Possible involvement of caveolin in attenuation of cardioprotective effect of ischemic preconditioning in diabetic rat heart

<p>Abstract</p> <p>Background</p> <p>Nitric oxide (NO) has been noted to produce ischemic preconditioning (IPC)-mediated cardioprotection. Caveolin is a negative regulator of NO, which inhibits endothelial nitric oxide synthase (eNOS) by making caveolin-eNOS complex. The expression of caveolin is increased during diabetes mellitus (DM). The present study was designed to investigate the involvement of caveolin in attenuation of the cardioprotective effect of IPC during DM in rat.</p> <p>Methods</p> <p>Experimental DM was induced by single dose of streptozotocin (50 mg/Kg, <it>i.p</it>,) and animals were used for experiments four weeks later. Isolated heart was mounted on Langendorff's apparatus, and was subjected to 30 min of global ischemia and 120 min of reperfusion. IPC was given by four cycles of 5 min of ischemia and 5 min of reperfusion with Kreb's-Henseleit solution (K-H). Extent of injury was measured in terms of infarct size by triphenyltetrazolium chloride (TTC) staining, and release of lactate dehydrogenase (LDH) and creatin kinase-MB (CK-MB) in coronary effluent. The cardiac release of NO was noted by measuring the level of nitrite in coronary effluent.</p> <p>Results</p> <p>IPC- induced cardioprotection and release of NO was significantly decreased in diabetic rat heart. Pre-treatment of diabetic rat with daidzein (DDZ) a caveolin inhibitor (0.2 mg/Kg/s.c), for one week, significantly increased the release of NO and restored the attenuated cardioprotective effect of IPC. Also perfusion of sodium nitrite (10 μM/L), a precursor of NO, significantly restored the lost effect of IPC, similar to daidzein in diabetic rat. Administration of 5-hydroxy deaconate (5-HD), a mito K_ATPchannel blocker, significantly abolished the observed IPC-induced cardioprotection in normal rat or daidzein and sodium nitrite perfused diabetic rat heart alone or in combination.</p> <p>Conclusions</p> <p>Thus, it is suggested that attenuation of the cardioprotection in diabetic heart may be due to decrease the IPC mediated release of NO in the diabetic myocardium, which may be due to up -regulation of caveolin and subsequently decreased activity of eNOS.</p

CYP2D6 phenotyping in North Indian subjects in Delhi

The recognition of the importance of inter-subject variation in drug metabolism has increased markedly over the past 20 years. Inter-subject variation may be genetically determined, environmentally induced, or most commonly, a combination of both, resulting in genetic polymorphism. The objective of the present study is to examine the CYP2D6 phenotypes in north Indian population. The study was carried out on seventy-five unrelated healthy north Indian subjects. They were phenotyped with respect to their ability to metabolize dextromethorphan to dextorphan. Oral dextromethorphan (30 mg) was administered to each subject. Urine was collected during 0 to 8 h period after dosing and was analyzed for dextromethorphan and dextorphan by liquid chromatography mass spectrometry (LC-MS/MS). The log 10 (metabolic ratio), calculated as the ratio of dextromethorphan to dextorphan, was bimodally distributed. An antimode value of 0.3 was obtained by plotting a frequency histogram of the log metabolic ratios. The frequency of occurrence of poor metabolizers of dextromethorphan in north Indian subjects from Delhi was found to be 2.6%. Ethiopian Pharmaceutical Journal Vol. 24, 2006: 65-7

Data from: Improved access to early diagnosis and complete treatment of malaria in Odisha, India

Background In 2013, the Comprehensive Case Management Programme (CCMP) was initiated to assess the impact of universal access to diagnosis and treatment and improved surveillance on malaria transmission in different settings in Odisha state, India. Methods Pairs of intervention and control sub-districts (blocks), matched on malaria incidence were selected in four districts with different transmission intensities. CCMP activities included training and supervision, ensuring no stock-outs of malaria tests and drugs, analysing verified surveillance data, stratifying areas based on risk factors, and appointing alternative providers to underserved areas. Composite risk scores were calculated for each sub-centre using principal component analysis. Post−pre changes (2013–2015 versus 2011–2012) for annual blood examination rates (ABER) and annual parasite incidence (API) across intervention and control groups were assessed using difference-in-difference (DID) estimates, adjusted for malaria transmission risk. Results In the intervention sub-centres, the mean increase in ABER was 6.41 tests/sub-centre (95%CI 4.69, 8.14; p<0.01) and in API was 9.2 cases diagnosed/sub-centre (95%CI 5.18, 13.21; p<0.01). The control sub-centres reported lower increases in ABER (2.84 [95%CI 0.35, 5.34]; p<0.05) and API (3.68 [95%CI 0.45, 6.90]; p<0.05). The control-adjusted post–pre changes in API showed that 5.52 more cases (95%CI 0.34, 10.70; p<0.05) were diagnosed, and a 3.6 more cases (95%CI 0.58, 6.56; p<0.05) were tested per sub-centre in the intervention versus control areas. Larger differences in post–pre changes in API between intervention and control sub-centres were registered in the higher transmission-risk areas compared with the lower risk areas. All the changes were statistically significant. Conclusions Intensive intervention activities targeted at improved access to malaria diagnosis and treatment produced a substantial increase in blood examination and case notification, especially in inaccessible, hard-to-reach pockets. CCMP provides insights into how to achieve universal coverage of malaria services through a routine, state-run programme