal hepatitis or biliary atresia remain well nourished, and some older children with liver disease grow more rapidly and have fewer and less offensive stools and less abdominal discomfort. Where an abnormal number of faecal organisms colonize the small intestine (`contaminated small bowel syndrome' or `blind loop syndrome') intraluminal bile salts become deconjugated and cause steatorrhoea. A combination of antibiotic and surgical treatment is usually indicated, but MCT can be used to improve nutrition before operation and may be indicated for associated conditions, such as massive intestinal resection. MCT have also been helpful in patients with defective chylomicron formation due to a-?-lipoproteinaemia. In the congenital and less commonly encountered acquired lymphatic disorders in childhood, MCT have given encouraging results. This group includes patients with gross protein and fat loss due to intestinal lymphangiectasia and others with lymphatic anomalies at other sites. Hyperchylomicronaemia (familial fat-induced hypertriglyceridaemia) responds well to dietary treatment with MCT. PMID:4918706
Gracey, Michael; Burke, Valerie; Anderson, Charlotte M.
High performance reversed-phase chromatography of natural triglyceride mixtures
High performance reversed-phase chromatography (HPRC) is an efficient and powerful tool gaining momentum in the separation\\u000a of triglycerides and other lipid components. In the present study the effect of different variables in triglyceride separation\\u000a has been studied. It was found that a longer hydrocarbon chain bonded to silica gel as well as the percent coverage improved\\u000a the separation. Smaller particle
A. H. El-Hamdy; E. G. Perkins
Triglyceride as a risk factor for coronary artery disease
The data for an independent association between triglyceride concentrations and risk for coronary artery disease (CAD) are equivocal, unlike the data for low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol, which show strong, consistent, and opposing correlations with CAD risk. There is some evidence for triglyceride as an independent risk factor in certain subgroups, for example, women 50�69 years
Antonio M. Gotto
TG13 management bundles for acute cholangitis and cholecystitis.
Bundles that define mandatory items or procedures to be performed in clinical practice have been increasingly used in guidelines in recent years. Observance of bundles enables improvement of the prognosis of target diseases as well as guideline preparation. There were no bundles adopted in the Tokyo Guidelines 2007, but the updated Tokyo Guidelines 2013 (TG13) have adopted this useful tool. Items or procedures strongly recommended in clinical practice have been prepared in the practical guidelines and presented as management bundles. TG13 defined the mandatory items for the management of acute cholangitis and acute cholecystitis. Critical parts of the bundles in TG13 include diagnostic process, severity assessment, transfer of patients if necessary, therapeutic approach, and time course. Their observance should improve the prognosis of acute cholangitis and cholecystitis. When utilizing TG13 management bundles, further clinical research needs to be conducted to evaluate the effectiveness and outcomes of the bundles. It is also expected that the present report will lead to evidence construction and contribute to further updating of the Tokyo Guidelines. Free full-text articles and a mobile application of TG13 are available via http://www.jshbps.jp/en/guideline/tg13.html. PMID:23307002
Okamoto, Kohji; Takada, Tadahiro; Strasberg, Steven M; Solomkin, Joseph S; Pitt, Henry A; Garden, O James; B�chler, Markus W; Yoshida, Masahiro; Miura, Fumihiko; Kimura, Yasutoshi; Higuchi, Ryota; Yamashita, Yuichi; Mayumi, Toshihiko; Gomi, Harumi; Kusachi, Shinya; Kiriyama, Seiki; Yokoe, Masamichi; Lau, Wan-Yee; Kim, Myung-Hwan
Unrefined and refined black raspberry seed oils (RSOs) were examined for their lipid-modulating effects in male Syrian hamsters fed high-cholesterol (0.12% g/g), high-fat (9% g/g) diets. Hamsters fed the refined and the unrefined RSO diets had equivalently lower plasma total cholesterol and high-density lipoprotein (HDL) cholesterol in comparison with the atherogenic coconut oil diet. The unrefined RSO treatment group did not differ in liver total and esterified cholesterol from the coconut oil-fed control animals, but the refined RSO resulted in significantly elevated liver total and esterified cholesterol concentrations. The unrefined RSO diets significantly lowered plasma triglycerides (46%; P=.0126) in comparison with the coconut oil diet, whereas the refined RSO only tended to lower plasma triglyceride (29%; P=.1630). Liver triglyceride concentrations were lower in the unrefined (46%; P=.0002) and refined (36%; P=.0005) RSO-fed animals than the coconut oil group, with the unrefined RSO diet eliciting a lower concentration than the soybean oil diet. Both RSOs demonstrated a null or moderate effect on cholesterol metabolism despite enrichment in linoleic acid, significantly lowering HDL cholesterol but not non-HDL cholesterol. Dramatically, both RSOs significantly reduced hypertriglyceridemia, most likely due to enrichment in ?-linolenic acid. As a terrestrial source of ?-linolenic acid, black RSOs, both refined and unrefined, provide a promising alternative to fish oil supplementation in management of hypertriglyceridemia, as demonstrated in hamsters fed high levels of dietary triglyceride and cholesterol. PMID:21548801
Ash, Mark M; Wolford, Kate A; Carden, Trevor J; Hwang, Keum Taek; Carr, Timothy P
Regular physical exercise has emerged, together with dietary restriction, as an effective intervention in delaying degenerative diseases and augmenting life span in rodents. The mechanisms involved remain largely unknown, although a beneficial influence on the age-related alteration of insulin sensitivity has been hypothesized. As muscle triglyceride (TG) accumulation is considered a reliable index of muscle insulin resistance, in this study we explored muscle TG content in 23-month-old male Sprague-Dawley rats subjected to life-long training. Plasma glucose, insulin, free fatty acid (FFA) and leptin levels were also measured. Both voluntary running in wheels (RW) and forced training in treadmill (TM) were studied. As RW rats weighed less than controls, a cohort of untrained animals, fed to pair weight (PW) with RW, was added to discriminate the effect of exercise from that of food restriction. Sedentary ad libitum fed rats served as controls. In 23-month-old RW rats, muscle TG content was reduced by 50% with respect to age-matched sedentary controls, while in TM group this reduction was smaller but still highly significant, and occurred independently on the changes in body fat mass. In both the trained rat groups, there was a significant decrease in circulating FFA levels and a trend to reduced insulin levels. In PW rats, muscle TG levels decreased similarly to RW rats, while plasma parameters were less modified. In particular, RW training was more effective than PW in preventing the age-related increase in circulating leptin levels. Our results suggest that voluntary exercise effectively counteracts the development of insulin resistance in the muscles of ageing rats as well as other related changes such as hyperlipacidaemia and compensatory hyperleptinaemia. Forced training or moderate food restriction appear slightly less effective than voluntary exercise in preventing age-dependent alterations in nutrient distribution and/or utilization. PMID:15489056
Novelli, Michela; Pocai, Alessandro; Skalicky, Monika; Viidik, Andrus; Bergamini, Ettore; Masiello, Pellegrino
The inhibitory effect of Oren-gedoku-to (Huanglian-Jie-Du-Tang) extract (TJ-15) on hepatic triglyceride (TG) accumulation with the progression of acute liver injury was examined in rats intoxicated with carbon tetrachloride (CCl4). TJ-15 at a dose of 100, 250 or 500 mg\\/kg body weight (BW) was orally administered to male Wistar rats aged 7 weeks, 6 h after the intraperitoneal injection of CCl4
Yoshiji Ohta; Emi Sasaki; Keiji Nishida; Mutsumi Kongo; Takahiro Hayashi; Minoru Nagata; Isao Ishiguro
OBJECTIVES: This study was designed to test the hypothesis that at any low-density lipoprotein cholesterol (LDL-C) level, other lipid parameters such as non-high-density lipoprotein cholesterol (HDL-C) levels, triglyceride (TG) levels, and the total cholesterol (TC)\\/HDL-C are still associated with an increased coronary heart disease (CHD) risk. BACKGROUND: Although LDL-C is considered to be the primary target of lipid-lowering therapy, other
B. J. Arsenault; J. S. Rana; E. S. G. Stroes; J. P. Despr�s; P. K. Shah; J. J. P. Kastelein; N. J. Wareham; S. M. Boekholdt; K. T. Khaw
Application of AAPM TG 119 to volumetric arc therapy (VMAT).
The purpose of this study was to create AAPM TG 119 benchmark plans for volumetric arc therapy (VMAT) and to compare VMAT plans with IMRT plan data. AAPM TG 119 proposes a set of test clinical cases for testing the accuracy of IMRT planning and delivery system. For these test cases, we generated two treatment plans, the first plan using 7-9 static dMLC IMRT fields and a second plan utilizing one- or two-arc VMAT technique. Dose optimization and calculations performed using 6 MV photons and Eclipse treatment planning system. Dose prescription and planning objectives were set according to the TG 119 goals. Plans were scored based on TG 119 planning objectives. Treatment plans were compared using conformity index (CI) for reference dose and homogeneity index (HI) (for D(5)-D(95)). For test cases prostate, head-and-neck, C-shape and multitarget prescription dose are 75.6 Gy, 50.4 Gy, 50 Gy and 50 Gy, respectively. VMAT dose distributions were comparable to dMLC IMRT plans. Our planning results matched TG 119 planning results. For treatment plans studied, conformity indices ranged from 1.05-1.23 (IMRT) and 1.04-1.23 (VMAT). Homogeneity indices ranged from 4.6%-11.0% (IMRT) and 4.6%-10.5% (VMAT). The ratio of total monitor units necessary for dMLC IMRT to that of VMAT was in the range of 1.1-2.0. AAPM TG 119 test cases are useful to generate VMAT benchmark plans. At preclinical implementation stage, plan comparison of VMAT and IMRT plans of AAPM TG 119 test case allowed us to understand basic capabilities of VMAT technique. PMID:22955639
Mynampati, Dinesh Kumar; Yaparpalvi, Ravindra; Hong, Linda; Kuo, Hsiang-Chi; Mah, Dennis
Background Nonalcoholic fatty liver disease (NAFLD) is one of the critical public health problems in China. The full spectrum of the disease ranges from simple steatosis and nonalcoholic steatohepatitis (NASH) to cirrhosis and hepatocellular carcinoma(HCC). The infiltration of inflammatory cells characterizes NASH. This characteristic contributes to the progression of hepatitis, fibrosis, cirrhosis, and HCC. Therefore, distinguishing NASH from NAFLD is crucial. Objective and Methods Ninety-five patients with NAFLD, 44 with NASH, and 51 with non-NASH were included in the study to develop a new scoring system for differentiating NASH from NAFLD. Data on clinical and biological characteristics, as well as blood information, were obtained. Cytokeratin-18 (CK-18) fragments levels were measured using an enzyme-linked immunosorbant assay. Results Several indexes show significant differences between the two groups, which include body mass index (BMI), waist-on-hip ratio (WHR), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), ?-glutamyl transpeptidase (?-GT), platelets, uric acid (UA), hs-C-reactive protein (hs-CRP), triglycerides (TG), albumin (ALB), and CK-18 fragments (all P < 0.05). The CK-18 fragment levels showed a significant positive correlation with steatosis severity, ballooning, lobular inflammation, and fibrosis stage (all P < 0.05). Therefore, a new model that combines ALT, platelets, CK-18 fragments, and TG was established by logistic regression among NAFLD patients. The AUROC curve in predicting NASH was 0.920 (95% CI: 0.866 - 0.974, cutoff value = 0.361, sensitivity = 89%, specificity = 86%, positive predictive value = 89%, negative predictive value = 89%). Conclusion The novel scoring system may be considered as a useful model in predicting the presence of NASH in NAFLD patients. PMID:24324749
Cao, Wei; Zhao, Caiyan; Shen, Chuan; Wang, Yadong
Background Abnormal accumulation of amyloid ?-protein (A?) in the brain plays an important role in the pathogenesis \\of Alzheimer�s disease (AD). A? monomers assemble into oligomers and fibrils that promote neuronal dysfunction. This assembly pathway is influenced by naturally occurring brain molecules, the A? chaperone proteins, which bind to A? and modulate its aggregation. Myelin basic protein (MBP) was previously identified as a novel A? chaperone protein and a potent inhibitor for A? fibril assembly in vitro. Methods In this study, we determined whether the absence of MBP would influence A? pathology in vivo by breeding MBP knockout mice (MBP-/-) with Tg-5xFAD mice, a model of AD-like parenchymal A? pathology. Results Through biochemical and immunohistochemical experiments, we found that bigenic Tg-5xFAD/MBP-/- mice had a significant decrease of insoluble A? and parenchymal plaque deposition at an early age. The expression of transgene encoded human A?PP, the levels of C-terminal fragments generated during A? production and the intracellular A? were unaffected in the absence of MBP. Likewise, we did not find a significant difference in plasma A? or cerebrospinal fluid A?, suggesting these clearance routes were unaltered in bigenic Tg-5xFAD/MBP-/- mice. However, MBP-/- mice and bigenic Tg-5xFAD/MBP-/- mice exhibited elevated reactive astrocytes and activated microglia compared with Tg-5xFAD mice. The A? degrading enzyme matrix metalloproteinase 9 (MMP-9), which is expressed by activated glial cells, was significantly increased in the Tg-5xFAD/MBP-/- mice. Conclusions These findings indicate that the absence of MBP decreases A? deposition in transgenic mice and that this consequence may result from increased glial activation and expression of MMP-9, an A? degrading enzyme. PMID:24188129
Seventy percent ethanol-water extract from the leaves of Mangifera indica L. (Anacardiaceae) was found to show an inhibitory effect on triglyceride (TG) accumulation in 3T3-L1 cells. From the active fraction, six new benzophenone C-glucosides, foliamangiferosides A(3) (1), A(4) (2), C(4) (3), C(5) (4), C(6) (5), and C(7) (6) together with 11 known benzophenone C-glucosides (7-17) were obtained. In this paper, isolation, structure elucidation (1-6), and MS fragment cleavage pathways of all 17 isolates were studied. 1-6 showed inhibitory effects on TG and free fatty acid accumulation in 3T3-L1 cells at 10 ?M. PMID:23368644
Zhang, Yi; Han, Lifeng; Ge, Dandan; Liu, Xuefeng; Liu, Erwei; Wu, Chunhua; Gao, Xiumei; Wang, Tao
We examined cross-sectionally which lipid profiles are associated with better cognitive function among those aged 80 and older-free of dementia (Clinical Dementia Rating ? 0.5), functionally independent and community-dwelling. Our cohort consisted of 193 participants from the �Keys to Optimal Cognitive Aging (KOCOA) Project�, a prospective cohort study in Okinawa, Japan. Higher low-density lipoprotein cholesterol levels and lower triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) ratios were associated with higher scores in memory performance after controlling for confounders. Further research is required to clarify the associations among LDL-C levels, TG/HDL-C ratios, and healthy cognitive aging. PMID:23207484
Katsumata, Yuriko; Todoriki, Hidemi; Higashiuesato, Yasushi; Yasura, Shotoku; Ohya, Yusuke; Willcox, D. Craig; Dodge, Hiroko H.
Tg and Cure of a Polycyanurate at the Nanoscale
NASA Astrophysics Data System (ADS)
Nanoscale constraint is known to have a significant impact on the thermal properties of materials. Although thermosetting resins have been cured in the presence of nanoparticles and nanotubes, cure of thermosetting resins under the well defined nanoscale constraints imposed by controlled pore glass (CPG) or similar matrices has not been previously documented. In this work, we investigate the isothermal curing under nanoscale constraint of a thermosetting resin, bisphenol M dicyanate ester (BMDC), which trimerizes to form a polycyanurate network material. Differential scanning calorimeter is used to monitor the evolution of the glass transition temperature (Tg) and the conversion during cure as a function of the diameter of the silanized control pore glass matrix which is used for confinement. A Tg depression is observed for both the bisphenol M dicyanate ester monomer and the polycyanurate networks; the depression is only a few degrees for the monomer, whereas a 56 K depression is observed for the ``fully-cured'' network in 11.5 nm pores. The nanoscale constraint is also found to accelerate the cure of the bisphenol M dicyanate ester, but it does not affect the normalized Tg versus conversion relationship. The appearance of a secondary Tg above the primary Tg in the smaller pores and the associated length scale are discussed.
Simon, Sindee; Li, Qingxiu
Vector Percolation Analysis of Triglyceride-based Thermoset Polymers
NASA Astrophysics Data System (ADS)
Thermosetting Acrylated triglycerides (ATG) were prepared from various oils and model triglycerides. The distribution of acrylate groups was calculated from the distribution of unsaturation sites on unmodified oils, assuming a binomial distribution of acrylate groups. The ATG were both homopolymerized and copolymerized with styrene. The cross-link density v, of the polymers was calculated using the recursive method of Miller and Macosko from a knowledge of the acrylate distribution. The cross-link density was found to increase with the level of acrylation A, in a vector percolation manner, and the trends in the cross-link density predictions matched the experimental results. The deviation in the experimental results and model predictions were the result of intramolecular cross-linking. Approximately 0.5 and 0.8 acrylates per triglyceride were lost to intramolecular cyclization for homopolymerized acrylated triglycerides and triglycerides copolymerized with styrene, respectively. Equations for the level of perfection p, of the triglyceride networks and the percolation threshold pc, were developed using the calculated number of acrylates lost to cyclization. Polymers with p < 0.1 without styrene, and p < 0.39 with styrene did not have mechanical integrity, validating the definition of the level of perfection and percolation threshold pc. The tensile strength, S � [p-p]^1/2 and modulus E � [p-pc]^3 , were in accord with vector percolation theory, where p could be derived experimentally via A � [p-pc] , v � A and FTIR analysis of the extent of reaction of the C=C groups. These results also indicated how mechanical properties were controlled by the fatty acid distribution function of the plant oils, and which oil would give the best particular property. Supported by EPA and DoE.
Lascala, John J.; Wool, Richard P.
In Asian populations, diabetes mellitus is increasing and has become an important health problem in recent decades. Cardiovascular disease (CVD) is one of the most important complications and the most common cause of death in diabetic patients. Among the risk factors of CVD, elevated low-density lipoprotein cholesterol has been a major concern. Studies suggested that serum triglyceride may also play a role in predicting CVD in patients with type 2 diabetes mellitus, but the association is still debated. In this review, we summarized published studies focusing on the relationship between serum triglyceride and CVD disease in Asian diabetic patients. Ten studies conducted in six different Asian countries (three from Hong Kong, two from Taiwan, tow from Japan, one from Indonesia, one from South India, and one from South Korea) were summarized and discussed. CVD was subdivided into coronary heart disease, stroke, and peripheral arterial disease. Of the ten studies analyzed, one focused on CVD, five on coronary heart disease, three on stroke, three on peripheral arterial disease, and one on mortality from CVD. Studies from Hong Kong, Taiwan, and Japan suggested that triglyceride is a significant and independent risk factor for coronary heart disease, but not a significant risk factor for stroke (studies conducted in Japan and South Korea) or peripheral arterial disease (studies conducted in Taiwan, Indonesia, and South India). Although serum triglyceride may be a significant risk factor for coronary heart disease in Asian diabetic patients, clinical trials evaluating whether lowering triglycerides using fibrates can reduce the risk of coronary heart disease in these patients need to be initiated. PMID:24380086
Chen, Ai-Hua; Tseng, Chin-Hsiao
TG13 antimicrobial therapy for acute cholangitis and cholecystitis.
Therapy with appropriate antimicrobial agents is an important component in the management of patients with acute cholangitis and/or acute cholecystitis. In the updated Tokyo Guidelines (TG13), we recommend antimicrobial agents that are suitable from a global perspective for management of these infections. These recommendations focus primarily on empirical therapy (presumptive therapy), provided before the infecting isolates are identified. Such therapy depends upon knowledge of both local microbial epidemiology and patient-specific factors that affect selection of appropriate agents. These patient-specific factors include prior contact with the health care system, and we separate community-acquired versus healthcare-associated infections because of the higher risk of resistance in the latter. Selection of agents for community-acquired infections is also recommended on the basis of severity (grades I-III). Free full-text articles and a mobile application of TG13 are available via http://www.jshbps.jp/en/guideline/tg13.html. PMID:23340954
Gomi, Harumi; Solomkin, Joseph S; Takada, Tadahiro; Strasberg, Steven M; Pitt, Henry A; Yoshida, Masahiro; Kusachi, Shinya; Mayumi, Toshihiko; Miura, Fumihiko; Kiriyama, Seiki; Yokoe, Masamichi; Kimura, Yasutoshi; Higuchi, Ryota; Windsor, John A; Dervenis, Christos; Liau, Kui-Hin; Kim, Myung-Hwan
Background & objectives: Reusable biostrip consisting enzymes immobilized onto alkylamine glass beads affixed on plasticized PVC strip for determination of triglyceride (TG) suffers from high cost of beads and their detachments during washings for reuse, leading to loss of activity. The purpose of this study was to develop a cheaper and stable biostrip for investigation of TG levels in serum. Methods: A reusable enzyme-strip was prepared for TG determination by co-immobilizing lipase, glycerol kinase (GK), glycerol-3-phosphate oxidase (GPO) and peroxidase (HRP) directly onto plasticized polyvinyl chloride (PVC) strip through glutaraldehyde coupling. The method was evaluated by studying its recovery, precision and reusability. Results: The enzyme-strip showed optimum activity at pH 7.0, 35�C and a linear relationship between its activity and triolein concentration in the range 0.1 to 15 mM. The strip was used for determination of serum TG. The detection limit of the method was 0.1 mM. Analytical recovery of added triolein was 96 per cent. Within and between batch coefficients of variation (CV) were 2.2 and 3.7 per cent, respectively. A good correlation (r=0.99) was found between TG values by standard enzymic colrimetric method employing free enzymes and the present method. The strip lost 50 per cent of its initial activity after its 200 uses during the span of 100 days, when stored at 4�C. Interpretation & conclusions: The nitrating acidic treatment of plasticized PVC strip led to glutaraldehyde coupling of four enzymes used for enzymic colourimetric determination of serum TG. The strip provided 200 reuses of enzymes with only 50 per cent loss of its initial activity. The method could be used for preparation of other enzyme strips also. PMID:24927348
Chauhan, Nidhi; Narang, Jagriti; Pundir, Chandra Shekhar
Ultrasound assisted transesterification of triglycerides (TG) with methanol in the presence of KOH catalyst was investigated, where the changes in the reactants and products (diglycerides (DG), monoglycerides (MG), fatty acid methyl esters (FAME) and glycerin (GL)) concentrations were discussed to understand the reaction mechanism and kinetics under ultrasound irradiation. The optimum reaction condition for the FAME production was the concentration of KOH 1.0 wt.%, molar ratio of TG to methanol of 1:6, and irradiation time of 25 min. The rate constants during the TG transesterification with methanol into GL and FAME were estimated by a curve fitting method with simulated curves to the obtained experimental results. The rate constants of [Formula: see text] were estimated to be 0.21, 0.008, 0.23, 0.005, 0.14 and 0.001 L mol(-1)min(-1), respectively. The rate determining step for the TG transesterification with methanol into GL and FAME was the reaction of MG with methanol into GL and FAME. PMID:24161255
Thanh, Le Tu; Okitsu, Kenji; Maeda, Yasuaki; Bandow, Hiroshi
In a previous investigation, we found that murine MoAb 42C3, raised against human Tg, recognized Tg differently depending upon its level of iodination of Tg. A possible explanation for this finding is that iodine is directly involved with the specific epitope recognized by MoAb 42C3. In the present study, we report that the binding of MoAb 42C3 to iodinated Tg is inhibited by T4, T3, reverse T3 (rT3), triiodothyroacetic acid (triac), diiodothyronine (T2), diiodotyrosine (DIT), but not by thyronine (TO) or tyrosine. The order of inhibition of these iodinated compounds is T4 > T3 > rT3 > triac > T2 > DIT. The MoAb 42C3 does not have the same specificity as the T3, T4-receptor since the order of binding of these iodinated compounds on the receptor differed from the order of their inhibition of this MoAb. Monoclonal antibody 42C3 also recognized non-iodinated Tg that was subsequently iodinated in vitro. It failed to recognize another protein, bovine serum albumin, that was iodinated in vitro by the same method. These results suggest that iodinated tyrosines and thyronines determine the binding specificity of MoAb 42C3. The inhibitory effects of these compounds on MoAb 42C3 depend on their iodine content as well as location of iodine in the aromatic ring. PMID:9717982
Saboori, A M; Rose, N R; Burek, C L
A rare variant in APOC3 is associated with plasma triglyceride and VLDL levels in Europeans
The analysis of rich catalogues of genetic variation from population-based sequencing provides an opportunity to screen for functional effects. Here we report a rare variant in APOC3 (rs138326449-A, minor allele frequency ~0.25% (UK)) associated with plasma triglyceride (TG) levels (?1.43 s.d. (s.e.=0.27 per minor allele (P-value=8.0 � 10?8)) discovered in 3,202 individuals with low read-depth, whole-genome sequence. We replicate this in 12,831 participants from five additional samples of Northern and Southern European origin (?1.0 s.d. (s.e.=0.173), P-value=7.32 � 10?9). This is consistent with an effect between 0.5 and 1.5?mmol?l?1 dependent on population. We show that a single predicted splice donor variant is responsible for association signals and is independent of known common variants. Analyses suggest an independent relationship between rs138326449 and high-density lipoprotein (HDL) levels. This represents one of the first examples of a rare, large effect variant identified from whole-genome sequencing at a population scale. PMID:25225788
Timpson, Nicholas J.; Walter, Klaudia; Min, Josine L.; Tachmazidou, Ioanna; Malerba, Giovanni; Shin, So-Youn; Chen, Lu; Futema, Marta; Southam, Lorraine; Iotchkova, Valentina; Cocca, Massimiliano; Huang, Jie; Memari, Yasin; McCarthy, Shane; Danecek, Petr; Muddyman, Dawn; Mangino, Massimo; Menni, Cristina; Perry, John R. B.; Ring, Susan M.; Gaye, Amadou; Dedoussis, George; Farmaki, Aliki-Eleni; Burton, Paul; Talmud, Philippa J.; Gambaro, Giovanni; Spector, Tim D.; Smith, George Davey; Durbin, Richard; Richards, J Brent; Humphries, Steve E.; Zeggini, Eleftheria; Soranzo, Nicole; Al Turki, Saeed; Anderson, Carl; Anney, Richard; Antony, Dinu; Soler Artigas, Maria; Ayub, Muhammad; Balasubramaniam, Senduran; Barrett, Jeffrey C.; Barroso, In�s; Beales, Phil; Bentham, Jamie; Bhattacharya, Shoumo; Birney, Ewan; Blackwood, Douglas; Bobrow, Martin; Bochukova, Elena; Bolton, Patrick; Bounds, Rebecca; Boustred, Chris; Breen, Gerome; Calissano, Mattia; Carss, Keren; Chatterjee, Krishna; Chen, Lu; Ciampi, Antonio; Cirak, Sebhattin; Clapham, Peter; Clement, Gail; Coates, Guy; Collier, David; Cosgrove, Catherine; Cox, Tony; Craddock, Nick; Crooks, Lucy; Curran, Sarah; Curtis, David; Daly, Allan; Danecek, Petr; Davey Smith, George; Day-Williams, Aaron; Day, Ian N. M.; Down, Thomas; Du, Yuanping; Dunham, Ian; Durbin, Richard; Edkins, Sarah; Ellis, Peter; Evans, David; Faroogi, Sadaf; Fatemifar, Ghazaleh; Fitzpatrick, David R.; Flicek, Paul; Flyod, James; Foley, A Reghan; Franklin, Christopher S; Futema, Marta; Gallagher, Louise; Gaunt, Tom; Geihs, Matthias; Geschwind, Daniel; Greenwood, Celia; Griffin, Heather; Grozeva, Detelina; Guo, Xueqin; Guo, Xiaosen; Gurling, Hugh; Hart, Deborah; Hendricks, Audrey; Holmans, Peter; Howie, Bryan; Huang, Jie; Huang, Liren; Hubbard, Tim; Humphries, Steve E.; Hurles, Matthew E.; Hysi, Pirro; Jackson, David K.; Jamshidi, Yalda; Jing, Tian; Joyce, Chris; Kaye, Jane; Keane, Thomas; Keogh, Julia; Kemp, John; Kennedy, Karen; Kolb-Kokocinski, Anja; Lachance, Genevieve; Langford, Cordelia; Lawson, Daniel; Lee, Irene; Lek, Monkol; Liang, Jieqin; Lin, Hong; Li, Rui; Li, Yingrui; Liu, Ryan; L�nnqvist, Jouko; Lopes, Margarida; Lotchkova, Valentina; MacArthur, Daniel; Marchini, Jonathan; Maslen, John; Massimo, Mangino; Mathieson, Iain; Marenne, Ga�lle; McCarthy, Shane; McGuffin, Peter; McIntosh, Andrew; McKechanie, Andrew G.; McQuillin, Andrew; Memari, Yasin; Metrustry, Sarah; Min, Josine; Mitchison, Hannah; Moayyeri, Alireza; Morris, James; Muddyman, Dawn; Muntoni, Francesco; Northstone, Kate; O'Donnovan, Michael; Onoufriadis, Alexandros; O'Rahilly, Stephen; Oualkacha, Karim; Owen, Michael J.; Palotie, Aarno; Panoutsopoulou, Kalliope; Parker, Victoria; Parr, Jeremy R.; Paternoster, Lavinia; Paunio, Tiina; Payne, Felicity; Perry, John; Pietilainen, Olli; Plagnol, Vincent; Quaye, Lydia; Quail, Michael A.; Raymond, Lucy; Rehnstr�m, Karola; Richards, Brent; Ring, Susan; Ritchie, Graham R. S.; Roberts, Nicola; Savage, David B.; Scambler, Peter; Schiffels, Stephen; Schmidts, Miriam; Schoenmakers, Nadia; Semple, Robert K.; Serra, Eva; Sharp, Sally I.; Shihab, Hasheem; Shin, So-Youn; Skuse, David; Small, Kerrin; Soranzo, Nicole; Southam, Lorraine; Spasic-Boskovic, Olivera; Spector, Tim; St Clair, David; Stalker, Jim; Stevens, Elizabeth; St Pourcian, Beate; Sun, Jianping; Surdulescu, Gabriela; Suvisaari, Jaana; Tachmazidou, Ionna; Timpson, Nicholas; Tobin, Martin D.; Valdes, Ana; Van Kogelenberg, Margriet; Vijayarangakannan, Parthiban; Visscher, Peter M.; Wain, Louise V.; Walter, Klaudia; Walters, James T. R.; Wang, Guangbiao; Wang, Jun; Wang, Yu; Ward, Kirsten; Wheeler, Elanor; Whyte, Tamieka; Williams, Hywel; Williamson, Kathleen A.; Wilson, Crispian; Wilson, Scott G.; Wong, Kim; Xu, ChangJiang; Yang, Jian; Zeggini, Eleftheria; Zhang, Fend; Zhang, Pingbo; Zheng, Hou-Feng
In vivo clearance of chylomicron triglycerides containing w-3 eicosapentaenoic acid
The in vivo clearance of chylomicron triglycerides (TG) enriched in either oleic acid (OA) or w-3 eicosapentaenoic acid (EPA) was compared. Chylomicrons were obtained from the mesenteric lymph (0-6 h) of rats, administered either 0.3 mM (1-/sup 14/C) OA or (1-/sup 14/C) EPA as an intraduodenal aqueous emulsion. The chylomicrons enriched with (1-/sup 14/C) OA or (1-/sup 14/C) EPA were isolated and purified by ultracentrifugation, and were injected into the jugular vein of recipient anesthetized rats. There was no significant difference between the two groups when total serum radioactivity was compared at 2, 5, and 10 min. However, at 25, 60, and 90 min, the clearance of EPA-enriched chylomicrons was significantly slower (P < 0.05). At each time analyzed the distribution of (/sup 14/C) oleic acid and of EPA among serum lipoproteins was comparable. After 5 min of chylomicron infusion the d < 1.006 g/ml lipoproteins contained almost 90% of the injected chylomicron radioactivity, while by 240 min, this fraction retained 42% of the remaining isotope. These and earlier studies suggested that the absorption and chylomicron transport of EPA in the intestine is not unusual, and that clearance of EPA-enriched chylomicrons may be only slightly slower than those enriched with oleate.
Chen, I.S.; Satchithanandum, S.; Cassidy, M.M.; Sheppard, A.J.; Vahouny, G.V.
A rare variant in APOC3 is associated with plasma triglyceride and VLDL levels in Europeans.
The analysis of rich catalogues of genetic variation from population-based sequencing provides an opportunity to screen for functional effects. Here we report a rare variant in APOC3 (rs138326449-A, minor allele frequency ~0.25% (UK)) associated with plasma triglyceride (TG) levels (-1.43 s.d. (s.e.=0.27 per minor allele (P-value=8.0 � 10(-8))) discovered in 3,202 individuals with low read-depth, whole-genome sequence. We replicate this in 12,831 participants from five additional samples of Northern and Southern European origin (-1.0 s.d. (s.e.=0.173), P-value=7.32 � 10(-9)). This is consistent with an effect between 0.5 and 1.5?mmol?l(-1) dependent on population. We show that a single predicted splice donor variant is responsible for association signals and is independent of known common variants. Analyses suggest an independent relationship between rs138326449 and high-density lipoprotein (HDL) levels. This represents one of the first examples of a rare, large effect variant identified from whole-genome sequencing at a population scale. PMID:25225788
Timpson, Nicholas J; Walter, Klaudia; Min, Josine L; Tachmazidou, Ioanna; Malerba, Giovanni; Shin, So-Youn; Chen, Lu; Futema, Marta; Southam, Lorraine; Iotchkova, Valentina; Cocca, Massimiliano; Huang, Jie; Memari, Yasin; McCarthy, Shane; Danecek, Petr; Muddyman, Dawn; Mangino, Massimo; Menni, Cristina; Perry, John R B; Ring, Susan M; Gaye, Amadou; Dedoussis, George; Farmaki, Aliki-Eleni; Burton, Paul; Talmud, Philippa J; Gambaro, Giovanni; Spector, Tim D; Smith, George Davey; Durbin, Richard; Richards, J Brent; Humphries, Steve E; Zeggini, Eleftheria; Soranzo, Nicole
The inhibitory effect of Oren-gedoku-to (Huanglian-Jie-Du-Tang) extract (TJ-15) on hepatic triglyceride (TG) accumulation with the progression of acute liver injury was examined in rats intoxicated with carbon tetrachloride (CCl4). TJ-15 at a dose of 100, 250 or 500 mg/kg body weight (BW) was orally administered to male Wistar rats aged 7 weeks, 6 h after the intraperitoneal injection of CCl4 (1.0 ml/kg BW) at which time apparent liver injury and hepatic TG accumulation occurred. TJ-15 significantly prevented not only the progression of liver injury but also inhibited hepatic TG accumulation with the progression of the injury in a dose-dependent manner when these effects were examined 24 h after CCl4 injection. In CCl4-untreated rats with oral administration of TJ-15 at a dose of 100, 250 or 500 mg/kg BW, liver and serum TG concentrations decreased depending on the dose of the herbal medicine. These results indicate that in rats intoxicated once with CCl4, orally administered TJ-15 can inhibit hepatic TG accumulation with the progression of acute liver injury by its decreasing action on serum and liver TG levels, leading to a prevention of the progression of the liver injury. PMID:9687084
Ohta, Y; Sasaki, E; Nishida, K; Kongo, M; Hayashi, T; Nagata, M; Ishiguro, I
Mutations of the Microsomal Triglyceride-Transfer-Protein Gene in Abetalipoproteinemia
Elevated plasma levels of apolipoprotein B (apoB)�containing lipoproteins constitute a major risk factor for the development of coronary heart disease. In the rare recessively inherited disorder abetalipoproteinemia (ABL) the production of apoB-containing lipoproteins is abolished, despite no abnormality of the apoB gene. In the current study we have characterized the gene encoding a microsomal triglyceride-transfer protein (MTP), localized to chromosome 4q22-24, and have identified a mutation of the MTP gene in both alleles of all individuals in a cohort of eight patients with classical ABL. Each mutant allele is predicted to encode a truncated form of MTP with a variable number of aberrant amino acids at its C-terminal end. Expression of genetically engineered forms of MTP in Cos-1 cells indicates that the C-terminal portion of MTP is necessary for triglyceride-transfer activity. Deletion of 20 amino acids from the carboxyl terminus of the 894-amino-acid protein and a missense mutation of cysteine 878 to serine both abolished activity. These results establish that defects of the MTP gene are the predominant, if not sole, cause of hereditary ABL and that an intact carboxyl terminus is necessary for activity. ImagesFigure 1p1304-aFigure 3Figure 4 PMID:8533758
Narcisi, Teresa M. E.; Shoulders, Carol C.; Chester, S. Ann; Read, Jacqueline; Brett, David J.; Harrison, Georgina B.; Grantham, Tamsin T.; Fox, Margaret F.; Povey, Sue; de Bruin, Tjerk W. A.; Erkelens, D. Willem; Muller, David P. R.; Lloyd, June K.; Scott, James
Absence of Microsomal Triglyceride Transfer Protein in Individuals with Abetalipoproteinemia
Abetalipoproteinemia is a human genetic disease that is characterized by a defect in the assembly or secretion of plasma very low density lipoproteins and chylomicrons. The microsomal triglyceride transfer protein (MTP), which is located in the lumen of microsomes isolated from the liver and intestine, has been proposed to function in lipoprotein assembly. MTP activity and the 88-kilodalton component of
John R. Wetterau; Lawrence P. Aggerbeck; Marie-Elisabeth Bouma; Claude Eisenberg; Anne Munck; Michel Hermier; Jacques Schmitz; Gerard Gay; Daniel J. Rader; Richard E. Gregg
Triglyceride accumulation protects against fatty acid-induced lipotoxicity
Excess lipid accumulation in non-adipose tissues is associated with insulin resistance, pancreatic -cell apoptosis and heart failure. Here, we demonstrate in cultured cells that the relative toxicity of two common dietary long chain fatty acids is related to channeling of these lipids to distinct cellular metabolic fates. Oleic acid supplementation leads to triglyceride accumulation and is well tolerated, whereas excess
Laura L. Listenberger; Xianlin Han; Sarah E. Lewis; Sylvaine Cases; Robert V. Farese Jr.; Daniel S. Ory; Jean E. Schaffer
Phase behaviour in binary mixed Langmuir Blodgett monolayers of triglycerides
Binary mixed monolayers of the triglycerides (TAGs)-tripalmitin (PPP), tristearin (SSS) and triarachidin (AAA) at the air water interface are investigated with the Langmuir method. Langmuir Blodgett (LB) layers obtained by deposition on mica are investigated by Atomic Force Microscopy. Combining Langmuir and AFM results the relation between the phase behaviour of binary mixed TAGs and their chain length is established.
Aneliya N. Zdravkova; J. P. J. M. van der Eerden
Synthesis and characterization of triglyceride based thermosetting polymers
Plant oils, which are found in abundance in all parts of the world and are easily replenished annually, have the potential to replace petroleum as a chemical feedstock for making polymers. Within the past few years, there has been growing interest to use triglycerides as the basic constituent of thermosetting polymers with the necessary rigidity, strength and glass transition temperatures
Erde Can
Solvent free triglyceride synthesis using lipozyme TM IM20
Summary The synthesis of triglycerides using LipozymeTM IM-20 (Mucor miehei lipase immobilized on weak anion exchange resins by Novo) is described. Use of pure substrates in stoichiometric amounts in the absence of any organic solvent enables high conversion to be obtained with the addition of molecular sieves to remove water produced by the reaction.
F. Ergan; M. Trani; G. Andr�
Calorimetric Tg and Heat Capacity of Polystyrene Thin Films
NASA Astrophysics Data System (ADS)
The glass transition temperature and the absolute heat capacity of polystyrene thin films were measured using the step-scan method of differential scanning calorimetry. The glass transition temperature is found to be depressed 8 K for a sample of stacked 17 nm thick films and Tg is depressed 3 K for a sample of stacked 61 nm thick films. The results are consistent with data in the literature for the Tg depression in supported polystyrene films although our films are expected to be ``freely standing'' for the initial DSC scan. In addition, the absolute heat capacity in both the liquid and glassy states decreases with decreasing film thickness, the step change in heat capacity at the glass transition temperature decreases with decreasing film thickness, and the breadth of the transition region increases with decreasing film thickness. The effect of heating the thin film samples to 135 C, approximately 40 C above their Tgs, is a slight increase in the absolute heat capacity and a slight increase in Tg. No significant changes occur on subsequent scans. The ``thin film'' morphology is maintained in spite of scanning to above Tg where the stacked film sample is expected to lose its free surface.
Koh, Yung; McKenna, Gregory; Simon, Sindee
The map asymptotics constant tg Edward A. Bender
The map asymptotics constant tg Edward A. Bender Department of Mathematics University of California of the edge. With Mn,g the number of rooted maps on g with n edges, Bender and Canfield [1] showed that Mn are t0 = 2 , t1 = 1 24 and t2 = 7 4320 . Gao [3] showed that many other interesting families of maps
Gao, Jason Zhicheng
Neurobiology Impaired Rapid Eye Movement Sleep in the Tg2576
Neurobiology Impaired Rapid Eye Movement Sleep in the Tg2576 APP Murine Model of Alzheimer of Medicine, Philadelphia, Pennsylvania Impaired rapid eye movement sleep (REMS) is com- monly observed is rapid eye movement sleep (REMS) im- pairment that commonly includes reductions in both the total sleep
Wood, Marcelo A.
TG13 miscellaneous etiology of cholangitis and cholecystitis.
This paper describes typical diseases and morbidities classified in the category of miscellaneous etiology of cholangitis and cholecystitis. The paper also comments on the evidence presented in the Tokyo Guidelines for the management of acute cholangitis and cholecystitis (TG 07) published in 2007 and the evidence reported subsequently, as well as miscellaneous etiology that has not so far been touched on. (1) Oriental cholangitis is the type of cholangitis that occurs following intrahepatic stones and is frequently referred to as an endemic disease in Southeast Asian regions. The characteristics and diagnosis of oriental cholangitis are also commented on. (2) TG 07 recommended percutaneous transhepatic biliary drainage in patients with cholestasis (many of the patients have obstructive jaundice or acute cholangitis and present clinical signs due to hilar biliary stenosis or obstruction). However, the usefulness of endoscopic naso-biliary drainage has increased along with the spread of endoscopic biliary drainage procedures. (3) As for biliary tract infections in patients who underwent biliary tract surgery, the incidence rate of cholangitis after reconstruction of the biliary tract and liver transplantation is presented. (4) As for primary sclerosing cholangitis, the frequency, age of predilection and the rate of combination of inflammatory enteropathy and biliary tract cancer are presented. (5) In the case of acalculous cholecystitis, the frequency of occurrence, causative factors and complications as well as the frequency of gangrenous cholecystitis, gallbladder perforation and diagnostic accuracy are included in the updated Tokyo Guidelines 2013 (TG13). Free full-text articles and a mobile application of TG13 are available via http://www.jshbps.jp/en/guideline/tg13.html. PMID:23307005
Higuchi, Ryota; Takada, Tadahiro; Strasberg, Steven M; Pitt, Henry A; Gouma, Dirk J; Garden, O James; B�chler, Markus W; Windsor, John A; Mayumi, Toshihiko; Yoshida, Masahiro; Miura, Fumihiko; Kimura, Yasutoshi; Okamoto, Kohji; Gabata, Toshifumi; Hata, Jiro; Gomi, Harumi; Supe, Avinash N; Jagannath, Palepu; Singh, Harijt; Kim, Myung-Hwan; Hilvano, Serafin C; Ker, Chen-Guo; Kim, Sun-Whe
Adipose triglyceride lipase (ATGL), the rate-limiting enzyme for triacylglycerol (TG) hydrolysis, has long been known to be a phosphoprotein. However, the potential phosphorylation events that are involved in the regulation of ATGL function remain incompletely defined. Here, using a combinatorial proteomics approach, we obtained evidence that at least eight different sites of ATGL can be phosphorylated in adipocytes. Among them, Thr�?� resides within the hydrophobic region known to mediate lipid droplet (LD) targeting. Although it had no impact on the TG hydrolase activity, substitution of phosphorylation-mimic Asp for Thr�?� eliminated LD localization and LD-degrading capacity of ATGL expressed in HeLa cells. In contrast, mutation of Thr�?� to Ala gave a protein that bound LDs and functioned the same as the wild-type protein. In nonstimulated adipocytes, the Asp mutation led to decreased LD association and basal lipolytic activity of ATGL, whereas the Ala mutation produced opposite effects. Moreover, the LD translocation of ATGL upon ?-adrenergic stimulation was also compromised by the Asp mutation. In accord with these findings, the Ala mutation promoted and the Asp mutation attenuated the capacity of ATGL to mediate lipolysis in adipocytes under both basal and stimulated conditions. Collectively, these studies identified Thr�?� as a novel phosphorylation site that may play a critical role in determining subcellular distribution as well as lipolytic action of ATGL. PMID:24801391
Xie, Xitao; Langlais, Paul; Zhang, Xiaodong; Heckmann, Bradlee L; Saarinen, Alicia M; Mandarino, Lawrence J; Liu, Jun
Pancreatic cancer (PC) is among the deadliest cancers, with a median survival of six months. It is generally believed that infiltrating PC arises through the progression of early grade pancreatic intraepithelial lesions (PanINs). In one model of the disease, the K-ras mutation is an early molecular event during progression of pancreatic cancer; it is followed by the accumulation of additional genetic abnormalities. This model has been supported by animal studies in which activated K-ras and p53 mutations produced metastatic pancreatic ductal adenocarcinoma in mice. According to this model, oncogenic K-ras induces PanIN formation but fails to promote the invasive stage. However, when these mice are subjected to caerulein treatment, which induces a chronic pancreatitis-like state and inflammatory response, PanINs rapidly progress to invasive carcinoma. These results are consistent with epidemiologic studies showing that patients with chronic pancreatitis have a much higher risk of developing PC. In line with these observations, recent studies have revealed elevated expression of the pro-inflammatory protein tissue transglutaminase (TG2) in early PanINs, and its expression increases even more as the disease progresses. In this review we discuss the implications of increased TG2 expression in initiation, progression, and pathogenesis of pancreatic cancer. PMID:24212645
Mehta, Kapil; Han, Amy
Deficits of protein phosphatase-2A (PP2A) play a crucial role in tau hyperphosphorylation, amyloid overproduction, and synaptic suppression of Alzheimer's disease (AD), in which PP2A is inactivated by the endogenously increased inhibitory protein, namely inhibitor-2 of PP2A (I2(PP2A)). Therefore, in vivo silencing I2(PP2A) may rescue PP2A and mitigate AD neurodegeneration. By infusion of lentivirus-shRNA targeting I2(PP2A) (LV-siI2(PP2A)) into hippocampus and frontal cortex of 11-month-old tg2576 mice, we demonstrated that expression of LV-siI2(PP2A) decreased remarkably the elevated I2(PP2A) in both mRNA and protein levels. Simultaneously, the PP2A activity was restored with the mechanisms involving reduction of the inhibitory binding of I2(PP2A) to PP2A catalytic subunit (PP2AC), repression of the inhibitory Leu309-demethylation and elevation of PP2AC. Silencing I2(PP2A) induced a long-lasting attenuation of amyloidogenesis in tg2576 mice with inhibition of amyloid precursor protein hyperphosphorylation and ?-secretase activity, whereas simultaneous inhibition of PP2A abolished the antiamyloidogenic effects of I2(PP2A) silencing. Finally, silencing I2(PP2A) could improve learning and memory of tg2576 mice with preservation of several memory-associated components. Our data reveal that targeting I2(PP2A) can efficiently rescue A? toxicities and improve the memory deficits in tg2576 mice, suggesting that I2(PP2A) could be a promising target for potential AD therapies. PMID:23922015
Liu, Gong-Ping; Wei, Wei; Zhou, Xin; Shi, Hai-Rong; Liu, Xing-Hua; Chai, Gao-Shang; Yao, Xiu-Qing; Zhang, Jia-Yu; Peng, Cai-Xia; Hu, Juan; Li, Xia-Chun; Wang, Qun; Wang, Jian-Zhi
Genome-wide association studies have identified a locus on chromosome 19 associated with plasma triglyceride (TG) concentration and nonalcoholic fatty liver disease. However, the identity and functional role of the gene(s) responsible for these associations remain unknown. Of 19 expressed genes contained in this locus, none has previously been implicated in lipid metabolism. We performed gene expression studies and expression quantitative trait locus analysis in 206 human liver samples to identify the putative causal gene. Transmembrane 6 superfamily member 2 (TM6SF2), a gene with hitherto unknown function, expressed predominantly in liver and intestine, was identified as the putative causal gene. TM6SF2 encodes a protein of 351 amino acids with 7�10 predicted transmembrane domains. Otherwise, no other protein features were identified which could help to elucidate the function of TM6SF2. Protein subcellular localization studies with confocal microscopy demonstrated that TM6SF2 is localized in the endoplasmic reticulum and the ER-Golgi intermediate compartment of human liver cells. Functional studies for secretion of TG-rich lipoproteins (TRLs) and lipid droplet content were performed in human hepatoma Huh7 and HepG2 cells using confocal microscopy and siRNA inhibition and overexpression techniques. In agreement with the genome-wide association data, it was found that TM6SF2 siRNA inhibition was associated with reduced secretion of TRLs and increased cellular TG concentration and lipid droplet content, whereas TM6SF2 overexpression reduced liver cell steatosis. We conclude that TM6SF2 is a regulator of liver fat metabolism with opposing effects on the secretion of TRLs and hepatic lipid droplet content. PMID:24927523
Mahdessian, Hovsep; Taxiarchis, Apostolos; Popov, Sergej; Silveira, Angela; Franco-Cereceda, Anders; Hamsten, Anders; Eriksson, Per; van't Hooft, Ferdinand
Objective: To determine whether substituting carbohydrate for saturated fat has any adverse effects on serum high density lipoprotein (HDL) cholesterol and triglycerides in free-living individuals.Design: Randomised crossover trial.Setting: General community.Subjects: Volunteer sample of 38 healthy free-living men with mean (s.d.) age 37 (7) y, moderately elevated serum total cholesterol 5.51 (0.93) mmol\\/l and body mass index 26.0 (3.6) kg\\/m2.Interventions: Participants
ML Turley; CM Skeaff; JI Mann; B Cox
Epi.q-TG: mobile robot for surveillance
Purpose � The purpose of this paper is to describe the development of a robot for surveillance able to move in structured and unstructured environments and able to overcome obstacles with high energetic efficiency. Design\\/methodology\\/approach � The proposed Epi.q-TG hybrid robot combines wheeled and legged locomotion. It is equipped with four three-wheeled locomotion units; traction is generated by the two
Giuseppe Quaglia; Luca Bruzzone; Giorgio Bozzini; Riccardo Oderio; Roberto P. Razzoli
A method for the structural analysis of triglycerides and lecithins
The structural analysis of lecithins and triglycerides is described. The procedure is carried out on 2�5 mg of sample by a\\u000a combination of reductive ozonolysis and thin-layer chromatography (TLC). The ozonides as well as the aldehyde �cores� derived\\u000a from reduction of the ozonides are separated by TLC and analyzed quantitatively by densitometry. The constituent saturated\\u000a fatty acids of the separated
O. S. Privett; M. L. Blank
Studies on the Absorptive Defect for Triglyceride in Abetalipoproteinemia*
The nature of the gastrointestinal absorptive defect for triglyceride in three subjects with abetalipoproteinemia has been investigated by studying peroral biopsies of the gastrointestinal mucosa. The following conclusions were reached. 1) In confirmation of other studies, the abnormal vacuoles within the duodenal absorptive cells of these individuals were lipophilic. 2) On chemical analysis there was significantly more mucosal lipid than found in normal fasting specimens, and almost the entire increase was due to triglyceride. 3) This excess mucosal lipid was reduced by a low fat diet, but even after 34 days on such a diet there was still an excess of lipophilic material near the villus tip and increased quantities of total lipid and triglyceride when compared with material from normal subjects similarly treated. 4) Although there are demonstrable qualitative changes in mucosal and plasma lipids after an acute fat load, they are not quantitatively as great as in normal individuals. Fat balance studies and the qualitative changes in plasma and tissue lipids that do occur after more extended periods on different types of dietary fat do indicate that a considerable percentage of the dietary fat is assimilated. The route by which it is absorbed remains to be clarified. Images PMID:6018748
Ways, P. O.; Parmentier, C. M.; Kayden, H. J.; Jones, J. W.; Saunders, D. R.; Rubin, C. E.
A method is described for construction of an amperometric triglyceride (TG) biosensor based on covalent co-immobilization of lipase, glycerol kinase and glycerol-3-phosphate oxidase onto gold polypyrrole nanocomposite decorated poly indole-5-carboxylic acid electrodeposited on the surface of a gold electrode. The enzyme electrode was characterized by transmission electron microscopy, scanning electron microscopy, electrochemical impedance studies, Fourier transform infrared spectroscopy and cyclic voltammetry. Biosensor showed optimum response within 4 s at pH 6.5 and 35 �C, when polarized at +0.1 V against Ag/AgCl. There was a linear relationship between sensor response and triolein concentration in the range 50-700 mg/dl. Biosensor was employed for determination of TG in serum. Detection limit of the biosensor was 20 mg/dl. Biosensor was evaluated with 91-95 % recovery of added triolein in sera and 4.14 and 5.85 % within and between batch coefficients of variation, respectively. There was a good correlation (r = 0.99) between sera TG values by standard method (Enzymic colorimetric) and the present method. The biosensor was unaffected by a number of serum substances at their physiological concentration. Biosensor lost 50 % of its initial activity after its 100 uses over 7 months, when stored at 4 �C. PMID:22903594
Narang, Jagriti; Chauhan, Nidhi; Rani, Poonam; Pundir, C S
(tgltg) and available allelic variants (lg~lrg~, rgltg+ demonstrate three major neurologic disorders: 1) generalized epilepsy, 2) ataxia, and 3) intermittent, myoclonus-like movements (Meier and Macpike, 1971; Isaacs and Abbott, 1992). Collectively...; Syapin, 1982). Compound heterozygous tottering/leaner (tg/tg ) mice exhibit epilepsy similar to tottering (tg/rg) mice with a slightly earlier onset (Tsuji and Meier, 1971; Isaacs and Abbott, 1992; 1995). Leaner (/gk'/rg ) mice show spike...
Walker, Dana B
The chemical composition of monogalactosyldiacylglycerols (MGDGs) from brown alga Sargassum horneri and their inhibitory effects on lipid accumulation were investigated in this study. A total of 10 molecular species of MGDGs were identified using nuclear magnetic resonance, alkaline hydrolysis, gas chromatography-flame ionization detector, and high-performance liquid chromatography-tandem mass spectrometry methods. Individual molecular species of MGDGs, including (2S)-1-O-myristoyl-2-O-palmitoleoyl-3-O-?-d-galactopyranosyl-sn-glycerol (1), (2S)-1-O-myristoyl-2-O-linoleyl-3-O-?-d-galactopyranosyl-sn-glycerol (3), (2S)-1-O-palmitoyl-2-O-linolenoyl-3-O-?-d-galactopyranosyl-sn-glycerol (5), (2S)-1-O-myristoyl-2-O-oleyl-3-O-?-d-galactopyranosyl-sn-glycerol (7), (2S)-1-O-palmitoyl-2-O-palmitoleoyl-3-O-?-d-galactopyranosyl-sn-glycerol (8), (2S)-1-O-palmitoyl-2-O-linoleyl-3-O-?-d-galactopyranosyl-sn-glycerol (9), and (2S)-1-O-palmitoyl-2-O-oleyl-3-O-?-d-galactopyranosyl-sn-glycerol (10), were then furnished using semi-preparative high-performance liquid chromatography, and their inhibitory effects on triglyceride (TG) accumulation and free fatty acid (FFA) levels in 3T3-L1 adipocytes were evaluated. Compounds 3 and 9 showed inhibitory effects on TG and FFA accumulation, with TG levels of 1.568 � 0.2808 and 1.701 � 0.1460 ?mol/L and FFA levels of 0.149 � 0.0258 and 0.198 � 0.0229 mequiv/L, respectively, which were more effective than other compounds. The primary structure-activity relationship suggested that linoleyl [18:2(?-6)] in the sn-2 position played an important role on triglyceride accumulation inhibition. PMID:25363514
Ma, Ai-Cui; Chen, Zhen; Wang, Tao; Song, Ni; Yan, Qian; Fang, Yu-Chun; Guan, Hua-Shi; Liu, Hong-Bing
Fat Mobilization in Adipose Tissue Is Promoted by Adipose Triglyceride Lipase
Mobilization of fatty acids from triglyceride stores in adipose tissue requires lipolytic enzymes. Dysfunctional lipolysis affects energy homeostasis and may contribute to the pathogenesis of obesity and insulin resistance. Until now, hormone-sensitive lipase (HSL) was the only enzyme known to hydrolyze triglycerides in mammalian adipose tissue. Here, we report that a second enzyme, adipose triglyceride lipase (ATGL), catalyzes the initial
Robert Zimmermann; Juliane G. Strauss; Guenter Haemmerle; Gabriele Schoiswohl; Ruth Birner-Gruenberger; Monika Riederer; Achim Lass; Georg Neuberger; Frank Eisenhaber; Albin Hermetter; Rudolf Zechner
Rapid and sensitive enzymatic-radiochemical assay for the determination of triglycerides
An enzymatic-radiochemical method suitable for the determination of triglyceride levels of cells in culture is described. The method is based on the enzymatic hydrolysis of triglycerides to free fatty acids which then complex with /sup 63/Ni. The method is rapid, accurate, and inexpensive. The procedure extends the sensitivity of triglyceride measurement to as low as 0.25 nanomoles.
Khoo, J.C.; Miller, E.; Goldberg, D.I.
Aims\\/hypothesis��Elevated fasting and postprandial plasma levels of triglyceride-rich lipoproteins (TGRLs), i.e. VLDL\\/remnants and chylomicrons\\/remnants, are a characteristic feature of insulin resistance and are considered a consequence of this state. The aim of this study was to investigate whether intact TGRL particles are capable of inducing insulin resistance.Methods��We studied the effect of highly purified TGRLs on glycogen synthesis, glycogen synthase activity,
M. T. Pedrini; M. Kranebitter; A. Niederwanger; S. Kaser; J. Engl; P. Debbage; L. A. Huber; J. R. Patsch
Long term aging of selenide glasses: evidence of sub-Tg endotherms and pre-Tg exotherms
NASA Astrophysics Data System (ADS)
Long term aging, extending from months to several years, is studied on several families of chalcogenide glasses including the Ge-Se, As-Se, and Ge-As-Se systems. Special attention is given to the As-Se binary, a system that displays a rich variety of aging behavior intimately tied to sample synthesis conditions and the ambient environment in which samples are aged. Calorimetric (modulated DSC) and Raman scattering experiments are undertaken. Our results show all samples display a sub-Tg endotherm typically 10-70 �C below Tg in glassy networks possessing a mean coordination number r in the 2.25 < r < 2.45 range. Two sets of AsxSe100-x samples aged for eight years were compared, set A consisted of slow cooled samples aged in the dark, and set B consisted of melt-quenched samples aged at laboratory environment. Samples of set B in the As concentration range, 35% < x < 60%, display a pre-Tg exotherm, but the feature is not observed in samples of set A. The aging behavior of set A presumably represents intrinsic aging in these glasses, while that of set B is extrinsic due to the presence of light. The reversibility window persists in both sets of samples, but is less well defined in set B. These findings contrast with a recent study by Golovchak et al (2008 Phys. Rev. B 78 014202), which finds the onset of the reversibility window moved up to the stoichiometric composition (x = 40%). Here we show that the up-shifted window is better understood as resulting due to demixing of As4Se4 and As4Se3 molecules from the backbone, i.e., nanoscale phase separation (NSPS). We attribute sub-Tg endotherms to compaction of the flexible part of the networks upon long term aging, while the pre-Tg exotherm is to NSPS. The narrowing and sharpening of the reversibility window upon aging is interpreted as the slow 'self-organizing' stress relaxation of the phases just outside the intermediate phase, which itself is stress free and displays little aging.
Chen, Ping; Boolchand, P.; Georgiev, D. G.
Omega3 fatty acid supplementation accelerates chylomicron triglyceride clearance
Omega-3 fatty acids (FAs) reduce postprandial triacylglycerol (TG) concentrations. This study was under- taken to determine whether this effect was due to reduced production or increased clearance of chylomicrons. Healthy subjects (n ? 33) began with a 4-week, olive oil placebo (4 g\\/d) run-in period. After a 4-week wash-out period, subjects were randomized to supplementation with 4 g\\/d of ethyl
Yongsoon Park; William S. Harris
Increasing evidence suggests that the metabolism of arachidonic acid (AA) may be different in inflammatory cells isolated from blood or migrating into tissues. To explore the possibility that changes in AA metabolism between blood and tissue inflammatory cells could be due in part to a different content or distribution of AA in glycerolipid classes, we studied these parameters in six human inflammatory cells isolated from blood (eosinophils, monocytes, neutrophils, and platelets) or from the lung tissue (mast cells and macrophages). Lung cells generally had a higher total cellular content of AA than that found in the blood cells. In addition, both mast cells and macrophages had a large endogenous pool of AA associated with triglycerides (TG), containing 45 and 22% of their total cellular AA, respectively. To address the hypothesis that cells migrating into the lung had a higher cellular level of AA and a larger AA pool in TG, we studied neutrophils isolated from the bronchoalveolar lavage (BAL) of patients with adult respiratory distress syndrome. BAL neutrophils had a fourfold increase in cellular AA as compared with blood neutrophils and contained 25% of their AA in TG versus 3% in blood neutrophils. BAL neutrophils also had a higher number of cytoplasmic lipid bodies (8 +/- 3/cell) relative to blood neutrophils (2 +/- 1/cell). High concentrations of free AA were also found in the cell-free BAL fluid of adult respiratory distress syndrome patients. To explore whether changes in BAL neutrophils may be due to the exposure of the cells to high concentrations of exogenous AA found in BAL, we incubated blood neutrophils in culture with AA (10-100 microM) for 24 h. Neutrophils supplemented with AA had a 10-fold increase in the amount of AA associated with TG and a sixfold increase in the number of lipid bodies. In addition, supplementation with AA induced a dose-dependent formation of hypodense cells. Taken together, these data indicate that human inflammatory cells undergo a fundamental and consistent remodeling of AA pools as they mature or enter the lung from the blood. These biochemical and morphological changes can be mimicked in vitro by exposing the cells to high levels of AA. This mechanism may be responsible for the changes in AA mobilization and eicosanoid metabolism observed in tissue inflammatory cells. PMID:7595189
A Report of High Triglyceride Level in Cord Blood of Iranian Newborns
Background: Since cord blood triglyceride level have been reported very different in recent articles, the purpose of this study is determination of triglyceride level in cord blood of Iranian newborns and compare it with other reports. Methods: In this study, cord blood of 174 healthy term newborn infants (97 girls, 77 boys) born from healthy mothers have been used. Triglyceride level has been measured by calorie metric method Statistical analysis was performed by independent t test, Mann-Whitney regression test and Spearman correlation coefficient method using SPSS 16 .0 software (SPSS, USA). Results: The mean of cord blood triglyceride was 1.37 � 4.81 mg /dl and there was no statistical difference between two sexes. There was not exist linear relationship between triglyceride and weight, height, head circumference, body mass index and sex of the babies. In 8.6% of our new born infants, triglyceride levels were more than 95th percentile of triglyceride level reported in Iranian population. In 33.9% of our cases, triglyceride levels were more than 95th percentile of triglyceride level reported in the Nelson text book of Pediatrics. In this study, the 95th percentile of triglyceride level in cord blood was 132.5 mg /dl. Conclusion: The mean and 95th percentiles of triglyceride levels in cord blood of our newborn infants were higher than other reports. We recommend that larger studies should be conducted in this area to establish preventive ways for increasing epidemic of the metabolic syndrome. PMID:24049593
Kazemi, Seyed Ali Naghi; Mousavinasab, Nooreddin; Mellati, Ali Awsat; Sadeghzadeh, Mansour
Lipids, including triglycerides, are important variables in fish bioenergetics and can be used to estimate overall fish condition. Triglycerides are the major energy storage form in fish and therefore are a more ecologically and physiologically relevant measure of bioenergetics than total lipids. Chloroform-methanol-extracted total body lipids (Bligh and Dyer) and total body triglycerides determined in chloroform-methanol extracts and unextracted whole-body fractions were measured in four fish species: northern pike Esox lucius, burbot Lota lota, slimy sculpin Cottus cognatus, and spottail shiners Notropis hudsonius. Determinations of total body lipids were consistently greater than those of total body triglycerides when measured in the same solvent-extracted fraction, although both measures followed similar trends. In an effort to eliminate the need for extraction with organic solvents, we compared the performance of an enzyme-based triglyceride assay in both the solvent-extracted fraction and a whole-body unextracted homogenate for each fish. The chloroform-methanol-extracted triglyceride values were consistently lower than triglycerides measured in the unextracted whole-body homogenate. In addition, comparison of triglyceride measurements revealed limitations to the solvent extraction and subsequent triglyceride determinations in lean fish. Thus, in addition to being simple, rapid, and not requiring organic solvents, determination of triglycerides in an unextracted whole-fish homogenate may be a useful alternative to chloroform-methanol-based methods of lipid extraction and subsequent triglyceride measurement. PMID:18201059
Bennett, Pamela M; Weber, Lynn P; Janz, David M
Both elevated plasma free fatty acids (FFA) and accumulating triglyceride in adipose tissue are observed in the process of obesity and insulin resistance. This contradictory phenomenon and its underlying mechanisms have not been thoroughly elucidated. Recent studies have demonstrated that pigment epithelium-derived factor (PEDF) contributes to elevated plasma FFA and insulin resistance in obese mice via the activation of adipose triglyceride lipase (ATGL). However, we found that PEDF downregulated adipose ATGL protein expression despite of enhancing lipolysis. Plasma PEDF and FFA were increased in associated with a progressive high-fat-diet, and those outcomes were also accompanied by fat accumulation and a reduction in adipose ATGL. Exogenous PEDF injection downregulated adipose ATGL protein expression and elevated plasma FFA, while endogenous PEDF neutralization significantly rescued the adipose ATGL reduction and also reduced plasma FFA in obese mice. PEDF reduced ATGL protein expression in a time- and dose-dependent manner in differentiated 3T3-L1 cells. Small interfering RNA-mediated PEDF knockdown and antibody-mediated PEDF blockage increased endogenous ATGL expression, and PEDF overexpression downregulated ATGL. PEDF resulted in a decreased half-life of ATGL and regulated ATGL degradation via ubiquitin-dependent proteasomal degradation pathway. PEDF stimulated lipolysis via ATGL using ATGL inhibitor bromoenol lactone, and PEDF also downregulated G0/G1 switch gene 2 (G0S2) expression, which is an endogenous inhibitor of ATGL activation. Overall, PEDF attenuated ATGL protein accumulation via proteasome-mediated degradation in adipocytes, and PEDF also promoted lipolysis by activating ATGL. Elevated PEDF may contribute to progressive obesity and insulin resistance via its dual regulation of ATGL. PMID:23850519
Dai, Zhiyu; Qi, Weiwei; Li, Cen; Lu, Juling; Mao, Yuling; Yao, Yachao; Li, Lei; Zhang, Ting; Hong, Honghai; Li, Shuai; Zhou, Ti; Yang, Zhonghan; Yang, Xia; Gao, Guoquan; Cai, Weibin
Synthesis and characterization of triglyceride based thermosetting polymers
NASA Astrophysics Data System (ADS)
Plant oils, which are found in abundance in all parts of the world and are easily replenished annually, have the potential to replace petroleum as a chemical feedstock for making polymers. Within the past few years, there has been growing interest to use triglycerides as the basic constituent of thermosetting polymers with the necessary rigidity, strength and glass transition temperatures required for engineering applications. Plant oils are not polymerizable in their natural form, however various functional groups that can polymerize can easily be attached to the triglyceride structure making them ideal cross-linking monomers for thermosetting liquid molding resins. Through this research project a number of thermosetting liquid molding resins based on soybean and castor oil, which is a specialty oil with hydroxyls on its fatty acids, have been developed. The triglyceride based monomers were prepared via the malination of the alcoholysis products of soybean and castor oil with various polyols, such as pentaerythritol, glycerol, and Bisphenol A propoxylate. The malinated glycerides were then cured in the presence of a reactive diluent, such as styrene, to form rigid glassy materials with a wide range of properties. In addition to maleate half-esters, methacrylates were also introduced to the glyceride structure via methacrylation of the soybean oil glycerolysis product with methacrylic anhydride. This product, which contains methacrylic acid as by-product, and its blends with styrene also gave rigid materials when cured. The triglyceride based monomers were characterized via conventional spectroscopic techniques. Time resolved FTIR analysis was used to determine the curing kinetics and the final conversions of polymerization of the malinated glyceride-styrene blends. Dynamic Mechanical Analysis (DMA) was used to determine the thermomechanical behavior of these polymers and other mechanical properties were determined via standard mechanical tests. The use of lignin, another renewable resource, as a filler and its effects on the mechanical properties of the polymers based on soybean oil pentaerythritol glyceride maleates and styrene (SOPERMA) was also explored. These novel soybean and castor oil based thermosetting resins show comparable properties to those of commercially successful unsaturated polyester resins and show promise as an alternative to replace these completely petroleum based materials.
Can, Erde
The triglyceride composition of butea monosperma seed oil
Fatty acid and triglyceride composition ofButea monosperma seed oil have been determined by a combination of the techniques of systematic crystallization at low temperature, pancreatic\\u000a lipase hydrolysis, and gas chromatography. The percentages of individual fatty acids are: myristic 0.2, palmitic 19.3, stearic\\u000a 7.4, arachidic 1.8, behenic 14.0, lignoceric 6.2, oleic 21.8, linoleic 27.8, and linolenic 1.7.B.monosperma seed oil is constituted
A. Sengupta; S. P. Basu
Heats of combustion of fatty esters and triglycerides
Gross heats of combustion (HG) have been measured for three classes of fatty esters and two classes of triglycerides (TGs).\\u000a The esters included saturated methyl esters, Me 6:0�22:0; saturated ethyl esters, Et 8:0�22:0; and unsaturated methyl esters,\\u000a Me 12:1�22:1, Me 18:2 and Me 18:3. The TGs included the saturated TGs, C 8:0�22:0, and unsaturated TGs, C 11:1, C 16:1, C
B. Freedman; M. O. Bagby
Postabsorptive VLDL-TG Fatty Acid Storage in Adipose Tissue in Lean and Obese Women
Adipose tissue lipoprotein lipase (LPL) is a necessary enzyme for storage of VLDL-TG, but whether it is a rate determining step is unknown. To test this hypothesis we included 10 upper-body obese (UBO), 11 lower-body obese (LBO) and 8 lean women. We infused ex-vivo labeled VLDL-14C-TG and then performed adipose tissue biopsies to understand the relationship between VLDL-TG storage and LPL-activity in femoral and upper-body subcutaneous fat. Both fractional tracer storage and rate of storage of the VLDL-TG tracer were evaluated. VLDL-TG storage was also examined as a function of regional adipose tissue blood flow (ATBF), insulin, VLDL-TG turnover, regional fat mass, FFM, and fat cell size. LPL-activity per adipocyte was significantly greater in obese than lean women but not significantly different per gram lipid. Both VLDL-TG fractional tracer storage per kg lipid and VLDL-TG storage rate per kg lipid were similar in abdominal and femoral fat in all three groups and not significantly different between groups. Multiple regression analysis identified FFM and femoral fat mass as significant independent predictors of VLDL-TG fractional tracer storage and insulin as a significant predictor of VLDL-TG fatty acid storage rate. LPL-activity, ATBF, and VLDL-TG turnover did not predict VLDL-TG storage. We conclude that lower FFM and greater plasma insulin is associated with greater VLDL-TG deposition in abdominal subcutaneous and femoral fat. Greater femoral fat mass signals greater femoral VLDL-TG storage. We suggest that the differences in VLDL-TG storage in abdominal and femoral fat that occur with progressive obesity are regulated through mechanisms other than LPL-activity. PMID:19875996
Nellemann, B; Gormsen, LC; Christiansen, JS; Jensen, MD; Nielsen, S
TG16 point target detection experiment POLLEX, Livorno 2001
NASA Astrophysics Data System (ADS)
NATO Task group TG16 is cooperating on topics related to ship self-defence. One of these topics is related to IR Search and Track sensors, which are in development for detection of low altitude air targets. In particular the group is working on models to predict the range performance of these sensors. Newly developed models include marine boundary layer effects such as refraction due to temperature gradients, scintillation due to turbulence and particle size distributions. TG16 organized in May 2001a trial in the Mediterranean Sea near Livorno, Italy, called POLLEX to further validate these models. Seven nations particulated with complementary instruments for measurements of the target signatures and environmental characteristics. Three targets were provided, a series of small visual/IR sources at a fixed distance, visual/IR soruces on a ship moving in and out up-to and beyond the horizon and a helicopter. The weather conditions during the measurement period showed interesting variations in Air to Sea Temperature DIfference and atmospheric turbulence. Data have been analzyed and samples of the results, as collected and/or analyzed by the participants, are discussed in this paper.
de Jong, Arie N.; Winkel, Hans; Moerman, Marcel M.; Stein, Karin; Weiss-Wrana, Karin; Forand, J. Luc; Potvin, Guy; Buss, James R.; Cini, Andrea; Vogel, Henrik H.; Stark, Espen
Long term aging of selenide glasses: evidence of sub-Tg endotherms and pre-Tg exotherms.
Long term aging, extending from months to several years, is studied on several families of chalcogenide glasses including the Ge-Se, As-Se, and Ge-As-Se systems. Special attention is given to the As-Se binary, a system that displays a rich variety of aging behavior intimately tied to sample synthesis conditions and the ambient environment in which samples are aged. Calorimetric (modulated DSC) and Raman scattering experiments are undertaken. Our results show all samples display a sub-Tg endotherm typically 10-70 �C below Tg in glassy networks possessing a mean coordination number r in the 2.25 < r < 2.45 range. Two sets of As(x)Se(100-x) samples aged for eight years were compared, set A consisted of slow cooled samples aged in the dark, and set B consisted of melt-quenched samples aged at laboratory environment. Samples of set B in the As concentration range, 35% < x < 60%, display a pre-T(g) exotherm, but the feature is not observed in samples of set A. The aging behavior of set A presumably represents intrinsic aging in these glasses, while that of set B is extrinsic due to the presence of light. The reversibility window persists in both sets of samples, but is less well defined in set B. These findings contrast with a recent study by Golovchak et al (2008 Phys. Rev. B 78 014202), which finds the onset of the reversibility window moved up to the stoichiometric composition (x = 40%). Here we show that the up-shifted window is better understood as resulting due to demixing of As4Se4 and As4Se3 molecules from the backbone, i.e., nanoscale phase separation (NSPS). We attribute sub-Tg endotherms to compaction of the flexible part of the networks upon long term aging, while the pre-Tg exotherm is to NSPS. The narrowing and sharpening of the reversibility window upon aging is interpreted as the slow 'self-organizing' stress relaxation of the phases just outside the intermediate phase, which itself is stress free and displays little aging. PMID:21389364
Chen, Ping; Boolchand, P; Georgiev, D G
Even at low-density lipoprotein cholesterol (LDL-C) goal, patients with cardiometabolic abnormalities remain at high risk of cardiovascular events. This paper aims (i) to critically appraise evidence for elevated levels of triglyceride-rich lipoproteins (TRLs) and low levels of high-density lipoprotein cholesterol (HDL-C) as cardiovascular risk factors, and (ii) to advise on therapeutic strategies for management. Current evidence supports a causal association between elevated TRL and their remnants, low HDL-C, and cardiovascular risk. This interpretation is based on mechanistic and genetic studies for TRL and remnants, together with the epidemiological data suggestive of the association for circulating triglycerides and cardiovascular disease. For HDL, epidemiological, mechanistic, and clinical intervention data are consistent with the view that low HDL-C contributes to elevated cardiovascular risk; genetic evidence is unclear however, potentially reflecting the complexity of HDL metabolism. The Panel believes that therapeutic targeting of elevated triglycerides (?1.7 mmol/L or 150 mg/dL), a marker of TRL and their remnants, and/or low HDL-C (<1.0 mmol/L or 40 mg/dL) may provide further benefit. The first step should be lifestyle interventions together with consideration of compliance with pharmacotherapy and secondary causes of dyslipidaemia. If inadequately corrected, adding niacin or a fibrate, or intensifying LDL-C lowering therapy may be considered. Treatment decisions regarding statin combination therapy should take into account relevant safety concerns, i.e. the risk of elevation of blood glucose, uric acid or liver enzymes with niacin, and myopathy, increased serum creatinine and cholelithiasis with fibrates. These recommendations will facilitate reduction in the substantial cardiovascular risk that persists in patients with cardiometabolic abnormalities at LDL-C goal. PMID:21531743
Chapman, M. John; Ginsberg, Henry N.; Amarenco, Pierre; Andreotti, Felicita; Boren, Jan; Catapano, Alberico L.; Descamps, Olivier S.; Fisher, Edward; Kovanen, Petri T.; Kuivenhoven, Jan Albert; Lesnik, Philippe; Masana, Luis; Nordestgaard, B?rge G.; Ray, Kausik K.; Reiner, Zeljko; Taskinen, Marja-Riitta; Tokgozoglu, Lale; Tybjaerg-Hansen, Anne; Watts, Gerald F.
The mechanisms by which high-carbohydrate, low-saturated-fat diets lower LDL cholesterol (LDLC) concentrations are unknown. In this study, kinetics of VLDL, intermediate density lipoprotein (IDL), and LDL apoprotein B and VLDL triglyceride were determined in seven nondiabetic (ND) and seven non-insulin-dependent diabetic (NIDDM) Pima Indian subjects on high-fat and high-carbohydrate (HICHO) diets. Metabolic changes were similar in ND and NIDDM. On the HICHO diet, LDLC decreased (131 +/- 8 vs. 110 +/- 7 mg/dl, P less than 0.0001) in all subjects. Mean fasting and 24-h triglyceride (TG) concentrations were unchanged, as were mean production rates and fractional clearance rates (FCR) of VLDL apoB and VLDL TG. The mean VLDL apoB pool size (303 +/- 20 vs. 371 +/- 38 mg, P = 0.01) increased owing to a decrease in the mean transport rate (10.7 +/- 1.1 vs. 8.4 +/- 0.9 mg/kg fat-free mass (ffm) per day, P less than 0.0001) and the mean rate constant (2.3 +/- 0.2 vs. 1.5 +/- 0.2, P less than 0.001) for the VLDL apoB to IDL apoB conversion pathway. The mean transport rate of VLDL apoB to LDL apoB via IDL (10.2 +/- 0.9 vs. 8.0 +/- 0.8 mg/kg ffm per day, P less than 0.001) decreased. Mean LDL apoB concentrations decreased (70 +/- 5 vs. 61 +/- 5 mg/dl, P less than 0.001) on the HICHO diet. Means for total LDL apoB transport rate, LDL apoB FCR, and LDLC/apoB ratios were unchanged. In summary, the HICHO diet decreased the activity of mechanisms that convert VLDL to LDL, which contributed to the decrease in LDLC in all subjects. There was also evidence in some subjects for increased activity of LDL apoB clearance mechanisms, and a decrease in the LDLC to apoB ratio. PMID:2200808
Abbott, W G; Swinburn, B; Ruotolo, G; Hara, H; Patti, L; Harper, I; Grundy, S M; Howard, B V
Uniaxial Extension of Entangled Polymer Melts close to Tg
NASA Astrophysics Data System (ADS)
Transient (nonlinear) responses of entangled polymers to startup deformation indicate a transition from the initial elastic deformation to irreversible deformation (flow) [1-3]. This yielding behavior varies with the applied rate: at a higher rate the entanglement network can be strained to a higher degree before its breakdown. In this work, we subject entangled melts such as polystyrene to startup uniaxial extension to show how yielding takes place as a function of temperature. The objective is to explore whether there would be any mechanical signature of emergence of any secondary structure as the glass transition temperature Tg is approached from above. [4pt] [1] S. Q. Wang, S. Ravindranath, Y. Wang and P. Boukany, J. Chem. Phys. 127, 064903 (2007).[0pt] [2] Y. Y. Wang and S. Q. Wang, J. Rheol. 53, 1389 (2009).[0pt] [3] S. Q. Wang, S. Ravindranath and P. E. Boukany, Macromolecules 44, 183 (2011).
Sun, Hao; Wang, Shi-Qing
TG-DSC-FTIR Analysis of Cyanobacteria Pyrolysis
NASA Astrophysics Data System (ADS)
Pyrolysis of cyanobacteria from Dianchi lake was investigated by TG-DSC-FTIR analysis at different heating rates (10, 20, 40�C/min). The results indicated that the pyrolysis of cyanobacteria can be divided into four stages: evaporation, depolymerization, devolatilization and carbonization. Meanwhile, the initial weight-loss temperature, weight-loss extreme position, endothermic and exothermic peaks were moved to higher temperature with the increaseing of the heating rate. The kinetic analysis was made with Popescu method. It indicated that the best kinetic model for the pyrolysis of cyanobacteria was the cylindrical symmetry of the phase boundary reaction model. The main pyrolysis gases checked with real-time online FTIR were HCN, NH3, CO, CO2, water vapor and hydrocarbons.
Supeng, Luo; Guirong, Bao; Hua, Wang; Fashe, Li; Yizhe, Li
A systematic analysis of genomic changes in Tg2576 mice.
Alzheimer's disease (AD) is an age-related neurodegenerative disorder characterized by intelligence decline, behavioral disorders and cognitive disability. The purpose of this study was to investigate gene expression in AD, based on published microarray data on Tg2576 mice. Hierarchical Cluster Analysis and Gene Ontology were employed to group genes together on the basis of their product characteristics and annotation data. Genes with prominent alterations were clustered into apoptosis and axon guidance pathways. Based on our findings and those of previous studies, we propose that the mitochondria-mediated apoptotic pathway plays a crucial role in the neuronal loss and synaptic dysfunction associated with AD. Furthermore, based on the findings of Positional Gene Enrichment analysis and Gene Set Enrichment analysis, we propose that the regulation of transcription of AD genes may be an important pathogenic factor in this neurodegenerative disease. Our results highlight the importance of genes that could subsequently be examined for their potential as prognostic markers for AD. PMID:23242760
Tan, Lu; Wang, Xiong; Ni, Zhong-Fei; Zhu, Xiuming; Wu, Wei; Zhu, Ling-Qiang; Liu, Dan
Lipids, including triglycerides, are important variables in fish bioenergetics and can be used to estimate overall fish condition. Triglycerides are the major energy storage form in fish and therefore are a more ecologically and physiologically relevant measure of bioenergetics than total lipids. Chloroform�methanol-extracted total body lipids (Bligh and Dyer) and total body triglycerides determined in chloroform�methanol extracts and unextracted whole-body
Pamela M. Bennett; Lynn P. Weber; David M. Janz
A rapid method for the stereospecific analysis of triglycerides based on enzymatic hydrolysis on thin layer plates was applied\\u000a to a number ofGlycine max, Glycine soya, Avena sativa andAvena sterilis strains. The percentage of each fatty acid on thesn-1,sn-2- andsn-3-positions was linearly related to the total percentage of the fatty acid in the triglyceride. Large deviations from the\\u000a common triglyceride
W. P. Pan; E. G. Hammond
Improved triglyceride transesterification by circular permuted Candida antarctica lipase B.
Lipases represent a versatile class of biocatalysts with numerous potential applications in industry including the production of biodiesel via enzyme-catalyzed transesterification. In this article, we have investigated the performance of cp283, a variant of Candida antarctica lipase B (CALB) engineered by circular permutation, with a series of esters, as well as pure and complex triglycerides. In comparison with wild-type CALB, the permutated enzyme showed consistently higher catalytic activity (2.6- to 9-fold) for trans and interesterification of the different substrates with 1-butanol and ethyl acetate as acyl acceptors. Differences in the observed rates for wild-type CALB and cp283 are believe to be related to changes in the rate-determining step of the catalytic cycle as a result of circular permutation. PMID:19609971
Yu, Ying; Lutz, Stefan
A series of lipid-accumulating yeasts was examined for their potential to saccharify xylan and accumulate triglyceride. Of the genera tested, including Candida, Cryptococcus, Lipomyces, Rhodosporidium, Rhodotorula, and Trichosporon, only Crytococcus and Trichosporon isolates saccharified xylan. All of the strains could assimilate xylose and accumuate triglyceride under nitrogen-limiting conditions. Strains of Cryptococcus albidus were found to be especially useful for a one-step saccharification of xylan coupled to triglyceride synthesis. Crytococcus terricolus, a strain constitutive for lipid accumulation, lacked extracellular xylanase, but did assimilate xylose and xylobiose and was able to continuously convert xylan to triglyceride if the culture medium was supplemented with xylanase. 22 references.
Fall, R.; Phelps, P.; Spindler, D.
Fracture Simulation of Highly Crosslinked Polymer Networks: Triglyceride-Based Adhesives
NASA Astrophysics Data System (ADS)
The ACRES program at the U. of Delaware has shown that triglyceride oils derived from plants are a favorable alternative to the traditional adhesives. The triglyceride networks are formed from an initial mixture of styrene monomers, free-radical initiators and triglycerides. We have performed simulations to study the effect of physical composition and physical characteristics of the triglyceride network on the strength of triglyceride network. A coarse-grained, bead-spring model of the triglyceride system is used. The average triglyceride consists of 6 beads per chain, the styrenes are represented as a single bead and the initiators are two bead chains. The polymer network is formed using an off-lattice 3D Monte Carlo simulation, in which the initiators activate the styrene and triglyceride reactive sites and then bonds are randomly formed between the styrene and active triglyceride monomers producing a highly crosslinked polymer network. Molecular dynamics simulations of the network under tensile and shear strains were performed to determine the strength as a function of the network composition. The relationship between the network structure and its strength will also be discussed.
Lorenz, Christian; Stevens, Mark; Wool, Richard
The hereditary spastic paraplegia-related enzyme DDHD2 is a principal brain triglyceride lipase.
Complex hereditary spastic paraplegia (HSP) is a genetic disorder that causes lower limb spasticity and weakness and intellectual disability. Deleterious mutations in the poorly characterized serine hydrolase DDHD2 are a causative basis for recessive complex HSP. DDHD2 exhibits phospholipase activity in vitro, but its endogenous substrates and biochemical functions remain unknown. Here, we report the development of DDHD2(-/-) mice and a selective, in vivo-active DDHD2 inhibitor and their use in combination with mass spectrometry-based lipidomics to discover that DDHD2 regulates brain triglycerides (triacylglycerols, or TAGs). DDHD2(-/-) mice show age-dependent TAG elevations in the central nervous system, but not in several peripheral tissues. Large lipid droplets accumulated in DDHD2(-/-) brains and were localized primarily to the intracellular compartments of neurons. These metabolic changes were accompanied by impairments in motor and cognitive function. Recombinant DDHD2 displays TAG hydrolase activity, and TAGs accumulated in the brains of wild-type mice treated subchronically with a selective DDHD2 inhibitor. These findings, taken together, indicate that the central nervous system possesses a specialized pathway for metabolizing TAGs, disruption of which leads to massive lipid accumulation in neurons and complex HSP syndrome. PMID:25267624
Inloes, Jordon M; Hsu, Ku-Lung; Dix, Melissa M; Viader, Andreu; Masuda, Kim; Takei, Thais; Wood, Malcolm R; Cravatt, Benjamin F
Peripheral neuropathy develops in human subjects with prediabetes and metabolic syndrome, prior to overt hyperglycemia. The contributions of impaired glucose tolerance and insulin signaling, hypertriglyceridemia and/or increased NEFA, and hypercholesterolemia to this condition remain unknown. Niacin and its derivatives alleviate dyslipidemia with a minor effect on glucose homeostasis. This study evaluated the roles of impaired glucose tolerance versus dyslipidemia in prediabetic neuropathy using Zucker fatty (fa/fa) rats and the niacin derivative acipimox, as well as the interplay of hypertriglyceridemia, increased NEFA, and oxidative-nitrosative stress. 16 wk-old Zucker fatty rats with impaired glucose tolerance, obesity, hyperinsulinemia, hypertriglyceridemia, hypercholesterolemia, and increased NEFA, displayed sensory nerve conduction velocity deficit, thermal and mechanical hypoalgesia, and tactile allodynia. Acipimox (100 mgkg?1d?1, 4 weeks) reduced serum insulin, NEFA, and triglyceride concentrations without affecting glucose tolerance and hypercholesterolemia. It alleviated sensory nerve conduction velocity deficit, changes in behavioral measures of sensory function, and corrected oxidative-nitrosative stress, but not impaired insulin signaling, in peripheral nerve. Elevated NEFA increased total and mitochondrial superoxide production and NAD(P)H oxidase activity in cultured human Schwann cells. In conclusion, hypertriglyceridemia and/or increased NEFA concentrations cause prediabetic neuropathy through oxidative-nitrosative stress. Lipid-lowering agents and antioxidants may find use in management of this condition. PMID:22366714
Lupachyk, Sergey; Watcho, Pierre; Hasanova, Nailia; Julius, Ulrich; G.Obrosova, Irina
Peripheral neuropathy develops in human subjects with prediabetes and metabolic syndrome before overt hyperglycemia. The contributions of impaired glucose tolerance and insulin signaling, hypertriglyceridemia and/or increased nonesterified fatty acids (NEFA), and hypercholesterolemia to this condition remain unknown. Niacin and its derivatives alleviate dyslipidemia with a minor effect on glucose homeostasis. This study evaluated the roles of impaired glucose tolerance versus dyslipidemia in prediabetic neuropathy using Zucker fatty (fa/fa) rats and the niacin derivative acipimox, as well as the interplay of hypertriglyceridemia, increased NEFA, and oxidative-nitrosative stress. Sixteen-week-old Zucker fatty rats with impaired glucose tolerance, obesity, hyperinsulinemia, hypertriglyceridemia, hypercholesterolemia, and increased NEFA displayed sensory nerve conduction velocity deficit, thermal and mechanical hypoalgesia, and tactile allodynia. Acipimox (100 mg kg(-1) day(-1), 4 weeks) reduced serum insulin, NEFA, and triglyceride concentrations without affecting glucose tolerance and hypercholesterolemia. It alleviated sensory nerve conduction velocity deficit and changes in behavioral measures of sensory function and corrected oxidative-nitrosative stress, but not impaired insulin signaling, in peripheral nerve. Elevated NEFA increased total and mitochondrial superoxide production and NAD(P)H oxidase activity in cultured human Schwann cells. In conclusion, hypertriglyceridemia and/or increased NEFA concentrations cause prediabetic neuropathy through oxidative-nitrosative stress. Lipid-lowering agents and antioxidants may find a use in the management of this condition. PMID:22366714
Lupachyk, Sergey; Watcho, Pierre; Hasanova, Nailia; Julius, Ulrich; Obrosova, Irina G
To identify the genes controlling plasma concentrations of triglycerides (TGs), FFAs, and glucose, we carried out a quantitative trait loci (QTL) analysis of the closely related mouse strains New Zealand Black (NZB/B1NJ) and New Zealand White (NZW/LacJ), which share 63% of their genomes. The NZB � NZW F2 progeny were genotyped and phenotyped to detect QTL, and then comparative genomics, bioinformatics, and sequencing were used to narrow the QTL and reduce the number of candidate genes. Triglyceride concentrations were linked to loci on chromosomes (Chr) 4, 7, 8, 10, and 18. FFA concentrations were affected by a significant locus on Chr 4, a suggestive locus on Chr 16, and two interacting loci on Chr 2 and 15. Plasma glucose concentrations were affected by QTL on Chr 2, 4, 7, 8, 10, 15, 17, and 18. Comparative genomics narrowed the QTL by 31% to 86%; haplotype analysis was usually able to further narrow it by 80%. We suggest several candidate genes: Gba2 on Chr 4, Irs2 on Chr 8, and Ppargc1b on Chr 18 for TG; A2bp1 on Chr 16 for FFA; and G6pc2 on Chr 2 and Timp3 on Chr 10 for glucose. PMID:18362393
Su, Zhiguang; Tsaih, Shirng-wern; Szatkiewicz, Jin; Shen, Yuan; Paigen, Beverly
To determine the effects of the level of zinc (Zn) and copper (Cu) supplementation and of Zn/Cu ratio on serum triglycerides (TG), total-cholesterol (TC), and HDL-cholesterol (HDL-C) concentrations, groups of weanling male Sprague Dawley rats were fed diets containing 4 levels of Cu (0, 0.56, 1.68, and 5.04 ppm) and 4 levels of Zn (0, 5, 10 and 20 ppm) for 6 weeks (Low supplementation, Expt I), or a high Zn and Cu supplements each at 4 levels (0, 5.6, 16.8, and 50.4 ppm Cu, plus 0, 50, 100, and 200 ppm Zn) for 6 weeks (Expt II). The effects of Zn/Cu ratios on the parameters were evaluated by combining data from Expt I and Expt II treatments with the same Zn/Cu ratios but different levels of Zn and Cu. Results of the combined data indicated that an increase in dietary Zn was associated with significant (p less than or equal to 0.01) increase in serum triglyceride concentrations, while an increase in dietary Cu was associated with significant (p less than or equal to 0.01) decrease in serum TC and HDL-C concentrations. Dietary Zn/Cu ratios had no significant effect on serum lipids. There is the indication that the absolute levels of the minerals in the diet may be more important in lipid metabolism. These results are in agreement with previous reports.
Frimpong, N.A.; Magee, A.C.
TG13 diagnostic criteria and severity grading of acute cholecystitis (with videos).
Since its publication in 2007, the Tokyo Guidelines for the management of acute cholangitis and cholecystitis (TG07) have been widely adopted. The validation of TG07 conducted in terms of clinical practice has shown that the diagnostic criteria for acute cholecystitis are highly reliable but that the definition of definite diagnosis is ambiguous. Discussion by the Tokyo Guidelines Revision Committee concluded that acute cholecystitis should be suspected when Murphy's sign, local inflammatory findings in the gallbladder such as right upper quadrant abdominal pain and tenderness, and fever and systemic inflammatory reaction findings detected by blood tests are present but that definite diagnosis of acute cholecystitis can be made only on the basis of the imaging of ultrasonography, computed tomography or scintigraphy (HIDA scan). These proposed diagnostic criteria provided better specificity and accuracy rates than the TG07 diagnostic criteria. As for the severity assessment criteria in TG07, there is evidence that TG07 resulted in clarification of the concept of severe acute cholecystitis. Furthermore, there is evidence that severity assessment in TG07 has led to a reduction in the mean duration of hospital stay. As for the factors used to establish a moderate grade of acute cholecystitis, such as leukocytosis, ALP, old age, diabetes, being male, and delay in admission, no new strong evidence has been detected indicating that a change in the criteria used in TG07 is needed. Therefore, it was judged that the severity assessment criteria of TG07 could be applied in the updated Tokyo Guidelines (TG13) with minor changes. TG13 presents new standards for the diagnosis, severity grading and management of acute cholecystitis. Free full-text articles and a mobile application of TG13 are available via http://www.jshbps.jp/en/guideline/tg13.html. PMID:23340953
Yokoe, Masamichi; Takada, Tadahiro; Strasberg, Steven M; Solomkin, Joseph S; Mayumi, Toshihiko; Gomi, Harumi; Pitt, Henry A; Garden, O James; Kiriyama, Seiki; Hata, Jiro; Gabata, Toshifumi; Yoshida, Masahiro; Miura, Fumihiko; Okamoto, Kohji; Tsuyuguchi, Toshio; Itoi, Takao; Yamashita, Yuichi; Dervenis, Christos; Chan, Angus C W; Lau, Wan-Yee; Supe, Avinash N; Belli, Giulio; Hilvano, Serafin C; Liau, Kui-Hin; Kim, Myung-Hwan; Kim, Sun-Whe; Ker, Chen-Guo
Interactions of carbonyl {sup 13}C-enriched triacylglycerols (TG) with phospholipid bilayers were studied by {sup 13}C NMR spectroscopy. In spectra of DPPC vesicles with TG at 40-50{degree}C, both triolein (TO) and tripalmitin (TP) had narrow carbonyl resonances, indicative of rapid motions, and chemical shifts indicative of H bonding of the TG carbonyls with solvent (H{sub 2}O) at the aqueous interfaces of the vesicle bilayer. Below the phase transition temperature of the DPPC/TG vesicles, most phospholipid peaks broadened markedly. In DPPC vesicles with TP, the TP carbonyl peaks broadened beyond detection below the transition, whereas in vesicles with TO, the TO carbonyl peaks showed little change in line width or chemical shift and no change in the integrated intensity. These properties (extent of solubility in the PC surface, conformation, solvent accessibility, and molecular mobility) may be important for enzymatic hydrolysis and protein-mediated transfer of TG. In gel-phase DPPC, the molecular mobility of the TG depends on the nature of the TG acyl chains. In the DPPC/TG mixtures studied, attempts to incorporate TG in excess of the bilayer solubility resulted in production of emulsion particles. The significance of these results for TG metabolism is discussed.
Hamilton, J.A. (Boston Univ. School of Medicine, MA (USA))
Pilgrim Dark Energy in $f(T, T_G)$ cosmology
We work on the reconstruction scenario of pilgrim dark energy" (PDE) in $f(T, T_G)$. In PDE model it is assumed that a repulsive force that is accelerating the Universe is phantom type with $(w_{DE}T, T_G)$ models and correspondingly evaluate equation of state parameter for various choices of scale factor. Also, we assume polynomial form of $f(T, T_G)$ in terms of cosmic time and reconstruct $H$ and $w_{DE}$ in this manner. Through discussion, it is concluded that PDE shows aggressive phantom-like behaviour for$s=-2$ in $f(T, T_G)$ gravity.
Surajit Chattopadhyay; Abdul Jawad; Davood Momeni; Ratbay Myrzakulov
Common variants associated with plasma triglycerides and risk for coronary artery disease
Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiologic studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P<5�10?8 for each) to examine the role of triglycerides on risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglycerides, and show that the direction and magnitude of both are factors in determining CAD risk. Second, we consider loci with only a strong magnitude of association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol, a polymorphism's strength of effect on triglycerides is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD. PMID:24097064
Do, Ron; Willer, Cristen J.; Schmidt, Ellen M.; Sengupta, Sebanti; Gao, Chi; Peloso, Gina M.; Gustafsson, Stefan; Kanoni, Stavroula; Ganna, Andrea; Chen, Jin; Buchkovich, Martin L.; Mora, Samia; Beckmann, Jacques S.; Bragg-Gresham, Jennifer L.; Chang, Hsing-Yi; Demirkan, Ayse; Den Hertog, Heleen M.; Donnelly, Louise A.; Ehret, Georg B.; Esko, Tonu; Feitosa, Mary F.; Ferreira, Teresa; Fischer, Krista; Fontanillas, Pierre; Fraser, Ross M.; Freitag, Daniel F.; Gurdasani, Deepti; Heikkila, Kauko; Hypponen, Elina; Isaacs, Aaron; Jackson, Anne U.; Johansson, Asa; Johnson, Toby; Kaakinen, Marika; Kettunen, Johannes; Kleber, Marcus E.; Li, Xiaohui; Luan, Jian'an; Lyytikainen, Leo-Pekka; Magnusson, Patrik K.E.; Mangino, Massimo; Mihailov, Evelin; Montasser, May E.; Muller-Nurasyid, Martina; Nolte, Ilja M.; O'Connell, Jeffrey R.; Palmer, Cameron D.; Perola, Markus; Petersen, Ann-Kristin; Sanna, Serena; Saxena, Richa; Service, Susan K.; Shah, Sonia; Shungin, Dmitry; Sidore, Carlo; Song, Ci; Strawbridge, Rona J.; Surakka, Ida; Tanaka, Toshiko; Teslovich, Tanya M.; Thorleifsson, Gudmar; Van den Herik, Evita G.; Voight, Benjamin F.; Volcik, Kelly A.; Waite, Lindsay L.; Wong, Andrew; Wu, Ying; Zhang, Weihua; Absher, Devin; Asiki, Gershim; Barroso, Ines; Been, Latonya F.; Bolton, Jennifer L.; Bonnycastle, Lori L; Brambilla, Paolo; Burnett, Mary S.; Cesana, Giancarlo; Dimitriou, Maria; Doney, Alex S.F.; Doring, Angela; Elliott, Paul; Epstein, Stephen E.; Eyjolfsson, Gudmundur Ingi; Gigante, Bruna; Goodarzi, Mark O.; Grallert, Harald; Gravito, Martha L.; Groves, Christopher J.; Hallmans, Goran; Hartikainen, Anna-Liisa; Hayward, Caroline; Hernandez, Dena; Hicks, Andrew A.; Holm, Hilma; Hung, Yi-Jen; Illig, Thomas; Jones, Michelle R.; Kaleebu, Pontiano; Kastelein, John J.P.; Khaw, Kay-Tee; Kim, Eric; Klopp, Norman; Komulainen, Pirjo; Kumari, Meena; Langenberg, Claudia; Lehtimaki, Terho; Lin, Shih-Yi; Lindstrom, Jaana; Loos, Ruth J.F.; Mach, Francois; McArdle, Wendy L; Meisinger, Christa; Mitchell, Braxton D.; Muller, Gabrielle; Nagaraja, Ramaiah; Narisu, Narisu; Nieminen, Tuomo V.M.; Nsubuga, Rebecca N.; Olafsson, Isleifur; Ong, Ken K.; Palotie, Aarno; Papamarkou, Theodore; Pomilla, Cristina; Pouta, Anneli; Rader, Daniel J.; Reilly, Muredach P.; Ridker, Paul M.; Rivadeneira, Fernando; Rudan, Igor; Ruokonen, Aimo; Samani, Nilesh; Scharnagl, Hubert; Seeley, Janet; Silander, Kaisa; Stancakova, Alena; Stirrups, Kathleen; Swift, Amy J.; Tiret, Laurence; Uitterlinden, Andre G.; van Pelt, L. Joost; Vedantam, Sailaja; Wainwright, Nicholas; Wijmenga, Cisca; Wild, Sarah H.; Willemsen, Gonneke; Wilsgaard, Tom; Wilson, James F.; Young, Elizabeth H.; Zhao, Jing Hua; Adair, Linda S.; Arveiler, Dominique; Assimes, Themistocles L.; Bandinelli, Stefania; Bennett, Franklyn; Bochud, Murielle; Boehm, Bernhard O.; Boomsma, Dorret I.; Borecki, Ingrid B.; Bornstein, Stefan R.; Bovet, Pascal; Burnier, Michel; Campbell, Harry; Chakravarti, Aravinda; Chambers, John C.; Chen, Yii-Der Ida; Collins, Francis S.; Cooper, Richard S.; Danesh, John; Dedoussis, George; de Faire, Ulf; Feranil, Alan B.; Ferrieres, Jean; Ferrucci, Luigi; Freimer, Nelson B.; Gieger, Christian; Groop, Leif C.; Gudnason, Vilmundur; Gyllensten, Ulf; Hamsten, Anders; Harris, Tamara B.; Hingorani, Aroon; Hirschhorn, Joel N.; Hofman, Albert; Hovingh, G. Kees; Hsiung, Chao Agnes; Humphries, Steve E.; Hunt, Steven C.; Hveem, Kristian; Iribarren, Carlos; Jarvelin, Marjo-Riitta; Jula, Antti; Kahonen, Mika; Kaprio, Jaakko; Kesaniemi, Antero; Kivimaki, Mika; Kooner, Jaspal S.; Koudstaal, Peter J.; Krauss, Ronald M.; Kuh, Diana; Kuusisto, Johanna; Kyvik, Kirsten O.; Laakso, Markku; Lakka, Timo A.; Lind, Lars; Lindgren, Cecilia M.; Martin, Nicholas G.; Marz, Winfried; McCarthy, Mark I.; McKenzie, Colin A.; Meneton, Pierre; Metspalu, Andres; Moilanen, Leena; Morris, Andrew D.; Munroe, Patricia B.; Nj?lstad, Inger; Pedersen, Nancy L.; Power, Chris; Pramstaller, Peter P.; Price, Jackie F.; Psaty, Bruce M.; Quertermous, Thomas; Rauramaa, Rainer; Saleheen, Danish; Salomaa, Veikko; Sanghera, Dharambir K.; Saramies, Jouko; Schwarz, Peter E.H.; Sheu, Wayne H-H; Shuldiner, Alan R.; Siegbahn, Agneta; Spector, Tim D.; Stefansson, Kari; Strachan, David P.; Tayo, Bamidele O.; Tremoli, Elena; Tuomilehto, Jaakko; Uusitupa, Matti; van Duijn, Cornelia M.; Vollenweider, Peter; Wallentin, Lars; Wareham, Nicholas J.; Whitfield, John B.; Wolffenbuttel, Bruce H.R.; Altshuler, David; Ordovas, Jose M.; Boerwinkle, Eric; Palmer, Colin N.A.; Thorsteinsdottir, Unnur; Chasman, Daniel I.; Rotter, Jerome I.; Franks, Paul W.
Use of filter paper stored dried blood for measurement of triglycerides
Adaptation of assays on dried blood has advantages of ease of collection, transportation, minimal invasiveness and requirement of small volume. A method for extraction and estimation of triglyceride from blood spots dried on filter paper (Whatman no. 3) has been developed. A single dried blood spot containing 10 ?L blood was used. Triglyceride was efficiently extracted in methanol from blood
Rizwana Quraishi; Ramakrishnan Lakshmy; Dorairaj Prabhakaran; Ashok Kumar Mukhopadhyay; Bansilal Jailkhani
Common variants associated with plasma triglycerides and risk for coronary artery disease.
Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P < 5 � 10(-8) for each) to examine the role of triglycerides in risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and we show that the direction and magnitude of the associations with both traits are factors in determining CAD risk. Second, we consider loci with only a strong association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol (HDL-C) levels, the strength of a polymorphism's effect on triglyceride levels is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD. PMID:24097064
Do, Ron; Willer, Cristen J; Schmidt, Ellen M; Sengupta, Sebanti; Gao, Chi; Peloso, Gina M; Gustafsson, Stefan; Kanoni, Stavroula; Ganna, Andrea; Chen, Jin; Buchkovich, Martin L; Mora, Samia; Beckmann, Jacques S; Bragg-Gresham, Jennifer L; Chang, Hsing-Yi; Demirkan, Ay?e; Den Hertog, Heleen M; Donnelly, Louise A; Ehret, Georg B; Esko, T�nu; Feitosa, Mary F; Ferreira, Teresa; Fischer, Krista; Fontanillas, Pierre; Fraser, Ross M; Freitag, Daniel F; Gurdasani, Deepti; Heikkil�, Kauko; Hypp�nen, Elina; Isaacs, Aaron; Jackson, Anne U; Johansson, Asa; Johnson, Toby; Kaakinen, Marika; Kettunen, Johannes; Kleber, Marcus E; Li, Xiaohui; Luan, Jian'an; Lyytik�inen, Leo-Pekka; Magnusson, Patrik K E; Mangino, Massimo; Mihailov, Evelin; Montasser, May E; M�ller-Nurasyid, Martina; Nolte, Ilja M; O'Connell, Jeffrey R; Palmer, Cameron D; Perola, Markus; Petersen, Ann-Kristin; Sanna, Serena; Saxena, Richa; Service, Susan K; Shah, Sonia; Shungin, Dmitry; Sidore, Carlo; Song, Ci; Strawbridge, Rona J; Surakka, Ida; Tanaka, Toshiko; Teslovich, Tanya M; Thorleifsson, Gudmar; Van den Herik, Evita G; Voight, Benjamin F; Volcik, Kelly A; Waite, Lindsay L; Wong, Andrew; Wu, Ying; Zhang, Weihua; Absher, Devin; Asiki, Gershim; Barroso, In�s; Been, Latonya F; Bolton, Jennifer L; Bonnycastle, Lori L; Brambilla, Paolo; Burnett, Mary S; Cesana, Giancarlo; Dimitriou, Maria; Doney, Alex S F; D�ring, Angela; Elliott, Paul; Epstein, Stephen E; Eyjolfsson, Gudmundur Ingi; Gigante, Bruna; Goodarzi, Mark O; Grallert, Harald; Gravito, Martha L; Groves, Christopher J; Hallmans, G�ran; Hartikainen, Anna-Liisa; Hayward, Caroline; Hernandez, Dena; Hicks, Andrew A; Holm, Hilma; Hung, Yi-Jen; Illig, Thomas; Jones, Michelle R; Kaleebu, Pontiano; Kastelein, John J P; Khaw, Kay-Tee; Kim, Eric; Klopp, Norman; Komulainen, Pirjo; Kumari, Meena; Langenberg, Claudia; Lehtim�ki, Terho; Lin, Shih-Yi; Lindstr�m, Jaana; Loos, Ruth J F; Mach, Fran�ois; McArdle, Wendy L; Meisinger, Christa; Mitchell, Braxton D; M�ller, Gabrielle; Nagaraja, Ramaiah; Narisu, Narisu; Nieminen, Tuomo V M; Nsubuga, Rebecca N; Olafsson, Isleifur; Ong, Ken K; Palotie, Aarno; Papamarkou, Theodore; Pomilla, Cristina; Pouta, Anneli; Rader, Daniel J; Reilly, Muredach P; Ridker, Paul M; Rivadeneira, Fernando; Rudan, Igor; Ruokonen, Aimo; Samani, Nilesh; Scharnagl, Hubert; Seeley, Janet; Silander, Kaisa; Stan?�kov�, Alena; Stirrups, Kathleen; Swift, Amy J; Tiret, Laurence; Uitterlinden, Andre G; van Pelt, L Joost; Vedantam, Sailaja; Wainwright, Nicholas; Wijmenga, Cisca; Wild, Sarah H; Willemsen, Gonneke; Wilsgaard, Tom; Wilson, James F; Young, Elizabeth H; Zhao, Jing Hua; Adair, Linda S; Arveiler, Dominique; Assimes, Themistocles L; Bandinelli, Stefania; Bennett, Franklyn; Bochud, Murielle; Boehm, Bernhard O; Boomsma, Dorret I; Borecki, Ingrid B; Bornstein, Stefan R; Bovet, Pascal; Burnier, Michel; Campbell, Harry; Chakravarti, Aravinda; Chambers, John C; Chen, Yii-Der Ida; Collins, Francis S; Cooper, Richard S; Danesh, John; Dedoussis, George; de Faire, Ulf; Feranil, Alan B; Ferri�res, Jean; Ferrucci, Luigi; Freimer, Nelson B; Gieger, Christian; Groop, Leif C; Gudnason, Vilmundur; Gyllensten, Ulf; Hamsten, Anders; Harris, Tamara B; Hingorani, Aroon; Hirschhorn, Joel N; Hofman, Albert; Hovingh, G Kees; Hsiung, Chao Agnes; Humphries, Steve E; Hunt, Steven C; Hveem, Kristian; Iribarren, Carlos; J�rvelin, Marjo-Riitta; Jula, Antti; K�h�nen, Mika; Kaprio, Jaakko; Kes�niemi, Antero; Kivimaki, Mika; Kooner, Jaspal S; Koudstaal, Peter J; Krauss, Ronald M; Kuh, Diana; Kuusisto, Johanna; Kyvik, Kirsten O; Laakso, Markku; Lakka, Timo A; Lind, Lars; Lindgren, Cecilia M; Martin, Nicholas G; M�rz, Winfried; McCarthy, Mark I; McKenzie, Colin A; Meneton, Pierre; Metspalu, Andres; Moilanen, Leena; Morris, Andrew D; Munroe, Patricia B; Nj�lstad, Inger; Pedersen, Nancy L; Power, Chris; Pramstaller, Peter P; Price, Jackie F; Psaty, Bruce M; Quertermous, Thomas; Rauramaa, Rainer; Saleheen, Danish; Salomaa, Veikko; Sanghera, Dharambir K; Saramies, Jouko; Schwarz, Peter E H; Sheu, Wayne H-H; Shuldiner, Alan R; Siegbahn, Agneta; Spector, Tim D; Stefansson, Kari; Strachan, David P; Tayo, Bamidele O; Tremoli, Elena; Tuomilehto, Jaakko; Uusitupa, Matti; van Duijn, Cornelia M; Vollenweider, Peter; Wallentin, Lars; Wareham, Nicholas J; Whitfield, John B; Wolffenbuttel, Bruce H R; Altshuler, David; Ordovas, Jose M; Boerwinkle, Eric; Palmer, Colin N A; Thorsteinsdottir, Unnur; Chasman, Daniel I; Rotter, Jerome I; Franks, Paul W; Ripatti, Samuli; Cupples, L Adrienne; Sandhu, Manjinder S; Rich, Stephen S
William T.G. Morton and "The Great Moment".
The Great Moment, a Paramount movie released in 1944 about dentist William T.G. Morton's discovery of ether anesthesia a century earlier, was the odd-man-out among the movies made by the highly acclaimed director Preston Sturges in that period. It failed to attract large audiences and generally received only lukewarm reviews. Several biographies of Sturges have discussed the reasons for this anomaly; but only recently have drafts of the various versions of Sturges' scripts been published, plus additional background material about the film's production, revisions and editing. Using all this information, the author analyzes the movie and its history and asks what went wrong - and, more importantly, what went right. The general conclusion is that this little-known film has stood the test of time and is worthy of a revival among enthusiasts of dental history and a serious reassessment by movie critics in general. Despite some flaws in the final version, The Great Moment is in fact a remarkable medical biography, incorporating innovative flashback techniques and themes of inspiration and sacrifice mixed with some humor, while remaining reasonably true to historical facts surrounding dentistry's greatest triumph. PMID:12641171
Heynick, Frank
Oral zinc reduces amyloid burden in Tg2576 mice.
The aggregation of amyloid-? in Alzheimer's disease can be affected by free transition metals such as copper and zinc in the brain. Addition of copper and zinc with amyloid acts to increase aggregation and copper additionally promotes the formation of reactive oxygen species. We propose that reduction of brain copper by blocking uptake of copper from the diet is a viable strategy to regulate the formation of insoluble amyloid-? in the brain of Tg2576 mice. Mice were treated with regimens of zinc acetate, which acts with metallothionein to block copper uptake in the gut, at various times along their lifespan to model prevention and treatment paradigms. We found that the mice tolerated zinc acetate well over the six month course of study. While we did not observe significant changes in cognition and behavior, there was a reduction in insoluble amyloid-? in the brain. This observation coincided with a reduction in brain copper and interestingly no change in brain zinc. Our findings show that blocking copper uptake from the diet can redistribute copper from the brain and reduce amyloid-? aggregation. PMID:24595193
Harris, Christopher J; Voss, Kellen; Murchison, Charles; Ralle, Martina; Frahler, Kate; Carter, Raina; Rhoads, Allison; Lind, Betty; Robinson, Emily; Quinn, Joseph F
Oral zinc reduces amyloid burden in Tg2576 mice
The aggregation of amyloid beta in Alzheimer�s disease can be affected by free transition metals such as copper and zinc in the brain. Addition of copper and zinc with amyloid acts to increase aggregation and copper additionally promotes the formation of reactive oxygen species. We propose that reduction of brain copper by blocking uptake of copper from the diet is a viable strategy to regulate the formation of insoluble amyloid beta in the brain of Tg2576 mice. Mice were treated with regimens of zinc acetate, which acts with metallothionein to block copper uptake in the gut, at various times along their lifespan to model prevention and treatment paradigms. We found that the mice tolerated zinc acetate well over the six month course of study. While we did not observe significant changes in cognition and behavior, there was a reduction in insoluble amyloid beta in the brain. This observation coincided with a reduction in brain copper and interestingly no change in brain zinc. Our findings show that blocking copper uptake from the diet can redistribute copper from the brain and reduce amyloid beta aggregation. PMID:24595193
Harris, Christopher J.; Voss, Kellen; Murchison, Charles; Ralle, Martina; Frahler, Kate; Carter, Raina; Rhoads, Alison; Lind, Betty; Robinson, Emily; Quinn, Joseph F.
Modeling the solid-liquid phase transition in saturated triglycerides
NASA Astrophysics Data System (ADS)
We investigated theoretically two competing published scenarios for the melting transition of the triglyceride trilaurin (TL): those of (1) Corkery et al. [Langmuir 23, 7241 (2007)], in which the average state of each TL molecule in the liquid phase is a discotic ``Y'' conformer whose three chains are dynamically twisted, with an average angle of ~120� between them, and those of (2) Cebula et al. [J. Am. Oil Chem. Soc. 69, 130 (1992)], in which the liquid-state conformation of the TL molecule in the liquid phase is a nematic h*-conformer whose three chains are in a modified ``chair'' conformation. We developed two competing models for the two scenarios, in which TL molecules are in a nematic compact-chair (or ``h'') conformation, with extended, possibly all-trans, chains at low-temperatures, and in either a Y conformation or an h* conformation in the liquid state at temperatures higher than the phase-transition temperature, T*=319 K. We defined an h-Y model as a realization of the proposal of Corkery et al. [Langmuir 23, 7241 (2007)], and explored its predictions by mapping it onto an Ising model in a temperature-dependent field, performing a mean-field approximation, and calculating the transition enthalpy ?H. We found that the most plausible realization of the h-Y model, as applied to the solid-liquid phase transition in TL, and likely to all saturated triglycerides, gave a value of ?H in reasonable agreement with the experiment. We then defined an alternative h-h* model as a realization of the proposal of Cebula et al. [J. Am. Oil Chem. Soc. 69, 130 (1992)], in which the liquid phase exhibits an average symmetry breaking similar to an h conformation, but with twisted chains, to see whether it could describe the TL phase transition. The h-h* model gave a value of ?H that was too small by a factor of ~3-4. We also predicted the temperature dependence of the 1132 cm-1 Raman band for both models, and performed measurements of the ratios of three TL Raman bands in the temperature range of -20 �C<=T<=90 �C. The experimental results were in accord with the predictions of the h-Y model and support the proposal of Corkery et al. [Langmuir 23, 7241 (2007)] that the liquid state is made up of molecules that are each, on average, in a Y conformation. Finally, we carried out computer simulations of minimal-model TLs in the liquid phase, and concluded that although the individual TL molecules are, on average, Y conformers, long-range discotic order is unlikely to exist.
Pink, David A.; Hanna, Charles B.; Sandt, Christophe; MacDonald, Adam J.; MacEachern, Ronald; Corkery, Robert; Rousseau, D�rick
Decomposition of an amorphous precursor for S-doped titania (TiO2) nanopowders, prepared by controlled sol�gel hydrolysis�condensation of titanium(IV) tetraisopropoxide and thiourea in aqueous isopropanol, has been studied up to 800�C in flowing air by simultaneous thermogravimetric and differential thermal analysis coupled online with quadrupole mass spectrometer (TG\\/DTA�MS) and FTIR spectrometric gas cell (TG�FTIR) for analysis of gases and their evolution dynamics
J�nos Madar�sz; Ana Br?ileanu; Gy�rgy Pokol
Changes in Triglyceride Levels Over Time and Risk of Type 2 Diabetes in Young Men
OBJECTIVE�The association between changes in triglyceride concentrations over time and diabetes is unknown. We assessed whether two triglyceride determinations obtained 5 years apart can predict incident type 2 diabetes. RESEARCH DESIGN AND METHODS�Triglyceride levels at baseline (time 1) and 5 years later (time 2), followed by subsequent follow-up of 5.5 years, were measured in 13,953 apparently healthy men (age 26�45 years) with triglycerides <300 mg/dl (<3.39 mmol/l). RESULTS�During 76,742 person-years, 322 cases of diabetes occurred. A multivariate model adjusted for age, BMI, total cholesterol�to�HDL cholesterol ratio, family history of diabetes, fasting glucose, blood pressure, physical activity, and smoking status revealed a continuous independent rise in incident diabetes with increasing time 1 triglyceride levels (Ptrend < 0.001). Men in the lowest tertile of time 1 triglyceride levels who progressed to the highest tertile over follow-up (low-high) exhibited a hazard ratio (HR) of 12.62 (95% CI 3.52�31.34) compared with those remaining in the lowest tertile at both time points (reference group: low-low). Whereas men who were at the top triglyceride level tertile throughout follow-up (high-high) had a HR for diabetes of 7.08 (2.52�14.45), those whose triglyceride level decreased to the lowest tertile (high-low) exhibited a HR of 1.97 (0.67�6.13). Alterations in triglyceride levels during follow-up were associated with changes in BMI, physical activity, and eating breakfast habit (P < 0.05), but remained an independent modifier of diabetes risk even after adjustment for such changes. CONCLUSIONS�Two measurements of fasting triglyceride levels obtained 5 years apart can assist in identifying apparently healthy young men at increased risk for diabetes, independent of traditional risk factors and of associated changes in BMI and lifestyle parameters. PMID:18591400
Tirosh, Amir; Shai, Iris; Bitzur, Rafael; Kochba, Ilan; Tekes-Manova, Dorit; Israeli, Eran; Shochat, Tzippora; Rudich, Assaf
Polymorphism and kinetic behavior of binary mixtures of triglycerides.
The work is aimed at investigating the polymorphism and the phase transition kinetics of binary lipid mixtures with potential application in controlled drug delivery. The lipid systems, constituted of glyceryl tristearate (GTS) added with different amounts (1.0-7.5% w/w) of a medium-chain liquid triglyceride (C10-C12 acyl derivative - MCT), were studied by differential scanning calorimetry, by X-ray diffraction and hot-stage microscopy. The liquid lipid, although present in small amount, modified the thermal profile and the diffraction pattern of the systems, indicating that it promoted the formation of the GTS stable polymorph, ?, during the re-solidification of the melted mixture. This promotion effect of MCT was concentration-dependent and evident for systems containing MCT>2.5%. Also the kinetics of transformation of GTS polymorphs was affected by the percentage of the liquid component. The ???-transition was a biphasic process which for GTS-MCT mixture (99:1) superimposed that of pure GTS, while followed a different trend for systems containing percentages of MCT higher than 2.5. PMID:24971693
Pattarino, Franco; Bettini, Ruggero; Foglio Bonda, Andrea; Della Bella, Andrea; Giovannelli, Lorella
The mechanism of protein release from triglyceride microspheres.
The purpose of this study was to reveal factors that have an impact on the protein release kinetics from triglyceride microspheres prepared by spray congealing. We investigated the effect of protein particle size, morphology and distribution on protein release from microspheres by confocal laser scanning microscopy (CLSM)(.) The microspheres were loaded with three types of model particles made of FITC-labeled bovine serum albumin: freeze dried protein, spherical particles obtained by precipitation in the presence of PEG and micronized material. Investigation by light microscopy and laser light diffraction revealed that the freeze dried material consisted mainly of app. 29 ?m elongated shaped particles. The precipitated BSA consisted mainly of 9.0 ?m diameter spherically shaped particles while the micronized protein prepared by jet milling consisted of 4.9 ?m sized rounded particles of high uniformity. Microspheres were embedded into a cold-curing resin and cut with a microtome. Subsequent investigation by CLSM revealed major differences of distribution of the polydisperse protein particles inside the microsphere sections depending on the type of BSA that was used. Particles of micronized and precipitated protein were distributed almost throughout the microsphere cross section. The protein distribution had a marked impact on the release kinetics in phosphate buffer. Large protein particles led to a considerably faster release than small ones. By staining the release medium we demonstrated that in all three cases there was a strong correlation between protein release and buffer intrusion. PMID:20659511
Zaky, A; Elbakry, A; Ehmer, A; Breunig, M; Goepferich, A
Modeling the liquid-solid transition in saturated triglycerides
NASA Astrophysics Data System (ADS)
Corkery et al. have proposed that the high-temperature state of the triglyceride trilaurin (TL) is a Y-conformer, in which the three hydrocarbon chains are dynamically twisted with an average angle of �120 between them. Using computer simulations, we first show that the high-temperature state is indeed the Y conformation. We then develop a theory of the liquid-solid transition of this system, in which TL molecules are in a chair (h) conformation, with extended, possibly all-trans, chains at low-temperatures, and are in a Y conformation in the liquid phase at temperatures higher than the transition temperature, T* 319K. We map this ``h-Y model'' onto an Ising model in a temperature-dependent field, perform a mean-field approximation, and calculate the transition enthalpy, which is in good agreement with experiment. We also predict the temperature-dependence of the 1132 cm-1 Raman band. Our results support the proposal that the liquid state is made up of molecules in the Y conformation.
Hanna, C. B.; Pink, D. A.; MacDonald, A. J.; Thillainadarajah, K.; Corkery, R.; Rousseau, D.
Anisotropy energy of spin glasses at Tg studied by transverse susceptibility
691 Anisotropy energy of spin glasses at T Tg studied by transverse susceptibility F. Hippert and H. 2014 We have investigated the anisotropic properties of CuMn, AgMn, CuMnAux, AuFe spin glasses at T Tg characterized by a macroscopic anisotropy field HA for small deviations. At a given temperature the anisotropy
Boyer, Edmond
1. GREAT NORTHERN ELEVATORS. 1900 STEEL ELEVATOR WITH SQUARE BINS (AS OPPOSED) TO THE SIMILAR STEEL ELEVATOR IN BUFFALO NEW YORK WITH ROUND ELEVATOR BINS. - Great Northern Elevator "S", Saint Louis Bay, Superior, Douglas County, WI
Autophagy, the major lysosomal pathway for the turnover of intracellular organelles is markedly impaired in neurons in Alzheimer's disease and Alzheimer mouse models. We have previously reported that severe lysosomal and amyloid neuropathology and associated cognitive deficits in the TgCRND8 Alzheimer mouse model can be ameliorated by restoring lysosomal proteolytic capacity and autophagy flux via genetic deletion of the lysosomal protease inhibitor, cystatin B. Here we present evidence that macroautophagy is a significant pathway for lipid turnover, which is defective in TgCRND8 brain where lipids accumulate as membranous structures and lipid droplets within giant neuronal autolysosomes. Levels of multiple lipid species including several sphingolipids (ceramide, ganglioside GM3, GM2, GM1, GD3 and GD1a), cardiolipin, cholesterol and cholesteryl esters are elevated in autophagic vacuole fractions and lysosomes isolated from TgCRND8 brain. Lipids are localized in autophagosomes and autolysosomes by double immunofluorescence analyses in wild-type mice and colocalization is increased in TgCRND8 mice where abnormally abundant GM2 ganglioside-positive granules are detected in neuronal lysosomes. Cystatin B deletion in TgCRND8 significantly reduces the number of GM2-positive granules and lowers the levels of GM2 and GM3 in lysosomes, decreases lipofuscin-related autofluorescence, and eliminates giant lipid-containing autolysosomes while increasing numbers of normal-sized autolysosomes/lysosomes with reduced content of undigested components. These findings have identified macroautophagy as a previously unappreciated route for delivering membrane lipids to lysosomes for turnover, a function that has so far been considered to be mediated exclusively through the endocytic pathway, and revealed that autophagic-lysosomal dysfunction in TgCRND8 brain impedes lysosomal turnover of lipids as well as proteins. The amelioration of lipid accumulation in TgCRND8 by removing cystatin B inhibition on lysosomal proteases suggests that enhancing lysosomal proteolysis improves the overall environment of the lysosome and its clearance functions, which may be possibly relevant to a broader range of lysosomal disorders beyond Alzheimer's disease. PMID:25270989
Yang, Dun-Sheng; Stavrides, Philip; Saito, Mitsuo; Kumar, Asok; Rodriguez-Navarro, Jose A; Pawlik, Monika; Huo, Chunfeng; Walkley, Steven U; Saito, Mariko; Cuervo, Ana M; Nixon, Ralph A
TG13 guidelines for diagnosis and severity grading of acute cholangitis (with videos).
Since the publication of the Tokyo Guidelines for the management of acute cholangitis and cholecystitis (TG07), diagnostic criteria and severity assessment criteria for acute cholangitis have been presented and extensively used as the primary standard all over the world. However, it has been found that there are crucial limitations in these criteria. The diagnostic criteria of TG07 do not have enough sensitivity and specificity, and its severity assessment criteria are unsuitable for clinical use. A working team for the revision of TG07 was organized in June, 2010, and these criteria have been updated through clinical implementation and its assessment by means of multi-center analysis. The diagnostic criteria of acute cholangitis have been revised as criteria to establish the diagnosis where cholestasis and inflammation demonstrated by clinical signs or blood test in addition to biliary manifestations demonstrated by imaging are present. The diagnostic criteria of the updated Tokyo Guidelines (TG13) have high sensitivity (87.6 %) and high specificity (77.7 %). TG13 has better diagnostic capacity than TG07. Severity assessment is classified as follows: Grade III: associated with organ failure; Grade II: early biliary drainage should be conducted; Grade1: others. As for the severity assessment criteria of TG07, separating Grade II and Grade I at the time of diagnosis was impossible, so they were unsuitable for clinical practice. Therefore, the severity assessment criteria of TG13 have been revised so as not to lose the timing of biliary drainage or treatment for etiology. Based on evidence, five predictive factors for poor prognosis in acute cholangitis--hyperbilirubinemia, high fever, leukocytosis, elderly patient and hypoalbuminemia--have been extracted. Grade II can be diagnosed if two of these five factors are present. Free full-text articles and a mobile application of TG13 are available via http://www.jshbps.jp/en/guideline/tg13.html. PMID:23307001
Kiriyama, Seiki; Takada, Tadahiro; Strasberg, Steven M; Solomkin, Joseph S; Mayumi, Toshihiko; Pitt, Henry A; Gouma, Dirk J; Garden, O James; B�chler, Markus W; Yokoe, Masamichi; Kimura, Yasutoshi; Tsuyuguchi, Toshio; Itoi, Takao; Yoshida, Masahiro; Miura, Fumihiko; Yamashita, Yuichi; Okamoto, Kohji; Gabata, Toshifumi; Hata, Jiro; Higuchi, Ryota; Windsor, John A; Bornman, Philippus C; Fan, Sheung-Tat; Singh, Harijt; de Santibanes, Eduardo; Gomi, Harumi; Kusachi, Shinya; Murata, Atsuhiko; Chen, Xiao-Ping; Jagannath, Palepu; Lee, SungGyu; Padbury, Robert; Chen, Miin-Fu; Dervenis, Christos; Chan, Angus C W; Supe, Avinash N; Liau, Kui-Hin; Kim, Myung-Hwan; Kim, Sun-Whe
Inhibition of JAK2 Signaling by TG101209 Enhances Radiotherapy in Lung Cancer Models
Introduction Persistent STAT3 activation contributes to lung carcinogenesis. Survivin, one of STAT3-regulated genes, is antiapoptotic and confers cancer radioresistance. Methods We tested whether TG101209, a small-molecule inhibitor of JAK2 (a STAT3-activating tyrosine kinase), affected survivin expression and sensitized lung cancer to radiation. We investigated whether inhibition of JAK2 signaling with TG101209 can be used to reduce survivin expression and enhance radiosensitivity of lung cancer cells in vitro and tumor growth delay in vivo. JAK2 downstream signaling, including PI3-K/Akt and Ras/MAPK/ERK pathways, was also explored. Results TG101209 inhibited STAT3 activation and survivin expression, and sensitized HCC2429 (DER=1.34,p=0.002) and H460 (DER=1.09,p=0.006) cells to radiation in clonogenic assays. Radiation promoted phospho-Akt and phospho-ERK in H460 cells, while their levels were unchanged in HCC2429. After treatment with TG101209, phospho-ERK protein levels were reduced in both HCC2429 and H460 cells. HCC2429 cells transfected with K-Ras-12V mutant were more resistant to radiation- and TG101209-induced apoptosis than wild-type control cells. In vivo, addition of TG101209 to radiation in lung xenografts produced a significant tumor growth delay (>10 days) compared to radiation alone and was well tolerated. Immunohistochemistry staining of tumor sections showed that TG101209 increased apoptosis and decreased cell proliferation and vascular density, suggesting that TG101209 also has antiangiogenic effects. Conclusions TG101209 enhanced the effects of radiation in lung cancer in vitro and in vivo. This study suggests the potential utility of selecting lung cancer patients according to K-Ras mutation status for future clinical trials testing combination of TG101209 and radiotherapy. PMID:21325979
Sun, Yunguang; Moretti, Luigi; Giacalone, Nicholas J; Schleicher, Stephen; Speirs, Christina K.; Carbone, David P.; Lu, Bo
Lipoprotein production by the heart: a novel pathway of triglyceride export from cardiomyocytes.
The current knowledge on lipoprotein secretion from the heart is examined in this article. The ability of cells to secrete apolipoprotein B (apo-B) containing lipoproteins depends on expression of the apo-B and microsomal triglyceride transfer protein (MTP) genes. Initially, it was shown that both genes are expressed in cardiac myocytes of mice and humans. Electron microscopy of human cardiac myocytes revealed lipoproteins in the secretory pathway and metabolic labelling studies demonstrated the secretion of LDL-like lipoproteins from minced heart biopsies. To examine the role of lipoprotein formation in the heart, we tested whether overexpression of a human apo-B transgene in the heart affects cardiac triglyceride accumulation. In wild-type mice, diabetes conferred an increase in heart triglycerides. In apo-B transgenic mice, diabetes did not affect heart triglycerides. Also, apo-B overexpression prevents fasting-induced heart triglyceride accumulation, whereas inhibition of MTP expression increases heart triglycerides in mice. In hypoxic human hearts, MTP mRNA expression was negatively associated with triglyceride contents. These findings suggest that lipoprotein formation rates affect cardiac triglyceride stores. The MTP mRNA levels are approximately 2-fold higher in hypoxic compared with normoxic human myocardium and in diabetic compared with non-diabetic mouse hearts. In both hypoxia and diabetes, the delivery of triglycerides to the heart exceeds their utilization for beta-oxidation. Thus, endogenous lipoprotein secretion rates might be upregulated to remove surplus fat from the heart. Diabetes negatively affected indexes of systolic and diastolic function in wild-type mice. However, the diabetogenic effects on the heart were absent or much less pronounced in apo-B transgenic mice. This suggests that accelerated lipoprotein formation by the heart attenuates development of diabetic cardiomyopathy in mice. In conclusion, current evidence suggests that lipoprotein secretion from the heart plays an integrated role in cardiac lipid homeostasis and that it can affect the biomechanical function of the heart. PMID:12570165
Nielsen, L B
Both the apolipoprotein A5 and C3 genes have repeatedly been shown to play an important role in determining plasma triglyceride concentrations in humans and mice. In mice, transgenic and knockout experiments indicate that plasma triglyceride levels are negatively and positively correlated with APOA5 and APOC3 expression, respectively. In humans, common polymorphisms in both genes have also been associated with plasma triglyceride concentrations. The evolutionary relationship among these two apolipoprotein genes and their close proximity on human chromosome 11q23 have largely precluded the determination of their relative contribution to altered Both the apolipoprotein A5 and C3 genes have repeatedly been shown to play an important role in determining plasma triglyceride concentrations in humans and mice. In mice, transgenic and knockout experiments indicate that plasma triglyceride levels are negatively and positively correlated with APOA5 and APOC3 expression, respectively. In humans, common polymorphisms in both genes have also been associated with plasma triglyceride concentrations. The evolutionary relationship among these two apolipoprotein genes and their close proximity on human chromosome 11q23 have largely precluded the determination of their relative contribution to altered triglycerides. To overcome these confounding factors and address their relationship, we generated independent lines of mice that either over-expressed (''double transgenic'') or completely lacked (''double knockout'') both apolipoprotein genes. We report that both ''double transgenic'' and ''double knockout'' mice display intermedia tetriglyceride concentrations compared to over-expression or deletion of either gene alone. Furthermore, we find that human ApoAV plasma protein levels in the ''double transgenic'' mice are approximately 500-fold lower than human ApoCIII levels, supporting ApoAV is a potent triglyceride modulator despite its low concentration. Together, these data indicate that APOA5 and APOC3 independently influence plasma triglyceride concentrations but in an opposing manner.
Baroukh, Nadine N.; Bauge, Eric; Akiyama, Jennifer; Chang, Jessie; Fruchart, Jean-Charles; Rubin, Edward M.; Fruchart, Jamila; Pennacchio, Len A.
Patients with sickle cell anemia (SCA) have usually lower diastolic, systolic and mean blood pressure (BP) than the general population. However, BP values ?120/70 mmHg considerably increase the risk for acute and chronic complications in SCA. The aim of this study was to identify biological factors associated with relative hypertension in adults with SCA. We compared the hematological, lipid and hemolytic profiles, as well as blood viscosity, between SCA patients with normal BP (<120/70 mmHg, n?=?54) and those with relative hypertension (BP?120/70 mmHg, n?=?43). Our results demonstrated that male gender (OR: 3.49; 95%CI 1.20 to 10.16, p<0.05), triglycerides (OR: 9.19; 95% CI 2.29 to 36.95, p<0.01), blood viscosity (OR: 1.35; 95% CI 1.01 to 1.81, p<0.05) and body mass index (OR: 1.37; 95% CI 1.14 to 1.64, p<0.01) were independent risks factors for relative hypertension in SCA. No association was found between the BP status and the positive history of painful vaso-occlusive crisis or acute chest syndrome. An association between triglycerides level and the occurrence of these two major acute complications was detected. Our study suggests that male gender, increased triglycerides level, BMI and blood viscosity could increase the risk for developing relative hypertension in SCA. In addition, our results support a role of moderately elevated triglycerides in the pathophysiology of vaso-occlusive events. PMID:23785465
Lamarre, Yann; Lalanne-Mistrih, Marie-Laure; Romana, Marc; Lemonne, Nathalie; Mougenel, Daniele; Waltz, Xavier; Tressi�res, Beno�t; Etienne-Julan, Maryse; Tarer, Vanessa; Hardy-Dessources, Marie-Dominique; Connes, Philippe
Vaccenic acid in serum triglycerides is associated with markers of insulin resistance in men.
Serum triglyceride levels are associated with metabolic disorders; however, it remains unclear whether the fatty acid (FA) composition of triglycerides is also changed. Although there were no differences in circulating triglyceride levels between normoglycaemic-normoinsulinaemic and hyperglycaemic-hyperinsulinaemic men, inspection of individual FA revealed that vaccenic acid was enriched with hyperglycaemia-hyperinsulinaemia. Moreover, vaccenic acid levels were positively correlated with insulin and HOMA-IR. This reinforces that examination of individual FA in the context of insulin resistance is warranted. PMID:22720879
Zulyniak, Michael A; Ralston, Jessica C; Tucker, Amy J; MacKay, Kathy A; Hillyer, Lyn M; McNicholas, Paul D; Graham, Terry E; Robinson, Lindsay E; Duncan, Alison M; Ma, David W L; Mutch, David M
Increased ?-amyloid deposition in Tg-SWDI transgenic mouse brain following in vivo lead exposure.
Previous studies in humans and animals have suggested a possible association between lead (Pb) exposure and the etiology of Alzheimer's disease (AD). Animals acutely exposed to Pb display an over-expressed amyloid precursor protein (APP) and the ensuing accumulation of beta-amyloid (A?) in brain extracellular spaces. This study was designed to examine whether in vivo Pb exposure increased brain concentrations of A?, resulting in amyloid plaque deposition in brain tissues. Human Tg-SWDI APP transgenic mice, which genetically over-express amyloid plaques at age of 2-3 months, received oral gavages of 50mg/kg Pb acetate once daily for 6 weeks; a control group of the same mouse strain received the same molar concentration of Na acetate. ELISA results revealed a significant increase of A? in the CSF, brain cortex and hippocampus. Immunohistochemistry displayed a detectable increase of amyloid plaques in brains of Pb-exposed animals. Neurobehavioral test using Morris water maze showed an impaired spatial learning ability in Pb-treated mice, but not in C57BL/6 wild type mice with the same age. In vitro studies further uncovered that Pb facilitated A? fibril formation. Moreover, the synchrotron X-ray fluorescent studies demonstrated a high level of Pb present in amyloid plaques in mice exposed to Pb in vivo. Taken together, these data indicate that Pb exposure with ensuing elevated A? level in mouse brains appears to be associated with the amyloid plaques formation. Pb apparently facilitates A? fibril formation and participates in deposition of amyloid plaques. PMID:22796588
Gu, Huiying; Robison, Gregory; Hong, Lan; Barrea, Raul; Wei, Xing; Farlow, Martin R; Pushkar, Yulia N; Du, Yansheng; Zheng, Wei
Thermodyanmic Scaling of Polymer Dynamics versus Shifting by T-Tg
NASA Astrophysics Data System (ADS)
A universal scaling law for the relaxation time (?) of amorphous liquids as a function of temperature and volume has been proposed by Roland and coworkers: ?(T,V) = F(TV^?), where ? is a material-dependent constant. We test this law for four materials, linear polystyrene, star polystyrene, and two polycyanurate networks using PVT data obtained in our laboratory coupled with the temperature dependent shift factors used to reduce the viscoelastic bulk modulus at different pressures and the dynamic shear properties at ambient pressure. In all cases, ? can be reduced both by the scaling law and by shifting to account for the changes in Tg with pressure, i.e., by plotting versus T - Tg(P). In the polycyanurate case, time-crosslink density superposition holds and ? for the two materials can be reduced simply by shifting the temperature with respect to Tg to account for the changes in Tg with crosslink density; however, the thermodynamic scaling for the two materials does not superpose unless the thermodynamic function is normalized by TgVg^?. The validity of the scaling function and its relationship to T - Tg will be further examined. In addition, the impact of errors in T, Tg, and V on the ability to satisfactorily reduce data and obtain universal scaling will be discussed.
Guo, Jiaxi; Simon, Sindee
Phase behaviour in binary mixed Langmuir Blodgett monolayers of triglycerides
NASA Astrophysics Data System (ADS)
Binary mixed monolayers of the triglycerides (TAGs)-tripalmitin (PPP), tristearin (SSS) and triarachidin (AAA) at the air-water interface are investigated with the Langmuir method. Langmuir-Blodgett (LB) layers obtained by deposition on mica are investigated by Atomic Force Microscopy. Combining Langmuir and AFM results the relation between the phase behaviour of binary mixed TAGs and their chain length is established. TAG mixtures form monolayers with molecules in trident conformation at the air-water interface, like pure TAGs. The area Acond=63 � 2 and the pressure ?cond=8-10 mN/m that separate "gas" and "condensed" film structures are the same for all mixtures and pure systems. In the ?- A isotherms the sharpness of the transition from "gas" to "condensed" phase decreases with the average chain length for all systems. Using AFM data the monolayer thicknesses for mixtures and pure systems is found to be linearly dependent on the average chain length of the TAG molecules. A linear relation between film thickness and applied AFM force is established. The corresponding coefficient K� is higher for mixed monolayers ( K�=0.08�0.01 nN) than for pure systems ( K�=0.07�0.01 nN). AFM images show phase separation in the systems PPP-SSS and PPP-AAA. The solubility of the shorter PPP molecules in the "long" (SSS- and AAA-rich) phase is significant. For the mixture SSS-AAA, phase separation is not observed. In that mixture the monolayer thickness varies linearly with composition, supporting the conclusion that SSS and AAA mix almost ideally. The main driving force for phase separation is the difference in the alkyl chain length. Indeed PPP-AAA (length difference 4 C atoms) shows the most clear phase separation. The relatively weak phase separation in PPP-SSS and the absence of phase separation in SSS-AAA show that the influence of chain length difference decreases with increasing average chain length. In air PPP-SSS and PPP-AAA mixed monolayers are unstable and crystals with ?- and ?-like structure are formed on top of the monolayer as in pure PPP and SSS systems.
Zdravkova, Aneliya N.; van der Eerden, J. P. J. M.
NASA Astrophysics Data System (ADS)
In order to measurement of Triglycerides in human serum with reagent-less using near-infrared (NIR) spectroscopy. Interval partial least square (iPLS) was proposed as an effective variable selection approach for multivariate calibration. For this purpose, an independent sample set was employed to evaluate the prediction ability of the resulting model. The spectrum was split into different interval. Then, the informative region of Triglycerides (1654-1746nm), in which the PLS model has a low RMSEP with 0.157mmol/L and a high R with 0.967, is selected with 18 intervals. The results show that the informative region of Triglycerides can be obtained by iPLS and applied to design the simpler reagent-less NIR instruments for inexpensive Triglycerides measurement in future.
Huang, Furong; Yu, Jianhui; Li, Shiping
The impact of exams anxiety on the level of triglycerides in university female students.
Anxiety affects the level of blood fats such as the triglycerides according to several studies conducted in various conditions causing anxiety as exam for the university students. The health experts suggested that the anxiety works to stimulate the autonomic nervous system which in turn leads to the appearance of a group of physiologic symptoms. The current study showed the changes happened in the triglycerides' levels in the female university students before and after exams at the intermediate anxiety level compared to other high and low levels of anxiety. In addition, there was a difference in triglycerides' levels in female students of college of Science before and after exam. This difference did not appear in case of other colleges. The exam type had an impact as the significant difference appeared in the triglycerides' levels during the periodical tests and these differences did not appear in the final exam. PMID:20503603
Maimanee, Tahia A
Earlier work in our laboratory indicated that ethanolic extracts of Tabebuia impetiginosa, Arctium lappa L., Calendula officinalis, Helianthus annuus, Linum usitatissimum and L. propolis, inhibit pancreatic lipase in vitro. In a follow-up study we assessed their effects on plasma triglycerides in rats fed on a fatty meal. Extracts, orlistat or only ethanol were given orally to the rats together with the test meal and the rate of increase of postprandial triglycerides was assessed over 4?h. Clearing of the triglycerides from the blood compartment was abolished by inhibiting lipoprotein lipase with Triton WR-1339. Our results showed that out of all the extracts, the bark of Tabebuia impetiginosa led to a significant delay in the postprandial increase of plasma triglycerides. However, lapachol, which is contained in the bark of Tabebuia impetiginosa and soluble in ethanol, had no lipase inhibitory effect in vitro and hence this substance did not seem to mediate the pertinent effect. PMID:22431070
Kiage-Mokua, Beatrice Nyanchama; Roos, Nils; Schrezenmeir, J�rgen
Introduction:��Lipopolysaccharide (endotoxin, LPS) is an important potential virulence factor of Proteus rods. The serological specificity of the bacteria is defined by the structure of the O-polysaccharide chain (O-antigen) of\\u000a the LPS. Until now, 76 O-serogroups have been differentiated among Proteus strains.\\u000a \\u000a \\u000a \\u000a Materials and Methods:��LPSs were isolated from Proteus mirabilis TG 83, TG 319, and CCUG 10700 (OA) strains by phenol\\/water
Agnieszka Zab?otni; Krystyna Zych; Anna N. Kondakova; Ma?gorzata Siwi?ska; Yuriy A. Knirel; Zygmunt Sidorczyk
Tg737 signaling is required for hypoxia-enhanced invasion and migration of hepatoma cells
Background Although hypoxia is known to promote hepatoma cell invasion and migration, little is known regarding the molecular mechanisms of this process. Our previous research showed that loss of Tg737 is associated with hepatoma cell invasion and migration; therefore, we hypothesized that the Tg737 signal might be required for hypoxia-enhanced invasion and migration. Methods We established in vitro normoxic or hypoxic models to investigate the role of Tg737 in the hypoxia-enhanced invasion and migration of hepatoma cells. The hepatoma cell lines HepG2 and MHCC97-H were subjected to normoxic or hypoxic conditions, and the cell adhesion, invasion, and migration capabilities were tested. The expression of Tg737 under normoxia or hypoxia was detected using western blot assays; cell viability was determined using flow cytometry. Furthermore, we created HepG2 and MHCC97-H cells that over expressed Tg737 prior to incubation under hypoxia and investigated their metastatic characteristics. Finally, we analyzed the involvement of critical molecular events known to regulate invasion and migration. Results In this study, Tg737 expression was significantly inhibited in HepG2 and MHCC97-H cells following exposure to hypoxia. The down regulation of Tg737 expression corresponded to significantly decreased adhesion and increased invasion and migration. Hypoxia also decreased the expression/secretion of polycystin-1, increased the secretion of interleukin-8 (IL-8), and increased the levels of active and total transforming growth factor ? 1 (TGF-?1), critical regulators of cell invasion and migration. Moreover, the decrease in adhesiveness and the increase in the invasive and migratory capacities of hypoxia-treated hepatoma cells were attenuated by pcDNA3.1-Tg737 transfection prior to hypoxia. Finally, following the up regulation of Tg737, the expression/secretion of polycystin-1 increased, and the secretion of IL-8 and the levels of active and total TGF-?1 decreased correspondingly. Conclusions These data provide evidence that Tg737 contributes to hypoxia-induced invasion and migration, partially through the polycystin-1, IL-8, and TGF-?1 pathway. Taken together, this work suggests that Tg737 is involved in the invasion and migration of hepatoma cells under hypoxia, with the involvement of the polycystin-1, IL-8, and TGF-?1 signaling pathway. Tg737 is a potential therapeutic target for inhibiting the high invasion and migration potential of hepatoma cells in hypoxic regions. PMID:22974282
Studies on effects of dietary fatty acids as related to their position on triglycerides
This article reviews published literature on how the stereospecific structure of dietary triglycerides may affect lipid metabolism\\u000a in humans. Animal studies have shown enhanced absorption of fatty acids in the sn-2 position of dietary triglycerides. Increasing the level of the saturated fatty acid palmitic acid in the sn-2 position (e.g., by interesterification of the fat to randomize the positions of
J. Edward Hunter
The present study was aimed at answering the question why feeding rats an oligofructose (OFS) supplemented diet could cause\\u000a a significant reduction in plasma lipid levels. Daily administration of a 10% (w\\/w) OFS-containing diet to normolipidemic\\u000a male rats resulted in a decrease in plasma triglycerides, phospholipids and cholesterol. The triglyceride-lowering effect\\u000a was observed after one week and lasted for at
Maria Fiordaliso; Nadine Kok; Jean-Pierre Desager; Fabienne Goethals; Dominique Deboyser; Marcel Roberfroid; Nathalie Delzenne
To address the relationship between the apolipoprotein A5 and C3 genes, we generated independent lines of mice that either over-expressed or completely lacked both genes. We report both lines display normal triglyceride concentrations compared to over-expression or deletion of either gene alone. Together, these data support that APOA5 and APOC3 independently influence plasma triglyceride concentrations but in an opposing manner.
Baroukh, Nadine; Bauge, Eric; Akiyama, Jennifer; Chang, Jessie; Afzal, Veena; Fruchart, Jean-Charles; Rubin, Edward M.; Fruchart, Jamila; Pennacchio, Len A.
THE microsomal triglyceride transfer protein (MTP), which catalyses the transport of triglyceride, cholesteryl ester and phospho-lipid between phospholipid surfaces, is a heterodimer composed of the multifunctional protein, protein disulphide isomerase, and a unique large subunit with an apparent Mr of 88K (refs 1-3). It is isolated as a soluble protein from the lumen of the microsomal fraction of liver and
Daru Sharp; Laura Blinderman; Kelly A. Combs; Bernadette Kienzle; Beverly Ricci; Karen Wager-Smith; Cleris M. Gil; Christoph W. Turck; Marie-Elizabeth Boumas; Daniel J. Rader; Lawrence P. Aggerbeck; Richard E. Gregg; David A. Gordon; John R. Wetterau
Two independent apolipoprotein a5 Haplotypes influence human plasma triglyceride levels
The recently identified apolipoprotein A5 gene (APOA5) has been shown to play an important role in determining plasma triglyceride concentrations in humans and mice. We previously identified an APOA5 haplotype (designated APOA5*2) that is present in �16 percent of Caucasians and is associated with increased plasma triglyceride concentrations. In this report we describe another APOA5 haplotype (APOA5*3) containing the rare
Len A. Pennacchio; Michael Olivier; Jaroslav A. Hubacek; Ronald M. Krauss; Edward M. Rubin; Jonathan C. Cohen
Bleed of and biologic response to triglyceride filler used in radiolucent breast implants.
Radiolucent breast implants filled with triglyceride oil have recently entered limited clinical trials. To investigate the questions of oil bleed and the fate of triglycerides that might escape from ruptured breast implants, experiments reported here used peanut oil labeled with radioisotopes so that it could be traced in the urine, feces, and organs of two groups of rabbits. In one experiment, 18 rabbits were implanted with peanut oil-filled implants labeled with tritium to determine whether triglycerides diffuse across silicone elastomer shells. In another experiment, 19 rabbits were injected with 14C-labeled peanut oil to study what might happen to the oil if an implant ruptures. At the end of the follow-up period, we measured radioisotope levels in tissue samples taken from the periprosthetic capsule or injection site of each rabbit, as well as from major organs and the subcutaneous fat on the dorsum opposite the experimental site. One experiment revealed that triglycerides do bleed across the implant shells. Tritium levels were highest in the implant capsule, the omentum, the aorta, and the subcutaneous fat on the nonexperimental side. In the experiment simulating implant rupture, 14C levels were above the background radiation count at the injection site and in the same tissue sites as in the bleed experiment. Both in vivo radiolabeling studies indicate that triglycerides freed from implants by means of bleed or rupture would be absorbed, metabolized, and either excreted or redistributed to the body's normal fat storage sites if they are not needed for energy. In a third in vitro experiment, triglyceride oil specimens were inoculated with various microorganisms associated with wound infections: Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Staphylococcus epidermidis, and diphtheroids. The data demonstrate that neutral triglycerides used as a breast implant filler do not support growth of common infection-producing bacteria and suggest that triglycerides may have bactericidal properties. PMID:8628800
Young, V L; Lund, H; Ueda, K; Pidgeon, L; Schorr, M W; Kreeger, J
Stearoyl-CoA desaturase (SCD) is expressed at high levels in several human tissues and is required for the biosynthesis of oleate (18:1) and palmitoleate (16:1). These monounsaturated fatty acids are the major components of phospholipids, triglycerides, wax esters, and cholesterol es- ters. Mice with a targeted disruption of the SCD1 gene have very low levels of VLDL and impaired triglyceride and
Alan D. Attie; Ronald M. Krauss; Mark P. Gray-Keller; Alison Brownlie; Makoto Miyazaki; John J. Kastelein; Aldons J. Lusis; Anton F. H. Stalenhoef; Jonathan P. Stoehr; Michael R. Hayden; James M. Ntambi
Analysis of triglycerides in food items by desorption electrospray ionization mass spectrometry.
The triglyceride composition and oxidation behavior of edible oil and margarine samples were analyzed by desorption electrospray ionization mass spectrometry (DESI-MS). For the characterization of the lipids, the chain length and the degree of unsaturation of the fatty acids were determined. The measurements were carried out in positive ion mode; the triglycerides were detected as alkali metal or ammonium adducts. The DESI solvent was water/methanol 1:1 (v/v); measurements were carried out both with and without the addition, as an ionizing agent, of ammonium acetate that enhances the signal intensity of the ammonium adduct ions. The spectra were interpreted for both cases and intensities were compared. Triglyceride monomers and dimers were observed in the spectra. Tandem mass spectrometric (MS/MS) measurements were carried out to determine the structure of the triglycerides. It was demonstrated that the terminal fatty acids in the sn1- or sn3-position are more likely to be cleaved than the internal fatty acid (sn2-position). Characteristic triglyceride patterns were obtained using a simple and rapid sample preparation protocol comprising the simple deposition of samples onto a glass carrier surface. The triglyceride data was analyzed by principal component analysis (PCA). The different edible oils were clearly separated and the hydrogenated derivatives were identified by their triglyceride spectra. The oxidation of the oil samples was observed and the oxidation products were detected and identified. This method provides a fast and simple technique for the detection and analysis of triglycerides in oil- or fat-containing samples ranging from food items to tissue samples. The potential application areas include nutritional studies, the food industry and cosmetics. PMID:20583323
Gerbig, Stefanie; Tak�ts, Zolt�n
To explore the role of hepatic sympathetic nerves on the secretion of very low density lipoprotein (VLDL), the effects of\\u000a sympathetic neurotransmitters, noradrenaline and ATP, on the secretion of triglyceride and apoprotein B (ApoB) from the liver\\u000a were studied using rat liver perfused in situ with recirculation. During liver perfusion with physiological medium, the amount\\u000a of triglyceride in the perfusate
Tadashige Yamauchi; M. Iwai; Nobuaki Kobayashi; Takashi Shimazu
Objective Non-high-density lipoprotein cholesterol (non-HDL-C) and the triglyceride to high-density lipoprotein cholesterol ratio (TG:HDL-C) are predictors of cardiovascular risk. This post-hoc analysis assessed changes in these parameters during treatment with the atypical antipsychotics olanzapine or aripiprazole using pooled data from three randomized, long-term clinical studies in patients with schizophrenia. Methods Data were pooled from one open-label and two double-blind (26- or 52-week) studies in patients randomized to olanzapine (5�20 mg/day) or aripiprazole (15�30 mg/day). Change from baseline in non-HDL-C levels between groups was analyzed in the Observed Case (OC) dataset at each time point and Last Observation Carried Forward (LOCF) dataset at endpoint using analysis of covariance, with treatment as main effect and baseline non-HDL-C as covariate. Differences between groups in median changes from baseline in TG:HDL-C were assessed with Kruskal�Wallis tests. Results This analysis included 546 patients (olanzapine, n=274; aripiprazole, n=272). Mean changes from baseline in non-HDL-C levels were significantly different (p<0.0001) with olanzapine versus aripiprazole at Weeks 26 (+13.0 vs. ?7.5 mg/dL) and 52 (+12.2 vs. ?8.1 mg/dL). Baseline TG:HDL-C was high in the olanzapine (3.73) and aripiprazole (3.79) groups. Differences in median changes from baseline in TG:HDL-C were significant with olanzapine versus aripiprazole at Weeks 26 (+0.22 vs. ?0.54; p<0.0001) and 52 (+0.24 vs. ?0.62; p=0.004). Conclusions Long-term aripiprazole treatment is associated with improvements in lipid profiles of schizophrenia patients versus no improvement or worsening during olanzapine treatment. Consideration of cardiovascular risk is needed when prescribing antipsychotics, as is close monitoring for metabolic changes during treatment. PMID:18973991
Newcomer, John W.; Meyer, Jonathan M.; Baker, Ross A.; Eudicone, James M.; Pikalov, Andrei; Vester-Blokland, Estelle; McQuade, Robert D.; Crandall, David T.; Carson, William H.; Marcus, Ronald N.; L'Italien, Gilbert
There is growing evidence that vagus nerve stimulation (VNS) exerts a suppressive effect on both short- and long-term feeding in animal models. We previously showed that VNS with high-frequency (10 Hz) electrical impulses decreased food intake and body weight in rats. In the present study, we investigated the effect of VNS with a low frequency (1 Hz) on the serum lipid concentrations, feeding behavior and appetite in rats fed a high-fat diet. The levels of appetite-regulating peptides were also assessed. Adult male Wistar rats were subcutaneously implanted with a microstimulator (MS) and fed a high-fat diet throughout the entire study period (42 days). The left vagus nerve was stimulated subdiaphragmatically by rectangular electrical pulses (10 ms, 200 mV, 1 Hz, 12 h a day) generated by the MS. The daily food intake and body weight were measured each morning. At the end of the experiments, the serum glucose, cholesterol, triglycerides, low-density lipoproteins, high-density lipoproteins, ghrelin, leptin and nesfatin-1 concentrations were measured. The adipose tissue content was evaluated by the assessment of the weight of the epididymal fat pads. Chronic VNS significantly decreased food intake, body weight gain and epididymal fat pad weight. VNS also lowered the total plasma cholesterol concentrations and triglyceride levels. Finally, the serum concentrations of nesfatin-1 were elevated, leptin levels were decreased, and ghrelin levels remained unchanged after VNS. The study demonstrates that chronic electrical VNS exerts anorexigenic effects, lowering the blood concentration of lipids. Increased nesfatin-1 levels may contribute to these effects. PMID:24852689
Gil, Krzysztof; Bugajski, Andrzej; Kurnik, Magdalena; Thor, Piotr
The effects of bitter melon (Momordica charantia) on serum and liver triglyceride levels in rats.
Effects of three different varieties (Koimidori, Powerful-Reishi, and Hyakunari) of bitter melon (Momordica charantia) and those of methanol fraction extract of Koimidori variety on serum and liver triglycerides were studied in rats. Feeding of diets containing either bitter melon or various fractions isolated by organic solvents caused no adverse effects on food intake or growth of rats. When the effect of three different varieties of bitter melon was compared, the Koimidori variety was found to be the most effective in lowering hepatic triglyceride levels as compared to the other two varieties, suggesting a variety-dependent difference in their activity. Furthermore, the active component(s) responsible for the liver triglyceride lowering activity of Koimidori variety was assumed to be concentrated in the methanol fraction, but not in other fractions such as the n-hexane, the acetone, or the residual fraction. The triglyceride lowering activity was furthermore confirmed by the dose-dependent reduction of hepatic triglyceride, resulting the lowest level in rats fed 3.0% supplementation. In these experiments, the effects on serum lipids were marginal. The results of the present and previous studies clearly show that bitter melon, especially Koimidori variety, exhibits a potent liver triglyceride-lowering activity. PMID:15120448
Senanayake, Gamarallage V K; Maruyama, Mitsuru; Shibuya, Kei; Sakono, Masanobu; Fukuda, Nobuhiro; Morishita, Toshiro; Yukizaki, Chizuko; Kawano, Mikio; Ohta, Hideaki
The mechanisms underlying alterations in muscle lipid metabolism in obesity are poorly understood. The primary aim of this study was to compare the abundance and/or activities of key proteins that regulate intramyocellular triglyceride (IMTG) concentration in the skeletal muscle obtained from obese (OB; n = 8, BMI 38 � 1 kg/m(2)) and nonobese (NOB; n = 9, BMI 23 � 1 kg/m(2)) women. IMTG concentration was nearly twofold greater in OB vs. NOB subjects (75 � 15 vs. 40 � 8 ?mol/g dry wt, P < 0.05). In contrast, the activity and protein abundance of key enzymes that regulate the esterification of IMTG (i.e., glycerol-3-phosphate acyltransferase and diacylglycerol acyltransferase) were not elevated. We also found no differences between groups in muscle adipose triglyceride lipase and hormone-sensitive lipase (HSL) protein abundance and no differences in phosphorylation of specific sites known to affect HSL activity. However, we did find the elevated IMTG in obesity to be accompanied by a greater abundance of the fatty acid transporter FAT/CD36 in the membrane fraction of muscle from OB vs. NOB subjects (P < 0.05), suggestive of an elevated fatty acid transport capacity. Additionally, protein abundance of the lipid-trafficking protein perilipin 3 was lower (P < 0.05) in muscle from OB vs. NOB when expressed relative to IMTG content. Our findings indicate that the elevated IMTG content found in obese women was not due to an upregulation of key lipogenic proteins or to the suppression of lipolytic proteins. The impact of a low perilipin protein abundance relative to the amount of IMTG in obesity remains to be clarified. PMID:21285405
Li, Minghua; Paran, Christopher; Wolins, Nathan E; Horowitz, Jeffrey F
Background Fatty acid absorption patterns can have a major impact on the fatty acid composition in the portal, intestinal lymph, and systemic circulation. This study sought to determine the effects of long-chain triglycerides (LCT), medium-chain triglycerides (MCT), and 2-monododecanoin (2mono) on intestinal fatty acid composition during continuous feeding over a brief period. Methods The lipid sources were 100% LCT, 100% MCT, a 50:50 mixture of LCT and MCT (LCT/MCT), and a 50:50 mixture of LCT and 2mono (LCT/2mono). A total of 27 rats were randomly given 1 of the 4 diets at 200 kcal/kg/d, with 30% of total calories from lipids over 3 hours. Results MCT significantly increased each of the medium-chain fatty acids (C6:0, C8:0, and C10:0) as free fatty acids in the portal vein and about 10%/mol of C10:0 as triglycerides in the lymph compared with the other groups. There was significantly less C10:0 in lymphatic triglycerides with LCT/MCT than with MCT, but more than in the LCT and LCT/2mono diets. MCT also significantly increased the contents of C16:0, C18:0, C18:1, and C20:4 in the lymphatic triglycerides compared with all other groups including LCT/MCT. The amount of linoleic acid (C18:2) in lymphatic triglycerides followed the relative amounts of this fatty acid in the diet, with the greatest in LCT followed by LCT/MCT and LCT/2mono and least in MCT. A so-called structured lipid composed of the medium-chain fatty acid dodecanoic acid on the 2 position and long-chain fatty acids on the 1 and 3 positions appeared to be endogenously synthesized in response to the LCT/2mono diet. Conclusions The original differences in MCT and LCT content in the diets were preserved in the fatty acid composition in the intestinal free fatty acids and triglycerides during feeding. In addition, the duration of lipid administration can play a role in altering fatty acid composition in the intestine. PMID:18407910
Nancy You, Yi-Qian; Ling, Pei-Ra; Qu, Jason Zhensheng; Bistrian, Bruce R.
One Dimensional Magnetized TG Gas Properties in an External Magnetic Field
With Girardeau's Fermi-Bose mapping, we have constructed the eigenstates of a TG gas in an external magnetic field. When the number of bosons $N$ is commensurate with the number of potential cycles $M$, the probability of this TG gas in the ground state is bigger than the TG gas raised by Girardeau in 1960. Through the comparison of properties between this TG gas and Fermi gas, we find that the following issues are always of the same: their average value of particle's coordinate and potential energy, system's total momentum, single-particle density and the pair distribution function. But the reduced single-particle matrices and their momentum distributions between them are different.
Zhao Liang Wang; An Min Wang
The inclusion complex of ?-cyclodextrin (?-CD) and 4-methylbenzyl-4'-[trans-4- (guanidinomethyl)cylohexylcarbonyloxy]-biphenyl-4-carboxlylate monohydrochloride (TG44) had been investigated by using densify functional theory (DFT) and PM3 semiempirical method. The results indicate that the ?-CD includes predominantly the biphenyl moiety of TG44, and the inclusion complex formed by TG44 entering into the cavity of ?-CD from its narrow side (the primary hydroxyl group side) is more stable than that formed by TG44 entering into the cavity of ?-CD from its wide side (the secondary hydroxyl group side). The negative enthalpy changes calculated from the statistical thermodynamic calculations at 1 atm and 298.15 K suggest that the inclusion complexes are favored enthalpy-driven processes. The molecular modeling results are in good agreement with the experiment for 2D (1)H-(13)C H HETCOR spectroscopic and H-NMR spectroscopic observations. PMID:20607331
Jin, Xin; Wang, Xueye; Ren, Cuihuan; Miao, Yuan; Yi, Ling
AAPM TG-43 formalism for brachytherapy dose calculation of a 137Cs tube source.
We present a development of the use of the AAPM TG-43 dose formalism applied to 137Cs gynecological implant sources. The geometry factor, radial dose function, and anisotropy function of a 137Cs source modeled after the Nuclear Associates 67-809 series stainless steel jacketed tube source were derived following the AAPM TG-43 formalism. The dose rate distribution through the center of the source using the AAPM TG-43 dose formalism is calculated and compared with the calculations obtained using the Sievert summation and Monte Carlo simulation. The three methods resulted in an agreement within less than 5%, or an isodose rate line agreement within 2 mm. We demonstrate that the AAPM TG-43 formalism can be applied to 137Cs linear sources and is capable of serving as a 137Cs dose calculation algorithm that can be used for treatment planning purpose. PMID:15124992
Zhang, Pengpeng; Beddar, A Sam; Sibata, Claudio H
TG13: Updated Tokyo Guidelines for the management of acute cholangitis and cholecystitis.
In 2007, the Tokyo Guidelines for the management of acute cholangitis and cholecystitis (TG07) were first published in the Journal of Hepato-Biliary-Pancreatic Surgery. The fundamental policy of TG07 was to achieve the objectives of TG07 through the development of consensus among specialists in this field throughout the world. Considering such a situation, validation and feedback from the clinicians' viewpoints were indispensable. What had been pointed out from clinical practice was the low diagnostic sensitivity of TG07 for acute cholangitis and the presence of divergence between severity assessment and clinical judgment for acute cholangitis. In June 2010, we set up the Tokyo Guidelines Revision Committee for the revision of TG07 (TGRC) and started the validation of TG07. We also set up new diagnostic criteria and severity assessment criteria by retrospectively analyzing cases of acute cholangitis and cholecystitis, including cases of non-inflammatory biliary disease, collected from multiple institutions. TGRC held meetings a total of 35 times as well as international email exchanges with co-authors abroad. On June 9 and September 6, 2011, and on April 11, 2012, we held three International Meetings for the Clinical Assessment and Revision of Tokyo Guidelines. Through these meetings, the final draft of the updated Tokyo Guidelines (TG13) was prepared on the basis of the evidence from retrospective multi-center analyses. To be specific, discussion took place involving the revised new diagnostic criteria, and the new severity assessment criteria, new flowcharts of the management of acute cholangitis and cholecystitis, recommended medical care for which new evidence had been added, new recommendations for gallbladder drainage and antimicrobial therapy, and the role of surgical intervention. Management bundles for acute cholangitis and cholecystitis were introduced for effective dissemination with the level of evidence and the grade of recommendations. GRADE systems were utilized to provide the level of evidence and the grade of recommendations. TG13 improved the diagnostic sensitivity for acute cholangitis and cholecystitis, and presented criteria with extremely low false positive rates adapted for clinical practice. Furthermore, severity assessment criteria adapted for clinical use, flowcharts, and many new diagnostic and therapeutic modalities were presented. The bundles for the management of acute cholangitis and cholecystitis are presented in a separate section in TG13. Free full-text articles and a mobile application of TG13 are available via http://www.jshbps.jp/en/guideline/tg13.html. PMID:23307006
Takada, Tadahiro; Strasberg, Steven M; Solomkin, Joseph S; Pitt, Henry A; Gomi, Harumi; Yoshida, Masahiro; Mayumi, Toshihiko; Miura, Fumihiko; Gouma, Dirk J; Garden, O James; B�chler, Markus W; Kiriyama, Seiki; Yokoe, Masamichi; Kimura, Yasutoshi; Tsuyuguchi, Toshio; Itoi, Takao; Gabata, Toshifumi; Higuchi, Ryota; Okamoto, Kohji; Hata, Jiro; Murata, Atsuhiko; Kusachi, Shinya; Windsor, John A; Supe, Avinash N; Lee, SungGyu; Chen, Xiao-Ping; Yamashita, Yuichi; Hirata, Koichi; Inui, Kazuo; Sumiyama, Yoshinobu
Maximal steady-state intestinal absorption rates in unanesthetized rats for triolein, a long-chain triglyceride, and for trioctanoin, a medium-chain triglyceride, are known to differ. Both these lipids are hydrolyzed in the intestinal lumen but the products of hydrolysis are metabolized differently by the mucosal cell. Intraduodenal infusion of trioctanoin was found to reduce steady-state triolein absorption. Luminal lipolysis was shown not to be rate-controlling. High rates of trioctanoin infusion significantly lowered the pH of the luminal aqueous phase and altered the partition of oleic acid between aqueous and oil phases. Two possible mechanisms for the inhibition of triolein uptake are considered. In the intestinal lumen medium chain lipids might have lowered the activity of oleic acid monomers in the aqueous phase and reduced passive diffusion into mucosal cells. Alternatively, competition between long and medium chain fatty acids for some common receptor during transport into the intestinal mucosal cell may have occurred. Despite significant inhibition of triolein absorption by high levels of trioctanoin, the maximum number of calories absorbed from mixtures of triglycerides exceeded the maxima from either glyceride alone. The optimum proportion of triolein to trioctanoin in lipid infusion mixtures was about 3:4 by weight and the optimum dosages about half maximal for each triglyceride, which represented a caloric intake of 4 kcal/rat per 2 hr. The absorption coefficient for this lipid mixture was about 90%. It is suggested that in patients who have a limited intestinal absorptive capacity dietary fat intake might be doubled with a caloric supplement of medium-chain triglycerides without increase in steatorrhea of long-chain fat. PMID:5355337
Clark, Susanne Bennett; Holt, Peter R.
High critical temperature above T(g) may contribute to the stability of biological systems.
In this study, we characterized the molecular mobility around T(g) in sugars, poly-L-lysine and dry desiccation-tolerant biological systems, using ST-EPR, (1)H-NMR, and FTIR spectroscopy, to understand the nature and composition of biological glasses. Two distinct changes in the temperature dependence of the rotational correlation time (tau(R)) of the spin probe 3-carboxy-proxyl or the second moment (M(2)) were measured in sugars and poly-L-lysine. With heating, the first change was associated with the melting of the glassy state (T(g)). The second change (T(c)), at which tau(R) abruptly decreased over several orders of magnitude, was found to correspond with the so-called cross-over temperature, where the dynamics changed from solid-like to liquid-like. The temperature interval between T(g) and T(c) increased in the order of sucrose < trehalose < raffinose = staychose < poly-L-lysine < biological tissues, from 17 to >50 degrees C, implying that the stability above T(g) improved in the same order. These differences in temperature-dependent mobilities above T(g) suggest that proteins rather than sugars play an important role in the intracellular glass formation. The exceptionally high T(c) of intracellular glasses is expected to provide excellent long-term stability to dry organisms, maintaining a slow molecular motion in the cytoplasm even at temperatures far above T(g). PMID:10920041
Buitink, J; van den Dries, I J; Hoekstra, F A; Alberda, M; Hemminga, M A
Ocular Changes in TgF344-AD Rat Model of Alzheimer's Disease
Purpose. Alzheimer's disease (AD) is the most common neurodegenerative disorder characterized by progressive decline in learning, memory, and executive functions. In addition to cognitive and behavioral deficits, vision disturbances have been reported in early stage of AD, well before the diagnosis is clearly established. To further investigate ocular abnormalities, a novel AD transgenic rat model was analyzed. Methods. Transgenic (Tg) rats (TgF344-AD) heterozygous for human mutant APPswe/PS1?E9 and age-matched wild type (WT) rats, as well as 20 human postmortem retinal samples from both AD and healthy donors were used. Visual function in the rodent was analyzed using the optokinetic response. Immunohistochemistry on retinal and brain sections was used to detect various markers including amyloid-? (A?) plaques. Results. As expected, A? plaques were detected in the hippocampus, cortex, and retina of Tg rats. Plaque-like structures were also found in two AD human whole-mount retinas. The choroidal thickness was significantly reduced in both Tg rat and in AD human eyes when compared with age-matched controls. Tg rat eyes also showed hypertrophic retinal pigment epithelial cells, inflammatory cells, and upregulation of complement factor C3. Although visual acuity was lower in Tg than in WT rats, there was no significant difference in the retinal ganglion cell number and retinal vasculature. Conclusions. Further studies are needed to elucidate the significance and mechanisms of this pathological change and luminance threshold recording from the superior colliculus. PMID:24398104
Tsai, Yuchun; Lu, Bin; Ljubimov, Alexander V.; Girman, Sergey; Ross-Cisneros, Fred N.; Sadun, Alfredo A.; Svendsen, Clive N.; Cohen, Robert M.; Wang, Shaomei
NASA Astrophysics Data System (ADS)
Although the glass transition temperature (Tg) and dynamics of polymers confined to the nanoscale have been studied for twenty years, a physical understanding is still lacking. The reason for a polymer species dependent Tg-confinement effect and the role of neighboring polymer domains in perturbing the Tg of a confined species are areas with a need for greater study as they will inform many of the decisions regarding the use of polymers in nanomaterials. In this work, fluorescence spectroscopy is used as the primary tool to characterize Tg in a number of systems. First, micelle core Tg and critical micelle temperatures can be determined via pyrenyl label fluorescence for block copolymers in organic solvent at polymer contents which cannot be reliably characterized by other standard methods. Next, measurements were extended to miscible polymer-polymer blend systems where two component Tgs can be determined via a single pyrene-labeled component. Fluorescence can characterize systems with small component Tg differences and near-infinitely dilute blend components unlike scanning calorimetry. Studies of the near-infinitely dilute blend components reveal that a 0.1 wt% polystyrene component can have its Tg tuned over a 150 �C range depending on the blend partner. Analogous tunability of Tg is also reported in multilayer film systems with an ultrathin PS layer surrounding by bulk neighboring domains. The same limiting Tg is reported by PS for a given neighbor indicating a common physical origin of perturbations in both systems. The perturbations are correlated with fragility which also tracks with the magnitude of Tg-confinement effects in single layer polymer films. Thus, fragility provides a unifying explanation of confinement effects in multilayer films, blends, and single layer films (in the absence of attractive interactions). Surface wave dynamics are also examined in ultrathin polystyrene layers on various substrates. It is demonstrated that surface dynamics become much slower than anticipated by capillary wave theory as the film thickness decreases. Additionally, surface wave dynamics become orders of magnitude faster as the modulus of the supporting substrate decrease.
Evans, Christopher Michael
The USGS National Elevation Dataset (NED) has been developed by merging the highest-resolution, best-quality elevation data available across the United States into a seamless raster format. NED is the result of the maturation of the USGS effort to provide 1:24,000-scale Digital ...
The USGS National Elevation Dataset (NED) has been developed bymerging the highest-resolution, best-quality elevation data available across the United States into a seamless raster format. NED is the result of the maturation of the USGS effort to provide 1:24,000-scale Digital E...
Recent genome-wide association studies have identified Tribbles homolog 1 (TRIB1) as one of the candidate genes associated with lipid profiles. TRIB1 is known to interact with MAP kinases, thereby regulating their activities. The single nucleotide polymorphism rs2954029 of TRIB1 is located within an intron and is associated with lipid profiles. The aim of the present study is to investigate the TRIB1 rs2954029 (A>T polymorphism) with conventional predictors of coronary artery diseases such as carotid intima-media thickness (CIMT) and cardio-ankle vascular index (CAVI), and with lipid profiles in general population. This study enrolled 2,581 Japanese adults, 942 men and 1,639 women with a median age of 68 years (range 29 to 94 years), who participated in a screening program for the general population living in Goto City, Nagasaki Prefecture, Japan from 2008 to 2010. For the determination of TRIB1 rs2954029 genotypes, the polymerase chain reaction method was used. The differences in each parameter among the TRIB1 rs2954029 genotypes were evaluated using analysis of covariance. Genotype frequencies of TRIB1 rs2954029 in all participants were 25.5% for AA, 50.4% for AT, and 24.0% for TT. In women, the AA genotype showed significantly higher log triglyceride (TG) concentrations than the AT genotype (P = 0.004) and the AT + TT genotypes (P = 0.004). On the other hand, there were no associations with CIMT and CAVI among the TRIB1 rs2954029 genotypes. In conclusion, the TRIB1 rs2954029 is associated with serum TG concentrations in Japanese community-dwelling women. PMID:24910200
Ikeoka, Toshiyuki; Hayashida, Naomi; Nakazato, Mio; Sekita, Takaharu; Murata-Mori, Fumi; Ando, Takao; Abiru, Norio; Yamasaki, Hironori; Kudo, Takashi; Maeda, Takahiro; Kawakami, Atsushi; Takamura, Noboru
Purpose of review Comparative gene identification-58 (CGI-58) is a lipid droplet-associated protein that controls intracellular triglyceride levels by its ability to activate adipose triglyceride lipase (ATGL). Additionally, CGI-58 was described to exhibit lysophosphatidic acid acyl transferase (LPAAT) activity. This review focuses on the significance of CGI-58 in energy metabolism in adipose and nonadipose tissue. Recent findings Recent studies with transgenic and CGI-58-deficient mouse strains underscored the importance of CGI-58 as a regulator of intracellular energy homeostasis by modulating ATGL-driven triglyceride hydrolysis. In accordance with this function, mice and humans that lack CGI-58 accumulate triglyceride in multiple tissues. Additionally, CGI-58-deficient mice develop an ATGL-independent severe skin barrier defect and die soon after birth. Although the premature death prevented a phenotypical characterization of adult global CGI-58 knockout mice, the characterization of mice with tissue-specific CGI-58 deficiency revealed new insights into its role in neutral lipid and energy metabolism. Concerning the ATGL-independent function of CGI-58, a recently identified LPAAT activity for CGI-58 was shown to be involved in the generation of signaling molecules regulating inflammatory processes and insulin action. Summary Although the function of CGI-58 in the catabolism of cellular triglyceride depots via ATGL is well established, further studies are required to consolidate the function of CGI-58 as LPAAT and to clarify the involvement of CGI-58 in the metabolism of skin lipids. PMID:24565921
Zierler, Kathrin A.; Zechner, Rudolf; Haemmerle, Guenter
Genomic interval engineering of mice identified a novel modulator of triglyceride production
To accelerate the biological annotation of novel genes discovered in sequenced of mammalian genomes, we are creating large deletions in the mouse genome targeted to include clusters of such genes. Here we describe the targeted deletion of a 450 kb region on mouse chromosome 11 which, based on computational analysis of the deleted murine sequences and human 5q orthologous sequences, codes for nine putative genes. Mice homozygous for the deletion had a variety of abnormalities including severe hypertriglyceridemia, hepatic and cardiac enlargement, growth retardation and premature mortality. Analysis of triglyceride metabolism in these animals demonstrated a several-fold increase in hepatic very-low density lipoprotein (VLDL) triglyceride secretion, the most prevalent mechanism responsible for hypertriglyceridemia in humans. A series of mouse BAC and human YAC transgenes covering different intervals of the 450 kb deleted region were assessed for their ability to complement the deletion induced abnormalities. These studies revealed that OCTN2, a gene recently shown to play a role in carnitine transport, was able to correct the triglyceride abnormalities. The discovery of this previously unappreciated relationship between OCTN2, carnitine and hepatic triglyceride production is of particular importance due to the clinical consequence of hypertriglyceridemia and the paucity of genes known to modulate triglyceride secretion.
Zhu, Y.; Jong, M.C.; Frazer, K.A.; Gong, E.; Krauss, R.M.; Cheng, J.F.; Boffelli, D.; Rubin, E.M.
Cholesterol and triglyceride-rich Western diets are typically associated with an increased occurrence of type 2 diabetes and vascular diseases. This study aimed to assess the relative impact of dietary cholesterol and triglycerides on glucose tolerance, insulin sensitivity, atherosclerotic plaque formation, and endothelial function. C57BL6 wild-type (C57) mice were compared with atherosclerotic LDLr(-/-) ApoB(100/100) (LRKOB100) and atherosclerotic/diabetic IGF-II � LDLr(-/-) ApoB(100/100) (LRKOB100/IGF) mice. Each group was fed either a standard chow diet, a 0.2% cholesterol diet, a high-fat diet (HFD), or a high-fat 0.2% cholesterol diet for 6 mo. The triglyceride-rich HFD increased body weight, glucose intolerance, and insulin resistance but did not alter endothelial function or atherosclerotic plaque formation. Dietary cholesterol, however, increased plaque formation in LRKOB100 and LRKOB100/IGF animals and decreased endothelial function regardless of genotype. However, cholesterol was not associated with an increase of insulin resistance in LRKOB100 and LRKOB100/IGF mice and, unexpectedly, was even found to reduce the insulin-resistant effect of dietary triglycerides in these animals. Our data indicate that dietary triglycerides and cholesterol have distinct metabolic and vascular effects in obese atherogenic mouse models resulting in dissociation between the impairment of glucose homeostasis and the development of atherosclerosis. PMID:23820620
Laplante, Marc-Andr�; Charbonneau, Alexandre; Avramoglu, Rita Kohen; Pelletier, Patricia; Fang, Xiangping; Bachelard, H�l�ne; Yl�-Herttuala, Seppo; Laakso, Markku; Despr�s, Jean-Pierre; Deshaies, Yves; Sweeney, Gary; Mathieu, Patrick; Marette, Andr�
Comparative kinetic analysis on thermal degradation of some cephalosporins using TG and DSC data
Background The thermal decomposition of cephalexine, cefadroxil and cefoperazone under non-isothermal conditions using the TG, respectively DSC methods, was studied. In case of TG, a hyphenated technique, including EGA, was used. Results The kinetic analysis was performed using the TG and DSC data in air for the first step of cephalosporin�s decomposition at four heating rates. The both TG and DSC data were processed according to an appropriate strategy to the following kinetic methods: Kissinger-Akahira-Sunose, Friedman, and NPK, in order to obtain realistic kinetic parameters, even if the decomposition process is a complex one. The EGA data offer some valuable indications about a possible decomposition mechanism. The obtained data indicate a rather good agreement between the activation energy�s values obtained by different methods, whereas the EGA data and the chemical structures give a possible explanation of the observed differences on the thermal stability. A complete kinetic analysis needs a data processing strategy using two or more methods, but the kinetic methods must also be applied to the different types of experimental data (TG and DSC). Conclusion The simultaneous use of DSC and TG data for the kinetic analysis coupled with evolved gas analysis (EGA) provided us a more complete picture of the degradation of the three cephalosporins. It was possible to estimate kinetic parameters by using three different kinetic methods and this allowed us to compare the Ea values obtained from different experimental data, TG and DSC. The thermodegradation being a complex process, the both differential and integral methods based on the single step hypothesis are inadequate for obtaining believable kinetic parameters. Only the modified NPK method allowed an objective separation of the temperature, respective conversion influence on the reaction rate and in the same time to ascertain the existence of two simultaneous steps. PMID:23594763
NASA Technical Reports Server (NTRS)
A Digital Terrain Model (DTM) of Mars was derived with both Mercator and Sinusoidal Equal-Area projections from the global topographic map of Mars (scale 1:15 million, contour interval 1 km). Elevations on the map are referred to Mars' topographic datum that is defined by the gravity field at a 6.1-millibar pressure surface with respect to the center of mass of Mars. The DTM has a resolution at the equator of 1/59.226 degrees (exactly 1 km) per pixel. By using the DTM, the volumetric distribution of Mars topography above and below the datum has previously been calculated. Three types of elevation distributions of Mars' topography were calculated from the same DTM: (1) the frequency distribution of elevations at the pixel resolution; (2) average elevations in increments of 6 degrees in both longitude and latitude; and (3) average elevations in 36 separate blocks, each covering 30 degrees of latitude and 60 degrees of longitude.
Wu, Sherman S. C.; Howington-Kraus, Annie E.; Ablin, Karyn K.
Cellular TG stores are efficiently hydrolyzed by adipose TG lipase (ATGL). Its coactivator comparative gene identification-58 (CGI-58) strongly increases ATGL-mediated TG catabolism in cell culture experiments. To investigate the consequences of CGI-58 deficiency in murine macrophages, we generated mice with a targeted deletion of CGI-58 in myeloid cells (macCGI-58?/? mice). CGI-58?/? macrophages accumulate intracellular TG-rich lipid droplets and have decreased phagocytic capacity, comparable to ATGL?/? macrophages. In contrast to ATGL?/? macrophages, however, CGI-58?/? macrophages have intact mitochondria and show no indications of mitochondrial apoptosis and endoplasmic reticulum stress, suggesting that TG accumulation per se lacks a significant role in processes leading to mitochondrial dysfunction. Another notable difference is the fact that CGI-58?/? macrophages adopt an M1-like phenotype in vitro. Finally, we investigated atherosclerosis susceptibility in macCGI-58/ApoE-double KO (DKO) animals. In response to high-fat/high-cholesterol diet feeding, DKO animals showed comparable plaque formation as observed in ApoE?/? mice. In agreement, antisense oligonucleotide-mediated knockdown of CGI-58 in LDL receptor?/? mice did not alter atherosclerosis burden in the aortic root. These results suggest that macrophage function and atherosclerosis susceptibility differ fundamentally in these two animal models with disturbed TG catabolism, showing a more severe phenotype by ATGL deficiency. PMID:25316883
Goeritzer, Madeleine; Schlager, Stefanie; Radovic, Branislav; Madreiter, Corina T.; Rainer, Silvia; Thomas, Gwynneth; Lord, Caleb C.; Sacks, Jessica; Brown, Amanda L.; Vujic, Nemanja; Obrowsky, Sascha; Sachdev, Vinay; Kolb, Dagmar; Chandak, Prakash G.; Graier, Wolfgang F.; Sattler, Wolfgang; Brown, J. Mark; Kratky, Dagmar
A method for the sequential colorimetric determination of serum triglycerides and cholesterol.
A simple spectrophotometric method for the sequential determination of triglycerides and cholesterol from a single serum sample was developed. In this two-stage procedure, the triglycerides and cholesterol esters are first hydrolysed to glycerol and free cholesterol respectively, with simultaneous scavenging of the liberated free fatty acids, a technique that ensures clarity of the sample. The glycerol is subsequently reacted to result in an intense red chromogen with a peak absorption maximum at 510 nm following a series of enzymic reactions. In the second stage, addition of cholesterol oxidase leads to oxidation of free cholesterol generated from the cholesterol esters in the first stage and the free cholesterol normally present in the sample, yielding in a similar fashion the identical red chromogen whose absorbance is also measured at 510 nm. Results obtained with the proposed method demonstrate good correlation with established individual procedures for triglycerides and cholesterol. PMID:3652437
Sharma, A; Artiss, J D; Zak, B
Rhomboids are serine proteases that cleave their substrates within the transmembrane domain. Toxoplasma gondii contains six rhomboids that are expressed in different life cycle stages and localized to different cellular compartments. Toxoplasma rhomboid protein 1 (TgROM1) has previously been shown to be active in vitro, and the orthologue in Plasmodium falciparum processes the essential microneme protein AMA1 in a heterologous system. We investigated the role of TgROM1 to determine its role during in vitro growth of T. gondii. TgROM1 was localized in the secretory pathway of the parasite, including the Golgi apparatus and micronemes, which contain adhesive proteins involved in invasion of host cells. However, unlike other micronemal proteins, TgROM1 was not released onto the parasite surface during cell invasion, suggesting it does not play a critical role in cell invasion. Suppression of TgROM1 using the tetracycline-regulatable system revealed that ROM1-deficient parasites were outcompeted by wild-type T. gondii. ROM1-deficient parasites showed only modest decrease in invasion but replicated more slowly than wild-type cells. Collectively, these results indicate that ROM1 is required for efficient intracellular growth by T. gondii. PMID:18310358
Brossier, Fabien; Starnes, G. Lucas; Beatty, Wandy L.; Sibley, L. David
Object recognition memory and BDNF expression are reduced in young TgCRND8 mice.
The TgCRND8 mouse model of Alzheimer's disease exhibits progressive cortical and hippocampal ?-amyloid accumulation, resulting in plaque pathology and spatial memory impairment by 3 months of age. We tested whether TgCRND8 cognitive function is disrupted prior to the appearance of macroscopic plaques in an object recognition task. We found profound deficits in 8-week-old mice. Animals this age were not impaired on the Morris water maze task. TgCRND8 and littermate controls did not differ in their duration of object exploration or optokinetic responses. Thus, visual and motor dysfunction did not confound the phenotype. Object memory deficits point to the frontal cortex and hippocampus as early targets of functional disruption. Indeed, we observed altered levels of brain-derived neurotrophic factor (BDNF) messenger ribonucleic acid (mRNA) in these brain regions of preplaque TgCRND8 mice. Our findings suggest that object recognition provides an early index of cognitive impairment associated with amyloid exposure and reduced brain-derived neurotrophic factor expression in the TgCRND8 mouse. PMID:20447730
Francis, Beverly M; Kim, John; Barakat, Meredith E; Fraenkl, Stephan; Y�cel, Yeni H; Peng, Shiyong; Michalski, Bernadeta; Fahnestock, Margaret; McLaurin, Joanne; Mount, Howard T J
Object recognition memory and BDNF expression are reduced in young TgCRND8 mice
The TgCRND8 mouse model of Alzheimer�s disease exhibits progressive cortical and hippocampal ?-amyloid accumulation, resulting in plaque pathology and spatial memory impairment by 3 months of age. We tested whether TgCRND8 cognitive function is disrupted prior to the appearance of macroscopic plaques in an object recognition task. We found profound deficits in 8-week-old mice. Animals this age were not impaired on the Morris water maze task. TgCRND8 and littermate controls did not differ in their duration of object exploration or optokinetic responses. Thus, visual and motor dysfunction did not confound the phenotype. Object memory deficits point to the frontal cortex and hippocampus as early targets of functional disruption. Indeed, we observed altered levels of brain-derived neurotrophic factor (BDNF) messenger ribonucleic acid (mRNA) in these brain regions of preplaque TgCRND8 mice. Our findings suggest that object recognition provides an early index of cognitive impairment associated with amyloid exposure and reduced brain-derived neurotrophic factor expression in the TgCRND8 mouse. PMID:20447730
Francis, Beverly M.; Kim, John; Barakat, Meredith E.; Fraenkl, Stephan; Yucel, Yeni H.; Peng, Shiyong; Michalski, Bernadeta; Fahnestock, Margaret; McLaurin, JoAnne; Mount, Howard T.J.
Sub-Tg relaxation patterns in Cu-based metallic glasses far from equilibrium.
We investigate the sub-Tg relaxation patterns (RPs) in binary and quaternary Cu-based glass ribbons (GRs) by using the hyperquenching-sub-Tg annealing-calorimetric approach. This study contributes to revealing the structural or dynamic evolution in liquids related to the observed three-stage sub-Tg relaxation processes in GRs. In this work, we have achieved the following three findings. First, the abnormal three-stage relaxation behavior is not a general phenomenon for Cu-based metallic glasses and could not be simply predicted by the large difference in the enthalpy of mixing between different elements in alloys. Second, the abnormal three-stage RP is associated with the non-monotonic change of cluster size with medium range order in supercooled liquids. Third, the existence of the liquid-liquid phase transition depicted by anomalous viscosity drop during cooling in superheated liquids could be a signature of the unusual structural change causing the abnormal three-step sub-Tg RP in the GRs. This work helps to better understand the complex structural evolution from superheated to supercooled liquids approaching Tg. PMID:25362325
Wang, Caiwei; Hu, Lina; Wei, Chen; Tong, Xu; Zhou, Chao; Sun, Qijing; Hui, Xidong; Yue, Yuanzheng
Sub-Tg relaxation patterns in Cu-based metallic glasses far from equilibrium
NASA Astrophysics Data System (ADS)
We investigate the sub-Tg relaxation patterns (RPs) in binary and quaternary Cu-based glass ribbons (GRs) by using the hyperquenching-sub-Tg annealing-calorimetric approach. This study contributes to revealing the structural or dynamic evolution in liquids related to the observed three-stage sub-Tg relaxation processes in GRs. In this work, we have achieved the following three findings. First, the abnormal three-stage relaxation behavior is not a general phenomenon for Cu-based metallic glasses and could not be simply predicted by the large difference in the enthalpy of mixing between different elements in alloys. Second, the abnormal three-stage RP is associated with the non-monotonic change of cluster size with medium range order in supercooled liquids. Third, the existence of the liquid-liquid phase transition depicted by anomalous viscosity drop during cooling in superheated liquids could be a signature of the unusual structural change causing the abnormal three-step sub-Tg RP in the GRs. This work helps to better understand the complex structural evolution from superheated to supercooled liquids approaching Tg.
Wang, Caiwei; Hu, Lina; Wei, Chen; Tong, Xu; Zhou, Chao; Sun, Qijing; Hui, Xidong; Yue, Yuanzheng
Clarifying the controversy of the Tg depression in polystyrene thin films
The glass transition temperature ($T_g$) of polymer thin films has been a subject of controversy in the last two decades. (Pseudo)thermodynamic determinations of $T_g$ generally suggest a significant depression, whereas the molecular mobility is found to be unchanged. The present study clarifies this apparent controversy by assuming that the $T_g$ in thin films is determined not only by the molecular mobility but also by the thickness of the film. This hypothesis is supported by the analysis of literature results on polystyrene thin films showing that the $T_g$ dependence on the cooling rate obtained on samples with different thicknesses can be rescaled onto a master curve. The thickness dependence of $T_g$ is quantitatively captured by an equilibration mechanism based on free volume holes diffusion. This dependence emerges from the ability of thinner films to maintain equilibrium, due to the shorter distance free volume holes have to diffuse to the polymer interface, the molecular motion determining the diffusion coefficient being thickness independent.
V. M. Boucher; D. Cangialosi; A. Alegr�a; J. Colmenero
We isolated hybrids and cybrids using HeLaTG cells and human normal primary fibroblasts to examine the functional differences between the mitochondria! genomes of tumor and normal cells with respect to their possible involvement in the regulation of tumorigenicity. Hybrids contained mitochondria! DNA (miDNA) predominantly from the fibro- blast parent and their tumorigenicity was suppressed completely. Then, cytoplasmic transmission of primary
Jun-Ichi Hayashi; Harold Werbin; Jerry W. Shay
The triglyceride composition ofEphedra nevadensis seed fat, which contains 16 different fatty acids, has been analyzed by a combination of liquid-liquid partition and gas-liquid\\u000a chromatography. Triglycerides were first separated by liquid-liquid partition chromatography. The recovered fractions were\\u000a then analyzed by gas-liquid chromatography to determine the molecular weights of the triglycerides present. Consecutive separation\\u000a by these two techniques resolved this complex
Carter Litchfield
GCKR Variants Increase Triglycerides While Protecting from Insulin Resistance in Chinese Children
Background Variants in gene encoding glucokinase regulator protein (GCKR) were found to have converse effects on triglycerides and glucose metabolic traits. We aimed to investigate the influence of GCKR variants for triglycerides and glucose metabolic traits in Chinese children and adults. Methods and Results We genotyped two GCKR variants rs1260326 and rs1260333 in children and adults, and analyzed the association between two variants and triglycerides, glucose, insulin and HOMA-IR using linear regression model, and estimated the effect on insulin resistance using logistic regression model. Rs1260326 and rs1260333 associated with increased triglycerides in children and adults (p<0.05). In children, both variants significantly reduced insulin (p<0.05. for rs1260326, ??=??0.07; for rs1260333, ??=??0.07) and HOMA-IR (p<0.05. for rs1260326, ??=??0.03; for rs1260333, ??=??0.03). There were significant associations between two variants and insulin resistance for children. Under co-dominant model, for CT vs. CC, OR is 0.83 (95%CI 0.69�1.00) for rs1260326, and 0.83 (95%CI 0.68�1.00) for rs1260333; for TT vs. CC, OR is 0.72 (95%CI 0.58�0.88) for rs1260326, and 0.72 (95%CI 0.58�0.89) for rs1260333. Under allele model, for allele T vs. C, the ORs are 0.85 (95%CI 0.76�0.94) and 0.85 (95%CI 0.76�0.94) for rs1260326 and rs1260333, respectively). Conclusions Our study confirmed the associations between GCKR variants and triglycerides in Chinese children and adults. Triglycerides-increasing alleles of GCKR variants reduce insulin and HOMA-IR index, and protect from insulin resistance in children. Our results suggested GCKR has an effect on development of insulin resistance in Chinese children. PMID:23383164
Shen, Yue; Wu, Lijun; Xi, Bo; Liu, Xin; Zhao, Xiaoyuan; Cheng, Hong; Hou, Dongqing; Wang, Xingyu; Mi, Jie
Objective To assess the feasibility of renal proton magnetic resonance spectroscopy for quantification of triglyceride content and to compare spectral quality and reproducibility without and with respiratory motion compensation in vivo. Materials and Methods The Institutional Review Board of our institution approved the study protocol, and written informed consent was obtained. After technical optimization, a total of 20 healthy volunteers underwent renal proton magnetic resonance spectroscopy of the renal cortex both without and with respiratory motion compensation and volume tracking. After the first session the subjects were repositioned and the protocol was repeated to assess reproducibility. Spectral quality (linewidth of the water signal) and triglyceride content were quantified. Bland-Altman analyses and a test by Pitman were performed. Results Linewidth changed from 11.5�0.4 Hz to 10.7�0.4 Hz (all data pooled, p<0.05), without and with respiratory motion compensation respectively. Mean % triglyceride content in the first and second session without respiratory motion compensation were respectively 0.58�0.12% and 0.51�0.14% (P?=?NS). Mean % triglyceride content in the first and second session with respiratory motion compensation were respectively 0.44�0.10% and 0.43�0.10% (P?=?NS between sessions and P?=?NS compared to measurements with respiratory motion compensation). Bland-Altman analyses showed narrower limits of agreement and a significant difference in the correlated variances (correlation of ?0.59, P<0.05). Conclusion Metabolic imaging of the human kidney using renal proton magnetic resonance spectroscopy is a feasible tool to assess cortical triglyceride content in humans in vivo and the use of respiratory motion compensation significantly improves spectral quality and reproducibility. Therefore, respiratory motion compensation seems a necessity for metabolic imaging of renal triglyceride content in vivo. PMID:23620813
de Heer, Paul; Bizino, Maurice B.; Wolterbeek, Ron; Rabelink, Ton J.; Doornbos, Joost; Lamb, Hildo J.
Metabolism of triglyceride-rich nascent rat hepatic high density lipoproteins
Nascent high density lipoprotein (HDL) and nascent very low density lipoprotein (VLDL) were isolated from rat livers that had been perfused with (3H)glycerol to label the triglyceride. When injected into intact rats, the labeled HDL-triglyceride disappeared as rapidly as the VLDL-triglyceride, with only 10% of the injected label remaining in the plasma after 30 min. The protein moiety of nascent HDL was labeled with (35S)methionine in a similar fashion and the labeled nascent HDL was separated into nonretained (NR) and retained (R) fractions by heparin-Sepharose affinity chromatography. When injected into rats, 55% of the injected label in nascent fraction NR and 72% of that in nascent fraction R was recovered from plasma at 30 min, compared to only 10% of the triglyceride label from unfractionated nascent HDL, indicating dissociation of triglyceride and apolipoprotein clearance. The plasma decay curves for both triglyceride and protein were biexponential. By 5 min, 15% of the 35S label remaining in plasma represented apoE and apoC that had been transferred from nascent HDL fractions NR and R to the d less than 1.063 g/ml fraction of plasma. Plasma HDL was labeled in vivo with (35S)methionine, separated into fractions NR and R, and the clearance of the two plasma HDL fractions was compared with that of the corresponding nascent HDL fractions. Except for a faster rate of removal of the nascent HDL fractions during the first 5 min, the serum decay curves were very similar.
Winkler, K.E.; Marsh, J.B. (Medical College of Pennsylvania, Philadelphia (USA))
Association of HS6ST3 gene polymorphisms with obesity and triglycerides: gene x gender interaction.
The heparan sulfate 6-O-sulfotransferase 3 (HS6ST3) gene is involved in heparan sulphate and heparin metabolism, and has been reported to be associated with diabetic retinopathy in type 2 diabetes.We hypothesized that HS6ST3 gene polymorphisms might play an important role in obesity and related phenotypes (such as triglycerides). We examined genetic associations of 117 single-nucleotide polymorphisms (SNPs) within the HS6ST3 gene with obesity and triglycerides using two Caucasian samples: the Marshfield sample (1442 obesity cases and 2122 controls), and the Health aging and body composition (Health ABC) sample (305 cases and 1336 controls). Logistic regression analysis of obesity as a binary trait and linear regression analysis of triglycerides as a continuous trait, adjusted for age and sex, were performed using PLINK. Single marker analysis showed that six SNPs in the Marshfield sample and one SNP in the Health ABC sample were associated with obesity (P < 0.05). SNP rs535812 revealed a stronger association with obesity in meta-analysis of these two samples (P = 0.0105). The T-A haplotype from rs878950 and rs9525149 revealed significant association with obesity in the Marshfield sample (P = 0.012). Moreover, nine SNPs showed associations with triglycerides in the Marshfield sample (P < 0.05) and the best signal was rs1927796 (P = 0.00858). In addition, rs7331762 showed a strong gene x gender interaction (P = 0.00956) for obesity while rs1927796 showed a strong gene x gender interaction (P = 0.000625) for triglycerides in the Marshfield sample. These findings contribute new insights into the pathogenesis of obesity and triglycerides and demonstrate the importance of gender differences in the aetiology. PMID:24371161
Wang, Ke-Sheng; Wang, Liang; Liu, Xuefeng; Zeng, Min
A new approach to intraoperative radiation therapy led to the development of mobile linear electron accelerators that provide lower electron energy beams than the usual conventional accelerators commonly encountered in radiotherapy. Such mobile electron accelerators produce electron beams that have nominal energies of 4, 6, 9 and 12 MeV. This work compares the absorbed dose output calibrations using both the AAPM TG-51 and TG-21 dose calibration protocols for two types of ion chambers: a plane-parallel (PP) ionization chamber and a cylindrical ionization chamber. Our results indicate that the use of a 'Markus' PP chamber causes 2-3% overestimation in dose-output determination if accredited dosimetry-calibration laboratory based chamber factors (N(60Co)(D,w,) Nx) are used. However, if the ionization chamber factors are derived using a cross-comparison at a high-energy electron beam, then a good agreement is obtained (within 1%) with a calibrated cylindrical chamber over the entire energy range down to 4 MeV. Furthermore, even though the TG-51 does not recommend using cylindrical chambers at the low energies, our results show that the cylindrical chamber has a good agreement with the PP chamber not only at 6 MeV but also down to 4 MeV electron beams. PMID:15152696
Beddar, A S; Tailor, R C
NASA Astrophysics Data System (ADS)
A new approach to intraoperative radiation therapy led to the development of mobile linear electron accelerators that provide lower electron energy beams than the usual conventional accelerators commonly encountered in radiotherapy. Such mobile electron accelerators produce electron beams that have nominal energies of 4, 6, 9 and 12 MeV. This work compares the absorbed dose output calibrations using both the AAPM TG-51 and TG-21 dose calibration protocols for two types of ion chambers: a plane-parallel (PP) ionization chamber and a cylindrical ionization chamber. Our results indicate that the use of a 'Markus' PP chamber causes 2 3% overestimation in dose output determination if accredited dosimetry-calibration laboratory based chamber factors \\big(N_{{\\rm D},{\\rm w}}^{{}^{60}{\\rm Co}}, N_x\\big) are used. However, if the ionization chamber factors are derived using a cross-comparison at a high-energy electron beam, then a good agreement is obtained (within 1%) with a calibrated cylindrical chamber over the entire energy range down to 4 MeV. Furthermore, even though the TG-51 does not recommend using cylindrical chambers at the low energies, our results show that the cylindrical chamber has a good agreement with the PP chamber not only at 6 MeV but also down to 4 MeV electron beams.
Beddar, A. S.; Tailor, R. C.
Analysis of mixtures of mono-, di-, and triglycerides by molecular distillation and thin-layer chromatography is described.\\u000a \\u000a Mono- and diglycerides undergo appreciable acyl migration through the effect of heat during molecular distillation. Nevertheless\\u000a this technique may be used for the quantitative analysis of mixtures of mono-, di-, and triglycerides, provided there are\\u000a no substances present which catalyze, disproportionation.\\u000a \\u000a \\u000a \\u000a Thin-layer chromatographic (TLC)
O. S. Privett; M. L. Blank; W. O. Lundberg
Analysis of triglycerides by consecutive chromatographic techniques. i. cuphea llavia seed fat
The triglycerides ofCuphea llavia var.miniata seed fat were separated according to the number of double bonds\\/molecule using preparative thin layer chromatography (TLC)\\u000a on silicic acid impregnated with silver ion. The recovered frac-tions were quantitated by the chromotropic acid technique.\\u000a Each fraction was then separated ac-cording to mol wt using gas-liquid chromatog-raphy (GLC). This multiple chromatography\\u000a procedure resolvedC. llavia triglycerides into
Carter Litchfield; Margaret Farquhar; Raymond Reiser
A combined QXRD/TG method to quantify the phase composition of hydrated Portland cements
A new method is reported for quantifying the mineral phases in hydrated cement pastes that is based on a combination of quantitative X-ray diffractometry (QXRD) and thermogravimetry (TG). It differs from previous methods in that it gives a precise measure of the amorphous phase content without relying on an assumed stoichiometric relationship between the principal hydration products, calcium hydroxide (CH) and calcium silicate hydrate (C�S�H). The method was successfully applied to gray and white ordinary Portland cements (GOPC and WOPC, respectively) that were cured for up to 56 days. Phase distributions determined by QXRD/TG closely matched those from gray-level analysis of backscattered scanning electron microscope (BSEM) images, whereas elemental compositions obtained for the amorphous phase by QXRD/TG agreed well with those measured by quantitative energy dispersive X-ray spectroscopy (EDS)
Soin, Alexander V.; Catalan, Lionel J.J. [Department of Chemical Engineering, Lakehead University, 955 Oliver Road, Thunder Bay, Ontario P7B 5E1 (Canada)] [Department of Chemical Engineering, Lakehead University, 955 Oliver Road, Thunder Bay, Ontario P7B 5E1 (Canada); Kinrade, Stephen D., E-mail: email@example.com [Department of Chemistry, Lakehead University, 955 Oliver Road, Thunder Bay, Ontario P7B 5E1 (Canada)
Effects of repetitive exposure to anesthetics and analgesics in the Tg2576 mouse Alzheimer's model.
The use of anesthetics and sedatives has been suggested to be a contributor to Alzheimer's disease neuropathogenesis. We wanted to address the in vivo relevance of those substances in the Tg2576 Alzheimer's mouse model. Tg7526 mice were anesthesia-sedated for 90�min once a week for 4�weeks. Y maze, Congo Red, and amyloid beta (A?) immunochemistry were performed. We did not find any significant change in the navigation behavior of the exposed mice compared to the controls. Significantly less deposition of A? in the CA1 area of the hippocampus and frontal cortex of mice exposed to isoflurane, propofol, diazepam, ketamine, and pentobarbital was observed. In the dentate gyrus, A? deposition was significantly greater in the group treated with pentobarbital. Congo Red staining evidenced significantly fewer fibrils in the cortex of mice exposed to diazepam, ketamine, or pentobarbital. The adopted repetitive exposure did not cause a significant detriment in Tg7526 mouse. PMID:24927827
Quiroga, Carolina; Chaparro, Rafael E; Karlnoski, Rachel; Erasso, Diana; Gordon, Marcia; Morgan, David; Bosco, Gerardo; Rubini, Alessandro; Parmagnani, Andrea; Paoli, Antonio; Mangar, Devanand; Camporesi, Enrico M
NSDL National Science Digital Library
In this video adapted from NOVA scienceNOW, find out about the discovery of a new building material, the carbon nanotube, whose physical properties could theoretically enable the creation of a 22,000-mile elevator to space.
Foundation, Wgbh E.
3. WEST ELEVATION; ELEVATIONS OF ROOM 'C' (DRAWING ROOM); EXTERIOR ELEVATION DOORS A & B; REFLECTED PLAN PANELLED SOFFIT, DOORS A & B - Wakefield, State Route 204, Wakefield Corner, Westmoreland County, VA
As a peroxisome proliferator-activated receptor alpha (PPAR?) agonist, fenofibrate favorably modulates dyslipidemia and inflammation markers, which are associated with cardiovascular risk. To determine whether variation in the PPAR? receptor gene was associated with lipid and inflammatory marker response, we conducted a 3-week trial of fenofibrate in 861 men and women. Mixed linear models that controlled for age and sex, as well as family pedigree and study center, were constructed using single-nucleotide polymorphisms (SNPs) in the PPAR? gene as predictors and changes in fasting triglycerides (TGs), cholesterol and inflammatory markers as outcomes. Significant associations with low-density cholesterol and interleukin-2 (P<0.001) responses to fenofibrate were found. Although there were suggestive associations with tumor necrosis factor-alpha and TG responses (P<0.05), these did not survive the correction for multiple testing. We conclude that variants in the PPAR? gene may contribute to future pharmacogenomic paradigms seeking to predict fenofibrate responders from both an anti-dyslipidemic and anti-inflammatory perspective. PMID:22547144
Frazier-Wood, A C; Ordovas, J M; Straka, R J; Hixson, J E; Borecki, I B; Tiwari, H K; Arnett, D K
As a peroxisome proliferator-activated receptor alpha (PPAR?) agonist, fenofibrate favorably modulates dyslipidemia and inflammation markers, which are associated with cardiovascular risk. To determine whether variation in the PPAR? receptor gene was associated with lipid and inflammatory marker response, we conducted a three week trial of fenofibrate in 861 men and women. Mixed linear models which controlled for age and sex, as well as family pedigree and study-center, were constructed using SNPs in the PPAR? gene as predictors and changes in fasting triglycerides (TGs), cholesterol and inflammatory markers as outcomes. Significant associations with low-density cholesterol (LDL-C) and interleukin-2 (IL-2; P<.001) responses to fenofibrate were found. Although there were suggestive associations with tumour necrosis factor-alpha (TNF-?) and TG responses (P<.05), these did not survive the correction for multiple testing. We conclude that variants in the PPAR? gene may contribute to future pharmacogenomic paradigms seeking to predict fenofibrate responders from both an anti-dyslipidemic and anti-inflammatory perspective. PMID:22547144
Frazier-Wood, A.C.; Ordovas, J.M; Straka, R.J.; Hixson, J.E.; Borecki, I.B.; Tiwari, H.K.; Arnett, D.K.
Cholinotrophic basal forebrain system alterations in 3xTg-AD transgenic mice.
The cholinotrophic system, which is dependent upon nerve growth factor and its receptors for survival, is selectively vulnerable in Alzheimer's disease (AD). But, virtually nothing is known about how this deficit develops in relation to the hallmark lesions of this disease, amyloid plaques and tau containing neurofibrillary tangles. The vast majority of transgenic models of AD used to evaluate the effect of beta amyloid (A?) deposition upon the cholinotrophic system over-express the amyloid precursor protein (APP). However, nothing is known about how this system is affected in triple transgenic (3xTg)-AD mice, an AD animal model displaying A? plaque- and tangle-like pathology in the cortex and hippocampus, which receive extensive cholinergic innervation. We performed a detailed morphological and biochemical characterization of the cholinotrophic system in young (2-4 months), middle-aged (13-15 months) and old (18-20 months) 3xTg-AD mice. Cholinergic neuritic swellings increased in number and size with age, and were more conspicuous in the hippocampal-subicular complex in aged female than in 3xTg-AD male mice. Stereological analysis revealed a reduction in choline acetyltransferase (ChAT) positive cells in the medial septum/vertical limb of the diagonal band of Broca in aged 3xTg-AD mice. ChAT enzyme activity levels decreased significantly in the hippocampus of middle-aged 3xTg-AD mice compared to age-matched non-transgenic (or wild type) mice. ProNGF protein levels increased in the cortex of aged 3xTg-AD mice, whereas TrkA protein levels were reduced in a gender-dependent manner in aged mutant mice. In contrast, p75(NTR) protein cortical levels were stable but increased in the hippocampus of aged 3xTg-AD mice. These data demonstrate that cholinotrophic alterations in 3xTg-AD mice are age- and gender-dependent and more pronounced in the hippocampus, a structure more severely affected by A? plaque pathology. PMID:20937383
Perez, Sylvia E; He, Bin; Muhammad, Nadeem; Oh, Kwang-Jin; Fahnestock, Margaret; Ikonomovic, Milos D; Mufson, Elliott J
Toxoplasma gondii is a ubiquitous protozoan parasite that can infect all warm-blooded animals, including both mammals and birds. Protein disulfide isomerase (PDI) localises to the surface of T. gondii tachyzoites and modulates the interactions between parasite and host cells. In this study, the protective efficacy of recombinant T. gondii PDI (rTgPDI) as a vaccine candidate against T. gondii infection in BALB/c mice was evaluated. rTgPDI was expressed and purified from Escherichia coli. Five groups of animals (10 animals/group) were immunised with 10, 20, 30, 40 ?g of rTgPDI per mouse or with PBS as a control group. All immunisations were performed via the nasal route at 1, 14 and 21 days. Two weeks after the last immunisation, the immune responses were evaluated by lymphoproliferative assays and by cytokine and antibody measurements. The immunised mice were challenged with tachyzoites of the virulent T. gondii RH strain on the 14th day after the last immunisation. Following the challenge, the tachyzoite loads in tissues were assessed, and animal survival time was recorded. Our results showed that the group immunised with 30 ?g rTgPDI showed significantly higher levels of specific antibodies against the recombinant protein, a strong lymphoproliferative response and significantly higher levels of IgG2a, IFN-gamma (IFN-?), IL-2 and IL-4 production compared with other doses and control groups. While no changes in IL-10 levels were detected. After being challenged with T. gondii tachyzoites, the numbers of tachyzoites in brain and liver tissues from the rTgPDI group were significantly reduced compared with those of the control group, and the survival time of the mice in the rTgPDI group was longer than that of mice in the control group. Our results showed that immunisation with rTgPDI elicited a protective immune reaction and suggested that rTgPDI might represent a promising vaccine candidate for combating toxoplasmosis. PMID:23967128
Wang, Hai-Long; Li, Ya-Qing; Yin, Li-Tian; Meng, Xiao-Li; Guo, Min; Zhang, Jian-Hong; Liu, Hong-Li; Liu, Juan-Juan; Yin, Guo-Rong
Structural evolution during the sub-Tg relaxation of hyperquenched metallic glasses
NASA Astrophysics Data System (ADS)
We report the structural characteristics during the sub-Tg relaxation in hyperquenched La55Al25Ni20 glasses. The sub-Tg relaxation is associated with the structural change in intermediate range order, as manifested by the appearance of a prepeak in the x-ray diffraction spectrum. Such structural change could be the source of the Johari-Goldstein relaxation in metallic glasses. The mechanism governing the evolution of the prepeak is different between the glasses with the fictive temperature below 604 K and those above 604 K. Cooperative motion of atoms in La-centered clusters was further discussed in terms of the atomic bond deficiency model.
Hu, Lina; Zhang, Chunzhi; Yue, Yuanzheng
Rabbits with hereditary postprandial hypertriglyceridemia exhibit central obesity and are regarded as a reliable model for metabolic syndrome. This study was performed to gain insight into the affected process of lipid metabolism and into the causative genes of the postprandial hypertriglyceridemia rabbits. Eleven genes that play key roles in lipid metabolism were selected, their mRNA levels were assessed by quantitative PCR, and their expressions were compared among postprandial hypertriglyceridemia rabbits using Japanese white rabbits as the control. Two genes appeared to be in causal connection with postprandial hypertriglyceridemia, and these were regarded as likely candidates for the pathogenesis. One was the fatty acid synthase gene, which had an expression constitutively higher in postprandial hypertriglyceridemia rabbits than in Japanese white rabbits during the fasting state and reached quite high levels after feeding. The other was the gene for hepatic triglyceride lipase with an expression that was approximately one order lower than that found in the Japanese white rabbits. The low plasma hepatic triglyceride lipase activities were consistent with the low levels of the transcript in the livers of the postprandial hypertriglyceridemia rabbits. Thus, elevated fatty acid synthesis and defected lipid hydrolysis together would cause the postprandial hypertriglyceridemia in postprandial hypertriglyceridemia rabbits. PMID:24062609
Fukuda, Naoki; Ito, Tsunekata; Ohwada, Kazuo; Fujii, Junichi
Patient Guide to the Assessment and Treatment of Hypertriglyceridemia (High Triglycerides)
... the risks and benefits of all these drugs. Medications do not cure the problem of high triglycerides, so you will need to take them long term. However, weight loss and other lifestyle changes ... need for medication. Ask your doctor if you should see an ...
Effects of amount of dietary triglycerides on postprandial serum vitamin A in
Effects of amount of dietary triglycerides on postprandial serum vitamin A in heathly adults. P-Marguerite, 13000 Marseille, France) Absorption of fat-soluble vitamins is generally claimed to be dependent, no definite evi- dence has been established for vitamin A. Thus, the aim of this study was to evaluate
Paris-Sud XI, Université de
NASA Astrophysics Data System (ADS)
The results of studies devoted to the catalysts for transformation of fatty acid triglycerides and their derivatives to fuel hydrocarbons are presented and described systematically. Various approaches to the use of heterogeneous catalysts for the production of biofuel from these raw materials are considered. The bibliography includes 134 references.
Yakovlev, Vadim A.; Khromova, Sofia A.; Bukhtiyarov, Valerii I.
The interrelationships among fatness measures, plasma triglycerides and high density lipoproteins (HDL) were examined in 131 normal adult subjects: 38 men aged 27 to 46, 50 men aged 47 to 66, 29 women aged 27 to 46 and 24 women aged 47 to 66. None of the women were taking estrogens or oral contraceptive medication. The HDL concentration was subdivided into HDL/sub 2b/, HDL/sub 2a/ and HDL by a computerized fitting of the total schileren pattern to reference schlieren patterns. Anthropometric measures employed included skinfolds at 3 sites, 2 weight/height indices and 2 girth measurements. A high correlation was found among the various fatness measures. These measures were negatively correlated with total HDL, reflecting the negative correlation between fatness measures and HDL/sub 2/ (as the sum of HDL/sub 2a/ and /sub 2b/). Fatness measures showed no relationship to HDL/sub 3/. There was also an inverse correlation between triglyceride concentration and HDL/sub 2/. No particular fatness measure was better than any other for demonstrating the inverse correlation with HDL but multiple correlations using all of the measures of obesity improved the correlations. Partial correlations controlling for fatness did not reduce any of the significnt correlations between triglycerides and HDL/sub 2/ to insignificance. The weak correlation between fatness and triglycerides was reduced to insigifnicance when controlled for HDL/sub 2/.
Albrink, M.J. (West Virgina Unov., Morgantown); Krauss, R.M.; Lindgren, F.T.; von der Groeben, J.; Pan, S.; Wood, P.D.
Reactivity of triglycerides and fatty acids of rapeseed oil in supercritical alcohols
A catalyst-free biodiesel production method with supercritical methanol has been developed that allows a simple process and high yield because of simultaneous transesterification of triglycerides and methyl esterification of fatty acids. From these lines of evidence, we expected that similar results would be attained with the use of various alcohols by the supercritical treatment. However, it still remains unclear which
Yuichiro Warabi; Dadan Kusdiana; Shiro Saka
Das Triglyceridmuster eines Fettes l��t sich ohne vorherige chromatographische Fraktionierung auf rein massenspektrometrischem Wege ermitteln. Dabei werden die Triglyceride nach ihrer C-Zahl und der Zahl der in ihnen vorkommenden Doppelbindungen getrennt. Die Probeneingabe in die Ionenquelle erfolgte mit Hilfe einer DCI-Schubstange, die eine schnelle Gesamtverdampfung gestattet. Die chemische Ionisation mit Ammoniak als Reaktantgas ergibt haupts�chlich das Quasimolekularion (M + NH4)+.
E. Schulte; M. H�hn; U. Rapp
The effects of bitter melon ( Momordica charantia) on serum and liver triglyceride levels in rats
Effects of three different varieties (Koimidori, Powerful-Reishi, and Hyakunari) of bitter melon (Momordica charantia) and those of methanol fraction extract of Koimidori variety on serum and liver triglycerides were studied in rats. Feeding of diets containing either bitter melon or various fractions isolated by organic solvents caused no adverse effects on food intake or growth of rats. When the effect
Gamarallage V. K Senanayake; Mitsuru Maruyama; Kei Shibuya; Masanobu Sakono; Nobuhiro Fukuda; Toshiro Morishita; Chizuko Yukizaki; Mikio Kawano; Hideaki Ohta
Effects of dietary cholesterol on hepatic metabolism of triglyceride-rich lipopro-
Effects of dietary cholesterol on hepatic metabolism of triglyceride-rich lipopro- teins to stimulate hepatic production of VLDL, cholesterol was given to 5 male Frie- sian preruminant calves (1 month replacer with or without cholesterol in which lipids (tallow) con- stituted 22.1 % dry matter (DM
Paris-Sud XI, Université de
13Carbon mixed triglyceride breath test and pancreatic enzyme supplementation in cystic fibrosis
Children with cystic fibrosis have variable degrees of exocrine pancreatic insufficiency which, if untreated, is the main cause of fat malabsorption. The impact of pancreatic enzyme supplementation on fat digestion was measured in 41 children with cystic fibrosis, 11 healthy controls, and five children with mucosal diseases by a non-invasive test of intraluminal lipolysis using 13carbon (13C) labelled mixed triglyceride
S Amarri; M Harding; W A Coward; T J Evans; L T Weaver
Comparative effects of some carbohydrates on serum sugars, triglycerides and digestive hydrolases
Comparative effects of some carbohydrates on serum sugars, triglycerides and digestive hydrolases carbohydrate in the form of starch (wheat flour), purified sucrose, commercial sugar or a commercial sweetner. Introduction. The nutritional impact of the dietary carbohydrate source has been widely studied
Boyer, Edmond
Background�The role of triglycerides as a risk factor of ischemic heart disease (IHD) remains controversial. For the present study, we examined the relation between fasting triglycerides and risk of IHD in the Copenhagen Male Study. Methods and Results�Baseline measurements of fasting lipids and other IHD risk factors were obtained for 2906 white men (age range, 53 to 74 years) who
J�rgen Jeppesen; Hans Ole Hein; Poul Suadicani; Finn Gyntelberg
The effects of KRN4884, a novel pyridinecarboxamidine type KATP channel opener, on serum triglyceride levels were investigated in Sprague-Dawley rats.Oral administration of KRN4884 (3?mg kg?1) for 10 days caused a significant reduction in serum triglyceride levels, which was comparable to that of clofibrate (160?mg kg?1). Reduction in serum triglyceride levels by KRN4884 and clofibrate were accompanied by a reduction in triglyceride levels both in chylomicron and in very low density lipoprotein. KRN4884 treatment did not affect serum concentrations of total cholesterol and phospholipid, but did increase free fatty acid levels. Clofibrate reduced total cholesterol, phospholipid and free fatty acid levels.Administration of clofibrate significantly decreased triglyceride secretion rate as measured by the Triton WR-1339 injection procedure, while KRN4884 did not.Rats receiving KRN4884 exhibited an increase in lipoprotein lipase (LPL) activity both in adipose tissue and in skeletal muscle. There was an inverse correlation between serum triglyceride levels and tissue LPL activities. KRN4884 did not change hepatic triglyceride lipase (HTGL) activity. Clofibrate affected neither LPL nor HTGL activities.It is concluded that administration of KRN4884 results in reduced serum triglyceride levels which may be due to the enhancement of LPL activity in peripheral tissues. PMID:9113367
Yokoyama, Takashi; Izumi, Hideakira; Endoh, Megumi; Izawa, Toshio; Ogawa, Nobuyuki; Okada, Yuji
Postheparin plasma lipolytic activity consists of two hydrolytic activities, hepatic triglyceride lipase and lipoprotein lipase. These two enzymes were separated and partially purified by means of ammonium sulfate precipita- tion and affinity chromatography using Sepharose with covalently linked heparin and concanavalin A, respectively. Antibodies were produced against hepatic triglyceride lipase and they did not cross react with lipoprotein lipase. Optimal
H. Greten; R. DeGrella; G. Klose; W. Rascher; J. L. de Gennes; E. Gjone
Because the renin-angiotensin-aldosterone system has been implicated in the development of insulin resistance and promotion of fibrosis in some tissues, such as the vasculature, we examined the effect of eplerenone, a selective mineralocorticoid receptor (MR) antagonist, on nonalcoholic steatohepatitis (NASH) and metabolic phenotypes in a mouse model reflecting metabolic syndrome in humans. We adopted liver-specific transgenic (Tg) mice overexpressing the active form of sterol response element binding protein-1c (SREBP-1c) fed a high-fat and fructose diet (HFFD) as the animal model in the present study. When wild-type (WT) C57BL/6 and liver-specific SREBP-1c Tg mice grew while being fed HFFD for 12 wk, body weight and epididymal fat weight increased in both groups with an elevation in blood pressure and dyslipidemia. Glucose intolerance and insulin resistance were also observed. Adipose tissue hypertrophy and macrophage infiltration with crown-like structure formation were also noted in mice fed HFFD. Interestingly, the changes noted in both genotypes fed HFFD were significantly ameliorated with eplerenone. HFFD-fed Tg mice exhibited the histological features of NASH in the liver, including macrovesicular steatosis and fibrosis, whereas HFFD-fed WT mice had hepatic steatosis without apparent fibrotic changes. Eplerenone effectively ameliorated these histological abnormalities. Moreover, the direct suppressive effects of eplerenone on lipopolysaccharide-induced TNF? production in the presence and absence of aldosterone were observed in primary-cultured Kupffer cells and bone marrow-derived macrophages. These results indicated that eplerenone prevented the development of NASH and metabolic abnormalities in mice by inhibiting inflammatory responses in both Kupffer cells and macrophages. PMID:24129399
Wada, Tsutomu; Miyashita, Yusuke; Sasaki, Motohiro; Aruga, Yusuke; Nakamura, Yuto; Ishii, Yoko; Sasahara, Masakiyo; Kanasaki, Keizo; Kitada, Munehiro; Koya, Daisuke; Shimano, Hitoshi; Tsuneki, Hiroshi; Sasaoka, Toshiyasu
Magnetic Reconnection Theory Left to right: TG Forbes, ER Priest and J Birn
____ 18 Magnetic Reconnection Theory Left to right: TG Forbes, ER Priest and J Birn Scientific Background Magnetic reconnection is a fundamental process in a plasma of high magnetic Reynolds number, whereby magnetic field lines (which are normally attached firmly to the plasma as it moves) become
Proteolytic processing of TgIMC1 during maturation of the membrane skeleton of Toxoplasma gondii.
Proteolytic processing of TgIMC1 during maturation of the membrane skeleton of Toxoplasma gondii title: Assembly of Toxoplasma gondii membrane skeleton ¶ To whom correspondence should be addressed: Con;Summary Membrane skeletons play an important role in the maintenance of cell shape and integrity in many
Arnold, Jonathan
Evaluation of the accuracy of fetal dose estimates using TG-36 data
The American Association of Physicists in Medicine Radiation Therapy Committee Task Group 36 report (TG-36) provides guidelines for managing radiation therapy of pregnant patients. Included in the report are data that can be used to estimate the dose to the fetus. The purpose of this study is to evaluate the accuracy of these fetal dose estimates as compared to clinically measured values. TG-36 calculations were performed and compared with measurements of the fetal dose made in vivo or in appropriately-designed phantoms. Calculation and measurement data was collected for eight pregnant patients who underwent radiation therapy at the MD Anderson Cancer Center as well as for several fetal dose studies in the literature. The maximum measured unshielded fetal dose was 47 cGy, which was 1.5% of the prescription dose. For all cases, TG-36 calculations and measured fetal doses differed by up to a factor of 3--the ratio of the calculated to measured dose ranged from 0.34 to 2.93. On average, TG-36 calculations underestimated the measured dose by 31%. No significant trends in the relationship between the calculated and measured fetal doses were found based on the distance from, or the size of, the treatment field.
Kry, Stephen F.; Starkschall, George; Antolak, John A.; Salehpour, Mohammad [Department of Radiation Physics, University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030 (United States); Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota 55905 (United States); Department of Radiation Physics, University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030 (United States)
Panic attacks are a hallmark in panic disorder (PAND). During the panic attack, a strong association with the surrounding context is established suggesting that the hippocampus may be critically involved in the pathophysiology of PAND, given its role in contextual processing. We previously showed that variation in the expression of the neurotrophin tyrosine kinase receptor type 3 (NTRK3) in both PAND patients and a transgenic mouse model (TgNTRK3) may have a role in PAND pathophysiology. Our study examines hippocampal function and activation of the brain fear network in TgNTRK3 mice. TgNTRK3 mice showed increased fear memories accompanied by impaired extinction, congruent with an altered activation pattern of the amygdala-hippocampus-medial prefrontal cortex fear circuit. Moreover, TgNTRK3 mice also showed an unbalanced excitation-to-inhibition ratio in the hippocampal cornu ammonis 3 (CA3)-CA1 subcircuit toward hyperexcitability. The resulting hippocampal hyperexcitability underlies the enhanced fear memories, as supported by the efficacy of tiagabine, a GABA reuptake inhibitor, to rescue fear response. The fearful phenotype appears to be the result of hippocampal hyperexcitability and aberrant fear circuit activation. We conclude that NTRK3 plays a role in PAND by regulating hippocampus-dependent fear memories. PMID:24048855
Santos, M�nica; D'Amico, Davide; Spadoni, Ornella; Amador-Arjona, Alejandro; Stork, Oliver; Dierssen, Mara
Creatine reduces hepatic TG accumulation in hepatocytes by stimulating fatty acid oxidation.
Non-alcoholic fatty liver disease encompasses a wide spectrum of liver damage including steatosis, non-alcoholic steatohepatitis, fibrosis and cirrhosis. We have previously reported that creatine supplementation prevents hepatic steatosis and lipid peroxidation in rats fed a high-fat diet. In this study, we employed oleate-treated McArdle RH-7777 rat hepatoma cells to investigate the role of creatine in regulating hepatic lipid metabolism. Creatine, but not structural analogs, reduced cellular TG accumulation in a dose-dependent manner. Incubating cells with the pan-lipase inhibitor diethyl p-nitrophenylphosphate (E600) did not diminish the effect of creatine, demonstrating that the TG reduction brought about by creatine does not depend on lipolysis. Radiolabeled tracer experiments indicate that creatine increases fatty acid oxidation and TG secretion. In line with increased fatty acid oxidation, mRNA analysis revealed that creatine-treated cells had increased expression of PPAR? and several of its transcriptional targets. Taken together, this study provides direct evidence that creatine reduces lipid accumulation in hepatocytes by the stimulation of fatty acid oxidation and TG secretion. PMID:25205520
da Silva, Robin P; Kelly, Karen B; Leonard, Kelly-Ann; Jacobs, Ren� L
Is a distinctive single Tg a reliable indicator for the homogeneity of amorphous solid dispersion?
For an amorphous drug-polymer solid dispersion, a distinctive single T(g) intermediate of the two T(g) values of the two components has been widely considered as an indication of the mixing uniformity, which is critical for the stability of the amorphous drug against crystallization. In this study, two batches of amorphous solid dispersions consisting of BMS-A, a poorly water-soluble drug, and PVP-VA, were made by a twin-screw hot-melt extruder using different processing conditions. Both batches displayed an identical distinctive single T(g) that is consistent with the prediction of Fox equation assuming homogeneous mixing of the two components. Neither DSC nor PXRD detected any drug crystallinity in either batch. However, the two batches exhibited different physical stability against crystallization over time. The application of a Raman mapping method showed that the drug distributed over a much wider concentration range in the less stable solid dispersion. It is therefore experimentally demonstrated that, in the characterization of amorphous solid dispersions, a distinctive single T(g) may not always be a reliable indicator of homogeneity and optimal stability, and more examinations and new techniques may be required other than conventional studies. PMID:20562003
Qian, Feng; Huang, Jun; Zhu, Qing; Haddadin, Raja; Gawel, John; Garmise, Robert; Hussain, Munir
Background Central to the pathogenesis of Alzheimer�s disease (AD) and many other neurodegenerative diseases is the conformational change of a normal self-protein into toxic oligomeric species and amyloid deposits. None of these disorders have an effective therapy, but immunization approaches hold great promise. We have previously shown that active immunization with a novel peptide when polymerized into a stable oligomeric conformation, pBri, induced a humoral immune response to toxic A? species in an AD model, APP/PS1 transgenic (Tg) mice, reducing plaque deposits. pBri is a glutaraldehyde polymerized form of the carboxyl fragment of an amyloidogenic protein, which is deposited in the brains of patients with a rare autosomal dominant disease due to a missense mutation in a stop codon, resulting in the translation of an intronic sequence, with no known sequence homology to any mammalian protein. Methods In the current study we tested whether pBri-peptide-based immunomodulation is effective at reducing both vascular amyloid deposits and tau-related pathology using TgSwDI mice with extensive congophilic angiopathy and 3xTg mice with tau pathology. Results Our results indicate that this immunomodulation approach, which produces a humoral response to proteins in a pathological conformation, is effective at reducing both A? and tau-related pathologies. Conclusions This immunomodulatory approach has the advantage of using a non-self-immunogen that is less likely to be associated with autoimmune toxicity. Furthermore we found that it is able to target all the cardinal features of AD concurrently. PMID:24330773
Knockout of 5-lipoxygenase prevents dexamethasone-induced tau pathology in 3xTg mice.
Emerging evidence suggests that dysregulation stress hormones, such as glucocorticoids, in aged persons put them at a higher risk to develop Alzheimer's disease (AD). However, the mechanisms underlying such vulnerability remain to be unraveled. Pharmacologic inhibition of 5-lipoxygenase (5LO), an active player in AD pathogenesis whose protein level increases with aging in the human, has been shown to blunt glucocorticoid-mediated amyloid ? (Ab) formation in vitro. In this article, we investigated the role of this pathway in modulating the development of the corticosteroid-dependent AD-like phenotype in the triple transgenic mice (3xTg). Dexamethasone was administered for 1 week to 3xTg or 3xTg genetically deficient for 5LO (3xTg/5LO-/-) mice, and its effect on memory, amyloid-? and tau levels, and metabolism assessed. At the end of the treatment, we observed that dexamethasone did not induce changes in behavior. Compared with controls, treated mice did not show significant alterations in brain soluble A? levels. While total tau protein levels were unmodified in all groups, we found that dexamethasone significantly increased tau phosphorylation at S396, as recognized by the antibody PHF-13, which was specifically associated with an increase in the GSK3? activity. Additionally, dexamethasone-treated mice had a significant increase in the tau insoluble fraction and reduction in the postsynaptic protein PDS-95. By contrast, these modifications were blunted in the 3xTg/5LO-/- mice. Our findings highlight the functional role that 5LO plays in stress-induced AD tau pathology and support the hypothesis that pharmacologic inhibition of this enzyme could be a useful tool for individuals with this risk factor. PMID:23634895
Joshi, Yash B; Chu, Jin; Pratic�, Domenico
TgCDPK3 Regulates Calcium-Dependent Egress of Toxoplasma gondii from Host Cells
The phylum Apicomplexa comprises a group of obligate intracellular parasites of broad medical and agricultural significance, including Toxoplasma gondii and the malaria-causing Plasmodium spp. Key to their parasitic lifestyle is the need to egress from an infected cell, actively move through tissue, and reinvade another cell, thus perpetuating infection. Ca2+-mediated signaling events modulate key steps required for host cell egress, invasion and motility, including secretion of microneme organelles and activation of the force-generating actomyosin-based motor. Here we show that a plant-like Calcium-Dependent Protein Kinase (CDPK) in T. gondii, TgCDPK3, which localizes to the inner side of the plasma membrane, is not essential to the parasite but is required for optimal in vitro growth. We demonstrate that TgCDPK3, the orthologue of Plasmodium PfCDPK1, regulates Ca2+ ionophore- and DTT-induced host cell egress, but not motility or invasion. Furthermore, we show that targeting to the inner side of the plasma membrane by dual acylation is required for its activity. Interestingly, TgCDPK3 regulates microneme secretion when parasites are intracellular but not extracellular. Indeed, the requirement for TgCDPK3 is most likely determined by the high K+ concentration of the host cell. Our results therefore suggest that TgCDPK3's role differs from that previously hypothesized, and rather support a model where this kinase plays a role in rapidly responding to Ca2+ signaling in specific ionic environments to upregulate multiple processes required for gliding motility. PMID:23226109
McCoy, James M.; Whitehead, Lachlan; van Dooren, Giel G.; Tonkin, Christopher J.
TG13 current terminology, etiology, and epidemiology of acute cholangitis and cholecystitis.
While referring to the evidence adopted in the Tokyo Guidelines 2007 (TG07) as well as subsequently obtained evidence, further discussion took place on terminology, etiology, and epidemiological data. In particular, new findings have accumulated on the occurrence of symptoms in patients with gallstones, frequency of severe cholecystitis and cholangitis, onset of cholecystitis and cholangitis after endoscopic retrograde cholangiopancreatography and medications, mortality rate, and recurrence rate. The primary etiology of acute cholangitis/cholecystitis is the presence of stones. Next to stones, the most significant etiology of acute cholangitis is benign/malignant stenosis of the biliary tract. On the other hand, there is another type of acute cholecystitis, acute acalculous cholecystitis, in which stones are not involved as causative factors. Risk factors for acute acalculous cholecystitis include surgery, trauma, burn, and parenteral nutrition. After 2000, the mortality rate of acute cholangitis has been about 10 %, while that of acute cholecystitis has generally been less than 1 %. After the publication of TG07, diagnostic criteria and severity assessment criteria were standardized, and the distribution of cases according to severity and comparison of clinical data among target populations have become more subjective. The concept of healthcare-associated infections is important in the current treatment of infection. The treatment of acute cholangitis and cholecystitis substantially differs from that of community-acquired infections. Cholangitis and cholecystitis as healthcare-associated infections are clearly described in the updated Tokyo Guidelines (TG13). Free full-text articles and a mobile application of TG13 are available via http://www.jshbps.jp/en/guideline/tg13.html. PMID:23307004
Kimura, Yasutoshi; Takada, Tadahiro; Strasberg, Steven M; Pitt, Henry A; Gouma, Dirk J; Garden, O James; B�chler, Markus W; Windsor, John A; Mayumi, Toshihiko; Yoshida, Masahiro; Miura, Fumihiko; Higuchi, Ryota; Gabata, Toshifumi; Hata, Jiro; Gomi, Harumi; Dervenis, Christos; Lau, Wan-Yee; Belli, Giulio; Kim, Myung-Hwan; Hilvano, Serafin C; Yamashita, Yuichi
Synaptic alterations in the rTg4510 mouse model of tauopathy
Synapse loss, rather than the hallmark amyloid-? (A?) plaques or tau filled neurofibrillary tangles (NFT), is considered the most predictive pathological feature associated with cognitive status in the Alzheimer disease (AD) brain. The role of A? in synapse loss is well established, but despite data linking tau to synaptic function, the role of tau in synapse loss remains largely undetermined. Here we test the hypothesis that human mutant P301L tau over-expression in a mouse model (rTg4510) will lead to age-dependent synaptic loss and dysfunction. Using array tomography and two methods of quantification (automated, threshold-based counting and a manual stereology based technique) we demonstrate that overall synapse density is maintained in the neuropil, implicating synapse loss commensurate with the cortical atrophy known to occur in this model. Multi-photon in-vivo imaging reveals close to 30% loss of apical dendritic spines of individual pyramidal neurons suggesting these cells may be particularly vulnerable to tau-induced degeneration. Post-mortem, we confirm the presence of tau in dendritic spines of rTg4510-YFP mouse brain by array tomography. These data implicate tau-induced loss of a subset of synapses that may be accompanied by compensatory increases in other synaptic subtypes thereby preserving overall synapse density. Biochemical fractionation of synaptosomes from rTg4510 brain demonstrates a significant decrease in expression of several synaptic proteins, suggesting a functional deficit of remaining synapses in the rTg4510 brain. Together these data show morphological and biochemical synaptic consequences in response to tau over-expression in the rTg4510 mouse model. PMID:23047530
Kopeikina, Katherine J; Polydoro, Manuela; Tai, Hwan-Ching; Yaeger, Erich; Carlson, George A; Pitstick, Rose; Hyman, Bradley T; Spires-Jones, Tara L
Synaptic alterations in the rTg4510 mouse model of tauopathy.
Synapse loss, rather than the hallmark amyloid-? (A?) plaques or tau-filled neurofibrillary tangles (NFT), is considered the most predictive pathological feature associated with cognitive status in the Alzheimer's disease (AD) brain. The role of A? in synapse loss is well established, but despite data linking tau to synaptic function, the role of tau in synapse loss remains largely undetermined. Here we test the hypothesis that human mutant P301L tau overexpression in a mouse model (rTg4510) will lead to age-dependent synaptic loss and dysfunction. Using array tomography and two methods of quantification (automated, threshold-based counting and a manual stereology-based technique) we demonstrate that overall synapse density is maintained in the neuropil, implicating synapse loss commensurate with the cortical atrophy known to occur in this model. Multiphoton in vivo imaging reveals close to 30% loss of apical dendritic spines of individual pyramidal neurons, suggesting these cells may be particularly vulnerable to tau-induced degeneration. Postmortem, we confirm the presence of tau in dendritic spines of rTg4510-YFP mouse brain by array tomography. These data implicate tau-induced loss of a subset of synapses that may be accompanied by compensatory increases in other synaptic subtypes, thereby preserving overall synapse density. Biochemical fractionation of synaptosomes from rTg4510 brain demonstrates a significant decrease in expression of several synaptic proteins, suggesting a functional deficit of remaining synapses in the rTg4510 brain. Together, these data show morphological and biochemical synaptic consequences in response to tau overexpression in the rTg4510 mouse model. PMID:23047530
Kopeikina, Katherine J; Polydoro, Manuela; Tai, Hwan-Ching; Yaeger, Erich; Carlson, George A; Pitstick, Rose; Hyman, Bradley T; Spires-Jones, Tara L
Background Although altered lipid metabolism has been extensively implicated in the pathogenesis of Alzheimer disease (AD) through cell biological, epidemiological, and genetic studies, the molecular mechanisms linking cholesterol and AD pathology are still not well understood and contradictory results have been reported. We have used a Mendelian randomization approach to dissect the causal nature of the association between circulating lipid levels and late onset AD (LOAD) and test the hypothesis that genetically raised lipid levels increase the risk of LOAD. Methods and Findings We included 3,914 patients with LOAD, 1,675 older individuals without LOAD, and 4,989 individuals from the general population from six genome wide studies drawn from a white population (total n?=?10,578). We constructed weighted genotype risk scores (GRSs) for four blood lipid phenotypes (high-density lipoprotein cholesterol [HDL-c], low-density lipoprotein cholesterol [LDL-c], triglycerides, and total cholesterol) using well-established SNPs in 157 loci for blood lipids reported by Willer and colleagues (2013). Both full GRSs using all SNPs associated with each trait at p<5�10?8 and trait specific scores using SNPs associated exclusively with each trait at p<5�10?8 were developed. We used logistic regression to investigate whether the GRSs were associated with LOAD in each study and results were combined together by meta-analysis. We found no association between any of the full GRSs and LOAD (meta-analysis results: odds ratio [OR]?=?1.005, 95% CI 0.82�1.24, p?=?0.962 per 1 unit increase in HDL-c; OR?=?0.901, 95% CI 0.65�1.25, p?=?0.530 per 1 unit increase in LDL-c; OR?=?1.104, 95% CI 0.89�1.37, p?=?0.362 per 1 unit increase in triglycerides; and OR?=?0.954, 95% CI 0.76�1.21, p?=?0.688 per 1 unit increase in total cholesterol). Results for the trait specific scores were similar; however, the trait specific scores explained much smaller phenotypic variance. Conclusions Genetic predisposition to increased blood cholesterol and triglyceride lipid levels is not associated with elevated LOAD risk. The observed epidemiological associations between abnormal lipid levels and LOAD risk could therefore be attributed to the result of biological pleiotropy or could be secondary to LOAD. Limitations of this study include the small proportion of lipid variance explained by the GRS, biases in case-control ascertainment, and the limitations implicit to Mendelian randomization studies. Future studies should focus on larger LOAD datasets with longitudinal sampled peripheral lipid measures and other markers of lipid metabolism, which have been shown to be altered in LOAD. Please see later in the article for the Editors' Summary PMID:25226301
Proitsi, Petroula; Lupton, Michelle K.; Velayudhan, Latha; Newhouse, Stephen; Fogh, Isabella; Tsolaki, Magda; Daniilidou, Makrina; Pritchard, Megan; Kloszewska, Iwona; Soininen, Hilkka; Mecocci, Patrizia; Vellas, Bruno; Williams, Julie; Stewart, Robert; Sham, Pak; Lovestone, Simon; Powell, John F.
Toxoplasma gondii is an intracellular protozoan parasite, which relies on a specialized compartment, the parasitophorous vacuole (PV), to survive within host cells. Dense granules within the parasite release a large variety of proteins to maintain the integrity of the vacuole structure. Here, we identified a novel dense granule protein in T. gondii, TgGRA23, which is a homolog of the Sarcocystis muris dense granule protein, SmDG32. Recombinant TgGRA23 (rTgGRA23) expressed in Escherichia coli as a glutathione S-transferase (GST) fusion protein was used to raise antisera in mice and rabbits. Immunoblotting showed that antisera from the immunized mice and rabbits reacted with parasite lysates to yield a 21-kDa native protein. In addition, immuno-electron microscopic examination showed that TgGRA23 resides in the dense granules, PV membrane and intravacuolar network of the parasite. To confirm the precise subcellular localization of TgGRA23 in T. gondii, an immunofluorescent antibody test was performed using dense granule markers. Notably, TgGRA23 co-localized with other dense granule proteins including TgGRA4 and TgGRA7, in the extracellular-stage parasites. Biochemical experiments indicated that TgGRA23 is insoluble and may form an electrostatic complex that is resistant to non-ionic detergents. Furthermore, specific antibodies to TgGRA23 were detected during the chronic stage of Toxoplasma infection in mice. Our results suggest that TgGRA23 is an as yet unknown member of the T. gondii dense granule proteins, and that it may be involved in remodeling or maintenance of the PV. PMID:23583316
Masatani, Tatsunori; Matsuo, Tomohide; Tanaka, Tetsuya; Terkawi, Mohamad Alaa; Lee, Eung-Goo; Goo, Youn-Kyoung; Aboge, Gabriel Oluga; Yamagishi, Junya; Hayashi, Kei; Kameyama, Kyohko; Cao, Shinuo; Nishikawa, Yoshifumi; Xuan, Xuenan
Self-reactive B cells in BALB/c AM14 transgenic (AM14 Tg) rheumatoid factor (RF) mice are not subject to central or peripheral toleralization. Instead, they remain at a stage of �clonal ignorance�, i.e. they do not proliferate and differentiate into Ab-producing cells. However, the immunoregulatory mechanisms that prevent autoantibody production in these mice remain unclear. In this study, we show that crossing AM14 Tg mice to a mouse strain deficient in Act1, a molecule involved in the regulation of BAFF-R and CD40-signaling in B cells, results in spontaneous activation of AM14 Tg B cells and production of AM14-specific antibodies. Three to five-month old AM14 Tg Act1?/? mice showed significant expansion of AM14 Tg B cells, including a 2�3 fold increase in the spleen and cLNs compared to AM14 Tg Act1+/+ mice. Furthermore, in the presence of endogenous self-Ag (IgHa congenic background), AM14 Tg Act1?/? B cells were spontaneously activated and differentiated into antibody forming cells (AFC). In contrast with previous studies using AM14 Tg MLR.Faslpr mice, we found that a significant number of AM14 Tg cells AM14 Tg Act1?/? mice displayed phenotypic characteristics of GC B cells. Anti-CD40L treatment significantly limited the expansion and activation of AM14 Tg Act1?/? B cells, suggesting that CD40L-mediated signals are required for the retention of these cells. Our results support the important role of Act1 in the regulation of self-reactive B cells and reveal how Act1 functions to prevent the production of autoantibodies. PMID:23904159
Giltiay, Natalia V.; Lu, Yi; Cullen, Jaime L.; J?rgensen, Trine N.; Shlomchik, Mark J.; Li, Xiaoxia
Heparan Sulfate 2-O-Sulfotransferase Is Required for Triglyceride-rich Lipoprotein Clearance*
Hepatic clearance of triglyceride-rich lipoproteins depends on heparan sulfate and low density lipoprotein receptors expressed on the basal membrane of hepatocytes. Binding and uptake of the lipoproteins by way of heparan sulfate depends on the degree of sulfation of the chains based on accumulation of plasma triglycerides and delayed clearance of triglyceride-rich lipoproteins in mice bearing a hepatocyte-specific alteration of N-acetylglucosamine (GlcNAc) N-deacetylase-N-sulfotransferase 1 (Ndst1) (MacArthur, J. M., Bishop, J. R., Stanford, K. I., Wang, L., Bensadoun, A., Witztum, J. L., and Esko, J. D. (2007) J. Clin. Invest. 117, 153�164). Inactivation of Ndst1 led to decreased overall sulfation of heparan sulfate due to coupling of uronyl 2-O-sulfation and glucosaminyl 6-O-sulfation to initial N-deacetylation and N-sulfation of GlcNAc residues. To determine whether lipoprotein clearance depends on 2-O-and 6-O-sulfation, we evaluated plasma triglyceride levels in mice containing loxP-flanked conditional alleles of uronyl 2-O-sulfotransferase (Hs2stf/f) and glucosaminyl 6-O-sulfotransferase-1 (Hs6st1f/f) and the bacterial Cre recombinase expressed in hepatocytes from the rat albumin (Alb) promoter. We show that Hs2stf/fAlbCre+ mice accumulated plasma triglycerides and exhibited delayed clearance of intestinally derived chylomicrons and injected human very low density lipoproteins to the same extent as observed in Ndst1f/fAlbCre+ mice. In contrast, Hs6st1f/fAlbCre+ mice did not exhibit any changes in plasma triglycerides. Chemically modified heparins lacking N-sulfate and 2-O-sulfate groups did not block very low density lipoprotein binding and uptake in isolated hepatocytes, whereas heparin lacking 6-O-sulfate groups was as active as unaltered heparin. Our findings show that plasma lipoprotein clearance depends on specific subclasses of sulfate groups and not on overall charge of the chains. PMID:19889634
Stanford, Kristin I.; Wang, Lianchun; Castagnola, Jan; Song, Danyin; Bishop, Joseph R.; Brown, Jillian R.; Lawrence, Roger; Bai, Xaiomei; Habuchi, Hiroko; Tanaka, Masakazu; Cardoso, Wellington V.; Kimata, Koji; Esko, Jeffrey D.
-domain effect (MDE), sourcesink dy- namics, speciesarea relationships, heterogeneity, and history. I changes in climate, plant communities, and faunal assemblages with increasing elevation have led of plants and animals was higher in the low- lands than at the mountaintops. Willdenow, von Hum- boldt
McCain, Christy M.
control group. In HDL2, a low CE level and a high amount of UC, TG and PL were
control group. In HDL2, a low CE level and a high amount of UC, TG and PL were observed in the 3, between the LCAT activity and TG-HDL3 (r=-0.87, p UC-HDL3 (r=-0 in Western society, and is commonly associated with hyper- triglyceridemia. A hypocaloric diet is accom
Boyer, Edmond
temperature Tg for various glasses brings out general features. At low temperature, Q-1 is only weakly dependent on the material. At high temperature but still below Tg the internal friction for strong glasses shows a T-independent plateau in a very wide domain of temperature; in contrast, for fragile glass
Paris-Sud XI, Université de
Pyrolysis of triglyceride materials for the production of renewable fuels and chemicals.
Conversion of vegetable oils and animal fats composed predominantly of triglycerides using pyrolysis type reactions represents a promising option for the production of renewable fuels and chemicals. The purpose of this article was to collect and review literature on the thermo-chemical conversion of triglyceride based materials. The literature was divided and discussed as (1) direct thermal cracking and (2) combination of thermal and catalytic cracking. Typically, four main catalyst types are used including transition metal catalysts, molecular sieve type catalysts, activated alumina, and sodium carbonate. Reaction products are heavily dependant on the catalyst type and reaction conditions and can range from diesel like fractions to gasoline like fractions. Research in this area is not as advanced as bio-oil and bio-diesel research and there is opportunity for further study in the areas of reaction optimization, detailed characterization of products and properties, and scale-up. PMID:17166713
Maher, K D; Bressler, D C
NASA Astrophysics Data System (ADS)
We compared four esterifiable enzymes. The lipase Novozym 435 possessed the highest activity for the conjugated linoleic acid esterification during the synthesis of triglycerides. The triglycerides were synthesized by esterification of glycerol and conjugated linoleic acid (CLA) in a no-solvent system using lipase catalysis. We investigated the effects of temperature, enzyme concentration, water content, and time on esterification. Enzyme and water concentrations of up to 1% of the total reaction volume and a system temperature of 60�C proved optimal for esterification. Similarly, when the esterification was carried out for 24 h, the reaction ratio improved to 94.11%. The esterification rate of the rotating screen basket remained high (87.28%) when the enzyme was re-used for the 5th time. We evaluated the substrate selectivity of lipase (NOVO 435) and determined that this lipase prefers the 10,12-octadacadienoic acid to the 9,11-octadecadienoic acid.
Yi, Dan; Sun, Xiuqin; Li, Guangyou; Liu, Fayi; Lin, Xuezheng; Shen, Jihong
We have previously characterized an activity from human plasma that markedly stimulates triglyceride synthesis in cultured human skin fibroblasts and human adipocytes. Based on its in vitro activity we named the active component acylation stimulating protein (ASP). The molecular identity of the active serum component has now been determined. NH2-terminal sequence analysis, ion spray ionization mass spectroscopy, and amino acid composition analysis all indicate that the active purified protein is a fragment of the third component of plasma complement, C3a-desArg. As well, reconstitution experiments with complement factors B, D, and complement C3, the components necessary to generate C3a, have confirmed the identity of ASP as C3a. ASP appears to be the final effector molecule generated by a novel regulatory system that modulates the rate of triglyceride synthesis in adipocytes. Images PMID:8376604
Baldo, A; Sniderman, A D; St-Luce, S; Avramoglu, R K; Maslowska, M; Hoang, B; Monge, J C; Bell, A; Mulay, S; Cianflone, K
Medium chain triglyceride rich margarines were prepared using palm, coconut oil blends in the ratio of 80:20 (Margarine 1) and 60:40 (Margarine 2). The margarines were used to prepare burfi and compared with products prepared using commercial margarine, ghee and butter. The physicochemical characteristics such as texture, color, free fatty acid, peroxide value, saponification value, unsaponifiable matter and fatty acid composition of oils, fats and margarines were carried out. Results showed that 11.0 and 21.9% of medium chain triglycerides were present in margarine 1 and 2 respectively. The texture, colour, moisture content, peroxide value and sensory evaluation were carried out for the burfi samples. Laboratory prepared margarines improved the textural quality of burfi compared to commercial margarine, ghee and butter. The sensory analyses of the burfi samples revealed that burfi prepared from margarine 1 was more acceptable compared to commercial margarine. PMID:24426059
Tiwari, Shipra; Chetana, Ramakrishna; Puttaraju, Shashikala; Khatoon, Sakina
Process for enzymatic hydrolysis of fatty acid triglycerides with oat caryopses
This patent describes the process for enzymatic hydrolysis of fatty acid triglycerides to obtain free fatty acids and glycerol. It comprises: increasing the water content of dehulled whole oat caryopses to a total water content of 17 to 44% the thus moistened caryopses having active oat lipase associated with the outer surfaces thereof; contacting the moistened whole caryopses with a liquid medium, continuing the contacting until at least 20% by volume of the triglyceride reactant has been hydrolyzed to free fatty acids and glycerol, most of the free fatty acids dissolving in the oil phase external to the caryopses and most of the glycerol being absorbed into the water within the caryopses; and separating the glycerol-containing caryopses from the fatty acid-containing oil phase.
Hammond, E.G.; Lee, I.
TOMM40 SNP rs157580 has been associated with triglyceride levels in Genome-wide association studies (GWAS). Chronic caregiving stress moderates the association between triglyceride levels and a nearby SNP rs439401 that is associated with triglyceride levels in GWAS. Here, we report data from two independent Caucasian samples (242 U.S. women and men; 466 Danish men) testing the hypothesis that chronic family stress also moderates the association between rs157580 and triglyceride levels. The interaction of rs157580 and family stress in predicting triglyceride levels was statistically significant in the U.S. sample (p = 0.004) and marginally significant (p = 0.075) in the Danish sample. The G allele of rs157580 was associated with increased triglyceride levels among family stressed cases in both samples compared with A/A cases, but not among controls. Chronic family stress moderates the association of rs157580 variants with triglyceride levels and should be taken into account for disease risk assessment and potential intervention. PMID:23435269
Jiang, Rong; Brummett, Beverly H.; Hauser, Elizabeth R.; Babyak, Michael A.; Siegler, Ilene C.; Singh, Abanish; Astrup, Arne; Pedersen, Oluf; Hansen, Torben; Holst, Claus; S?rensen, Thorkild I.A.; Williams, Redford B.
Plasma triglyceride turnover was measured during steady-state conditions in 22 postoperative patients. Nine had received nutritional support with an enteral regimen, seven had received an equivalent regimen as continuous parenteral nutrition, and six received the same parenteral regimen as a cyclical infusion. After 5 days of nutritional support, each patient received an intravenous bolus of tritiated glycerol. Plasma radiolabeled triglyceride content was measured during the subsequent 24 hours. The data were analyzed by means of a simple deterministic model of plasma triglyceride kinetics and compared with the results obtained by stochastic analysis. The rates of hepatic triglyceride secretion obtained by deterministic analysis were higher than those obtained by the stochastic approach. However, the mode of delivery of the nutritional regimen did not affect the rate of hepatic triglyceride secretion regardless of the method of analysis. The results suggest that neither complete nutritional bypass of the gastrointestinal tract nor interruption of parenteral nutrition in an attempt to mimic normal eating has any effect on hepatic triglyceride secretion. Any beneficial effect that enteral feeding or cyclical parenteral nutrition may have on liver dysfunction associated with standard parenteral nutrition appears to be unrelated to changes in hepatic triglyceride secretion.
Isabel-Martinez, L.; Skinner, C.; Parkin, A.; Hall, R.I.
... different laboratories. Talk to your doctor about the meaning of your specific test results. The examples above show the common measurements for results for these tests. Some laboratories use different measurements or may test different specimens.
Glucocorticoids are antiinflammatory therapeutics that have potent effects on cell differentiation. The aim of this study was to establish whether systemic glucocorticoid exposure significantly affects pancreatic differentiation in vivo because hepatocyte-like cells have been documented to occur in the diseased rodent pancreas. Expression of hepatic markers was examined in pancreata from mice genetically modified to secrete elevated circulating endogenous glucocorticoid [Tg(Crh)]. Tg(Crh) mice with elevated glucocorticoid appeared cushingoid and by 21 weeks of age were obese, insulin-resistant, and had extensive areas of hepatic gene expression in exocrine tissue. Acinar cells from Tg(Crh) mice costained for both amylase and cyp2e1, suggesting direct acinar-hepatic transdifferentiation. Hepatic expression increased with age in the pancreas to such an extent that malabsorption and rapid weight loss occurred in a subset of aging mice; this effect was reversed by dietary porcine pancreatic enzyme supplementation. Indeed, pancreatic expression of hepatic markers was prevented by adrenalectomy, establishing a direct role for glucocorticoid. Elevated levels of circulating glucocorticoid therefore promote a transdifferentiation of adult exocrine pancreas into hepatocyte-like cells, and chronic exposure results in pancreatic malfunction. Glucocorticoids are thus capable of modulating the differentiation of terminally differentiated adult cells. PMID:20651242
Wallace, Karen; Flecknell, Paul A.; Burt, Alastair D.; Wright, Matthew C.
Cholesterol and Triglycerides in Antipsychotic-Naive Patients with Nonaffective Psychosis
Patients with psychosis have an increased prevalence of hyperlipidemia. We compared fasting concentrations of lipids in newly diagnosed, antipsychotic-na�ve patients with nonaffective psychosis (N-87) and control subjects (N=92). After accounting for gender, age, smoking, socioeconomic status, and body mass index, there was no significant difference between the two groups in total cholesterol, high-density lipoproteins, low-density lipoproteins, or triglycerides. PMID:20576293
Kirkpatrick, Brian; Garcia-Rizo, Clemente; Tang, Kun; Fernandez-Egea, Emilio; Bernardo, Miguel
Separation and determination of mono-, Di, and triglycerides in monoglyceride concentrates
Summary��Monoglyceride concentrates are quantitatively separated into mono-, di-, and triglyceride components on silica gel columns\\u000a by an adsorption chromatographic technique. The separated glycerides are determined gravimetrically. The adsorption on silica\\u000a gel is dependent on the number of hydroxyl groups in the molecule, and the influence of unsaturation and chain length is minimized.\\u000a Combinations of benzene and ethyl ether are used
Patricia Quinlin; Herman J. Weiser
High-density lipoprotein and transport of cholesterol and triglyceride in blood.
High-density lipoproteins (HDL) contain approximately 25% of the cholesterol and <5% of the triglyceride in the plasma of human blood. However, the dynamic exchange of lipids and lipid-binding proteins is not revealed by simply considering the mass of material at any point in time. HDL are the most complex of lipoprotein species with multiple protein constituents, which facilitate cholesterol secretion from cells, cholesterol esterification in plasma, and transfer of cholesterol to other lipoproteins and to the liver for excretion. They also play a major role in triglyceride transport by providing for activation of lipoprotein lipase, exchange of triglyceride among the lipoproteins, and removal of triglyceride rich remnants of chylomicrons and very-low-density lipoproteins after lipase action. In addition, antioxidative enzymes and phospholipid transfer proteins are important components of HDL. Many of the proteins of HDL are exchangeable with other lipoproteins, including chylomicrons and very-low-density lipoproteins. The constantly changing content of lipids and apolipoproteins in HDL particles generate a series of structures that can be analyzed by using separation techniques that depend on size or charge of the particles. Interaction of these various structures can be very different with cell surfaces depending on the size or apolipoprotein content. A series of different transport proteins preferentially exchange lipids with specific structures among the HDL but interact poorly or not at all with others. The role of these differing forms of HDL and their interactions with cells and other lipoprotein species in plasma is the subject of intense study stimulated by the potential for reducing atherogenesis. The strength of this is only partially indicated by the correlation of higher total levels of the HDL particles with reduced incidence of vascular disease in various clinical trials and epidemiological studies. PMID:21291664
Brown, William Virgil
Phase behaviour in binary mixed Langmuir�Blodgett monolayers of triglycerides
Binary mixed monolayers of the triglycerides (TAGs)-tripalmitin (PPP), tristearin (SSS) and triarachidin (AAA) at the air�water interface are investigated with the Langmuir method. Langmuir�Blodgett (LB) layers obtained by deposition on mica are investigated by Atomic Force Microscopy. Combining Langmuir and AFM results the relation between the phase behaviour of binary mixed TAGs and their chain length is established. TAG mixtures
Aneliya N. Zdravkova; J. P. J. M. van der Eerden
Rescue of cardiac leptin receptors in db/db mice prevents myocardial triglyceride accumulation.
Increased leptin levels have been suggested to contribute to cardiac hypertrophy and attenuate cardiac lipid accumulation in obesity, although it has been difficult to separate leptin's direct effects from those caused by changes in body weight and adiposity. To determine whether leptin attenuates cardiac lipid accumulation in obesity or directly causes left ventricular hypertrophy (LVH), we generated a novel mouse model in which the long form of the leptin receptor (LepR) was "rescued" only in cardiomyocytes of obese db/db mice. Reexpression of cardiomyocyte leptin receptors in db/db mice did not cause LVH but reduced cardiac triglycerides and improved cardiac function. Compared with lean wild-type (WT) or db/db-cardiac LepR rescue mice, db/db mice exhibited significantly lower E/A ratio, a measurement of early to late diastolic filling, which averaged 1.5 � 0.07 in db/db vs. 1.9 � 0.08 and 1.8 � 0.11 in WT and db/db-cardiac LepR rescue mice, respectively. No differences in systolic function were observed. Although db/db and db/db-cardiac LepR rescue mice exhibited similar increases in plasma triglycerides, insulin, glucose, and body weight, cardiac triglycerides were significantly higher in db/db compared with WT and db/db cardiac LepR rescue mice, averaging 13.4 � 4.2 vs. 3.8 � 1.6 vs. 3.8 � 0.7 mg/g, respectively. These results demonstrate that despite significant obesity and increases in plasma glucose and triglycerides, db/db cardiac LepR rescue mice are protected against myocardial lipid accumulation. However, we found no evidence that leptin directly causes LVH. PMID:24939734
Hall, Michael E; Maready, Matthew W; Hall, John E; Stec, David E
Members of the genusLesquerella, native to North America, have oils containing large amounts of hydroxy fatty acids and are under investigation as potential\\u000a new crops. The triglyceride structure of oils from twenty-fiveLesquerella species in the seed collection at our research center has been examined after being hydrolysis-catalyzed by reverse micellar-encapsulated\\u000a lipase and alcoholysis-catalyzed by immobilized lipase. These reactions, when coupled
Douglas G. Hayes; Robert Kleiman; Bliss S. Phillips
The seed oil ofLesquerella auriculata contains 32% of a previously unknown fatty acid, 14-hydroxy-cis-11,cis-17-eicosadienoic acid; we propose for it the trivial name �auricolic acid.� In addition, the oil contains 2% densipolic (12-hydroxy-cis-9,cis-15-octadecadienoic) acid, 10% lesquerolic (14-hydroxy-cis-11-eicosenoic) acid and 5% ricinoleic acid. The oil ofL. auriculata is also unusual, because a large part of the total oil consists of triglycerides containing
R. Kleiman; G. F. Spencer; F. R. Earle; H. J. Nieschlag; A. S. Barclay
Recent studies suggest that hyperinsulinemia and insulin resistance are linked to Alzheimer�s disease (AD). In this study, we used Tg2576 transgenic (Tg) mice, a widely used transgenic mouse model for AD, to explore the relationship between increased amyloid ?-peptide (A?) and insulin resistance. When fed a high-fat diet (HFD), Tg mice developed obesity and insulin resistance at 16 wk of age. Furthermore, HFD-fed Tg mice displayed abnormal feeding behavior and increased caloric intake with time. Although caloric intake of HFD-fed Tg mice was similar to that of normal diet-fed Tg or wild-type mice during 4 to 8 wk of age, it increased sharply at 12 wk, and went up further at 16 wk, which paralleled changes in the level of A?40 and A?42 in the brain of these mice. Limiting food intake in HFD-fed Tg mice by pair-feeding a caloric intake identical with that of normal diet-fed mice completely prevented the obesity and insulin intolerance of HFD-fed Tg mice. The hypothalamus of HFD-fed Tg mice had a significant decrease in the expression of the anorexigenic neuropeptide, brain-derived neurotrophic factor, at both the mRNA and protein levels. These findings suggest that the increased A? in the brain of HFD-fed Tg2576 mice is associated with reduced brain-derived neurotrophic factor expression, which led to abnormal feeding behavior and increased food intake, resulting in obesity and insulin resistance in these animals. PMID:20176720
Kohjima, Motoyuki; Sun, Yuxiang; Chan, Lawrence
Characterization of TgPuf1, a member of the Puf family RNA-binding proteins from Toxoplasma gondii
Background Puf proteins act as translational regulators and affect many cellular processes in a wide range of eukaryotic organisms. Although Puf proteins have been well characterized in many model systems, little is known about the structural and functional characteristics of Puf proteins in the parasite Toxoplasma gondii. Methods Using a combination of conventional molecular approaches, we generated endogenous TgPuf1 tagged with hemagglutinin (HA) epitope and investigated the TgPuf1 expression levels and localization in the tachyzoites and bradyzoites. We used RNA Electrophoretic Mobility Shfit Assay (EMSA) to determine whether the recombination TgPuf1 has conserverd RNA binding activity and specificity. Results TgPuf1 was expressed at a significantly higher level in bradyzoites than in tachyzoites. TgPuf1 protein was predominantly localized within the cytoplasm and showed a much more granular cytoplasmic staining pattern in bradyzoites. The recombinant Puf domain of TgPuf1 showed strong binding affinity to two RNA fragments containing Puf-binding motifs from other organisms as artificial target sequences. However, two point mutations in the core Puf-binding motif resulted in a significant reduction in binding affinity, indicating that TgPuf1 also binds to conserved Puf-binding motif. Conclusions TgPuf1 appears to exhibit different expression levels in the tachyzoites and bradyzoites, suggesting that TgPuf1 may function in regulating the proliferation or/and differentiation that are important in providing parasites with the ability to respond rapidly to changes in environmental conditions. This study provides a starting point for elucidating the function of TgPuf1 during parasite development. PMID:24685055
In 1999, the AAPM introduced a reference dosimetry protocol, known as TG51, based on an absorbed dose standard. This replaced the previous protocol, known as TG21, which was based on an air kerma standard. A significant body of literature has emerged discussing the improved accuracy and robustness of the absorbed dose standard, and quantifying the changes in baseline dosimetry with the introduction of the absorbed dose protocol. A significant component playing a role in the overall accuracy of beam output determination is the variability due to the use of different dosimeters. This issue, not adequately addressed in the past, is the focus of the present study. This work provides a comparison of absorbed dose determinations using 21 different makes and models of ion chambers for low- and high-energy photon and electron beams. The study included 13 models of cylindrical ion chambers and eight models of plane-parallel chambers. A high degree of precision (<0.25%) resulted from measurements with all chambers in a single setting, a sufficient number of repeat readings, and the use of high quality ion chambers as external monitors. Cylindrical chambers in photon beams show an improvement in chamber-to-chamber consistency with TG51. For electron dosimetry with plane-parallel chambers, the parameters N{sub gas} and the product N{sub D,w}{center_dot}k{sub ecal} were each determined in two ways, based on (i) an ADCL calibration, and (ii) a cross comparison with an ADCL-calibrated cylindrical chamber in a high-energy electron beam. Plane-parallel chamber results, therefore, are presented for both methods of chamber calibration. Our electron results with technique (i) show that plane-parallel chambers, as a group, overestimate the beam output relative to cylindrical chambers by 1%-2% with either protocol. Technique (ii), by definition, normalizes the plane-parallel results to the cylindrical results. In all cases, the maximum spread in output from the various cylindrical chambers is <2% implying a standard deviation of less than 0.5%. For plane-parallel chambers, the maximum spread is somewhat larger, up to 3%. A few chambers have been identified as outliers.
Tailor, Ramesh C.; Hanson, William F.; Wells, Nathan; Ibbott, Geoffrey S. [MD Anderson Cancer Center, University of Texas, Houston, Texas 77030 (United States)
Cilostazol is clinically used for the treatment of ischemic symptoms in patients with chronic peripheral arterial obstruction and for the secondary prevention of brain infarction. Recently, it has been reported that cilostazol has preventive effects on atherogenesis and decreased serum triglyceride in rodent models. There are, however, few reports on the evaluation of cilostazol using atherosclerotic rabbits, which have similar lipid metabolism to humans, and are used for investigating the lipid content in aorta and platelet aggregation under conditions of hyperlipidemia. Therefore, we evaluated the effect of cilostazol on the atherosclerosis and platelet aggregation in rabbits fed a normal diet or a cholesterol-containing diet supplemented with or without cilostazol. We evaluated the effects of cilostazol on the atherogenesis by measuring serum and aortic lipid content, and the lesion area after a 10-week treatment and the effect on platelet aggregation after 1- and 10-week treatment. From the lipid analyses, cilostazol significantly reduced the total cholesterol, triglyceride and phospholipids in serum, and moreover, the triglyceride content in the atherosclerotic aorta. Cilostazol significantly reduced the intimal atherosclerotic area. Platelet aggregation was enhanced in cholesterol-fed rabbits. Cilostazol significantly inhibited the platelet aggregation in rabbits fed both a normal diet and a high cholesterol diet. Cilostazol showed anti-atherosclerotic and anti-platelet effects in cholesterol-fed rabbits possibly due to the improvement of lipid metabolism and the attenuation of platelet activation. The results suggest that cilostazol is useful for prevention and treatment of atherothrombotic diseases with the lipid abnormalities. PMID:22761774
Ito, Hideki; Uehara, Kenji; Matsumoto, Yutaka; Hashimoto, Ayako; Nagano, Chifumi; Niimi, Manabu; Miyakoda, Goro; Nagano, Keisuke
Summary We narrowed chromosome 15q21-23 linkage to plasma high density lipoprotein cholesterol (HDL-C) levels in atherogenic dyslipidemic Turkish families by fine mapping, then focused on glucuronic acid epimerase (GLCE), a heparan sulfate proteoglycan (HSPG) biosynthesis enzyme. HSPGs participate in lipid metabolism along with apolipoprotein (apo) E. Of 31 SNPs in the GLCE locus, nine analyzed by haplotype were associated with plasma HDL-C and triglyceride levels (permuted p = 0.006 and 0.013, respectively) in families. Of five tagging GLCE SNPs in two cohorts of unrelated subjects, three (rs16952868, rs11631403, rs3865014) were associated with triglyceride and HDL-C levels in males (non-permuted p < 0.05). The association was stronger in APOE 2/3 subjects (apoE2 has reduced binding to HSPGs) and reached multiple-testing significance (p < 0.05) in both males and females (n = 2612). Similar results were obtained in the second cohort (n = 1164). Interestingly, at the GLCE locus, bounded by recombination hotspots, Turks had a minor allele frequency of SNPs resembling Chinese more than European ancestry; adjoining regions on chromosome 15 resembled the European pattern. Studies of glce+/�apoe�/� mice fed a chow or high-fat diet supported a role for GLCE in lipid metabolism. Thus, SNPs in GLCE are associated with triglyceride and HDL-C levels in Turks, and mouse studies support a role for glce in lipid metabolism. PMID:21488854
Hodoglugil, Ugur; Williamson, David W.; Yu, Yi; Farrer, Lindsay A.; Mahley, Robert W.
Elevated temperature crack growth
NASA Technical Reports Server (NTRS)
The objective of the Elevated Temperature Crack Growth Project is to evaluate proposed nonlinear fracture mechanics methods for application to combustor liners of aircraft gas turbine engines. During the first year of this program, proposed path-independent (P-I) integrals were reviewed for such applications. Several P-I integrals were implemented into a finite-element postprocessor which was developed and verified as part of the work. Alloy 718 was selected as the analog material for use in the forthcoming experimental work. A buttonhead, single-edge notch specimen was designed and verified for use in elevated-temperature strain control testing with significant inelastic strains. A crack mouth opening displacement measurement device was developed for further use.
Yau, J. F.; Malik, S. N.; Kim, K. S.; Vanstone, R. H.; Laflen, J. H.
An evaluation of primary water standards by TG\\/DTA and vapor sorption analysis
Sodium tartrate dihydrate, lactose monohydrate, potassium citrate monohydrate, and calcium oxalate monohydrate are commonly\\u000a used as primary standards for methods that determine water content. Identification of the type of water of hydration (channel,\\u000a lattice, or ion associated) is provided herein for each standard based upon thermogravimetry\\/differential thermal analysis\\u000a (TG\\/DTA) and dynamic vapor sorption data. Sodium tartrate dihydrate was found to
Nancy Redman-Furey; Kate Poiesz; James Miller; Carol Grundner
Characterization of the Brain ?-Amyloid Isoform Pattern at Different Ages of Tg2576 Mice
Background: Although genetic and biochemical studies have suggested a cardinal role for ?-amyloid (A?) in Alzheimer�s disease, the underlying mechanism(s) of how A? induces neurodegeneration is still unclear. Our objective was to investigate the consequences of A?, especially on tau phosphorylation at specific epitopes important for Alzheimer�s disease. Methods: We used cortices from Tg2576 mice at 7 days to 15
Tamanna Mustafiz; Erik Portelius; Mikael K. Gustavsson; Mikko H�ltt�; Henrik Zetterberg; Kaj Blennow; Agneta Nordberg; Christina Unger Lithner
(e.g. SiO2) Strong and high Tg, Tm
/s) Pentene Butene Propanol ( 10 K/s) ( 107 K/s) Toluene OTP Ethanol Propene Benzene CCl4 Methanol Ethane effect Low-energy excitation #12;#12;Propane Propene 1-Butene 1-Pentene 3-Methylpentane Tg / K 45.5 56-Gibbs Theory) Propene 1-Butene 1-Pentene 3MP Propane #12;CS2 60 K 70 K #12;Q Q #12;Sm (Q) = Sm u (Q) + Sm (Q
Katsumoto, Shingo
Elevated temperature crack growth
NASA Technical Reports Server (NTRS)
The objective of the Elevated Temperature Crack Growth Program is to evaluate proposed nonlinear fracture mechanics methods for application to hot section components of aircraft gas turbine engines. Progress during the past year included linear-elastic fracture mechanics data reduction on nonlinear crack growth rate data on Alloy 718. The bulk of the analytical work centered on thermal gradient problems and proposed fracture mechanics parameters. Good correlation of thermal gradient experimental displacement data and finite element prediction was obtained.
Malik, S. N.; Vanstone, R. H.; Kim, K. S.; Laflen, J. H.
Effects of the C57BL/6 strain background on tauopathy progression in the rTg4510 mouse model
Background Cross-breeding of transgenic mice is commonly used to assess gene-gene interactions, particularly in the context of disease. Strain background changes can influence the phenotype of mouse models and can confound crossbreeding studies. We sought to determine if changing the strain background of a commonly used mouse model of tauopathy (rTg4510) would significantly impact the originally reported phenotype. On the original F1 FVB/N x 129S6 background, rTg4510 mice present with progressive cognitive decline, increased insoluble tau, robust tau pathology and age-dependent neurodegeneration. One of the most common strains in mouse modeling is C57BL/6. We and others have previously reported that this strain background alters the phenotypes of various models, including the JNPL3 model of tauopathy. To determine if the phenotype of rTg4510 mice was similarly affected by the introduction of the C57BL/6 background, we compared rTg4510 mice on the original F1 FVB/N x 129S6 background to rTg4510 mice on an F1 FVB/N x C57BL/6NTac (B6/NTac) background, herein termed rTg4510B6. Results Despite a small, but significant increase in soluble human tau levels, young rTg4510B6 mice had equivalent levels of tau phosphorylation, aggregation and cognitive impairments as age-matched rTg4510 mice. At 6.5�months of age, rTg4510B6 mice displayed hyperphosphorylated insoluble tau and robust cortical tau neuropathology that was equivalent to age-matched rTg4510 mice; however, 10.5-month-old rTg4510B6 mice had greater amounts of phospho-tau in the cortex and hippocampus when compared to age-matched rTg4510 mice. Non-transgenic (NT) littermates of rTg4510B6 (NTB6) mice also had greater amounts of cortical and hippocampal phospho-tau at 10.5�months of age when compared to NT littermates of rTg4510 mice. Additionally, older rTg4510B6 mice had gross forebrain neurodegeneration that was equivalent to age-matched rTg4510 mice. Conclusions Overall, our data shows that introduction of the C57BL/6 strain into the rTg4510 mouse background modestly alters the tau pathology that was originally reported in rTg4510 on the F1 FVB/129 background. In contrast, behavioral and neurodegenerative outcomes were not altered. These studies support the use of the rTg4510 mouse model on a partial C57BL/6 strain background without losing fidelity of the phenotype and suggest that the C57BL/6 background does not inherently protect against tauopathy. PMID:24428919
BACKGROUNDOmega-3 fatty acids, such as those present in fish oil, have been reported to prolong life in myocardial infarction survivors. These fatty acids can decrease serum triglyceride concentrations, but so far the doses used in trials examining their effects on coronary end points have had only minimal triglyceride lowering effects.OBJECTIVETo examine the triglyceride lowering effectiveness, safety, and tolerability of Omacor,
P N Durrington; D Bhatnagar; M I Mackness; J Morgan; K Julier; M A Khan
The Bradykinin B1 Receptor Regulates A? Deposition and Neuroinflammation in Tg-SwDI Mice
The deposition of amyloid-? peptides (A?) in the cerebral vasculature, a condition known as cerebral amyloid angiopathy, is increasingly recognized as an important component leading to intracerebral hemorrhage, neuroinflammation, and cognitive impairment in Alzheimer disease (AD) and related disorders. Recent studies demonstrated a role for the bradykinin B1 receptor (B1R) in cognitive deficits induced by A? in mice; however, its involvement in AD and cerebral amyloid angiopathy is poorly understood. Herein, we investigated the effect of B1R inhibition on AD-like neuroinflammation and amyloidosis using the transgenic mouse model (Tg-SwDI). B1R expression was found to be up-regulated in brains of Tg-SwDI mice, specifically in the vasculature, neurons, and astrocytes. Notably, administration of the B1R antagonist, R715, to 8-month-old Tg-SwDI mice for 8 weeks resulted in higher A?40 levels and increased thioflavin S�positive fibrillar A? deposition. Moreover, blockage of B1R inhibited neuroinflammation, as evidenced by the decreased accumulation of activated microglia and reactive astrocytes, diminished NF-?B activation, and reduced cytokine and chemokine levels. Together, our results indicate that B1R activation plays an important role in limiting the accumulation of A? in AD-like brain, likely through the regulation of activated glial cell accumulation and release of pro-inflammatory mediators. Therefore, the modulation of the receptor may represent a novel therapeutic approach for AD. PMID:23470163
Passos, Giselle F.; Medeiros, Rodrigo; Cheng, David; Vasilevko, Vitaly; LaFerla, Frank M.; Cribbs, David H.
2. EAST ELEVATION. IT IS CURRENTLY THE ENTRANCE ELEVATION. THE STREET TO THE LEFT IS RANSTEAD STREET, AND THE STREET TO THE RIGHT IS LUDLOW STREET - Philadelphia Bourse, 11-21 South Fifth Street, Philadelphia, Philadelphia County, PA
49. EAST ELEVATION OF ASSEMBLING BUILDING #2 AND SOUTH ELEVATION OF BODY BUILDING, 1980 (MMI) - Dodge Brothers Motor Car Company Plant, Between Joseph Campau & Conant Avenues, Hamtramck, Wayne County, MI
43. ELEVATOR HEADHOUSE INTERIOR: Interior view towards southeast of elevator ...
43. ELEVATOR HEAD-HOUSE INTERIOR: Interior view towards southeast of elevator head-house at the Washington and Mason Street powerhouse. - San Francisco Cable Railway, Washington & Mason Streets, San Francisco, San Francisco County, CA
Building C west elevation showing south elevation of Building B ...
Building C west elevation showing south elevation of Building B (on left) and north elevation of Building D (on right). The Germantown Dyeworks complex and smoke stack appear in the background. View looking east - Hinckley Knitting Mills, Building C, 21-35 East Wister Street, Philadelphia, Philadelphia County, PA
Elevations and Floor Plan of Shed No. 1, Elevations and ...
Elevations and Floor Plan of Shed No. 1, Elevations and Floor Plan of Work Shed, Elevations and Floor Plan of Garage - Roberts-Dolezal Farmstead, 75 miles northeast of the intersection of CR27 and FM 1722, Garrett, Ellis County, TX
Objective--ApoAV, a newly discovered apoprotein, affectsplasma triglyceride level. To determine how this occurs, we studiedtriglyceride-rich lipoprotein (TRL) metabolism in mice deficient inapoAV. Methods and Results No significant difference in triglycerideproduction rate was found between apoa5_/_ mice and controls. Thepresence or absence of apoAV affected TRL catabolism. After the injectionof 14C-palmitate and 3H-cholesterol labeled chylomicrons and 125I-labeledchylomicron remnants, the disappearance of 14C, 3H, and 125I wassignificantly slower in apoa5_/_ mice relative to controls. This wasbecause of diminished lipolysis of TRL and the reduced rate of uptake oftheir remnants in apoa5_/_ mice. Observed elevated cholesterol level wascaused by increased high-density lipoprotein (HDL) cholesterol inapoa5_/_ mice. VLDL from apoa5_/_ mice were poor substrate forlipoprotein lipase, and did not bind to the low-density lipoprotein (LDL)receptor as well as normal very-low-density lipoprotein (VLDL). LDLreceptor levels were slightly elevated in apoa5_/_ mice consistent withlower remnant uptake rates. These alterations may be the result of thelower apoE-to-apoC ratio found in VLDL isolated from apoa5_/_mice.Conclusions These results support the hypothesis that the absence ofapoAV slows lipolysis of TRL and the removal of their remnants byregulating their apoproteins content after secretion.
Grosskopf, Itamar; Baroukh, Nadine; Lee, Sung-Joon; Kamari,Yehuda; Harats, Dror; Rubin, Edward M.; Pennacchio, Len A.; Cooper, AllenD.
National Technical Information Service (NTIS)
Endogenous lipid storage components are accumulated or utilized by both microorganisms and marine invertebrates, depending upon their nutritional status. Triglycerides are commonly the lipid endogenous storage materials utilized by fungi, marine vertebrat...
M. J. Gehron, D. C. White
Endogenous lipid storage components are accumulated or utilized by both microorganisms and marine invertebrates, depending upon their nutritional status. Triglycerides are commonly the lipid endogenous storage materials utilized by fungi, marine vertebrates and many invertebrates...
Objective: To compare the effects of a lipid emulsion containing medium-chain triglycerides (MCT) and supplemented with ?-tocopherol to a conventional long-chain triglyceride (LCT) emulsion.Design: Randomised double blind study.Setting: Department of Internal Medicine, Antwerp University Hospital.Subjects and interventions: Twenty-four patients with an indication for total parenteral nutrition for a minimum of 10 days were randomly assigned to two groups: group E
B Manuel-y-Keenoy; L Nonneman; H De Bosscher; J Vertommen; S Schrans; K Kl�tsch; I De Leeuw
Background Although epidemiological studies have demonstrated an increased predisposition to low HDL cholesterol (HDL-C) and high triglyceride (TG) levels in the Mexican population, Mexicans have not been included in any of the previously reported genome-wide association studies (GWAS) for lipids. Results We investigated six SNPs associated with TGs, seven with HDL-C and one with both TGs and HDL-C in recent Caucasian GWAS in Mexican familial combined hyperlipidemia families and hypertriglyceridemia case-control study samples. These variants were within or near the genes ABCA1, ANGPTL3, APOA5, APOB, CETP, GALNT2, GCKR, LCAT, LIPC, LPL (2), MMAB-MVK, TRIB1 and XKR6-AMAC1L2. We performed a combined analysis of the family-based and case-control studies (n=2,298) using the Z-method to combine statistics. Ten of the SNPs were nominally significant and five were significant after Bonferroni correction (P = 2.20 � 10-3 � 2.6 � 10-11) for the number of tests performed (APOA5, CETP, GCKR and GALNT2). Interestingly, our strongest signal was obtained for TGs with the minor allele of rs964184 (P=2.6 � 10-11) in the APOA1/C3/A4/A5 gene cluster region that is significantly more common in Mexicans (27%) than in Caucasians (12%). Conclusions It is important to confirm whether known loci have a consistent effect across ethnic groups. We show replication of five Caucasian GWAS lipid associations in Mexicans. The remaining loci will require a comprehensive investigation to exclude or verify their significance in Mexicans. We also demonstrate that rs964184 has a large effect (OR=1.74) and is more frequent in the Mexican population, and thus it may contribute to the high predisposition to dyslipidemias in Mexicans. PMID:20160193
Weissglas-Volkov, Daphna; Aguilar-Salinas, Carlos A.; Sinsheimer, Janet S.; Riba, Laura; Huertas-Vazquez, Adriana; Ordonez-Sanchez, Maria L.; Rodriguez-Guillen, Rosario; Cantor, Rita M.; Tusie-Luna, Teresa; Pajukanta, Paivi
Elevate America's State Voucher Strategy
the first Elevate America offering--a partnership with state governments to provide computer skills train the Elevate America veterans initiative, a two-year program to help U.S. military veterans and their spouses transition to civilian employment. In February 2011, we launched the Elevate America community initiative
Bernstein, Phil
Elevated temperature crack growth
NASA Technical Reports Server (NTRS)
Alloy 718 crack growth experiments were conducted to assess the ability of the selected path-independent (P-I) integrals to describe the elevated temperature crack growth behavior. These tests were performed on single edge notch (SEN) specimens under displacement control with multiple extensometers to monitor the specimen and crack mouth opening displacement (CMOD). The displacements in these tests were sufficiently high to induce bulk cyclic inelastic deformation of the specimen. Under these conditions, the linear elastic fracture mechanics (LEFM) parameter K does not correlate the crack growth data. The experimentally measured displacement gradients at the end of specimen gage length were used as the boundary conditions in elastic-plastic finite element method (FEM) analyses. These analyses were performed with a node release approach using CYANIDE, a GEAE FEM code, which included a gap element which is capable of efficiently simulating crack closure. Excellent correlation was obtained between the experimentally measured and predicted variation of stress and CMOD with crack length and the stress-CMOD loops for Alloy 718 tests conducted at 538 C. This confirmed the accuracy of the FEM crack growth simulation approach. The experimentally measured crack growth rate data correlated well the selected P-I integrals. These investigations have produced significant progress in developing P-I integrals as non-linear fracture mechanics parameters. The results suggest that this methodology has the potential of accurately describing elevated temperature crack growth behavior under the combined influence of thermal cycling and bulk elastic-inelastic deformation states.
Kim, K. S.; Vanstone, R. H.
The Earth Science Information Center (ESIC) distributes digital cartographic/geographic data files produced by the U.S. Geological Survey (USGS) as part of the National Mapping Program. Digital cartographic data files may be grouped into four basic types. The first of these, called a Digital Line Graph (DLG), is the line map information in digital form. These data files include information on base data categories, such as transportation, hypsography, hydrography, and boundaries. The second type, called a Digital Elevation Model (DEM), consists of a sampled array of elevations for a number of ground positions at regularly spaced intervals. The third type is Land Use and Land Cover digital data which provides information on nine major classes of land use such as urban, agricultural, or forest as well as associated map data such as political units and Federal land ownership. The fourth type, the Geographic Names Information System, provides primary information for all known places, features, and areas in the United States identified by a proper name.
Calibration of the Gamma Knife Perfexion using TG-21 and the solid water Leksell dosimetry phantom
Purpose: To calibrate a Gamma Knife (GK) Perfexion using TG-21 with updated chamber-dependent values for modern microionization chambers in the new solid water Leksell dosimetry phantom. This work illustrates a calibration method using commercially available equipment, instruments, and an established dosimetry protocol that may be adopted at any GK center, thus reducing the interinstitutional variation in GK calibration. The calibration was verified by three third-party dosimetry checks. In addition, measurements of the relative output factors are presented and compared to available data and the new manufacturer-provided relative output factors yet to be released. Methods: An absolute dose calibration based on the TG-21 formalism, utilizing recently reported phantom material and chamber-dependent factors, was performed using a microionization chamber in a spherical solid water phantom. The result was compared to other calibration protocols based on TG-51. Independent verification of the machine output was conducted through M.D. Anderson Dosimetry Services (MDADS), using thermoluminescent dosimeters (TLDs) in an anthropomorphic head phantom; the Radiological Physics Center (RPC), using TLDs in the standard Elekta ABS plastic calibration phantom (gray phantom), included with the GK; and through a collaborative international calibration survey by the University of Pittsburgh Medical Center (UPMC) using alanine dosimeters, also in the gray phantom. The alanine dosimeters were read by the National Institute of Standards and Technology. Finally, Gafchromic EBT film was used to measure relative output factors and these factors were compared to values reported in the literature as well as new values announced for release by Elekta. The films were exposed in the solid water phantom using an included film insert accessory. Results: Compared to the TG-21 protocol in the solid water phantom, the modified and unmodified TG-51 calibrations resulted in dose rates which were 1.8% and 1.3% lower, respectively. Ratios of the doses measured by third parties to the dose reported showed excellent agreement. MDADS returned ratios of 1.00 and 0.98 for the two TLDs irradiated. The RPC returned a mean ratio of 0.98 of the dose reported and the UPMC alanine study returned a mean ratio of 1.008. Relative output factors were found to be 0.817{+-}0.009 and 0.897{+-}0.008 for the 4 and 8 mm collimators, respectively, which are in excellent agreement with revised Monte Carlo-derived relative output factors Elekta is expected to recommend with the next version of the GK treatment planning software (GAMMAPLAN version 10). Conclusions: The TG-21 dosimetry protocol, performed in a solid water phantom in conjunction with modern dosimeters and phantom material and chamber-dependent factors, can yield an accurate dose measurement in the unique GK treatment geometry. The technique described here can be easily adopted by institutions worldwide since all equipment and instruments used are commercially available, thus reducing the existing interinstitutional variation in GK calibration techniques. Relative output factor measurements made in this same solid water phantom were used to verify the relative output factors provided by Elekta and agreed excellently with output factors expected to be released in conjunction with GAMMAPLAN version 10.
McDonald, Daniel; Yount, Caroline; Koch, Nicholas; Ashenafi, Michael; Peng, Jean; Vanek, Kenneth [Department of Radiation Oncology, Medical University of South Carolina, 169 Ashley Avenue, Charleston, South Carolina 29425 (United States)
We have previously shown that treatment of Zucker rats and mice with diet-induced obesity with dietary docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids in the form of krill oil reduces peripheral levels of endocannabinoids, ectopic fat formation and hyperglycemia. We reported that such treatment reduces plasma endocannabinoid levels also in overweight and obese human individuals, in whom high triglycerides may correlate with high circulating endocannabinoid levels. In this study, we report the effects of krill powder, which contains proteins (34%) in addition to krill oil (61.8%), on these two parameters. We submitted 11 obese men (average BMI of 32.3 kg/m2, age of 42.6 years and plasma triglycerides of 192.5?�?96.3 mg/dl) to a 24 week dietary supplementation with krill powder (4 g/day per os) and measured anthropometric and metabolic parameters, as well as blood endocannabinoid (anandamide and 2-arachidonoylglycerol) and esterified DHA and EPA levels. Six subjects were included as control subjects and not given any supplements. The treatment produced, after 12 and 24 weeks, a significant increase in DHA and EPA in total plasma, a 59 and 84% decrease in anandamide plasma levels, and a 22.5 and 20.6% decrease in triglyceride levels, respectively. There was also a significant decrease in waist/hip ratio and visceral fat/skeletal muscle mass ratio at 24 weeks, but no change in body weight. These data confirm that dietary krill powder reduces peripheral endocannabinoid overactivity in obese subjects, and might ameliorate some parameters of the metabolic syndrome. PMID:23706001
We have previously shown that treatment of Zucker rats and mice with diet-induced obesity with dietary docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids in the form of krill oil reduces peripheral levels of endocannabinoids, ectopic fat formation and hyperglycemia. We reported that such treatment reduces plasma endocannabinoid levels also in overweight and obese human individuals, in whom high triglycerides may correlate with high circulating endocannabinoid levels. In this study, we report the effects of krill powder, which contains proteins (34%) in addition to krill oil (61.8%), on these two parameters. We submitted 11 obese men (average BMI of 32.3 kg/m�, age of 42.6 years and plasma triglycerides of 192.5?�?96.3 mg/dl) to a 24 week dietary supplementation with krill powder (4 g/day per os) and measured anthropometric and metabolic parameters, as well as blood endocannabinoid (anandamide and 2-arachidonoylglycerol) and esterified DHA and EPA levels. Six subjects were included as control subjects and not given any supplements. The treatment produced, after 12 and 24 weeks, a significant increase in DHA and EPA in total plasma, a 59 and 84% decrease in anandamide plasma levels, and a 22.5 and 20.6% decrease in triglyceride levels, respectively. There was also a significant decrease in waist/hip ratio and visceral fat/skeletal muscle mass ratio at 24 weeks, but no change in body weight. These data confirm that dietary krill powder reduces peripheral endocannabinoid overactivity in obese subjects, and might ameliorate some parameters of the metabolic syndrome. PMID:23706001
Berge, Kjetil; Piscitelli, Fabiana; Hoem, Nils; Silvestri, Cristoforo; Meyer, Ingo; Banni, Sebastiano; Di Marzo, Vincenzo
Higher Insulin, Triglycerides, and Blood Pressure With Greater Trunk Fat in Tanner 1 Chinese
Objective The aims of this study were to investigate the body fat distribution pattern in prepubertal Chinese children and to investigate the relationship between central fat distribution and specific biomarkers of cardiovascular disease. Research Methods and Procedures The study was conducted in an urban Mainland Chinese (Jinan, Shandong) sample of children using a cross-sectional design. Pubertal status was determined by Tanner criteria. Measurements included weight, height, waist circumference, DXA measures of total body fat and trunk fat; fasting serum measures of glucose, insulin, triglyceride, cholesterol, high-density lipoprotein-cholesterol; and systolic and diastolic blood pressure. Multiple regression models were developed with the biomarkers of cardiovascular risk factor as the dependent variables, and adjustments were made for significant covariates, including sex, age, height, weight, waist circumference, total body fat, trunk fat, and interactions. Results A total of 247 healthy prepubertal subjects were studied. After co-varying for age, weight, height, and extremity fat (the sum of arm fat and leg fat), girls had greater trunk fat than boys (p < 0.0001, R2 for model = 0.95). Insulin and triglyceride were positively related to central fat measured by DXA-trunk fat (p < 0.05) but not related to the waist circumference. In the blood pressure model, waist circumference was a significant predictor of both systolic blood pressure and diastolic blood pressure, while DXA-trunk fat was associated with diastolic blood pressure only. Significant interactions between sex and trunk fat, and sex and total fat, were found in relation to diastolic blood pressure. Discussion In prepubertal Chinese children, greater trunk fat was significantly associated with higher insulin and triglyceride in boys and girls and was associated with higher diastolic blood pressure in boys only. PMID:17426336
He, Qing; Zhang, Xiaojing; He, Suyuan; Gong, Luxia; Sun, Yungao; Heshka, Stanley; Deckelbaum, Richard J.; Gallagher, Dympna
To understand the impact of C?=?C double bonds in acyl chains of unsaturated triglycerides on the reaction mechanism and product composition in their initial pyrolysis process, ReaxFF molecular dynamics simulations were carried out using a molecular model, trilinolenin, at temperatures of 2000, 2250, and 2500 K. Analyses indicated that the observed pyrolysis mechanisms of unsaturated triglyceride are nearly identical to the saturated triglyceride, and the pyrolysis products also include alkanes, alkenes, alkadienes, aromatics, oxygenated species, CO?, and H?. The formation of intermediates and products is a sequential process. Three C--O bonds in trilinolenin molecule are usually successive dissociated first, leading to the formation of unsaturated C?H?� radical and straight-chain C??H??O?� (RCOO�) radicals. Following that, the deoxygenated alkenyl chain is produced through decarboxylation of RCOO?�?radicals with consequent release of CO?. The resulting hydrocarbon radicals undergo a variety of disproportionation, isomerization, and hydrogen-transfer reactions, yielding straight and branched-chain hydrocarbons. It was found that the scission of C--O bond and decarboxylation should preferentially occur before the cleavage of the C--C bond ? to the C?=?C bond in the initial decomposition process of unsaturated trilinolenin. In addition, the formation of cyclic hydrocarbons could proceed through intramolecular cyclization mechanisms, including non-radical electrocyclic, biradical cyclization and cyclization of alkenyl radical, which are inconsistent with previously proposed bimolecular Diels-Alder addition mechanisms. More rapid pyrolysis of trilinolenin would occur at higher temperatures without significantly affecting the apparent reaction mechanisms of trilinolenin pyrolysis in the considered temperature range. Aromatic ring structures are observed to be stable after formation and do not decay within the 500 ps simulation period. PMID:24567153
Zhang, Zhiqiang; Yan, Kefeng; Zhang, Jilong
Lipase-catalyzed interesterification was used to prepare structured TG from coconut oil TG by partially replacing some of\\u000a the atherogenic saturated FA with stearic acid, which is known to have a neutral effect on lipid levels in the body. The level\\u000a of stearic acid was increased from 4% in the native coconut oil to 40% in the structured lipids, with most
Reena Rao; Belur R. Lokesh
Room temperature (TR) elastic constants and compressive yield strengths of �30 metallic glasses reveal an average shear limit gammaC=0.0267�0.0020, where tauY=gammaCG is the maximum resolved shear stress at yielding, and G the shear modulus. The gammaC values for individual glasses are correlated with t=TR\\/Tg, and gammaC for a single glass follows the same correlation (vs t=T\\/Tg). A cooperative shear model,
W. L. Johnson; K. Samwer
Elevated temperature biaxial fatigue
NASA Technical Reports Server (NTRS)
A three year experimental program for studying elevated temperature biaxial fatigue of a nickel based alloy Hastelloy-X has been completed. A new high temperature fatigue test facility with unique capabilities has been developed. Effort was directed toward understanding multiaxial fatigue and correlating the experimental data to the existing theories of fatigue failure. The difficult task of predicting fatigue lives for non-proportional loading was used as an ultimate test for various life prediction methods being considered. The primary means of reaching improved undertanding were through several critical non-proportional loading experiments. It was discovered that the cracking mode switched from primarily cracking on the maximum shear planes at room temperature to cracking on the maximum normal strain planes at 649 C.
Jordan, E. H.
The role of aluminum (Al) in Alzheimer disease is highly controversial. However, this element has been detected in neuritic plaques and neurofibrillary tangles in patients with Alzheimer disease. Its presence in neuritic plaques in hippocampus is especially relevant, as this is an area closely related to spatial learning and memory. In this study, the diet of wild-type and Tg2576 mice (animals overexpressing the human amyloid precursor protein) was supplemented with Al lactate (1 mg/g). General neurotoxic Al effects were evaluated using a functional observational battery and a novel object recognition task. Four experimental groups were used: Control-wild, Al-wild, Control-Tg, and Al-Tg mice. The results show a decreased home-cage activity and an increase in piloerection in all Al-exposed animals, and an increased sensorimotor reactivity in Tg2576 mice given Al. Neither Al treatment nor genotype had any noticeable effect on corticosterone levels and Al concentrations in frontal cortex and cerebellum of the mice. Recognition memory was impaired in Tg2576 mice, whereas ?-amyloid plaque depositions were observed in all these animals. However, Al did not alter the recognition memory and ?-amyloid plaque loads of Tg2576 mice. PMID:21642811
Ribes, Diana; Torrente, Margarita; Vicens, Paloma; Colomina, Maria Teresa; G�mez, Mercedes; Domingo, Jos� L
An undercooled liquid is unstable. The driving force of the glass transition at Tg is a change of the undercooled-liquid Gibbs free energy. The classical Gibbs free energy change for a crystal formation is completed including an enthalpy saving. The crystal growth critical nucleus is used as a probe to observe the Laplace pressure change Dp accompanying the enthalpy change -Vm*Dp at Tg where Vm is the molar volume. A stable glass-liquid transition model predicts the specific heat jump of fragile liquids at temperatures smaller than Tg, the Kauzmann temperature TK where the liquid entropy excess with regard to crystal goes to zero, the equilibrium enthalpy between TK and Tg, the maximum nucleation rate at TK of superclusters containing magic atom numbers, and the equilibrium latent heats at Tg and TK. Strong-to-fragile and strong-to-strong liquid transitions at Tg are also described and all their thermodynamic parameters are determined from their specific heat jumps. The existence of fragile liquids quenched in the amorphous state, which do not undergo liquid-liquid transition during heating preceding their crystallization, is predicted. Long ageing times leading to the formation at TK of a stable glass composed of superclusters containing up to 147 atoms, touching and interpenetrating, are evaluated from nucleation rates.
Robert Felix Tournier
Human lactation: maternal transfer of dietary triglycerides labeled with stable isotopes
A stable isotope tracer method was utilized to measure quantitatively the secretion of diet-derived fatty acids (FA) into human milk. A mixture of (/sup 2/H6)tripalmitin, (/sup 2/H18)-triolein, and (/sup 2/H12)trilinolein was administered to three healthy, lactating women 22 to 30 years of age. Milk and blood samples were collected sequentially for 72 hr. The FA composition and concentration of total plasma, lipoprotein, and milk triglycerides were determined by gas-liquid chromatography (GLC) and the isotopic enrichment was determined by gas-liquid chromatography-mass spectrometry (GLC-MS). There were no statistically significant differences in mammary secretion of the individual fats, either by a single individual or between subjects. The mean secretion of fat by one breast was 5.11 +/- 1.26% of the dose (CV = 25%). There was a significant 6.0-hr delay between peak occurrence of the tracer in plasma and its occurrence in milk. The lipids are transported to the mammary gland primarily by the chylomicron and very low density lipoprotein triglycerides.
Hachey, D.L.; Thomas, M.R.; Emken, E.A.; Garza, C.; Brown-Booth, L.; Adlof, R.O.; Klein, P.D.
Efficient dietary fat digestion is essential for newborns who consume more dietary fat per body weight than at any other time of life. In many mammalian newborns, pancreatic lipase related protein 2 (PLRP2) is the predominant duodenal lipase. Pigs may be an exception since PLRP2 expression has been documented in the intestine but not in the pancreas. Because of the differences in tissue-specific expression, we hypothesized that the kinetic properties of porcine PLRP2 would differ from those of other mammals. To characterize its properties, recombinant porcine PLRP2 was expressed in HEK293T cells and purified to homogeneity. Porcine PLRP2 had activity against tributyrin, trioctanoin and triolein. The activity was not inhibited by bile salts and colipase, which is required for the activity of pancreatic triglyceride lipase (PTL), minimally stimulated PLRP2 activity. Similar to PLRP2 from other species, PLRP2 from pigs had activity against galactolipids and phospholipids. Importantly, porcine PLRP2 hydrolyzed a variety of dietary substrates including pasteurized human mother's milk and infant formula and its activity was comparable to that of PTL. In conclusion, porcine PLRP2 has broad substrate specificity and has high triglyceride lipase activity even in the absence of colipase. The data suggest that porcine PLRP2 would be a suitable lipase for inclusion in recombinant preparations for pancreatic enzyme replacement therapy. PMID:23770034
Xiao, Xunjun; Ross, Leah E; Sevilla, Wednesday A; Wang, Yan; Lowe, Mark E
The usefulness of dietary medium-chain triglycerides in body weight control: fact or fancy?
Compared to long-chain triglycerides (LCT), medium-chain triglycerides (MCT) display some specific physico-chemical, and biological characteristics. Thus, MCT are currently used in clinical nutrition as energy-yielding substrates, and have been advocated for three decades as a useful mean for body weight reduction. This review encompasses most aspects of MCT metabolism arguing this slimming hypothesis pro and con. Findings in support of the opinion (lower energy density, control of satiety, rapid intrahepatic delivery and oxidation rates, poor adipose tissue incorporation) may be invalidated by counteracting data (stimulation of insulin secretion and of anabolic-related processes, increased de novo fatty acid synthesis, induced hypertriglyceridemia). The balance between these two opposing influences depends on the composition (energy intake, nature of ingredients, MCT/LCT ratio, octanoate/decanoate ratio) and duration of the regimen. Due to the high energy level (around 50%) of MCT necessary to achieve body weight loss, long-term compliance to such slimming regimens is unlikely in human nutrition. PMID:8732772
Bach, A C; Ingenbleek, Y; Frey, A
The plasma level of apolipoprotein B (apoB) is among the strongest risk factors for coronary artery disease. Microsomal triglyceride transfer protein (MTP) plays a key role in the lipidation of nascent apoB and the secretion of apoB-containing lipoproteins enriched with triglycerides and is thus a promising target for the treatment of hyperlipidemia. Yet, the development of MTP inhibitors to lower plasma lipid concentrations has been hindered by adverse effects on hepatic steatosis. A study recently published in Nature Medicine identifies microRNA-30c (miR-30c) as a potent repressor of MTP that controls plasma apoB-containing lipoprotein levels, in addition to decreasing hepatic lipid synthesis through direct targeting of lysophosphatidylglycerol acyltransferase 1 (LPGAT1). These findings identify miR-30c as a novel therapeutic target that coordinately reduces lipid biosynthesis and lipoprotein secretion to suppress circulating apoB lipoproteins, while sparing the liver from steatosis. PMID:24201112
Vickers, Kasey C.; Moore, Kathryn J.
Objective To investigate the impact of eating frequency on dietary intake, physical activity (PA), metabolic, and adiposity measures in minority youth. Design and Methods This analysis included 185 overweight (?85th BMI percentile) Hispanic and African American youth (8�18 years) with the following cross-sectional measures: height, weight, BMI, dietary intake, body composition, metabolic parameters, PA, visceral adipose tissue (VAT), and subcutaneous adipose tissue. Each eating occasion (EO) was defined as ?50 calories and ?15 minutes from any previous EO. Participants were dichotomized based on EOs per 24-h into meal skippers <3 EO (MS; n=27) or normal/frequent eaters ?3 EO (NFE; n=158). ANCOVAs were used to assess dietary intakes, metabolic outcomes, adiposity, and PA between eating frequency groups. Results MS compared to NFE consumed 24% fewer calories per 24-h (p?0.01), 21% more calories per EO (p?0.01), ate 40% less often (p?0.01), had 18% higher triglycerides (p=0.03), and 26% more VAT (p=0.03), with no differences in PA. Conclusions Although meal skipping was associated with decreased energy intake, it was linked to increased calories per EO and higher triglycerides and VAT, which are strong indicators of deleterious metabolic profiles. These findings elucidate that meal skipping may be associated with increased VAT and related metabolic diseases in high-risk minority youth. PMID:23613461
House, Benjamin T.; Cook, Lauren T.; Gyllenhammer, Lauren E.; Schraw, Jeremy M.; Goran, Michael I.; Spruijt-Metz, Donna; Weigensberg, Marc J.; Davis, Jaimie N.
Significant resources have been invested in sequencing studies to investigate the role of rare variants in complex disease etiology. However, the diagnostic interpretation of individual rare variants remains a major challenge, and may require accurate variant functional classification and the collection of large numbers of variant carriers. Utilizing sequence data from 458 individuals with hypertriglyceridemia and 333 controls with normal plasma triglyceride levels, we investigated these issues using GCKR, encoding glucokinase regulatory protein. Eighteen rare non-synonymous GCKR variants identified in these 791 individuals were comprehensively characterized by a range of biochemical and cell biological assays, including a novel high-throughput-screening-based approach capable of measuring all variant proteins simultaneously. Functionally deleterious variants were collectively associated with hypertriglyceridemia, but a range of in silico prediction algorithms showed little consistency between algorithms and poor agreement with functional data. We extended our study by obtaining sequence data on family members; however, functional variants did not co-segregate with triglyceride levels. Therefore, despite evidence for their collective functional and clinical relevance, our results emphasize the low predictive value of rare GCKR variants in individuals and the complex heritability of lipid traits. PMID:24879641
Rees, Matthew G; Raimondo, Anne; Wang, Jian; Ban, Matthew R; Davis, Mindy I; Barrett, Amy; Ranft, Jessica; Jagdhuhn, David; Waterstradt, Rica; Baltrusch, Simone; Simeonov, Anton; Collins, Francis S; Hegele, Robert A; Gloyn, Anna L
Alterations of hippocampal glucose metabolism by even versus uneven medium chain triglycerides.
Medium chain triglycerides (MCTs) are used to treat neurologic disorders with metabolic impairments, including childhood epilepsy and early Alzheimer's disease. However, the metabolic effects of MCTs in the brain are still unclear. Here, we studied the effects of feeding even and uneven MCTs on brain glucose metabolism in the mouse. Adult mice were fed 35% (calories) of trioctanoin or triheptanoin (the triglycerides of octanoate or heptanoate, respectively) or a matching control diet for 3 weeks. Enzymatic assays and targeted metabolomics by liquid chromatography tandem mass spectrometry were used to quantify metabolites in extracts from the hippocampal formations (HFs). Both oils increased the levels of ?-hydroxybutyrate, but no other significant metabolic alterations were observed after triheptanoin feeding. The levels of glucose 6-phosphate and fructose 6-phosphate were increased in the HF of mice fed trioctanoin, whereas levels of metabolites further downstream in the glycolytic pathway and the pentose phosphate pathway were reduced. This indicates that trioctanoin reduces glucose utilization because of a decrease in phosphofructokinase activity. Trioctanoin and triheptanoin showed similar anticonvulsant effects in the 6?Hz seizure model, but it remains unknown to what extent the anticonvulsant mechanism(s) are shared. In conclusion, triheptanoin unlike trioctanoin appears to not alter glucose metabolism in the healthy brain. PMID:24169853
McDonald, Tanya S; Tan, Kah Ni; Hodson, Mark P; Borges, Karin
The microsomal triglyceride transfer protein (MTP) complexed to protein disulphide isomerase (PDI) is obligatory for the assembly of chylomicrons and very-low-density lipoproteins. The determination of the atomic structure of the MTP-PDI heterodimer has important implications for the treatment of those forms of hyperlipidaemia associated with the overproduction of very-low-density lipoproteins, which predispose to premature coronary heart disease. To perform structural studies of the human MTP-PDI complex it was necessary to produce milligram quantities of pure protein. We chose the baculovirus expression system for this purpose. Insects cells were co-infected with recombinant viruses encoding FLAG-tagged MTP and His-tagged PDI; the resulting heterodimer was purified by affinity chromatography. From 5 litres of insect cells, 4-6 mg of more than 95% pure recombinant protein was obtained. CD and attenuated total reflection Fourier-transform infrared spectroscopy indicate that the purified protein has around 34% alpha-helical and 33% beta-structure content. The recombinant protein had a comparable triglyceride transfer activity to that of bovine MTP-PDI. The production of polyclonal antibodies raised against the MTP and PDI subunits of the purified protein is described. The present study demonstrates the feasibility of expressing two proteins at high levels in insect cells and describes a transferable methodology for the purification of the resulting protein complex. PMID:10036224
Ritchie, P J; Decout, A; Amey, J; Mann, C J; Read, J; Rosseneu, M; Scott, J; Shoulders, C C
TG13 indications and techniques for gallbladder drainage in acute cholecystitis (with videos).
Percutaneous transhepatic gallbladder drainage (PTGBD) is considered a safe alternative to early cholecystectomy, especially in surgically high-risk patients with acute cholecystitis. Although randomized prospective controlled trials are lacking, data from most retrospective studies demonstrate that PTGBD is the most common gallbladder drainage method. There are several alternatives to PTGBD. Percutaneous transhepatic gallbladder aspiration is a simple alternative drainage method with fewer complications; however, its clinical usefulness has been shown only by case-series studies. Endoscopic naso-gallbladder drainage and gallbladder stenting via a transpapillary endoscopic approach are also alternative methods in acute cholecystitis, but both of them have technical difficulties resulting in lower success rates than that of PTGBD. Recently, endoscopic ultrasonography-guided transmural gallbladder drainage has been reported as a special technique for gallbladder drainage. However, it is not yet an established technique. Therefore, it should be performed in high-volume institutes by skilled endoscopists. Further prospective evaluations of the feasibility, safety, and efficacy of these various approaches are needed. This article describes indications and techniques of drainage for acute cholecystitis.Free full-text articles and a mobile application of TG13 are available via http://www.jshbps.jp/en/guideline/tg13.html. PMID:23307009
Tsuyuguchi, Toshio; Itoi, Takao; Takada, Tadahiro; Strasberg, Steven M; Pitt, Henry A; Kim, Myung-Hwan; Supe, Avinash N; Mayumi, Toshihiko; Yoshida, Masahiro; Miura, Fumihiko; Gomi, Harumi; Kimura, Yasutoshi; Higuchi, Ryota; Okamoto, Kohji; Yamashita, Yuichi; Gabata, Toshifumi; Hata, Jiro; Kusachi, Shinya
A mouse model of amyloid pathology was used to first examine using a cross-sectional designchanges in retrosplenial cortex activity in transgenic mice aged 5, 11, 17, and 23 months. Attention focused on: 1) overt amyloid labeled with ?-amyloid(1-42) and Congo Red staining, 2) metabolic function assessed by the enzyme, cytochrome oxidase, and 3) neuronal activity as assessed indirectly by the immediate-early gene, c-Fos. Changes in cytochrome oxidase and c-Fos activity were observed in the retrosplenial cortex in Tg2576 mice as early as 5 months of age, long before evidence of plaque formation. Subsequent analyses concentrating on this early dysfunction revealed at 5-months pervasive, amyloid precursor protein (APP)-derived peptide accumulation in the retrosplenial cortex and selective afferents (anterior thalamus, hippocampus), which was associated with the observed c-Fos hyporeactivity. These findings indicate that retrosplenial cortex dysfunction occurs during early stages of amyloid production in Tg2576 mice and may contribute to cognitive dysfunction. PMID:21093545
Poirier, Guillaume L.; Amin, Eman; Good, Mark A.; Aggleton, John P.
Positron Emission Tomography Imaging of Fibrillar Parenchymal and Vascular Amyloid-? in TgCRND8 Mice
Few quantitative diagnostic and monitoring, tools are available to clinicians treating patients with Alzheimer�s disease. Further, many of the promising quantitative imaging tools under development lack clear specificity toward different types of Amyloid-? (A?) pathology such as vascular or oligomeric species. Antibodies offer an opportunity to image specific types of A? pathology because of their excellent specificity. In this study, we developed a method to translate a panel of anti-A? antibodies, which show excellent histological performance, into live animal imaging contrast agents. In the TgCRND8 mouse model of Alzheimer�s disease, we tested two antibodies, M64 and M116, that target parenchyma aggregated A? plaques and one antibody, M31, that targets vascular A?. All three antibodies were administered intravenously after labeling with both poly(ethylene glycol) to enhance circulation and 64Cu to allow detection via positron emission tomography (PET) imaging. We were clearly able to differentiate TgCRND8 mice from wild type controls by PET imaging using either M116, the anti-A? antibody targeting parenchymal A? or M31, the antivascular A? antibody. To confirm the validity of the noninvasive imaging of specific A? pathology, brains were examined after imaging and showed clear evidence of binding to A? plaques. PMID:23509918
Gender-Specific Neuroimmunoendocrine Response to Treadmill Exercise in 3xTg-AD Mice
The 3xTg-AD mouse develops a progressive Alzheimer's disease- (AD-) like brain pathology that causes cognitive- and neuropsychiatric-like symptoms of dementia. Since its neuroimmunoendocrine axis is likewise impaired, this mouse is also useful for modelling complex age-related neurodegeneration. This study analyzed behavioral, physiological, neurochemical, pathological and immunoendocrine alterations in male and female 3xTg-AD mice and assayed the effects of a short therapy of forced physical exercise at the moderate pathology stage of 6 months of age. Gender effects were observed in most AD-related pathology and dysfunctions. Five weeks of treadmill training produced beneficial effects, such as the reduction of brain oxidative stress and GABA-A receptor dysfunction in males and improvement of sensorimotor function in females. In both sexes, exercise decreased the brain amyloid ? 42/40 ratio levels. The results highlight the importance of analyzing experimental therapies in both mouse model genders in order to improve our understanding of the disease and develop more appropriate therapies. PMID:20981262
Gimenez-Llort, Lydia; Garcia, Yoelvis; Buccieri, Karla; Revilla, Susana; Sunol, Cristina; Cristofol, Rosa; Sanfeliu, Coral
Nitazoxanide suppresses IL-6 production in LPS-stimulated mouse macrophages and TG-injected mice.
Suppression of interleukin (IL)-6 production has beneficial effects against various inflammatory diseases. Through a rapid screening system, we found that nitazoxanide, or 2-acetyloxy-N-(5-nitro-2-thiazolyl) benzamide, which is a well-known antiparasitic agent, suppressed lipopolysaccharide (LPS)-induced production of IL-6 from RAW 264.7 cells and mouse peritoneal macrophages, with 50% inhibitory concentrations (IC(50)s) of 1.54 mM and 0.17 mM, respectively. Nitazoxanide also inhibited the LPS-induced expression of IL-6 mRNA in RAW 264.7 cells. To investigate the effects of nitazoxanide in vivo, we orally administered nitazoxanide at a dose of 100mg/kg to mice 2h before a 1-mL intraperitoneal injection of 4% thioglycollate (TG). Six hours after TG injection, plasma IL-6 levels were markedly lower (by 90%) than the levels in vehicle-treated mice. These data suggest that nitazoxanide could be a promising lead compound for agents against various diseases associated with overproduction of IL-6. PMID:22430099
Hong, Seong Keun; Kim, Hee Joo; Song, Chang Seon; Choi, In Soo; Lee, Joong Bok; Park, Seung Yong
To confirm the hypotriglyceridemic effect of aluminum (Al), male weanling and adult Wistar rats were fed sucrose diets with the addition of aluminum hydroxide (Al(OH)3) or aluminum potassium sulfate (AlK(SO4)2) for 67 days. As in the foregoing report (C. Sugawara, N. Sugawara, H. Kiyosawa, and H. Miyake, Fundam. Appl. Toxicol. 10, 607-615), no Al-induced anemia or hypophosphatemia was observed and serum Al did not exceed 20 ng/ml. Serum triglyceride (TG) was decreased by aluminum. Serum TG was significantly correlated with the serum nonesterified fatty acid (NEFA) concentration in both the Young groups (R = 0.757, n = 22, p less than 0.01) and the Adult groups (R = 0.727, n = 19, p less than 0.01). Neither serum cholesterol nor phospholipids was affected by Al ingestion. Aluminum caused a decrease in hepatic glycogen in all groups, but the decrease was significant only in Adult groups. Glycerol tri[9,10(n)-3H]oleate was administered by gastric tube into rats fed for 81 days with experimental diets. In all the Al-treated groups serum 3H was significantly greater than in control groups at 3 hr after intubation. At 24 hr after intubation, serum 3H did not differ between Control and Al-treated groups. Total 3H at 24 hr found in serum, liver, and epididymal adipose tissue was not changed significantly by Al feeding. These effects were observed without measurable increase of Al in the serum.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3396789
Sugawara, C; Sugawara, N; Kiyosawa, H; Miyake, H
MBX-102/JNJ-39659100 (MBX-102) is a selective, partial PPAR-? agonist that lowers glucose in the absence of some of the side effects, such as weight gain and edema, that are observed with the TZDs. Interestingly MBX-102 also displays pronounced triglyceride lowering in preclinical rodent models and in humans. Although in vitro reporter gene studies indicated that MBX-102 acid is a highly selective PPAR-? agonist that lacks PPAR-? activity, we sought to determine if PPAR-? activation in vivo could possibly contribute to the triglyceride lowering abilities of MBX-102. In vivo studies using ZDF and ZF rats demonstrated that MBX-102 lowered plasma triglycerides. However in ZF rats, MBX-102 had no effect on liver weight or on hepatic expression levels of PPAR-? target genes. Further in vitro studies in primary human hepatocytes supported these findings. Finally, the ability of MBX-102 to lower triglycerides was maintained in PPAR-? knockout mice, unambiguously establishing that the triglyceride lowering effect of MBX-102 is PPAR-? independent. The in vivo lipid lowering abilities of MBX-102 are therefore mediated by an alternate mechanism which is yet to be determined. PMID:19404482
Chandalia, Apurva; Clarke, Holly J.; Clemens, L. Edward; Pandey, Bindu; Vicena, Vic; Lee, Paul; Lavan, Brian E.; Gregoire, Francine M.
Elevated temperature biaxial fatigue
NASA Technical Reports Server (NTRS)
A 3 year experimental program for studying elevated temperature biaxial fatigue of a nickel based alloy Hastelloy-X has been completed. A new high temperature fatigue test facility with unique capabilities has been developed. Effort was directed toward understanding multiaxial fatigue and correlating the experimental data to the existing theories of fatigue failure. The difficult task of predicting fatigue lives for nonproportional loading was used as an ultimate test for various life prediction methods being considered. The primary means of reaching improved understanding were through several critical nonproportional loading experiments. The direction of cracking observed on failed specimens was also recorded and used to guide the development of the theory. Cyclic deformation responses were permanently recorded digitally during each test. It was discovered that the cracking mode switched from primarily cracking on the maximum shear planes at room temperature to cracking on the maximum normal strain planes at 649 C. In contrast to some other metals, loading path in nonproportional loading had little effect on fatigue lives. Strain rate had a small effect on fatigue lives at 649 C. Of the various correlating parameters the modified plastic work and octahedral shear stress were the most successful.
Jordan, E. H.
There has been considerable interest in the use of genetically modified mice for detecting potential environmental carcinogens. For this reason, the National Toxicology Program has been evaluating Tg.AC hemizygous and p53 haploinsufficient mice as models to detect potential carcinogens. It was reasoned that these mouse models might also prove more effective than standard rodent models in evaluating the numerous disinfection byproducts that are found in low concentrations in drinking water. Dichloroacetic acid (DCA) is one of the most frequently found disinfection byproducts and DCA has been consistently shown to cause hepatocellular tumors in rats and mice in standard rodent studies. Tg.AC hemizygous and p53 haploinsufficient mice were exposed in the drinking water to DCA for up to 41 weeks. In a second study Tg.AC mice were subjected to dermal DCA exposure for up to 39 weeks. Increased incidences and severity of cytoplasmic vacuolization of hepatocytes were seen in the p53 mice, but there was no evidence of carcinogenic activity at exposures of up to 2000 mg/l in the drinking water. Increased incidences and severity of cytoplasmic vacuolization of hepatocytes were seen in the drinking water study with Tg.AC mice and a modest non-dose-related increase in pulmonary adenomas was observed in males exposed to 1000 mg/l in the drinking water. Dermal exposure up to 500 mg/kg for 39 weeks resulted in increased dermal papillomas at the site of application in Tg.AC mice. No significant increase in papillomas under the same study conditions was seen in the 26-week study. For DCA under these study conditions, the p53 and Tg.AC mice appear less sensitive to hepatocarcinogenesis than standard rodent models. These results suggest caution for the use of Tg.AC and p53 mice to screen unknown chemicals in drinking water for potential carcinogenicity. PMID:18974089
Kissling, Grace E.; Malarkey, David E.; Vallant, Molly K.; Johnson, Jerry D.; Hejtmancik, Milton R.; Herbert, Ronald A.; Boorman, Gary A.
38. Second Floor Plan, North Elevation, South Elevation and Details. ...
38. Second Floor Plan, North Elevation, South Elevation and Details. Addition to Bacteriology Laboratory at Letterman General Hospital, San Francisco, Cal. January 1916. BUILDING 1006. - Presidio of San Francisco, Letterman General Hospital, Building No. 27, Letterman Hospital Complex, Edie Road, San Francisco, San Francisco County, CA
34. Coal Fuel Elevator (diagonal in foreground), Fuel Elevator (left), ...
34. Coal Fuel Elevator (diagonal in foreground), Fuel Elevator (left), Fuel Storage Bins (center), and Power Plant (far center), and Retail Coal Storage Bins (right) Photograph taken by George Harven - Huber Coal Breaker, 101 South Main Street, Ashley, Luzerne County, PA
35. Coal Fuel Elevator (diagonal in center), Fuel Elevator (left), ...
35. Coal Fuel Elevator (diagonal in center), Fuel Elevator (left), Fuel Storage Bins (center), and Power Plant (far center), and Retail Coal Storage Bins (right) Photograph taken by George Harven - Huber Coal Breaker, 101 South Main Street, Ashley, Luzerne County, PA
U.S. Army RDECOM-ARDEC's results of the TG-53 experiment and field test
NASA Astrophysics Data System (ADS)
Herein is described the U.S. Army RDECOM-ARDEC's purpose and series of activities conducted at the 2008 NATO SET-093 TG-53 experiment and field test. The overall purpose of the field test as stated by SET-093 panel was to provide a baseline test capable of providing relevant scenarios and data regarding a variety of impulsive generated acoustic events. As organized, the field experiment also allowed the room o study sensor interoperability across multiple platforms and multi-national users via the spider communication framework/reporting structure. This multinational network maintained by the host ETBS with a standardized messaging format with specific goals for each participating organization. ARDEC's role and purpose for the test was to provide situational awareness via the Spider and associated messaging format to the ETBS command center while continuing to gather unique acoustic data from various vantage points. ARDEC had several deliverables for the TG-53 field experiment derived from the mission and spirit of the field test. The most relevant deliverable was to demonstrate sensor interoperability via the Spider network and provide situational awareness by describing the said mortar/artillery events. The second purpose revolved around a relevant environment algorithm validation of the muzzle blast discrimination for future UGS transition in particular the UTAMS II. The algorithm validation information remained internal to the specific data acquisition system and not broadcasted out on the Spider network. The TG-53 field experiments provided the added opportunity to further test and refine the algorithm based on the discrete wavelet transform (DWT) and multiresolution analysis. These techniques are used to classify and reliably discriminates between launch and impact artillery and/or mortar events via acoustic signals produced during detonation. Distinct characteristics are found within the acoustic signatures since impact events emphasize concussive and shrapnel effects, while launch events are similar to explosions, designed to expel and propel an artillery round from a gun. The ensuing signatures are readily characterized by variations in the corresponding peak pressure and rise time of the waveform, differences in the ratio of positive pressure amplitude to the negative amplitude, variations in the prominent frequencies associated with the blast events and variations in the overall duration of the resulting waveform. Unique attributes can also be identified that depend upon the properties of the gun tube, projectile speed at the muzzle, and the explosive/concussive properties associated with the events. The event allows the examination of particular extreme battlefield acoustic challenges not normally documented or readily studied. The final portion will focus on the unique acoustic signatures data collected and how it allowed very relevant situations to be tested in a variety of scenarios.
Desai, Sachi V.; Morcos, Amir
Kinetic studies of plasma free fatty acid and triglyceride metabolism in man
Plasma transport of free fatty acids (FFA) and triglyceride fatty acids (TGFA) was studied in seven subjects with normal lipid metabolism, one case of total lipodystrophy, and one case of familial hyperlipemia (Type V). Studies were carried out after intravenous injection of radioactive FFA, of lipoproteins previously labeled in vitro in the triglyceride moiety, or both. Computer techniques were used to evaluate a series of multicompartmental models, and a general model is proposed that yields optimum fitting of experimental data for both FFA and TGFA. The results show that as much as 20-30% of FFA leaving the plasma compartment in normal subjects is transported to an exchanging extravascular pool and quickly reenters the plasma pool as FFA. The rate of irreversible delivery of FFA from plasma to tissues averaged 358 ?Eq/min in normals. The lipodystrophy patient, despite the virtual absence of adipose tissue (confirmed at autopsy), had a plasma FFA concentration and a total FFA transport, both more than twice normal. Total TGFA transport ranged from 25 to 81 ?Eq/min in four normal controls. The rate constant for TGFA turnover in the patient with Type V hyperlipemia was so small that total transport could not be quantified from the data available; the TGFA half-life was over 500 min. In two normal subjects given injections of autologous lipoproteins labeled in vitro with triolein-14C and simultaneously given oleic acid-3H, it was shown that the time course for the disappearance of the TGFA in the in vitro labeled samples conformed almost exactly to that of the physiologically labeled lipoprotein TGFA synthesized from injected FFA (as evidenced by the simultaneous fitting of both sets of data using the same multicompartmental model and the same rate constants). Radioactivity appeared in the plasma FFA fraction at a significant rate after injection of plasma labeled in vitro with TGFA. It was estimated that as much as 50% of the total TGFA transported underwent rapid and rather direct conversion to FFA in the two normal subjects studied this way. The kinetic data suggest that such conversion of TGFA to FFA was not preceded by any extensive dilution, such as would result from complete mixing with tissue triglyceride stores. Images PMID:5796365
Eaton, R. Philip; Berman, Mones; Steinberg, Daniel
The lower jaw fat of the Amazon River dolphinInia geoffrensis contains 52.8% wax ester, 44.7% triglyceride and 2.5% diacyl glyceryl ether, while its dorsal blubber fat is >98% triglyceride.\\u000a Examination of the intact lipids, the derived fatty acids and the derived fatty alcohols by gas chromatography reveals that\\u000a the blubber triglycerides show characteristics of freshwater fish fats, but the jaw
R. G. Ackman; C. A. Eaton; Carter Litchfield
Physical exercise has become a potentially beneficial therapy for reducing neurodegeneration symptoms in Alzheimer's disease. Previous studies have shown that cognitive deterioration, anxiety and the startle response observed in 7-month-old 3xTg-AD mice were ameliorated after 6 months of free access to a running wheel. Also, alterations in synaptic response to paired-pulse stimulation were improved. The present study further investigated some molecular mechanisms underlying the beneficial effects of 6 months of voluntary exercise on synaptic plasticity in 7-month-old 3xTg-AD mice. Changes in binding parameters of [(3)H]-flunitrazepam to GABAA receptor and of [(3)H]-MK-801 to NMDA receptor in cerebral cortex of 3xTgAD mice were restored by voluntary exercise. In addition, reduced expression levels of NMDA receptor NR2B subunit were reestablished. The synaptic proteins synaptophysin and PSD-95 and the neuroprotective proteins GDNF and SIRT1 were downregulated in 3xTgAD mice and were recovered by exercise treatment. Overall, in this paper we highlight the fact that different interrelated mechanisms are involved in the beneficial effects of exercise on synaptic plasticity alterations in the 3xTg-AD mouse model. PMID:24486380
Revilla, Susana; Su�ol, Cristina; Garc�a-Mesa, Yoelvis; Gim�nez-Llort, Lydia; Sanfeliu, Coral; Crist�fol, Rosa
The growth of thyroid cells is tightly regulated by thyroid stimulating hormone (TSH) through the cyclic adenosine 3', 5'-monophosphate (cAMP) signaling pathway by potentiating the mitogenic activity of insulin and insulin-like growth factors (IGFs). However, we recently reported that thyroglobulin (Tg), a major product of the thyroid, also induces the growth of thyroid cells cultured in 0.2% serum in the absence of TSH and insulin. In this report, we demonstrate that Tg induced phosphorylation of molecules of the c-Raf/MEK/ERK pathway of the mitogen-activated protein kinase (MAPK). The MEK-1/2 inhibitor PD98059 suppressed Tg-induced phosphorylation of ERK1/2 and reduced bromodeoxyuridine (BrdU) incorporation. Tg also induced expression of the essential transcriptional factors c-Myc, c-Fos and c-Jun and phosphorylation of the retinoblastoma (Rb) protein. The present results, together with the previous report, suggest that Tg utilizes multiple signaling cascades to induce thyroid cell growth independent of TSH/cAMP stimulation. PMID:22445893
Sue, Mariko; Hayashi, Moyuru; Kawashima, Akira; Akama, Takeshi; Tanigawa, Kazunari; Yoshihara, Aya; Hara, Takeshi; Ishido, Yuko; Ito, Tetsuhide; Takahashi, Shin-Ichiro; Ishii, Norihisa; Suzuki, Koichi
Purpose: Commercial CT-based image-guided radiotherapy (IGRT) systems allow widespread management of geometric variations in patient setup and internal organ motion. This document provides consensus recommendations for quality assurance protocols that ensure patient safety and patient treatment fidelity for such systems. Methods: The AAPM TG-179 reviews clinical implementation and quality assurance aspects for commercially available CT-based IGRT, each with their unique capabilities and underlying physics. The systems described are kilovolt and megavolt cone-beam CT, fan-beam MVCT, and CT-on-rails. A summary of the literature describing current clinical usage is also provided. Results: This report proposes a generic quality assurance program for CT-based IGRT systems in an effort to provide a vendor-independent program for clinical users. Published data from long-term, repeated quality control tests form the basis of the proposed test frequencies and tolerances.Conclusion: A program for quality control of CT-based image-guidance systems has been produced, with focus on geometry, image quality, image dose, system operation, and safety. Agreement and clarification with respect to reports from the AAPM TG-101, TG-104, TG-142, and TG-148 has been addressed.
Bissonnette, Jean-Pierre; Balter, Peter A.; Dong Lei; Langen, Katja M.; Lovelock, D. Michael; Miften, Moyed; Moseley, Douglas J.; Pouliot, Jean; Sonke, Jan-Jakob; Yoo, Sua [Task Group 179, Department of Radiation Physics, Princess Margaret Hospital, University of Toronto, Toronto, Ontario, M5G 2M9 (Canada); Department of Radiation Physics, University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030 (United States); Department of Radiation Oncology, M. D. Anderson Cancer Center Orlando, Orlando, Florida 32806 (United States); Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, New York 10021 (United States); Department of Radiation Oncology, University of Colorado School of Medicine, Aurora, Colorado 80045 (United States); Department of Radiation Physics, Princess Margaret Hospital, University of Toronto, Toronto, Ontario, M5G 2M9 (Canada); Department of Radiation Oncology, UCSF Comprehensive Cancer Center, 1600 Divisadero St., Suite H 1031, San Francisco, California 94143-1708 (United States); Department of Radiation Oncology, Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX Amsterdam (Netherlands); Department of Radiation Oncology, Duke University, Durham, North Carolina 27710 (United States)