Monogenic diabetes: A single center experience from South India

Monogenic forms of diabetes in children are frequently misclassified as either type 1 diabetes or young‐onset type 2 diabetes. There is a paucity of literature regarding pediatric monogenic diabetes in the Indian population. A retrospective analysis of case records of 37 children with monogenic diabetes who were diagnosed between 2008 and 2019 in a South Indian tertiary care center was performed. The write‐up describes the clinical, biochemical, and genetic characterization of these patients with the diagnoses of neonatal diabetes mellitus (15 patients), MODY (five patients), and various forms of syndromic diabetes (13 with Wolfram syndrome, two with H syndrome, one with mitochondrial diabetes, and one with thiamine responsive megaloblastic anemia).     

Lipid profile and apolipoprotein E polymorphism in essential hypertension

BACKGROUND: Studies in several populations have indicated that genetic variation at the apolipoprotein E structural locus influences atherosclerosis leading to cardiovascular diseases. The possible role of apolipoprotein E polymorphism in the development of essential hypertension has not been sufficiently investigated. In this case-control study, we aimed to determine the significance of association between essential hypertension and apolipoprotein E genotypes. In addition, apolipoprotein E genotypes were correlated with serum lipid levels in order to understand the possible interaction between the specific genotype and the lipid profiles that can contribute to hypertension. METHODS AND RESULTS: The apolipoprotein E genotypes were assayed in 185 patients and 200 controls by polymerase chain reaction followed by enzymatic digestion with Hha I. Using logistic regression analysis, the multivariate-adjusted odds of hypertension were calculated. The incidence of epsilon4 allele was found to be significantly higher in patients (12.16%) than in controls (5.75%, chi2=10.87; p<0.05) and also in patients with positive family history (16.7%) as compared to negative family history (8.87%, chi2 = 8.45; p<0.1). Further, it was observed that carriers of epsilon4 allele have twice as much risk (p<0.05) for developing hypertension as compared to carriers of other alleles. Patients with epsilon4 allele had significantly higher levels of total cholesterol and low-density lipoprotein- cholesterol as compared to epsilon4 allele non-carriers (p<0.05). The adjusted odds ratios for epsilon4 and epsilon2 alleles versus epsilon3 allele were 2.2 (95% confidence interval 1.2 to 3.8, p<0.05) and 1.2 (95% CI, 0.75 to 1.77, p<0.514), respectively. CONCLUSIONS: Our study revealed a strong association of apolipoprotein E locus with hypertension and lipid profile. However, large population-based studies are needed to understand the exact role played by the locus in causing the condition.     

Punica granatum flower extract, a potent alpha-glucosidase inhibitor, improves postprandial hyperglycemia in Zucker diabetic fatty rats

Postprandial hyperglycemia plays an important role in the development of type 2 diabetes and has been proposed as an independent risk factor for cardiovascular diseases. The flowering part of Punica granatum Linn. (Punicaceae) (PGF) has been recommended in Unani literature as a remedy for diabetes. We investigated the effect and action mechanism of a methanolic extract from PGF on hyperglycemia in vivo and in vitro. Oral administration of PGF extract markedly lowered plasma glucose levels in non-fasted Zucker diabetic fatty rats (a genetic model of obesity and type 2 diabetes), whereas it had little effect in the fasted animals, suggesting it affected postprandial hyperglycemia in type 2 diabetes. In support of this conclusion the extract was found to markedly inhibit the increase of plasma glucose levels after sucrose loading, but not after glucose loading in mice, and it had no effect on glucose levels in normal mice. In vitro, PGF extract demonstrated a potent inhibitory effect on alpha-glucosidase activity (IC50: 1.8 microg/ml). The inhibition is dependent on the concentration of enzyme and substrate, as well as on the length of pretreatment with the enzyme. These findings strongly suggest that PGF extract improves postprandial hyperglycemia in type 2 diabetes and obesity, at least in part, by inhibiting intestinal alpha-glucosidase activity.     

Pomegranate flower improves cardiac lipid metabolism in a diabetic rat model: role of lowering circulating lipids

Excess triglyceride (TG) accumulation and increased fatty acid (FA) oxidation in the diabetic heart contribute to cardiac dysfunction. Punica granatum flower (PGF) is a traditional antidiabetic medicine. Here, we investigated the effects and mechanisms of action of PGF extract on abnormal cardiac lipid metabolism both in vivo and in vitro. Long-term oral administration of PGF extract (500 mg kg(-1)) reduced cardiac TG content, accompanied by a decrease in plasma levels of TG and total cholesterol in Zucker diabetic fatty (ZDF) rats, indicating improvement by PGF extract of abnormal cardiac TG accumulation and hyperlipidemia in this diabetic model. Treatment of ZDF rats with PGF extract lowered plasma FA levels. Furthermore, the treatment suppressed cardiac overexpression of mRNAs encoding for FA transport protein, peroxisome proliferator-activated receptor (PPAR)-alpha, carnitine palmitoyltransferase-1, acyl-CoA oxidase and 5'-AMP-activated protein kinase alpha2, and restored downregulated cardiac acetyl-CoA carboxylase mRNA expression in ZDF rats, whereas it showed little effect in Zucker lean rats. The results suggest that PGF extract inhibits increased cardiac FA uptake and oxidation in the diabetic condition. PGF extract and its component oleanolic acid enhanced PPAR-alpha luciferase reporter gene activity in human embryonic kidney 293 cells, and this effect was completely suppressed by a selective PPAR-alpha antagonist MK-886, consistent with the presence of PPAR-alpha activator activity in the extract and this component. Our findings suggest that PGF extract improves abnormal cardiac lipid metabolism in ZDF rats by activating PPAR-alpha and thereby lowering circulating lipid and inhibiting its cardiac uptake.     

Performance of Clinical Laboratories in South African Parasitology Proficiency Testing Surveys between 2004 and 2010

Performance in proficiency testing (PT) schemes is an objective measure of a laboratory's best performance. We examined the performance of participants in two parasitology PT schemes in South Africa from 2004 through 2010. The average rates of acceptable scores over the period were 58% and 66% for the stool and blood parasite schemes, respectively. In our setting, participation in PT alone is insufficient to improve performance; a policy that provides additional resources and training seems necessary.     

Inhibition of ROS-induced apoptosis in endothelial cells by nitrone spin traps via induction of phase II enzymes and suppression of mitochondria-dependent pro-apoptotic signaling

Oxidative stress is the main etiological factor behind the pathogenesis of various diseases including inflammation, cancer, cardiovascular and neurodegenerative disorders. Due to the spin trapping abilities and various pharmacological properties of nitrones, their application as therapeutic agent has been gaining attention. Though the antioxidant properties of the nitrones are well known, the mechanism by which they modulate the cellular defense machinery against oxidative stress is not well investigated and requires further elucidation. Here, we have investigated the mechanisms of cytoprotection of the nitrone spin traps against oxidative stress in bovine aortic endothelial cells (BAEC). Cytoprotective properties of both the cyclic nitrone 5,5-dimethyl-pyrroline N-oxide (DMPO) and linear nitrone α-phenyl N-tert-butyl nitrone (PBN) against H₂O₂-induced cytotoxicity were investigated. Preincubation of BAEC with PBN or DMPO resulted in the inhibition of H₂O₂-mediated cytotoxicity and apoptosis. Nitrone-treatment resulted in the induction and restoration of phase II antioxidant enzymes via nuclear translocation of NF-E2-related factor 2 (Nrf-2) in oxidatively-challenged cells. Furthermore, the nitrones were found to inhibit the mitochondrial depolarization and subsequent activation of caspase-3 induced by H₂O₂. Significant down-regulation of the pro-apoptotic proteins p53 and Bax, and up-regulation of the anti-apoptotic proteins Bcl-2 and p-Bad were observed when the cells were preincubated with the nitrones prior to H₂O₂-treatment. It was also observed that Nrf-2 silencing completely abolished the protective effects of nitrones. Hence, these findings suggest that nitrones confer protection to the endothelial cells against oxidative stress by modulating phase II antioxidant enzymes and subsequently inhibiting mitochondria-dependent apoptotic cascade.