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Biomedical subjects

Somnath Mukhopadhyay

Publications and source records attributed to Somnath Mukhopadhyay.

13 recordsLinked to original sources
PubMed2006

Lipopolysaccharide and cyclic AMP regulation of CB(2) cannabinoid receptor levels in rat brain and mouse RAW 264.7 macrophages.

CB(2) cannabinoid receptors exist in immune cells including macrophages. Affinity-purified antibodies against the CB(2) receptor identified a 45 kDa protein in rat brain, human tonsil and rat and mouse microglia, but not mouse N18TG2 neuroblastoma cells. Intracerebroventricular lipopolysaccharide (LPS) increased immunoreactive CB(2) receptors in brain membranes detected by Western blot. LPS increased immunodetectable CB(2) receptors in cultured RAW 264.7 macrophages, and this was partially attenuated by cyclohexamide or the protein kinase A and C inhibitors H8 and bis-indolylmaleimide. Forskolin or dibutyryl cyclic AMP increased CB(2) receptor immunoreactivity, suggesting the involvement of the cyclic AMP-protein kinase A-Cyclic AMP response element pathway in the regulation of CB(2) receptor levels.

Animals↗
PubMed2006

Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis.

Atopic disease, including atopic dermatitis (eczema), allergy and asthma, has increased in frequency in recent decades and now affects approximately 20% of the population in the developed world. Twin and family studies have shown that predisposition to atopic disease is highly heritable. Although most genetic studies have focused on immunological mechanisms, a primary epithelial barrier defect has been anticipated. Filaggrin is a key protein that facilitates terminal differentiation of the epidermis and formation of the skin barrier. Here we show that two independent loss-of-function genetic variants (R510X and 2282del4) in the gene encoding filaggrin (FLG) are very strong predisposing factors for atopic dermatitis. These variants are carried by approximately 9% of people of European origin. These variants also show highly significant association with asthma occurring in the context of atopic dermatitis. This work establishes a key role for impaired skin barrier function in the development of atopic disease.

Alleles↗
PubMed2006

Vitamin A and lung function in CF.

Laboratory evidence suggests that vitamin A could have a protective effect on respiratory status in patients with cystic fibrosis (CF). This study shows a significant correlation between serum vitamin A concentrations and every aspect of lung function tested in 38 patients with stable CF. Serum vitamin D and vitamin E concentrations were also measured but did not show any significant correlations with lung function.

Adolescent↗
PubMed2006

Greater knowledge gain with structured than student-directed learning in Child Health: cluster randomized trial.

The aim of this study was to detect a difference in knowledge gain between students receiving structured versus student-directed learning for the two-week Child Health outpatient module. A total of 138 phase 3 (year 4) medical students in 10 two-week paediatric outpatient blocks at the Department of Child Health, University of Dundee, Scotland, were randomized to student-directed or structured learning between January and December 2002. Pre- and post-course tests were administered at the start and the end of the attachment; 129 students sat both tests. Results are presented as mean scores with standard deviations or 95% confidence intervals (CI) in parentheses. The primary outcome measure was gain in knowledge of the Child Health core curriculum that is covered in the outpatient setting. Although pre-course scores were similar (student-directed 25.3 (7.3); structured 24.8 (7.5)) the structured approach resulted in higher post-course scores in comparison with the student-directed approach (student-directed 41.8 (9.4); structured 53.8 (8.8); p < 0.01). Knowledge gain showed significant differences between the two learning approaches (student-directed 16.5 (3.7); structured 29.1 (3.8), difference = 12.6 (95% CI 11.3 to 13.9)). Low pre-course scores or gender did not affect knowledge gain. In the Child Health outpatient setting, the 'traditional' structured approach led to significantly greater knowledge gain in comparison with the 'novel' student-directed approach. The findings emphasize the importance of careful evaluation of novel medical education strategies before their implementation in medical schools, and the need for further research to define the effective methods for delivering medical education in Child Health.

Child↗
PubMed2006

Glutathione S-transferase M1 and P1 genotype, passive smoking, and peak expiratory flow in asthma.

OBJECTIVES: Our purpose with this work was to assess the contribution of glutathione S-transferase gene variants to asthma susceptibility and pulmonary function in relation to tobacco smoke exposure in the home. METHODS: Young individuals with asthma (age: 3-21 years; n = 504) were recruited through primary and secondary care throughout Tayside, Scotland (BREATHE Study). Spirometry was obtained on 407 individuals. Binary logistic regression and general linear modeling were used to explore phenotypic characteristics by genotype and tobacco smoke exposure status in younger children (3-12 years; n = 384) and teenagers and young adults (13-21 years; n = 120). RESULTS: Three- to 12-year-olds with asthma, null for the GSTM1 gene or homozygous for the GSTP1Val105 allele, were overrepresented in the group exposed to environmental tobacco smoke. No differences in lung function values could be detected in this group. In contrast, 13- to 21-year-olds with the GSTM1-null genotype or homozygous for the GSTP1Val105 allele from smoking households were more likely to have a substantially lower percentage of predicted peak expiratory flow rates than those from nonsmoking households (83% vs 98%). CONCLUSIONS: Three- to 12-year-olds who are null for GSTM1 or homozygous for the GSTP1Val105 allele are more susceptible to asthma associated with environmental tobacco smoke exposure than those with more intact glutathione S-transferase status. In the 13- to 21-year-olds, GSTM1-null status interacts with environmental tobacco smoke exposure to substantially reduce peak expiratory flow rate. The environmental tobacco smoke effect in GSTM1-null children with asthma could be cumulative over time, resulting in detrimental effects on peak expiratory flow rate in 13- to 21-year-olds with asthma.

Adolescent↗
PubMed2005

Chemically distinct ligands promote differential CB1 cannabinoid receptor-Gi protein interactions.

To understand how structurally distinct ligands regulate CB(1) receptor interactions with Gi1, Gi2, and Gi3, we quantified the Galphai and betagamma proteins that coimmunoprecipitate with the CB(1) receptor from a detergent extract of N18TG2 membranes in the presence of ligands. A mixture of A, R, G(GDP) (or G_), and ARG(GDP) (or ARG_) complexes was observed in the presence of aminoalkylindole (R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naphthalenylmethanone (WIN 55,212-2) for all three RGalphai complexes, cannabinoid desacetyllevonantradol for Galphai1 and Galphai2, and eicosanoid (R)-methanandamide for Galphai3. Desacetyllevonantradol maintained RGalphai3 complexes and (R)-methanandamide maintained RGalphai1 and RGalphai2 complexes even in the presence of a nonhydrolyzable GTP analog. The biaryl pyrazole antagonist N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboximide hydrochloride (SR141716) maintained all three RGalphai complexes. Gbeta proteins, and to a certain extent Ggamma2, exhibited the same association/dissociation pattern as the Galpha proteins. A GDP analog had no influence on any of these association/dissociation reactions and failed to promote sequestration of G proteins. These results can be explained by invoking the existence of an inverse agonist-supported inactive state in the ternary complex equilibrium model. WIN 55,212-2 behaves as an agonist for all three Gi subtypes; SR141716 behaves as an inverse agonist for all three Gi subtypes; desacetyllevonantradol behaves as an agonist for Gi1 and Gi2, and an inverse agonist at Gi3; and (R)-methanandamide behaves as an inverse agonist at Gi1 and Gi2, and an agonist at Gi3. These ligand-selective G protein responses imply that multiple conformations of the receptor could be evoked by ligands to regulate individual G proteins.

Animals↗
PubMed2005

Annual increase in body mass index in children with asthma on higher doses of inhaled steroids.

There is a greater annual increase in body mass index in children with asthma receiving inhaled steroids at a dose > or =400 microg/day (0.5 kg/m2/year; n=100) compared with those receiving < or =200 microg/day (0.1 kg/m2/year; n=98) (P=.0003). This is consistent with an annual increase in body fat in children with asthma receiving > or =400 microg/day of inhaled steroids.

Administration, Inhalation↗
PubMed2005

Overweight and obesity in deltaF508 homozygous cystic fibrosis.

Overweight (9%) and obesity (1%) in patients with cystic fibrosis homozygous for the deltaF508 mutation (CFdeltaF508) were non-trivial. Children with CFdeltaF508, in contrast to the general population, showed a positive association between body mass index and lung function for all body mass index z-scores.

Adolescent↗
PubMed2004

Wheeze and urban variation in South Asia.

Typically, urban South Asia is characterised by narrow streets, heavy traffic, visible haze, unplanned city architecture and the use of kerosene or wood-burning stoves at home. However, some urban areas in South Asia are clean and modern, with concrete housing, vehicle emission regulations and use of smoke-free household fuel. The purpose of this study was to compare wheeze prevalence in 13-14-year-olds between two South Asian cities (Galle, Chandigarh), representing each of the above two archetypes. The validated one-page International Study on Asthma and Allergies in Childhood (ISAAC) questionnaire for 13-14-year-olds was used for the study. Of 1814 distributed questionnaires, 1737 (95.8%) were completed correctly and returned (Galle: n=1162; Chandigarh: n=575). Crude prevalence rates, and prevalence odds ratios (with 95% two-sided confidence intervals (CI) for comparison of prevalence rates), were calculated. The prevalence rate for wheezing in Galle (28.7%) was higher than in Chandigarh (12.5%). The prevalence odds ratios (Galle versus Chandigarh) for lifetime wheezing (2.3; 1.8-2.9), wheezing in the previous year (2.1; 1.6-2.7), exercise-related wheeze (4.8; 3.5-6.7) and physician-diagnosed wheeze (1.7; 1.2-2.3) demonstrated significant differences in wheeze prevalence between the two cities ( P<0.05). The numbers of 13-14-year-olds experiencing less than 12 wheezing episodes per year or sleep disturbance due to wheeze of less than 1 night per week were also significantly higher for Galle than Chandigarh. There is a higher prevalence of wheeze in 13-14-year-old children living in an old-fashioned, congested city than in a clean and modern city in South Asia.

Adolescent↗
PubMed2002

CB(1) cannabinoid receptor-G protein association: a possible mechanism for differential signaling.

Effects of cannabinoid compounds on neurons are predominantly mediated by the CB(1) cannabinoid receptor. Onset of signaling cascades in response to cannabimimetic drugs is triggered by the interaction of the cannabinoid receptor with G(i/o) proteins. Much work has been done to delineate the cannabinoid agonist-induced downstream signaling events; however, it remains to define the molecular basis of cannabinoid receptor-G protein interactions that stimulate these signaling pathways. In this review, we discuss several signal transduction pathways, focusing on studies that demonstrate the efficacy of CB(1) receptor agonists through G protein mediated pathways.

Adenylyl Cyclases↗
PubMed2002

Anandamide-induced vasorelaxation in rabbit aortic rings has two components: G protein dependent and independent.

The endogenous cannabinoid anandamide (arachidonylethanolamide) produces vasorelaxation in different vascular beds. In the present study, we found that anandamide and a metabolically stable analog, methanandamide, produced dose-dependent (10 nM-10 microM) vasorelaxation of approximately 80% in a rabbit aortic ring preparation in an endothelium-dependent manner. Non-endothelium-dependent vasorelaxation was observed to be a maximum of 20-22% at >10 microM methanandamide. The efficacious CB(1) receptor analogs desacetyllevonantradol (10 microM) and WIN55212-2 (10 microM) failed to produce vasorelaxation; however, the endothelium-dependent vasorelaxation evoked by methanandamide was partially (75%) blocked by the CB(1) receptor antagonist SR141716A. The VR(1) vanilloid receptor antagonist capsazepine or the calcitonin gene-related peptide (CGRP) antagonist CGRP-(8-37) partially attenuated (25%) the vasorelaxation in endothelium-intact preparations and greatly reduced the response in endothelium-denuded preparations. Pretreatment of aortic rings with N(G)-nitro-L-arginine methyl ester completely blocked the methanandamide-, capsaicin-, and CGRP-induced vasorelaxation. Pretreatment of aortic rings with pertussis toxin attenuated the methanandamide-induced vasorelaxation in endothelium-intact aortic rings, indicating the involvement of G(i/o) proteins in the vasorelaxation; however, pertussis toxin treatment failed to block the endothelium-independent response. Thus, in the rabbit aorta, methanandamide-induced vasorelaxation exhibits two components: 1) in endothelium-intact rings, an SR141716A-sensitive, non-CB(1) receptor component that requires pertussis toxin-sensitive G proteins and nitric oxide (NO) production; and 2) in endothelium-denuded rings, a component that is mediated by VR(1) vanilloid receptors and possibly by the subsequent release of CGRP that requires NO production but is independent of pertussis toxin-sensitive G proteins.

Animals↗