Synthesis and goat pulmonary vasodilatory activity of some novel 1,3,4-oxadiazoles

AbstractA novel series of[(1Z)-1-(2,2-disubstituted-5-pyridin-4-yl-1,3,4-oxadiazol-3(2H)-yl) ethylidene] (PSMB1–PSMB15) were synthesized as title compounds. The synthesis route included the cyclization of carbonyl hydrazone in the presence of excess of acetic anhydride and subsequent condensation with various aromatic amines. All the title compounds were characterized by IR, 1H NMR, MS and elemental analysis. They were screened for their goat pulmonary vein relaxant activity. Compound PSMB9 was found the most active derivative exhibiting 83.33% relaxation. Isosorbide dinitrate was used as the standard drug for goat pulmonary vein relaxant activity

Synthesis and anti-inflammatory activity of 2-{[3-(trifluoromethyl) phenyl] amino} N, N'-bis (aryl) pyridine-3-carboximidamide

A novel compounds of 2-{[3-(trifluoromethyl) phenyl] amino} N, N'-bis (aryl) pyridine-3-carboximidamide (PJS1-PJS6) were synthesized by condensation of niflumic acid with aromatic amines using most reactive Lewis reagent: polyphosphoric acid trimethyl silyl ester (PPSE). These compounds were characterized by IR, 1H-NMR, HRMS-FAB and elemental analysis and evaluated for anti-inflammatory activity using carrageenin- induced rat paw oedema method. Compound PJS 5 showed significant activity exhibiting comparable reduction in edema.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Synthesis and anti-inflammatory activity of 2-{[3-(trifluoromethyl) phenyl] amino} N, N'-bis (aryl) pyridine-3-carboximidamide

A novel compounds of 2-{[3-(trifluoromethyl) phenyl] amino} N, N'-bis (aryl) pyridine-3-carboximidamide (PJS1-PJS6) were synthesized by condensation of niflumic acid with aromatic amines using most reactive Lewis reagent: polyphosphoric acid trimethyl silyl ester (PPSE). These compounds were characterized by IR, 1H-NMR, HRMS-FAB and elemental analysis and evaluated for anti-inflammatory activity using carrageenin- induced rat paw oedema method. Compound PJS 5 showed significant activity exhibiting comparable reduction in edema.Colegio de Farmacéuticos de la Provincia de Buenos Aire

2D and 3D QSAR studies and antibacterial activity of 4-methyl-3-(6-{[arylmethylene] amino}pyridin-3-YL)-2H-chromen-2-one derivatives

4-methyl-3-(6-{[arylmethylene] amino} pyridin-3-yl)-2H-chromen-2-one derivatives containing different functional groups have been synthesized and screened for their antibacterial activity against four different strains of bacteria. 2D and 3D QSAR analysis of synthesized derivatives were performed on Vlife MDS 3.5 software. The data set for QSAR studies encompassed activities of 64 molecules divided into training and test set. The best models were selected on basis of correlation coefficient (r2) and internal and external predictivity (Pred_r2) of the QSAR model. QSAR models reveled that electronic, steric and liphophillic parameters have correlation with antibacterial activity. The 3D interactions and their contributions indicate multi-targeted mode of action of the compounds.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Six months therapy for tuberculous meningitis.

BACKGROUND Tuberculous meningitis (TBM) is the main form of tuberculosis that affects the central nervous system and is associated with high rates of death and disability. Most international guidelines recommend longer antituberculous treatment (ATT) regimens for TBM than for pulmonary tuberculosis disease to prevent relapse. However, longer regimens are associated with poor adherence, which could contribute to increased relapse, development of drug resistance, and increased costs to patients and healthcare systems. OBJECTIVES To compare the effects of short-course (six months) regimens versus prolonged-course regimens for people with tuberculous meningitis (TBM). SEARCH METHODS We searched the following databases up to 31 March 2016: the Cochrane Infectious Diseases Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL), published in the Cochrane Library; MEDLINE; EMBASE; LILACS; INDMED; and the South Asian Database of Controlled Clinical Trials. We searched the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) and ClinicalTrials.gov for ongoing trials. We also checked article reference lists and contacted researchers in the field. SELECTION CRITERIA We included randomized controlled trials (RCTs) and prospective cohort studies of adults and children with TBM treated with antituberculous regimens that included rifampicin for six months or longer than six months. The primary outcome was relapse, and included studies required a minimum of six months follow-up after completion of treatment. DATA COLLECTION AND ANALYSIS Two review authors (SJ and HR) independently assessed the literature search results for eligibility, and performed data extraction and 'Risk of bias' assessments of the included studies. We contacted study authors for additional information when necessary. Most data came from single arm cohort studies without a direct comparison so we pooled the findings for each group of cohorts and presented them separately using a complete-case analysis. We assessed the quality of the evidence narratively, as using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was inappropriate with no direct comparisons between short- and prolonged-course regimens. MAIN RESULTS Four RCTs and 12 prospective cohort studies met our inclusion criteria, and included a total of 1881 participants with TBM. None of the included RCTs directly compared six months versus longer regimens, so we analysed all data as individual cohorts to obtain relapse rates in each set of cohorts.We included seven cohorts of participants treated for six months, with a total of 458 participants. Three studies were conducted in Thailand, two in South Africa, and one each in Ecuador and Papua New Guinea between the 1980s and 2009. We included 12 cohorts of participants treated for longer than six months (ranging from eight to 16 months), with a total of 1423 participants. Four studies were conducted in India, three in Thailand and one each in China, South Africa, Romania, Turkey and Vietnam, between the late 1970s and 2011.The proportion of participants classified as having stage III disease (severe) was higher in the cohorts treated for six months (33.2% versus 16.9%), but the proportion with known concurrent HIV was higher in the cohorts treated for longer (0/458 versus 122/1423). Although there were variations in the treatment regimens, most cohorts received isoniazid, rifampicin, and pyrazinamide during the intensive phase.Investigators achieved follow-up beyond 18 months after completing treatment in three out of the seven cohorts treated for six months, and five out of the 12 cohorts treated for eight to 16 months. All studies had potential sources of bias in their estimation of the relapse rate, and comparisons between the cohorts could be confounded.Relapse was an uncommon event across both groups of cohorts (3/369 (0.8%) with six months treatment versus 7/915 (0.8%) with longer), with only one death attributed to relapse in each group.Overall, the proportion of participants who died was higher in the cohorts treated for longer than six months (447/1423 (31.4%) versus 58/458 (12.7%)). However, most deaths occurred during the first six months in both treatment cohorts, which suggested that the difference in death rate was not directly related to duration of ATT but was due to confounding. Clinical cure was higher in the group of cohorts treated for six months (408/458 (89.1%) versus longer than six months (984/1336 (73.7%)), consistent with the observations for deaths.Few participants defaulted from treatment with six months treatment (4/370 (1.1%)) versus longer treatment (8/355 (2.3%)), and adherence was not well reported. AUTHORS' CONCLUSIONS In all cohorts most deaths occurred in the first six months; and relapse was uncommon in all participants irrespective of the regimen. Further inferences are probably inappropriate given this is observational data and confounding is likely. These data are almost all from participants who are HIV-negative, and thus the inferences will not apply to the efficacy and safety of the six months regimens in HIV-positive people. Well-designed RCTs, or large prospective cohort studies, comparing six months with longer treatment regimens with long follow-up periods established at initiation of ATT are needed to resolve the uncertainty regarding the safety and efficacy of six months regimens for TBM

Synthesis of Glycoconjugates in Potentiating Pharmacological and Pharmaceutical Activity

The full range of glycoconjugates made up of glycans, or carbohydrate chains, that are covalently joined to lipid or protein molecules is known as the glycome. Glycoconjugates are created, through the process of glycosylation (vary in length, glycan sequence, and the connections that connect them). The creation of therapies can now take advantage of new knowledge about the structure and operation of the glycome, which may enhance our capacity to control inflammation and immune responses, maximize the efficacy of therapeutic antibodies, and enhance immune responses to cancer. These instances highlight the promise of the young discipline of “glycomedicine.” The prevalence of glycoconjugates in nature and their significance in various biological processes have prompted the development of numerous synthesizing techniques for these molecules. Today, synthetic glycoconjugates are utilized to address a wide range of biological concerns linked to glycoconjugates. This study seeks to update earlier reviews on the topic as well as gather and compile the most recent developments in the fields of glycopeptide, glycoprotein, and glycolipid synthesis. Finally, we hope that this study may stimulate fruitful research in this significant area of medicinal chemistry by highlighting the triumphs and shortcomings of prior research

Comparing socio-economic inequalities in self-reported and undiagnosed hypertension among adults 45 years and over in India: what explains these inequalities?

Background: Hypertension (HTN) is a leading cause of mortality and morbidity in developing countries. For India, the hidden burden of undiagnosed hypertension is a major concern. This study aims to assess and explain socio-economic inequalities among self-reported and undiagnosed hypertensives in India. Methods: The study utilized data from the Longitudinal Aging Study in India (LASI), a nationally-representative survey of more than 72,000 older adults. The study used funnel plots, multivariable logistic regression, concentration indices, and decomposition analysis to explain the socio-economic gap in the prevalence of self-reported and undiagnosed hypertension between the richest and the poorest groups. Results: The prevalence of self-reported and undiagnosed hypertension was 27.4 and 17.8% respectively. Monthly per capita consumption expenditure (MPCE) quintile was positively associated with self-reported hypertension but negatively associated with undiagnosed hypertension. The concentration index for self-reported hypertension was 0.133 (p < 0.001), whereas it was − 0.047 (p < 0.001) for undiagnosed hypertension. Over 50% of the inequalities in self-reported hypertension were explained by the differences in the distribution of the characteristics whereas inequalities remained unexplained for undiagnosed hypertension. Obesity and diabetes were key contributors to pro-rich inequality. Conclusions: Results imply that self-reported measures underestimate the true prevalence of hypertension and disproportionately affect the poorer MPCE groups. The prevalence of self-reported HTN was higher in the richest group, whereas socio-economic inequality in undiagnosed hypertension was significantly concentrated in the poorest group. As majority of the inequalities remain unexplained in case of undiagnosed hypertension, broader health systems issues including barriers to access to health care may be contributing to inequalities

A longitudinal study of incident hypertension and its determinants in Indian adults aged 45 years and over: evidence from nationally representative WHO-SAGE study (2007-2015) Running head Incident hypertension and its determinants

Objectives: Hypertension (HT) is a leading cause of mortality and morbidity in developing countries. This study aimed to estimate the incidence of HT among adults aged 45 years and older in India and its associated risk factors. Methods: This study used longitudinal data from the Indian sample of the first and second waves of the World Health Organization Study on Global Ageing and Adult Health (WHO-SAGE). A bivariate analysis using Pearson's chi-square test was done to examine the associations of individual, lifestyle, and household characteristics with HT status reported in Wave 2. Incident HT changes were analyzed by adjusting for various covariates in the generalized estimating equation (logit link function) with an exchangeable correlation matrix and robust standard errors. Results: The study found that during the 8-year period from 2007 to 2015, the incidence of HT in individuals aged 45 years and over was 20.8%. Pre-hypertensive individuals had an overall incidence rate of 31.1 per 1,000 [95% confidence interval (CI): 26.20–35.9] and a 2.24 times higher odds ratio: 2.24 (95% CI: 1.65–3.03) of developing incident HT compared to those who were normotensive. Adults aged 45 years and older, overweight/obese individuals, and women were more at risk of incident HT. Conclusion: One in five individuals had developed HT over 8 years, with a greater risk of incident HT among women than men. Pre-hypertensive individuals were at a greater risk of developing incident HT compared to normotensive individuals. The study recommends comprehensive and effective management of pre-HT to tackle the burden of H