Influence of Bcl-1 Gene Polymorphism of Glucocorticoid Receptor Gene (NR3C1, rs41423247) on Blood Pressure,Glucose in Northern Indians

Glucocorticoids and its receptor are known to be involved in the dysregulation of hormone and lipid levels. Therefore, we evaluated the association of Bcl1 gene polymorphism of glucocorticoids receptor (GCR) gene variant with hormone and lipid levels in Northern Indians obese. A total of 435 obese and non-obese age matched subjects were included in the case–control study. Lipid and hormonal levels were estimated using standard protocols. Analysis of +646 C>G NR3C1 gene polymorphism was done using PCR–RFLP. The frequencies of GR Bcl1, C>G genotypes and alleles did not differ significantly (P > 0.05) between obese and non-obese. The +646 G allele carriers had higher waist to hip ratio, blood pressure, insulin and glucose levels than non-carriers in obese subjects while diastolic blood pressure and glucose in non-obese. The NR3C1, +646 C>G polymorphism did not associate with obesity. However, the GG genotype may modulate blood pressure, blood glucose and hormonal levels in northern Indians.     

Effect of Pre-Analytical Errors on Quality of Laboratory Medicine at a Neuropsychiatry Institute in North India

Advances in instrument technology and automation have simplified tasks in laboratory diagnostics reducing errors during analysis thereby improving the quality of test results. However studies show that most laboratory errors occur in the pre-analytical phase. In view of the paucity of studies examining pre-analytical errors, we examined a total of 1513 request forms received at our laboratory during a 3 month period. The forms were scrutinized for the presence of specific parameters to assess the pre-analytical errors affecting the laboratory results. No diagnosis was provided on 61.20% of forms. Type of specimen was not mentioned in 61.60% of the forms and 89.25% of all forms were illegible. Critical results were encountered in 17.30% of patients, and of these 76.60% were not communicated due to incomplete forms. Thus, by following standard operating procedures vigorously from patient preparation to sample processing the laboratory results can be significantly improved without any extra cost.     

Redistribution of glucose-6-phosphate dehydrogenase in response to cerebral ischemia in rat brain

Glucose-6-phosphate dehydrogenase (G6PD), a cytoplasmic enzyme, plays a protective role during oxidative stress in eucaryotic cells, since they provide coenzymes and substrates to the primary antioxidant enzymes. The redistribution of G6PD in the hippocampus was studied post-ischemia (PI). There was a characteristic localisation of G6PD in pyramidal cell layers of the rat hippocampus. In hippocampus CA1 cells were stained weakly whereas CA3 cells showed strong histochemical staining. Ischemia induced up-regulation of G6PD in the hippocampus was in a specific manner. First, the activity increased in the whole hippocampus (at 4 hours PI) which persisted 6 hrs PI in CA1 area. However G6PD activity decreased in the CA3 area & dentate gyrus. At 10 & 24 hrs PI, activity decreased in CA1 area but normalised in CA3 area & dentate gyrus compared to controls. This suggests that the sensitive CA1 neurons are transiently capable of generating an anti-oxidative arsenal to cope with the oxidative stress in the first few hours PI. We can conclude that the brain contains inducible endogenous mechanisms that are capable of enhancing the ability of neurons to withstand lethal ischemic challenge. (Presently working in Vardhman Mahavir Medical College & Safdarjung Hospital, New Delhi)     

Effect of latent iron deficiency on GABA and glutamate neuroreceptors in rat brain

Eight weeks of latent iron deficiency in weaned female rats of Sprague Dawley strain maintained on experimental low-iron diet (18–20 mg/kg) did not significantly change the gross body, weight and tissue weights of brain and liver. Packed cell volume (PCV) and hemoglobin concentration remained unaltered. However, non-heme iron content in liver and brain decreased significantly (p<0.001). The activities of glutamate dehydrogenase, glutamic acid decarboxylase, and GABA-transaminase (GABA-T) in brain decreased by 15%, 11.4% and 25.7% respectively. However, this decrease was not statistically significant. Binding of³H Muscimol at pH 7.5 and 1 mg protein/assay increased by 143% (p<0.001) in synaptic vesicular membranes from iron-deficient rats as compared to the controls.³H glutamate binding to the synaptic vesicles was also carried out under similar condition. However, the L-glutamate binding was reduced by 63% in the vesicular membranes of iron deficient animals. These studies indicate that iron plays important functional role in both excitatory and inhibitory neurotransmitter receptors.     

Study of apolipoproteinc3 Sstl polymorphism in healthy volunteers from Northern India

Several studies including a small case-control (hypertriglyceridemic/normotriglyceridemic individuals) study by us revealed close association between rare S2 allele ofAPOC3 Sstl polymorphism and hypertriglyceridemia. With the understanding that Asian Indians are highly vulnerable to the adverse effects of hypertriglyceridemia, we extended the investigation and studied the frequency distribution of this polymorphism in 216 healthy volunteers from Northern plains of India. We found that more than 50% of the study population had one or two S2 allele. This may suggest that a larger fraction of this population is genetically predisposed to hypertriglyceridemia.     

Metabolic Syndrome in Childhood: Rare Case of Alstrom Syndrome with Blindness

Alstrom’s syndrome (AS) is a rare autosomal recessive ciliopathic condition affecting 1:10,00,000 children. It’s a single gene disorder of ALMS1 on chromosome 2 with multisystem involvement with cone-rod retinal dystrophy causing juvenile blindness, obesity, insulin resistance, type 2 Diabetes mellitus, hypogonadism and sensorineural hearing loss. Till now only 800 patients with this disorder has been identified so far. In this report, we describe the case of a 9-year old male boy from south India. He had been initially referred for polyphagia, polyuria, polydipsia, generalized weakness from 1 weeks. On examination he was demonstrated features suggestive of AS, including blindness, obesity, type 2 diabetes, altered lipid profile, hypogonadism, acanthosis nigricans, seborrheic dermatitis, right ear discharge and episodes of respiratory tract infections. So, diagnosis of AS is critical as it can easily be overlooked because of the many features associated with metabolic syndrome starting at age 7, a relatively early age.     

Effect of latent iron deficiency on gaba and glutamate neuroreceptors in rat brain

Eight weeks of latent iron deficiency in weaned female rats of Sprague Dawley strain maintained on experimental low-iron diet (18–20 mg/Kg) did not significantly change the gross body weight and tissue weights of brain and liver. Packed cell volume (PCV) and hemoglobin concentration remained unaltered. However, non-heme iron content in liver and brain decreased significantly (P<0.001). The activities of glutamate dehydrogenase, glutamic acid decarboxylase, and GABA-transaminase (GABA-T) in brain decreased by 15%, 11.4% and 25.7% respectively. However, this decrease was not statistically significant. Binding of³H Muscimol at pH 7.5 and 1 mg protein/assay increased by 143% (P<0.001) in synaptic vesicular membranes from iron-deficient rats as compared to the controls.³H glutamate binding to the synaptic vesicles was also carried out under similar condition. However, the L-glutamate binding was reduced by 63% in the vesicular membranes of iron deficient animals. These studies in dicate that iron plays an important functional role in both excitatory and inhibitory neurotransmitter receptors.     

An opium alkaloid-papaverine ameliorates ethanol-induced hepatotoxicity: Diminution of oxidative stress

In this communication, we show the modulatory potential of papaverine, an opium alkaloid and a well known vasodilator agent on the ethanol-induced hepatic oxidative stress in male Wistar rats. Ethanol treatment (50% v/v) enhanced lipid peroxidation significantly accompanied by a decline in the activities of glutathione peroxidase (G-Px), glutathione reductase (GR) and depletion in levels of hepatic glutathione (GSH). Ethanol administration increased hepatic glutathione-s-transferases (GST). Enhanced lipid peroxidation induced by ethanol was significantly reduced when papverine was coadministered (P<0.05). In addition, the depleted levels of glutathione and inhibited activities of G-Px and GR recovered significantly (P<0.05) levelling off to control values on co-exposure. Papaverine (200 mg/kg bw) effectively antagonised the ethanol-induced lipid peroxidation and impaired glutathione levels and glutathione dependent enzyme systems. Our results suggest that papaverine is an effective chemopreventive agent in the liver and may suppress the ethanol-induced hepatotoxicity.