Antihypertensive agents in systemic hypertension associated with Type 2 diabetes in a tertiary care hospital

Background: Hypertension and diabetes mellitus are both chronic disorders and when they occur as co-morbidities create havoc by presenting with a plethora of morbidity and mortality. Both require drug treatment over a long period of time, which calls for stringent analysis of prescribing trends of the same.Objectives: The present study was intended to analyze prescribing pattern and establish prescribing trends of anti-hypertensive drugs (AHD) in hypertensive diabetic patients.Methods: The present study was a record based, randomized, non-interventional study of 2 years duration conducted at a tertiary care hospital of central India. Prescriptions from 400 case records of hypertensive diabetics were obtained from the medical record section. Demographic details, blood pressure, and AHDs prescribed were systematically entered in pre-validated case record form. All data were thoroughly analyzed for fallacies and appropriateness.Results: Among 400 patients, 221 were males, and 179 were females. Monotherapy was used in 366 (91.5%) patients while combination therapy was used in 34 (8.5%) patients. Most commonly used combination was angiotensin converting enzyme inhibitor (ACEI)+calcium channel blocker (CCB), while in monotherapy CCB≥ACEI>beta blocker>diuretic>angiotensin II receptor blocker were most commonly prescribed.Conclusion: The present study represents trend and attitude of physicians in prescribing AHDs. On comparing with Joint National Committee 7 guidelines, the majority of the cases deviated from the guidelines, mostly in a choice of AHDs and Fixed dose combination

Study of variation in price of various antidiabetic drugs available in Indian market

Background: Diabetes mellitus in early age is on the alarming rise in India, requiring lifelong treatment. There is a wide range of variation in the prices of antidiabetic drugs marketed in India. Hence, we decided to study price variations in the oral antidiabetic drugs available, either singly or in combination, and number of manufacturing companies for each, and to evaluate the difference in cost of different brands of same active drug by calculating percentage variation of cost.Methods: Cost of a particular drug being manufactured by different companies, in the same strength and dosage forms was obtained from “Current Index of Medical Specialties” July-October 2014 and “Indian Drug Review” July 2014. The difference in the maximum and minimum price of the same drug, manufactured by different pharmaceutical companies and percentage variation in price was calculated.Results: Percentage price variation among different group of drugs was found to be as follows: in sulfonylureas, it was highest in glimepiride 2 mg 836.44%, among biguanides - metformin 500 mg 245.55%, among thiazolidionediones-pioglitazone 15 mg 600%, among α glucosidase inhibitors - voglibose 284.61% and meglitinides - repaglinide 0.5 mg 181.40%. Among combination therapy glimepiride 1 mg + metformin 500 mg 366.66%, pioglitazone + metformin 207.51%, pioglitazone + glimepiride 268.42% showed maximum variation in price.Conclusion: The average percentage price variation of different brands of the same oral antidiabetic drug manufactured in India is very wide. The appropriate changes in the government policy, sensitizing the prescribers about cost of therapy and proper management of marketing drugs should be directed toward maximizing the benefits of therapy and minimizing negative economic consequences

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Investigation of potential antiurolithiatic activity and in silico docking studies of Karpura shilajit

In this present study, Karpura shilajit, an Ayurvedic herbo-mineral, currently used in the Ayurvedic clinical practice for various ailments, was investigated chemically and pharmacologically.To screen anti-lithiatic activity of Karpura shilajit against sodium oxalate (70 mg/kg, i.p) for 7 days and in vitro activity by nucleation-aggregation assay. Cystone (500 mg/kg, p.o.)used as a standard drug in the present study.Nephrolithiasis may also be associated with nephrocalcinosis,&nbsp;i.e., crystal depositions in tubular lumen and/or interstitium, an entity which suggests specific pathological processes. Preliminary Phytochemical screening resulted in the presence of alkaloids, flavonoids, saponins, carbohydrates, terpenoids and steroids. Karpura shilajit significantly restored creatinine, urea, uric acid, calcium, total protein, sodium and potassium levels insodium oxalate induced urolithiasis model. Histopathological examination further confirmed the induction of a long standing hypercalciuria or hyperoxaluria, conversely to nephrocalcinosis in the sections of kidney treated with sodium oxalate. Karpura shilajit treatment normalized the biochemical and renal stone markers in the experimental rats and showed better activity in vitro and in vivo models. Karpura shilajit had shown significant effect on urine volume, urine pH, urine excretion, sodium and potassium levels.&nbsp

Curcumin Protects Diabetic Mice against Isoproterenol-Induced Myocardial Infarction by Modulating CB2 Cannabinoid Receptors

Molecular docking revealed curcumin as a potent CB2 cannabinoid receptor (CB2R) agonist. Since CB2R is involved in cardioprotective functions, we explored its role in ameliorative actions of curcumin against myocardial damage triggered by isoproterenol in diabetic animals. Mice were kept on a high-fat diet (HFD) throughout the experiment (30 days). Following 7 days of HFD feeding, streptozotocin was administered (150 mg/kg, intraperitoneal) to induce diabetes. From day 11 to 30, diabetic mice received either curcumin (100 or 200 mg/kg/day, oral), CB2R antagonist AM630 (1 mg/kg/day, intraperitoneal) or both, with concurrent isoproterenol (150 mg/kg, subcutaneous) administration on day 28 and 29. Diabetic mice with myocardial infarction showed an altered hemodynamic pattern and lipid profile, reduced injury markers, antioxidants with increased lipid peroxidation in the myocardium, and elevated glucose and liver enzymes in the blood. Moreover, an increased pro-inflammatory markers, histological severity, myonecrosis, and edema were observed. Curcumin compensated for hemodynamic fluctuations, restored biochemical markers, preserved antioxidant capacity, decreased cytokines levels, and restored cardiac functionality. However, the AM630 pre-treatment attenuated the effects of curcumin. The data suggest the involvement of CB2R in the actions of curcumin such as in the prevention of myocardial stress and in the improvement of the normal status of the myocardial membrane associated with diabetes

Comparison of virtual wheelchair driving performance of people with traumatic brain injury using an isometric and a conventional joystick

Objective: To compare wheelchair driving performance in a driving simulator using a conventional joystick and an isometric joystick. Design: Randomized, cohort study. Setting: A research facility based in a hospital or in an independent living center. Participants: Participants (N=20; 12 men, 8 women; mean age ± SD, 30.62±10.91y) who were at least 1 year post-TBI. Interventions: Driving performance using an isometric joystick compared with a conventional movement joystick. Main Outcome Measures: Average trial completion time, and trajectory-specific measures measured orthogonal to the center of driving tasks: root mean squared error, movement offset, movement error, and number of significant changes in heading. Results: After statistically controlling for driving speed, participants were able to complete the driving tasks faster with an isometric joystick than while using a conventional movement joystick. Compared with the conventional joystick, an isometric joystick used for driving forward demonstrated fewer driving errors. During reverse driving the conventional joystick performed better. Conclusions: The customizable isometric joystick seems to be a promising interface for driving a powered wheelchair for individuals with TBI. © 2011 American Congress of Rehabilitation Medicine

Genome-Wide Association Analysis of Pancreatic Beta-Cell Glucose Sensitivity

Context: Pancreatic beta-cell glucose sensitivity is the slope of the plasma glucose-insulin secretion relationship and is a key predictor of deteriorating glucose tolerance and development of type 2 diabetes. However, there are no large-scale studies looking at the genetic determinants of beta-cell glucose sensitivity. Objective: To understand the genetic determinants of pancreatic beta-cell glucose sensitivity using genome-wide meta-analysis and candidate gene studies. Design: We performed a genome-wide meta-analysis for beta-cell glucose sensitivity in subjects with type 2 diabetes and nondiabetic subjects from 6 independent cohorts (n = 5706). Beta-cell glucose sensitivity was calculated from mixed meal and oral glucose tolerance tests, and its associations between known glycemia-related single nucleotide polymorphisms (SNPs) and genome-wide association study (GWAS) SNPs were estimated using linear regression models. Results: Beta-cell glucose sensitivity was moderately heritable (h2 ranged from 34% to 55%) using SNP and family-based analyses. GWAS meta-analysis identified multiple correlated SNPs in the CDKAL1 gene and GIPR-QPCTL gene loci that reached genome-wide significance, with SNP rs2238691 in GIPR-QPCTL (P value = 2.64 x 10(-9)) and rs9368219 in the CDKAL1 (P value = 3.15 x 10(-9)) showing the strongest association with beta-cell glucose sensitivity. These loci surpassed genome-wide significance when the GWAS meta-analysis was repeated after exclusion of the diabetic subjects. After correction for multiple testing, glycemia-associated SNPs in or near the HHEX and IGF2B2 loci were also associated with beta-cell glucose sensitivity. Conclusion: We show that, variation at the GIPR-QPCTL and CDKAL1 loci are key determinants of pancreatic beta-cell glucose sensitivity.Peer reviewe