Susceptibility of the Bhopal-methyl isocyanate (MIC)-gas-tragedy survivors and their offspring to COVID-19: What we know, what we don't and what we should?

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.

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.

Cross-sectional survey of workers exposed to aliphatic diisocyanates using detailed respiratory medical history and questions regarding accidental skin and respiratory exposures.

OBJECTIVES: To identify possible cases of occupational asthma and assess accidental skin and inhalation exposures to aliphatic diisocyanates. METHODS: Seventy-three employees from two plants, manufacturing or producing aliphatic diisocyanates, were surveyed using a detailed respiratory history questionnaire with additional questions on accidental skin and inhalation exposures. Further reviews of medical records and interviews were used to determine whether any of 15 employees with questionable responses had developed occupational asthma. RESULTS: No cases of occupational asthma were identified. Nevertheless, many employees reported occasional accidental unprotected skin exposures and/or detecting the odor of 1,6-hexamethylene diisocyanate or isophorone diisocyanate. CONCLUSIONS: Consistent with a previous study, no cases of occupational asthma were identified from exposure to 1,6-hexamethylene diisocyanate, isophorone diisocyanate, methylene bis(4-cyclohexyl isocyanate), or their polyisocyanates even though many employees reported detection of odors (93%) or skin exposures (53%).

Inflammatory response to isocyanates and onset of genomic instability in cultured human lung fibroblasts.

Lungs comprise the primary organ exposed to environmental toxic chemicals, resulting in diverse respiratory ailments and other disorders, including carcinogenesis. Carcinogenesis is a multi-stage phenomenon, which involves a series of genetic alterations that begin with genomic instability provoked by certain factors such as inflammation and DNA damage and end with the development of cancer. Isocyanates such as methyl isocyanate are the chief metabolic intermediates in many industrial settings with diverse applications; exposure to them can lead to severe hypersensitive, mutagenic and genotoxic alterations. We examined the molecular mechanisms underlying isocyanate-mediated inflammatory responses and their probable role in the onset of genomic instability in cultured IMR-90 human lung fibroblasts. The isocyanates induced inflammation, resulting in extensive DNA damage, evidenced by increases in ATM, ATR, gammaH2AX, and p53 expression levels. The apoptotic index also increased. Chromosomal anomalies in treated cells included over-expression of centrosome protein and variable amplification of inter-simple sequence repeats, further demonstrating isocyanate-induced genomic instability. This information could be useful in the design of new approaches for risk assessment of potential industrial disasters.