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1.
Nutr Cancer ; 66(5): 857-71, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24820939

RESUMO

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. Medium-term anticarcinogenicity and 2-stage skin papillomagenesis studies conducted in benzopyrene-induced lung carcinogenesis and 7,12-dimethyl benz(a)anthracene-mediated skin papillomagenesis mouse models further validated our in vitro observations. This is the first demonstration of chemopreventive activities of papaya seed products, however, further studies to understand the subtle targets of intracellular signaling pathways, pharmacological profile and toxicological safety of this bioactive fraction are essential to pave the way for successful clinical translation. Our study supports the inverse association between dietary flavonoid intake and cancer risk.


Assuntos
Anticarcinógenos/farmacologia , Carica/química , Flavonoides/farmacologia , Extratos Vegetais/farmacologia , Sementes/química , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Quimioprevenção , Dano ao DNA/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Células HEK293 , Humanos , Camundongos , Estresse Fisiológico/efeitos dos fármacos
2.
Environ Toxicol ; 29(3): 284-97, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22223508

RESUMO

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. Here, we sequentially delineated the status of different proteins arbitrating the deregulation of cell cycle in liver epithelial cells treated with MIC. Our data reaffirms the oncogenic capability of MIC with elevated DNA damage response proteins pATM and γ-H2AX, deregulation of DNA damage check point genes CHK1 and CHK2, altered expression of p53 and p21 proteins involved in cell cycle arrest with perturbation in GADD-45 expression in the treated cells. Further, alterations in cyclin A, cyclin E, CDK2 levels along with overexpression of mitotic spindle checkpoints proteins Aurora A/B, centrosomal pericentrin protein, chromosomal aberrations, and loss of Pot1a was observed. Thus, MIC impacts key proteins involved in cell cycle regulation to trigger genomic instability as a possible mechanism of developmental basis of liver carcinogenesis.


Assuntos
Ciclo Celular/efeitos dos fármacos , Dano ao DNA , Isocianatos/toxicidade , Fígado/efeitos dos fármacos , Animais , Carcinogênese , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular , Aberrações Cromossômicas/induzido quimicamente , Células Epiteliais/efeitos dos fármacos , Fígado/citologia , Camundongos
3.
Int J Occup Med Environ Health ; 26(3): 324-36, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23857370

RESUMO

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. The thrust area was identified in terms of genetic disorders, low birth weight, developmental/growth disorders and congenital malformations. Also the impact on epigenetic factors, which may have contributed to variations in the functional expression of genes, was not negated, stimulating intense scientific research on in utero exposure and the progeny of the exposed population. To accomplish this mammoth task, molecular cytogenetic investigations must be undertaken in conjunction with conventional cytogenetics, using techniques such as FISH, Immuno-FISH, SKY and SNP analysis, to build up a cytogenetic database of the surviving population.


Assuntos
Vazamento Acidental em Bhopal , Análise Citogenética , Dano ao DNA , Isocianatos/toxicidade , Animais , Feminino , Humanos , Linfócitos , Gravidez , Efeitos Tardios da Exposição Pré-Natal/genética
4.
Asian Pac J Trop Med ; 6(3): 216-9, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23375036

RESUMO

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. Sputa were tested for antibodies to HIV using OraQuick® HIV-1/2 Assay (OraSure Technologies, Inc., Bethlehem, PA, USA). The results were compared with results of serum ELISA. RESULTS: Compared to serum ELISA, the OraQuick® HIV-1/2 Assay in sputum specimens reported 90% sensitivity (9/10) and 100% specificity (307/307), with a positive predictive value of 100% (95%CI: 66.37%-100.00%) and a negative predictive value of 99.68% (95%CI: 98.20%-99.99%). CONCLUSIONS: This testing method may provide a useful strategy for conducting HIV surveillance in possible co-infected TB patients at peripheral centres. Since there is no investment on infrastructure, it may be possible for paramedical health professionals to carry out the test, particularly in areas with low HIV endemicity.


Assuntos
Infecções por HIV/diagnóstico , HIV-1/isolamento & purificação , HIV-2/isolamento & purificação , Programas de Rastreamento/métodos , Escarro/química , Adolescente , Adulto , Idoso , Estudos Transversais , Ensaio de Imunoadsorção Enzimática , Feminino , Infecções por HIV/sangue , Infecções por HIV/complicações , Humanos , Índia , Masculino , Pessoa de Meia-Idade , Sistemas Automatizados de Assistência Junto ao Leito , Sensibilidade e Especificidade , Tuberculose Pulmonar/sangue , Tuberculose Pulmonar/complicações , Adulto Jovem
5.
Gene ; 511(1): 109-12, 2012 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-23000017

RESUMO

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. Also being documented for the first time is the immuno-FISH analysis revealing differential expression of hTERT and a linked over expression of TRF2 in proband, probably corresponding to a high percentage of acrocentric associations.


Assuntos
Síndrome de Down/genética , Mosaicismo , Cromossomos em Anel , Criança , Cromossomos Humanos Par 21/genética , Anormalidades Craniofaciais/genética , Feminino , Expressão Gênica , Humanos , Hibridização in Situ Fluorescente , Índia , Deficiência Intelectual/genética , Cariotipagem , Masculino , Telomerase/genética , Proteína 2 de Ligação a Repetições Teloméricas/genética
6.
Int J Occup Med Environ Health ; 24(1): 94-101, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21468906

RESUMO

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. We have performed a molecular surveillance study to characterize hepatitis and tuberculosis infections amongst the first and the second generation of survivors exposed to MIC. MATERIALS AND METHODS: Both outdoor and indoor patients referred for molecular diagnosis of hepatitis B virus (HBV), hepatitis C virus (HCV) and Mycobacterium tuberculosis (MTB) were examined. Qualitative analysis for HBsAg, anti-HBc, anti-HCV through ELISA was performed, while BacT/ALERT and Ziehl-Neelson technique were utilized for the assessment of tuberculosis. Detection and quantification of viral and bacterial nucleic acid and characterization of hepatitis genotypes were analyzed using real-time and end-point PCR techniques. RESULTS: The results suggest that HBV infections are most common among the MIC-exposed cohort, followed by extra-pulmonary and pulmonary MTB and HCV infections. Genotype 3 is the most prevalent HCV genotype among the survivors. Failure to detect HBsAg, anti-HBc and anti-HCV through ELISA, and tuberculosis by culture and Ziehl-Neelson stain, indicates higher prevalence of occult hepatitis and latent tuberculosis in the affected population. CONCLUSIONS: Our study underscores the importance of hospital-based records used as a data source for monitoring possible environmental health hazards. As the risk of progress of infection is often influenced by conditions and periods of environmental chemical exposure, therefore, insights of interconnected molecular pathways will further illuminate the gene-environment association and might offer valuable information for rational drug design.


Assuntos
Poluentes Atmosféricos/efeitos adversos , Hepatite B/epidemiologia , Hepatite B/virologia , Hepatite C/epidemiologia , Hepatite C/virologia , Isocianatos/efeitos adversos , Tuberculose/epidemiologia , Tuberculose/virologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Vazamento Acidental em Bhopal , Estudos de Coortes , DNA Bacteriano/genética , DNA Viral/genética , Feminino , Hepacivirus/genética , Hepacivirus/imunologia , Anticorpos Anti-Hepatite B/imunologia , Antígenos de Superfície da Hepatite B/imunologia , Vírus da Hepatite B/genética , Vírus da Hepatite B/imunologia , Anticorpos Anti-Hepatite C/imunologia , Humanos , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Epidemiologia Molecular , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/imunologia , RNA Viral/genética
7.
Indian J Clin Biochem ; 26(2): 161-8, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22468043

RESUMO

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. Although, multi-centric studies including large cohorts are required for translating our findings to clinical practice, however, role of these biomarkers with potential diagnostic or prognostic significance might be helpful in clinical assessment of high-risk individuals, thereby, designing interventional strategies, towards development of personalized medicare. The results of our study also offer valuable insights of immune signaling mediators engaged in development of hepatocellular carcinoma.

8.
Int J Occup Med Environ Health ; 22(3): 193-202, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19819837

RESUMO

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. Survivors continue to experience higher incidence of reported health problems including febrile illnesses, respiratory, neurologic, psychiatric and ophthalmic symptoms. In-utero exposure to methyl isocyanate in the first trimester of pregnancy caused a persistent immune system hyper-responsiveness, which was in an evident way genetically linked with the organic exposure. Recent experimental studies have provided mechanistic understanding of methyl isocyanate exposure at a molecular level. Immunotoxic implications, toxico-genomic effect, inflammatory response, elicitation of mitochondrial oxidative stress, chromosomal and microsatellite instability have been studied comprehensively in cultured mammalian cells. Besides providing a framework for understanding potential mechanisms of toxicity of a host of other exposures, these studies may also uncover unique abnormalities thereby stimulating efforts to design newer and effective diagnostic and therapeutic strategies. The authors recommend long-term monitoring of the affected area and use of appropriate methods of investigation that include well-designed cohort studies, case-control studies for rare condition, characterization of personal exposure and accident analysis to determine the possible elements of the gas cloud.


Assuntos
Poluentes Atmosféricos/toxicidade , Vazamento Acidental em Bhopal , Exposição por Inalação/efeitos adversos , Isocianatos/toxicidade , Anormalidades Induzidas por Medicamentos , Animais , Doença Crônica , Dano ao DNA/efeitos dos fármacos , Oftalmopatias/induzido quimicamente , Feminino , Doenças dos Genitais Femininos/induzido quimicamente , Doenças dos Genitais Masculinos/induzido quimicamente , Humanos , Doenças do Sistema Imunitário/induzido quimicamente , Masculino , Exposição Materna/efeitos adversos , Doenças do Sistema Nervoso/induzido quimicamente , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Doenças Respiratórias/induzido quimicamente
9.
Free Radic Res ; 43(8): 718-28, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19513903

RESUMO

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. Cells treated with 0.005 microM concentration of methyl isocyanate displayed morphological transformation and stress-induced senescence. Along the time course, an increase in DCF fluorescence indicative of oxidative stress, depletion of superoxide dismutase (SOD) and glutathione reductase (GR) and consistent accumulation of 8-oxo-dG were noticed. Thus, endogenous oxidative stress resulted in aberrant expression of p53, p21, cyclin E and CDK2 proteins, suggestive of deregulated cell cycle, chromosomal aberrations, centromeric amplification, aneuploidy and genomic instability.


Assuntos
Instabilidade Cromossômica/efeitos dos fármacos , Cromossomos Humanos/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Isocianatos/farmacologia , Rim/citologia , Mitocôndrias/efeitos dos fármacos , Estresse Oxidativo , 8-Hidroxi-2'-Desoxiguanosina , Antígenos/análise , Ciclo Celular/efeitos dos fármacos , Linhagem Celular/efeitos dos fármacos , Forma Celular/efeitos dos fármacos , Senescência Celular/efeitos dos fármacos , Centrômero/efeitos dos fármacos , Centrômero/ultraestrutura , Aberrações Cromossômicas , Cromossomos Humanos/genética , Desoxiguanosina/análogos & derivados , Desoxiguanosina/análise , Células Epiteliais/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Glutationa Redutase/análise , Humanos , Mitocôndrias/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/análise
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