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NACE-ESI-MS combined with on-line concentration for high-sensitivity analysis of quinolizidine alkaloids.
A rapid, reproducible and high-sensitivity NACE-ESI-MS method was developed for the analysis of sophoridine, matrine, sophocarpine and oxymatrine in the roots of Sophora flavescens Ait. and S. tonkinensis Gagnep. Field-amplified sample stacking with electromigration-injection (FASS-EMI) was first used in NACE for the on-line concentration of the alkaloids. The conditions of NACE separation, FASS-EMI stacking and MS detection were systematically optimized. The optimum NACE buffer was an electrolyte containing 50 mM ammonium acetate, 0.5% acetic acid and 30% ACN in methanol. The sensitivity was improved by about 100-fold by the FASS-EMI technique, which was further improved by more than 1000-fold with MS detection. The RSDs (n = 6) of the relative migration time and relative peak area of each peak were less than 0.3 and 2.4% for intra-day and less than 5.1 and 6.0% for inter-day, respectively. The LODs (S/N = 3) of analytes were determined to be 0.0210-0.0446 ng/mL. A bioanalytical method based on this NACE-ESI-MS method may be developed for the analysis of the alkaloids in biological sample matrices (plasma, urine, etc.) after effective ion removal. | {
"pile_set_name": "PubMed Abstracts"
} |
Impact of titanium dioxide nanoparticles on the bacterial communities of biological activated carbon filter intended for drinking water treatment.
Titanium dioxide nanoparticles (TiO2 NPs) are inevitably present in the aquatic environment owing to their increasing production and use. However, knowledge of the potential effects of TiO2 NPs on the treatment of drinking water is scarce. Herein, the effects of two types of anatase TiO2 NPs (TP1, 25 nm; TP2, 100 nm) on the bacterial community in a biological activated carbon (BAC) filter were investigated via quantitative polymerase chain reaction (Q-PCR) analysis, ATP quantification, and 454 pyrosequencing analysis. Both TP1 and TP2 significantly inhibited the bacterial ATP level (p < 0.01) and induced a decrease in the abundance of bacterial 16S rDNA gene copies at doses of 0.1 and 100 mg L(-1). Simultaneously, the diversity and evenness of the bacterial communities were considerably reduced. The relative abundances of bacteria annotated to OTUs from Nitrospira class and Betaproteobacteria class decreased upon TiO2 NP treatment, whereas those of Bacilli class and Gammaproteobacteria class increased. TiO2 NP size showed a greater effect on the bacterial composition than did the dose based on Bray-Curtis distances. These findings identified negative effects of TiO2 NPs on the bacterial community in the BAC filter. Given the fact that BAC filters are used widely in drinking water treatment plants, these results suggested a potential threat by TiO2 NP to drinking water treatment system. | {
"pile_set_name": "PubMed Abstracts"
} |
The Low-Grade Lymphomas.
The lymphomas comprise a spectrum of diseases with vast variation in histologic appearance, presentation and natural history, and response to therapy. At one end of the spectrum are the low-grade lymphomas (LGLs), indolent malignancies characterized by paradox. Despite an exceedingly low growth fraction, the LGLs are usually extensive at presentation, and yet they rarely involve privileged sites, such as cortical bone or central nervous system, and rarely destroy adjacent tissue. They are exquisitely responsive to many different therapeutic interventions, but responses to most agents are transient and similar. Finally, although survival of most LGL patients is measured in years, the course of the disease is punctuated by both transient and long-term responses to treatment, and also by spontaneous regression and transformation to more aggressive lymphomas in the absence of therapy, rendering the evaluation of the true impact of treatment quite difficult. The focus of this review is on the management of the LGLs, in particular the role of radiotherapy. | {
"pile_set_name": "PubMed Abstracts"
} |
Tuning of Enthalpic/Entropic Parameters of a Protein Redox Center through Manipulation of the Electronic Partition Function.
Manipulation of the partition function (Q) of the redox center CuA from cytochrome c oxidase is attained by tuning the accessibility of a low lying alternative electronic ground state and by perturbation of the electrostatic potential through point mutations, loop engineering and pH variation. We report clear correlations of the entropic and enthalpic contributions to redox potentials with Q and with the identity and hydrophobicity of the weak axial ligand, respectively. | {
"pile_set_name": "PubMed Abstracts"
} |
[New oncolytic agents and immunomodulators and their application].
After a long period without change, colorectal oncology has in recent years entered the frontline of progress in cancer treatment and research. Improved diagnostic techniques have brought forward the diagnosis of metastatic disease, enabling potential curative surgery in the case of liver metastases. Due to both the earlier start of systemic treatment and the increase in number of active drugs, survival of patients with metastatic disease has increased to a median of approximately 18 months. Two important cytotoxic drugs, oxaliplatin and irinotecan, have contributed to this progress. Recently, it was demonstrated that addition ofa monoclonal antibody against vascular endothelial growth factor, bevacizumab, led to an increase in survival comparable to the effects of both cytotoxic agents. Increase in survival, as a hallmark for drug efficacy, is an endpoint that patients and the medical community seem to agree on. The financial consequences of these combinations for the hospital budget are considerable, but their share in the total drug economy is still small. Oxaliplatin has also emerged as a useful drug in the adjuvant setting, after surgery for primary colon cancer. | {
"pile_set_name": "PubMed Abstracts"
} |
Towards zero waste: a case study in the City of Tshwane.
Tshwane is presently landfilling all of its municipal solid waste (MSW) with no pre-processing or minimization efforts. This is a result of the available capacity of its existing landfills, thought to be able to satisfy the city's needs for, at most, the next 10 years. It is possible that the authorities will not wake up to the problem before it is too late. This study addresses these challenges. This study first identified and evaluated technologies available in developed countries for processing the various components of the MSW stream, appropriate to local conditions, as an alternative to landfilling, to ensure that these components will be either reused, recycled or rendered harmless to the environment before disposal. Then most appropriate technologies for Tshwane were selected and assembled into an optimal configuration to achieve a zero waste situation in Tshwane within a decade or two. This represents a significant change in MSW management in Tshwane, from total landfill to zero waste to landfill. Although the study focused on Tshwane, it can be argued that the findings can be implemented in any other South African municipality, and even implemented in other emerging countries. | {
"pile_set_name": "PubMed Abstracts"
} |
Regulated ARE-mediated mRNA decay in Saccharomyces cerevisiae.
The stability of several oncogene, cytokine, and growth factor transcripts is tightly regulated by signaling pathways through an ARE (AU-rich element) present in their 3'-UTRs. We have identified a yeast transcript, TIF51A, whose stability is regulated through its AU-rich 3'-UTR. We demonstrate that the mammalian TNFalpha and c-fos AREs regulate turnover of a reporter yeast transcript in a similar manner. AREs stabilize the transcript in glucose media and function as destabilizing elements in media lacking glucose or when the Hog1p/p38 MAP kinase pathway is inhibited. Significantly, both yeast and mammalian AREs promote deadenylation-dependent decapping in the yeast system. Furthermore, the yeast ELAV homolog, Pub1p, regulates the stability mediated by the TNFalpha ARE. These results demonstrate that yeast possess a regulatable mechanism for ARE-mediated decay and suggest conservation of this turnover process from yeast to humans. | {
"pile_set_name": "PubMed Abstracts"
} |
Cost-effective procedure for Streptococcus pyogenes immobilized DNA preparation and miniPFGE subtyping.
Group A streptococci (GAS) is responsible of several human diseases ranging from mild infection to severe invasive toxin-mediated disease and post-infectious sequelae. Accordingly, a GAS surveillance program based on molecular techniques is advisable for its epidemiological control. Pulsed-field gel electrophoresis (PFGE) is the gold standard for GAS molecular subtyping, but a major disadvantage is the length of the procedure, which takes 1-3 days of work, minimum. The aim of this study was to develop a rapid and cost-effective procedure for PFGE subtyping of GAS isolates. Different incubation times of GAS, immobilized in agarose miniplugs, in solutions containing lysozyme and/or mutanolysine followed by solutions with urea instead of proteinase K, were assayed. DNA was restricted with SmaI and the fingerprints were obtained in clamped homogeneous electric field (CHEF) chambers and minichambers. The modified procedure was used to subtype 22 GAS isolates. Intact DNA molecules of GAS immobilized in agarose miniplugs were prepared incubating the cells, in situ, with a solution containing lysozyme for 4 hours, followed by the incubation in a non-enzymatic solution with urea for 2 hours. SmaIDNA macrorestriction fragments were well resolved in 5 hours and 14 minutes by electrophoresis in a CHEF minichamber at 10 V/cm. This procedure for GAS DNA preparation was useful for fingerprinting GAS strains in the format of CHEF Mapper (BioRad). The procedure took 13 hours for GAS strains subtyping. Both sample preparation and electrophoresis in CHEF minichamber represent an economic alternative for performing massive epidemiological studies of this human pathogen. | {
"pile_set_name": "PubMed Abstracts"
} |
Benthodytes marianensis, a new species of abyssal elasipodid sea cucumbers (Elasipodida: Psychropotidae) from the Mariana Trench area.
Benthodytes marianensis sp. nov., is described from the Mariana Trench at the depth of 5567 m. This is the thirteenth species in Benthodytes Théel, 1882. The new species has a broad brim around the body, dark violet skin, 9 pairs of large dorsal papillae with other papillae of equal or smaller size situated elsewhere, forming two zigzag rows, and some minute papillae scattered around the anterior region. Body wall ossicles are rods, crosses with three or four arms and central apophyses, and crosses of an unusual type. Crosses with four arms and central bipartite, tripartite and tetrapartite apophyses and peculiar cross-shaped ossicles with high apophyses ending in two horizontal arms are present in the dorsum. Large rod-shaped ossicles with bipartite apophyses and crosses with three or four arms and rudimentary apophyses are present on the ventrum. B. marianensis is morphologically most similar to B. incerta, but it is distinguished from B. incerta by the number and arrangement of dorsal large papillae, the broad brim and details of ossicle morphology. The phylogenetic analyses based on (16S, COI) and nuclear genes (H3) all confirm the morphological identification. | {
"pile_set_name": "PubMed Abstracts"
} |
Effects of melatonin on cytokine release and healing of colonic anastomoses in an experimental sepsis model.
The present objective was to identify effects of early melatonin application on healing of anastomotic wound and inflammation in an experimental sepsis model. A total of 60 Wistar albino rats were divided into 2 groups. Cecal ligation puncture (CLP) and colonic resection anastomosis were performed on both the control group and the melatonin treatment group. Both groups were divided into 3 subgroups consisting of 10 rats each. One subgroup from each group underwent re-laparotomy at the 16th hour, the next on the 3rd day, and the final subgroup on the 7th day. Presently evaluated were effects of melatonin treatment of early sepsis on interleukin-6 (IL-6), interleukin-10 (IL-10), interferon gamma (INF-γ), and C-reactive protein (CRP) levels, as well as burst pressures (BPs), collagen and hydroxyproline (OHP) content of the anastomotic segments, histopathologic healing, immunohistochemical expressions, CD34, and transforming growth factor beta (TGF-ß). IL-6 and INF-γ levels of the treatment group showed a significant decrease at the 16th hour and an increase on the 3rd and 7th postoperative days. IL-10 levels were significantly higher at the 16th hour and significantly lower on the 3rd and 7th postoperative days in the control group (p<0.001 for each). The treatment group also showed significantly higher capillary permeability, fibroblast proliferation, and collagen deposits (p<0.001 for each). CD34 expression was significantly increased in the treatment group on the 7th postoperative day (p=0.005). Application of melatonin in early sepsis significantly improved colonic anastomotic healing in a rat model. | {
"pile_set_name": "PubMed Abstracts"
} |
A vitamin-free minimal synthetic medium for Cryptococcus neoformans.
The use of a simple synthetic medium is essential for study on the growth and physiology of Cryptococcus neoformans. In the present study, a minimal synthetic liquid medium (MSM) was tested for the growth of 23 C. neoformans strains. This medium contained a low concentration of glucose, ammonium sulphate and inorganic salts with a pH value of 4.5, but no amino acids or vitamins. The strains were starved for 4 days to eliminate nutrients which might have been carried over from their pre-culture medium. Then, they were inoculated in the MSM as an initial OD of 0.020 at 550 nm and incubated at 37 degrees C for 20 days. Cell growth was generally monitored daily by measuring the absorbance at 550 nm. The medium supported the growth of the strains tested and gave an average final OD of 0.500. The results obtained indicate that C. neoformans may be autotrophic with respect to vitamins and in particular to thiamine. The MSM medium is easy to prepare and store. It is highly reproducible and useful for studies on the growth and physiology of C. neoformans. | {
"pile_set_name": "PubMed Abstracts"
} |
Self- and rater-assessed effectiveness of "thinking-aloud" and "regular" morning report to intensify young physicians' clinical skills.
This study compared the effects of the "thinking aloud" (TA) morning report (MR), which is characterized by sequential and interactive case discussion by all participants, with "regular" MR for clinical skill training of young physicians. Between February 2011 and February 2014, young physicians [including postgraduate year-1 (PGY1) residents, interns, and clerks) from our hospital were sequentially enrolled and followed for 3 months. The self- and rater-assessed educational values of two MR models for building up clinical skills of young physicians were compared. The junior (intern and clerk) attendees had higher self-assessed educational values scores and reported post-training application frequency of skills trained by TA MR compared with the senior (PGY1 resident) attendees. Higher average and percentage of increased overall rater-assessed OSCE scores were noted among the regular MR senior attendees and TA MR junior attendees than in their corresponding control groups (regular MR junior attendees and TA MR senior attendees). Interestingly, regular MRs provided additional beneficial effects for establishing the "professionalism, consulting skills and organization efficiency" aspects of clinical skills of senior/junior attendees. Moreover, senior and junior attendees benefited the most by participating in seven sessions of regular MR and TA MR each month, respectively. TA MR effectively trains junior attendees in basic clinical skills, whereas regular MR enhances senior attendees' "work reports, professionalism, organizational efficiency, skills in dealing with controversial and professional issues." Undoubtedly, all elements of the two MR models should be integrated together to ensure patient safety and good discipline among young physicians. | {
"pile_set_name": "PubMed Abstracts"
} |
Determination of flunarizine in rat brain by liquid chromatography-electrospray mass spectrometry.
A rapid liquid chromatography-electrospray mass spectrometry (LC-ES-MS) assay for the determination of flunarizine (FZ) in rat brain has been developed. A C18 column and an isocratic elution were employed for the separation. Using post-column split, 64% of the eluent was introduced into the ES-MS system for detection. The [M+H]+ (m/z 406) and a fragmented ion (m/z 203) were detected using selected ion monitoring. The linear range of this assay was good, ranging from 0.05 to 5 microM (r2=0.99). The intra- and inter-day precisions showed relative standard deviations ranging from 1.4% to 2.0% and 1.3% to 2.9%, respectively. The application of this newly developed method was demonstrated by examining the pharmacokinetics of FZ in rat brain. | {
"pile_set_name": "PubMed Abstracts"
} |
Treatment of pathologic laughing and crying.
Pathologic laughing and crying (PLC) denotes paroxysms of involuntary and uncontrollable crying and/or laughing resulting from neurologic illnesses. These paroxysms of affect are often provoked by nonsentimental stimuli; even when the inciting stimulus is sentimentally meaningful, the intensity of the affective response is excessive. The crying and/or laughing of PLC are variably accompanied by episode-congruent subjective emotional feelings. In unusual cases, episode-related feelings are of a valence contradictory to the expressed affect (ie, feeling happy while crying, or vice versa). PLC does not bear a predictable relationship to the prevailing mood of the patient, and the occurrence of such episodes does not produce a sustained mood disturbance. Therefore, patients with PLC must not be misunderstood as "depressed" or "manic" solely on the basis of their frequent episodic crying or laughing. In rare circumstances, PLC or PLC-like symptoms may be the presenting symptom of a neurologic illness. In such circumstances, a prompt and thorough diagnostic evaluation for that neurologic illness should be undertaken before initiating treatment for PLC. Selective serotonin reuptake inhibitors (SSRIs) are efficacious, safe, and well-tolerated treatments for PLC and are recommended as first-line treatments for this condition. Tricyclic antidepressants, dextromethorphan/quinidine, or dopaminergic agents may be useful alternative treatments in patients in whom SSRIs are ineffective or poorly tolerated. Education and supportive therapy may help patients and families mitigate the social isolation and embarrassment that PLC episodes frequently produce. | {
"pile_set_name": "PubMed Abstracts"
} |
Parents of children diagnosed with cancer: work situation and sick leave, a five-year post end-of-treatment or a child's death follow-up study.
Cancer in a child is associated with a significant impact on parental employment. We assessed the proportions of parents of survivors and bereaved parents working and reporting sick leave five years after end of successful treatment (ST)/child's death (T7) compared with one year after end of ST/child's death (T6) and the association between partial post-traumatic stress disorder (PTSD) and work situation and sick leave at T7. Participants and procedure: The sample included 152 parents of survivors (77 mothers, 75 fathers) and 42 bereaved parents (22 mothers, 20 fathers) of children diagnosed with cancer in Sweden. The proportions of parents working or reporting sick leave did not differ among mothers and fathers of survivors (92% vs. 96% working, 20% vs. 18% on sick leave) or among bereaved mothers and fathers (91% vs. 90% working, 14% vs. 20% on sick leave) at T7. There was no change from T6 to T7 in the proportion of fathers working (fathers of survivors 91% vs. 96%, bereaved fathers 95% vs. 90%). Although more mothers of survivors (92% vs. 82%) and bereaved mothers (91% vs. 77%) worked at T7 than at T6, this increase was not significant. Fewer bereaved mothers reported sick leave at T7 than at T6 (14% vs. 59%, p < 0.05). Although more fathers reported sick leave at T7 than at T6 (fathers of survivors 18% vs. 8%, bereaved fathers 20% vs. 15%), this was not significant. Partial PTSD was not associated with parents' work situation or sick leave at T7. Results suggest little adverse effect on work situation and sick leave among parents of survivors and bereaved parents five years after end of ST/child's death from cancer. However, the pattern of change observed differed between parents, which could potentially indicate possible delayed consequences for fathers not captured in the present paper. | {
"pile_set_name": "PubMed Abstracts"
} |
[Nuclear medicine studies of the heart].
Nuclear imaging methods provide noninvasive indexes of myocardial function, perfusion, and metabolism and are well accepted in clinical cardiology. Advances in prevention and treatment of cardiac disease have resulted in decreasing cardiovascular mortality in industrialized nations. The improvement in therapeutic options has increased the demand for diagnostic tests that might guide clinical decision making. Information beyond the pure anatomic characterization of coronary stenoses is required. Nuclear imaging can be used for early detection and monitoring of the severity and extent of disease. The prognostic potential of such functional testing is being increasingly appreciated and used to guide therapy, thereby resulting in improvement of the quality and cost-effectiveness of the workup of patients with cardiovascular disease. Extensive clinical validation has resulted in growing acceptance of these techniques. Furthermore, ongoing improvement of imaging techniques and development of new radiopharmaceuticals will pave the way for disease-specific, molecular-targeted cardiac imaging in the future. | {
"pile_set_name": "PubMed Abstracts"
} |
Investigation of vasoactive ion content of herbs used in hemorrhoid treatment in Turkey.
The aim of the present study is to determine anion and cation contents of the herbals used in Turkish folk remedy to explore the rationale of their use in hemorrhoid treatment in the context of the vasoactivity of these elements. Herbs used in the treatment of hemorrhoid were determined by the way of literature search. These herbs were obtained from certified herb sellers. Ground herb samples were placed in individual tubes containing methanol and incubated for 48 hours at 30 degrees C. At the end of the incubation, supernatants were analyzed for their ion concentrations by using ion chromatography. The difference between ion levels between systemic and locally used herbs, was not statistically significant (p>0.05). Anion concentrations (except nitrate) of locally used herbs were slightly higher than systemically used herbs (p>0.05). Cation levels (except magnesium) of systemically used herbs were slightly higher than locally used herbs (p>0.05). It was shown that the concentration of vasoconstrictor effective ions was higher than the concentration of vasodilator effective ions (p<0.001). While vasoconstrictor ion concentration of systemically used herbs was 88.06 +/- 147.42 mg, vasodilator ion concentration of locally used herbs was 90.15 +/- 136.94 mg. The difference between vasodilator concentrations of groups was more evident; 5.39 +/- 9.80 mg and 14.32 +/- 66.48 mg for locally and systemically used herbs respectively. This study showed that herbal remedies used for the treatment of hemorrhoid in Turkey contain vasoactive and especially vasoconstrictor ions. Vasoconstrictor agents could amplify each others' effects as it has been previously shown, therefore, it is probable that the vasoconstrictor ion contents could contribute to the curative effects of herbals in the treatment of hemorrhoids. | {
"pile_set_name": "PubMed Abstracts"
} |
The Potential Role of Protein Leverage in the US Obesity Epidemic.
The protein leverage model of obesity posits that decreasing the protein fraction of the diet leads to compensatory increases in total energy intake in an attempt to maintain a target amount of absolute protein consumed. The resulting increased energy intake thereby causes weight gain. According to food balance sheets published by the Food and Agriculture Organization of the United Nations, while the absolute protein content of the US food supply has increased since the early 1970s, the fraction of available calories from protein has decreased by ~1% because of greater increases in available carbohydrate and fat. Counterintuitively, even such a small decrease in the protein fraction of the food supply has the potential to result in relatively large increases in energy intake according to the protein leverage model. Therefore, while the protein leverage effect is unlikely to fully explain the obesity epidemic, its potential contribution should not be ignored. | {
"pile_set_name": "PubMed Abstracts"
} |
Mice transgenic for HTLV-I LTR-tax exhibit tax expression in bone, skeletal alterations, and high bone turnover.
HTLV-I infection can result in adult T cell leukemia with accompanying hypercalcemia and increased bone resorption. A viral etiology has also been invoked for Paget's disease, a disease of high bone turnover. Delineation of pathogenetic mechanisms of viral-associated bone diseases has been impeded by the complexity of viral and host factors. In order to consider the relationship of HTLV-I infection to skeletal changes we have evaluated the role of a single viral gene in mice transgenic for HTLV-I tax under the control of the viral promoter. Tax mice exhibited severe skeletal abnormalities characterized by high bone turnover, increases in osteoblast and osteoclast numbers and activity, and myelofibrosis. These changes were apparent as early as two months of age. Tax mRNA and protein were highly expressed in bone but not in bone marrow nor in any other tissues except, as previously reported, salivary gland and neurofibromas when they did develop. Within bone, tax protein was detected in only two cell types, mature osteoclasts and spindle-shaped cells within the endosteal myelofibrosis. These observations suggest that local expression of the tax gene, which encodes a viral regulatory protein known to influence host gene expression, can induce within the bone environment marked changes in bone cell activity, resulting in profound skeletal alterations. | {
"pile_set_name": "PubMed Abstracts"
} |
Oophorectomy/adrenalectomy.
Oophorectomy is indicated for premenopausal women who have disseminated breast cancer and who are estrogen receptor positive. Adrenalectomy is indicated in women who have advanced disseminated breast cancer and who have hormonally dependent tumors as evidenced by estrogen receptors in the tumor tissue, or by virtue of regression from previous oophorectomy, anti-estrogens, or medical adrenalectomy. Endocrine ablation should be performed early in the course of the disease. For perimenopausal women or for those who are immediately postmenopausal, combined oophorectomy/adrenalectomy are performed. Adrenalectomy is contraindicated in those women with fulminant recurrent disease with a short interval from mastectomy to time of recurrence. It is also contraindicated in those with advanced liver metastasis, extensive pulmonary metastasis, especially of the lymphangitic type, or symptomatic brain metastasis. Clinical assessment together with estrogen receptor assay wil permit more careful patient selection so that ablative procedures will be performed only in those patients most likely to have a good response. | {
"pile_set_name": "PubMed Abstracts"
} |
Theoretical studies on the hydrolysis mechanism of N-(2-oxo-1,2-dihydro-pyrimidinyl) formamide.
Density functional theory (B3LYP) and ab initio (MP2) methods with the 6-31G(d,p) basis set are used to study the mechanisms for the hydrolysis of N-(2-oxo-1,2-dihydro-pyrimidinyl) formamide (PFA) in the gas phase. The direct and the water-assisted hydrolysis processes are considered, involving one and two water molecules, respectively. Three different pathways are explored in each case. In the first pathway, the O atom of water first attacks at the C atom of amide while one H atom of water transfers toward the oxygen of amide, leading to an intermediate of tetrahedral coordinated carbon with two OH groups. In the subsequent step, the hydroxyl H atom transfers to the N atom of pyrimidine ring and the C-N covalent bond of amide dissociates simultaneously. In the second path, the O and one H of water attack at the C of amide and the N of pyrimidine ring, respectively, while the C-N bond of amide dissociates. In the third path, three processes occur simultaneously: the O of water attacks at the C of amide, one H atom attacks at the N of amide, and the C-N bond of amide is broken. It is shown that the second pathway is favored for the direct hydrolysis while the first pathway is favored for the water-assisted hydrolysis. It is also shown that the water-assisted hydrolysis is slightly more favorable than the direct hydrolysis. Moreover, solvent effects on five pathways are evaluated with Monte Carlo simulation (MC) and free energy perturbation methods. It is shown that the solvent water slightly reduces the energy barrier in each pathway. The first pathway in the water-assisted hydrolysis remains the most favorable when the solvent effects of bulk water are taken into account. | {
"pile_set_name": "PubMed Abstracts"
} |
[Galand disk implant and pupillary block].
We have implanted 530 Galand's disc lens in the last 15 months. Stability and self-centering of implant were good when peroperative vitreous pressure was normal and in any case when wound was closed. Pupillary blocks, specific complications of this lens were rare (less than 1%); they can be prevented occurred by simple and adequate protocols. | {
"pile_set_name": "PubMed Abstracts"
} |
Detection beyond Debye's length with an electrolyte-gated organic field-effect transistor.
Electrolyte-gated organic field-effect transistors are successfully used as biosensors to detect binding events occurring at distances from the transistor electronic channel that are much larger than the Debye length in highly concentrated solutions. The sensing mechanism is mainly capacitive and is due to the formation of Donnan's equilibria within the protein layer, leading to an extra capacitance (CDON) in series to the gating system. | {
"pile_set_name": "PubMed Abstracts"
} |
High-pressure liquid chromatographic analysis of estrogens in pharmaceuticals by measurement of their dansyl derivatives.
A high-pressure liquid chromatographic method is described for the analysis of estrogens in pharmaceutical tablet and injectable dosage forms. In general, the estrogens are isolated, an internal standard is added, the dansyl derivatives are formed, and the dansyl estrogen solution is injected into a liquid chromatograph. Linear response is experienced between the mass of estrogen and the ratio of the estrogen peak height to the internal standard peak height, using a microparticle silica column and chloroform--n-heptane mobile phases. With fluorometric measurement, limits of detectability for ethinyl estradiol and estradiol were 0.04 and 0.05 ng, respectively. Methyltestosterone, an androgen in combination with ethinyl estradiol, was analyzed simultaneously. Commercial pharmaceutical preparations containing estrone, ethinyl estradiol, and estradiol were analyzed by the proposed method. The results indicate the method to be sensitive, reasonably precise (less than 2%), and accurate in the analysis of estrogen in dosage forms. | {
"pile_set_name": "PubMed Abstracts"
} |
Geographical variations in the concentration of biliary free fatty acids with anti-mutagenic action.
The concentrations and compositions of free fatty acids (FFAs) in human bile, especially of inhibitory free fatty acids (IFFAs), were analyzed in terms of anti-mutagenic effects in relation to the mutagenic activity of bile. Bile samples were collected from patients with cholelithiasis residing in either Niigata or Kochi prefectures of Japan, regions characterized as the highest and lowest risk areas for gallbladder cancer (GBC), respectively. Biliary FFAs and IFFAs were analyzed by high-performance liquid chromatography and mutagenicity was examined in by the Ames test (TA98+S9mix) after blue rayon treatment. There was a tendency for higher biliary FFA and IFFA concentrations in the Kochi subjects, but the proportion of IFFA to the total FFA concentration did not differ between the two areas. There was an inverse correlation between the concentrations of IFFAs and the numbers of revertant colonies in both Niigata and Kochi subjects. However, at a dose of 591 micromol/l, (calculated based on the average amount of IFFAs absorbed in blue rayon) IFFAs did not exhibit anti-mutagenic actions in the blue rayon extracts. Within this range, more positive samples were seen in Niigata than in Kochi, suggesting the presence of more active mutagen(s) in Niigata samples. | {
"pile_set_name": "PubMed Abstracts"
} |
Protein kinase C ligands based on tetrahydrofuran templates containing a new set of phorbol ester pharmacophores.
A series of substituted tetrahydrofurans with an embedded glycerol backbone carrying additional tetrahydrofuranylideneacetate or tetrahydrofuranylacetate motifs were grouped into four distinct templates (I-IV) according to stereochemistry. The compounds were designed to mimic three essential pharmacophores (C(3)-C=O, C(20)-OH and C(13)-C=O) of the phorbol esters according to a new, revised model. The tetrahydrofuran ring was constructed from glycidyl 4-methoxyphenyl ether, and the structures of the isomeric templates were assigned by NMR spectroscopy, including NOE. The binding affinity for protein kinase C (PKC) was assessed in terms of the ability of the ligands to displace bound [(3)H-20]phorbol 12, 13-dibutyrate (PDBU) from a recombinant alpha isozyme of PKC. Geometric Z- and E-isomers (1 and 3, respectively) containing a tetrahydrofuranylideneacetate motif were the most potent ligands with identical K(i) values of 0.35 microM. Molecular modeling studies of the four templates showed that the rms values when fitted to a prototypical phorbol 12,13-diacetate ester correlated inversely with affinities in the following order: I approximately II > III > IV. These compounds represent the first generation of rigid glycerol templates seeking to mimic the binding of the C(13)-C=O of the phorbol esters. The binding affinities of the most potent compounds are in the same range of the diacylglycerols (DAGs) despite the lack of a phorbol ester C(9)-OH pharmacophore surrogate. This finding confirms that mimicking the binding of the C(13)-C=O pharmacophore of phorbol is a useful strategy. However, since the C(9)-OH and C(13)-C=O in the phorbol esters appear to form an intramolecular hydrogen bond that functions as a combined pharmacophore, it is possible the lack of this combined motif in the target templates restricts the compounds from reaching higher binding affinities. | {
"pile_set_name": "PubMed Abstracts"
} |
Inositol 1,4,5-trisphosphate receptors are essential for the development of the second heart field.
Congenital heart defects (CHDs) occur in 0.5-1% of live births, yet the underlying genetic etiology remains mostly unknown. Recently, a new source of myocardial cells, namely the second heart field (SHF), was discovered in the splanchnic mesoderm. Abnormal development of the SHF leads to a spectrum of outflow tract defects, such as persistent truncus arteriosus and tetralogy of Fallot. Intracellular Ca(2+) signaling is known to be essential for many aspects of heart biology including heart development, but its role in the SHF is uncertain. Here, we analyzed mice deficient for genes encoding inositol 1,4,5-trisphosphate receptors (IP(3)Rs), which are intracellular Ca(2+) release channels on the endo/sarcoplasmic reticulum that mediate Ca(2+) mobilization. Mouse embryos that are double mutant for IP(3)R type 1 and type 3 (IP(3)R1(-/-)IP(3)R3(-/-)) show hypoplasia of the outflow tract and the right ventricle, reduced expression of specific molecular markers and enhanced apoptosis of mesodermal cells in the SHF. Gene expression analyses suggest that IP(3)R-mediated Ca(2+) signaling may involve, at least in part, the Mef2C-Smyd1 pathway, a transcriptional cascade essential for the SHF. These data reveal that IP(3)R type 1 and type 3 may play a redundant role in the development of the SHF. | {
"pile_set_name": "PubMed Abstracts"
} |
Putative interaction of presynaptic dopamine and serotonin receptors modulating synaptosomal tyrosine hydroxylase activity in the nucleus accumbens of rats.
Inhibition of synaptosomal tyrosine hydroxylase activity by dopamine (DA) autoreceptors and serotonin (5-HT) heteroreceptors was used as a functional measure for the receptor activity in the nucleus accumbens of rats. Kinetic analysis of the concentration dependence of inhibition with and without antagonists indicates that the sensitivity of the autoreceptor to DA is significantly increased by blockade of the 5-HT heteroreceptor and vice versa. The results provide evidence for autoreceptor-heteroreceptor interactions at the presynaptic membrane level on dopaminergic nerve terminals. | {
"pile_set_name": "PubMed Abstracts"
} |
Balancing mitochondrial dynamics via increasing mitochondrial fusion attenuates infarct size and left ventricular dysfunction in rats with cardiac ischemia/reperfusion injury.
An uncontrolled balance of mitochondrial dynamics has been shown to contribute to cardiac dysfunction during ischemia/reperfusion (I/R) injury. Although inhibition of mitochondrial fission could ameliorate cardiac dysfunction, modulation of mitochondrial fusion by giving a fusion promoter at different time-points during cardiac I/R injury has never been investigated. We hypothesized that giving of a mitochondrial fusion promoter at different time-points exerts cardioprotection with different levels of efficacy in rats with cardiac I/R injury. Forty male Wistar rats were subjected to a 30-min ischemia by coronary occlusion, followed by a 120-min reperfusion. The rats were then randomly divided into control and three treated groups: pre-ischemia, during-ischemia, and onset of reperfusion. A pharmacological mitochondrial fusion promoter-M1 (2 mg/kg) was used for intervention. Reduced mitochondrial fusion protein was observed after cardiac I/R injury. M1 administered prior to ischemia exerted the highest level of cardioprotection by improving both cardiac mitochondrial function and dynamics regulation, attenuating incidence of arrhythmia, reducing infarct size and cardiac apoptosis, which led to the preservation of cardiac function and decreased mortality. M1 given during ischemia and on the onset of reperfusion also exerted cardioprotection, but with a lower efficacy than when given at the pre-ischemia time-point. Attenuating a reduction in mitochondrial fusion proteins during myocardial ischemia and at the onset of reperfusion exerted cardioprotection by attenuating mitochondrial dysfunction and dynamic imbalance, thus reducing infarct size and improving cardiac function. These findings indicate that it could be a promising intervention with the potential to afford cardioprotection in the clinical setting of acute myocardial infarction. | {
"pile_set_name": "PubMed Abstracts"
} |
Genetic syndromes and prenatally detected renal anomalies.
Renal anomalies are frequently detected on the routine second trimester scan offered to all pregnant women in the UK. These anomalies may be isolated but can also be associated with other congenital anomalies. Many combinations of ultrasound scan findings constitute recognised genetic entities. Knowledge of these conditions is essential for adequate management of the pregnancy and subsequent balanced parental counselling. This short review discusses the common genetic syndromes associated with the renal abnormalities identified on the antenatal ultrasound scan, and also provides an overview of renal symptoms in chromosome imbalances and after teratogenic influences. | {
"pile_set_name": "PubMed Abstracts"
} |
[Search of heavy metals biosorbents among yeasts of different taxonomic groups].
The use of microbial cells as heavy metal biosorbents is a potential alternative for the existing methods of the environment treatment for pollution by these metals. Yeast may be successfully used in the metals sorption. An agar-plate screening method was used for rapid isolation of metal-accumulating strains of yeast and preliminary estimation of their biosorption capacity. The capacity to accumulate heavy metals, such as copper, zinc, lead, chrome and cobalt was estimated in 68 pigmented and pigmentless yeast strains isolated from different sources. The best capacity of copper and zinc accumulation was shown by pink-coloured Rhodotorula mucilaginosa, Rhodotorula aurantiaca, Rhodotorula glutinis and pigmentless strains of the yeast Candida krusei, Williopsis california. | {
"pile_set_name": "PubMed Abstracts"
} |
Feasibility of photodynamic therapy for secondary hyperparathyroidism in chronic renal failure rats.
Feasibility of photodynamic therapy (PDT) for secondary hyperparathyroidism (SHPT) was examined in a rat model of SHPT. A photosensitizer, 5-aminolevulinic acid (5-ALA), was injected intraperitoneally, and the parathyroid glands were irradiated either after surgical exposure with 385-nm light or transdermally with 630-nm light from a light-emitting diode (LED) lamp. PDT with high 5-ALA and irradiation doses caused severe hypoparathyroidism in SHPT rats within two days. Low-dose invasive PDT reduced intact parathyroid hormone (iPTH) levels in all rats from 748.9 ± 462.6 pg/mL at baseline to 138.7 ± 117.5 pg/mL at week 6, followed by a further decrease to 80.5 ± 54.0 pg/mL at week 9 in 60 % of rats or an increase to 970.0 ± 215.6 pg/mL at week 9 in 40 % of rats. Low-dose noninvasive PDT reduced iPTH levels from 1612.5 ± 607.8 pg/mL at baseline to 591.9 ± 480.1 pg/mL at week 4 in all rats. Thereafter, iPTH levels remained low in 43 % of rats and were 233.7 ± 51.6 pg/mL at week 9, whereas 57 % showed an increase, reaching 3305.9 ± 107.3 pg/mL at week 9. Control SHPT rats had iPTH levels of 2487.8 ± 350.9 and 2974.6 ± 372.1 pg/mL at week 4 and 9, respectively. The parathyroid glands of the rats with low iPTH levels were atrophied and had few parathyroid cells surrounded by fibrotic materials and no recognizable blood vessels. Those of the rats with high iPTH levels showed well-preserved gland structure, clusters of parathyroid cells, and blood vessels. These results demonstrate that 5-ALA-mediated PDT for SHPT is feasible. | {
"pile_set_name": "PubMed Abstracts"
} |
Vaccinia Related Kinase 2 (VRK2) expression in neurological disorders: schizophrenia, epilepsy and multiple sclerosis.
Schizophrenia (SCZ), epilepsy and Multiple Sclerosis (MS) are neurological disorders with increasing prevalence disturb the patients' lives and are regarded as burdens to the society. As multifactorial disorders, genetic susceptibility factors are involved in their pathogenesis. The Vaccinia-Related Kinase 2 (VRK2) gene codes for a serine threonine kinase recently reported to be contributed in the pathogenesis of some neurological disorders. In the present case-control study we compared the VRK2 gene expression in peripheral blood samples from SCZ, epilepsy and MS patients with normal subjects. A total of 300 subjects comprising 50 patients in each disease category (SCZ, epilepsy and MS) as well as 150 healthy individuals (50 matched controls for each disorder) participated in the current study. The VRK2 blood mRNA expression level was measured using the TaqMan real time PCR. The results demonstrated significant down-regulation of VRK2 gene in SCZ (P<0.0001), epilepsy (P=0.008) and MS (P=0.029) compared with the healthy subjects. Consequently, VRK2 is suggested as a candidate gene for neurological disorders through its role in signaling pathway, the neuronal loss and stress response. | {
"pile_set_name": "PubMed Abstracts"
} |
Boron complexes of aromatic 5-substituted iminopyrrolyl ligands: synthesis, structure, and luminescence properties.
A group of new mononuclear boron chelate compounds [BPh2{κ2N,N'-5-R-NC4H2-2-C(H)[double bond, length as m-dash]N-Ar}] (R = Ar = C6H57; R = C6H5, Ar = 2,6-iPr2C6H38; R = Anthracen-9-yl (Anthr), Ar = C6H59; R = Anthr, Ar = 2,6-iPr2C6H310) were synthesized via the reaction of B(C6H5)3 with the corresponding 5-substituted 2-(N-arylformimino)pyrrole ligand precursors 3-6. These complexes were prepared in order to evaluate the luminescence potential derived from the substitution of the position 5 of the pyrrolyl ring with an aromatic group. Compounds 7-10 were photophysically characterized in solution and in the solid state. The 5-phenyl-2-iminopyrrolyl-BPh2 complexes 7 and 8 are blue emitters and have enhanced photoluminescence quantum yields in the solid state (ΦPL) up to 0.95, whereas the 5-anthracenyl derivatives 9 and 10 have green-bluish fluorescence and a ΦPL of 0.49 and 0.24, respectively. DFT and TDDFT studies were performed, considering the effect of solvent and dispersion, in order to show how the geometries of compounds 7-10 changed from the ground to the excited state, to assign electronic transitions, and to rationalize the observed luminescence. These materials were applied in organic light-emitting diodes (OLEDs), with various device structures, the best showing an external quantum efficiency of 2.75% together with a high luminance of 23 530 cd m-2. | {
"pile_set_name": "PubMed Abstracts"
} |
[Analysis of weekly paclitaxel chemotherapy for esophageal cancer].
Public knowledge-based application for paclitaxe(l PAC) has been approved for advanced or recurrent esophageal cancer. We investigated the feasibility of weekly PAC chemotherapy as a second-line or subsequent regimen for metastatic or recurrent esophageal cancer. Patients received PAC( 100 mg/m2 intravenously) on days 1, 8, 15, 22, 29, and 36 of each 8-week period. We analyzed the toxicity and efficacy in 6 patients treated with the weekly PAC chemotherapy. Grade 3-4 toxicities were neutropenia, leukopenia, and anemia. Two patients had stable disease and 2 had progressive disease. By managing the side effects, weekly PAC therapy is considered a feasible regimen that can be administered on an outpatient basis. | {
"pile_set_name": "PubMed Abstracts"
} |
[Primers of gag gene for HIV-1 subtyping in China and application thereof in practice].
To design the appropriate primers of gag gene for HIV-1 subtyping in molecular epidemiology survey based on the genetic characteristics derived from the main HIV-1 strains prevailing in China. The gag genes of HIV-1 CRF07_BC, CRF08_BC, and subtype C, together with subtyping reference sequences, were obtained from HIV sequence database. Referring to the alignments and genetic characteristics of HIV-1 full gag sequences, new primers of gag gene for amplification and subtyping were designed. The target fragment was used to construct neighbor-joining phylogenetic tree and evaluate its reliability. The newly designed primers (GUX/GDX) were used to amplify the plasma samples to evaluate their efficiency. The phylogenetic tree of 306/c-gag fragments (positions 836-1507 of HIV-1 strain HXB2) showed that CRF07_BC and subtype C strains formed clusters with low bootstrap values (59% for CRF07_BC and 70% for subtype C), and the phylogenetic tree could not distinguish the sequences of CRF07_BC, CRF08_BC, and subtype C very well. Whereas the sequences of CRF07_BC, CRF08_BC, and subtype C from GUX/GDX (positions 781-1861) were clustered separately with higher bootstrap values (99%, 99%, and 77% respectively). In practice, a very good amplification and sequencing efficiency with over 90% positive results on average were obtained with GUX/GDX. Five clusters of subtype B, C, CRF01_AE, CRF07_BC, and CRF08_BC were formed with higher confidence (Bootstrap values all above 80%). The reliable phylogenetic tree could be constructed based on the fragments sequenced only with antisense primer (GDX). Fragments obtained with GUX/GDX primers of gag gene can be used to reconstruct phylogenetic tree with high reliability to distinguish the HIV-1 strains circulating in China, especially for the major BC recombinant and subtype C strains, which provides a useful tool in HIV molecular epidemiologic research. | {
"pile_set_name": "PubMed Abstracts"
} |
Formation of antigenic quinolone photoadducts on Langerhans cells initiates photoallergy to systemically administered quinolone in mice.
Quinolone antibacterial agents are well known to cause photoallergy as a side-effect. Murine photoallergy to fluoroquinolones is a T cell-mediated immune response, evoked either by systemic fluoroquinolone and subsequent exposure of skin to ultraviolet A light or by subcutaneous injection of fluoroquinolone-photomodified epidermal cells. In this photosensitivity, epidermal Langerhans cells may be photomodified initially with the drug and thus present photohaptenic moieties to sensitize and restimulate T cells. Although we have shown that Langerhans cells photocoupled in vitro with fluoroquinolones are capable of stimulating sensitized T cells, it remains unclear whether systemically given fluoroquinolone photomodifies Langerhans cells upon ultraviolet A irradiation of the skin and the Langerhans cells become photohapten-bearing, T cell-stimulatory cells. In a murine model of fleroxacin photoallergy induced by intraperitoneal injection of the drugs plus ultraviolet A irradiation of skin, we found that Langerhans cells as well as keratinocytes are photoderivatized with fleroxacin as demonstrated with a fluoroquinolone-specific monoclonal antibody. Langerhans-cell-enriched epidermal cells prepared from mice treated with fleroxacin and ultraviolet A induced proliferation of sensitized T cells, indicating that photomodified Langerhans cells are functional. There was an optimal range of ultraviolet A dose to quantitatively and qualitatively form fleroxacin-photomodified Langerhans cells, as excess ultraviolet A rather reduced the photoantigen-presenting capacity of Langerhans cells presumably because of drug phototoxicity. Our study suggests that Langerhans cells serve as photoantigen-presenting cells in drug photoallergy. | {
"pile_set_name": "PubMed Abstracts"
} |
Structural basis for olivetolic acid formation by a polyketide cyclase from Cannabis sativa.
In polyketide biosynthesis, ring formation is one of the key diversification steps. Olivetolic acid cyclase (OAC) from Cannabis sativa, involved in cannabinoid biosynthesis, is the only known plant polyketide cyclase. In addition, it is the only functionally characterized plant α+β barrel (DABB) protein that catalyzes the C2-C7 aldol cyclization of the linear pentyl tetra-β-ketide CoA as the substrate, to generate olivetolic acid (OA). Herein, we solved the OAC apo and OAC-OA complex binary crystal structures at 1.32 and 1.70 Å resolutions, respectively. The crystal structures revealed that the enzyme indeed belongs to the DABB superfamily, as previously proposed, and possesses a unique active-site cavity containing the pentyl-binding hydrophobic pocket and the polyketide binding site, which have never been observed among the functionally and structurally characterized bacterial polyketide cyclases. Furthermore, site-directed mutagenesis studies indicated that Tyr72 and His78 function as acid/base catalysts at the catalytic center. Structural and/or functional studies of OAC suggested that the enzyme lacks thioesterase and aromatase activities. These observations demonstrated that OAC employs unique catalytic machinery utilizing acid/base catalytic chemistry for the formation of the precursor of OA. The structural and functional insights obtained in this work thus provide the foundation for analyses of the plant polyketide cyclases that will be discovered in the future. Structural data reported in this paper are available in the Protein Data Bank under the accession numbers 5B08 for the OAC apo, 5B09 for the OAC-OA binary complex and 5B0A, 5B0B, 5B0C, 5B0D, 5B0E, 5B0F and 5B0G for the OAC His5Q, Ile7F, Tyr27F, Tyr27W, Val59M, Tyr72F and His78S mutant enzymes, respectively. | {
"pile_set_name": "PubMed Abstracts"
} |
Abnormal activator protein 1 transcription factor expression in CD30-positive cutaneous large-cell lymphomas.
CD30+ cutaneous large-cell lymphomas (CLCL) represent a heterogeneous subgroup of skin lymphomas including primary cutaneous CD30+ anaplastic large-cell lymphoma (C-ALCL), lymphomatoid papulosis (LyP), transformed mycosis fungoides (T-MF) and Hodgkin's lymphoma (HL) with cutaneous involvement. The activator protein 1 (AP-1) transcription factor consists of JUN, FOS and other protein families. Recent studies have revealed upregulation of JUNB in both MF and C-ALCL and overexpression of JUNB and CD30 in systemic HL and ALCL. To assess systematically the expression pattern of AP-1 transcription factors in CLCL. We analysed paraffin tissue sections from 27 patients with LyP, 10 with C-ALCL, eight with T-MF and two with cutaneous HL by immunohistochemistry with antibodies against c-JUN, JUNB, JUND, c-FOS and RAF-1. We also stained samples from 10 patients with C-ALCL, seven with Sézary syndrome (SS), six with T-MF, three with cutaneous HL, two with LyP and control samples with total and phosphorylated mitogen-activated protein kinase (MAPK) antibodies. Results Positive staining for JUND (++) was observed in 13 cases of LyP (48%), 10 C-ALCL, six T-MF (75%) and two cutaneous HL cases. Positive JUNB protein expression was present in four cases of T-MF (50%), four C-ALCL (44%), three LyP (11%) and two cutaneous HL. Expression of total (p44/42) MAP kinase and phosphorylated p44/42 MAP kinase were detected in nine cases of C-ALCL (90%), seven SS (88%), five T-MF (89%) and three cutaneous HL. Most of these samples also showed positive staining for JUNB. These results suggest the presence of abnormal AP-1 protein expression in CLCL, which may be relevant to CLCL. | {
"pile_set_name": "PubMed Abstracts"
} |
[Needle biopsy in childhood and infancy hepatic disease (author's transl)].
Experiences are reported gained from 764 liver biopsies in children ad infants. Indications and contraindications are the same as in adults. The normal liver of infants and young children exhibits some particular differences as compared to the adult liver. Formation of giant cells is a striking pathological finding in various early childhood liver diseases. Needle biopsy is imperative in children with longstanding jaundice when it has to be decided, if surgery is to be done or not. Histology yielded the decisive diagnostic information in 80% of the cases in our hands. Needle biopsy may yield important or decisive information in the other liver diseases of childhood as well. | {
"pile_set_name": "PubMed Abstracts"
} |
Energy loss and impact of various stunning devices used for the slaughtering of water buffaloes.
Stock management of the Swiss water buffalo livestock results in the slaughtering of about 350 animals per year. As the stunning of water buffaloes still is an unresolved issue, we investigated the terminal ballistics of currently used perforating stunning devices. Cartridge fired captive bolt devices, handguns and a bullet casing gun were tested in a shooting steep by firing on bisected heads, forehead plates and soap blocks. Energy loss of captive bolts confirmed their inadequacy when used for heavy water buffaloes, notably adult males. As for the free projectiles, ballistics revealed that beyond the impact energy, bullet deformation has a strong impact on the outcome. Light 9mm Luger or .38 Spl bullets as well as large deformable .44 Rem. Magnum bullets should be avoided in favor of heavier .357 Magnum deformation ammunition. These data have been translated into the development of a new stunning device for water buffaloes meeting both animal welfare and occupational safety requirements. | {
"pile_set_name": "PubMed Abstracts"
} |
Enzymatic synthesis of two fucose-containing glycolipids with fucosyltransferases of human serum.
Lacto-N-neotetraosylceramide incubated with human serum fucosyltransferase preparations gave rise to two fucoglycolipids. The faster migrating fucoglycolipid I on the basis of its thin-layer chromatographic mobility, susceptibility to alpha(1 leads to 2) fucosidase from Trichomonas foetus, radio-immunoprecipitation with Ulex europeus lectin and studies with Oh (Bombay) sera was identified as H-active glycolipid (H-I). The most probable structure of fucoglycolipid II should be that with fucose linked alpha(1 leads to 3) to N-acetylglucosamine. Lactosylceramide, ceramide trihexoside and globoside were not substrates for human serum fucosyltransferases. Lacto-N-neotetraosyl ceramide served as a fucose acceptor for all serum preparations tested while asialoganglioside was a substrate only when serum preparations containing H-gene dependent alpha-2-L-fucosyltransferase were used. With asialoganglioside only one radioactive reaction product was formed. | {
"pile_set_name": "PubMed Abstracts"
} |
Prognostic stratification of diabetic patients by exercise echocardiography.
The aim of this study was to assess the incremental value of exercise echocardiography for the risk stratification of diabetic patients. There are currently insufficient outcome data in diabetic patients to define the role of stress echocardiography as a prognostic tool. We studied the prognostic value of exercise echocardiography in 563 patients with diabetes mellitus (mean age 64 +/- 11 years, 336 men) and known or suspected ischemic heart disease (IHD). Cardiac events occurred in 50 patients (cardiac death in 23 and nonfatal myocardial infarction [MI] in 27) during a median follow-up period of three years. Event rate was lower in patients with normal as compared to those with abnormal exercise echocardiography at one year (0% vs. 1.9%), three years (1.8% vs. 11.9%), and five years (7.6% vs. 23.3%), respectively (p = 0.0001). Patients with multivessel distribution of echocardiographic abnormalities had the highest event rate (2.9% at one year, 15.2% at three years, and 32.8% at five years). In an incremental multivariate analysis model, exercise echocardiography increased the chi-square of the clinical and exercise ECG model from 29 to 44.8 (p = 0.0001). Exercise echocardiography provides incremental data for risk stratification of diabetic patients with known or suspected IHD. Patients with a normal exercise echocardiogram have a low event rate. Patients with multivessel distribution of exercise echocardiographic abnormalities are at the highest risk of cardiac events, as one-third of these patients experience cardiac death or nonfatal MI during the five years following exercise echocardiography. | {
"pile_set_name": "PubMed Abstracts"
} |
The changing spectrum of rheumatic disease in human immunodeficiency virus infection.
Although it has been known for over 15 years that a number of rheumatic diseases occur in patients with human immunodeficiency virus (HIV) infection, increasing knowledge about these disorders and advances in HIV treatment need to be considered in approaching patients with HIV-associated rheumatic disease. To examine the clinical, pathologic, and therapeutic features of HIV-associated rheumatic diseases in the context of what is known about the immunology of HIV infection. The author's own extensive collection of references, supplemented by PubMed Medline searches for articles in English-language journals published between 1985 and 2000. The indexing term HIV and the following coindexing terms were used for searching: arthritis, Reiter's syndrome, psoriatic arthritis, rheumatoid arthritis, osteonecrosis, vasculitis, pulmonary hypertension, myositis, myopathy, fibromyalgia, septic arthritis, parotid enlargement, diffuse infiltrative lymphocytosis syndrome, systemic lupus erythematosus, septic arthritis, mycobacterial arthritis, fungal arthritis, autoantibodies, anti-cardiolipin antibodies, and anti-neutrophilic cytoplasmic antibodies. All papers identified in the literature search were reviewed. Studies presenting data that merely confirmed previous studies were not included in the analysis. All identified papers were abstracted by the author. Letters to the editor were included only if a new observation had been made. This was a qualitative review of papers published, with new knowledge about these disorders summarized and presented. Despite new treatments for HIV, reports of rheumatic diseases presenting in AIDS patients persist, especially in HIV-associated arthritis, diffuse infiltrative lymphocytosis syndrome, HIV-associated vasculitis, and polymyositis. However, new HIV treatments may ameliorate these diseases. The spectrum of HIV-associated rheumatic disease remains a diagnostic and therapeutic challenge for the clinician. The impact of changes in HIV treatment on these disorders requires further assessment. | {
"pile_set_name": "PubMed Abstracts"
} |
Plasma cortisol levels in mania: associated clinical ratings and changes during treatment with haloperidol.
Plasma cortisol levels were elevated in a large proportion of samples from manic patients. Although a correlation was found between clinical ratings of the severity of mania and the degree of elevation of daytime cortisol levels, some patients with low clinical ratings had elevated cortisol levels. During treatment with haloperidol, cortisol levels returned to normal earlier that the clinical state. The underlying mechanisms are discussed. | {
"pile_set_name": "PubMed Abstracts"
} |
MHC class II molecules control murine B cell responsiveness to lipopolysaccharide stimulation.
LPS is a strong stimulator of the innate immune system and inducer of B lymphocyte activation. Two TLRs, TLR4 and RP105 (CD180), have been identified as mediators of LPS signaling in murine B cells, but little is known about genetic factors that are able to control LPS-induced cell activation. We performed a mouse genome-wide screen that aside from identifying a controlling locus mapping in the TLR4 region (logarithm of odds score, 2.77), also revealed that a locus closely linked to the MHC region (logarithm of odds score, 3.4) governed B cell responsiveness to LPS stimulation. Using purified B cells obtained from MHC congenic strains, we demonstrated that the MHC(b) haplotype is accountable for higher cell activation, cell proliferation, and IgM secretion, after LPS stimulation, when compared with the MHC(d) haplotype. Furthermore, B cells from MHC class II(-/-) mice displayed enhanced activation and proliferation in response to LPS. In addition, we showed that the MHC haplotype partially controls expression of RP105 (a LPS receptor molecule), following a pattern that resembles the LPS responsiveness phenotype. Together, our results strongly suggest that murine MHC class II molecules play a role in constraining the B cell response to LPS and that genetic variation at the MHC locus is an important component in controlling B cell responsiveness to LPS stimulation. This work raises the possibility that constraining of B cell responsiveness by MHC class II molecules may represent a functional interaction between adaptive and innate immune systems. | {
"pile_set_name": "PubMed Abstracts"
} |
Dilational properties of anionic gemini surfactants with polyoxyethylene spacers at water-air and water-decane interfaces.
The dilational properties of anionic gemini surfactants (oligooxa)-alpha,omega-bis(m-octylbenzene sulfonate) (C(8)E(x)C(8)) with polyoxyethylene spacers at the water-air and water-decane interfaces were investigated via the oscillating barriers method. The influences of oscillating frequency and bulk concentration on dilational properties were explored. The interfacial tension relaxation method was employed to obtain dilational parameters in a reasonably broad frequency range. The experimental results show that the number of ethylene oxide groups is one of the principal factors to control the nature of the interfacial film. With an increase of ethylene oxide groups, the dilational modulus of C(8)E(8)C(8) shows two maxima with the increasing concentration. Furthermore, the dilational moduli at the water-decane interface are remarkably lower than those at the water-air interface for C(8)E(1)C(8) and C(8)E(4)C(8), while the dilational modulus at the water-decane interface is close to that at the water-air interface for C(8)E(8)C(8), which indicates that the structure of the adsorption sublayer plays a more important role. Possible schematic diagrams of adsorbed molecules with different polyoxyethylene spacers at the water-air and water-decane interfaces are proposed. The results of relaxation experiments and Cole-Cole plots can support our provided mechanism strongly. | {
"pile_set_name": "PubMed Abstracts"
} |
DNA methylation variations at CETP and LPL gene promoter loci: new molecular biomarkers associated with blood lipid profile variability.
Recent findings suggest that DNA methylation, a well-known epigenetic mechanism, is involved in high-density lipoprotein cholesterol (HDL-C) metabolism and increased cardiovascular disease risk. The aim of this study was thus to assess whether DNA methylation within key genes of lipoprotein metabolism is associated with blood lipid profile variability. Ninety-eight untreated familial hypercholesterolaemia patients (61 men and 37 women) were recruited for leucocyte DNA methylation analyses at the LDLR, CETP, LCAT and LPL gene promoter loci using bisulfite pyrosequencing. LPL DNA methylation was correlated with HDL-C (r = 0.22; p = 0.031) and HDL particle size (r = 0.47, p = 0.013). In both sex, CETP DNA methylation was negatively associated with low-density lipoprotein cholesterol levels (r < -0.32; p < 0.05). In men, CETP DNA methylation was associated with HDL-C (r = -0.36; p = 0.006), HDL-triglyceride levels (r = 0.59; p < 0.001) and HDL particle size (r = -0.44, p = 0.019). In visceral adipose tissue from 30 men with severe obesity, the associations between LPL DNA methylation, HDL-C (r = -0.40; p = 0.03) and LPL mRNA levels (r = -0.61, p < 0.001) were confirmed. CETP and LPL DNA methylation levels are associated with blood lipid profile, suggesting that further studies of epipolymorphisms should most certainly contribute to a better understanding of the molecular bases of dyslipidemia. | {
"pile_set_name": "PubMed Abstracts"
} |
Downregulation of interleukin-12 (IL-12) responsiveness in human T cells by transforming growth factor-beta: relationship with IL-12 signaling.
Interleukin-12 (IL-12) is a cytokine that plays a central role in the control of cell-mediated immunity. We have previously shown that transforming growth factor-beta1 (TGF-beta) inhibitory effects on human primary allogeneic cytotoxicity and proliferative responses interfere with IL-12 pathway. The present study was undertaken to further elucidate the biochemical basis of the functional interaction between these two cytokines and to define the site of TGF-beta action on the signaling pathway activated by IL-12. Our data indicate that TGF-beta induced an inhibition of interferon-gamma (IFN-gamma) production without affecting the IL-12Rbeta1 and IL-12Rbeta2 subunits mRNA expression by activated T cells. We further show that TGF-beta has a significant inhibitory effect on the early signal transduction events following interaction of IL-12 with its receptor on activated T cells, resulting in the inhibition of both JAK2 and Tyk2 phosphorylation. In addition, TGF-beta was found to significantly inhibit IL-12-induced phosphorylation of the STAT4 transcription factor. Electrophoretic mobility shift assay indicated that TGF-beta induced a decrease in IL-12-induced STAT4 DNA binding activity in T lymphocytes. This study suggests that TGF-beta influences IL-12 responsiveness at least in part by inhibiting early signaling events essential to gene induction in IL-12-activated T cells. | {
"pile_set_name": "PubMed Abstracts"
} |
[Effect of seven kinds of flavonoids on recombinant human protein tyrosine phosphatase].
To observe the effects of seven kinds of flavonoids on recombinant human phosphatase of regenerating liver-3 activity. The inhibitory effect of flavonoids was tested by DiFMUP assay. Calculation of IC50 values was performed according to the law of semi-effect-probit. Myricetin and gossypin could significantly inhibit recombinant PRL-3 activity in a concentration dependent manner with IC50 values of 55.54 and 68.86 micromol/L, respectively. Quercetin, luteolin and 7,8-Dihydroxyflavone had a weak inhibitory effect with IC50 values of 113.38, 151.56 and 249.49 micromol/L. respectively. While 3-hydroxyflavone and 6-hydroxyflavone had no significant effect on PRL-3 activity. Structure activity study indicated that C4 and C7 hydroxyls on the flavone skeleton were key functional groups to influencing PRL-3 inhibotory activity. The inhibitory effect of flavonoids on PRL-3 was increased with the number of hydroxyl group. Myricetin and gossypin were two strong inhibitors on recombinant human protein tyrosine phosphatase PRL-3. | {
"pile_set_name": "PubMed Abstracts"
} |
Excess catecholamine syndrome. Pathophysiology and therapy.
In addition to genetic factors, lifestyle has a predominant influence on primary hypertension and noninsulin-dependent diabetic mellitus (NIDDM). We initiated studies using radiotelemetry for characterizing molecular events linked with excess calorie intake and psychologic stress. An increased calorie intake was associated with raised (p < 0.05) systolic and diastolic blood pressure as well as heart rate independent of day-night cycle. Sympathetic activity was in excess when related to the unchanged motility. The hyperkinetic hypertension is expected to result in adverse remodeling of resistance vessels and to aggravate insulin resistance. To examine adverse effects of psychological stress, rats were subjected to intermittent food pellet feeding. Urinary catecholamines and cardiac norepinephrine stores were increased (p < 0.05). The depressed (p < 0.05) rate of Ca2+ uptake of sarcoplasmic reticulum is expected to contribute to cellular Ca2+ overload. These lifestyle influences strengthen the notion of an excess catecholamine syndrome which requires selective reduction of sympathetic outflow of the brain by I1-receptor agonists. | {
"pile_set_name": "PubMed Abstracts"
} |
Modulation of human α4β2 nicotinic acetylcholine receptors by brominated and halogen-free flame retardants as a measure for in vitro neurotoxicity.
Brominated flame retardants (BFRs) are abundant persistent organic pollutants with well-studied toxicity. The toxicological and ecological concern associated with BFRs argues for replacement by safer alternatives. However, the (neuro)toxic potential of alternative halogen-free flame retardants (HFFRs) is unknown. Previous research identified the nervous system as a sensitive target organ for BFRs, with modulation of excitatory nicotinic acetylcholine (nACh) receptors as one of the modes of action. Since it is essential to assess the (neuro)toxic potential of HFFRs before large scale use, we measured the effects of three BFRs and 13 HFFRs on the function of human α(4)β(2) nACh receptors, expressed in Xenopus oocytes, using the two-electrode voltage-clamp technique. The results demonstrate that some BFRs (TBBPA and to a lesser extent BDE-209) and HFFRs (TPP, Alpi, APP, MMT and to a lesser extent ATH, ATO, MHO, MPP, RDP and ZHS) act as nACh receptor antagonists. Contrary, BPS, BDP, DOPO and ZS were unable to modulate nACh receptors. Despite the lack of toxicological data on HFFRs and the need for additional studies to perform a full (neuro)toxic risk assessment, the current data on antagonistic effects on nACh receptors could be an important step in prioritizing viable HFFRs for substitution of BFRs. | {
"pile_set_name": "PubMed Abstracts"
} |
Interacting gears synchronize propulsive leg movements in a jumping insect.
Gears are found rarely in animals and have never been reported to intermesh and rotate functionally like mechanical gears. We now demonstrate functional gears in the ballistic jumping movements of the flightless planthopper insect Issus. The nymphs, but not adults, have a row of cuticular gear (cog) teeth around the curved medial surfaces of their two hindleg trochantera. The gear teeth on one trochanter engaged with and sequentially moved past those on the other trochanter during the preparatory cocking and the propulsive phases of jumping. Close registration between the gears ensured that both hindlegs moved at the same angular velocities to propel the body without yaw rotation. At the final molt to adulthood, this synchronization mechanism is jettisoned. | {
"pile_set_name": "PubMed Abstracts"
} |
Removal of a large number of foreign bodies in the maxillofacial region with navigation system.
The removal of a large number of foreign bodies in the maxillofacial region can be complicated and challenging. In this case report, a specific strategy for removal of multiple foreign bodies in the maxillofacial region is presented. A girl diagnosed with 24 foreign bodies in her left lower face and neck underwent the surgery using a computer-assisted navigation system. A specific strategy was used in this case, which included from one sub-region to the next and from the easiest to the most difficult. This strategy is recommended for the removal of a large number of foreign bodies in the maxillofacial region with a navigation system. | {
"pile_set_name": "PubMed Abstracts"
} |
Efficient and persistent transduction of exocrine and endocrine pancreas by adeno-associated virus type 8.
Efficient delivery of therapeutic proteins into the pancreas represents a major obstacle to gene therapy of pancreatic disorders. The current study compared the efficiency of recombinant lentivirus and adeno-associated virus (AAV) serotypes 1, 2, 5, 8 vectors delivered by intrapancreatic injection for gene transfer in vivo. Our results indicate that lentivirus and AAV 1, 2, 8 are capable of transducing pancreas with the order of efficiency AAV8 >>AAV1 > AAV2 >/= lentivirus, whereas AAV5 was ineffective. AAV8 resulted in an efficient, persistent (150 days) and dose-dependent transduction in exocrine acinar cells and endocrine islet cells. Pancreatic ducts and blood vessels were also transduced. Extrapancreatic transduction was restricted to liver. Leukocyte infiltration was not observed in pancreas and blood glucose levels were not altered. Thus, AAV8 represents a safe and effective vehicle for therapeutic gene transfer to pancreas in vivo. | {
"pile_set_name": "PubMed Abstracts"
} |
Levodopa induced motor complications in Thai Parkinson's disease patients.
Long-term levodopa usage in Parkinson's disease (PD) patients is known to cause several motor complications. It may be related to several factors such as levodopa dosage, duration of treatment and severity of disease. To study the prevalence of levodopa motor complications and associated factors in Thai Parkinson's disease patients. The authors prospectively collected baseline characteristics of PD patients, details of treatment and complications from 3 hospitals in various parts of Thailand. These patients were diagnosed by UK PD Brain Bank criteria. A total of 154 patients aged 68.1 +/- 9.5 years were recruited. Age of onset was 61.2 +/- 9.8 years. Most patients were in Hoehn-Yahr stage 1-3. The common clinical features were bradykinesia, rigidity and resting tremor Treatments were levodopa (98.1 per cent), anticholinergic (29.9 per cent), dopamine agonists (26 per cent) and COMT inhibitor (9.1 per cent). Eighty-five per cent of the patients had excellent response to levodopa. However, 25 per cent of patients developed motor complications, which were wearing off (79 per cent), on-off fluctuation (45 per cent), freezing (42 per cent), morning dyskinesia (10.5 per cent) and permanent dyskinesia (23.7 per cent). Twelve patients developed severe levodopa induced chorea. Factors associated with levodopa side effects were earlier age of onset, long duration of disease, advanced stage, higher levodopa dosage and long duration of levodopa treatment. In the present study, age of onset was inversely correlated with H-Y stage, while dosage of levodopa was positively correlated with H-Y stage but inversely correlated with lower ADL score, which may be due to advanced disease state. Levodopa motor complications are common in Thai PD patients. Wearing off on-off fluctuation and freezing are common forms of motor complications. | {
"pile_set_name": "PubMed Abstracts"
} |
A new analytical method based on anti-EPO monolith column and LC-FAIMS-MS/MS for the detection of rHuEPOs in horse plasma and urine samples.
Recombinant human erythropoietin (rHuEPO) is a 30-34 kDa glycoprotein banned by the racing authorities. For some years this molecule has been detected in race horses in USA and in Europe, and even in racing camels. Although direct methods to differentiate horse endogenous EPO and rHuEPO have been developed either by LC-MS/MS or by isoelectric focusing (IEF) with double-blotting, the short confirmation time of such prohibited hormone in plasma remains a problem for horseracing doping control laboratories. In order to improve the rHuEPOs confirmation process in horse plasma or urine in terms of reliability and delay, a small anti-EPO monolith membrane contained in a disposable column (anti-EPO monolith column) has been successfully used and validated (n = 10). This new sample preparation, combined with LC-FAIMS-MS/MS, has been performed on plasma and urine samples collected from one horse which received an Eprex® treatment during six consecutive days and a second one with a single injection of Aranesp®. This inventive technology allowed the possibility to confirm the presence of rHuEPO within one day with a limit of detection validated for both urine and plasma at 250 pg mL(-1) by means of a disposable, ready to use immunoaffinity column. The lower limit of detection (LLOD) obtained for each matrix was 100 pg mL(-1). These results provide an important improvement for rHuEPO doping control in horseracing especially the possibility to confirm these banned molecules in both matrices, urine and plasma, with a confidence of two specific target peptides. | {
"pile_set_name": "PubMed Abstracts"
} |
Noosa, 2 years later… a critical analysis of recent literature.
Since the second World Congress on the Abdominal Compartment Syndrome (WCACS) in Noosa 2 years ago, interest and publications on intra-abdominal hypertension (IAH) and ACS have increased exponentially. This paper aimed to critically review recent publications and put this new data into the context of already acquired knowledge concerning IAH/ACS. A Medline and PubMed search was performed from January 2005 up to now using "intra-abdominal pressure (IAP)", "intra-abdominal hypertension (IAH)", "abdominal compartment syndrome (ACS)" and "decompressive laparotomy" as search items. Although consensus definitions of IAH/ACS have been formulated recently, data on awareness are still disconcerting. Several groups refined current IAP measurement techniques and tested new direct IAP measurement devices for use in selected subpopulations. A series of recent publications identified specific patient subpopulations in IAH/ACS, like patients with burns or severe acute pancreatitis, with their specific pathophysiology and therapy. Although many studies already assessed the effect of elevated IAP on regional and micro-circulatory organ perfusion, a number of new publications attempted to unravel the link between elevated IAP and more "downstream" organ function or histology. Finally, therapy for IAH/ACS still reveals more questions than it answers. Global resuscitation does not necessarily equate with organ resuscitation. In fact, fluid-resuscitation may even induce IAH/ACS. After publication of consensus guidelines on IAH/ACS, there is an urgent need for human intervention studies and, in parallel, clinically relevant animal models. Given moderately low incidence of ACS and the complex and interrelated pathologies of the critically ill patient with IAH/ACS, large animal models of pathology-induced IAH/ACS might create the opportunity to gain clinically relevant knowledge on the treatment of IAH/ACS. | {
"pile_set_name": "PubMed Abstracts"
} |
Renal disease as a predictor of increased mortality among patients with rheumatoid arthritis.
Mortality among RA patients and controls was analyzed with special attention to renal disease in population-based material (originally screened in 1988) of 604 patients with RA (470 females, 134 males) and 457 age- and sex-matched controls (352 females, 105 males). In the original RA population, isolated hematuria (HU) was observed in 54, isolated proteinuria (PU) in 27, combined hematuria and proteinuria (HUPU) in 7, chronic renal failure (CRFtot) in 36 and isolated chronic renal failure without HU or PU (CRFisol) in 15 patients. Among the controls, HU was observed in 39, PU in 11, CRFtot in 32 and CRFisol in 16 subjects. HUPU was not observed in any of the controls. Microalbuminuria (20-200 microg/min) was observed in 34 RA patients and in 27 controls. Histologically confirmed amyloidosis was found in 13 RA patients and mesangial glomerulonephritis (MesGN) in 17 patients. The mortality was evaluated in 1999 from data of the Statistical Office of Finland. Statistical analysis was performed by Cox regression analysis. Mortality was significantly increased in the RA population as compared to controls: hazard ratio (HR) 1.78 (95% CI 1.34-2.31) for all RA patients; HR 2.12 (1.52-2.94) for females; HR 1.15 (0.75-1.77) for males. In the RA material, increased mortality was detected in patients with HUPU (HR 4.45; 1.54-12.84), PU (HR 3.54; 1.88-6.65), CRFtot (HR 3.74; 2.55-5.56) or microalbuminuria (HR 2.77; 1.64-4.69) when compared to those with normal clinical renal findings, whereas HU (HR 1.49; 0.88-2.52), CRFisol (HR 1.71; 0.82-3.54), bacteriuria (HR 0.96; 0.35-2.59) or pyuria (HR 0.65; 0.09-4.65) did not predict mortality. Renal amyloidosis was associated with an over twofold mortality rate (HR 2.31; 1.03-5.15), whereas mortality was within expected limits in RA patients with MesGN (HR 1.61; 0.49-5.24). Our results show that nephropathy presenting with combined hematuria and proteinuria, proteinuria, microalbuminuria or histologically confirmed amyloidosis is associated with increased mortality in RA patients, whereas mortality is within expected limits in those with isolated hematuria or mesangial glomerulonephritis. | {
"pile_set_name": "PubMed Abstracts"
} |
Ferric and ferrous iron in nitroso-myoglobin: computer simulations of stable and metastable States and their infrared spectra.
The binding of NO to iron is involved in the biological function of many heme proteins. Contrary to ligands like CO and O(2), which only bind to ferrous (Fe(II)) iron, NO binds to both ferrous and ferric (Fe(III)) iron. In a particular protein, the natural oxidation state can therefore be expected to be tailored to the required function. Herein, we present an ab initio potential-energy surface for ferric iron interacting with NO. This potential-energy surface exhibits three minima corresponding to eta(1)-NO coordination (the global minimum), eta(1)-ON coordination and eta(2) coordination. This contrasts with the potential-energy surface for Fe(II)-NO, which exhibits only two minima (the eta(2) coordination mode for Fe(II) is a transition state, not a minimum). In addition, the binding energies of NO are substantially larger for Fe(III) than for Fe(II). We have performed molecular dynamics simulations for NO bound to ferric myoglobin (Mb(III)) and compare these with results obtained for Mb(II). Over the duration of our simulations (1.5 ns), all three binding modes are found to be stable at 200 K and transiently stable at 300 K, with eventual transformation to the eta(1)-NO global-minimum conformation. We discuss the implication of these results related to studies of rebinding processes in myoglobin. | {
"pile_set_name": "PubMed Abstracts"
} |
Negative feedback by SNAI2 regulates TGFβ1-induced amelotin gene transcription in epithelial-mesenchymal transition.
Junctional epithelium (JE) demonstrates biological responses with the rapid turnover of gingival epithelial cells. The state occurs in inflammation of gingiva and wound healing after periodontal therapy. To understand the underlying mechanisms and to maintain homeostasis of JE, it is important to investigate roles of JE-specific genes. Amelotin (AMTN) is localized at JE and regulated by inflammatory cytokines and apoptotic factors that represent a critical role of AMTN in stabilizing the dentogingival attachment, which is an entrance of oral bacteria. In this study, we demonstrated that the AMTN gene expression was regulated by SNAI2 and transforming growth factor β1 (TGFβ1)-induced epithelial-mesenchymal transition (EMT) that occurs in wound healing and fibrosis during chronic inflammation. SNAI2 downregulated AMTN gene expression via SNAI2 bindings to E-boxes (E2 and E4) in the mouse AMTN gene promoter in EMT of gingival epithelial cells. Meanwhile, TGFβ1-induced AMTN gene expression was attenuated by SNAI2 and TGFβ1-induced SNAI2, without inhibition of the TGFβ1-Smad3 signaling pathway. Moreover, SNAI2 small interfering RNA (siRNA) rescued SNAI2-induced downregulation of AMTN gene expression, and TGFβ1-induced AMTN gene expression was potentiated by SNAI2 siRNA. Taken together, these data demonstrated that AMTN gene expression in the promotion of EMT was downregulated by SNAI2. The inhibitory effect of AMTN gene expression was an independent feedback on the TGFβ1-Smad3 signaling pathway, suggesting that the mechanism can be engaged in maintaining homeostasis of gingival epithelial cells at JE and the wound healing phase. | {
"pile_set_name": "PubMed Abstracts"
} |
Fluctuated changes in the rat hypothalamic content of corticotropin releasing factor around the peak of the circadian rhythm.
It is well known that hypothalamic corticotropin releasing factor (CRF) activity shows a marked circadian rhythm with the peak around 16 o'clock and the minimal level around 8 o'clock, followed by almost parallel changes of plasma corticosterone. But the circadian variations of CRF activity at short intervals (22 or 23 min) around 16 o'clock has not been obvious. In this experiment, we demonstrated fluctuated changes of CRF content in the non-stressed rat hypothalamus with 22 or 23 min intervals around the peak at a quarter past 16 o'clock. | {
"pile_set_name": "PubMed Abstracts"
} |
Applying the methodology of Design of Experiments to stability studies: a Partial Least Squares approach for evaluation of drug stability.
The aim of the present research is to show that the methodology of Design of Experiments can be applied to stability data evaluation, as they can be seen as multi-factor and multi-level experimental designs. Linear regression analysis is usually an approach for analyzing stability data, but multivariate statistical methods could also be used to assess drug stability during the development phase. Data from a stability study for a pharmaceutical product with hydrochlorothiazide (HCTZ) as an unstable drug substance was used as a case example in this paper. The design space of the stability study was modeled using Umetrics MODDE 10.1 software. We showed that a Partial Least Squares model could be used for a multi-dimensional presentation of all data generated in a stability study and for determination of the relationship among factors that influence drug stability. It might also be used for stability predictions and potentially for the optimization of the extent of stability testing needed to determine shelf life and storage conditions, which would be time and cost-effective for the pharmaceutical industry. | {
"pile_set_name": "PubMed Abstracts"
} |
Interchangeability between heart rate and photoplethysmography variabilities during sympathetic stimulations.
Photoplethysmography variability (PPGV) is currently considered to be a good surrogate to heart rate variability (HRV) measurements using the time between two pulse waves instead of RR intervals. Nevertheless, the interchangeability between HRV and PPGV has never been evaluated in situations with severe alterations in the autonomic nervous system (ANS). We aimed to identify the conditions for a correct utilization of PPGV in evaluating the consequences of sympathetic stimulations. Nine subjects performed three tests: active orthostatic test, slow walk and moderate and exhaustive cycling exercises in the supine position. Pulse waves at the fingertip and RR intervals were recorded at the same time. We used correlations and the Bland and Altman method to compare and evaluate interchangeability between several HRV indices. Bland and Altman analysis highlighted small discrepancies between PPGV and HRV for all HRV indices in the supine position and for LF(ms)(2), HF(ms)(2), LF(peak) and RMSSD in the upright position. During the slow walk, it was impossible to detect properly PPG peaks. We observed large differences between the two methods during the cycling exercise. In conclusion, PPGV can be used instead of HRV without reserve in the supine position but only for some HRV indices in the upright position and not during slow walk and cycling exercise. | {
"pile_set_name": "PubMed Abstracts"
} |
Operational taxonomic units (OTUs) of endophytic bacteria isolated from banana cultivars in the Amazon.
Endophytic microorganisms colonize plants, inhibit the growth of pathogens (by competing for nutrients and/or space), or produce antagonistic substances. Fifty-five endophytic bacteria were isolated from the leaf tissue of the FHIA 18 banana cultivar. Genetic diversity analyses were performed using the enterobacterial repetitive intergenic consensus sequence polymerase chain reaction method and BOX molecular markers. These analyses resulted in 33 and 21 polymorphic bands, respectively. The similarity data, obtained using the Dice coefficient based on the polyphasic analysis method, ranged from 22 to 100%. This indicated a high genetic diversity among the analyzed isolates. Sixty percent similarity was utilized as the cut-off criterion for the formation of operational taxonomic units (OTUs); this resulted in the identification of 32 possible OTUs, indicating a high number of potential species. | {
"pile_set_name": "PubMed Abstracts"
} |
Association between nutrition knowledge and nutritional intake in middle-aged men from Northern France.
The way in which nutrition knowledge transforms into dietary behaviour and nutrient intake may vary among populations. Therefore, the goal of the study was to examine whether nutrition knowledge is associated with nutritional intake in middle-aged men who are at major risk of cardiovascular disease. Cross-sectional population study aimed at comparing the response to a nutrition quiz with food habits and nutrient intake determined by a 3-day food record. Men of the Urban Community of Lille (France) examined at home. 361 men aged 45-64 y, randomly selected from the electoral rolls. Subjects were separated in a high-score and a low-score group according to their responses to the nutrition quiz. Subjects in the high-score group had better educational and higher income levels than those from the low-score group. Multivariate analysis, adjusting on educational and socio-economic levels and other confounding variables - such as age, body mass index, cigarette smoking, physical activity and energy intake underreporting - showed that subjects in the high-score group were more often consumers of olive oil (36 vs. 12%; ), cheese (85 vs. 76%; or cereals (27 vs. 15%; and less often consumers of sunflower oil (51 vs. 68%; or dry vegetables (12 vs. 22%; than those in the low-score group. Subjects in the high-score group had lower intakes of fat vs. and especially of monounsaturated fat of animal origin vs. than individuals in the low-score group. Nutrition quiz score is associated with specific patterns of food choices and nutrient intake suggesting that nutrition knowledge influences dietary behaviour in middle-aged men from Northern France. | {
"pile_set_name": "PubMed Abstracts"
} |
Hypomagnesemia and hypophosphatemia at admission in patients with severe head injury.
Low serum levels of electrolytes such as magnesium (Mg), potassium (K), calcium (Ca), and phosphate (P) can lead to a number of clinical problems in intensive care unit (ICU) patients, including hypertension, coronary vasoconstriction, disturbances in heart rhythm, and muscle weakness. Loss of these electrolytes can be caused, among other things, by increased urinary excretion. Cerebral injury can lead to polyuresis through a variety of mechanisms. We hypothesized that patients with cranial trauma might be at risk for electrolyte loss through increased diuresis. The objective of this study was to assess levels of Mg, P, and K at admission in patients with severe head injury. We measured plasma levels of Mg, P, K, Ca, and sodium at admission in 18 consecutive patients with severe head injury admitted to our ICU (group 1). As controls, we used 19 trauma patients with two or more bone fractures but no significant cranial trauma (group 2). University teaching hospital. Eighteen patients with severe head injury admitted to our surgical ICU (group 1) and 19 controls (trauma patients with no significant cranial trauma; group 2). Electrolyte levels at admission (group 1 vs. group 2; mean +/- SD, units: mmol/L) were as follows. Mg, 0.57 +/- 0.17 (range, 0.24-0.85) vs. 0.88 +/- 0.21 (range, 0.66-1.42 mmol/L; p < .01). P, 0.56 +/- 0.15 (range, 0.20-0.92) vs. 1.11 +/- 0.15 (range, 0.88-1.44 mmol/L; p < .01). K, 3.54 +/- 0.59 (range, 2.4-4.8) vs. 4.07 +/- 0.45 (range, 3.6-4.8 mmol/L; p < .02). Ca, 2.02 +/- 0.24 (range, 1.45-2.51) vs. 2.14 +/- 0.20 (range, 1.88-2.46; p = NS). In group 1, 12/18 patients had Mg levels <0.70 mmol/L vs. 2/19 patients in group 2 (p < .01); in group 1, 11/18 patients had P levels below 0.60 mmol vs. 0/19 patients in group 2 (p < .01). Moderate hypokalemia (K levels, <3.6 mmol/L) was present in 8/18 patients in group 1 vs. 1/19 patients in group 2 (p < .01). Severe hypokalemia (K levels, < or =3.0) was present in 4/18 patients in group 1 vs. 0/19 patients in group 2 (p < .05). We conclude that patients with severe head injury are at high risk for the development of hypomagnesemia, hypophosphatemia, and hypokalemia. One of the causes of low electrolyte levels in these patients may be an increase in the urinary loss of various electrolytes caused by neurologic trauma. Mannitol administration may be a contributing factor. Intensivists should be aware of this potential problem. If necessary, adequate supplementation of Mg, P, K, and Ca should be initiated promptly. | {
"pile_set_name": "PubMed Abstracts"
} |
An unexpected role for RNA in the recognition of DNA by the innate immune system.
A central function of our innate immune system is to sense microbial pathogens through the presence of their nucleic acid genomes or their transcriptional or replicative activity. In mammals, a receptor-based system is mainly responsible for the detection of these "non self" nucleic acids. Tremendous progress has been made in the past years in identifying the host constituents that are required for this intricate task. With regard to the sensing of RNA genome based pathogens by our innate immune system, a picture is emerging that includes certain families of the toll-like receptor family (TLR3, TLR7, TLR8) and the RIG-I like helicases (RIG-I, MDA5 and LGP2). Genetic loss of function studies implicate that the absence of these pathways can lead to a complete lack of recognition of certain RNA viruses. At the same time, intracellular DNA can also trigger potent innate immune responses, yet the players in this field are less clear. We and another group have recently identified a role for RNA polymerase III in the conversion of AT-rich DNA into an RNA ligand that is sensed by the RIG-I pathway. In this review article, we will discuss the mechanisms and implications of this novel pathway. | {
"pile_set_name": "PubMed Abstracts"
} |
[Arteriovenous shunting in obesity, its relation to lung volume].
Thirty-five patients with an average overweight of 67.1% were studied. Pulmonary restriction of a variable degree was found in 68.6/; in 60% due to reduction of respiratory reserve volume. Bronchial obstruction was detected in 57% as measured by forced midexpiratory flow (25-75%). In addition, 14% showed a decrease of 75-85% in forced expiratory flow, which suggested that the pathology was located in the small respiratory airways. The PaO2 while breathing room air and in a resting state was of 52.6 +/- 9.42 mmHg, and after breathing it increased to 69.07 +/- 11.01 mmHg. The PaO2 breathing inspiratory fractions of 99.6% O2 in a resting condition was 309.34 +/- 70.07 mmHg, and after deep breathing it rose to 354.0 +/- 64.27 mmHg. The mechanisms which produce hypoxemia in the obese were analysed and it was concluded that they were due fundamentally to alterations of the ventilation perfusion ratio and to an increase of the venous-arterial shunt. In some cases, alveolar hypoventilation contributed (Pickwick syndrome). By increasing the pulmonary volume with deep breathing, the ventilation perfusion ratio improves or becomes normal, likewise, the venous-arterial shunt can improve or persist as the only cause of hypoxemia. | {
"pile_set_name": "PubMed Abstracts"
} |
PTGDR polymorphisms and susceptibility to asthma: a meta-analysis.
The aim of this study was to explore whether prostaglandin D2 receptor (PTGDR) polymorphisms confer susceptibility to asthma. A meta-analysis was conducted on the associations between the PTGDR -549 C/T, -441 C/T, and -197 C/T polymorphisms and asthma using: (1) allele contrast, (2) the recessive model, (3) the dominant model, and (4) the additive model. Three polymorphism haplotypes were constructed in the order -549/-441/-179. Meta-analysis was performed on the haplotype CCC (high transcriptional activity) and of TCT (low transcriptional activity). A total of 13 separate comparative studies in 9 articles involving 7,155 patients with asthma and 7,285 control subjects were included in this meta-analysis. An association between asthma and the PTGDR -549 C/T polymorphism was found by allele contrast (OR = 1.133, 95 % CI = 1.004-1.279, P = 0.043). Ethnicity-specific meta-analysis showed an association between asthma and the PTGDR -549 C allele in Europeans (OR = 1.192, 95 % CI = 1.032-1.377, P = 0.017). Furthermore, stratifying subjects by age indicated an association between the PTGDR -549 C allele and asthma in adults (OR = 1.248, 95 % CI = 1.076-1.447, P = 0.003), but no association in children (OR = 0.933, 95 % CI = 0.756-1.154, P = 0.324). Analyses using the dominant and additive models showed the similar pattern as that observed for the PTGDR -549 C allele, that is, a significant association in Europeans and adults, but not in children. No association was found between asthma and the PTGDR -441 C/T or -197 C/T polymorphisms, and meta-analysis stratified by ethnicity and age also revealed no association between asthma and these polymorphisms. Furthermore, no association was found between asthma and the CCC and TCT haplotypes of PTGDR, and meta-analysis stratified by ethnicity and age revealed no association between asthma and the CCC and TCT PTGDR haplotypes. This meta-analysis demonstrates that the PTGDR -549 C/T polymorphism confers susceptibility to asthma in Europeans and adults. However, no association was found between the PTGDR 441 C/T and -197 C/T polymorphisms or the CCC and TCT haplotypes and asthma susceptibility. | {
"pile_set_name": "PubMed Abstracts"
} |
Insulin and wound healing.
Skin is a dynamic and complex organ that relies on the interaction of different cell types, biomacromolecules and signaling molecules. Injury triggers a cascade of events designed to quickly restore skin integrity. Depending on the size and severity of the wound, extensive physiological and metabolic changes can occur, resulting in impaired wound healing and increased morbidity resulting in higher rates of death. While wound dressings provide a temporary barrier, they are inherently incapable of significantly restoring metabolic upsets, post-burn insulin resistance, and impaired wound healing in patients with extensive burns. Exogenous insulin application has therefore been investigated as a potential therapeutic intervention for nearly a century to improve wound recovery. This review will highlight the important achievements that demonstrate insulin's ability to stimulate cellular migration and burn wound recovery, as well as providing a perspective on future therapeutic applications and research directions. | {
"pile_set_name": "PubMed Abstracts"
} |
The influence of repeated transfusions and cyclosporine on secondary alloantibody responses in inbred rats.
The influence of cyclosporine (CsA) on secondary and established alloantibody responses was evaluated in inbred Lewis rats and (AO x PVG)F1 hybrid rats. Lewis rats received weekly transfusions of DA whole blood for 8 weeks either with or without cyclosporine (15 mg/kg/day) after sensitization with DA splenocytes. Hybrid rats received only CsA (10 mg/kg/day) after similar sensitization. Administration of CsA did not affect the spontaneous decline in alloantibody titers against class I (RT1A) antigens, but it was associated with a significantly reduced response to class II (RT1B) antigens at the end of the study. CsA prevented maintenance of high alloantibody titers to RT1A antigens in Lewis rats transfused repeatedly following sensitization. IgG alloantibody subclass responses were also altered by CsA with significant reduction in titers of IgG1, 2a, and 2b against RT1A antigens in rats transfused repeatedly; CsA did not, however, suppress IgG2c alloantibody levels in these animals. Responses to public RT1A antigens disappeared in most animals irrespective of their treatment group, whereas those to private and public RT1B antigens persisted unless CsA was administered. The results suggest that, contrary to results obtained with other antigens, CsA does influence secondary alloantibody responses. CsA may thus prove of value in highly sensitized dialysis patients who require further blood transfusions. | {
"pile_set_name": "PubMed Abstracts"
} |
[Is lanthanum carbonate a safe drug?].
Lanthanum carbonate is drawing attention as a new effective oral phosphate binder. This drug shares a character that "heavy metal that is not the natural constituent of human body and ionizes into free cations in gastrointestinal tract" with aluminum hydroxide gel. In fact, although the amount is much less than that of aluminum hydroxide gel, lanthanum is absorbed through intestine and accumulated in the body. Fortunately, there has been no report about the toxicity of such accumulated lanthanum. However, it does never mean that "lanthanum carbonate is harmless", since it usually takes years to demonstrate metal toxicity. | {
"pile_set_name": "PubMed Abstracts"
} |
Anticonvulsant activity of alcoholic extract of bark of Pinus roxburghii Sarg.
To study the anticonvulsant activity of alcoholic extract of bark of Pinus roxburghii Sarg. (AEPR) used in Indian traditional medicine system in treating convulsion. Anticonvulsant activity was evaluated by maximal electroshock (MES) and pentylenetetrazole (PTZ)-induced seizures in Wistar albino rats. In the MES model, 150 mA current for 0.2 s was given through ear electrodes to induce convulsions in rats. The duration of tonic extension of hind limb was used as the end point, namely, prevention or decrease in the duration of hind limb extension was considered as a protective action. In the PTZ model, the anticonvulsant property of AEPR was assessed by its ability to delay the onset of myoclonic spasm and clonic convulsions produced by intraperitoneal administration of PTZ. In the MES-induced seizure model, AEPR in doses of 300 and 500 mg/kg body weight reduced all the phases of convulsion significantly (P<0.01). Standard drug phenytoin at a dose of 25 mg/kg significantly reduced flexion phase (P<0.01) and abolished all phases of convulsion. In the PTZ-induced seizure model, the administration of the extract at doses of 300 and 500 mg/kg 30 min prior to injection of PTZ significantly delayed the onset of clonic seizure (P<0.01). AEPR at the dose of 100 mg/kg body weight could not exert any significant protective effect on PTZ-induced convulsions. Standard drug diazepam at a dose of 4 mg/kg showed much delayed onset of clonic seizure. The study suggests that AEPR would be effective against generalized tonic-clonic and partial seizures. Thus AEPR possesses anticonvulsant property against MES- and PTZ-induced seizures in Wistar rats. However, further research is in progress to isolate the compound responsible for its activity. | {
"pile_set_name": "PubMed Abstracts"
} |
Activation of GPR81 by lactate inhibits oscillatory shear stress-induced endothelial inflammation by activating the expression of KLF2.
Atherosclerosis is a common and deadly cardiovascular disease with extremely high prevalence. Areas of the vasculature exposed to oscillatory shear stress (OSS) or disturbed blood flow are particularly prone to the development of atherosclerotic lesions. In part, various mechanosensitive receptors on the surface of endothelial cells play a role in regulating the ability of the vasculature to cope with variations in blood flow patterns. However, the exact mechanisms behind flow-mediated endothelial responses remain poorly understood. Along with the development of highly specific receptor agonists, the class of G coupled-protein receptors has been receiving increasing attention as potential therapeutic targets. G coupled-protein receptor 81 (GPR81), also known as hydroxycarboxylic acid receptor 1 (HCA1 ), is activated by lactate, its endogenous ligand. In the present study, we show for the first time that expression of GPR81 is significantly downregulated in response to OSS in endothelial cells and that activation of GPR81 using physiologically relevant doses of lactate can rescue OSS-induced reduced GPR81 expression. Importantly, our findings demonstrate that activation of GPR81 can exert valuable atheroprotective effects in endothelial cells exposed to OSS by reducing oxidative stress and significantly downregulating the expression of inflammatory cytokines including interleukin (IL)-6, IL-8, monocyte chemoattractant protein (MCP)-1, and high mobility group box 1 (HMGB1). We also show that activation of GPR81 can potentially prevent the attachment of monocytes to the endothelium by suppressing OSS-induced secretion of vascular cellular adhesion molecule (VCAM)-1 and endothelial-selectin (E-selectin). Finally, we show that activation of GPR81 can rescue OSS-induced reduced expression of the key atheroprotective transcription factor Kruppel-like factor 2 (KLF2), which is mediated through the extracellular-regulated kinase 5 (ERK5) pathway. These findings demonstrate a potential protective role of GPR81 against atherogenesis and that targeted activation of GPR81 may inhibit endothelial inflammation and dysfunction induced by OSS. | {
"pile_set_name": "PubMed Abstracts"
} |
Immediate knowledge increase from an oral cancer information leaflet in patients attending a primary health care facility: a randomised controlled trial.
The aim was to determine the immediate influence of a validated patient information leaflet (PIL) on oral cancer and knowledge in primary care attenders. Participants were patients (n=800) attending their primary health care provider from 14 general practices (eight dental and six medical) in the north west of England. Measures were a previously validated knowledge questionnaire (36 dichotomous items), self-reported dental service attendance history and demographic variables. The results showed that patients who had read the oral cancer PIL demonstrated a significant increase in knowledge regardless of clinical setting (F[1,739]=246.24, P<0.0001). Patients showed improvements in selecting the correct signs and risk factors associated with disease. Immediate knowledge gain from a simple PIL about oral cancer was found and independent of the primary care facility, where the PIL was distributed. | {
"pile_set_name": "PubMed Abstracts"
} |
[Not Available].
Summary In human beings, androgen metabolism plays an important role in mediating the action of male hormones upon target structures of the skin. First, human skin is capable of transforming inactive steroids supplied through the blood, such as androstenedione and dehydroisoandrosterone, into the active androgen testosterone. Second, human skin is able to reduce testosterone to 5alpha-DHT, an essential prerequisite, during embryogenesis, for the male differentiation of target structures derived from urogenital sinus. At puberty, hair growth in sexual areas of skin also requires the transformation of testosterone to DHT. Regulation of 5alpha-reductase activity varies according to the anatomical site of the enzyme. In foetuses, 5alpha-reductase activity present in tissues derived from the urogenital tract does not seem to be androgen-dependent, since it is acquired before the onset of testosterone secretion by foetal testis. By contrast, the enzyme that mediates development of certain secondary sex characteristics, such as pilosebaceous gland activity in sexual areas, is clearly androgen-dependent, since it is absent before puberty and in persons with hypogonadism. These differences in the control of the 5alpha-reductase activity mediating the appearance of either primary or secondary sex characteristics are important and may explain the differences in 5a-reductase activity observed in adult skin of both sexes derived from different sexual areas. In addition, the knowledge of androgen relation to the skin is necessary in order to understand the action of the anti-androgens, particularly the compounds which may be used by topical administration. | {
"pile_set_name": "PubMed Abstracts"
} |
Persistent hypoglossal artery and its variants diagnosed by CT and MR angiography.
Persistent hypoglossal artery (PHA) is the second most common anastomosis between the carotid and vertebrobasilar systems and demonstrates some variations. We evaluated the prevalence of PHA on computed tomography (CT) angiography. We also evaluated characteristic features of PHA and its variants on magnetic resonance (MR) angiography. We retrospectively reviewed our database of 2,074 CT angiographic images obtained using either of two 64-slice multidetector CT scanners. We also reviewed our database of 7,646 MR angiographic images obtained using either of two 1.5-T or one 3.0-T imager. We could not determine the exact number of patients whose MR angiography included the hypoglossal canal. Most patients had or were suspected of having cerebrovascular diseases. We found six usual PHAs arising from the cervical internal carotid artery on CT angiography among 2,074 patients. On MR angiography, we also found six additional usual PHAs (total 12, right/left = 6/6, male/female = 3/9), three right PHAs originating from the external carotid artery (ECA), and two posterior inferior cerebellar arteries (PICAs) arising from the ECA without connection to the vertebral artery. The prevalence of usual PHA diagnosed by CT angiography was 0.29 %, slightly higher than that reported for angiography and may be due to selection bias in the examined patients. We propose naming usual PHA "type 1 PHA"; PHA originating from the ECA, of which we found three, "type 2 PHA"; and PICA arising from the ECA, of which we found two, "type 2 PHA variant." | {
"pile_set_name": "PubMed Abstracts"
} |
[Comparative analysis of MDP bone imaging agents used in Taiwan].
Bone scans have been established as a major investigative procedure for various bone, muscle and joint diseases, and for the detection of bony metastases. MDP (methylene diphosphate) labeled with Tc-99m is currently used for bone imaging. The quality of bone imaging agents can affect the quality of the bone image. In this work we compared the quality control for three commercially available MDP kits (Daiichi, Amersham, NEN) in Taiwan, and the imaging quality among the various MDP kits. Our results revealed a slight difference of quality control in various brands of Tc-99m MDP. However, there was no significant difference in the imaging quality among the various MDP kits. | {
"pile_set_name": "PubMed Abstracts"
} |
Patients with non-substance-related disorders report a similar profile of childhood trauma experiences compared to heroin-dependent patients.
Exposure to traumatic events is common among patients with substance use disorders (SUD). In patients with non-substance-related disorders, especially with gambling disorders (GD) and internet addiction (IA), traumatic childhood experiences have not been investigated extensively. The objective of this study was to compare trauma histories in patients with GD and IA to patients with heroin dependence. Cross-sectional surveys including the childhood trauma questionnaire (CTQ) and clinical data among 107 participants; 59 patients with non-substance-related disorders (GD [n = 39]; IA [n = 20]) were compared to 28 patients prescribed injectable heroin for opioid dependence in heroin-assisted treatment (HAT) and to a healthy control group (HC) (n = 20). The findings revealed a high prevalence of trauma exposure in all three clinical groups, with 74.4% of patients with GD, 80.0% of patients with IA, and 93.0% of patients in HAT compared to 40% in HC. All three groups (GD, IA, HAT) reported significantly higher levels of "emotional neglect" compared to HC. The results provide clinically relevant information suggesting that the burden of childhood traumatic experiences may be as common in patients with GD and IA as in patients with heroin dependence. These findings could pose an important starting-point for treatment. (Am J Addict 2017;26:215-220). | {
"pile_set_name": "PubMed Abstracts"
} |
Neurogenic tumors of the neck.
Neurogenic tumors of the neck occur in children and adults. Important parameters to aid in the differential diagnosis are age at presentation, location, and a history of NF or multiple endocrine neoplasia. Schwannoma is the most common solitary neurogenic tumor in the neck and is usually seen in patients between 20 and 50 years of age. The plexiform neurofibroma and multiple localized neurofibromas are characteristic of NF1. MPNSTs are uncommon aggressive lesions that can arise de novo in patients with NF (10% to 30%) and postirradiation. Neuroblastic tumors consist of neuroblastoma, ganglioneuroblastoma, and ganglioneuroma. These tumors typically arise in the chest and abdomen but occasionally present as a primary neck mass. A neck mass with a histologic diagnosis of neuroblastoma is, however, more commonly metastatic from an abdominal neuroblastoma. | {
"pile_set_name": "PubMed Abstracts"
} |
The water binding behavior of kappa-carrageenan determined by three different methods.
kappa-Carrageenan is a biopolymer extracted from red seaweeds which has been in the focus of pharmaceutical development for many years. Most applications make use of the large water binding capacity of kappa-carrageenan. The primary limitation of kappa-carrageenan is the variation in the substance quality. Therefore, the water binding capacity of different kappa-carrageenan products was investigated by dynamic vapor adsorption, freezing and non-freezing bound water and water retention value. The kappa-carrageenans were observed to have a higher water binding capacity than microcrystalline cellulose (MCC) in all three methods. The amount of adsorbed water is similar for all carrageenans. Differences between the carrageenan types (kappa, iota, and lambda) were remarkable for the freezing bound water and centrifugation bound water as well as between the kappa-carrageenans of different suppliers. | {
"pile_set_name": "PubMed Abstracts"
} |
A novel glycerophosphodiesterase from Bacillus pumilus.
A novel glycerophosphodiesterase activity was detected in extracts from phosphate-starved Bacillus pumilus DSM27 cells. The enzyme had a substrate specificity for glycerophosphodiester bonds and the reaction product formed with partially purified enzyme was (sn)-glycero-3-phosphate. Purified cell wall teichoic acid of the polyglycerophosphate type, as well as deacylated, unsubstituted lipoteichoic acid of the polyglycerophosphate type, di(glycerophospho)glycerol (deacylated cardiolipin) and mono(glycerophospho)glycerol (deacylated phosphatidylglycerol) served as substrates for the enzyme. Their native counterparts, however, cell wall-bound polyglycerophosphate, lipoteichoic acid (D-alanine substituted and dealanylated), cardiolipin and phosphatidylglycerol were poor or no substrates, respectively. Enzyme activity was inhibited by purified cell walls and by heparin. The enzyme was partially purified using a column of Heparin-Sepharose. | {
"pile_set_name": "PubMed Abstracts"
} |
Features of subsyndromal and persistent delirium.
Longitudinal studies of delirium phenomenology are lacking. We studied features that characterise subsyndromal delirium and persistent delirium over time. Twice-weekly evaluations of 100 adults with DSM-IV delirium using the Delirium Rating Scale-Revised-98 (DRS-R98) and Cognitive Test for Delirium (CTD). The generalised estimating equation method identified symptom patterns distinguishing full syndromal from subsyndromal delirium and resolving from persistent delirium. Participants (mean age 70.2 years (s.d. = 10.5)) underwent 323 assessments (range 2-9). Full syndromal delirium was significantly more severe than subsyndromal delirium for DRS-R98 thought process abnormalities, delusions, hallucinations, agitation, retardation, orientation, attention, and short- and long-term memory items, and CTD attention, vigilance, orientation and memory. Persistent full syndromal delirium had greater disturbance of DRS-R98 thought process abnormalities, delusions, agitation, orientation, attention, and short- and long-term memory items, and CTD attention, vigilance and orientation. Full syndromal delirium differs from subsyndromal delirium over time by greater severity of many cognitive and non-cognitive symptoms. Persistent delirium involves increasing prominence of recognised core diagnostic features and cognitive impairment. | {
"pile_set_name": "PubMed Abstracts"
} |
Lithium and hair texture.
Patients receiving lithium who had noticed changes in hair texture since starting that drug, described variously as hair losing its curl or wave, have a greater lithium concentration in hair than patients on lithium with no such complaints. | {
"pile_set_name": "PubMed Abstracts"
} |
Validation of the VISA-A questionnaire for Turkish language: the VISA-A-Tr study.
To evaluate the validity and reliability of the Turkish version of the Victorian Institute of Sports Assessment-Achilles (VISA-A) questionnaire for patients with Achilles tendinopathy. Fifty-five patients with a diagnosis of Achilles tendinopathy and 55 healthy subjects were included in the study. VISA-A questionnaires were translated and culturally adapted into Turkish. The final Turkish version (VISA-A-Tr) was tested for reliability on healthy individuals and patients. Tests for internal consistency, validity and structure were performed on 55 patients. The VISA-A-Tr showed good test-retest reliability (Pearson's r=0.99, p<0.001). The patients with Achilles tendinopathy had a significantly lower score (p<0.001) than the healthy individuals. The VISA-A-Tr score correlated significantly with the Stanish tendon grading system (Spearman's r=-0.86; p<0.001). The VISA-A-Tr is a valid and reliable tool for evaluating the severity of Achilles tendinopathy. | {
"pile_set_name": "PubMed Abstracts"
} |
A direct vasoconstrictor effect of mannitol on the renal artery.
The direct effect of mannitol on the renal artery was studied using spiral cut strips of canine renal arteries. Spiral strips were equilibrated in Krebs-Henseleit bicarbonate buffer at 37 degrees C. The strips contracted when challenged with increasing doses of mannitol. The force of contraction was directly proportional to the dose of mannitol used. Vasoconstriction is a direct effect of mannitol on the renal artery in the dose range of 10 to 70 milligrams per milliliter. This observation may explain some of the seemingly contradictory data which have accumulated in studies using mannitol. | {
"pile_set_name": "PubMed Abstracts"
} |
Phenobarbital prevents the inhibitory effects of tumor necrosis factor on glutathione-S-transferase mu in primary culture rat hepatocytes.
During inflammation and infection, overexpression of the tumor necrosis factor (TNF) is associated with changes in cytochromes P-450 levels in rat and human hepatocytes. The aim of this study was to investigate the effect of TNF on the expression of the glutathione-S-transferases (GSTs) in rat hepatocytes. TNF was added in vitro alone or simultaneously with phenobarbital (PB) into hepatocytes in primary culture or in vivo, before TNF, injected directly to rats. GST activity was assayed by spectrophotometry; protein GSTs alpha, mu and pi were evaluated by immunoblotting. When TNF was added alone to rat hepatocytes in vitro, total GST activity and GST alpha levels were not affected, while GST mu protein levels significantly decreased by 35%. GST pi protein was undetectable in hepatocytes whether treated or not with TNF. When PB was administered in vitro simultaneously to rat hepatocytes with TNF, the decrease observed for GST mu subunit was suppressed while total GST activity and GST alpha content were not affected. When hepatocytes were treated with TNF after PB given in vivo directly to the rat by i.p. injection, GST activity and GSTs subunits were induced by PB, while TNF did not exert any effect. These results indicate that TNF has an inhibitory effect on GST mu and PB abrogates this effect in primary cultured rat hepatocytes. Then, PB could prevent some TNF toxic effects. | {
"pile_set_name": "PubMed Abstracts"
} |
Irrigation eliminates smoke formation in laser laparoscopic surgery: ex vivo results.
To evaluate the desmoke effects of irrigation on surgical smoke generated during laser laparoscopic surgery using ex vivo model. A hand-piece was devised as both an irrigation tube and a laser fiber holder. The laser system used was a diode pumped continuous wave Thulium YAG laser (Lisa laser products OHG, Katlenburg-Lindau, Germany) emitting at 2.01-mum through a quartz fiber with a core diameter of 365 mum. Using a transparent container as experimental model (approximately 3 L in volume), 6 irrigation rates (0, 20, 40, 60, 80, and 100 mL/min) were tested combining with 4 laser power settings (20, 30, 40, and 50 W). To evaluate the desmoke efficiency of irrigation, lasing time with effective visibility under different combination of irrigation rates and laser powers were documented, and corresponding smoke generation rate were calculated (=3 L/lasing time). Analysis of variance was used to compare difference and significance was indicated at P<0.05. Calculated smoke generation rate was increased with laser power whereas decreased with irrigation rate. At 4 tested laser powers, calculated smoke generation rates were high (mean: 91.4 to 306.6 mL/s) when no water presented, but were significantly decreased (mean: 12.6 to 55.0 mL/s, P<0.001) with the lowest water flow rate (20 mL/min) and further decreased with higher rates. The proper range of irrigation rate for future clinical practice would be around 40 mL/min. Irrigation eliminates smoke formation accompanying laser tissue irradiation. It shows promise for future application in laser laparoscopic surgery. | {
"pile_set_name": "PubMed Abstracts"
} |
Subtyping of Y-chromosomal haplogroup E-M78 (E1b1b1a) by SNP assay and its forensic application.
The continual discovery of new single-nucleotide polymorphisms (SNPs) has led to an increased resolution of the Y chromosome phylogeny. Some of these Y-SNPs have shown to be restricted to small geographical regions and therefore may prove useful in the forensic field as tools for the prediction of population of origin of unknown casework samples. Here, we describe a system for the molecular dissection of haplogroup E-M78 (E1b1b1a), consisting of multiplex polymerase chain reaction and minisequencing of M78 and nine population-informative Y-SNPs (M148, M224, V12, V13, V19, V22, V27, V32, V65) in a single reaction. Sensitivity and admixture studies demonstrated that the SNP protocol allows robust genotyping from as little as 50 pg of male DNA, even in the presence of 500-fold amounts of female DNA. In order to evaluate the suitability of E1b1b1a, subhaplogrouping for population-of-origin prediction, the distribution of E-M78 and its derived variants was determined in an Italian population sample (n = 326). | {
"pile_set_name": "PubMed Abstracts"
} |
Identification and functional significance of N-glycosylation of the 5-ht5A receptor.
The presence and roles of N-glycosylation of the human (h) 5-ht(5A) receptor were investigated using a heterologous expression system. Following transient transfection of COS-7 cells with h5-ht(5A) receptor cDNA, SDS-PAGE/Western blot analysis of immunoreactivity demonstrated two protein species; a predominant species with a molecular weight of approximately 35-45 kDa and a minor species of approximately 45-55 kDa. Transfected cells grown in the presence of the N-glycosylation inhibitor tunicamycin, failed to express the minor immunoreactive species indicating this represented the N-glycosylated form of the h5-ht(5A) receptor. Comparison of the molecular weights of immunoreactive bands arising from the wild-type and each of the mutant 5-ht(5A) receptors with disruption of the predicted N-glycosylation sites (N6S and N21S) demonstrated that both identified asparagines were N-glycosylated. Immunocytochemical and ELISA studies demonstrated that the [N6S]h5-ht(5A) receptor mutation, but not the [N21S]h5-ht(5A) receptor mutation, reduced protein expression in the cell membrane, indicating that N-glycosylation of the N6 residue is important for the membrane expression of this neurotransmitter receptor; a requirement for receptor function. | {
"pile_set_name": "PubMed Abstracts"
} |
[Recent advance in head and neck cancer surgery].
In order to remove a tumor radically, it is necessary to resect the tumor en-bloc together with surrounding normal tissues as much as possible. This results in a large tissue defect. Since the head and neck region has important functions for daily life such as respiration, speech, chewing, swallowing, the size of tissue defect directly affects post-operative functions and cosmetic results. Recently, the use of free flaps has made it possible to resect the advanced tumor which had been thought to be inoperable before. The introduction of free flaps has permitted reconstruction of the skull base, the nasopharynx, the mandible and the face. These were impossible to reconstruct with pedicled flaps such as delto-pectoral flap and pectoral major musculo-cutaneous flap. Therefore, the indication of reconstructive surgery has been remarkably enlarged for advanced head and neck cancer. We employed reconstructive surgery using free flaps for head and neck cancer in 1982, and, in August 1994, the number of patients operated on with free flaps reached 1,000. Through our experience of head and neck reconstructive surgery, we can conclude that the use of free flaps for the reconstruction in the head and neck region has permitted enlarging surgical indication for far advanced head and neck cancers. And the free flaps have made it possible to assure oral functions such as speech and chewing after reconstruction of the palate or the mandible. The use of free flaps has also decreased the incidence of postoperative complications such as fistula, infection, etc. It is incontestable that reconstructive surgery is indispensable for the treatment of head and neck cancer. | {
"pile_set_name": "PubMed Abstracts"
} |
Ca2+-dependent activation of phosphorylase by phosphorylase kinase in adipose tissue.
Phosphorylase kinase (EC 2.7.1.38) activity in crude cytosol preparations of chicken adipose tissue was assayed using as substrate either the endogenous phosphorylase b in the preparation or added purified rabbit skeletal muscle phosphorylase b. The results obtained with the two substrates were similar. The phosphorylase kinase reaction was markedly inhibited by ethyleneglycol-bis(beta-aminoethylether)-N,N',-tetraacetic acid (EGTA), maximum inhibition (about 90%) occurring at approx. 0.2 mM. This inhibition was readily reversed by addition of Ca2+. Full reversal was achieved with 0.3 mM Ca2+ in the presence of 0.5 mM EGTA; the estimated free Ca2+ concentration required was 4 muM. The activation of phosphorylase b was blocked immediately and completely by EGTA added during the course of the assay; reversal was achieved without a time lag by the addition of Ca2+. The Ca2+ requirement was also demonstrated directly by preparing an enzyme fraction from which Ca2+ had been removed and by using Ca2+-free reagents. Under these conditions the Ca2+ concentration needed for half maximum activation was 10 muM and maximum activation was obtained at about 100 muM. The possibility that the effects of EGTA and Ca2+ might be related to changes in phosphorylase phosphatase activity rather than phosphorylase kinase was considered unlikely since the phosphorylase phosphatase activity was inhibited during the phosphorylase kinase assay step by the inclusion of fluoride and beta-glycerophosphate. Phosphorylase kinase activity in rat adipocytes, using endogenous phosphorylase as substrate, was also inhibited EGTA but, whereas the activity in chicken adipose tissue was inhibited by 90%, the activity in rat adipose tissue was inhibited only 60%. These data indicate that adipose tissue phosphorylase kinase has a Ca2+ requirement for optimal activity and is thus qualitatively similar to the enzyme in contractile tissues. | {
"pile_set_name": "PubMed Abstracts"
} |
Fixation increases sensitivity of India ink staining of proteins and peptides on nitrocellulose paper.
The detectability by India ink staining of proteins and peptides dot-blotted on nitrocellulose paper was assessed before and after fixation. Fixation considerably increased the detectability of proteins and peptides. Denaturation by KOH treatment or baking at 100 degrees C for 15 min gave the best results. Precipitation by isopropanol/acetic acid gave intermediate results, whereas crosslinking with glutaraldehyde improved the detectability of small peptides, but not of proteins. Ferridye and Aurodye were also tested after baking. Both dyes were more sensitive and stained more proteins and peptides than India ink. In all cases the detectability of peptides smaller than Mr 1500 was poor. | {
"pile_set_name": "PubMed Abstracts"
} |
Immunohistochemical diagnosis of Neospora caninum in tissue sections.
An avidin-biotin-peroxidase complex immunoperoxidase staining method was developed to detect Neospora caninum in formalin-fixed, paraffin-embedded tissue sections. Specific antiserum to N caninum was made in rabbits and used to probe tissues from dogs naturally and experimentally infected with N caninum. The test detected tachyzoites and bradyzoites of N caninum. A reaction was not observed to Toxoplasma gondii, Hammondia hammondi, Sarcocystis cruzi, S capricanis, S tenella, Besnoitia jellisoni, Caryospora bigenetica, Hepatazoon canis, Atoxoplasma sp, or the organism causing canine dermal coccidiosis. When antiserum made in rabbits to T gondii was used in the test, reaction to N caninum was not observed. | {
"pile_set_name": "PubMed Abstracts"
} |
Pulmonary hypertension is associated with worse early and late outcomes after aortic valve replacement: implications for transcatheter aortic valve replacement.
Our objectives were to determine the prevalence of pulmonary hypertension (PHT) in patients undergoing aortic valve replacement (AVR) for severe aortic stenosis (AS), characterize risk for PHT, assess changes in PHT, and analyze its effect on outcomes. From January 1996 to July 2010, a total of 4372 patients with severe AS underwent primary AVR. Right ventricular systolic pressure (RVSP), a surrogate for PHT, was estimated echocardiographically in 2385, the study group. Preoperative RVSP was less than 35 mm Hg (low pressure) in 611, 35 to 50 mm Hg (moderate PHT) in 1199, and greater than 50 mm Hg (high PHT) in 575. From active follow-up, 10,218 patient-years were available for survival analysis and 3716 echocardiograms after AVR for assessing RVSP. Median preoperative RVSP was 41 mm Hg (range, 10-104 mm Hg). Older, more symptomatic female patients with more comorbidities and tricuspid or mitral regurgitation had higher RVSP. Hospital mortality was higher in those with higher RVSP (0.9% low presssure, 1.9% moderate PHT, 3.1% high PHT, P = .03), as was risk of renal (P < .0001) or respiratory failure (P < .0001), sepsis (P = .01), and prolonged hospitalization (P < .0001). Initial post-AVR RVSP improvement was not maintained but rose to preoperative levels by 3 to 4 years. Long-term survival was worse in patients with higher RVSP (P < .0001): 85% and 63% low pressure; 77% and 45% moderate PHT; and 62% and 31% high PHT at 5 and 10 years, respectively. Most patients undergoing primary AVR have at least moderate PHT that is not relieved by AVR; its severity is associated with mortality, serious complications, and worse late survival. PHT severity should be included in risk assessment before aortic valve intervention. These outcomes suggest that earlier intervention for AS warrants further study. | {
"pile_set_name": "PubMed Abstracts"
} |
Microvascular Mural Cells in Cancer.
Microvascular mural cells (MMCs) are important regulators of tumor vessel properties, such as endothelial cell differentiation and vessel permeability, and are recognized as modulators of tumor angiogenesis and growth. Emerging experimental studies suggest impact of MMCs on additional aspects of tumor biology, exerted by functionally distinct subsets. These have been shown to control metastasis both in primary tumors and in the premetastatic niche. Other studies link marker-defined MMCs to tumor immune surveillance and drug sensitivity. In parallel, recent efforts to profile MMCs in clinical samples are confirming the existence of clinically relevant marker-defined MMC subsets which show marker- and tumor-type- specific associations with prognosis and response to treatment. Collectively, findings encourage to continued analyses of MMC subsets as candidate biomarkers and drug targets. | {
"pile_set_name": "PubMed Abstracts"
} |
Analysis of a stable halogenated derivative of muramic acid by gas chromatography-negative ion chemical ionization tandem mass spectrometry.
Muramic acid (Mur) is present in the cell wall of Eubacteria and serves as a chemical marker for the trace detection of bacteria and bacterial cell wall debris in complex matrices. There have been numerous studies using a variety of derivatives of Mur, particularly in combination with gas chromatography-tandem mass spectrometry (GC-MS-MS) where the detection limit has been steadily lowered. A stable, halogenated derivative, the pentafluorobenzyl oxime (PFBO) acetate of Mur, has been developed by others and successfully used for GC with electron-capture detection. The current report is the first use of this derivative for GC-MS-MS analysis of Mur, or indeed any other carbohydrate, using negative ion chemical ionization (NICI) with GC-MS-MS. Mur was readily detected in settled surface dust (166 ng/mg), as well as dust collected from indoor air (1.4-5.9 ng/mg). Analyses of Mur as a PFBO acetate by GC-NICI-MS-MS or as alditol acetates by electron impact GC-electron impact ionization MS-MS serve as complementary approaches for trace detection in complex matrices. | {
"pile_set_name": "PubMed Abstracts"
} |
[Illicit drug trade on the markets of Yaounde (Cameroon) and Niamey (Niger): characteristics of salesmen and quality of drugs].
This study characterizes salesmen and evaluates the drugs offer and quality of the drugs in the illicit selling network in Yaoundé (Cameroon) and Niamey (Niger). A sample of 75 and 124 drug salesmen working in these cities was questioned using a standardized questionnaire. The prescription of drugs and the advices provided by these poorly trained salesmen could have an important impact in term of public health: 32% and 67% of the salesmen in Yaoundé give systematically or occasionally advices regarding the prescription. The active substances are always present in the 153 drugs of our analysed sample, except for chloroquine-based drugs, among which 5/30 samples did not contain active substance. However, the rate of nonconformity is approximately 50% in the two cities. Complementary studies are needed to explore the origin of these nonconformities, between counterfeiting, low quality of the products provided by the factories, defects of conservation or instability of the formulations. | {
"pile_set_name": "PubMed Abstracts"
} |
Dynamic Characteristic of Surface Phenotype of Peripheral Blood Lymphocytes in Myocarditis Patients.
A study of the expression of activated markers in peripheral blood lymphocytes makes it possible to carry out continuous monitoring of the immune system of a patient by means of a non-invasive method. This is of great importance for patients with acute myocarditis with immunopathological processes. However, there are very few papers in medical literature which are dedicated to this problem. Wherein, the number of lymphocyte markers being studied is, as a rule, very small. In order to characterize changes in the surface phenotype of lymphocytes during myocarditis, a study was conducted of the dynamics of surface lymphocyte markers in 45 patients with acute myocarditis during 12 weeks from the beginning of the illness. It is shown that a characteristic feature of myocarditis is a reduction in the number of T helpers (CD4(+)) and B lymphocytes (CD72(+)). However, the most marked changes were detected during evaluation of the expression of lymphocyte activation markers. An increase in the expression of all of the activation markers studied was noted two weeks after the beginning of myocarditis exacerbation. However, the earliest and most significant immunological feature indicating that the course of myocarditis has exacerbated is an increase in the portion of CD25(+) cells (the maximum increase is in the third week of the illness). The maximum of the increase of CD71(+) lymphocytes is in the fourth week of the illness, and an increase in the number of cells carrying the antigen HLA DR reaches a peak during the fifth-sixth week of myocarditis. The obtained results show that specific dynamics of expression of lymphocyte activation markers are typical for the immune status of patients with myocarditis. Exacerbation of the process is characterized by a substantial increase in the number of lymphocytes expressing CD25 antigen, later an increase in the number of CD71(+) lymphocytes is observed, and finally, an increase in the content of HLA DR(+) lymphocytes is typical for the inflammatory process developing in the myocardium. | {
"pile_set_name": "PubMed Abstracts"
} |
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