Polymorphisms of DNA repair genes XRCC1 and XRCC3, interaction with environmental exposure and risk of chronic gastritis and gastric cancer

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Polymorphisms of DNA repair genes XRCC1 and XRCC3, interaction with environmental exposure and risk of chronic gastritis and grastic cancer

Aim: To evaluate the association between polymorphisms XRCC1 Arg194Trp and Arg399Gln and XRCC3 Thr241Met and the risk for chronic gastritis and gastric cancer, in a Southeastern Brazilian population. Methods: Genotyping by PCR-RFLP was carried out on 202 patients with chronic gastritis (CG) and 160 patients with gastric cancer (GC), matched to 202 (C1) and 150 (C2) controls, respectively. Results: No differences were observed among the studied groups with regard to the genotype distribution of XRCC1 codons 194 and 399 and of XRCC3 codon 241. However, the combined analyses of the three variant alleles (194Trp, 399Gln and 241Met) showed an increased risk for chronic gastritis when compared to the GC group. Moreover, an interaction between the polymorphic alleles and demographic and environmental factors was observed in the CG and GC groups. XRCC1 194Trp was associated with smoking in the CG group, while the variant alleles XRCC1 399Gln and XRCC3 241Met were related with gender, smoking, drinking and H pylori infection in the CG and GC groups. Conclusion: Our results showed no evidence of a rela-tionship between the polymorphisms XRCC1 Arg194Trp and Arg399Gln and XRCC3 Thr241Met and the risk of chronic gastritis and gastric cancer in the Brazilian population, but the combined effect of these variants may interact to increase the risk for chronic gastritis, considered a premalignant lesion. Our data also indicate a gene-environment interaction in the susceptibility to chronic gastritis and gastric cancer. © 2005 The WJG Press and Elsevier Inc. All rights reserved.

Organotins: A review of their reproductive toxicity, biochemistry, and environmental fate

The review purposes are to (1) evaluate the experimental evidence for adverse effects on reproduction and metabolism and (2) identify the current knowledge of analytical procedures, biochemistry and environmental aspects relating to organotins. Organotins are pollutants that are used as biocides in antifouling paints. They produce endocrine-disrupting effects in mollusks, such as imposex. In rodents, organotin exposure induces developmental and reproductive toxicity as well as alteration of metabolic homeostasis through its action as an obesogen. The adverse effects that appear in rodents have raised concerns about organotins' potential health risk to humans in relation to organotin exposure. At present, triorganotin, such as tributyltin, have been demonstrated to produce imposex, and mammalian reproductive and metabolic toxicity. For most mammals, triorganotin exposure predominantly occurs through the ingestion, and this compound can cross the placenta. With these risks in mind, it is important to improve our knowledge of organotins' effects on environmental health. © 2012 Elsevier Inc.

Morphologic and biomechanical changes of thoracic and abdominal aorta in a rat model of cigarette smoke exposure

Background: Smoking is the most relevant environmental factor that affects the development of aortic aneurysm. Smokers have elevated levels of elastase activity in the arterial wall, which leads to weakening of the aorta. The aim of this study was to verify whether cigarette smoke exposure itself is capable of altering the aortic wall. Methods: Forty-eight Wistar rats were divided into 2-, 4-, and 6-month experimental periods and into 2 groups: smokers (submitted to smoke exposure at a rate of 40 cigarettes/day) and nonsmokers. At the end of the experimental periods, the aortas were removed and cross-sectioned to obtain histologic specimens for light microscopic and morphometric analyses. The remaining longitudinal segments were stretched to rupture and mechanical parameters were determined. Results: A degenerative process (i.e., a reduction in elastic fibers, the loss of lamellar arrangement, and a reduction of smooth muscle cells) was observed, and this effect was proportional in intensity to the period of tobacco exposure. We observed a progressive reduction in the yield point of the thoracic aorta over time (P < 0.05). There was a decrease in stiffness (P < 0.05) and in failure load (P < 0.05) at 6 months in the abdominal aorta of rats in the smoking group. Conclusions: Chronic exposure to tobacco smoke can affect the mechanical properties of the aorta and can also provoke substantial structural changes of the arterial wall. © 2013 Elsevier Inc. All rights reserved.

Fish exposure to nano-TiO2 under different experimental conditions: Methodological aspects for nanoecotoxicology investigations

The ecotoxicology of nano-TiO2 has been extensively studied in recent years; however, few toxicological investigations have considered the photocatalytic properties of the substance, which can increase its toxicity to aquatic biota. The aim of this work was to evaluate the effects on fish exposed to different nano-TiO2 concentrations and illumination conditions. The interaction of these variables was investigated by observing the survival of the organisms, together with biomarkers of biochemical and genetic alterations. Fish (Piaractus mesopotamicus) were exposed for 96h to 0, 1, 10, and 100mg/L of nano-TiO2, under visible light, and visible light with ultraviolet (UV) light (22.47J/cm2/h). The following biomarkers of oxidative stress were monitored in the liver: concentrations of lipid hydroperoxide and carbonylated protein, and specific activities of superoxide dismutase, catalase, and glutathione S-transferase. Other biomarkers of physiological function were also studied: the specific activities of acid phosphatase and Na,K-ATPase were analyzed in the liver and brain, respectively, and the concentration of metallothionein was measured in the gills. In addition, micronucleus and comet assays were performed with blood as genotoxic biomarkers. Nano-TiO2 caused no mortality under any of the conditions tested, but induced sublethal effects that were influenced by illumination condition. Under both illumination conditions tested, exposure to 100mg/L showed an inhibition of acid phosphatase activity. Under visible light, there was an increase in metallothionein level in fish exposed to 1mg/L of nano-TiO2. Under UV light, protein carbonylation was reduced in groups exposed to 1 and 10mg/L, while nucleus alterations in erythrocytes were higher in fish exposed to 10mg/L. As well as improving the understanding of nano-TiO2 toxicity, the findings demonstrated the importance of considering the experimental conditions in nanoecotoxicological tests. This work provides information for the development of protocols to study substances whose toxicity is affected by illumination conditions. © 2013 Elsevier B.V..

Identificação de enfermidades agudas causadas por animais e plantas em ambientes rurais e litorâneos: auxílio à prática dermatológica

FUNDAMENTOS: Nos últimos anos, existe um aumento progressivo do contato de moradores urbanos com ambientes selvagens devido a atividades de lazer. Com isso, algumas dermatites pouco conhecidas podem ser observadas nas clínicas privadas e ambulatórios dermatológicos, especialmente nos inícios de semana e finais de férias. OBJETIVOS: Obter e fornecer informações para dermatologistas sobre o problema. PACIENTES E MÉTODOS: O autor observou, em adultos e crianças, dermatites agudas associadas a plantas ou animais em Ubatuba, cidade litorânea de São Paulo, por dois meses (junho/julho de 2006) e na Faculdade de Medicina de Botucatu, também por dois meses (junho/julho de 2007). RESULTADOS: Foram observados 25 pacientes na área rural e 43 na área litorânea nas condições estabelecidas. em áreas rurais, foram mais observadas fitofotodermatites e picadas de insetos, enquanto em áreas litorâneas traumas por ouriços-do-mar e fitofotodermatites predominaram; entretanto, em ambas as áreas ocorreram outros acidentes de difícil identificação na prática diária. CONCLUSÕES: Devemos estar atentos ao fato de o paciente procurar o dermatologista somente após as fases agudas dos acidentes. Informações sobre as enfermidades mais comuns e suas características podem ser muito úteis para a prática nos consultórios. O autor sugere uma tabela algorítmica para auxílio diagnóstico.

Levels of toxic and essential metals in maternal and umbilical cord blood from selected areas of South Africa-results of a pilot study

This pilot study uses concentrations of metals in maternal and cord blood at delivery, in seven selected geographical areas of South Africa, to determine prenatal environmental exposure to toxic metals. Samples of maternal and cord whole blood were analysed for levels of cadmium, mercury, lead, manganese, cobalt, copper, zinc, arsenic and selenium. Levels of some measured metals differed by site, indicating different environmental pollution levels in the regions selected for the study. Mercury levels were elevated in two coastal populations studied (Atlantic and Indian Ocean sites) with mothers from the Atlantic site having the highest median concentration of 1.78 mu g/L ranging from 0.44 to 8.82 mu g/L, which was found to be highly significant (p < 0.001) when compared to other sites, except the Indian Ocean site. The highest concentration of cadmium was measured in maternal blood from the Atlantic site with a median value of 0.25 mu g/L (range 0.05-0.89 mu g/L), and statistical significance of p < 0.032, when compared to all other sites studied, and p < 0.001 and p < 0.004 when compared to rural and industrial sites respectively, confounding factor for elevated cadmium levels was found to be cigarette smoking. Levels of lead were highest in the urban site, with a median value of 32.9 mu g/L (range 16-81.5 mu g/L), and statistically significant when compared with other sites (p < 0.003). Levels of selenium were highest in the Atlantic site reaching statistical significance (p < 0.001). All analysed metals were detected in umbilical cord blood samples and differed between sites, with mercury being highest in the Atlantic site (p < 0.001), lead being highest in the urban site (p < 0.004) and selenium in the Atlantic site (p < 0.001). To the best of our knowledge this pilot investigation is the first study performed in South Africa that measured multiple metals in delivering mothers and umbilical cord blood samples. These results will inform the selection of the geographical sites requiring further investigation in the main study.

Seroprevalence of Toxoplasma gondii infection in cats from Curitiba, Paraná, Brazil

A toxoplasmose é uma zoonose de distribuição mundial, causada pelo protozoário Toxoplasma gondii que infecta os vertebrados de sangue quente. Este estudo objetiva estabelecer a prevalência de anticorpos anti-Toxoplasma gondii e o estudo de associação em uma população de gatos domésticos atendidos em uma clínica veterinária exclusiva de gatos localizada em Curitiba, estado do Paraná, Brasil. As amostras de soro foram obtidas e processadas pela reação de imunofluorescência indireta IgG. Títulos de anticorpos foram encontrados em 46/282 (16,3%) das amostras analisadas, com título de 16 em oito gatos, 64 em 23, 256 em 14 e 1024 em um gato. Diferenças estatísticas não foram encontradas no estudo de associação entre idade, gênero e região da cidade (p > 0,05). Nenhuma diferença significativa foi encontrada para qualquer variável, quando comparando a soropositividade com a ocorrência do possível fator de risco. A soroprevalência foi relativamente menor quando comparada a outras regiões brasileiras, provavelmente por serem gatos de proprietários, que tinham hábito domiciliado e alimentação restrita baseada em alimentos industrializados, com acesso restrito a rua e sem acesso a caça. em conclusão, a baixa soroprevalência de toxoplasmose felina pode estar relacionada a gatos com proprietários devido aos cuidados alimentares e acesso restrito à rua, e também pode estar associada à baixa exposição ambiental local

Fetotoxicity caused by the interaction between zinc and arsenic in mice

Arsenic is an environmental pollutant that induces congenital malformations in experimental models and can contribute to human birth defects. The environmental exposure to arsenic is relatively small when compared with the doses required to cause teratogenicity in mice and other laboratory animals. In order to study the action of zinc in the arsenic-induced teratogenicity, in the present work mice were either pretreated with zinc and later with arsenic or were treated simultaneously with zinc and arsenic in vivo and in vitro. Following administration of arsenate on gestation day 8, pregnant females were killed on the 17th day of gestation; maternal and fetal data were collected by laparotomy and used to calculate reproductive parameters. Fetuses were analyzed for the presence of external malformation and, after the appropriate processing, visceral and skeletal analyses were accomplished. Conceptuses were exposed in whole embryo culture to arsenicals on gestation day 8 (3-6 somite stage). After a 26 h culture period, morphological development was assessed. Neither pretreatment with zinc nor simultaneous administration of zinc prevented arsenic teratogenicity in these experimental models. (C) 2002 Wiley-Liss, Inc.

Reajustando o limite de tolerância biológica aplicado à plumbemia no Brasil

Foram alocados aleatoriamente vinte trabalhadores expostos ocupacionalmente ao chumbo em uma indústria de acumuladores elétricos de médio porte, no interior do Estado de São Paulo, os quais apresentavam plumbemia e excreção urinária do ácido delta-aminolevulínico, nos últimos dois anos, sempre menores que 60 µg/dL e 10 mg/L, respectivamente. Os trabalhadores foram submetidos a eletroneurografia do nervo radial direito e a dosagem de plumbemia. Com estas medidas ajustou-se um modelo de regressão linear simples de primeira ordem, tendo como variável dependente a velocidade de condução e como variável independente a plumbemia. Analisando-se a regressão ajustada, infere-se que o valor preditivo negativo do limite de tolerância biológica brasileiro aplicado à plumbemia seja de apenas 0,63. O estudo sugere que o valor do referido limite de tolerância deva ser reduzido do atual valor de 60 µg/dL para 32 µg/dL, para ter um valor preditivo negativo de 0,99.

Genetic polymorphism and their contribution to cancer susceptibility

Uma vez que a maioria dos carcinogênicos químicos não é capaz de causar efeitos danosos per se, o metabolismo desses compostos é a parte crucial da resposta inicial à exposição ambiental. Os distúrbios causados no balanço entre os processos de ativação e destoxificação podem, assim, explicar as variações individuais em resposta à exposição aos carcinogênicos. A quantidade de compostos carcinogênicos finais produzida depende da ação competitiva entre os passos de ativação e destoxificação, envolvendo as enzimas do citocromo P450 e das S-glutatião transferases.

Pyrethroid residues in milk and blood of dairy cows following single topical applications

The presence of the pyrethroid insecticides flumethrin, deltamethrin, cypermethrin and cyhalothrin in milk and blood of 10 cows was determined after single dermal applications of recommended doses. Milk and blood samples were collected every 7 days over a 35 d period and analyzed by high performance liquid chromatography. The highest residues in milk were found on day 28 for flumethrin and day 1 for deltamethrin, cypermethrin and cyhalothrin, while in blood the highest concentrations were present on day 28 for flumethrin and deltamethrin, the first day for cypermethrin, and day 14 for cyhalothrin.

Kras oncogene analysis of non-melanoma skin tumors in Southeastern Brazil

Skin cancers are the most common human malignant neoplasia and their incidence is growing, chiefly in tropical countries. There is evidence that ultraviolet (UV) radiation present in sunlight is important for genetic damage. Mutations due to such damage could be responsible for alterations in oncogenes and tumor suppressor genes. Recent studies have reported remarkable differences in mutation frequency of the RAS proto-oncogene in non-melanoma skin cancers. These findings may reflect differences in the molecular epidemiology of cutaneous tumors found in geographical areas with diverse sun exposure and ethnical origins of their populations. Our study proposed to perform molecular analyses of skin tumors on patients living in southeastern Brazil, in areas with high levels of sun exposure. DNA from eight solar keratose (SK), 26 basal cell carcinomas (BCC) and 19 squamous cell carcinomas (SCC) was submitted to PCR-SSCP analysis for codons 12, 13 and 61. Contradicting other authors, we found no mutations in codons 12,13 but detected two BCCs and one SCC with a mutation in codon 61. These findings suggest that the activation of KRAS oncogene may contribute to the pathogenicity of cutaneous lesions in southeastern Brazil.

Psicoterapia grupal no transtorno obsessivo-compulsivo

There are few published papers about group psychotherapy for patients with obsessive-compulsive disorder (OCD), and usually restricted psychoeducational, support or cognitive-behavioral approaches. This article describes the experience of group psychotherapy for OCD patients started in 1996 in Botucatu Medical School - Unesp, São Paulo, Brazil. The two-hour sessions occur once a month, with 6 to 10 female patients, and are based on psychodramatic techniques. Psychotropic prescriptions are given after the sessions. In the beginning, aggressive obsessions were more prominent and were reported with much anguish and shame. Gradually, the themes changed from OCD specific issues (symptoms, pharmacological treatment, outcome, need of exposure and response prevention) to deeper and more personal psychodynamic aspects. The psychodramatic approach (techniques of double, mirror, role inversion, search for prymary scenes) has mostly shown: difficulty in accepting their own human mistakes or negative emotions due to excessive personal demands. This seems to generate guilt, low self-esteem, idealization of others, difficulty in enjoying pleasant situations, fear of taking responsibilities and of losing control (madness/aggressiveness). The group has been considered very important by the patients, since sharing experiences helps to diminish feelings of isolation, shame and guilt, stimulates the exposure to feared situations and enhances self-esteem. The fact that all participants have the same disorder favors group cohesion and provides relief, as they see in the others some of their afflictions and are able to share similar feelings and experiences. Many times the burden of the symptoms are dealt with humor. The confidence in such therapeutic setting is helping the identification and resolution of personal conflicts and contributing to the adherence to pharmacological treatment. The group also provides valuable training experiences for resident physicians in psychiatry.