High Prevalence of Additional Cardiovascular Risk Factors in Eastern-Indian Young Adults with Type 2 Diabetes Mellitus.

Background and Aims: The American Diabetes Association recommends statin therapy for young type 2 diabetes mellitus (T2DM) adults only if one additional cardiovascular (CV) risk factor coexists. The data regarding CV risk factors in young Indian T2DM adults is limited. Hence, we assessed the prevalence of CV risk factors in young adults with T2DM from eastern India. Methods: In this cross-sectional study, diabetic medical health check records of eastern-Indian T2DM patients performed between March 2018 and March 2019 were retrospectively reviewed and the relevant data of T2DM patients (n = 3564) including CV risk factors [serum LDL-cholesterol of ≥100 mg/dL, hypertension (>140/90 mmHg), smoking, chronic kidney disease (eGFR of <60 ml/min), microalbumin to creatinine ratio of ≥30 mg/mg, and obesity/overweight (body mass index ≥23 kg/m2)] were analysed. Results: There were 3280 T2DM patients from eastern India and 679 (20.7%) were ≤40 years of age. Overweight/obesity (74.3%) and serum LDL-cholesterol of ≥100 mg/dL (69.2%) were the two most common additional CV risk factors. At least one additional CV risk factor was present in 576 (95.36%) patients, whereas at least two additional CV risk factors were present in 409 (67.7%) patients. At least one non-obesity/overweight CV risk factor was present in 472 (78.1%) patients. Conclusions: The study demonstrates a high prevalence of additional CV risk factors in young eastern-Indian adults with T2DM. Hence, there is a need for an intensive approach to managing the CV risk factors in young Indian adults with T2DM.

Calculated plasma osmolality at hospital admission correlates well with eGFR and D-Dimer, a simple outcome predictor and guiding tool for management of severe COVID-19 patients.

AIMS: To evaluate calculated total plasma osmolality as a marker of outcome prediction, fluid and metabolic balance, thrombotic risk in severe COVID-19 patients. METHODS: Retrospective data of RT-PCR confirmed hospitalized severe COVID-19 patients (total: n = 175 patients, including diabetic subset: n = 102) were analyzed. Clinically applicable cut-offs were derived using receiver operating characteristic (ROC) curve analysis for calculated total osmolality, eGFR, and D-dimer, and their correlations were studied. RESULTS: Among 175 severe COVID-19 patients, a significant association with mortality was seen with respect to calculated total osmolality (p < 0.001), eGFR (p < 0.001), and D-dimer (p < 0.001). In the total cohort, applicable cut-offs based on ROC curve in predicting outcome were, for total osmolality 299 mosm/kg (area under the curve (AUC)-0.773, odds ratio (OR)-1.09), eGFR 61.5 ml/min/m2 (AUC-0.789, OR-0.96), D-dimer 5.13 (AUC-0.814, OR-2.65) respectively. In diabetic subset, the cut-offs for total osmolality were 298 mosm/kg (AUC-0.794, OR-1.12), eGFR 44.9 ml/min/m2 (AUC-0.774, OR-0.96) and D-dimer 1.59 (AUC-0.769, OR-1.52) respectively. CONCLUSIONS: Applicable cut-offs for calculated total plasma osmolality, eGFR, and D-dimer predicts clinical outcome in severe COVID-19 with and without diabetes. Correlation studies validated calculated total osmolality as a marker of the combined effect of fluid and metabolic imbalance, compromised renal function and hypercoagulability.

Evaluation of simple and cost-effective immuno- haematological markers to predict outcome in hospitalized severe COVID-19 patients, with a focus on diabetes mellitus - A retrospective study in Andhra Pradesh, India.

BACKGROUND AND AIMS: COVID-19 pandemic has strained the health infrastructure globally, providing an opportunity to identify cost-effective biomarkers. We aimed to identify simple hematological prognostic markers in hospitalized severe COVID-19 patients with and without diabetes. METHODS: Retrospective study of RT-PCR confirmed hospitalized severe COVID-19 patients (total: n = 154 patients, including diabetic subset n = 57) were analyzed. Clinically applicable cut-offs were derived using receiver operating characteristic (ROC) curve analysis for total leucocyte count (TLC), absolute neutrophil count (ANC), neutrophil lymphocyte ratio (NLR), and derived neutrophil lymphocyte ratio (dNLR) in order to prognosticate the outcome. RESULTS: Among 154 severe COVID-19 patients, significant association with mortality was seen with respect to TLC(p < 0.001), ANC (p < 0.001), NLR(p < 0.001) and dNLR(p < 0.001). In the total cohort, applicable cut-offs based on ROC curve in predicting outcome were, for TLC 8950 cells/mm3 (area under curve (AUC)-0.764, odds ratio (OR)-7.53), ANC 7679 cells/mm3 (AUC-0.789, OR-8.14), NLR 5.13 (AUC-0.741, OR-4.77), dNLR 3.44 (AUC -0.741, OR-4.43) respectively.In diabetic subset, the cut-offs for TLC was 8950 cells/mm3 (AUC -0.762, OR-14.9), ANC 6510 cells/mm3 (AUC -0.773, OR-16.8), NLR 5.13(AUC -0.678, OR-6) and dNLR 3.25(AUC -0.685, OR-4.7) respectively. CONCLUSIONS: In severe COVID-19 patients irrespective of diabetes, a simple, applicable total leucocyte count cut-off, 8950 cells/mm3 , together with easily derived cut-offs for ANC, NLR, dNLR may serve as cost-effective prognosticators of clinical outcome. A normal TLC may be misleading in the intensive care and the above applicable cut-off for TLC serves as an early warning tool for high-risk identification and better in-hospital management. Even with similar or lower cut-offs, diabetics had a higher mortality.

Lead induced alterations in nitrite and nitrate levels in different regions of the rat brain.

Nitric oxide (NO) is a free radical synthesized by nitric oxide synthase (NOS) during the conversion of L-arginine to citrulline. Lead (Pb) affects neuronal functioning in the rat brain. Nitric oxide, a neuronal messenger has a short half life and converts immediately into nitrite and nitrate. The present study is designed to determine lead-induced alterations in NO production by measuring nitrite and nitrate in the cerebellum, the hippocampus, the frontal cortex and the brain stem of the rat brain. Male Sprague-Dawley rats were treated with lead acetate (5 and 15 mg/kg body wt.) by intraperitoneal injection. The control and experimental rats were sacrificed at the end of 7 and 14 days after treatment and different regions of the brain were isolated. Nitrite and nitrate (NOx) levels were estimated by the chemiluminescent method using the NOA 280 (Sievers). The data suggested dose-dependent and region-specific responses to lead. Both treatments of lead reduced NOx levels in the cerebellum and the hippocampus. However, the frontal cortex and the brain stem responded differently to Pb exposure. NOx levels in the frontal cortex were significantly increased in rats treated with low and high doses of Pb for 7 days but not in rats treated for 14 days, whereas in the brain stem, NOx levels were increased in a dose- and time-dependent manner. Although, the response was time-dependent, the variation between 7- and 14-day treatment was not clearly delineated. These results provide additional evidence that Pb exposure alters NO-production in rat brain leading to neuronal dysfunction.

Diquat- and acetaminophen-induced alterations of biliary efflux of iron in rats.

The effects of diquat on the biliary efflux of nonheme iron in rats were studied as a means of examining the possible effects of diquat metabolism on hepatocellular iron metabolism and the association of altered iron metabolism with the initiation of acute hepatic necrosis. Administration of hepatotoxic doses (0.1 mmol/kg) of diquat to male Fischer-344 rats increased biliary iron concentrations from 6 microM to more than 15 microM. However, increases in biliary efflux of iron were not observed during the first 60 min following exposure to diquat, despite the rapid increases in biliary glutathione disulfide concentrations, which increased maximally within 40 min. Biliary efflux of iron was not altered by diquat in Sprague-Dawley rats, which are resistant to hepatic necrosis in response to diquat, despite the marked oxidant stress responses observed in these animals. Conversely, hepatotoxic doses of acetaminophen (1500 mg/kg) caused significant decreases in biliary iron efflux. The rapid decreases in biliary iron caused by acetaminophen and the delay in diquat-induced iron efflux suggested the possibility that some fraction of the biliary iron was being excreted as reversibly formed GS-Fe2+ chelates, with inhibition of export by glutathione disulfide (GSSG) in the case of diquat, or by 3-(glutathion-S-yl)-acetaminophen (GS-AAP) in the case of the acetaminophen-treated animals. However, 50-200 mg/kg doses of acetaminophen showed little effect on biliary iron excretion despite producing biliary GS-AAP conjugate concentrations almost 1000 times the 6 microM concentrations of iron, which would not appear to support the hypothesis of excretion of GS-Fe2+ chelates. The data demonstrate a significant effect of diquat on hepatic iron metabolism in Fischer-344 rats, and the possible importance of this iron redistribution to reactive oxygen-mediated cell damage in vivo is indicated by the absence of similar responses in diquat-treated Sprague-Dawley rats.

In vivo effects of trivalent and hexavalent chromium on renal and hepatic atpases of a freshwater teleost Anabas scandens.

The in vivo toxic effect of trivalent and hexavalent chromium (25 mg/L) on the renal and hepatic tissue ATPases of an edible teleost Anabas scandens was studied. In an exposure span of 30 days Na(+)-K(+) ATPase activity exhibited a progressive inhibition in the kidney, but marked inhibition in Na(+)-K(+) ATPase activity was observed in the liver. Mg(2+) ATPase activity, however, exhibited an elevation on early exposures, with a later inhibition.

Nephrotoxic and hepatotoxic effects of trivalent and hexavalent chromium in a teleost fish Anabas scandens: enzymological and biochemical changes.

The effects of trivalent and hexavalent chromium (Cr3+ and Cr6+) compounds on renal and hepatic respiratory enzymes and metabolites of a freshwater fish, Anabas scandens, were studied. In a subchronic exposure of 30 days, both forms of chromium inhibited the activities of lactate dehydrogenase, succinate dehydrogenase, malate dehydrogenase, and isocitrate dehydrogenase, whereas the hexavalent form induced greater effects. The levels of pyruvate and lactate are not exactly reflected in lactate dehydrogenase activity.

Effect of trivalent and hexavalent chromium on renal and hepatic tissue glycogen metabolism of a fresh water teleost Anabas scandens.

The in vivo toxic impact of chromium in its two forms (trivalent and hexavalent) on glycogen metabolism in the liver and kidney of a fresh water teleost Anabas scandens was studied. In a sub-chronic exposure of 30 days, depletion of glycogen and glucose reserves reflected in the activity patterns of glycogen phosphorylases 'a and ab'. While both forms of chromium induced alterations in enzyme activities and metabolite levels in the two tissues, Cr(+6) exerted greater effects in the kidney.

Pyridine effects on expression and molecular regulation of the cytochrome P450IA gene subfamily.

The expression and molecular regulation of the cytochrome P450IA (P450IA) gene subfamily have been examined in rat hepatic tissue after treatment with pyridine. The microsomal ethoxyresorufin O-deethylase activity, which has been shown to be specific for the P450IA subfamily, was increased approximately 2- and 3.5-fold over control values at 10 and 16 hr, respectively, after a single dose of pyridine (100 mg/kg, intraperitoneally). P450IA1 protein expression was also elevated in a time-dependent manner, with a maximal increase in P450IA1 protein being seen at approximately 16 hr after a single dose of pyridine (100 mg/kg, intraperitoneally), as detected by immunoblot analysis using a monoclonal antibody that detects both P450IA1 and P450IA2. The immunochemically detectable level of P450IA1 decreased to that of control at 48 hr after treatment. Oligonucleotide probes specific for P450IA1 and P450IA2 mRNA were used in hybridization analyses to examine mRNA levels of P450IA1 and P450IA2, respectively. The level of P450IA1 mRNA in poly(A)+ mRNA was increased approximately 3- and 2-fold at 5 and 12 hr, respectively, after a single injection of pyridine, as evidenced by both slot blot and Northern blot analyses. A lesser increase (approximately 1.5-2-fold) in P450IA2 mRNA was also seen at 5 and 12 hr after treatment. The P450IA1 and P450IA2 mRNA levels returned to control values at 48 hr after pyridine administration. These results were compared with those produced by 3-methylcholanthrene at 5 hr after treatment. A multiplex polymerase chain reaction assay was also used to monitor simultaneously the changes in P450IA1, P450IA2, and P450IIE1 mRNA levels, and the results showed induction of P450IA1, in agreement with the results of slot and Northern blot analyses. In summary, metabolic activity assays, immunochemical detection, and Northern and slot blot analyses provide evidence to support the conclusion that pyridine modulates the expression of the P450IA gene subfamily and does so by elevating P450IA1 and P450IA2 mRNAs, through either transcriptional activation or increased mRNA stabilization. These results are in sharp contrast to P450IIE1 induction by pyridine, which appears to proceed through increased translational efficiency. Thus, pyridine, which is present in tobacco and tobacco smoke, is capable of simultaneously elevating multiple forms of P450 that are active in carcinogen metabolism.

In vivo recovery of glycogen metabolism in hemolymph and tissues of a freshwater field crab Barytelphusa guerini on exposure to hexavalent chromium.

The in vivo toxic effects of hexavalent chromium (20 mg/liter) on hemolymph glucose, tissue glycogen, total free sugars, and active and total phosphorylases of an edible, freshwater crab Barytelphusa guerini were studied. In a 15-day exposure span followed by a 15-day postexposure recovery, the time-course alterations in these constituent segments of the glycogen metabolism indicate an inconsistent depletion in metabolite levels and elevated enzyme activities during exposure period as well as hyperglycemia. An insignificant recovery was observed in these parameters on the 15th day of the postexposure phase.

Fluoride induced changes in protein metabolism in the tissues of freshwater crab Barytelphusa guerini.

Exposure of the freshwater field crab Barytelphusa guerini to a sublethal concentration of NaF (30 mg litre(-1)) caused significant alterations in protein metabolism. After an exposure time of 15 days, the crab was found to have a marked depletion of total protein and free amino acid content. A significant elevation in transaminases, Aspartate aminotransferase (AAT) and Alanine aminotransferase (ALAT), and Glutamate dehydrogenase (GDH) activities was reflected in the free amino acid levels of the tissues.

Fluoride-induced changes in carbohydrate metabolism in the tissues of fresh water crab Barytelphusa querini.

Exposure of fresh water crab Barytelphusa querini to a sublethal concentration of NaF (30 ppm) caused significant alterations in the carbohydrate metabolism. In an exposure span of 15 days the crab was observed to have marked depletion in glycogen and total free sugar levels. A significant elevation in "active" and "total" glycogen phosphorylase activity was observed. The activity changes of lactate dehydrogenase reflected changes in tissue lactate levels and succinate dehydrogenase activity had a tissue specificity.