Chronic lung disease and detection of pulmonary artery dilatation in high resolution computerized tomography of chest in chronic arsenic exposure.

Lung affection in chronic arsenicosis developing from chronic ingestion of arsenic contaminated groundwater has been known but little is known on its effect on pulmonary arterial system. A cross sectional study was carried out at two geographically similar areas and demographically similar populations with or without evidence of chronic arsenic exposure in West Bengal, India. The willing participants in both the groups with chronic respiratory symptoms were evaluated with High Resolution Computerized Tomography (HRCT) of Chest. Evaluation of High Resolution Computerized Tomography of chest followed clinical assessment of lung disease in194 and 196 subjects from the arsenic exposed and unexposed people; the former had a higher prevalence of cough OR(Odds Ratio) 3.23 (95% CI(Confidence Interval): 1.72-6.07) and shortness of breath OR1.76 (95% CI: 0.84-3.71), respectively. The arsenic exposed individuals showed higher score for bronchiectasis [mean ± SD(Standard Deviation)] as 2.41 ± 2.32 vs. 1.22 ± 1.48 (P <0.001), pulmonary artery branch dilatation (PAD) as 2.48 ± 2.33 vs. 0.78 ± 1.56, (P <0.001) and pulmonary trunk dilatation as 0.26 ± 0.45 vs. nil. Age-adjusted prevalence odds ratio (POR) for Pulmonary Artery Dilatation Found in HRCT comparing those exposed to arsenic (Group 1) to unexposed participants (Group 2) was found to be 6.98 (CI: 2.26-16.48). There was a strong dose-response relationship between the PAD (Pulmonary Artery Dilatation) and cumulative arsenic exposure. Pulmonary trunk and branch dilatation in chronic arsenicosis is a frequent abnormality seen in HRCT Chest of arsenicosis patients. The significance of such finding needs further investigation.

Identification of potential biomarkers of hepatotoxicity by plasma proteome analysis of arsenic-exposed carp Labeo rohita.

Arsenic (As) is a toxic environmental contaminant and potential human carcinogen. Chronic intake of arsenic-contaminated water and food leads to arsenicosis, a major public health problem in many parts of the world. Early detection of arsenic toxicity would greatly benefit patients; however, the detection of arsenicosis needs to be done early before onset of severe symptoms in which case the tools used for detection have to be both sensitive and reliable. In this context, the present study investigated plasma proteome changes in arsenic-exposed Labeo rohita, with the aim of identifying biomarkers for arsenicosis. Changes in the plasma proteome were investigated using gel-based proteomics technology. Using quantitative image analysis of the 2D proteome profiles, 14 unique spots were identified by MALDI-TOF/TOF MS and/or LC-MS/MS which included Apolipoprotein-A1 (Apo-A1) (6 spots), α-2 macroglobulin-like protein (A2ML) (2 spots), transferrin (TF) (3 spots) and warm-temperature acclimation related 65kDa protein (Wap65). The proteome data are available via ProteomeXchange with identifier PXD003404. Highly abundant protein spots identified in plasma from arsenic-exposed fish i.e. Apo-A1 (>10-fold), A2ML (7-fold) and Wap65 (>2-fold) indicate liver damage. It is proposed that a combination of these proteins could serve as useful biomarkers of hepatotoxicity and chronic liver disease due to arsenic exposure.

Human GMDS gene fragment hypermethylation in chronic high level of arsenic exposure with and without arsenic induced cancer.

Arsenic, though a poor mutagen, is an accepted environmental carcinogen. Perturbation of DNA methylation pattern leading to aberrant gene expression has been hypothesized as the mechanism for arsenic induced carcinogenesis. We had earlier demonstrated the hypermethylation of promoter region of p53 and p16 genes in persons exposed to different doses of arsenic. Till now no genomic hot spot has been identified which is frequently hypermethylated or hypomethylated in persons chronically exposed to environmental arsenic. In the present work, we have identified one hypermethylated sequence by methyl-sensitive arbitrarily primed polymerase chain reaction in the peripheral blood leukocyte DNA of chronically arsenic exposed persons with and without arsenic induced skin cancer. The sequence is from GMDS gene responsible for fucose metabolism. Southern hybridization of the sequence to the amplification products of methyl sensitive restriction enzyme digested genome of persons exposed to different doses of arsenic indicated that methylation increased in a dose dependent manner.

E-cadherin polymorphisms and susceptibility to arsenic-related skin lesions in West Bengal, India.

OBJECTIVES: Although suppression of E-cadherin gene (CDH1) expression and exposure to arsenic have separately been associated with skin lesions, the combined effects of this "gene-environment" interaction have not been explored previously. STUDY DESIGN: A population-based cross-sectional survey. METHOD: This study involved 100 cases with skin lesions and 100 controls who were family members with no lesions. The subjects were recruited from villages and hamlets in northern Nadia Province, West Bengal. Each participant was required to undergo a detailed face-to-face interview; provide spot urine sample; provide saliva sample; and sign a consent form. The type and severity of skin lesions were assessed during a general medical examination of each participant in the field. The following 16 single nucleotide polymorphisms (SNPs) of the CDH1 were measured using DNA extracted from saliva samples: rs16260, rs5030625, rs155364, rs155808, rs155807, rs2303646, rs2059254, rs9925923, rs12919719, rs7188750, rs9989407, rs7196495, rs7196661, rs13689, rs12599393, and rs1862748. RESULTS: The main effects of SNPs on the risk for skin lesions were borderline for rs7196661 (p-value=0.092), rs7196495 (p-value=0.090), and rs12919719 (p-value=0.065); the strongest association was found for rs9989407 (p-value=0.058). Several SNPs, however, showed that the T>T genotype carriers are at higher relative risk for skin lesions compared to carriers of the C>C or C>T genotypes; these results need to be confirmed in a larger study. The main effects of some of the SNPs and genotype frequencies on the severity of skin lesions were found to be relatively weak. CONCLUSIONS: This is the first study that indicates that CDH1 polymorphisms can contribute to the etiology of premalignant skin lesions in people chronically exposed to arsenic in drinking water, and that this gene may be a factor in individual susceptibility to cutaneous diseases.

Primary prophylaxis of gastroesophageal variceal bleeding: consensus recommendations of the Asian Pacific Association for the Study of the Liver.

The Asian Pacific Association for the Study of the Liver (APASL) set up a Working Party on Portal Hypertension in 2002, with a mandate to develop consensus guidelines on various clinical aspects of portal hypertension relevant to disease patterns and clinical practice in the Asia-Pacific region. Variceal bleeding is a consequence of portal hypertension, which, in turn, is the major complication of liver cirrhosis. Primary prophylaxis to prevent the first bleed from varices is one of the most important strategies for reducing the mortality in cirrhotic patients. Experts predominantly from the Asia-Pacific region were requested to identify the different aspects of primary prophylaxis and develop the consensus guidelines. The APASL Working Party on Portal Hypertension evaluated the various therapies that have been used for the prevention of first variceal bleeding. A 2-day meeting was held on January 12 and 13, 2007, at New Delhi, India, to discuss and finalize the consensus statements. Only those statements that were unanimously approved by the experts were accepted. These statements were circulated to all the experts and were subsequently presented at the annual conference of the APASL at Kyoto, Japan, in March 2007.

Community-based epidemiology of hepatitis B virus infection in West Bengal, India: prevalence of hepatitis B e antigen-negative infection and associated viral variants.

BACKGROUND AND AIMS: There is a paucity of population-based epidemiological information regarding hepatitis B virus (HBV) infection in India. The present study was planned to outline the magnitude and pattern of HBV infection, hepatitis B e antigen (HBeAg)-negative infection and the associated viral mutants in India. METHODS: A community-based epidemiological study of HBV infection was carried out in West Bengal, India. Serological markers of infection and potential risk factors for HBV transmission were determined. Among the infected individuals, HBV-DNA, genotypes and mutations in the precore (PC) stop codon and basal core promoter (BCP) regions were determined by DNA sequencing and polymerase chain reaction (PCR) restriction fragment length polymorphism methods. RESULTS: Of the 7653 people included in the study, 227 (2.97%) tested positive for hepatitis B surface antigen (HBsAg), of whom 204 (90%) were HBeAg-negative and hepatitis B e antibody (anti-HBe)-positive, and 78% had normal alanine aminotransferase (ALT) levels. HBV-DNA could be detected by PCR in only 32% of people. G1896A PC stop codon mutants were present in 12% of people, BCP mutants in 18% and the remainder (70%) of the HBeAg-negative infections were associated with wild type sequences in these regions. CONCLUSIONS: This first general population-based epidemiological study of HBV infection from India suggests that HBV acquisition starts in early childhood and peaks in adulthood. Most infections in the community are e-negative and inactive. The point prevalence of PC stop codon and BCP mutants is low in this primarily inactive and asymptomatic HBV-infected population sample in eastern India.