Role of oxidative stress & transient receptor potential in chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) affect millions of people worldwide and is known to be one of the leading causes of death. The highly sensitive airways protect themselves from irritants by cough and sneeze which propel endogenous and exogenous substances to minimize airway noxious effects. One noxious effect of these substances is activation of peripheral sensory nerve endings of nociceptor neurons innervating these airways lining thus transmitting dangerous signals from the environment to the central nervous system (CNS).

Cancer chemopreventive effects of the flavonoid-rich fraction isolated from papaya seeds.

Intervention to decelerate, arrest, or reverse the process of carcinogenesis by the use of either natural or synthetic agents individually or in combination has emerged as a promising and pragmatic medical approach to reduce cancer risk. In the present study, we examined the cancer chemopreventive potential of a flavonoid-rich fraction isolated from the seeds of Carica papaya, a plant traditionally referred to as papaw. The flavonoid-enriched benzene fraction of the aqueous extract exerted its anticancer properties in vitro through cytoprotection, antioxidative and antiinflammatory mechanisms and genoprotection in response to isocyanate-induced carcinogenicity.

CD14 C-159T polymorphism and its association with chronic lung diseases: A pilot study on isocyanate exposed population of Central India.

Context: CD14 functions as a multifunctional receptor for bacterial cell wall components including endotoxin and lipopolysaccharide and is likely to influence the cytokine profile and subsequent immunoglobulin E production in response to antigen/allergen contact in allergic phenotypes.

Aims: The present study was to investigate genetic polymorphism in CD14 gene - 159C/T, which may be one of the risk factor for increased prevalence of Chronic Lung Diseases in the Central India.

Settings And Design: Survivors of Methyl isocyanates toxicity in Bhopal still suffering from various respiratory ailments were examined.

A retrospective review of cytogenetic studies on methyl isocyanate with special reference to the Bhopal gas tragedy: is the next generation also at risk?

The world's worst industrial disaster, at Union Carbide, Bhopal, India, took place on 2-3 December 1984, leading to the leakage of poisonous methyl-isocyanate into the environment, causing thousands of deaths, pregnancy loss and for some, incapacitation for life. More than a quarter of a century later, the Indian Council of Medical Research undertook to redefine the abysmal consequences of the toxic gas exposure on the exposed population. This invigorated the interest of scientific community in the evaluation of the long-term effects, with reference to cytogenetic parameters.

An HIV1/2 point of care test on sputum for screening TB/HIV co-infection in Central India - Will it work?

Objective: To determine whether the OraQuick® HIV-1/2 Assay (OraSure Technologies, Inc., Bethlehem, PA, USA) in sputum is a valid tool for HIV surveillance among TB patients.

Methods: A cross sectional study was carried out on sputa of patients diagnosed with tuberculosis.

Mosaicism for trisomy 21 and ring (21) in a male born to normal parents: a case report.

We present a case of a ring (21) in a mentally challenged patient with mosaicism for trisomy 21 showing karyotype 47, XY,+21/47,XY,+21(r)/46,XY, born to normal parents. The parents and female sibling were phenotypically normal. This is a unique case report from Central India, on occurrence of trisomy 21 and r (21) in the same individual born to normal parents.

Circulating Biomarkers and their Possible Role in Pathogenesis of Chronic Hepatitis B and C Viral Infections.

The present study evaluated the plausible role of circulating biomarkers in immune pathogenesis of chronic hepatitis considered a priority in clinical hepatology. Total viral load of chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) patients was quantified and correlation studies were performed with circulating levels of Th1/Th2 cytokines; C reactive protein and circulating nucleosomes; glutathione reductase (GR) and superoxide dismutase. To our knowledge, the study is first among its kind that validates strong positive correlation of viral load with IL-4, IL-6, GR in HBV and IL-6, IL-10, GR in HCV infections.

Cell cycle deregulation by methyl isocyanate: Implications in liver carcinogenesis.

Liver is often exposed to plethora of chemical toxins. Owing to its profound physiological role and central function in metabolism and homeostasis, pertinent succession of cell cycle in liver epithelial cells is of prime importance to maintain cellular proliferation. Although recent evidence has displayed a strong association between exposures to methyl isocyanate (MIC), one of the most toxic isocyanates, and neoplastic transformation, molecular characterization of the longitudinal effects of MIC on cell cycle regulation has never been performed.

Novel approach for quantification of hepatitis C virus in liver cirrhosis using real-time reverse transcriptase PCR.

Background: Hepatitis C virus (HCV) infects nearly 3% of the population worldwide and is a major cause of acute and chronic infections leading to fibrosis, cirrhosis, and hepatocellular carcinoma. Current laboratory diagnosis of HCV is based on specific antibody detection (anti-hepatitis C virus (anti-HCV)) in serum. As HCV replicates in the liver cells, detection and localization of HCV RNA in liver tissue are vital for diagnosis.

'Boiled egg' in the peritoneal cavity-a giant peritoneal loose body in a 64-year-old man: a case report.

Introduction: Peritoneal loose bodies, or peritoneal mice, are rare asymptomatic lesions that are usually found as an incidental finding during abdominal surgery or autopsy. Giant loose bodies, measuring more than 5 cm, are rare and only a few cases are reported in the literature. These bodies are usually infarcted appendices epiploicae, which become detached and appear as a peritoneal loose body in the abdominal cavity.

Molecular surveillance of hepatitis and tuberculosis infections in a cohort exposed to methyl isocyanate.

Objective: The potential toxic effects on the immune system exerted by occupational and accidental environmental exposures and underlying molecular regulatory mechanisms involved in the etiology and progression of infectious diseases are now being characterized. The Bhopal gas tragedy is undoubtedly one of the worst industrial disasters in the history of mankind. After 25 years of accidental exposure to methyl isocyanate (MIC), severe systemic ailments still continue to pre-occupy the lives of the affected population that survived this tragedy.

Molecular detection of Mycobacterium tuberculosis in formalin-fixed, paraffin-embedded tissues and biopsies of gastrointestinal specimens using real-time polymerase chain reaction system.

Background/aims: We aimed to perform the molecular detection of Mycobacterium tuberculosis in formalin-fixed, paraffin-embedded tissues and biopsies of gastrointestinal specimens using real-time polymerase chain reaction system.

Methods: The study included three groups: (A) control (n=24), with no previous signs of M. tuberculosis complex (MTBC), (B) patients (n=28) with known TB origin and (C) patients (n=50) with clinical and histopathological signs of TB but who were culture- and acid-fast bacilli (AFB)-negative.

Peri-operative outcomes for pancreatoduodenectomy in India: a multi-centric study.

Background: There have been an increasing number of reports world-wide relating improved outcomes after pancreatic resections to high volumes thereby supporting the idea of centralization of pancreatic resectional surgery. To date there has been no collective attempt from India at addressing this issue. This cohort study analysed peri-operative outcomes after pancreatoduodenectomy (PD) at seven major Indian centres.

Status of inflammatory biomarkers in the population that survived the Bhopal gas tragedy: a study after two decades.

Bhopal gas tragedy is considered as one of the world's worst industrial disaster. Approximately, 3,000-6,000 people died and 200,000 injured due to the leak of 40 tons of methyl isocyanate (MIC) gas from a pesticide plant. We aimed to decipher any persistent and subtle immunotoxic effects of MIC in the survivors of the tragedy.

Diagnosis of gastrointestinal tuberculosis: Using cytomorphological, microbiological, immunological and molecular techniques - A study from Central India.

The present study included three groups: (A) age and gender matched control (n=24) with no previous signs of M. tuberculosis complex (MTBC) infection, (B) patients (n=28) diagnosed with gastro-intestinal TB (GITB), (C) patients (n=50) with clinical and histo-pathological signs of GITB, but were culture and AFB negative. Real time assay performed using fluorescence resonance energy transfer hybridization probes showed a positivity index of 36 % in group C, i.

Correlation of aberrant expression of p53, Rad50, and cyclin-E proteins with microsatellite instability in gallbladder adenocarcinomas.

Gallbladder carcinoma is an uncommon, but highly malignant tumor, with poor prognostic, and diagnostic manifestations in early stages. The Indian Council of Medical Research reported increased incidence of gallbladder carcinoma in the surviving population of the Bhopal gas tragedy that involved exposure of more than 500,000 people to methyl isocyanate gas. The severity of exposure, and increased multi-systemic morbidity in the survivors stimulated us to examine the molecular changes leading to gallbladder carcinoma.

Bhopal Gas Tragedy: review of clinical and experimental findings after 25 years.

The Bhopal gas tragedy is undoubtedly one of the worst industrial disasters in the history of mankind resulting in mortality of 2500-6000 and debilitating over 200 000 people. Inhabitants in the township were exposed to different degrees and there are more than 500 000 registered victims that survived the tragedy. Clinical studies have shown chronic illnesses such as pulmonary fibrosis, bronchial asthma, chronic obstructive pulmonary disease (COPD), emphysema, recurrent chest infections, keratopathy and corneal opacities in exposed cohorts.

Mitochondrial oxidative stress elicits chromosomal instability after exposure to isocyanates in human kidney epithelial cells.

The role of oxidative stress is often attributed in environmental renal diseases. Isocyanates, a ubiquitous chemical group with diverse industrial applications, are known to undergo bio-transformation reactions upon accidental and occupational exposure. This study delineates the role of isocyanate-mediated mitochondrial oxidative stress in eliciting chromosomal instability in cultured human kidney epithelial cells.

Regulation of isocyanate-induced apoptosis, oxidative stress, and inflammation in cultured human neutrophils: isocyanate-induced neutrophils apoptosis.

Implications of environmental toxins on the regulation of neutrophil function are being significantly appraised. Such effects can be varied and markedly different depending on the type and extent of chemical exposure, which results in direct damage to the immune system. Isocyanates with functional group (-NCO), are considered as highly reactive molecules with diverse industrial applications.

Induction of genomic instability in cultured human colon epithelial cells following exposure to isocyanates.

The toxic response of cultured human colon epithelial-FHC cells to methyl isocyanate was investigated with regard to genomic instability. Qualitative and quantitative assessments of the extent of phosphorylation of DNA damage signaling factors such as ATM, gammaH2AX and p53, was increased in treated cells compared to controls. At the same time, many treated cells were arrested at the G2/M phase of the cell cycle, and had an elevated apoptotic index and increased inflammatory cytokine levels.

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.

Analysis of cellular response to isocyanate using N-succinimidyl N-methylcarbamate exposure in cultured mammalian cells.

Isocyanates (R--N==C==O), one of the highly reactive industrial intermediates, possess the capability to modulate the bio-molecules by forming toxic metabolites and adducts which may cause adverse health effects. Some of their toxic degradations have previously been unknown and overlooked; of which, molecular repercussions underlying their genetic hazards upon occupational/accidental exposures still remain as an intricate issue and are hitherto unknown. To assess the genotoxic potential of methyl isocyanate in cultured mammalian cells after in vitro exposure, we performed a study in three different normal cell lines MM55.

Isocyanates induces DNA damage, apoptosis, oxidative stress, and inflammation in cultured human lymphocytes.

Isocyanates, a group of low molecular weight aromatic and aliphatic compounds containing the isocyanate group (-NCO), are important raw materials with diverse industrial applications; however, pathophysiological implications resulting from occupational and accidental exposures of these compounds are hitherto unknown. Although preliminary evidence available in the literature suggests that isocyanates and their derivatives may have deleterious health effects including immunotoxicity, but molecular mechanisms underlying such an effect have never been addressed. The present study was carried out to assess the immunotoxic response of methyl isocyanate (MIC) on cultured human lymphocytes isolated from healthy human volunteers.