query: Dragon's Blood

positive: Studies on the antidiarrhoeal effect of dragon's blood from Croton urucurana. The red sap obtained by slashing the bark of Croton urucurana Baill. (Euphorbiaceae), also known as dragon's blood, was screened for a possible antidiarrhoeal activity on castor oil-induced diarrhoea in rats, cholera toxin-induced intestinal secretion in mice and on small intestinal transit in mice. Dragon's blood at an oral dose of 600 mg/kg caused in marked inhibition of the diarrhoeal response following castor oil administration as well as the intestinal fluid accumulation promoted by cholera toxin. At a similar dose the red sap significantly inhibited the small intestinal transit which was, however, found to be independent of the opioid mechanism. These results suggest a potential usefulness of the red sap from Croton urucurana Baill. in the control of secretory diarrhoea associated pathologies. Copyright 2001 John Wiley & Sons, Ltd.

positive: Mutagenic and antioxidant activities of Croton lechleri sap in biological systems. The sap of Croton lechleri Muell.-Arg (Euphorbiaceae), called Dragon's blood, is used in folk medicine as a cicatrizant, anti-inflammatory and to treat cancer. In this research, the antioxidant activity of Croton lechleri sap was evaluated against the yeast Saccharomyces cerevisiae and against maize plantlets treated with the oxidative agents apomorphine and hydrogen peroxide. The mutagenic activity of the sap was also analyzed using the Salmonella/microsome assay (Salmonella typhimurium TA97a, TA98, TA100, TA102, TA1535) and in cells of the yeast Saccharomyces cerevisiae. The results showed that Croton lechleri sap possesses significant antioxidant activity against the oxidative damages induced by apomorphine in Saccharomyces cerevisiae under all the conditions studied. However, in the case of hydrogen peroxide, antioxidant activity of the sap was detected only in cells in the stationary phase of growth. The sap was also able to protect cells of the maize plantlets from the toxic effect of apomorphine. This sap showed mutagenic activity for strain TA1535 of Salmonella typhimurium in the presence of metabolic activation and a weak mutagenic activity for strain TA98. These strains detect base pair substitutions and frameshift mutations, respectively. Mutagenicity was also observed in a haploid Saccharomyces cerevisiae strain XV185-14c for the lys1-1, his1-7 locus-specific reversion and hom3-10 frameshift mutations.

positive: Sangre de grado Croton palanostigma induces apoptosis in human gastrointestinal cancer cells. Sangre de grado is an ethnomedicinal red tree sap obtained from Croton spp. that is used to treat gastrointestinal ulcers, cancer and to promote wound healing. To evaluate the potential role of sangre de grado (SdG) in cancer we examined its effects on human cancer cells, AGS (stomach), HT29 and T84 (colon). Viability of cells treated with SdG (10-200 microg/ml) decreased (P<0.01) in a dose dependent manner measured over a 24-h period. Cell proliferation at 48 h decreased (P<0.01) in all cells treated with SdG (>100 microg/ml). When cells in suspension were treated with SdG (100 microg/ml) cell adherence was severely compromised (>85%). Cells treated with SdG (100 microg/ml) underwent apoptosis as detected by nucleus condensation and DNA fragmentation determined by ELISA, and flow cytometry. Morphological changes as assessed by acridine orange. These effects were similar to that observed with Taxol (30 microM). A significant alteration of microtubular architecture was equally observed in both stomach and colon cancer cells exposed to SdG (100 microg/ml). The induction of apoptosis and microtubule damage in AGS, HT29 and T84 cells suggest that sangre de grado should be evaluated further as a potential source of anti-cancer agents.

negative: Effect of dark chocolate on renal tissue oxygenation as measured by BOLD-MRI in healthy volunteers. BACKGROUND: Cocoa is rich in flavonoids, has anti-oxidative properties and increases the bioavailability of nitric oxide (NO). Adequate renal tissue oxygenation is crucial for the maintenance of renal function. The goal of this study was to investigate the effect of cocoa-rich dark chocolate (DC) on renal tissue oxygenation in humans, as compared to flavonoid-poor white chocolate (WC). METHODS: Ten healthy volunteers with preserved kidney function (mean age ± SD 35 ± 12 years, 70% women, BMI 21 ± 3 kg/m2) underwent blood oxygenation level-dependent magnetic resonance imaging (BOLD-MRI) before and 2 hours after the ingestion of 1 g/kg of DC (70% cocoa). Renal tissue oxygenation was determined by the measurement of R2* maps on 4 coronal slices covering both kidneys. The mean R2* (= 1/T2*) values in the medulla and cortex were calculated, a low R2* indicating high tissue oxygenation. Eight participants also underwent BOLD-MRI at least 1 week later, before and 2 hours after the intake of 1 g/kg WC. RESULTS: The mean medullary R2* was lower after DC intake compared to baseline (28.2 ± 1.3 s-1 vs. 29.6 ± 1.3 s-1, p = 0.04), whereas cortical and medullary R2* values did not change after WC intake. The change in medullary R2* correlated with the level of circulating (epi)catechines, metabolites of flavonoids (r = 0.74, p = 0.037), and was independent of plasma renin activity. CONCLUSION: This study suggests for the first time an increase of renal medullary oxygenation after intake of dark chocolate. Whether this is linked to flavonoid-induced changes in renal perfusion or oxygen consumption, and whether cocoa has potentially renoprotective properties, merits further study.

negative: Skin Blood Perfusion and Oxygenation Colour Affect Perceived Human Health Skin blood perfusion and oxygenation depends upon cardiovascular, hormonal and circulatory health in humans and provides socio-sexual signals of underlying physiology, dominance and reproductive status in some primates. We allowed participants to manipulate colour calibrated facial photographs along empirically-measured oxygenated and deoxygenated blood colour axes both separately and simultaneously, to optimise healthy appearance. Participants increased skin blood colour, particularly oxygenated, above basal levels to optimise healthy appearance. We show, therefore, that skin blood perfusion and oxygenation influence perceived health in a way that may be important to mate choice.

negative: The case of the purple colon. Purple discoloration of the large bowel at autopsy was related to beetroot ingestion and post-mortem changes.

negative: The effect of blood removal on oxidation and shelf life of broiler breast meat. Blood components, especially hemoglobin, are powerful promoters of lipid oxidation and may decrease the shelf life of meat products. Therefore, this study examined different slaughter techniques to determine their effects on pH (24 h), color (L*a*b* values at 24 h), lipid oxidation, residual hemoglobin concentration (24 h), and sensory evaluation (d 1 and 4 postmortem; PM) in broiler breast fillets. The treatments included 1) CO(2) slaughter and not bled, 2) no stunning and bled, 3) electrical stunning (ES) and bled, 4) CO(2) stunning and bled, and 5) ES and decapitation. The birds were conventionally processed, and analyses were performed at 24 h PM except residual hemoglobin for which the samples were frozen (-80 degrees C) until analyses ( < 2 mo). There were no significant differences in pH or b* values at 24 h PM among any of the treatments. L* values were significantly higher, indicating lighter fillets in the ES and decapitated birds compared with the darker fillets from the CO(2) stunned and bled birds. The CO(2) slaughter and not bled birds had significantly higher a* values, indicating more red color, when compared with the ES and bled and decapitated birds. There were no significant differences in the residual hemoglobin contents in the broiler breast muscle when comparing all of the treatments except CO(2) slaughter and not bled, which was significantly (around 15%) greater. Overall TBA-reactive substances (TBARS; raw, cooked at 24 h, and cooked at 72 h PM) indicated that ES and bled birds had the lowest TBARS when compared with the remaining treatments. Consumer panels detected increased aroma (chicken meaty and warmed-over aromas) and flavor (chicken meaty and warmed-over flavors) in not bled samples at 24 h PM. By 72 h PM, however, there were no significant differences in aroma or flavor. Therefore, different slaughter and bleeding method may affect color and sensory properties of the broiler breast fillets, and the ES and decapitation method had the most favorable results for sensory quality.

negative: Dark chocolate improves coronary vasomotion and reduces platelet reactivity. BACKGROUND: Dark chocolate has potent antioxidant properties. Coronary atherosclerosis is promoted by impaired endothelial function and increased platelet activation. Traditional risk factors, high oxidative stress, and reduced antioxidant defenses play a crucial role in the pathogenesis of atherosclerosis, particularly in transplanted hearts. Thus, flavonoid-rich dark chocolate holds the potential to have a beneficial impact on graft atherosclerosis. METHODS AND RESULTS: We assessed the effect of flavonoid-rich dark chocolate compared with cocoa-free control chocolate on coronary vascular and platelet function in 22 heart transplant recipients in a double-blind, randomized study. Coronary vasomotion was assessed with quantitative coronary angiography and cold pressor testing before and 2 hours after ingestion of 40 g of dark (70% cocoa) chocolate or control chocolate, respectively. Two hours after ingestion of flavonoid-rich dark chocolate, coronary artery diameter was increased significantly (from 2.36+/-0.51 to 2.51+/-0.59 mm, P<0.01), whereas it remained unchanged after control chocolate. Endothelium-dependent coronary vasomotion improved significantly after dark chocolate (4.5+/-11.4% versus -4.3+/-11.7% in the placebo group, P=0.01). Platelet adhesion decreased from 4.9+/-1.1% to 3.8+/-0.8% (P=0.04) in the dark chocolate group but remained unchanged in the control group. CONCLUSIONS: Dark chocolate induces coronary vasodilation, improves coronary vascular function, and decreases platelet adhesion 2 hours after consumption. These immediate beneficial effects were paralleled by a significant reduction of serum oxidative stress and were positively correlated with changes in serum epicatechin concentration.

negative: Role of environmental estrogens in the deterioration of male factor fertility. OBJECTIVE: To evaluate the role of the environmental estrogens polychlorinated biphenyls (PCBs) and phthalate esters (PEs) as potential environmental hazards in the deterioration of semen parameters in infertile men without an obvious etiology. DESIGN: Randomized controlled study. SETTING: Tertiary care referral infertility clinic and academic research center. PATIENT(S): Twenty-one infertile men with sperm counts <20 million/mL and/or rapid progressive motility <25% and/or <30% normal forms without evidence of an obvious etiology and 32 control men with normal semen analyses and evidence of conception. Semen and blood samples were obtained as part of the treatment protocol. MAIN OUTCOME MEASURE(S): Evaluation of semen parameters such as ejaculate volume, sperm count, motility, morphology, vitality, osmoregulatory capacity, sperm chromatin stability, and sperm nuclear DNA integrity. RESULT(S): PCBs were detected in the seminal plasma of infertile men but not in controls, and the concentration of PEs was significantly higher in infertile men compared with controls. Ejaculate volume, sperm count, progressive motility, normal morphology, and fertilizing capacity were significantly lower in infertile men compared with controls. The highest average PCB and PE concentrations were found in urban fish eaters, followed by rural fish eaters, urban vegetarians, and rural vegetarians. The total motile sperm counts in infertile men were inversely proportional to their xenoestrogen concentrations and were significantly lower than those in the respective controls. CONCLUSION(S): PCBs and PEs may be instrumental in the deterioration of semen quality in infertile men without an obvious etiology.

negative: Neurotoxic effects of aluminium among foundry workers and Alzheimer's disease. BACKGROUND: In a cross-sectional case-control study conducted in northern Italy, 64 former aluminium dust-exposed workers were compared with 32 unexposed controls from other companies matched for age, professional training, economic status, educational and clinical features. The findings lead the authors to suggest a possible role of the inhalation of aluminium dust in pre-clinical mild cognitive disorder which might prelude Alzheimer's disease (AD) or AD-like neurological deterioration. METHODS: The investigation involved a standardised occupational and medical history with particular attention to exposure and symptoms, assessments of neurotoxic metals in serum: aluminium (Al-s), copper (Cu-s) and zinc (Zn-s), and in blood: manganese (Mn-b), lead (Pb-b) and iron (Fe-b). Cognitive functions were assessed by the Mini Mental State Examination (MMSE), the Clock Drawing Test (CDT) and auditory evoked Event-Related Potential (ERP-P300). To detect early signs of mild cognitive impairment (MCI), the time required to solve the MMSE (MMSE-time) and CDT (CDT-time) was also measured. RESULTS: Significantly higher internal doses of Al-s and Fe-b were found in the ex-employees compared to the control group. The neuropsychological tests showed a significant difference in the latency of P300, MMSE score, MMSE-time, CDT score and CDT-time between the exposed and the control population. P300 latency was found to correlate positively with Al-s and MMSE-time. Al-s has significant effects on all tests: a negative relationship was observed between internal Al concentrations, MMSE score and CDT score; a positive relationship was found between internal Al concentrations, MMSE-time and CDT-time. All the potential confounders such as age, height, weight, blood pressure, schooling years, alcohol, coffee consumption and smoking habit were taken into account. CONCLUSIONS: These findings suggest a role of aluminium in early neurotoxic effects that can be detected at a pre-clinical stage by P300, MMSE, MMSE-time, CDT-time and CDT score, considering a 10 micrograms/l cut-off level of serum aluminium, in aluminium foundry workers with concomitant high blood levels of iron. The authors raise the question whether pre-clinical detection of aluminium neurotoxicity and consequent early treatment might help to prevent or retard the onset of AD or AD-like pathologies.

negative: Pharmacodynamic and pharmacokinetic study of oral Curcuma extract in patients with colorectal cancer. Curcuma spp. extracts, particularly the dietary polyphenol curcumin, prevent colon cancer in rodents. In view of the sparse information on the pharmacodynamics and pharmacokinetics of curcumin in humans, a dose-escalation pilot study of a novel standardized Curcuma extract in proprietary capsule form was performed at doses between 440 and 2200 mg/day, containing 36-180 mg of curcumin. Fifteen patients with advanced colorectal cancer refractory to standard chemotherapies received Curcuma extract daily for up to 4 months. Activity of glutathione S-transferase and levels of a DNA adduct (M(1)G) formed by malondialdehyde, a product of lipid peroxidation and prostaglandin biosynthesis, were measured in patients' blood cells. Oral Curcuma extract was well tolerated, and dose-limiting toxicity was not observed. Neither curcumin nor its metabolites were detected in blood or urine, but curcumin was recovered from feces. Curcumin sulfate was identified in the feces of one patient. Ingestion of 440 mg of Curcuma extract for 29 days was accompanied by a 59% decrease in lymphocytic glutathione S-transferase activity. At higher dose levels, this effect was not observed. Leukocytic M(1)G levels were constant within each patient and unaffected by treatment. Radiologically stable disease was demonstrated in five patients for 2-4 months of treatment. The results suggest that (a) Curcuma extract can be administered safely to patients at doses of up to 2.2 g daily, equivalent to 180 mg of curcumin; (b) curcumin has low oral bioavailability in humans and may undergo intestinal metabolism; and (c) larger clinical trials of Curcuma extract are merited.

negative: Flavones and flavonols at dietary levels inhibit a transformation of aryl hydrocarbon receptor induced by dioxin. Dioxins invade the body mainly through the diet, and produce toxicity through the transformation of aryl hydrocarbon receptor (AhR). An inhibitor of the transformation should therefore protect against the toxicity and ideally be part of the diet. We examined flavonoids ubiquitously expressed in plant foods as one of the best candidates, and found that the subclasses flavones and flavonols suppressed antagonistically the transformation of AhR induced by 1 nM of 2,3,7,8-tetrachlorodibenzo-p-dioxin, without exhibiting agonistic effects that transform AhR. The antagonistic IC(50) values ranged from 0.14 to 10 microM, close to the physiological levels in human.

negative: Two-year randomized, placebo-controlled study of black currant anthocyanins on visual field in glaucoma. AIM: To examine the influence of the black currant anthocyanins (BCACs) on the disease progression of open-angle glaucoma (OAG), a randomized, placebo-controlled, double-masked trial was made in 38 patients with OAG treated by antiglaucoma drops. METHODS: BCACs (50 mg/day, n = 19) or their placebos (n = 19) were orally administered once daily for a 24-month period. Systemic blood pressure, pulse rates, intraocular pressure (IOP), ocular blood circulation by laser-speckle flowgraphy, and Humphrey visual field mean deviation (MD) were measured during the 24-month period. RESULTS: As a main outcome measurement, we evaluated the difference between the groups in MD deterioration in the eye with a better MD from the trial's baseline through 24 months. A statistically significant difference was observed between the treatment groups in mean change from baseline in MD 24 months after therapy (p = 0.039, unpaired t test). Upon administration of BCACs, the ocular blood flows during the 24-month observational period increased in comparison with placebo-treated patients. However, no significant changes were observed in systemic and ocular conditions including IOP during the 24-month period. CONCLUSIONS: Our results suggest that oral administration of BCACs may be a safe and promising supplement for patients with OAG in addition to antiglaucoma medication. Copyright © 2012 S. Karger AG, Basel.

negative: Low vs. higher-dose dark chocolate and blood pressure in cardiovascular high-risk patients. BACKGROUND: Dark chocolate may have blood pressure-lowering properties. We conducted a prospective randomized open-label blinded end-point design trial to study a potential dose dependency of the presumed antihypertensive effect of dark chocolate by directly comparing low vs. higher doses of dark chocolate over the course of 3 months. METHODS: We enrolled a total of 102 patients with prehypertension/stage 1 hypertension and established cardiovascular end-organ damage or diabetes mellitus. Patients were randomly assigned to receive either 6 or 25 g/day of flavanol-rich dark chocolate for 3 months. The difference in 24-h mean blood pressure between groups was defined as the primary outcome measure. RESULTS: Significant reductions in mean ambulatory 24-h blood pressure were observed between baseline and follow-up in both groups (6 g/day: -2.3 mm Hg, 95% confidence interval -4.1 to -0.4; 25 g/day: -1.9 mm Hg, 95% confidence interval -3.6 to -0.2). There were no significant differences in blood pressure changes between groups. In the higher-dose group, a slight increase in body weight was noted (0.8 kg, 95% confidence interval 0.06 to 1.6). CONCLUSIONS: The findings are consistent with the hypothesis that dark chocolate may be associated with a reduction in blood pressure (BP). However, due to the lack of a control group, confounding may be possible and the results should be interpreted with caution.

negative: Hesperidin contributes to the vascular protective effects of orange juice: a randomized crossover study in healthy volunteers. BACKGROUND: Although numerous human studies have shown consistent effects of some polyphenol-rich foods on several intermediate markers for cardiovascular diseases, it is still unknown whether their action could be specifically related to polyphenols. OBJECTIVE: We investigated the effect of orange juice and its major flavonoid, hesperidin, on microvascular reactivity, blood pressure, and cardiovascular risk biomarkers through both postprandial and chronic intervention studies. DESIGN: Twenty-four healthy, overweight men (age 50-65 y) were included in a randomized, controlled, crossover study. Throughout the three 4-wk periods, volunteers daily consumed 500 mL orange juice, 500 mL control drink plus hesperidin (CDH), or 500 mL control drink plus placebo (CDP). All measurements and blood collections were performed in overnight-fasted subjects before and after the 4-wk treatment periods. The postprandial study was conducted at the beginning of each experimental period. RESULTS: Diastolic blood pressure (DBP) was significantly lower after 4 wk consumption of orange juice or CDH than after consumption of CDP (P = 0.02), whereas microvascular endothelium-related reactivity was not significantly affected when measured after an overnight fast. However, both orange juice and CDH ingestion significantly improved postprandial microvascular endothelial reactivity compared with CDP (P < 0.05) when measured at the peak of plasma hesperetin concentration. CONCLUSIONS: In healthy, middle-aged, moderately overweight men, orange juice decreases DBP when regularly consumed and postprandially increases endothelium-dependent microvascular reactivity. Our study suggests that hesperidin could be causally linked to the beneficial effect of orange juice. This trial is registered at clinicaltrials.gov as NCT00983086.

negative: Diet supplementation with donkey milk upregulates liver mitochondrial uncoupling, reduces energy efficiency and improves antioxidant and antiinflam... Dietary PUFA, mainly those of the n-3 family, are known to play essential roles in the maintenance of energy balance and in the reduction of body fat deposition through the upregulation of mitochondrial uncoupling that is the main source of reactive oxygen species. We hypothesized that rat supplementation with raw donkey's milk (DM), characterized by low-fat content and higher n3:n6 ratio, may affect energy balance, lipid metabolism, and prooxidant status as compared to animals treated with cow's milk. In the present study, the effects of drinking raw DM (for 4 weeks) on energy balance, lipid metabolism, antiinflammatory, and antioxidant/detoxifying defences was compared to that produced by rat intake of an iso-energetic amount of raw cow's milk. The hypolipidemic effect produced by DM paralleled with the enhanced mitochondrial activity/proton leakage and with the increased activity or expression of mitochondrial markers namely, carnitine palmitoyl transferase and uncoupling protein 2. The association of decreased energy efficiency with reduced proinflammatory signs (TNF-α and LPS levels) with the significant increase antioxidant (total thiols) and detoxifying enzyme activities (glutathione-S-transferase NADH quinone oxidoreductase) in DM-treated animals, indicated that beneficial effects were attributable, at least in part, to the activation of nuclear factor 2 erythroid-related factor 2 pathway. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

negative: Effects of low habitual cocoa intake on blood pressure and bioactive nitric oxide: a randomized controlled trial. CONTEXT: Regular intake of cocoa-containing foods is linked to lower cardiovascular mortality in observational studies. Short-term interventions of at most 2 weeks indicate that high doses of cocoa can improve endothelial function and reduce blood pressure (BP) due to the action of the cocoa polyphenols, but the clinical effect of low habitual cocoa intake on BP and the underlying BP-lowering mechanisms are unclear. OBJECTIVE: To determine effects of low doses of polyphenol-rich dark chocolate on BP. DESIGN, SETTING, AND PARTICIPANTS: Randomized, controlled, investigator-blinded, parallel-group trial involving 44 adults aged 56 through 73 years (24 women, 20 men) with untreated upper-range prehypertension or stage 1 hypertension without concomitant risk factors. The trial was conducted at a primary care clinic in Germany between January 2005 and December 2006. INTERVENTION: Participants were randomly assigned to receive for 18 weeks either 6.3 g (30 kcal) per day of dark chocolate containing 30 mg of polyphenols or matching polyphenol-free white chocolate. MAIN OUTCOME MEASURES: Primary outcome measure was the change in BP after 18 weeks. Secondary outcome measures were changes in plasma markers of vasodilative nitric oxide (S-nitrosoglutathione) and oxidative stress (8-isoprostane), and bioavailability of cocoa polyphenols. RESULTS: From baseline to 18 weeks, dark chocolate intake reduced mean (SD) systolic BP by -2.9 (1.6) mm Hg (P < .001) and diastolic BP by -1.9 (1.0) mm Hg (P < .001) without changes in body weight, plasma levels of lipids, glucose, and 8-isoprostane. Hypertension prevalence declined from 86% to 68%. The BP decrease was accompanied by a sustained increase of S-nitrosoglutathione by 0.23 (0.12) nmol/L (P < .001), and a dark chocolate dose resulted in the appearance of cocoa phenols in plasma. White chocolate intake caused no changes in BP or plasma biomarkers. CONCLUSIONS: Data in this relatively small sample of otherwise healthy individuals with above-optimal BP indicate that inclusion of small amounts of polyphenol-rich dark chocolate as part of a usual diet efficiently reduced BP and improved formation of vasodilative nitric oxide. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00421499.

negative: Absence of postprandial surge in coronary blood flow distal to significant stenosis: a possible mechanism of postprandial angina. OBJECTIVES: This study was designed to investigate a possible mechanism of postprandial angina. BACKGROUND: Postprandial angina has been recognized for more than two centuries; however, its mechanism is still controversial. The most widely accepted mechanism involves increased myocardial oxygen demand after food intake. Recently, the redistribution in coronary blood flow (CBF) was suggested as a possible mechanism. METHODS: Twenty young, healthy volunteer controls and 20 patients with significant stenosis in the left anterior descending (LAD) or left main coronary artery were enrolled in the study. Coronary blood flow was evaluated in the distal LAD by using transthoracic Doppler echocardiography before and 15, 30, 45, and 60 min after food intake. In the CBF curve, the time velocity integral of diastolic flow (Dtvi) and the product of Dtvi and heart rate (HR) were measured. In six patients, these measurements were repeated after successful coronary intervention. RESULTS: In the healthy volunteer controls, Dtvi and Dtvi x HR increased after food intake with a peak value at 15 min, which indicates the presence of postprandial surge in the CBF. Fasting values and peak values at 15 min were significantly different (Dtvi: 15.1 +/- 4.9 cm/s vs. 18.9 +/- 5.9 cm/s, p = 0.04, Dtvi x HR: 862.2 +/- 261.5 cm/min vs. 1,174.2 +/- 307.5, p = 0.002). In contrast with the controls, despite postprandial increase in double product (HR x blood pressure), Dtvi and Dtvi x HR in the patient group decreased after food intake, with a nadir value at 45 min. Fasting values and nadir values at 45 min were significantly different (Dtvi: 24.0 +/- 19.6 cm/s vs. 19.3 +/- 17.1 cm/s, p < 0.001, Dtvi x HR: 1,449.6 +/- 1,044.0 cm/min vs. 1,273.4 +/- 1,000.9 cm/min, p = 0.002). In six patients, the CBF pattern resumed the normal pattern of postprandial surge in the CBF after successful coronary intervention. CONCLUSIONS: Results of our study suggest that "steal phenomenon" may play a role in the mechanism of postprandial angina.

negative: Blood Harmane (1-methyl-9h-pyrido[3,4-b]indole) Concentrations in Essential Tremor: Repeat Observation in Cases and Controls in New York Essential tremor (ET) is a widespread late-life neurological disease. Genetic and environmental factors are likely to play important etiological roles. Harmane (1-methyl-9H-pyrido[3,4-b]indole) is a potent tremor-producing neurotoxin. Previously, elevated blood harmane concentrations were demonstrated in ET cases compared to controls, but these observations were all been cross-sectional, assessing each subject at only one time point. Thus, no one has ever repeat-assayed blood harmane in the same subjects twice. Whether the observed case-control difference persists at a second time point, years later, is unknown. The current goal was to re-assess a sample of our ET cases and controls to determine whether blood harmane concentration remained elevated in ET at a second time point. Blood harmane concentrations were quantified by a well-established high performance liquid chromatography method in 63 ET cases and 70 controls. A mean of approximately 6 years elapsed between the initial and this subsequent blood harmane determination. The mean log blood harmane concentration was significantly higher in cases than controls (0.30 ± 0.61 g−10/ml vs. 0.08 ± 0.55 g−10/ml), and the median value in cases was double that of controls: 0.22 g−10/ml vs. 0.11 g−10/ml. The log blood harmane concentration was highest in cases with a family history of ET. Blood harmane concentration was elevated in ET cases compared to controls when re-assessed at a second time point several years later, indicating what seems to be a stable association between this environmental toxin and ET.

negative: Insulin sensitivity in Chinese ovo-lactovegetarians compared with omnivores. AIM: To compare the insulin sensitivity indices between Chinese vegetarians and omnivores. METHODS: The study included 36 healthy volunteers (vegetarian, n=19; omnivore, n=17) who had normal fasting plasma glucose levels. Each participant completed an insulin suppression test. We compared steady-state plasma glucose (SSPG), fasting insulin, the homeostasis model assessment for insulin sensitivity (HOMA-IR and HOMA %S) and beta-cell function (HOMA %beta) between the groups. We also tested the correlation of SSPG with years on a vegetarian diet. RESULTS: The omnivore subjects were younger than the vegetarians (55.7+/-3.7 vs 58.6+/-3.6 year of age, P=0.022). There was no difference between the two groups in sex, blood pressure, renal function tests and lipid profiles. The omnivores had higher serum uric acid levels than vegetarians (5.25+/-0.84 vs 4.54+/-0.75 mg/dl, P=0.011). The results of the indices were different between omnivores and vegetarians (SSPG (mean+/-s.d.) 105.4+/-10.2 vs 80.3+/-11.3 mg/dl, P<0.001; fasting insulin, 4.06+/-0.77 vs 3.02+/-1.19 microU/ml, P=0.004; HOMA-IR, 6.75+/-1.31 vs 4.78+/-2.07, P=0.002; HOMA %S, 159.2+/-31.7 vs 264.3+/-171.7%, P=0.018) except insulin secretion index, HOMA %beta (65.6+/-18.0 vs 58.6+/-14.8%, P=0.208). We found a clear linear relation between years on a vegetarian diet and SSPG (r=-0.541, P=0.017). CONCLUSIONS: The vegetarians were more insulin sensitive than the omnivore counterparts. The degree of insulin sensitivity appeared to be correlated with years on a vegetarian diet.

negative: Genotoxic and mutagenic effects of erythrosine B, a xanthene food dye, on HepG2 cells. Erythrosine (ErB) is a xanthene and an US Food and Drug Administration approved dye used in foods, drugs and cosmetics. Although its utilization is permitted, ErB is described as inhibitor of enzymes and protein-protein interactions and is toxic to pituitary and spermatogenesis processes. However, the genotoxicity and mutagenicity of ErB is inconclusive in the literature. This study aimed to analyze the genotoxicity of this dye using the alkaline comet assay and is the first investigation to evaluate ErB mutagenicity using the cytokinesis block micronucleus cytome (CBMN-Cyt) assay in HepG2 cells. These cells were chosen because they produce phase I and phase II enzymes that can mimic in vivo metabolism. The cells were treated with seven concentrations (0.1-70.0 μg mL(-1)) of ErB, and the results showed genotoxicity at the two highest concentrations and mutagenicity at six concentrations. Furthermore, as micronuclei result from clastogenic and aneugenic processes, while comet assay is often considered more sensitive and detects DNA single strain breaks, we suggest that an aneugenic is responsible for the observed damage. Although ErB is approved for use in the food, cosmetic and pharmaceutical industries, it must be used carefully because it damages the DNA structure. Copyright © 2012 Elsevier Ltd. All rights reserved.

negative: Diethylstilboestrol--a long-term legacy. Diethylstilboestrol (DES) is an endocrine disrupter which causes cancer in rodents. It was prescribed in large amounts to treat women with gynaecological problems; some of the daughters of these women subsequently developed a rare cancer (vaginal clear cell adenocarcinoma) while genital abnormalities were found in some of the sons. It was used for decades in livestock feed and this may have contaminated the food chain leading to the exposure of the more general population. DES appears to cause epigenetic effects in animals and there is some evidence that this also occurs in man. The mechanisms of carcinogenesis are complex and the effects are difficult to prove due to the background of dietary and environmental phyto- and xenooestrogens. It has been suggested that, like other endocrine disrupters, DES may have acted as an obesogen in the human population. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

negative: Hemodynamic responses during prolonged sitting. Eight young men (group A) underwent 5 h of quiet sitting, preceded by 30 min of recumbency, 20 min of standing, and 20 s of walking, and five other young men (group B) underwent 70 min of sitting, preceded by recumbency only, to determine the effects of prolonged sitting and previous posture on hemodynamic responses (measured by impedance plethysmography). Group A showed more calf blood pooling and a decrease in thigh blood flow during sitting in comparison with the control group, but after 1 h of sitting hemodynamic responses of the two groups were similar. Sitting for 5 h (1st vs. 5th h) resulted in an increase in calf venous pooling (17%) and a decrease in calf BF (13%), a reduction in gravitational pooling in the thigh (corresponding to increased pooling in the calf), increases in diastolic and mean arterial pressures (6 and 7.3 mmHg, respectively), and minor changes in heart rate, stroke volume, and cardiac output. The results show that it is necessary to sit for 1 h before hemodynamic responses can be assessed in this position, regardless of the posture maintained previously. The main effect of prolonged sitting is pooling in the calf, which is compensated for by an increase in peripheral resistance.

negative: Plasma and erythrocyte biomarkers of dairy fat intake and risk of ischemic heart disease. BACKGROUND: The relation between dairy product intake and the risk of ischemic heart disease (IHD) remains controversial. OBJECTIVE: We aimed to explore biomarkers of dairy fat intake in plasma and erythrocytes and to assess the hypothesis that higher concentrations of these biomarkers are associated with a greater risk of IHD in US women. DESIGN: Among 32,826 participants in the Nurses' Health Study who provided blood samples in 1989-1990, 166 incident cases of IHD were ascertained between baseline and 1996. These cases were matched with 327 controls for age, smoking, fasting status, and date of blood drawing. RESULTS: Among controls, correlation coefficients between average dairy fat intake in 1986-1990 and 15:0 and trans 16:1n-7 content were 0.36 and 0.30 for plasma and 0.30 and 0.32 for erythrocytes, respectively. In multivariate analyses, with control for age, smoking, and other risk factors of IHD, women with higher plasma concentrations of 15:0 had a significantly higher risk of IHD. The multivariate-adjusted relative risks (95% CI) from the lowest to highest tertile of 15:0 concentrations in plasma were 1.0 (reference), 2.18 (1.20, 3.98), and 2.36 (1.16, 4.78) (P for trend = 0.03). Associations for other biomarkers were not significant. CONCLUSIONS: Plasma and erythrocyte contents of 15:0 and trans 16:1n-7 can be used as biomarkers of dairy fat intake. These data suggest that a high intake of dairy fat is associated with a greater risk of IHD.

negative: The rise and fall of horror autotoxicus and forbidden clones. Cui and associates show that healthy individuals have natural autoantibodies (NAAs) specific for myeloperoxidase, proteinase 3, and glomerular basement membrane (GBM) with the same specificity as anti-neutrophil cytoplasmic antibodies and anti-GBM antibodies that are pathogenic. Although Ehrlich proposed horror autotoxicus and Burnet envisioned elimination of forbidden clones, NAAs are present in all healthy individuals and play beneficial homeostatic roles. Pathogenic autoimmunity is dysregulation of natural homeostatic autoimmunity rather than onset of a previously absent self-recognition.

negative: Effective Heat Inactivation of Mycobacterium avium subsp. paratuberculosis in Raw Milk Contaminated with Naturally Infected Feces The effectiveness of high-temperature, short holding time (HTST) pasteurization and homogenization with respect to inactivation of Mycobacterium avium subsp. paratuberculosis was evaluated quantitatively. This allowed a detailed determination of inactivation kinetics. High concentrations of feces from cows with clinical symptoms of Johne's disease were used to contaminate raw milk in order to realistically mimic possible incidents most closely. Final M. avium subsp. paratuberculosis concentrations varying from 102 to 3.5 × 105 cells per ml raw milk were used. Heat treatments including industrial HTST were simulated on a pilot scale with 22 different time-temperature combinations, including 60 to 90°C at holding (mean residence) times of 6 to 15 s. Following 72°C and a holding time of 6 s, 70°C for 10 and 15 s, or under more stringent conditions, no viable M. avium subsp. paratuberculosis cells were recovered, resulting in >4.2- to >7.1-fold reductions, depending on the original inoculum concentrations. Inactivation kinetic modeling of 69 quantitative data points yielded an Ea of 305,635 J/mol and an lnk0 of 107.2, corresponding to a D value of 1.2 s at 72°C and a Z value of 7.7°C. Homogenization did not significantly affect the inactivation. The conclusion can be drawn that HTST pasteurization conditions equal to 15 s at ≥72°C result in a more-than-sevenfold reduction of M. avium subsp. paratuberculosis.

negative: Food intake and its relationship with semen quality: a case-control study. OBJECTIVE: To compare dietary habits in normospermic and oligoasthenoteratospermic patients attending a reproductive assisted clinic. DESIGN: An observational, analytical case-control study. SETTING: Private fertility clinics. PATIENT(S): Thirty men with poor semen quality (cases) and 31 normospermic control couples attending our fertility clinics. INTERVENTION(S): We recorded dietary habits and food consumption using a food frequency questionnaire adapted to meet specific study objectives. Analysis of semen parameters, hormone levels, Y microdeletions, and karyotypes were also carried out. MAIN OUTCOME MEASURE(S): Frequency of intake food items were registered in a scale with nine categories ranging from no consumption to repeated daily consumption. RESULT(S): Controls had a higher intake of skimmed milk, shellfish, tomatoes, and lettuce, and cases consumed more yogurt, meat products, and potatoes. In the logistic regression model cases had lower intake of lettuce and tomatoes, fruits (apricots and peaches), and significantly higher intake of dairy and meat processed products. CONCLUSION(S): Frequent intake of lipophilic foods like meat products or milk may negatively affect semen quality in humans, whereas some fruits or vegetables may maintain or improve semen quality.

negative: Correlation between penile duplex findings and stress electrocardiography in men with erectile dysfunction. The aim of this work is to assess the association between vasculogenic erectile dysfunction (ED) and coronary artery disease in men above the age of 40 y. The study included 40 patients above 40 y of age with vasculogenic ED of more than 3 months duration. A dynamic duplex study after intracavernosal injection of a bimix solution (60 mg papaverine + 2 mg phentolamine mesylate) was carried out using a color ultrasound machine. The patients underwent a stress ECG test, carried out on a motor-driven treadmill according to the 'Bruce Protocol'. A total of 12 patients were diagnosed with positive ischemic heart disease (IHD). Their mean peak systolic velocity (PSV) was PSV = 19.58 cm/s. In all, patients were diagnosed with negative IHD; their mean PSV was 36.21 cm/s. A statistically significant difference was observed between patients with positive IHD and patients with negative IHD regarding PSV (P = 0.003). The sensitivity of a PSV of less than 35 cm/s in predicting IHD was 50% with a specificity of 100%. Positive predictive value for abnormal stress ECG to predict a PSV of less than 35 cm/s was 100%. In conclusion, the PSV of cavernosal arteries is a reliable measure for predicting IHD in patients with vasculogenic ED. Patients with a PSV of less than 35 cm/s should be referred for cardiologic assessment as they carry a real risk of having silent IHD.

negative: The effects of peppermint on exercise performance Background Enhancing athletic performance is a great desire among the athletes, coaches and researchers. Mint is one of the most famous natural herbs used for its analgesic, anti-inflammatory, antispasmodic, antioxidant, and vasoconstrictor effects. Even though inhaling mint aroma in athletes has been investigated, there were no significant effects on the exercise performance. Methods Twelve healthy male students every day consumed one 500 ml bottle of mineral water, containing 0.05 ml peppermint essential oil for ten days. Blood pressure, heart rate, and spirometry parameters including forced vital capacity (FVC), peak expiratory flow rate (PEF), and peak inspiratory flow (PIF) were determined one day before, and after the supplementation period. Participants underwent a treadmill-based exercise test with metabolic gas analysis and ventilation measurement using the Bruce protocol. Results The FVC (4.57 ± 0.90 vs. 4.79 ± 0.84; p < 0.001), PEF (8.50 ± 0.94 vs. 8.87 ± 0.92; p < 0.01), and PIF (5.71 ± 1.16 vs. 6.58 ±1.08; p < 0.005) significantly changed after ten days of supplementation. Exercise performance evaluated by time to exhaustion (664.5 ± 114.2 vs. 830.2 ± 129.8 s), work (78.34 ±32.84 vs. 118.7 ± 47.38 KJ), and power (114.3 ± 24.24 vs. 139.4 ± 27.80 KW) significantly increased (p < 0.001). In addition, the results of respiratory gas analysis exhibited significant differences in VO2 (2.74 ± 0.40 vs. 3.03 ± 0.351 L/min; p < 0.001), and VCO2 (3.08 ± 0.47 vs. 3.73 ± 0.518 L/min; p < 0.001). Conclusions The results of the experiment support the effectiveness of peppermint essential oil on the exercise performance, gas analysis, spirometry parameters, blood pressure, and respiratory rate in the young male students. Relaxation of bronchial smooth muscles, increase in the ventilation and brain oxygen concentration, and decrease in the blood lactate level are the most plausible explanations.

negative: Thematic review series: the pathogenesis of atherosclerosis. An interpretive history of the cholesterol controversy, part V: the discovery of the s... The first four reviews in this series (Steinberg, D. 2004. J. Lipid Res. 45: 1583-1593; Steinberg, D. 2005. J. Lipid Res. 46: 179-190; Steinberg, D. 2005. J. Lipid Res. 46: 2037-2051; Steinberg, D. 2006. J. Lipid Res. 47: 1-14) traced the gradual accumulation of evidence, evidence of several different kinds, supporting the lipid hypothesis. They tracked the history from Anitschkow's 1913 classic work on the cholesterol-fed rabbit model to the breakthrough 1984 Coronary Primary Prevention Trial, the first large, randomized, double-blind primary intervention trial showing that decreasing blood cholesterol (using cholestyramine) significantly reduces coronary heart disease events. At that point, for the first time, decreasing blood cholesterol levels became an official national public health goal. Still, only a small fraction of patients at high risk were getting appropriate cholesterol-lowering treatment, and a number of important clinical questions remained unanswered. This final review in the series traces the early studies that led to the discovery of the statins and briefly reviews the now familiar large-scale clinical trials demonstrating their safety and their remarkable effectiveness in reducing coronary heart disease morbidity and mortality.

negative: Severe lactic acidosis associated with juice of the mangosteen fruit Garcinia mangostana. The tropical mangosteen fruit has long been prized in Southeast Asia for its traditional healing properties. Mangosteen fruit juice is now available in the United States and marketed for its purported health benefits. We describe a case of severe lactic acidosis associated with the use of mangosteen juice as a dietary supplement.

negative: Pseudo-maple syrup urine disease due to maternal prenatal ingestion of fenugreek. Fenugreek, maple syrup and the urine of maple syrup urine disease (MSUD) patients all share a characteristic odour originating from a common component, sotolone. Ingestion of fenugreek by mothers during labour resulted in a maple syrup-like odour in their newborn infants, leading to a false suspicion of MSUD.

negative: Pan retinal photocoagulation for proliferative diabetic retinopathy: pattern scan laser versus argon laser. PURPOSE OF REVIEW: Diabetic retinopathy is the leading cause of visual impairment in working-age adults worldwide. Pan retinal photocoagulation (PRP) has provided an effective treatment to decrease the risk of severe vision loss in patients with proliferative diabetic retinopathy for the past four decades. Pattern scan laser (PASCAL) was developed to minimize the side effects of PRP. The purpose of this review is to discuss the differences between the traditional argon laser and the PASCAL. RECENT FINDINGS: PASCAL can achieve comparable results with the conventional argon PRP in the treatment of patients with diabetic retinopathy. The PASCAL delivery system creates well aligned arrays of retinal lesions in a shorter period. PASCAL provides amore comfortable profile when compared to the argon laser. SUMMARY: The PASCAL is now being substituted for the conventional argon laser for PRP in many clinics. Ophthalmologists should keep in mind that adjusting the PASCAL settings (including the duration, number, and size of laser burns) might become necessary to maintain regression and eliminate recurrence of neovascularization in patients with proliferative diabetic retinopathy. Further studies are needed to determine the parameters for optimal safety and efficacy on the PASCAL.

negative: Inhibition of angiotensin convertin enzyme (ACE) activity by the anthocyanins delphinidin- and cyanidin-3-O-sambubiosides from Hibiscus sabdariffa. ETHNOPHARMACOLOGICAL RELEVANCE: The beverages of Hibiscus sabdariffa calyces are widely used in Mexico as diuretic, for treating gastrointestinal disorders, liver diseases, fever, hypercholesterolemia and hypertension. Different works have demonstrated that Hibiscus sabdariffa extracts reduce blood pressure in humans, and recently, we demonstrated that this effect is due to angiotensin converting enzyme (ACE) inhibitor activity. AIM OF THE STUDY: The aim of the current study was to isolate and characterizer the constituents responsible of the ACE activity of the aqueous extract of Hibiscus sabdariffa. MATERIALS AND METHODS: Bioassay-guided fractionation of the aqueous extract of dried calyces of Hibiscus sabdariffa using preparative reversed-phase HPLC, and the in vitro ACE Inhibition assay, as biological monitor model, were used for the isolation. The isolated compounds were characterized by spectroscopic methods. RESULTS: The anthocyanins delphinidin-3-O-sambubioside (1) and cyanidin-3-O-sambubioside (2) were isolated by bioassay-guided purification. These compounds showed IC(50) values (84.5 and 68.4 microg/mL, respectively), which are similar to those obtained by related flavonoid glycosides. Kinetic determinations suggested that these compounds inhibit the enzyme activity by competing with the substrate for the active site. CONCLUSIONS: The competitive ACE inhibitor activity of the anthocyanins 1 and 2 is reported for the first time. This activity is in good agreement with the folk medicinal use of Hibiscus sabdariffa calyces as antihypertensive. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

negative: Modern society and prospects of low vitamin B12 intake. BACKGROUND: Vitamin B(12) deficiency can occur in individuals with dietary patterns that exclude animal foods and patients who are unable to absorb vitamin B(12 )in food. MATERIAL AND METHOD: Our clinic serves a high-income population living in Southern Israel. We hypothesize that a tendency to decrease of level of vitamin B(12) in our population is caused by a premeditated decrease in consumption of animal products. We analyzed 512 medical histories of patients undergoing blood tests for vitamin B(12) level for various reasons. RESULT: The level of vitamin B(12) in 192 patients (37.5%) was less than 250 pg/ml. CONCLUSION: As a result of media information disseminating the relationship between meat, cholesterol and cardiovascular diseases, consumption of meat, particularly beef, has decreased. Changes in life style among segments of the population with high socioeconomic level, on one hand, and the existence of poverty, on the other, are two main factors in the decreasing consumption of animal products. This causes a decrease in the level of vitamin B(12) in the general population, and as a consequence, this will increase pathology due to vitamin B(12) deficiency. In lieu of these possible developments and in order to prevent serious health problems, vitamin B(12) fortification should be seriously considered and discussed. (c) 2007 S. Karger AG, Basel.