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Balaram Ghosh

Publications and source records attributed to Balaram Ghosh.

At least 19 recordsLinked to original sources
PubMed2007

A hexanucleotide repeat upstream of eotaxin gene promoter is associated with asthma, serum total IgE and plasma eotaxin levels.

BACKGROUND: Eotaxin (CCL11) is a small protein produced in the lungs of patients with asthma, and is a potent chemoattractant for eosinophils. AIM: To elucidate the role of eotaxin in asthma by an association study of functional and novel eotaxin polymorphisms in case-control and family-based study designs. METHODS: Eotaxin +67G/A, -384A/G and -426C/T single-nucleotide polymorphisms and a hexanucleotide (GAAGGA)(n) repeat 10.9 kb upstream of the gene were genotyped in a cohort of age, sex and ethnically matched patients with asthma (n = 235) and healthy controls (n = 239), and also in a study population of 230 families with asthma recruited from north/northwest India. Total serum IgE (TsIgE) and plasma eotaxin levels were measured using ELISA. RESULTS: +67G/A polymorphism was found to be significantly associated with asthma in case-control (p = 0.009) and family-based studies (p = 0.006). Its functional role, as it was correlated with plasma eotaxin levels (p = 0.006), was also demonstrated. Further, -384C/T single-nucleotide polymorphism was found to be significantly associated with log(10) TsIgE (p = 0.016 in case-control and p = 0.018 in families) and eotaxin levels (p = 0.007). Most interestingly, for the first time, a highly significant association of the newly studied (GAAGGA)(n) hexanucleotide repeat with asthma (p = 3x10(-6)), log(10)TsIgE (p = 0.006) and eotaxin levels (p = 0.004) was observed. G_A_C_8 was also identified as an important risk haplotype associated with high TsIgE and plasma eotaxin levels. CONCLUSIONS: This study provides further evidence that eotaxin polymorphisms are associated with the development of asthma by regulating eotaxin levels and reinforces towards the scanning of other chemokine genes present at 17q21 locus for their association with asthma and related phenotypes.

Adolescent↗
PubMed2007

Suppression of cell proliferation, induction of apoptosis and cell cycle arrest: chemopreventive activity of vanadium in vivo and in vitro.

In the present study, the authors evaluated the anticancer mechanism of vanadium, a dietary micronutrient and an important pharmacological agent, on a defined model of chemically induced rat mammary carcinogenesis in vivo and on human breast cancer cell line MCF7 in vitro. Female Sprague-Dawley rats were treated with 7,12-dimethylbenz(alpha)anthracene (0.5 mg/100 g body weight) by a single tail vein injection in an oil emulsion to induce mammary preneoplasia. Vanadium (ammonium monovanadate) at a concentration of 0.5 ppm (4.27 micromol/l) was supplemented in drinking water and given ad libitum to the experimental groups for 24 weeks. Histological finding showed substantial repair of hyperplastic lesions. There was a significant reduction in incidence, multiplicity (34%, p < 0.01), size of palpable mammary tumors and delay in mean latency period of tumor appearance. Immunohistochemical analysis in vivo indicated a decrease in cell proliferation (24.68% p < 0.05) and an increase among the TUNEL-positive apoptotic cells along with strong expressions of p53 and Bax, and downregulation of Bcl2 proteins in the mammary tissue of vanadium-treated animals. Further, MCF7 cells were cultured in minimal essential medium and were treated with 100, 175 and 250 microM of vanadium (ammonium monovanadate) for 36 hr. Exposure of MCF7 cells to vanadium led to induction of apoptosis in a dose-dependent manner. It was found further that vanadium treatment brought about a prominent cell cycle arrest and chromosomal condensation, leading to apoptosis (42.62%, p < 0.05). Results of both the in vivo and in vitro study demonstrate that vanadium has the potential to be developed into an anti-breast cancer drug in the near future.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed2007

Association of inducible nitric oxide synthase with asthma severity, total serum immunoglobulin E and blood eosinophil levels.

BACKGROUND: Nitric oxide is released by immune, epithelial and endothelial cells, and plays an important part in the pathophysiology of asthma. OBJECTIVE: To investigate the association of inducible nitric oxide synthases (iNOS) gene repeat polymorphisms with asthma. METHODS: 230 families with asthma (842 individuals) were recruited to identify and establish the genetic association of iNOS repeats with asthma and associated phenotypes. Serum nitric oxide levels in selected individuals were measured and correlated with specific genotypes. Multiple logistic regression analysis was performed to determine the effect of age and sex. RESULTS: A total of four repeats-a (CCTTT)n promoter repeat, a novel intron 2 (GT)n repeat (BV680047), an intron 4 (GT)n repeat (AFM311ZB1) and an intron 5 (CA)n repeat (D17S1878)-were identified and genotyped. A significant transmission distortion to the probands with asthma was seen for allele 3 of the AFM311ZB1 gene (p = 0.006). This allele was also found to be significantly associated with percentage blood eosinophils (p < 0.001) and asthma severity (p = 0.04). Moreover, it was functionally correlated with high serum nitric oxide levels (p = 0.006). Similarly, the promoter repeat was found to be associated with serum total immunoglobulin (Ig)E (p = 0.028). Individuals carrying allele 4 of this repeat have high serum IgE (p < 0.001) and nitric oxide levels (p = 0.03). CONCLUSION: This is the first study to identify the repeat polymorphisms in the iNOS gene that are associated with severity of asthma and eosinophils. The functional relevance of the associated alleles with serum nitric oxide levels was also shown. Therefore, these results could be valuable in elucidating the role of nitric oxide in asthma pathogenesis.

Adolescent↗
PubMed2006

Molecular basis of anticlastogenic potential of vanadium in vivo during the early stages of diethylnitrosamine-induced hepatocarcinogenesis in rats.

Carcinogen-induced DNA base modification and subsequent DNA lesions are the critical events for the expression of premalignant phenotype of the cell. We have therefore investigated the chemopreventive efficacy of a vanadium salt against diethylnitrosamine (DEN)-induced early DNA and chromosomal damages in rat liver. Hepatocarcinogenesis was induced in male Sprague-Dawley rats with a single, necrogenic, intraperitoneal injection of DEN (200mg/kg body weight). 8-Hydroxy-2'-deoxyguanosines (8-OHdGs), strand-breaks and DNA-protein crosslinks (DPCs) were measured by HPLC, comet assay and spectrofluorimetry, respectively. There was a significant and steady elevation of modified bases 8-OHdGs along with substantial increments of the extent of single-strand-breaks (SSBs), DPCs and chromosomal aberrations (CAs) following DEN exposure. Supplementation of vanadium as ammonium metavanadate (NH(4)VO(3), +V oxidation state) at a dose of 0.5ppm in terms of the salt weight throughout the experiment abated the formations of 8-OHdGs (P<0.0001; 79.54%), tailed DNA (P<0.05; 31.55%) and length:width of DNA mass (P<0.02; 61.25%) in preneoplastic rat liver. Vanadium treatment also inhibited DPCs (P<0.0001; 58.47%) and CAs (P<0.001; 45.17%) studied at various time points. The results indicate that the anticlastogenic potential of vanadium in vivo might be due to the observed reductions in liver-specific 8-OHdGs, SSBs and/or DPCs by this trace metal. We conclude that, vanadium plays a significant role in limiting DEN-induced genotoxicity and clastogenicity during the early stages of hepatocarcinogenesis in rats.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2006

Glycyrrhizin alleviates experimental allergic asthma in mice.

Asthma is a chronic respiratory disease, the incidence of which is increasing globally. The existing therapy is inadequate and has many adverse effects. It needs a better therapeutic molecule preferably of natural origin, which has negligible or no adverse effects. In view of this, we evaluated Glycyrrhizin (GRZ), a major constituent of a plant Glycyrrhiza glabra, for its efficacy on asthmatic features in a mouse model of asthma. BALB/c mice were sensitized and challenged with ovalbumin (OVA) to develop the asthmatic features such as airway hyperresponsiveness: allergen induced airway constriction and airway hyperreactivity (AHR) to methacholine (MCh), and pulmonary inflammation. The mice were orally treated with GRZ (2.5, 5, 10 and 20 mg/kg) during or after OVA-sensitization and OVA-challenge to evaluate its protective or reversal effect, respectively on the above asthmatic features. The status of airway hyperresponsiveness was measured by monitoring specific airway conductance (SGaw) using a non-invasive method and the pulmonary inflammation was assessed by haematoxylin and eosin staining of lung sections. Several other parameters associated with asthma such as interleukin (IL)-4, IL-5 interferon-gamma (IFN-gamma), OVA-specific IgE, total IgG(2a) and cortisol were measured by ELISA. GRZ (5 mg/kg) markedly inhibited OVA-induced immediate airway constriction, AHR to MCh (p<0.01), lung inflammation, and infiltration of eosinophils in the peribronchial and perivascular areas. It prevented the reduction of IFN-gamma (p<0.02), and decreased IL-4 (p<0.05), IL-5 (p<0.05) and eosinophils (p<0.0002) in the BAL fluid. Also, it reduced OVA-specific IgE levels (p<0.01) and prevented the reduction of total IgG(2a) (p<0.01) in serum. We have also showed that it has no effect on serum cortisol levels. Our results demonstrate that GRZ alleviates asthmatic features in mice and it could be useful towards developing a better therapeutic molecule in the future.

Allergens↗
PubMed2006

Association of TNF haplotypes with asthma, serum IgE levels, and correlation with serum TNF-alpha levels.

Both biochemical and genetic evidence have implicated the genes for TNF-alpha (TNFA) and lymphotoxin-alpha (LTA) in atopic asthma. Here, we report for the first time the association of their genotypes and haplotypes with atopic asthma in Indian populations. We genotyped seven single nucleotide polymorphisms, encompassing the two genes, in patients and control subjects in two independent cohorts. Serum TNF-alpha levels of selected individuals were measured and correlated with genotypes and haplotypes. The A allele of the TNFA-863C > A polymorphism was associated with reduced risk of asthma (P = 0.002 and 0.007 in Cohorts A and B, respectively), reduced TsIgE levels (P = 0.0024 and P = 0.0029 in Cohorts A and B, respectively), and reduced serum TNF-alpha levels (P < 0.05). A marginal association was also observed for LTA_NcoI polymorphism with asthma and TsIgE levels. Furthermore, analysis using HAPLO. STATS showed significant differences in the major haplotype frequencies (> 3%) between patients and control subjects (P = 0.002 and P = 0.006 for Cohorts A and B, respectively). Individually, the haplotype GATCCG was the most frequent in patients (P = 0.0029 and P = 0.0025 for Cohorts A and B, respectively), and was associated with high TsIgE and serum TNF-alpha levels, whereas AACACG was the most frequent in the control subjects (P = 0.0032 and P = 0.022 for Cohorts A and B, respectively), and was associated with low TsIgE and serum TNF-alpha levels. We also report here that the C > A substitution at position -863 of the TNFA influences the binding of nuclear proteins in electrophoretic mobility shift assay experiments. Thus, the TNFA-863C > A polymorphism in the promoter region of TNFA may influence TNF-alpha expression and affect TsIgE levels and susceptibility to asthma.

Adult↗
PubMed2006

Arylamine N-acetyltransferase gene polymorphisms: markers for atopic asthma, serum IgE and blood eosinophil counts.

INTRODUCTION: Polymorphisms in N-acetyltransferase 2 (NAT2), present on chromosome 8p22, are responsible for the N-acetylation variants, which segregate human populations into rapid, intermediate and slow acetylators and influence the susceptibility towards atopic disorders. We have undertaken a study of the North Indian population to screen for various NAT2 polymorphisms and to investigate their association with atopic asthma and related phenotypes. METHODS: First, to establish linkage of the 8p22 region with asthma, 158 families were recruited from North India. Next, a total of 219 unrelated atopic asthmatics and 210 unrelated healthy controls were recruited for case-control disease association studies. RESULTS: A suggestive linkage was observed with microsatellite marker D8S549, 2.6 MB upstream of NAT2. By sequencing the DNA of 40 individuals, the T111C, G191A, A434C and C759T single nucleotide polymorphisms (SNPs) in NAT2 were found to be nonpolymorphic in our population and a pattern of strong linkage disequilibrium was observed among the T341C, C481T and A803G polymorphisms. Thus, a total of 429 individuals were genotyped for the C481T and unlinked C282T polymorphisms. The C481T polymorphism was found to be significantly associated with asthma in our case-control studies at the genotype level (Armitage p = 0.00027). C481T also showed a marginal association with serum total IgE (TsIgE) (p = 0.022). Furthermore, percent blood eosinophil counts were found to be significantly higher in patients carrying the 481T allele (p = 0.0037). Significant association was also detected with respect to the C282T polymorphism and TsIgE (p = 0.008). Moreover, C_T was found to be an important risk (p = 0.001), while C_C was a major protective haplotype (p = 0.0005). The associations remained significant after Bonferroni correction for multiple testing. CONCLUSION: In summary, the genetic variants of the NAT2 gene do not seem to affect asthma alone, but act as modulators of asthma-related traits, such as serum IgE and blood eosinophil counts, and therefore could serve as genetic markers.

Adolescent↗
PubMed2005

Novel aromatic ester from Piper longum and its analogues inhibit expression of cell adhesion molecules on endothelial cells.

We report here the isolation and characterization of two active principles, ethyl 3',4',5'-trimethoxycinnamate (1) and piperine (2), from the combined hexane and chloroform extracts of Piper longum. Using primary human umbilical vein endothelial cells, we evaluated the activities of compound 1 on TNF-alpha-induced expression of cell adhesion molecules, viz., ICAM-1, VCAM-1, and E-selectin, which play key roles in controlling various inflammatory diseases. Both compounds 1 and 2 inhibited the TNF-alpha-induced expression of ICAM-1 in a dose- and time-dependent manner; however, the activity of ethyl 3',4',5'-trimethoxycinnamate (1) was approximately 1.3 times higher than that of piperine (2). As ethyl 3',4',5'-trimethoxycinnamate (1) has been isolated for the first time from a natural source, Piper longum, and it exhibited higher activity, we carried out further studies on it. To correlate its cell adhesion molecule inhibitory activity with its functional consequences, we showed that it significantly blocked the adhesion of neutrophils to endothelium in a time- and concentration-dependent manner. Importantly, the inhibitory effect of cinnamate 1 was found to be reversible. To elucidate its structure-function-activity relationship, we synthesized nine different analogues of ethyl 3',4',5'-trimethoxycinnamate, i.e., compounds 3-11, and compared the ICAM-1 inhibitory activity of compound 1 with those of its synthetic analogues as well as the corresponding acids 12-15. The structure-activity studies indicate that the chain length of the alcohol moiety, substituents in the aromatic ring, and alpha, beta-double bond of the cinnamic acid ester have significant effects on the inhibition of TNF-alpha-induced expression of ICAM-1 on endothelial cells. These findings have implications in developing compounds with a better therapeutic index against various inflammatory diseases.

Alkaloids↗
PubMed2005

Lack of association of histamine-N-methyltransferase (HNMT) polymorphisms with asthma in the Indian population.

Histamine plays a major role in allergic disorders, including asthma. A major pathway of histamine biotransformation in the lungs is mediated by histamine N-methyltransferase (HNMT). We investigated the association of a functional SNP C314T; a SNP A929G, a (CA)n repeat in intron 5, and a novel (CA)n repeat (BV677277), 7.5 kb downstream of the HNMT gene with asthma and its associated traits such as total serum IgE levels in a case-control as well as in a family-based study design. In contrast to a previous study, no association was observed for the polymorphisms investigated with asthma (P>0.05). When haplotypes were constructed for these loci and compared, no significant difference was observed in the distribution between cases and controls. In the family-based design, no biased transmission was observed for any of the polymorphisms and haplotypes with asthma using the additive model of inheritance in family-based association test (FBAT). Thus, consistent with the case-control findings, the polymorphisms and haplotypes in the HNMT gene are not associated with asthma in the Indian population.

Adolescent↗
PubMed2005

QSAR modeling on dopamine D2 receptor binding affinity of 6-methoxy benzamides.

QSAR modeling was performed on 58 (S) N-[(1-ethyl-2-pyrrolidinyl) methyl]-6-methoxy benzamides as dopamine (DA) D2 receptor antagonists to identify the structural requirements for DA D2 receptor binding affinity. The study pointed out that the presence of hydrophobic substituents at R3 position and electron-donating groups at R5 position increased the biological activity. Substitutions at phenyl ring favored the binding affinity of these benzamides. Ethyl group and iodine at R3 position were advantageous to the activity whereas nitro group at phenyl ring hindered the antagonistic activity.

Benzamides↗
PubMed2005

A novel (TG)n(GA)m repeat polymorphism 254 bp downstream of the mast cell chymase (CMA1) gene is associated with atopic asthma and total serum IgE levels.

The gene for mast cell chymase (CMA1) is an ideal candidate for investigating genetic predisposition to atopic asthma, as it is an important mediator of inflammation and remodeling in the asthmatic lung. Various studies have examined the association between -1903 G/A polymorphism and allergic phenotypes, but inconsistent results have been obtained. We investigated the association of this SNP and a novel (TG)(n)(GA)(m) repeat polymorphism (accession no. BV210164) 254 bp downstream of the gene with asthma and its associated traits in a case-control study in two independent cohorts recruited from the Indian population. A significant association was observed for the (TG)(n)(GA)(m) repeat with asthma (p<0.05) in both the cohorts. Although no association was observed for the -1903 G/A SNP with asthma, a significant association was observed between the genotypes and serum IgE levels (p=0.003 and 0.0004 for cohort A and B). When haplotypes were compared between patients and controls, the haplotype G_43 was found at higher frequency in controls (p=0.05). Also, on comparing major haplotypes (>5%) with respect to log total serum IgE levels, a significant difference was obtained (p=0.018 and p=0.046 for cohorts A and B). These results suggest that the CMA1 gene contributes to asthma susceptibility and may be involved in regulating IgE levels in atopic asthma.

Adult↗
PubMed2005

Vanadium induces apoptosis and modulates the expressions of metallothionein, Ki-67 nuclear antigen, and p53 during 2-acetylaminofluorene-induced rat liver preneoplasia.

Our previous studies have shown that vanadium, a dietary micronutrient, has an inhibitory effect against experimentally induced rat hepatocarcinogenesis. In this study, we evaluated the role of vanadium on some potential protein expression markers of carcinogenesis, such as metallothionein (MT), an intracellular metal-binding protein linked with cell proliferation and apoptosis, Ki-67 nuclear antigen, and p53 tumor suppressor during 2-acetylaminofluorene (2-AAF)-induced (0.05% in basal diet) rat liver preneoplasia. In a short-term regimen, supplementation of vanadium at a dose of 0.5 ppm effectively suppressed the formation of DNA 'comets' (29.55%; P < 0.02), thereby indicating its nongenotoxicity at this particular dose. Vanadium administration throughout the study reduced relative liver weight (RLW), nodular incidence (57.15%), total number, and multiplicity (48.45%) with restoration of hepatic zinc (Zn), magnesium (Mg), selenium (Se), copper (Cu), iron (Fe), and calcium (Ca) contents when compared to the carcinogen control. Moreover, treatment with vanadium significantly abated the expressions of MT and Ki-67, studied at four sequential time points. An increased immunopositivity of p53 protein (1.03 +/- 0.23%; P < 0.02) was found in vanadium-treated rat liver with an elevated apoptotic-labeling index (AI; P < 0.001) as documented by TUNEL assay. Furthermore, a positive correlation between MT expression and Ki-67 labeling along with a strong negative correlation between MT immunoreactivity and AI (r = -0.9000, P = 0.0004 at week 24) at various time intervals suggest that, vanadium-mediated suppression of MT and Ki-67 expressions may be associated with induction of apoptosis. The results thus provide evidence for the first time in support of the potential role of vanadium on induction of p53 and apoptosis with concurrent suppression of MT and Ki-67 in order to have an understanding, in part, of the chemopreventive mechanism of this trace element in limiting neoplastic transformation in a defined model of experimental rat hepatocarcinogenesis.

2-Acetylaminofluorene↗
PubMed2005

Novel thiocoumarins as inhibitors of TNF-alpha induced ICAM-1 expression on human umbilical vein endothelial cells (HUVECs) and microsomal lipid peroxidation.

Different coumarin/thiocoumarin derivatives, that is, 7-hydroxy-4-methylcoumarin, 7,8-dihydroxy-4-methylcoumarin, 7-acetoxy-4-methylcoumarin, 7,8-diacetoxy-4-methylcoumarin, 7-hydroxy-4-methylthiocoumarin, 7,8-dihydroxy-4-methylthiocoumarin, 7-acetoxy-4-methylthiocoumarin and 7,8-diacetoxy-4-methylthiocoumarin were synthesized and evaluated for their effects on TNF-alpha induced expression of intercellular adhesion molecule-1 (ICAM-1) on endothelial cells and on NADPH-catalyzed rat liver microsomal lipid peroxidation with a view to identify modulators for expression of cell adhesion molecules and to establish structure-activity relationship. We found that dihydroxy and diacetoxy derivatives of thiocoumarin were more potent in comparison to the corresponding coumarin derivatives in inhibiting TNF-alpha-induced expression of ICAM-1. However, coumarin derivatives were found to be more potent in comparison to the corresponding thiocoumarins in inhibiting microsomal lipid peroxidation. We have also tested the intermediate compounds 7,8-dibenzyloxy-4-methylcoumarin and 7,8-dibenzyloxy-4-methylthiocoumarin for their inhibitory activity on TNF-alpha-induced ICMA-1 expression. We found that dibenzyloxy-4-methylthiocoumarin is better than dibenzyloxy-4-methylcoumarin. The mechanisms underlying the observed activities of coumarins and thiocoumarins have been discussed with reference to their structures. Such structure-function relationship studies may help in developing molecules with better anti-inflammatory and anti-oxidant activities.

Animals↗
PubMed2005

Polarized helper T cells in tubercular pleural effusion: phenotypic identity and selective recruitment.

Containment of Mycobacterium tuberculosis critically depends on orchestrated generation of Th1 cells and their selective recruitment at the pathologic sites. Understanding the mechanism involved in this process is important for defining better intervention strategies. We investigated the surface phenotype of Th1 cells and the role of chemotactic factors in their selective recruitment in tuberculosis pleural effusion and tuberculin site. Memory T cells obtained from the pleural fluid expressed a battery of homing receptors such as CD11a, CCR5 and CXCR3. Similar expression profile was noted on T cells infiltrating the tuberculin site. Expression of their respective ligands such as ICAM-1, RANTES, MIP1-alpha, Mig and IP-10 were detected at pathologic sites. In vitro assay of T cell adherence to activated human umbilical vein endothelial cells (HUVEC) expressing chemotactic ligands suggests an important role of these homing molecules in their selective trafficking. Here, we demonstrate a hierarchy of CXCR3 in effector cell adhesion to HUVEC in vitro, although CD11a and CCR5 were also observed to mediate cell adhesion in an additive fashion. Findings of the present study provide mechanistic insights into the critical events of T cell trafficking in tuberculosis and may help designing better therapeutic modalities.

Adult↗
PubMed2005

TGFbeta1 haplotypes and asthma in Indian populations.

BACKGROUND: Asthma is a complex disorder of the airways of the lungs. TGF-beta1 plays a key role in airway remodeling and asthma by having both proinflammatory and anti-inflammatory activities, making TGFbeta1 an important candidate gene to study. OBJECTIVE: To investigate the association of TGFbeta1 gene polymorphisms with asthma. METHODS: A case-control study was designed for identifying polymorphisms and haplotypes associated with asthma and associated phenotypes. We have verified our results in 2 independent cohorts collected from northern (number of patients, 187; number of controls, 187) and western India (number of patients, 209; number of controls, 190). We measured the serum TGF-beta1 levels of selected individuals and correlated them with genotypes and haplotypes. RESULTS: A novel (CT)n(CA)m repeat polymorphism (BV209662) 24.9 kb upstream of TGFbeta1 was identified. A significant association was seen at the level of alleles and genotypes with asthma in the 2 cohorts studied independently (P < .05). Interestingly, a novel 3-locus haplotype, 23_G_T, was found to be significantly associated with asthma (P = .00001 in cohorts A and B) as well as with higher serum TGF-beta1 level (P = .01). On the other hand, a novel haplotype, 22_G_C, was negatively associated with asthma (P = .00001 for cohorts A and B) and with lower serum TGF-beta1 level (P = .0019). CONCLUSION: This is the first study identifying novel risk and protective haplotypes--23_G_T and 22_G_C, respectively--in the TGFbeta1 gene that are associated with asthma. We also demonstrate the functional significance of these haplotypes with serum TGF-beta1 levels. These results would be valuable in elucidating the role of TGF-beta1 in asthma pathogenesis.

Adult↗
PubMed2005

Vanadium, a versatile biochemical effector in chemical rat mammary carcinogenesis.

Recent studies indicate the role of the micronutrient vanadium in chemoprevention in many animal models, human cancer cell lines, and also in xenografted human carcinomas of the lung, breast, and gastrointestinal tract. The present studies were undertaken to ascertain the antineoplastic potential of vanadium in a defined model of mammary carcinogenesis. Female Sprague-Dawley rats, at 50 days of age, were treated with 7,12-dimethylbenz(alpha) anthracene (DMBA) (0.5 mg/100 g body weight) by a tail vein injection in oil emulsion. Vanadium (ammonium metavanadate) at a concentration of 0.5 ppm (4.27 micromol/l) was supplemented in drinking water and given ad libitum to the experimental group after the carcinogen treatment, and it continued until the termination of the study. In vivo studies of DNA chain breaks demonstrated that vanadium offered significant (61%, P<0.005) protection against generation of single-strand breaks when compared with the DMBA control group. Supplementation of vanadium normalizes the level of zinc, iron, and copper as revealed by proton-induced X-ray emission analysis to a substantial extent (P<0.01). In vitro study of chromosomal aberrations (CAs) revealed that vanadium triggered a protective effect (62.9%) on induction of CAs, which was maximum on structural aberrations followed by numerical and physiological types. Histopathological and morphological analyses were done as end-point biomarkers. We conclude herein that vanadium has the potential to reduce genomic instability in mammary carcinoma in rats.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed2005

Beta(2)-adrenergic receptor polymorphisms and response to salbutamol among Indian asthmatics*.

INTRODUCTION: The beta(2)-adrenergic receptor (beta(2)AR or ADRbeta(2)) is the target for beta(2)-agonist drugs used for bronchodilation in asthma and other respiratory diseases. The aim of this study was to identify common single nucleotide polymorphisms (SNPs) and haplotypes in asthmatics and healthy individuals from an Indian population, and determine the influence of beta(2)AR SNPs in responsiveness to beta(2)-agonist therapy in asthma patients. METHODS: Ten variable SNP sites within a span of 2.193 kb were identified in the beta(2)AR gene by sequencing and genotyping 374 bronchial asthma patients and healthy individuals from an Indian population. Spirometry tests were performed on 80 unrelated patients before and after administration of 200 microg of salbutamol. A post-bronchodilator forced expiratory volume in one second (FEV(1)) change of >or= 15.3% was considered a good response, and a change of<15.3% was defined as a poor response, to salbutamol. RESULTS: The pattern of linkage disequilibrium between the ten SNPs showed a single, linked SNP block consisting of sites -468, -367, -47, -20, and 79 having strong linkage disequilibrium, while the SNPs at sites -1023, -654, 46, 252, and 523 showed very low linkage with one another and with the linked region. The SNPs were found to be organized into 16 haplotypes in the studied population. We found that patients with a homozygous Arg-16 form at nucleotide position 46 are poor responders with probability of 0.81, and patients with a homozygous Gly-16 form are good responders with a probability of 0.73. The responder status to salbutamol treatment and the genotype at nucleotide position 46 in beta(2)AR gene of an asthmatic patient are significantly associated in the studied Indian population (chi2=9.98, df=2, p=0.0068). Most importantly, this association for responsiveness to salbutamol at nucleotide position 46 is independent of other SNPs in the beta(2)AR gene. CONCLUSION: This study suggests that the SNP at nucleotide position 46 has particular relevance to pharmacogenetics in the Indian population studied.

5' Untranslated Regions↗