Kv1.1 null mice have enlarged hippocampus and ventral cortex

BACKGROUND: Mutations in the Shaker-like voltage-gated potassium channel Kv1.1 are known to cause episodic ataxia type 1 and temporal lobe epilepsy. Mice that express a malfunctional, truncated Kv1.1 (BALB/cByJ-Kv1.1(mceph/mceph)) show a markedly enlarged hippocampus and ventral cortex in adulthood. RESULTS: To determine if mice lacking Kv1.1 also develop a brain enlargement similar to mceph/mceph, we transferred Kv1.1 null alleles to the BALB/cByJ background. Hippocampus and ventral cortex was then studied using in vivo 3D-magnetic resonance imaging and volume segmentation in adult Kv1.1 null mice, BALB/cByJ-Kv1.1(mceph/mceph), BALB/cByJ-Kv1.1(mceph/+), BALB.C3HeB -Kv1.1(-/+ )and wild type littermates. The Kv1.1 null brains had dramatically enlarged hippocampus and ventral cortex. Mice heterozygous for either the null allele or the mceph allele had normal-sized hippocampus and ventral cortex. CONCLUSION: Total absence of Kv1.1 can induce excessive overgrowth of hippocampus and ventral cortex in mice with a BALB/cByJ background, while mice with one wild type Kv1.1 allele develop normal-sized brains

Vitamin D supplementation on prediabetic adults with vitamin D deficiency: a double-blind placebo-controlled randomized clinical trial

Hypovitaminosis D (<20 ng/mL) is thought to increase insulin resistance and meta-inflammation contributing to the pathogenesis of diabetes mellitus (DM). Correcting vitamin D deficiency in people with prediabetes might halt its progression to DM. The aim of this study was to examine the effect of vitamin D supplementation on insulin resistance, glycemic status, and inflammation in prediabetic adults with vitamin D deficiency. This doubleblind randomized placebo-controlled trial was done among 27 newly detected prediabetic adults with hypovitaminosis D randomly assigned to 60,000 IU of vitamin D weekly for eight weeks followed by monthly for the next four months or placebo along with lifestyle modification in both groups [vitamin D (n= 14) vs. Placebo (n=13). They were comparable in terms of sex, age and borlymass index. Glycemic status, fasting plasma glucose (FPG) and Hemoglobin A1C (HbA1C), insulin resistance (homeostasis model assessment of insulin resistance (HOMA-IR) and inflammatory marker high sensitivity C reactive protein (hs-CRP) were measured at baseline and after six months of intervention. Vitamin D levels (ng/mL) increased in both groups from baseline (vitamin D vs. placebo: 12.2±5.9 vs. 3.9±3.5, mean±SD). FPG (mmol/L) significantly decreased in the Vitamin D group (before vs. after: 5.9±0.6 vs. 5.5±0.7, P=0.016, mean±SD), whereas HbA1C (%) and hs- CRP (mg/L) significantly increased in the placebo group (before vs. after- HbA1C: 5.8±0.3 vs. 6.0±0.4, P<0.001; hs-CRP: 5.0±4.4 vs. 5.6±4.9, P=0.039, mean±SD). Percent changes in glycemic status, HOMA-IR, and hs-CRP were statistically similar between the groups. Our study failed to demonstrate the positive effects of vitamin D supplementation on reducing glucose, insulin resistance, or inflammatory marker in prediabetic adult patients with hypovitaminosis D. BSMMU J 2022; 15(3): 167-17

Inhibition of rat brain mitochondrial electron transport chain activity by dopamine oxidation products during extended in vitro incubation: Implications for Parkinson's disease

AbstractSeveral studies on mitochondrial functions following brief exposure (5–15 min) to dopamine (DA) in vitro have produced extremely variable results. In contrast, this study demonstrates that a prolonged exposure (up to 2 h) of disrupted or lysed mitochondria to DA (0.1–0.4 mM) causes a remarkable and dose-dependent inhibition of complex I and complex IV activities. The inhibition of complex I and complex IV activities is not prevented by the antioxidant enzyme catalase (0.05 mg/ml) or the metal-chelator diethylenetriaminepentaacetic acid (0.1 mM) or the hydroxyl radical scavengers like mannitol (20 mM) and dimethyl sulphoxide (20 mM) indicating the non-involvement of ·OH radicals and Fenton's chemistry in this process. However, reduced glutathione (5 mM), a quinone scavenger, almost completely abolishes the DA effect on mitochondrial complex I and complex IV activities, while tyrosinase (250 units/ml) which catalyses the conversion of DA to quinone products dramatically enhances the former effect. The results suggest the predominant involvement of quinone products instead of reactive oxygen radicals in long-term DA-mediated inactivation of complex I and complex IV. This is further indicated from the fact that significant amount of quinones and quinoprotein adducts (covalent adducts of reactive quinones with protein thiols) are formed during incubation of mitochondria with DA. Monoamine oxidase A (MAO-A) inhibitor clorgyline also provides variable but significant protection against DA induced inactivation of complex I and complex IV activities, presumably again through inhibition of quinoprotein formation. Mitochondrial ability to reduce tetrazolium dye 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) in presence of a respiratory substrate like succinate (10 mM) is also reduced by nearly 85% following 2 h incubation with 0.4 mM DA. This effect of DA on mitochondrial function is also dose-dependent and presumably mediated by quinone products of DA oxidation. The mitochondrial dysfunction induced by dopamine during extended periods of incubation as reported here have important implications in the context of dopaminergic neuronal death in Parkinson's disease (PD)

Prevalence and patterns of dyslipidemia among lipid-lowering drug-naïve patients with type 2 diabetes mellitus – A countrywide study in Bangladesh

Background: Dyslipidemia is a major risk factor for cardiovascular disease in patients with type 2 diabetes mellitus (T2DM). This countrywide study explored the prevalence and patterns of dyslipidemia among patients with T2DM who were not taking lipid-lowering drugs (LLD). Methods: This cross-sectional study included 2241 subjects with T2DM visiting several endocrinology outpatient clinics throughout Bangladesh from January to December 2021. Lipid profiles were measured in fasting blood samples using automatic analyzers. Data were analyzed using Stata 17 (Stata Corp LLC, TX, USA). Results: 2241 patients were investigated; their mean age was 46.27 (±11.27, SD) years, and 57.16 % were women. Overall, the prevalence of dyslipidemia was 96.83 %. Total cholesterol (TC), low-density lipoprotein cholesterol (LDLC), and triglyceride (TG) were high in 42.88 %, 63.54 %, and 71.40 % of patients, respectively; high-density lipoprotein cholesterol (HDLC) was low in 77.60 %. Mixed dyslipidemia (including raised TC, LDLC, TG, and low HDLC) was the most prevalent (24.05 %) type. Being woman (adjusted OR: 5.63, 95%CI: 3.07–11.1) and uncontrolled diabetes (HbA1c <7 %) (adjusted OR: 2.64, 95%CI: 1.54–4.52) were independently associated with dyslipidemia. Dyslipidemia was associated with microvascular complications of diabetes. Conclusion: Dyslipidemia is a highly prevalent abnormality among LLD-naïve T2DM patients in Bangladesh. Early detection and prompt management are required to prevent complications arising from dyslipidemia