Common variants of IL6, LEPR, and PBEF1 are associated with obesity in Indian children

The increasing prevalence of obesity in urban Indian children is indicative of an impending crisis of metabolic disorders. Although perturbations in the secretion of adipokines and inflammatory molecules in childhood obesity are well documented, the contribution of common variants of genes encoding them is not well investigated. We assessed the association of 125 common variants from 21 genes, encoding adipocytokines and inflammatory markers in 1,325 urban Indian children (862 normal weight [NW group] and 463 overweight/obese [OW/OB group]) and replicated top loci in 1,843 Indian children (1,399 NW children and 444 OW/OB children). Variants of four genes (PBEF1 [rs3801266] [P = 4.5 × 10(-4)], IL6 [rs2069845] [P = 8.7 × 10(-4)], LEPR [rs1137100] [P = 1.8 × 10(-3)], and IL6R [rs7514452] [P = 2.1 × 10(-3)]) were top signals in the discovery sample. Associations of rs2069845, rs1137100, and rs3801266 were replicated (P = 7.9 × 10(-4), 8.3 × 10(-3), and 0.036, respectively) and corroborated in meta-analysis (P = 2.3 × 10(-6), 3.9 × 10(-5), and 4.3 × 10(-4), respectively) that remained significant after multiple testing corrections. These variants also were associated with quantitative measures of adiposity (weight, BMI, and waist and hip circumferences). Allele dosage analysis of rs2069845, rs1137100, and rs3801266 revealed that children with five to six risk alleles had an approximately four times increased risk of obesity than children with less than two risk alleles (P = 1.2 × 10(-7)). In conclusion, our results demonstrate the association of the common variants of IL6, LEPR, and PBEF1 with obesity in Indian children.     

Isolation of troponin-like complex from bovine brain cortex.

A troponin-like complex has been isolated from bovine brain cortex. This tropinin-like complex, with brain tropomyosin, confers Ca2+ sensitivity to the actin-activated myosin adenosinetriphosphatase (ATP phosphohydrolase, EC 3.6.1.3). That is, the Mg2+-stimulated ATPase activity generated by the interaction of purified muscle actin with muscle myosin is inhibited in the absence of Ca2+ but not in the presence of Ca2+ as a result of the addition of both brain tropomyosin and troponin-like complex. The troponin-like complex contains three components, one of which is similar in molecular weight to the troponin-T of skeletal actomyosin.     

The effects of paroxetine, alone and in combination with alcohol on psychomotor performance and cognitive function in the elderly.

Fifteen healthy male volunteers aged over 60 years received acute and repeated doses of paroxetine 20 mg or placebo, and acute doses of lorazepam 1 mg (as a positive internal control) with or without alcohol (0.6 g/kg of body weight) administered openly in a double blind balanced crossover study in which each subject acted as his own control. Psychomotor performance and cognitive function were assessed using a test battery which included critical flicker fusion, choice reaction time, compensatory tracking, Stroop and memory scanning tests. Subjective ratings of mood and sleep were recorded using line analogue rating scales. The pattern of results indicated that paroxetine had little or no effect on most of the test variables, and in some instances (critical flicker fusion thresholds) improved information processing ability. This was in marked contrast to the lorazepam verum which produced sedation and disruption of performance. Paroxetine had a slight antagonistic effect on alcohol induced sedation whereas impairment of performance with lorazepam was potentiated by co-administration of alcohol. The low behavioural toxicity of paroxetine in elderly volunteers has important implications for the pharmacotherapy of depression.     

Metabolic differences between Asian and Caucasian patients on clozapine treatment

OBJECTIVE: To establish if there are ethnic differences in the various metabolic disturbances that are common with clozapine treatment. METHOD: Forty subjects (20 Asians and 20 Caucasians) with a diagnosis of schizophrenia were recruited for the study. Clozapine blood levels as well as fasting blood glucose, lipid levels, and liver function tests were established. Other clinical parameters such as blood pressure and Body Mass Index (BMI) were recorded for each patient. RESULTS: The mean clozapine dose was significantly higher in the Caucasian subjects (432.5+/-194.7 mg) as compared to the Asian subjects (175.6+/-106.9 mg) (p<0.001) while the mean weight-corrected dose for Asian patients was lower (3.0+/-1.9 and 5.0+/-2.1 mg/kg, respectively, p=0.005). There were, however, no ethnic differences in the mean plasma clozapine concentration (415.3+/-185.8 ng/ml in Caucasians and 417.1+/-290.8 ng/ml in Asians). BMI were significantly higher in Caucasians, as were the number of subjects with hypertension; levels of hepatic enzymes were higher in the Asian group. CONCLUSIONS: Not only are there pharmacokinetic differences between Asian and Caucasian patients receiving clozapine, but there may also be differential emergence of certain metabolic abnormalities like hypertension and weight gain in these two ethnic groups. However, the effects of life style including diet and exercise cannot be excluded.