Synthesis, Characterization and Antimicrobial Studies of Some Novel 1,3,4-Thiadiazolium-2-thiolate Derivatives

In this study, ten new 5-substituted-3-[4,6-di(morpholine-4-yl)-1,3,5-triazine 2-yl]-1,3,5-thiadiazolium-2-thiolate 6(a–j) were prepared via a five step procedure from the starting material 1,3,5-triazine (1). Structures of all synthesized compounds were confirmed by spectral data and elemental analyses. Newly synthesized compounds were tested for their antibacterial and antifungal activities against some important bacterial and fungal species. Some of the compounds were found to be moderately active against the tested organisms.Keywords: Thiadiazol, s-triazine, Mesoionic, NMR spectroscopy, IR spectroscop

Prevalence of Chronic airflow limitation in Kashmir, North India: Results from the BOLD study.

BACKGROUND: Data on spirometrically defined chronic airflow limitation (CAL) are scarce in developing countries. OBJECTIVE: To estimate the prevalence of spirometrically defined CAL in Kashmir, North India. METHODS: Using Burden of Obstructive Lung Disease survey methods, we administered questionnaires to randomly selected adults aged 40 years. Post-bronchodilator spirometry was performed to estimate the prevalence of CAL and its relation to potential risk factors. RESULTS: Of 1100 participants initially recruited, 953 (86.9%) responded and 757 completed acceptable spirometry and questionnaires. The prevalence of a forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) ratio less than the lower limit of normal was 17.3% (4.5) in males and 14.8% (2.1) in females. Risk factors for CAL included higher age, cooking with wood and lower educational status. The prevalence of current smoking was 61% in males and 22% in females; most smoked hookahs. CAL was found equally in non-smoking males and females, and was independently associated with the use of the hookah, family history of respiratory disease and poor education. A self-reported doctor's diagnosis of chronic obstructive pulmonary disease was reported in 8.4/1000 (0.9% of females and 0.8% of males). CONCLUSION: Spirometrically confirmed CAL is highly prevalent in Indian Kashmir, and seems to be related to the high prevalence of smoking, predominantly in the form of hookah smoking

Enhancement of Gap Junction Function During Acute Myocardial Infarction Modifies Healing and Reduces Late Ventricular Arrhythmia Susceptibility

Objectives: To investigate the effects of enhancing gap junction (GJ) coupling during acute myocardial infarction (MI) on the healed infarct scar morphology and late post-MI arrhythmia susceptibility. Background: Increased heterogeneity of myocardial scarring after MI is associated with greater arrhythmia susceptibility. We hypothesized that short-term enhancement of GJ coupling during acute MI can produce more homogeneous infarct scars, reducing late susceptibility to post-MI arrhythmias. Methods: Following arrhythmic characterisation of the rat 4-week post-MI model (n=24), a further 27 Sprague-Dawley rats were randomised to receive rotigaptide to enhance GJ coupling (n=13) or saline control (n=14) by osmotic minipump immediately prior to, and for the first 7 days following surgical MI. At 4 weeks post-MI, hearts were explanted for ex vivo programmed electrical stimulation (PES) and optical mapping. Heterogeneity of infarct border zone (IBZ) scarring was quantified by histomorphometry. Results: Despite no detectable difference in infarct size at 4 weeks post-MI, rotigaptide-treated hearts had reduced arrhythmia susceptibility during PES (Inducibility score: rotigaptide 2.40.8, control 5.00.6, p=0.02) and less heterogeneous IBZ scarring (standard deviation of IBZ Complexity Score: rotigaptide 1.10.1, control 1.40.1, p=0.04), associated with an improvement in IBZ conduction velocity (rotigaptide 43.13.4 cm/s, control 34.82.0 cm/s, p=0.04). Conclusions: Enhancement of GJ coupling for only 7 days at the time of acute MI produced more homogeneous IBZ scarring and reduced arrhythmia susceptibility at 4 weeks post-MI. Short-term GJ modulation at the time of MI may represent a novel treatment strategy to modify the healed infarct scar morphology and reduce late post-MI arrhythmic risk

Systemic adverse effects from inhaled corticosteroid use in asthma: a systematic review.

BACKGROUND: Oral corticosteroid use increases the risk of systemic adverse effects including osteoporosis, bone fractures, diabetes, ocular disorders and respiratory infections. We sought to understand if inhaled corticosteroid (ICS) use in asthma is also associated with increased risk of systemic effects. METHODS: MEDLINE and Embase databases were searched to identify studies that were designed to investigate ICS-related systemic adverse effects in people with asthma. Studies were grouped by outcome: bone mineral density (BMD), respiratory infection (pneumonia or mycobacterial infection), diabetes and ocular disorder (glaucoma or cataracts). Study information was extracted using the PICO checklist. Risk of bias was assessed using the Cochrane Risk of Bias tool (randomised controlled trials) and Risk of Bias In Non-randomised Studies of Interventions-I tool (observational studies). A narrative synthesis was carried out due to the low number of studies reporting each outcome. RESULTS: Thirteen studies met the inclusion criteria, 2 trials and 11 observational studies. Study numbers by outcome were: six BMD, six respiratory infections (four pneumonia, one tuberculosis (TB), one non-TB mycobacteria), one ocular disorder (cataracts) and no diabetes. BMD studies found conflicting results (three found loss of BMD and three found no loss), but were limited by study size, short follow-up and lack of generalisability. Studies addressing infection risk generally found positive associations but suffered from a lack of power, misclassification and selection bias. The one study which assessed ocular disorders found an increased risk of cataracts. Most studies were not able to fully adjust for known confounders, including oral corticosteroids. CONCLUSION: There is a paucity of studies assessing systemic adverse effects associated with ICS use in asthma. Those studies that have been carried out present conflicting findings and are limited by multiple biases and residual confounding. Further appropriately designed studies are needed to quantify the magnitude of the risk for ICS-related systemic effects in people with asthma

Calcium signals and calpain-dependent necrosis are essential for release of coxsackievirus B from polarized intestinal epithelial cells

Coxsackievirus B (CVB), a member of the enterovirus family, targets the polarized epithelial cells lining the intestinal tract early in infection. Although the polarized epithelium functions as a protective barrier, this barrier is likely exploited by CVB to promote viral entry and subsequent egress. Here we show that, in contrast to nonpolarized cells, CVB-infected polarized intestinal Caco-2 cells undergo nonapoptotic necrotic cell death triggered by inositol 1,4,5-trisphosphate receptor-dependent calcium release. We further show that CVB-induced cellular necrosis depends on the Ca 2+-activated protease calpain-2 and that this protease is involved in CVB-induced disruption of the junctional complex and rearrangements of the actin cytoskeleton. Our study illustrates the cell signaling pathways hijacked by CVB, and perhaps other viral pathogens, to promote their replication and spread in polarized cell types. © 2011 Bozym et al.published_or_final_versio

TAC1 (tachykinin, precursor 1)

Review on TAC1 (tachykinin, precursor 1), with data on DNA, on the protein encoded, and where the gene is implicated

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