Randomized, interventional, prospective, comparative study to evaluate the antihypertensive efficacy and tolerability of ramipril versus telmisartan in stage 1 hypertensive patients with diabetes mellitus

Angiotensin converting enzyme inhibitors and angiotensin receptor blockers are keystones for therapy of hypertension in diabetes because they show favourable effects on diabetic nephropathy and cardiovascular disease outcomes. A prospective, randomized, interventional clinical study of one year duration was conducted to comparatively evaluate anti-hypertensive efficacy and tolerability profile of ramipril versus telmisartan in stage 1 hypertensive patients associated with type 2 diabetes mellitus, amongst patients of either sex attending the medicine OPD of Rohilkhand Medical College and Hospital, Bareilly. Clearance from institutional ethical committee and written informed consent of the participants was taken. The enrolled 222 patients were randomized into ramipril and telmisartan groups, of these only 192 patients completed the study. The data obtained were statistically analyzed by paired and unpaired t-test using SPSS software. Prevalence of hypertension in diabetics was more in 41 to 50 years age group, in females (male: female ratio= 0.92:1) and in rural areas (rural: urban ratio= 0.61:1). Baseline BP values were equally matched in both groups. The SBP and DBP were reduced from baseline in all the ten follow-ups and were statistically significant (p <0.0001 for both groups). Regarding adverse effects, both drugs were well tolerated though dry irritating cough and dizziness was more in ramipril group. Both ramipril and telmisartan as monotherapy were equally effective in lowering SBP and DBP on prolonged use in diabetic hypertensives but the incidence of adverse effects was higher with ramipril hence telmisartan be preferred.KEY WORDS: Ramipril; Telmisartan; Systolic; Diastolic blood pressure; Stage 1hypertensive patients; Diabetes mellitu

A comparative evaluation of Losartan/Hydrochlorothiazide (fixed combination) versus Amlodipine monotherapy in patients with hypertension in Rohilkhand region

The aim of this prospective randomized study is to comparatively evaluatethe antihypertensive efficacy of combination therapy   (losartan/hydrochlorothiazide) with monotherapy (amlodipine). This prospective randomized clinical study was carried out for twelve months (July 2012 – June 2013) and enrolled 250 newly diagnosed stage-I hypertensive patients (as per JNC-7 criteria), who attended medicine outdoor department of Rohilkhand Medical College & Hospital, Bareilly. Hypertensive patients between 18 - 70 years of age were included in the study. The patients were randomly divided into two groups. The Losartan / Hydrochlorothiazide (LST/HCTZ) group included 128 patients and amlodipine group (AMLO) included 122 patients. A total of 40 patients, 14 patients of LST/HCTZ group and 26 patients of AMLO group dropped out during the study. M/F ratio was 0.92:1, and urban/rural ratio was 1.06:1. Majority of patients were in the 41-50 years age group. Mean systolic blood pressure (SBP) and mean diastolic blood pressure (DBP) were comparable between both groups, being 152.97 mm Hg and 95.05mm Hg for LST/HCTZ group and 153.27mm Hg and 95.27 mm Hg for AMLO group. Both mean SBP and mean DBP blood were statistically significantly reduced in each of the six follow ups in both the groups (p<0.001). The mean SBP was reduced from 152.97±0.45 to 121.65±0.81 and mean DBP was reduced from 95.05±0.17 to 76.28±0.51(in the sixth follow-up) in  LST/HCTZ group. Similarly mean baseline SBP 153.270±64 was reduced to120.65±0.93 and mean baseline DBP was reduced from 95.270±38 to 75.54±0.67 after six months of therapy in AMLO group. The comparative evaluation of the two regimens revealed no statistically significant  difference (p>0.05) in both SBP and DBP reduction. Both LST/HCTZ and AMLO regimen were equally effective and well tolerated in lowering blood pressure.KEY WORDS: Anti-hypertensive efficacy, Losartan/ hydrochlorothiazide combination, Amlodipine; Hypertensive patient

Plumbagin inhibits invasion and migration of breast and gastric cancer cells by downregulating the expression of chemokine receptor CXCR4

<p>Abstract</p> <p>Background</p> <p>Increasing evidence indicates that the interaction between the CXC chemokine receptor-4 (CXCR4) and its ligand CXCL12 is critical in the process of metastasis that accounts for more than 90% of cancer-related deaths. Thus, novel agents that can downregulate the CXCR4/CXCL12 axis have therapeutic potential in inhibiting cancer metastasis.</p> <p>Methods</p> <p>In this report, we investigated the potential of an agent, plumbagin (5-hydroxy-2-methyl-1, 4-naphthoquinone), for its ability to modulate CXCR4 expression and function in various tumor cells using Western blot analysis, DNA binding assay, transient transfection, real time PCR analysis, chromatin immunoprecipitation, and cellular migration and invasion assays.</p> <p>Results</p> <p>We found that plumbagin downregulated the expression of CXCR4 in breast cancer cells irrespective of their HER2 status. The decrease in CXCR4 expression induced by plumbagin was not cell type-specific as the inhibition also occurred in gastric, lung, renal, oral, and hepatocellular tumor cell lines. Neither proteasome inhibition nor lysosomal stabilization had any effect on plumbagin-induced decrease in CXCR4 expression. Detailed study of the underlying molecular mechanism(s) revealed that the regulation of the downregulation of CXCR4 was at the transcriptional level, as indicated by downregulation of mRNA expression, inhibition of NF-κB activation, and suppression of chromatin immunoprecipitation activity. In addition, using a virtual, predictive, functional proteomics-based tumor pathway platform, we tested the hypothesis that NF-κB inhibition by plumbagin causes the decrease in CXCR4 and other metastatic genes. Suppression of CXCR4 expression by plumbagin was found to correlate with the inhibition of CXCL12-induced migration and invasion of both breast and gastric cancer cells.</p> <p>Conclusions</p> <p>Overall, our results indicate, for the first time, that plumbagin is a novel blocker of CXCR4 expression and thus has the potential to suppress metastasis of cancer.</p

Tuberculous dilated cardiomyopathy: an under-recognized entity?

BACKGROUND: Tuberculosis (TB) is a common public health problem in many parts of the world. TB is generally believed to spare these four organs-heart, skeletal muscle, thyroid and pancreas. We describe a rare case of myocardial TB diagnosed on a post-mortem cardiac biopsy. CASE PRESENTATION: Patient presented with history suggestive of congestive heart failure. We describe the clinical presentation, investigations and outcome of this case, and review the literature on the involvement of myocardium by TB. CONCLUSION: Involvement of myocardium by TB is rare. However it should be suspected as a cause of congestive heart failure in any patient with features suggestive of TB. Increasing recognition of the entity and the use of endomyocardial biopsy may help us detect more cases of this "curable" form of cardiomyopathy

Learning horizon and optimal alliance formation

We develop a theoretical Bayesian learning model to examine how a firm’s learning horizon, defined as the maximum distance in a network of alliances across which the firm learns from other firms, conditions its optimal number of direct alliance partners under technological uncertainty. We compare theoretical optima for a ‘close’ learning horizon, where a firm learns only from direct alliance partners, and a ‘distant’ learning horizon, where a firm learns both from direct and indirect alliance partners. Our theory implies that in high tech industries, a distant learning horizon allows a firm to substitute indirect for direct partners, while in low tech industries indirect partners complement direct partners. Moreover, in high tech industries, optimal alliance formation is less sensitive to changes in structural model parameters when a firm’s learning horizon is distant rather than close. Our contribution lies in offering a formal theory of the role of indirect partners in optimal alliance portfolio design that generates normative propositions amenable to future empirical refutation

Measuring the burden of arboviral diseases: the spectrum of morbidity and mortality from four prevalent infections

<p>Abstract</p> <p>Background</p> <p>Globally, arthropod-borne virus infections are increasingly common causes of severe febrile disease that can progress to long-term physical or cognitive impairment or result in early death. Because of the large populations at risk, it has been suggested that these outcomes represent a substantial health deficit not captured by current global disease burden assessments.</p> <p>Methods</p> <p>We reviewed newly available data on disease incidence and outcomes to critically evaluate the disease burden (as measured by disability-adjusted life years, or DALYs) caused by yellow fever virus (YFV), Japanese encephalitis virus (JEV), chikungunya virus (CHIKV), and Rift Valley fever virus (RVFV). We searched available literature and official reports on these viruses combined with the terms "outbreak(s)," "complication(s)," "disability," "quality of life," "DALY," and "QALY," focusing on reports since 2000. We screened 210 published studies, with 38 selected for inclusion. Data on average incidence, duration, age at onset, mortality, and severity of acute and chronic outcomes were used to create DALY estimates for 2005, using the approach of the current Global Burden of Disease framework.</p> <p>Results</p> <p>Given the limitations of available data, nondiscounted, unweighted DALYs attributable to YFV, JEV, CHIKV, and RVFV were estimated to fall between 300,000 and 5,000,000 for 2005. YFV was the most prevalent infection of the four viruses evaluated, although a higher proportion of the world's population lives in countries at risk for CHIKV and JEV. Early mortality and long-term, related chronic conditions provided the largest DALY components for each disease. The better known, short-term viral febrile syndromes caused by these viruses contributed relatively lower proportions of the overall DALY scores.</p> <p>Conclusions</p> <p>Limitations in health systems in endemic areas undoubtedly lead to underestimation of arbovirus incidence and related complications. However, improving diagnostics and better understanding of the late secondary results of infection now give a first approximation of the current disease burden from these widespread serious infections. Arbovirus control and prevention remains a high priority, both because of the current disease burden and the significant threat of the re-emergence of these viruses among much larger groups of susceptible populations.</p

A common haplotype lowers PU.1 expression in myeloid cells and delays onset of Alzheimer's disease

A genome-wide survival analysis of 14,406 Alzheimer's disease (AD) cases and 25,849 controls identified eight previously reported AD risk loci and 14 novel loci associated with age at onset. Linkage disequilibrium score regression of 220 cell types implicated the regulation of myeloid gene expression in AD risk. The minor allele of rs1057233 (G), within the previously reported CELF1 AD risk locus, showed association with delayed AD onset and lower expression of SPI1 in monocytes and macrophages. SPI1 encodes PU.1, a transcription factor critical for myeloid cell development and function. AD heritability was enriched within the PU.1 cistrome, implicating a myeloid PU.1 target gene network in AD. Finally, experimentally altered PU.1 levels affected the expression of mouse orthologs of many AD risk genes and the phagocytic activity of mouse microglial cells. Our results suggest that lower SPI1 expression reduces AD risk by regulating myeloid gene expression and cell function