Comparison of potential adjustment variables representing primary intellectual level in epidemiological studies on neurotoxicity

BACKGROUND: Primary intellectual abilities (PIA) are a confounder in epidemiological studies on neurotoxicity. A good measure of this confounder should be independent of age as PIA is an intrinsic ability. Furthermore, as PIA is related to health endpoints, any measure of PIA should reveal this association. This study is aimed at comparing vocabulary test, diploma and age at end of schooling properties as measures of PIA in a non-exposed population of workers. METHODS: The design was a cross-sectional study of 413 non-exposed workers (203 women and 210 men) selected from a health check-up center. The effect of age on the vocabulary score was assessed using an analysis of covariance adjusted for diploma. Relationships between neuropsychological performances and vocabulary score, diploma and end of schooling age were, respectively, assessed using multiple linear regressions adjusted for age and gender. RESULTS: Vocabulary score increased significantly with age, both for men and women. The increase was 0.14 word per year for women, and 0.18 word per year for men. The explained variance of the models evaluating the relationships between age at end of schooling, diploma, vocabulary test, and neuropsychological performances was quite similar for the three measures of PIA. CONCLUSIONS: Vocabulary score was found to be age-related, even after adjustment for diploma. No difference was found between these three variables in terms of their relationship to neuropsychological endpoints. Moreover, the literature shows that vocabulary test performances are influenced by exposure to neurotoxic agents. These results suggest that vocabulary score could be of interest for participants of similar ages and similar diplomas. Otherwise, the other two variables would be better PIA measures in neurotoxicology studies.

EORTC 26083 phase I/II trial of dasatinib in combination with CCNU in patients with recurrent glioblastoma.

The treatment of patients with recurrent glioblastoma remains a major oncologic problem, with median survival after progression of 7-9 months. To determine the maximum tolerated dose and dose-limiting toxicity (DLT), the combination of dasatinib and cyclonexyl-chloroethyl-nitrosourea (CCNU) was investigated in this setting. The study was designed as multicenter, randomized phase II trial, preceded by a lead-in safety phase. The safety component reported here, which also investigated pharmacokinetics and preliminary clinical activity, required expansion and is therefore considered a phase I part to establish a recommended dosing regimen of the combination of CCNU (90-110 mg/m(2)) and dasatinib (100-200 mg daily). Overall, 28 patients were screened, and 26 patients were enrolled. Five dose levels were explored. DLTs, mainly myelosuppression, occurred in 10 patients. Grade 3 or 4 neutropenia was recorded in 7 patients (26.9%) and thrombocytopenia in 11 patients (42.3%). No significant effect of CCNU coadministration on dasatinib pharmacokinetics was found. Median progression-free survival (PFS) was 1.35 months (95% confidence interval: 1.2-1.4) and 6-month PFS was 7.7%. In this phase I study of recurrent glioblastoma patients, the combination of CCNU and dasatinib showed significant hematological toxicities and led to suboptimal exposure to both agents.

Prévention de l’asthme professionnel : nouvelles perspectives

L’asthme professionnel est une maladie fréquente, qui coûte cher, qui touche des travailleurs jeunes, dont le diagnostic est difficile et avec d’importantes conséquences socio-économiques. La prévention occupe une place centrale dans la gestion de l’asthme professionnel, d’un point de vue de santé publique. Ce mémoire de maîtrise présente trois articles rapportant des développements récents en matière de prévention de l’asthme professionnel. Tout d’abord, une revue de la littérature sur les agents sensibilisants de bas poids moléculaire dans l’asthme professionnel entre 2000 et 2010 recense 41 nouveaux agents et insiste sur l’importance de mettre à jour régulièrement les bases de données afin d’améliorer la prévention primaire. Ensuite, basé sur un cas clinique, la deuxième publication présente l’utilité potentielle du modèle d’analyse de risque QSAR (Quantitative Structure-Activity Relationship) dans le processus diagnostique de l’asthme professionnel, notamment lors d’une exposition multiple à des agents sensibilisants. Enfin, le troisième article présente la performance en milieu clinique du premier questionnaire de dépistage spécifique à l’asthme professionnel. Un modèle simple associant 8 items du questionnaire, l’âge des travailleurs et leur durée d’exposition professionnelle permet de discriminer 80% des 169 sujets adressés pour suspicion d’asthme professionnel. Un tel modèle pourrait être intégré dans les programmes de surveillance médicale qui constituent la base de la prévention secondaire. Ces trois publications insistent sur les possibilités d’explorer de nouveaux outils préventifs dans le domaine de l’asthme professionnel, outils qui ouvrent des perspectives de développements futurs dont les implications cliniques et socio-économiques peuvent être importantes.

Consumption of black tea and coffee and the risk of lung cancer

Objectif: Étudier l’association entre la consommation de café, la consommation de thé noir et le risque de cancer du poumon. Méthodologie: Cette recherche utilise les données obtenues lors d’une étude cas-témoin effectuée à Montréal avec des résidents canadiens âgés entre 35 et 75 ans recrutés entre 1996 et 2001. Les cas étaient des individus atteints du cancer et diagnostiqués entre 1996 et 1997 dans l’un des 18 hôpitaux de la région du Grand-Montréal. Les contrôles on été sélectionnés à partir de la liste électorale et appariés selon la fréquence de distribution des cas par groupe d’âge de 5 ans, par sexe et par district électoral. Au total, 1130 cas et 1484 contrôles ont été inclus dans cette étude. Les rapports de cote (RC) et les intervalles de confiance de 95% (CI) des associations entre la consommation de thé noir, de café et le cancer du poumon ont été estimés à l’aide de la régression logistique non conditionnelle. Quatre aspects de la consommation ont été analysés dans des modèles multivariés distincts: la fréquence de consommation, la consommation journalière moyenne, la durée de consommation et la consommation cumulative. Les covariables potentielles considérées incluaient : l’âge, le sexe, l’historique de tabagisme, le statut du répondant, l’ethnicité, la consommation d’alcool, la consommation de fruit et de légume, l’apport énergétique journalier, l’exposition a des agents professionnelle et les variables socio-économiques . Des analyses secondaires par le sexe, le tabagisme et le type histologique de cancer on été effectuées. Résultats : Aucune association statistiquement significative n’a été observée entre la consommation de thé noir et le cancer du poumon. Nos résultats suggèrent qu’une consommation de ≥ 50 ans était associée avec une augmentation du risque d’adénocarcinome comparée à aucune consommation. Nous avons observé une association inverse statistiquement significative entre la consommation occasionnelle de café et le cancer du poumon (RC : 0.32, 95%CI : 0.17-0.59). La durée de consommation de café n’était pas associée avec le cancer du poumon. Conclusion : Nos résultats suggèrent que la consommation à long terme de thé noir pourrait augmenter le risque d’adénocarcinome. D’un autre côté, la consommation occasionnelle de café pourrait réduire le risque de cancer du poumon.

Determinacion de condiciones laborales de los trabajadores de cuatro hospitales de primer nivel y dos de segundo nivel en el departamento del Quindio – Colombia 2012

Objetivo: Determinar condiciones laborales de los trabajadores de cuatro hospitales de primer nivel y dos de segundo nivel en el departamento del Quindío - Colombia 2012. Metodología: Se realizó un estudio descriptivo de corte transversal con una muestra de 577 trabajadores del sector sanitario de cuatro hospitales de primer nivel y dos de segundo nivel en el departamento de Quindío – Colombia mediante la recolección de datos demográficos y la aplicación de las siguientes encuestas: “Encuesta Nacional de Condiciones de Trabajo” del Instituto Nacional de Seguridad e Higiene en el Trabajo de España (INSHT), en su versión validada para el idioma español: “Irritation Index”. Con fines de analizar la información obtenida se creó una base de datos con base en lo contenido en las encuestas válidas y se realizaron tablas dinámicas en Excel Resultados: participaron 577 trabajadores hospitalarios, encontrándose un 72% de personal femenino y un 28% de personal masculino con una relación H:M 2:6. De la población total encuestada, un 72% corresponde a trabajadores del área asistencial y un 28% al área administrativa. Se encontró una alta percepción de riesgo ergonómico (manejo de cargas, 81%, movimientos repetitivos 91%, posturas forzadas, 49%). Los síntomas osteomusculares referidos fueron: dolor cervical 20%, dolor en región dorsal media 17%, dolor en el hombro 62%, dolor en muñeca 27% y dolor en codo 10%. En la percepción de carga mental y factores de riesgo psicosocial se observó que el 92% de los trabajadores requiere un alto nivel de atención en la ejecución de sus tareas, el 77%, debe atender varias tareas al mismo tiempo, el 52% realiza tarea complejas, el 49% ve necesario esconder sus emociones en el sitio de trabajo, el 13% considera que su trabajo es excesivo, el 43% manifiesta la necesidad de trabajar rápido en el desarrollo de sus funciones, el 69% trabaja con plazos estrictos muy cortos el66% considera que el ritmo de trabajo está determinado por plazos temporales a cumplir. Por otro lado se encuentra una adecuada percepción de la autonomía (93-94%) en la escogencia del método de trabajo, ritmo de trabajo, establecimiento del orden de las tareas a cumplir. En general las relaciones interpersonales son percibidas de manera positiva encontrándose que el 98% recibe ayuda de sus compañeros y el 97% afirma contar con la ayuda de sus superiores. En cuanto a la violencia física en el lugar de trabajo se encuentra que un 6 % ha sido víctima de agresión por parte de personas ajenas al lugar de trabajo. En lo concerniente al percepción de la salud física, el 48% refiere un óptimo estado de salud, mientras que en lo referente a la salud mental se encuentra más frecuentemente alteraciones del sueño (20%), sensación de tensión (20%), tristeza y/o depresión (13%), dificultad para desconectarse del trabajo (15%). Discusión: En la población estudiada se encontró una alta percepción de condiciones ergonómicas inadecuadas dadas por posturas forzadas, manipulación de cargas y movimientos repetitivos, así como exposición a riesgo biológico y factores de riesgo psicosocial. Resulta importante destacar que los hallazgos obtenidos reflejan lo reportado en la literatura internacional y dejan de manifiesto la importancia de reflexionar sobre la necesidad de identificar los riesgos, sensibilizar a la población y de priorizar las actuaciones preventivas.

Trypanosoma cruzi MSH2: Functional analyses on different parasite strains provide evidences for a role on the oxidative stress response

Components of the DNA mismatch repair (MMR) pathway are major players in processes known to generate genetic diversity, such as mutagenesis and DNA recombination. Trypanosoma cruzi, the protozoan parasite that causes Chagas disease has a highly heterogeneous population, composed of a pool of strains with distinct characteristics. Studies with a number of molecular markers identified up to six groups in the T. cruzi population, which showed distinct levels of genetic variability. To investigate the molecular basis for such differences, we analyzed the T. cruzi MSH2 gene, which encodes a key component of MMR, and showed the existence of distinct isoforms of this protein. Here we compared cell survival rates after exposure to genotoxic agents and levels of oxidative stress-induced DNA in different parasite strains. Analyses of msh2 mutants in both T. cruzi and T. brucei were also used to investigate the role of Tcmsh2 in the response to various DNA damaging agents. The results suggest that the distinct MSH2 isoforms have differences in their activity. More importantly, they also indicate that, in addition to its role in MMR, TcMSH2 acts in the parasite response to oxidative stress through a novel mitochondrial function that may be conserved in T. brucei. (C) 2010 Elsevier B.V. All rights reserved.

Genotoxicity of antimicrobial endodontic compounds by single cell gel (comet) assay in Chinese hamster ovary (CHO) cells

Objective. In the current study, the potential DNA damage associated with exposure to a number of antimicrobial endodontic compounds was assessed by the single cell gel (comet) assay in vitro.Study design. Chinese hamster ovary (CHO) cells were exposed to formocresol, paramonochlorophenol, calcium hydroxide, or chlorhexidine at final concentration ranging from 0.01% to 1%.Results. Formocresol, paramonochlorophenol, and calcium hydroxide, as well as chlorhexidine in all concentrations tested did not contribute to the DNA damage.Conclusion. These findings are clinically relevant since they represent an important contribution to the correct evaluation of the potential health risk associated with exposure to dental agents.

COX-2 Inhibitors for Cancer Treatment in Dogs

Cancer is one of the main causes of death in canines and felines, and this fact is probably related to the increase in the longevity of these species. The longer the animals live, the higher the exposure to carcinogenic agents will be. With the high incidence of cancer in companion animals, new studies are currently being performed with the aim of finding therapeutic options which make the complete inhibition of the development of neoplasms in animals possible in the future. The correlation of cyclooxygenase-2 (COX-2) whith the development of cancer opens the way for the use of new therapeutic approaches. This relationship has been suggested based on various studies which established an association between the chronic use of nonsteroidal anti-inflammatory drugs (NSAID) and a decrease in the incidence of colon carcinoma. As cancer progresses, COX-2 participates in the arachidonic acid metabolism by synthesizing prostaglandins which can mediate various mechanisms related to cancer development such as: increase in angiogenesis, inhibition of apoptosis, suppression of the immune response, acquisition of greater invasion capacity and metastasis. Accordingly, overexpression of this enzyme in tumors has been associated with the most aggressive, poor-prognosis cancer types, especially carcinomas. Therefore, treatments which use COX-2 inhibitors such as coxibs, whether administered as single agents or in combination with conventional antineoplastic chemotherapy, are an alternative for extending the survival of our cancer patients.

Análise epidemiológica dos acidentes com material biológico registrados no Centro de Referência em Saúde do Trabalhador - Londrina-PR

OBJETIVO: Analisar a distribuição dos acidentes de trabalho com exposição a material biológico das fichas de notificação registradas no Centro de Referência de Saúde do Trabalhador de Londrina, traçando um perfil dos profissionais acidentados. MÉTODOS: Trata-se de um estudo retrospectivo descritivo, com abordagem quantitativa, realizado através de um levantamento nas 253 fichas de notificação de acidentes com material biológico que foram encaminhadas das instituições de saúde da área de abrangência ao Centro de Referência em Saúde do Trabalhador do município de Londrina-PR, no período de janeiro a dezembro de 2006. Os dados foram processados e tabulados eletronicamente, utilizando-se o programa Epi Info, de domínio público. RESULTADOS: Das 253 fichas de notificação de acidentes com material biológico analisadas, verificou-se que 92,5% foram causados por objetos perfuro-cortantes e 39,5% ocorreram em auxiliares de enfermagem. Constatou-se também que 73,5% eram do sexo feminino, 24,1% ocorreram em Unidades Básicas de Saúde, 74,3% encontravam-se com situação vacinal para Hepatite B atualizada e 49,8% ocorreram na rede pública de saúde. CONCLUSÃO: Com o levantamento do perfil dos profissionais acidentados com exposição a material biológico, o CEREST Londrina identificou que a profissão mais atingida foram os auxiliares de enfermagem, as mulheres, e que grande parte dos acidentes ocorreram nas UBSs com material perfuro-cortante. Mostrou-se que coletores de lixo passaram a fazer parte das profissões envolvidas nos acidentes.

In Vivo Models for Measuring Placental Glutatione-S-transferase (GST-P 7-7) Levels: A Suitable Biomarker for Understanding Cancer Pathogenesis

The Glutatione-S-transferases (GSTs) comprise a family of enzymes closely associated with the cell detoxification of xenobiotics. GSTs exist as homo- or heterodimers and have been grouped into at least seven distinct classes. The main function of GSTs is to catalyze the conjugation of reduced glutathione (GSH) to an electrophilic site of a broad range of potentially toxic and carcinogenic compounds, thereby making such compounds less dangerous and enabling their ready-excretion. Placental GST, known as GST-P 7-7, is the main isoform found in normal placental tissue and comprises 67% of the total GST concentration in this tissue. During development, GST-P 7-7 decreases in concentration and is absent in adult tissues. Interestingly, GST-P 7-7 expression has been detected in adult tissues after exposure to carcinogenic agents in several experimental test systems, being considered a reliable biomarker of exposure and susceptibility in early phases of carcinogenesis. In this article, we review a series of studies involving GST-P 7-7 expression as a suitable tool for understanding cancer pathogenesis, especially cancer risk.

Antiestrogen therapies affect tissue homeostasis of the gerbil (Meriones unguiculatus) female prostate and ovaries

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Fluoride does not induce DNA breakage in Chinese hamster ovary cells in vitro.

Fluoride has been widely used in dentistry because it is a specific and effective caries prophylactic agent. However, excess fluoride may represent a hazard to human health, especially by causing injury to genetic material. Genotoxicity tests represent an important part of cancer research to assess the risk of potential carcinogens. In the current study, the potential DNA damage associated with exposure to fluoride was assessed by the single cell gel (comet) assay in vitro. Chinese hamster ovary cells were exposed to sodium fluoride (NaF) at final concentration ranging from 7 to 100 micro/ml for 3 h, at 37 dgrees C. The results pointed out that NaF in all concentrations tested did not contribute to DNA damage as depicted by the mean tail moment and tail intensity. These findings are clinically important since they represent an important contribution to a correct evaluation of the potential health risk associated with the exposure to dental agents.

Birth defects in newborns and stillborns: An example of the Brazilian reality

Background: This study constitutes a clinical and genetic study of all newborn and stillborn infants with birth defects seen in a period of one year in a medical school hospital located in Brazil. The aims of this study were to estimate the incidence, causes and consequences of the defects. Methods. For all infants we carried out physical assessment, photographic records, analysis of medical records and collection of additional information with the family, besides the karyotypic analysis or molecular tests in indicated cases. Result: The incidence of birth defects was 2.8%. Among them, the etiology was identified in 73.6% (ci95%: 64.4-81.6%). Etiology involving the participation of genetic factors single or associated with environmental factors) was more frequent 94.5%, ci95%: 88.5-98.0%) than those caused exclusively by environmental factors (alcohol in and gestational diabetes mellitus). The conclusive or presumed diagnosis was possible in 85% of the cases. Among them, the isolated congenital heart disease (9.5%) and Down syndrome (9.5%) were the most common, followed by gastroschisis (8.4%), neural tube defects (7.4%) and clubfoot (5.3%). Maternal age, parental consanguinity, exposure to teratogenic agents and family susceptibility were some of the identified risk factors. The most common observed consequences were prolonged hospital stays and death. Conclusions: The current incidence of birth defects among newborns and stillbirths of in our population is similar to those obtained by other studies performed in Brazil and in other underdeveloped countries. Birth defects are one of the major causes leading to lost years of potential life. The study of birth defects in underdeveloped countries should continue. The identification of incidence, risk factors and consequences are essential for planning preventive measures and effective treatments. © 2011 Fett-Conte et al; licensee BioMed Central Ltd.

Análise da freqüência de micronúcleos frente à utilização de colutórios bucais

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Citotoxicidade, produção de espécies reativas de oxigênio, expressão de marcadores celulares e produção de TNFα em macrófagos após exposição a agentes clareadores

Pós-graduação em Odontologia Restauradora - ICT