Effects of turmeric extract supplementation on the lipid and lipoprotein subfraction profile in hemodialysis patients: A randomised, double-blind, crossover and controlled trial.

Dyslipidemia is common in patients with chronic kidney disease. Curcumin, a bioactive polyphenol from Curcuma longa, can improve lipid profile. This study aims to analyze the effects of Curcuma Longa extract supplementation on lipid profile and lipoprotein subfractions in hemodialysis (HD) patients. This is a longitudinal, double-blind, washout-period randomized clinical trial. The patients were randomized into two groups: the curcumin group (n = 10) (orange and carrot juice with 2.5 g of Curcuma Longa extract) and the control group (n = 11) (juice without curcumin) 3x/w during HD sessions for 3 months. After the washout period, patients continued the supplementation as a crossover for the same period. The lipid profile was measured using enzymatic assays. The high-density lipoprotein and low-density lipoprotein subfractions analyses were performed using LipoprintTM. In the curcumin group, the triglyceride values tended to decrease with a different triglyceride variation between the pre and post-intervention for the control and curcumin groups of 38.5 (19.8) mg/dL (p = 0.06). There was no statistical difference in the others parameters. In conclusion, Curcuma longa extract may be a good nutritional strategy to reduce triglyceride plasma levels in hemodialysis patients, but it seems ineffective for the other parameter.

Substance abuse amongst the medical graduate students in a developing country.

BACKGROUND & OBJECTIVES: Substance abuse is found worldwide including among students. We carried out this study to estimate the prevalence of substance abuse among medical student studying in a medical college in north India. METHODS: Using a validated questionnaire a cross-sectional survey was conducted among 230 undergraduate and postgraduate medical students in a private medical college. RESULTS: The prevalence of substance abuse was 20.43 per cent (47/230) among medical students. An increase in substance abuse was observed in the latter years of medical education. A total of 43 of 47 (91.7%) students using these substances were aware of the ill effects. The most common reasons for substance use were relief from psychological stress (34/47, 72.4%) and occasional celebration (34/47, 72.4%). Of the 47 substance users, 28 (59.6%) made past attempts to quit the substance abuse. INTERPRETATION & CONCLUSIONS: Nearly one-fifth of medical students abuse at least one substance despite knowing the ill effects with the main predisposing factor being the psychological stress.

Atypical Presentations of Melioidosis in North India: Report of Two Cases.

Melioidosis is an infection caused by Gram-negative bacterium, Burkholderia pseudomallei. This is a rare disease in India, more so in North India. We present two cases of melioidosis with unusual sites of infection. The first patient was a young diabetic male presenting to us with history of prolonged fever and upper abdominal discomfort, subsequently diagnosed as a case of pyogenic liver abscess. The second patient was a middle aged diabetic complaining of prolonged fever and headache and found to have right frontal lobe brain abscess.The pus cultured from the lesion in both cases showed growth of Burkholderia pseudomallei. These two cases are described to consider melioidosis as a differential diagnosis amongst pyrexia of unknown origin cases.

International Mycoplasma pneumoniae typing study: interpretation of M. pneumoniae multilocus variable-number tandem-repeat analysis.

Typing of Mycoplasma pneumoniae by multiple-locus variable-number tandem repeat analysis (MLVA) is increasingly in use. However, no specific internationally agreed guidance is available. Thirty M. pneumoniae DNA samples including serial dilutions of a type strain were sent to six international laboratories to perform MLVA and results were compared. Good correlation was observed, indicating that this methodology can be robustly performed in multiple sites. However, differences due to interpretation of fragment size, repeat sequence identification and repeat numbering led to inconsistency in the final profiles assigned by laboratories. We propose guidelines for interpreting M. pneumoniae MLVA typing and assigning the number of repeats.

Knowledge and perception of off-label drug use amongst prescribing physicians in a tertiary care hospital.

INTRODUCTION: Off-label drug use is commonly reported in various disciplines of medicine. Considering the lacunae of studies from prescribers in the Indian subcontinent, the present study was conducted to explore their awareness and views of off-label drug use. METHODS: A validated questionnaire was administered to interns, junior residents and faculty members who were recruited in the present study of various medical and surgical departments of Subharti Medical College, Meerut, India, a tertiary care teaching hospital. Descriptive statistics was used for analyzing the data. RESULTS: A total of 59/85 (69%) stated that they have used a drug in an off-label manner mainly [31/85 (36.5%)] related to indications. Nearly half of the study participants (41/85, 48.2%) considered prescribing an off-label drug illegal and only 25/85 (29.3%) participants felt that they had adequate knowledge regarding the use of drugs in off-label manner. Out of the total 70 participants who answered the question related to informing parents/relatives while prescribing an off label drug, only 39/70 (55.7%) answered affirmative. Out of the remaining 31/70 (44.3%) of participants who did not inform about prescribing an off label drug, 9/31 (29%) felt that it was illegal and more than two-third (24/31, 77%) felt their knowledge on off-label drug use was insufficient. Surprisingly, 74/82 (90.2%) participants felt that a drug approved to be used in adults cannot be used in children for the same indication despite not having any alternative in pediatric age group. CONCLUSION: We found an inadequate knowledge regarding the off-label drug use amongst the prescribers in a tertiary care medical college hospital. Many of the physicians felt such use as illegal and do not inform the patient's relatives about such acts. Considering the legal issues, clearly there exists a need to patch up this lacuna in developing countries like India.

Design and construction of a single tube, quantitative endpoint, LATE-PCR multiplex assay for ventilator-associated pneumonia.

AIMS: The goal of this study was to develop a molecular diagnostic multiplex assay for the quantitative detection of microbial pathogens commonly responsible for ventilator-associated pneumonia (VAP) and their antibiotic resistance using linear-after-the-exponential polymerase chain reaction (LATE-PCR). METHOD AND RESULTS: This multiplex assay was designed for the quantitative detection and identification of pathogen genomic DNA of methicillin-resistant Staphylococcus aureus (MRSA), Acinetobacter baumannii, Pseudomonas aeruginosa, plus a control target from Lactococcus lactis. After amplification, the single-stranded amplicons were detected simultaneously in the same closed tube by hybridization to low-temperature molecular beacon probes labelled with four differently coloured fluorophores. The resulting hybrids were then analysed by determining the fluorescence intensity of each of the four fluorophores as a function of temperature. CONCLUSIONS: This LATE-PCR single tube multiplex assay generated endpoint fluorescent contours that allowed identification of all microbial pathogens commonly responsible for VAP, including MRSA. The assay was quantitative, identifying the pathogens present in the sample, no matter whether there were as few as 10 or as many 100 000 target genomes. SIGNIFICANCE AND IMPACT OF THE STUDY: This assay is rapid, reliable and sensitive and is ready for preclinical testing using samples recovered from patients suffering from ventilator-associated pneumonia.

Egg breakfast enhances weight loss.

OBJECTIVE: To test the hypotheses that an egg breakfast, in contrast to a bagel breakfast matched for energy density and total energy, would enhance weight loss in overweight and obese participants while on a reduced-calorie weight loss diet. SUBJECTS: Men and women (n=152), age 25-60 years, body mass index (BMI) >or=25 and

Corticosteroids, 11beta-hydroxysteroid dehydrogenase isozymes and the rabbit choroid plexus.

The epithelial cells of the choroid plexus (CP) are responsible for cerebrospinal fluid (CSF) secretion into the ventricles of the brain. The balance between CSF production and drainage, in part, facilitates a normal intracranial pressure. The secretion of Na(+) and anions by the CP creates an osmotic gradient driving water into the ventricles. This is opposite to classical Na(+) transporting tissues, such as the kidney, where Na(+) and water reabsorption is mediated by 11beta-hydroxysteroid dehydrogenase type 2 that protects the mineralocorticoid receptor by abrogating active cortisol to inactive cortisone. In the human ocular ciliary epithelium, Na(+) and water secretion is dependent on a novel mediator of ciliary epithelial Na(+) transport, 11beta-HSD type 1 (11beta-HSD1), that generates intraocular cortisol. In a mechanism analogous to that of the embryologically related ocular ciliary epithelium, we propose that autocrine regulation of intracranial cortisol is dependent on 11beta-HSD1 expression in the CP epithelial cells. By conducting immunolocalisation studies on brains from New Zealand White Albino rabbits, we defined the expression of 11beta-HSD1 in the secretory CP epithelial cells. Enzyme assays performed on intact rabbit CP whole tissue explants confirmed predominant 11beta-HSD1 activity, generating cortisol that was inhibited by glycyrrhetinic acid (an 11beta-HSD inhibitor). Using the real time-polymerase chain reaction, rabbit CP tissue was found to express levels of 11beta-HSD1, glucocorticoid receptor alpha and serum and glucocorticoid-regulated kinase 1 mRNA comparable to that expressed in rabbit ocular ciliary body, thereby highlighting the similarity between these two tissues. Furthermore, an enzyme-linked immunosorbent assay of rabbit CSF revealed a median cortisol concentration of 1.7 nmol/l (range 1.4-4.3 nmol/l, n = 9). Our data have identified a functional 11beta-HSD1 within the CP, mediating intracranial cortisol bioavailability. Expression of 11beta-HSD1 may be fundamental in the regulation of CSF secretion and the local generation of cortisol may represent a pathophysiological mechanism underlying cortisol-dependent neuroendocrine diseases.

Combination therapy of low-dose atorvastatin and fenofibrate in mixed hyperlipidemia.

Mixed hyperlipidemia is a major cause of coronary artery disease. Monotherapy with statins is considered the gold standard for treatment of mixed hyperlipidemia. But greater benefit may be expected by combination therapy. Combination may allow lower doses of statins and less adverse effects. Hence, this preliminary study was designed to evaluate the efficacy and safety of low-dose atorvastatin in combination with fenofibrate in patients with mixed hyperlipidemia. Ninety patients were assigned into three groups and received atorvastatin (10-40 mg/day) or fenofibrate (160-200 mg/day) or combination of low-dose atorvastatin (5 mg/day) and fenofibrate (160 mg/day). There was a significant decrease in low-density lipoprotein (LDL), triglycerides (TG) and total cholesterol (TC), and a significant increase in high-density lipoprotein (HDL) in all the groups at the end of therapy. Combination therapy produced maximum decrease in LDL, TG and TC, and maximum increase in HDL when compared with monotherapies. No significant difference was reported in safety profile between the two groups. To conclude, the results suggest that combination therapy with low-dose atorvastatin and fenofibrate is more efficacious, with no increase in adverse effects when compared with monotherapies with individual drugs for mixed hyperlipidemia. The results are preliminary and suggestive only, as the study was open and nonrandomized.

Novel short-term effects of adenovirus Ad-36 on hamster lipoproteins.

OBJECTIVE: Human adenovirus Ad-36 induces adiposity and lowers total serum cholesterol in chickens, mice and marmosets and Ad-36 antibodies are associated with human obesity. We examined the early effects of Ad-36 inoculation on plasma cholesterol levels in hamsters fed a hyperlipidemic diet. DESIGN: A total of 32 male Golden Syrian hamsters were divided into two equal weight-matched groups and intranasally inoculated with Ad-36 (INF: infected) or media (CON: control). In each group, the animals were fed either a purified diet (PF, n=8) 40%en fat +/-194 mg cholesterol/1000 kcal or chow (C, n=8) ad libitum. Animals were killed 5 weeks postinoculation. RESULTS: Nested PCR assay detected Ad-36 DNA in the lung, liver, visceral adipose tissue and skeletal muscle of the INF group, but not in the CON animals. Ad-36 antibodies were detected in the INF group only. For all animals, total plasma cholesterol (TC) was not significantly affected by Ad-36 treatment (203+/-92 vs 193+/-75 mg/dl, P=NS; INF vs CON, respectively). In 5 weeks, Ad-36 infection had no effect on TC concentration in hamsters fed chow (128+/-39 vs 130+/-27 mg/dl, INF-C vs CON-C, respectively) or those fed PF (269+/-70 vs 256+/-47 mg/dl, INF-P vs CON-P, respectively). However, lipoproteins isolated by density gradient ultracentrifugation showed a greater proportion of LDL cholesterol in INF animals, as compared to CON (28.4+/-1.6% vs 16.4+/-1.2%, P=0.02), regardless of dietary treatment (INF-P vs CON-P: 27.3+/-2.1 vs 15.7+/-1.5%, P=0.07; and INF-C vs CON-C: 29.4+/-1.2 vs 17.0+/-1.1%, P=0.009). This shift appears to be from HDL cholesterol to the LDL fractions. CONCLUSION: These data suggest that in the hamster (a model resembling several aspects of human lipoprotein metabolism), Ad-36 infection may acutely affect the intravascular processing of lipoproteins resulting in a more atherogenic lipoprotein profile.

Effect of garlic oil on ethanol induced gastric ulcers in rats.

Garlic oil was evaluated for gastroprotective activity against ethanol induced ulcers. Reactive oxygen species are involved in the pathogenesis of these ulcers. The possible involvement of garlic oil in restraining the oxidation process produced in gastric tissue was also investigated. The ulcer index, lipid peroxidation and antioxidant enzyme activity (GPx, catalase, SOD) were determined. Pretreatment with garlic oil in doses of 0.25 and 0.5 mg/kg, 30 min before administration of ethanol (1 mL of 100%) caused a decrease in ulcer index and lipid peroxidation and ameliorated the decrease in antioxidant enzyme levels caused by ethanol. The result suggests that garlic oil possesses antioxidant properties and provides protection against ethanol induced gastric injury.

A study of cardiovascular effects of Azadirachta indica (neem) on isolated perfused heart preparations.

The effects of aqueous leaf extract of Azadirachta indica were evaluated on isolated prefused frog and rabbit heart. Dose dependent negative inotropic and chronotropic effects were observed in both the heart preparation. An increase in coronary blood flow in isolated rabbit heart was observed. The effects were not blocked by atropine and mepyramine in both the preparations. The data suggests that A. indica could be of benefit in coronary artery disease and arrhythmias.

Prevalence of risk factors to coronary heart disease in an Arab-American population in southeast Michigan.

Although significant advances have been made in the area of cardiovascular disease, few studies have targeted ethnic groups. There is a large and growing Arab-American (AA) population living in Southeast Michigan, whose risk of cardiovascular disease may be on the increase. The objective of this study was to evaluate the prevalence of cardiovascular disease risk factors and associated behavioral factors in an AA community with a large population of emigrants, subjected to significant lifestyle changes. Three hundred and fifty-two AA living in Southeast Michigan, mostly from the Middle East, were screened to determine their eating and smoking habits, body mass index (BMI) body fat analysis, blood pressure, and complete lipid profiling. Overweight was defined as a BMI greater than or equal to the 85th percentile value for age- and sex-specific reference data from the third National Health and Nutrition Examination Survey (NHANES III). Correlation analysis was used to examine factors associated with being overweight, with adjustment for age and sex. Blood cholesterol concentrations were compared with published data for Arabs from the Middle Eastern countries. The overall prevalence of being overweight in subjects aged 35 and older was significantly higher than NHANES III reference data (Men, 27.7% (95% confidence interval, 21.8-34.5); women, 33.7% (95% confidence interval, 27.9-40.1)). A mean cholesterol concentration of 210 +/- 4 mg/dl was observed in those over the age of 40. The mean high-density lipoprotein (HDL)-cholesterol levels for men and women were 38 and 48 mg/dl, respectively. Greater than 54.6% of all subjects had a total cholesterol:HDL ratio > 4.5. Although being overweight and obesity were prevalent in this population, the mean BMI for men was 25.7 +/- 0.34, compared with 27 +/- 0.58 for women. Increased BMI was significantly correlated (P < 0.01) with increased blood pressure, increased glucose levels, increased total cholesterol and decreased HDL-cholesterol levels (P < 0.01). Elevation in risk factors to cardiovascular disease is prevalent in this population and indicates a need for programs targeting primary prevention of obesity in men and women. These results, which could be attributed in part to lifestyle changes typical of most emigrant populations, suggest an increase in the risk for developing cardiovascular disease. In addition, this study provides a basis for future intervention to improve the health of this population.

Palmitic and stearic acids similarly affect plasma lipoprotein metabolism in cynomolgus monkeys fed diets with adequate levels of linoleic acid.

This study was designed to evaluate whether the exchange of specific saturated fatty acids [SFA; palmitic acid (16:0) for stearic acid (18:0)] would differentially affect plasma lipids and lipoproteins, when diets contained the currently recommended levels of total SFA, monounsaturated fatty acids and polyunsaturated fatty acids (PUFA). Ten male cynomolgus monkeys were fed one of two purified diets (using a cross-over design) enriched either in 16:0 (palmitic acid diet) or 18:0 (stearic acid diet). Both diets provided 30% of energy as fat (SFA/monounsaturated fatty acid/PUFA: 1/1/1). The palmitic acid and stearic acid diets were based on palm oil or cocoa butter (59% and 50% of the total fat, respectively). By adding different amounts of sunflower, safflower and olive oils, an effective exchange of 16:0 for 18:0 of approximately 5% of energy was achieved with all other fatty acids being held constant. Monkeys were rotated through two 10-wk feeding periods, during which time plasma lipids and in vivo lipoprotein metabolism (following the simultaneous injection of (131)I-LDL and (125)I- HDL were evaluated). Plasma triacyglycerol (0.40 +/- 0.03 vs. 0.37 +/- 0.03 mmol/L), plasma total cholesterol (3.59 +/- 0.18 vs. 3.39 +/- 0.23 mmol/L), HDL cholesterol (1.60 +/- 0.16 vs 1.53 +/- 0.16 mmol/L) and non-HDL cholesterol (2.02 +/- 0.26 vs. 1.86 +/- 0.23 mmol/L) concentrations did not differ when monkeys consumed the palmitic acid and stearic acid diets, respectively. Plasma lipoprotein compositional analyses revealed a higher cholesteryl ester content in the VLDL fraction isolated after consumption of the stearic acid diet (P < 0.10), as well as a larger VLDL particle diameter (16.3 +/- 1.7 nm vs. 13.8 +/- 3.6 nm; P < 0.05). Kinetic analyses revealed no significant differences in LDL or HDL transport parameters. These data suggest that when incorporated into diets following current guidelines, containing adequate PUFA, an exchange of 16:0 for 18:0, representing approximately 11 g/(d.10.46 mJ) [ approximately 11 g/(d.2500 kcal)] does not affect the plasma lipid profile and has minor effects on lipoprotein composition. Whether a similar effect would occur in humans under comparable dietary conditions remains to be established.

Conjugated linoleic acid: effects on plasma lipids and cardiovascular function.

Conjugated linoleic acid is a collective name for mixtures of several positional and geometric conjugated dienoic isomers of linoleic acid, which have been shown to impact favorably on several biological processes, particularly carcinogenesis. Recent studies have clearly established that the c9, t11 and t10, c12 isomers have distinct biological effects. The latter may be of particular importance in affecting blood lipids. Because conjugated linoleic acid has been suggested to be anti-atherogenic, this review is focused on its effects on cardiovascular function. Careful scrutiny of the literature suggests that at present it is premature to assign any beneficial role to conjugated linoleic acid in terms of its ability to impact either blood lipids or atherogenesis.

Intraoperative tremor monitoring for vitreoretinal microsurgery.

An instrument for intraoperative sensing of surgeons' hand tremor during vitreoretinal microsurgery has been developed. The instrument uses inertial sensing to detect tremor in six degrees of freedom. Instrument tip velocity is computed using the sensor data. The displacement amplitude of the tremor is then approximated analytically by modeling the velocity as sinusoidal. The instrument presently estimates oscillations at physiological tremor frequencies with error of less than 7%.

Differential modulation of nociceptive responses to mu and kappa opioid receptor directed drugs by blood glucose in experimentally induced diabetes rats.

The study has evaluated the effect of diabetes associated hyperglycaemia on nociception and antinociception induced by morphine, buprenorphine and pentazocine in female albino rats. Rats were allocated into 3 groups of 20 each--group I consisted of control having normal blood glucose levels (BGLs), group II consisted of streptozotocin-induced diabetics (STZ-D) having hyperglycaemia and group III consisted of diabetic rats controlled with insulin treatment. Immediately before and 15, 30 min, 1, 2 and 3 hr after injection with test drugs, rats were subjected to a thermal noxious stimulus using tail withdrawal from hot water and tail-flick latencies (TFL) so generated were recorded. Similarly, before and 30, 45 min and 1 hr after injection with drugs rats were subjected to abdominal writhing with hypertonic saline and number of writhes were counted per 90 sec. In STZ-D animals (BGLs 317.95 +/- 3.8 mg/dl) a decreased TFL with an increase in the number of writhes compared to control and diabetes controlled with insulin treatment was observed. Percent maximum possible effect of morphine (5 mg/kg, s.c.) and buprenorphine (2 mg/kg, s.c.) was significantly lower when compared to control as well as STZ-D controlled with insulin treatment groups. Similarly percent protection from writhing of morphine (0.05 mg/kg, s.c.) and buprenorphine (0.01 mg/kg, s.c.) was significantly less in comparison to control and STZ-D controlled with insulin treatment group. However, percent maximum possible effect of pentazocine (20 mg/kg, s.c.) and percent protection from writhing of pentazocine (1 mg/kg, s.c.) was significantly high in STZ-D rats when compared to control and STZ-D rats controlled with insulin treatment groups. The results suggest that both mu and kappa--opioid receptors may be modulated by blood glucose levels possibly involving cellular energetics mediated change in potassium (KATP) channels in females rats, albeit differentially.

Effect of Azadirachta indica (Neem) leaf aqueous extract on paracetamol-induced liver damage in rats.

The effect of aqueous leaf extract of Azadirachta indica (A. indica) was evaluated in paracetamol induced hepatotoxicity in rats. Liver necrosis was produced by administering single dose of paracetamol (2 g/kg, p.o.). The liver damage was evidenced by elevated levels of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyl transpeptidase (gamma-GT) and by histopathological observations of liver sections. Aqueous A. indica leaf extract (500 mg/kg, p.o.) significantly (P < 0.01) reduced these elevated levels of AST, ALT and gamma-GT. Paracetamol induced liver necrosis was also found to be reduced as observed macroscopically and histologically.