Susceptibility of the Bhopal-methyl isocyanate (MIC)-gas-tragedy survivors and their offspring to COVID-19: What we know, what we dont and what we should? / Suscetibilidade dos sobreviventes da tragédia de Bhopal-isocianato de metila (CIM)-gás e seus filhos ao COVID-19: O que sabemos, o que não sabemos e o que devemos?

Abstract There is credible evidence that the 1984-Bhopal-methyl isocyanate (MIC)-gas-exposed long-term survivors and their offspring born post-exposure are susceptible to infectious/communicable and non-communicable diseases. Bhopal's COVID-19 fatality rate suggests that the MIC-gas tragedy survivors are at higher risk, owing to a weakened immune system and co-morbidities. This situation emboldened us to ponder over what we know, what we don't, and what we should know about their susceptibility to COVID-19. This article aims at answering these three questions that emerge in the minds of public health officials concerning prevention strategies against COVID-19 and health promotion in the Bhopal MIC-affected population (BMAP). Our views and opinions presented in this article will draw attention to prevent and reduce the consequences of COVID-19 in BMAP. From the perspective of COVID-19 prophylaxis, the high-risk individuals from BMAP with co-morbidities need to be identified through a door-to-door visit to the severely gas-affected regions and advised to maintain good respiratory hygiene, regular intake of immune-boosting diet, and follow healthy lifestyle practices.

Resumo Há evidências plausíveis de que os sobreviventes a longo prazo da exposição a gás de 1984 e isocianato de metila (CIM), em Bhopal, e seus filhos nascidos após esse fato estão suscetíveis a doenças infecciosas/transmissíveis e não transmissíveis. A taxa de fatalidade COVID-19 de Bhopal sugere que os sobreviventes da tragédia do gás MIC estão em maior risco, devido a um sistema imunológico enfraquecido e comorbidades. Essa situação nos encorajou a refletir sobre o que sabemos, o que não sabemos e o que devemos saber sobre a suscetibilidade deles ao COVID-19. Este artigo objetiva responder a essas três perguntas que surgem na mente dos funcionários de saúde pública sobre estratégias de prevenção contra o COVID-19 e promoção da saúde na população afetada pelo Bhopal MIC (BMAP). Nossas visões e opiniões apresentadas neste artigo chamam a atenção para prevenir e reduzir as consequências do COVID-19 no BMAP. Da perspectiva da profilaxia com COVID-19, os indivíduos de alto risco do BMAP com condições comórbidas precisam ser identificados por meio de uma visita de porta em porta nas regiões severamente afetadas por gases e aconselhados a manter uma boa higiene respiratória, ingestão regular de dieta que estimule o sistema imunológico e seguir práticas de estilo de vida saudáveis.

PPARγ induces growth inhibition and apoptosis through upregulation of insulin-like growth factor-binding protein-3 in gastric cancer cells

Peroxisome proliferator activator receptor-gamma (PPARγ) is a ligand-activated transcriptional factor involved in the carcinogenesis of various cancers. Insulin-like growth factor-binding protein-3 (IGFBP-3) is a tumor suppressor gene that has anti-apoptotic activity. The purpose of this study was to investigate the anticancer mechanism of PPARγ with respect to IGFBP-3. PPARγ was overexpressed in SNU-668 gastric cancer cells using an adenovirus gene transfer system. The cells in which PPARγ was overexpressed exhibited growth inhibition, induction of apoptosis, and a significant increase in IGFBP-3 expression. We investigated the underlying molecular mechanisms of PPARγ in SNU-668 cells using an IGFBP-3 promoter/luciferase reporter system. Luciferase activity was increased up to 15-fold in PPARγ transfected cells, suggesting that PPARγ may directly interact with IGFBP-3 promoter to induce its expression. Deletion analysis of the IGFBP-3 promoter showed that luciferase activity was markedly reduced in cells without putative p53-binding sites (-Δ1755, -Δ1795). This suggests that the critical PPARγ-response region is located within the p53-binding region of the IGFBP-3 promoter. We further demonstrated an increase in PPARγ-induced luciferase activity even in cells treated with siRNA to silence p53 expression. Taken together, these data suggest that PPARγ exhibits its anticancer effect by increasing IGFBP-3 expression, and that IGFBP-3 is a significant tumor suppressor.

Association of microsatellite instability and chronic obstructive pulmonary disorder in isocyanate-exposed population of Bhopal.

Context: Survivors of the Bhopal gas disaster still suffer from various respiratory ailments. We examined the effects of exposures among a cross-section of current residents suffering from COPD by ISSR-PCR. Aims: Molecular screening of the gas-affected population of Bhopal with COPD for microsatellite instability due to exposure of MIC. Settings and Design: The isocyanate-exposed population of Bhopal city suffering from chronic obstructive pulmonary disorder. Materials and Methods: Inter-(SSR) analysis was used to characterize microsatellite instability in 52 MIC victims of Bhopal, suffering from COPD using (CA) 8 RG and (CA) 8 R[Y-Q] primer. Statistical Analysis Used: Association analyses were performed using regression analysis. Results: The study on the MIC-affected population in Bhopal showed weak association between microsatellite instability and age (r = + 0.37); exposure distance from site (r = −0.44); and smoking status(r = + 0.12); while regression analysis of the above parameters displayed supporting evidence. Conclusions: The high prevalence of smoking coupled with aging and poor living habits threatens, to further increase COPD incidences among this population, highlighting the need for enhanced screening efforts.

Retrospective analysis of lung function abnormalities of Bhopal gas tragedy affected population.

Background & objectives: A large numbers of subjects were exposed to the aerosol of methyl isocyanate (MIC) during Bhopal gas disaster and lung was one of the most commonly affected organs. The aim of the present study was to analyze retrospectively the lung function abnormalities among the surviving MIC exposed population (gas victims) and to compare it with the non-MIC exposed (non gas exposed) population. Methods: The spirometry data of both gas victims and non gas exposed population who attended the Bhopal Memorial Hospital & Research Centre for evaluation of their respiratory complaints from August 2001 to December 2009, were retrospectively evaluated and compared. Results: A total 4782 gas victims and 1190 non gas exposed individuals performed spirometry during the study period. Among the gas victims, obstructive pattern was the commonest (50.8%) spirometric abnormality followed by restrictive pattern (13.3%). The increased relative risk of developing restrictive abnormality among gas victims was observed in 20-29 yr age group only (adjusted relative risk: 2.94, P<0.001). Male gas victims were more affected by severe airflow obstruction than females and the overall increased relative risk (1.33 to 1.45, P<0.001) of developing obstructive pattern among gas victims was observed. Interpretation & conclusions: The present study showed that the relative risk for pulmonary function abnormalities in gas victims was significantly more among those who were young at the time of disaster. Increased smoking habit among gas victims might have played an additive effect on predominance of obstructive pattern in spirometry.

Role of vitamin D-binding protein in isocyanate-induced occupational asthma

The development of a serological marker for early diagnosis of isocyanate-induced occupational asthma (isocyanate-OA) may improve clinical outcome. Our previous proteomic study found that expression of vitamin D-binding protein (VDBP) was upregulated in the patients with isocyanate-OA. In the present study, we evaluated the clinical relevance of VDBP as a serological marker in screening for isocyanate-OA among exposed workers and its role in the pathogenesis of isocyanate-OA. Three study groups including 61 patients with isocyanate-OA (group I), 180 asymptomatic exposed controls (AECs, group II), 58 unexposed healthy controls (NCs, group III) were enrolled in this study. The baseline serum VDBP level was significantly higher in group I compared with groups II and III. The sensitivity and specificity for predicting the phenotype of isocyanate-OA with VDBP were 69% and 81%, respectively. The group I subjects with high VDBP (> or = 311 microg/ml) had significantly lower PC20 methacholine levels than did subjects with low VDBP. The in vitro studies showed that TDI suppressed the uptake of VDBP into RLE-6TN cells, which was mediated by the downregulation of megalin, an endocytic receptor of the 25-hydroxycholecalciferol-VDBP complex. Furthermore, toluene diisocyanate (TDI) increased VEGF production and secretion from this epithelial cells by suppression of 1,25-dihydroxycholecalciferol [1,25(OH)2D3] production. The findings of this study suggest that the serum VDBP level may be used as a serological marker for the detection of isocyanate-OA among workers exposed to isocyanate. The TDI-induced VEGF production/secretion was reversed by 1,25(OH)2D3 treatment, which may provide a potential therapeutic strategy for patients with isocyanate-OA.