Rol del consumo de alcohol y antioxidantes sobre la metilación global del ADN y cáncer / Role of alcohol consumption and antioxidants on global methylation of DNA and cancer

RESUMEN: El alcoholismo es una enfermedad crónica recidivante asociada a disfunción psicológica, social y física. El alcohol no sólo es una droga adictiva, también produce alteraciones en las actividades y funciones de múltiples sistemas y órganos. Actualmente, diversos estudios demuestran que el ambiente puede modular la expresión génica del ADN mediante mecanismos epigenéticos, sugiriendo de esta manera, que el consumo de alcohol es un factor que puede alterar los patrones epigenéticos y, por lo tanto, los niveles de expresión génica. La metilación del ADN es un proceso epigenético que participa en la regulación de la expresión génica, impidiendo la unión de factores de transcripción y propiciando la estructura cerrada de la cromatina. En este sentido, los cambios en la metilación del ADN se reconocen como una de las formas más comunes de alteración molecular en la dependencia al alcohol y los procesos neoplásicos humanos. El alcohol puede ser un factor importante en la iniciación del cáncer, aumentando la expresión de ciertos oncogenes o reprimiendo la capacidad de las células para reparar el ADN, lo que aumenta la probabilidad de que se produzcan mutaciones oncogénicas. Sin embargo, los mecanismos exactos de la patogénesis del cáncer ligada al consumo de alcohol aún permanecen sin ser dilucidados. Por lo anterior, el objetivo de la presente revisión fue describir los mecanismos de metilación del ADN y su relación con el consumo de alcohol y cáncer.

SUMMARY: Alcoholism is a chronic relapsing disease associated with psychological, social and physical dysfunction. Alcohol is not only an addictive substance, it also alters action and function of multiple systems and organs. Currently, several studies show that the environment can modulate gene expression of DNA by epigenetic mechanisms, thereby suggesting that alcohol consumption is a factor that can alter epigenetic patterns and therefore, the levels of gene expression. DNA methylation is an epigenetic process, that is a part of gene expression regulation preventing binding of transcription factors and encouraging the closed structure of chromatin. In this sense, changes in DNA methylation are recognized as one of the most common forms of molecular alteration in alcohol dependence and human neoplastic processes. Alcohol can be an important factor in activating the cancer by increasing the expression of certain oncogenes or repressing the ability of cells to repair DNA, which increases the likelihood of oncogenic mutations. However, the exact mechanisms of the pathogenesis of cancer linked to alcohol consumption remain unclear. Therefore, the objective of this review was to describe the mechanisms of DNA methylation and its relation to alcohol consumption and cancer.

Contaminación, disruptores endocrinos y cáncer / Contamination, endocrine disruptors and cancer

Desde mediados del siglo XX numerosas especies, muy diferentes entre sí y ubicadas en todas las áreas y rincones del planeta, comenzaron a presentar diversas alteraciones, muchas de las cuales sugerían estar relacionadas con trastornos del sistema endocrino. Las investigaciones demostraron que tales alteraciones eran producidas por la exposición a diferentes sustancias químicas contaminantes, las cuales podían alterar la salud y producir graves enfermedades. Dentro de ellas destacó un grupo heterogéneo de compuestos con estructuras químicas muy diferentes, capaces de actuar a dosis muy bajas, mostrar distintos mecanismos de acción y ser capaces de alterar el equilibrio hormonal, por lo que se les denominó “disruptores endocrinos químicos”. Estas sustancias, al ser liberadas al medioambiente o formar parte de objetos, alimentos o medicinas, constituyen un gran riesgo para los seres humanos y toda la vida del planeta, produciendo no solo disfunciones endocrinas sino también diferentes tipos de cáncer, destacando los más frecuentes. A pesar de la trascendencia y significado del impacto de estos compuestos, ellos no son suficientemente conocidos ni entendidos, por lo que el objetivo de esta revisión es mostrar su origen e impacto en la salud humana, resaltando su papel como inductores de cáncer, lo cual ha motivado múltiples investigaciones clínicas y biológicas.

Since the mid-twentieth century, many species, very different from each other and located in all areas and corners of the planet, began presenting various alterations, many of which suggested to be related to endocrine disorders. Research has shown that such alterations were caused by exposure to various chemical contaminants that could affect the health and cause serious illnesses. Among them stands a diverse and large group of compounds, with very different chemical structures, capable of altering the hormonal balance, act at very low doses and with different mechanisms of action, that are called “endocrine disrupting chemicals”. When released into the environment or as part of objects, food or medicines, constitute a major risk to animals and humans, which produces not only endocrine dysfunctions but also different cancers, which include the most common types. Despite the importance and significance of the impact of these compounds, they are not sufficiently known or understood, so the aim of this review is to show their origin and impact in the field of human health, highlighting their role as inducers of cancer, which has led to multiple clinical and biological investigations.

DNA methylation patterns of candidate genes regulated by thymine DNA glycosylase in patients with TP53 germline mutations

Li-Fraumeni syndrome (LFS) is a rare, autosomal dominant, hereditary cancer predisposition disorder. In Brazil, the p.R337H TP53 founder mutation causes the variant form of LFS, Li-Fraumeni-like syndrome. The occurrence of cancer and age of disease onset are known to vary, even in patients carrying the same mutation, and several mechanisms such as genetic and epigenetic alterations may be involved in this variability. However, the extent of involvement of such events has not been clarified. It is well established that p53 regulates several pathways, including the thymine DNA glycosylase (TDG) pathway, which regulates the DNA methylation of several genes. This study aimed to identify the DNA methylation pattern of genes potentially related to the TDG pathway (CDKN2A, FOXA1, HOXD8, OCT4, SOX2, and SOX17) in 30 patients with germline TP53 mutations, 10 patients with wild-type TP53, and 10 healthy individuals. We also evaluated TDG expression in patients with adrenocortical tumors (ADR) with and without the p.R337H TP53 mutation. Gene methylation patterns of peripheral blood DNA samples assessed by pyrosequencing revealed no significant differences between the three groups. However, increased TDG expression was observed by quantitative reverse transcription PCR in p.R337H carriers with ADR. Considering the rarity of this phenotype and the relevance of these findings, further studies using a larger sample set are necessary to confirm our results.

Estimativa da carga do tabagismo no Brasil: mortalidade, morbidade e custos / Estimación de la carga de enfermedad atribuible al tabaquismo en Brasil: mortalidad, morbilidad y costos / The burden of smoking-related diseases in Brazil: mortality, morbidity and costs

Os avanços no controle do tabagismo no Brasil podem ser verificados na redução da prevalência nas últimas duas décadas. As estatísticas de óbitos, ocorrência de eventos e custos diretos atribuíveis às doenças tabaco-relacionadas não são estimadas com frequência no país. O objetivo deste artigo foi estimar a carga do tabagismo em 2011, em termos de mortalidade, morbidade e custos da assistência médica das principais doenças tabaco-relacionadas. Desenvolveu-se um modelo econômico baseado em uma microssimulação probabilística de milhares de indivíduos através de coortes hipotéticas que considerou a história natural, os custos diretos em saúde e a qualidade de vida desses indivíduos. O tabagismo foi responsável por 147.072 óbitos, 2,69 milhões anos de vida perdidos, 157.126 infartos agudos do miocárdio, 75.663 acidentes vasculares cerebrais e 63.753 diagnósticos de câncer. O custo para o sistema de saúde foi de R$ 23,37 bilhões. O monitoramento da carga do tabagismo é uma importante estratégica para informar aos tomadores de decisão e fortalecer a política pública de saúde.

Los avances en el control del tabaquismo en Brasil pueden reflejarse en la reducción de la prevalencia observada en las últimas dos décadas. Las estadísticas de muertes, incidencia de eventos y costos directos atribuibles a las enfermedades, relacionadas con el tabaquismo, no han sido estimadas frecuentemente en el país. El objetivo de este estudio fue estimar la carga del tabaquismo en el año 2011, en términos de mortalidad, morbilidad y costos de asistencia médica para las patologías relacionadas con el tabaquismo. Se construyó un modelo de microsimulación probabilístico que incorpora la historia natural, los costos y la calidad de vida de los individuos. En 2011, el tabaquismo fue responsable de 147.072 muertes prematuras, 2,69 millones de años de vida perdidos, 157.126 infartos de miocardio, 75.663 accidentes cerebro-vasculares y 63.753 diagnósticos de cáncer. El costo directo fue de R$ 23,37 mil millones. El monitoreo de la carga de enfermedad atribuible al tabaquismo es una importante estrategia para informar a los responsables de las políticas públicas de salud.

Advances in tobacco control in Brazil can be reflected in the decrease in prevalence over the past two decades. Death statistics and the occurrence of events and direct costs attributable to tobacco-related diseases have not been frequently estimated in the country. The goal of this article is to estimate the burden of smoking in 2011 regarding mortality, morbidity and medical care costs of the main tobacco-related diseases. A probabilistic microsimulation health economic model was built. The model incorporates the natural history, costs and quality of life of all the tobacco-related adult-specific diseases. Smoking was accountable for 147,072 deaths, 2.69 million years of life lost, 157,126 acute myocardial infarctions, 75,663 strokes, and 63,753 cancer diagnoses. The direct cost for the health system was of BRL 23.37 billion. The monitoring of tobacco-related burden is an important strategy to guide decision-makers and to strenghten health public policies.

Heart transplantation: review / Transplante cardíaco: revisão

ABSTRACT Heart transplantation is currently the definitive gold standard surgical approach in the treatment of refractory heart failure. However, the shortage of donors limits the achievement of a greater number of heart transplants, in which the use of mechanical circulatory support devices is increasing. With well-established indications and contraindications, as well as diagnosis and treatment of rejection through defined protocols of immunosuppression, the outcomes of heart transplantation are very favorable. Among early complications that can impact survival are primary graft failure, right ventricular dysfunction, rejection, and infections, whereas late complications include cardiac allograft vasculopathy and neoplasms. Despite the difficulties for heart transplantation, in particular, the shortage of donors and high mortality while on the waiting list, in Brazil, there is a great potential for both increasing effective donors and using circulatory assist devices, which can positively impact the number and outcomes of heart transplants.

RESUMO O transplante cardíaco é atualmente a abordagem cirúrgica definitiva padrão-ouro no tratamento da insuficiência cardíaca refratária. No entanto, a escassez de doadores limita a realização de um número maior de transplantes cardíacos, situação em que vem aumentando a utilização de dispositivos de assistência circulatória mecânica. Com indicações e contraindicações bem estabelecidas, além de diagnóstico e tratamento de rejeição, por meio de protocolos definidos de imunossupressão, os resultados do transplante cardíaco são muito favoráveis. Dentre as complicações precoces que podem impactar a sobrevida, destacamos a disfunção primária do enxerto, a disfunção do ventrículo direito, rejeição e infecções; já as complicações tardias incluem a doença vascular do enxerto e as neoplasias. Apesar das dificuldades para realização do transplante cardíaco, em especial pela escassez de doadores e pela elevada mortalidade em fila de espera, no Brasil, existe um grande potencial, tanto no aumento de doadores efetivos, quanto na utilização de dispositivos de assistência circulatória, o que pode vir a impactar positivamente no número e nos resultados do transplante cardíaco.

Prevalence of Cigarette Smoking among Adult Cancer Survivors in Korea

PURPOSE: Cigarette smoking is associated not only with increased risk of cancer incidence, but also influences prognosis, and the quality of life of the cancer survivors. Thus, smoking cessation after cancer diagnosis is necessary. However, smoking behavior among Korean cancer-survivors is yet unknown. MATERIALS AND METHODS: We investigated the smoking status of 23770 adults, aged 18 years or older, who participated in the Health Interview Survey of the Korea National Health and Nutrition Examination Survey from 2007 to 2010. Data on the cancer diagnosis and smoking history were obtained from an interview conducted by trained personals. "Cancer-survivor" was defined as anyone who has been diagnosed with cancer by a physician regardless of time duration since diagnosis. Smoking status was classified into "never-smoker", "former-smoker", and "current-smoker". Former-smoker was further divided into "cessation before diagnosis" and "cessation after diagnosis". RESULTS: Overall, 2.1% of Korean adults were cancer-survivors. The smoking rate of Korean cancer-survivors was lower than that of non-cancer controls (7.8+/-1.3% vs. 26.4+/-0.4%, p<0.001). However, 53.4% of the cancer-survivors continued to smoke after their cancer diagnosis. In multivariate analysis, male gender [odds ratio (OR), 6.34; 95% confidence interval (CI), 2.62-15.31], middle-aged group (OR, 2.74; 95% CI, 1.12-6.72), the lowest income (OR, 4.10; 95% CI, 1.19-14.15), living with smoking family member(s) (OR, 5.49; 95% CI, 2.42-12.48), and the poor self-perceived health status (OR, 2.78; 95% CI, 1.01-7.71) were independently associated with persistent smoking among Korean cancer-survivors. CONCLUSION: The smoking rate among Korean cancer survivors is low. However, the smoking cessation rate after the cancer diagnosis is also low. This mandates comprehensive and systematic intervention for smoking cessation among cancer-survivors.

Carga de enfermedad atribuible al tabaquismo en Chile / Disease burden attributable to smoking in Chile

Objetivo: El objetivo inicial del proyecto, comenzado en el año 2005, fue seleccionar y desarrollar el marco metodológico más adecuado, así como elaborar un modelo económico común, con el fin de estimar la carga de enfermedad relacionada con el tabaquismo y la costo-efectividad de las intervenciones para controlar la epidemia del tabaco en América Latina.En este reporte se presentan los detalles del modelo económico, el proceso de calibración y validación para adecuarlo a la realidad de Chile y los resultados de carga de enfermedad atribuible al tabaquismo, medida tanto en términos de salud como económicos. Materiales e Métodos: Se describen a continuación los siguientes puntos relacionados con el desarrollo y utilización del modelo económico: 1) Etapa inicial de diagnóstico de situación, 2) Descripción del modelo, 3) Metodología utilizada para la selección de fuentes de información e incorporación de parámetros, 4) Proceso de calibración y validación, 5) Estimación de carga de enfermedad, 6) Aspectos metodológicos de los datos epidemiológicos considerados, y 7) Características de la información de costos de atención médica requerida para el modelo. Conclusión: En Chile el tabaquismo es responsable de una importante cantidad de muertes prematuras, enfermedad y costos sanitarios. El mayor peso está dado por las enfermedades cardiovasculares, la enfermedad pulmonar obstructiva crónica y el cáncer de pulmón. Su impacto en la mortalidad y en la calidad de vida es responsable en forma directa de la pérdida de 428.588 años de vida (por muerte prematura y discapacidad) cada año y explica el 18,5% de todas las muertes que se producen en el país. El tabaquismo genera además un costo directo anual de más de 1 billón de pesos chilenos. Es esperable que los resultados de este estudio contribuyan a tomar conciencia sobre los efectos del tabaco y sean un soporte para que los responsables de las políticas puedan llevar adelante intervenciones para reducir su consumo, lograr la implementación de mayores impuestos al tabaco e instalar las políticas de control promovidas por el Convenio Marco de la Organización Mundial de la Salud para el Control del Tabaco (CMCT-OMS).

The Scope and Specific Criteria of Compensation for Occupational Diseases in Korea

The range of diseases covered by workers' compensation is constantly expanding. However, new regulations are required for the recognition of occupational diseases (ODs) because OD types evolve with changes in industrial structures and working conditions. OD criteria are usually based on medical relevance, but they vary depending on the social security system and laws of each country. In addition, the proposed range and extent of work-relatedness vary depending on the socio-economic conditions of each country. The Labor Standards Act (LSA) and the Industrial Accident Compensation Insurance Act (IACIA) of Korea employ lists based on their requirements without listing causes and diseases separately. Despite a considerable reshuffle in 2003, the basic framework has been maintained for 50 yr, and many cases do not fit into the international disease classification system. Since July 1, 2013, Korea has expanded the range of occupational accidents to include occupational cancers and has implemented revised LSA and IACIA enforcement decrees. There have been improvements to OD recognition standards with the inclusion of additional or modified criteria, a revised and improved classification scheme for risk factors and ODs, and so on.

Compensation for Occupational Cancer

The legal scope and criteria for occupational cancer in Korea was out of date. The aim of this study was to review the current criteria for occupational cancer and amend the existent criteria on the basis of recent scientific evidence. The scientific evidence and the legal list of occupational cancer were analyzed to identify the causes of occupational cancer on a global scale. The relationship between compensated occupational cancer cases and carcinogen exposure in Korea was examined. The factors associated with specific causes and target cancers were determined to produce additional criteria. Five-hundred and nineteen cases of 2,468 were awarded compensation for occupational cancer including lung, malignant mesothelioma, lymphohematopoietic, and liver cancers from January 2000 to October 2012. Between 1996 and 2005, benzene accounted for 84.4% of cases, and between 1999 and 2005, asbestos was associated with 62.3% of cases. Fourteen novel causative agents and 12 additional target cancers were identified and the final guidelines were amended to include 23 causative agents and 21 target cancers. This amendment of the criteria for occupational cancer represents the widest change in Korean history and is expected to improve the understanding of occupational cancer by providing an up-to-date and accurate reference guide.

Health Effects of Chronic Arsenic Exposure / 예방의학회지

Arsenic is a unique element with distinct physical characteristics and toxicity whose importance in public health is well recognized. The toxicity of arsenic varies across its different forms. While the carcinogenicity of arsenic has been confirmed, the mechanisms behind the diseases occurring after acute or chronic exposure to arsenic are not well understood. Inorganic arsenic has been confirmed as a human carcinogen that can induce skin, lung, and bladder cancer. There are also reports of its significant association to liver, prostate, and bladder cancer. Recent studies have also suggested a relationship with diabetes, neurological effects, cardiac disorders, and reproductive organs, but further studies are required to confirm these associations. The majority of research to date has examined cancer incidence after a high exposure to high concentrations of arsenic. However, numerous studies have reported various health effects caused by chronic exposure to low concentrations of arsenic. An assessment of the health effects to arsenic exposure has never been performed in the South Korean population; thus, objective estimates of exposure levels are needed. Data should be collected on the biological exposure level for the total arsenic concentration, and individual arsenic concentration by species. In South Korea, we believe that biological exposure assessment should be the first step, followed by regular health effect assessments.

Health Effects of Chronic Arsenic Exposure / 예방의학회지

Arsenic is a unique element with distinct physical characteristics and toxicity whose importance in public health is well recognized. The toxicity of arsenic varies across its different forms. While the carcinogenicity of arsenic has been confirmed, the mechanisms behind the diseases occurring after acute or chronic exposure to arsenic are not well understood. Inorganic arsenic has been confirmed as a human carcinogen that can induce skin, lung, and bladder cancer. There are also reports of its significant association to liver, prostate, and bladder cancer. Recent studies have also suggested a relationship with diabetes, neurological effects, cardiac disorders, and reproductive organs, but further studies are required to confirm these associations. The majority of research to date has examined cancer incidence after a high exposure to high concentrations of arsenic. However, numerous studies have reported various health effects caused by chronic exposure to low concentrations of arsenic. An assessment of the health effects to arsenic exposure has never been performed in the South Korean population; thus, objective estimates of exposure levels are needed. Data should be collected on the biological exposure level for the total arsenic concentration, and individual arsenic concentration by species. In South Korea, we believe that biological exposure assessment should be the first step, followed by regular health effect assessments.

Mouthwashes with hydrogen peroxide are carcinogenic, but are freely indicated on the internet: warn your patients!

It all began in Ancient Egypt where people used to bleach their teeth with antiseptic mouthwashes made of urea from human urine. Teeth harmony is promoted by expression of feelings, communication, a real window of the brain and its content! Tooth bleaching products are medicines, not cosmetics! Mouth washing with hydrogen peroxide is an illogical and dangerous procedure! Hydrogen peroxide must be used in one's mouth only when employed by a dentist who has been properly instructed to protect the mucosa, preventing it from receiving these products. How and for how long these products are going to be used require caution in order to avoid or decrease any adverse effects on the tissues. Many websites instruct people on how to purchase and prepare hydrogen peroxide so that it is used as an antiseptic mouthwash and tooth bleaching agent. Some websites even refer to dentists as "exploiters", accusing them of not instructing patients properly. In this article, we aim at providing evidence and information upon which dentists and assistants may base their thinking as well as their opinion and procedures regarding "the indiscriminate and free use of hydrogen peroxide in the mouth, on teeth and oral mucosa". Those websites, blogs and social network profiles trespass the limits of public trust and should be immediately sued by the government for committing a crime against public health.

Tudo começou no Egito antigo, onde procurava-se clarear os dentes com bochechos antissépticos com ureia da urina humana. Os dentes se harmonizam com expressões de sentimentos, na comunicação, como uma verdadeira vitrine do cérebro e seus conteúdos! Clareadores dentários são medicamentos, e não cosméticos! Bochecho com água oxigenada representa um procedimento improcedente e perigoso! O uso do peróxido de hidrogênio ou água oxigenada na boca deve ser feito diretamente pelo profissional da Odontologia, treinado para proteger as mucosas contra o contato desses produtos. O tempo e a forma de uso requerem cuidados, para se proteger ou diminuir os efeitos indesejáveis sobre os tecidos. Vários websites "ensinam" como adquirir e preparar água oxigenada para fazer bochechos antissépticos e clarear os dentes. Alguns websites se referem ao profissional da Odontologia como um "explorador", por não ensinar isso ao paciente. No presente artigo, procuraremos informar e dar fundamentos para que os profissionais da Odontologia e auxiliares possam embasar suas reflexões, opiniões e condutas relacionadas ao tema "uso indiscriminado e livre de peróxido de hidrogênio na boca sobre os dentes e mucosa bucal". Esses websites, blogs e perfis em redes sociais abusam da fé pública e deveriam ser acionados judicialmente, imediatamente, pelas autoridades públicas, pelo crime contra a saúde das pessoas.

Trends of chronic health effects associated to pesticide use in fruit farming regions in the state of Ceara, Brazil / Tendencias de agravos cronicos a saude associados a agrotoxicos em regiao de fruticultura no Ceara, Brasil

The lower valley of Jaguaribe has registered, since the XXI century, the arrival of transnational and regional companies, which led to deep transformations in this region. The increased use of the pesticides is one of the most important ones, being able to cause alterations in human procreation and leading to congenital deformations, besides premature birth and low weight newborns. This article is an ecological study related to the period from 2000 to 2010 in the population of some cities in the state of Ceará, and it was divided in two parts: the first one, a draft of historical series of morbidity and mortality databases and trend verification performed by a simple linear regression; the second one comprehends the calculation of the ratio of rates between cities that are highly exposed to pestiides and the cities selected for comparison, with history of little use of these substances. There was statistically considerable growth tendency (p = 0.026) in the number of hospitalized people with neoplasms. Analyzing the ratios of the rates in these same indicators, it is observed that the rates of hospitalized people with neoplasms were 1.76 times higher in the studied cities than in control cities (p < 0.0010). With regard to to fetal deaths, a statistically considerable increase was observed (p < 0.05) as to the mortality rates in the studied cities. Results suggest there was higher morbidity and mortality caused by neoplasms in the cities with broader use of pesticides, which could be influenced by production, environmental and social transformations associated to the process of deterritorialization induced by the expansion of the agricultural modernization over the morbidity and mortality profile of the population of lower Jaguaribe. This process is a reflex of the production chemical-dependent model adopted by the agribusiness companies, expanding the vulnerability of the country side population.

O Baixo vale do Jaguaribe registra, a partir do século XXI, a chegada de empresas transnacionais e regionais, induzindo profundas transformações nos territórios, sendo a ampliação do uso de agrotóxicos uma das mais importantes, podendo provocar alterações na reprodução humana, malformações congênitas, além de partos prematuros e recém-nascidos de baixo peso. O presente artigo trata-se de um estudo ecológico, referente ao período de 2000 a 2010, conduzido em alguns municípios do Estado do Ceará, que foi dividido em duas fases: a primeira consiste na construção de séries históricas de indicadores de morbimortalidade e verificação da tendência realizada por meio de regressão linear simples; a segunda compreende o cálculo das razões das taxas entre municípios com alta exposição aos agrotóxicos e municípios de comparação com histórico de pouco uso dessas substâncias. Houve tendência de aumento estatisticamente significante (p = 0,026) das taxas de internações por neoplasias. Ao se analisar as razões de taxas desses mesmos indicadores percebe-se que a taxa de internações por neoplasias foi 1,76 vezes maior nos municípios de estudo em relação aos municípios controle (p < 0,001). Em relação aos óbitos fetais, observou-se uma tendência crescente (p < 0,05) da taxa de mortalidade nos municípios estudados. Os resultados sugerem que houve uma maior morbimortalidade por neoplasias nos municípios com maior consumo de agrotóxicos, podendo ser influenciados pelas transformações produtivas, ambientais e sociais associadas ao processo de desterritorialização induzido pela expansão da modernização agrícola sobre o perfil de morbimortalidade da população do baixo Jaguaribe. Esse processo é reflexo do modelo produtivo químico-dependente incorporado pelas empresas do agronegócio, ampliando a vulnerabilidade da população rural.

Tumor necrosis factor-α antagonists: Side effects and their management.

As elevated levels of tumor necrosis factor-alpha (TNF-α) are associated with disease severity in psoriasis and psoriatic arthritis, TNF-α antagonists are being used to treat moderate to severe disease in patients who have contraindications, fail to respond or develop side effects to conventional systemic therapies. It is of utmost importance to be well versed with the possible adverse effects and contraindications of TNF-α antagonists so that they can be used effectively and safely. Many of their adverse effects have been well studied in patients of rheumatoid arthritis (RA) and inflammatory bowel disease (IBD) and may not be completely applicable in psoriasis. This is because patients with RA and IBD are on multiple immunosuppressants while those with psoriasis are mostly receiving single systemic therapy and often have comorbidities that distinguish them from those with RA or IBD. Also, some of the side effects are still controversial and debated. Long-term prospective randomized controlled studies are needed to better understand the associated risk in patients of psoriasis. Baseline screening and periodic monitoring during treatment can reduce and help in early identification and appropriate management of the adverse outcomes. This article reviews the side effects known to be associated with TNF-α antagonists, their pathomechanisms and management guidelines. Some of the common side effects include infusion and injection site reactions, infections particularly reactivation of tuberculosis, autoantibody formation and drug induced lupus erythematosus, liver function abnormalities, hematological, and solid organ malignancies.

Tumor necrosis factor-α antagonists: Side effects and their management.

As elevated levels of tumor necrosis factor-alpha (TNF-α) are associated with disease severity in psoriasis and psoriatic arthritis, TNF-α antagonists are being used to treat moderate to severe disease in patients who have contraindications, fail to respond or develop side effects to conventional systemic therapies. It is of utmost importance to be well versed with the possible adverse effects and contraindications of TNF-α antagonists so that they can be used effectively and safely. Many of their adverse effects have been well studied in patients of rheumatoid arthritis (RA) and inflammatory bowel disease (IBD) and may not be completely applicable in psoriasis. This is because patients with RA and IBD are on multiple immunosuppressants while those with psoriasis are mostly receiving single systemic therapy and often have comorbidities that distinguish them from those with RA or IBD. Also, some of the side effects are still controversial and debated. Long-term prospective randomized controlled studies are needed to better understand the associated risk in patients of psoriasis. Baseline screening and periodic monitoring during treatment can reduce and help in early identification and appropriate management of the adverse outcomes. This article reviews the side effects known to be associated with TNF-α antagonists, their pathomechanisms and management guidelines. Some of the common side effects include infusion and injection site reactions, infections particularly reactivation of tuberculosis, autoantibody formation and drug induced lupus erythematosus, liver function abnormalities, hematological, and solid organ malignancies.

Efectos de las estatinas en cáncer: ¿potencial rol en terapéutica y prevención? / Effects of statins in cancer

This review explores the evidence supporting a potential benefit of statins in cancer. In particular, the lipophilic forms (i.e. lovastatin, simvastatin, or similar) would have a therapeutic but not a preventive role. The pleiotropic effects that statins possess mainly explain this phenomenon, influencing the natural history of disease and the response to currently available therapies. By inhibiting the mevalonate pathway, statins would have a systemic effect, similar to that observed in atherosclerosis, reducing the inflammatory stimuli present in the tumor micro-environment and inhibiting the activation of intracellular signaling cascades critical for proliferation, migration/invasion and metastasis of the cancer cell. Despite all this evidence, randomized trials are needed to confirm the benefit of statins on cancer, before promoting their widespread use as a therapeutic or preventive strategy for this condition.

A Terapia hormonal em pacientes com neurofibromatose tipo 1 é segura? / Hormonal therapy in patientes with neurofibromatosis type 1 is safe?

Nos pacientes com neurofibromatose tipo 1 (NF1), o número de neurofibromas varia grandemente de pessoa para pessoa, mesmo em casos intrafamiliares, com a mesma mutação na linhagem germinativa no gene NF1. Além das mutações nesse gene, provavelmente fatores adicionais são importantes no desenvolvimento ou no crescimento dos neurofibromas. O objetivo deste artigo é revisar a literatura sobre o papel dos hormônios no desenvolvimento e crescimento dos neurofibromas e a segurança da terapia hormonal nos pacientes com NF1

In patients with neurofibromatosis type 1 (NF1), the number of neurofibromas varies greatly from person to person, even in intrafamilial cases, with the same germline mutation in the NF1 gene. In addition to the mutations in this gene, it is likely that additional factors are important in neurofibroma development or growth. The purpose of this article is to review the literature on the role of hormones in the development and growth of neurofibromas and the safety of hormonal therapy in patients with NF1

Cáncer por contaminación química del agua de consumo humano en menores de 19 años: una revisión sistemática / Cancer in the population under 19 years of age caused by chemical contamination in drinking water: a systematic review

OBJETIVO: Evaluar la asociación entre la exposición a los principales contaminantes químicos del agua de consumo humano (ACH) y el aumento de casos de cáncer en menores de 19 años. MÉTODOS: Se realizó una revisión sistemática de la literatura científica recogida en las bases de datos MEDLINE (via PubMed©), EMBASE©, Web of Knowledge, Cochrane Library Plus, Literatura Latinoamericana y del Caribe en Ciencias de la Salud (LILACS), SCOPUS y SCIRUS. Los descriptores utilizados fueron "neoplasms" y "water pollution, chemical", limitado a estudios que incluyeran a menores de 19 años. Se seleccionaron los artículos científicos de cualquier tipo y en cualquier idioma, desde el inicio de la indización de la fuente primaria hasta marzo de 2011. RESULTADOS: Se recuperaron 266 artículos, de los que se seleccionaron 20 tras aplicar los criterios de inclusión y exclusión. Los contaminantes del ACH analizados fueron: arsénico, subproductos de la desinfección, compuestos nitrogenados, derivados del petróleo, plaguicidas agrícolas, radionúclidos, así como otros de origen industrial. La mayoría de los estudios no hallaron una asociación significativa entre la exposición a los contaminantes encontrados en el ACH y el aumento de casos de cáncer en menores de 19 años. En algunas de las poblaciones estudiadas se observó una relación significativa dosis-respuesta en el período de exposición. CONCLUSIONES: Teniendo en cuenta el insuficiente nivel de actualidad de los artículos encontrados, se requieren más estudios dirigidos a conocer el efecto real de la contaminación del ACH en la incidencia de cáncer en la población, en particular en los niños y jóvenes por su mayor susceptibilidad.

OBJECTIVE: To evaluate the association between exposure to the main chemical contaminants in drinking water and the rise in cancer cases among the population under age 19. METHODS: A systematic review was undertaken of the scientific literature compiled in the MEDLINE (via PubMed©), EMBASE©, Web of Knowledge, Cochrane Library Plus, Latin American and Caribbean Literature on Health Sciences (LILACS), SCOPUS, and SCIRUS databases. The descriptors used were "neoplasms" and "water pollution, chemical," limited to studies that included people under age 19. Articles selected were of any type in any language, from the inception of the indexing of the primary source until March of 2011. RESULTS: The search generated 266 articles, from which 20 were selected after applying the inclusion and exclusion criteria. Drinking water contaminants analyzed were arsenic, disinfection byproducts, nitrogen compounds, petroleum derivatives, agricultural pesticides, radionuclides, and others of industrial origin. The majority of the studies did not find a significant link between exposure to drinking water contaminants and the increase in cancer cases in the under-19 population segment. In some of the studied populations a significant dose-response relationship was observed. CONCLUSIONS: Taking into account that the articles located were insufficiently up-to-date, more studies are required in order to know the effect of drinking water contamination on cancer rates, in particular among children and youths, who are more susceptible.

4NQO carcinogenesis: a model of oral squamous cell carcinoma / Carcinogenesis inducida por 4NQO: un modelo de carcinoma oral de células escamosas

The experimental oral carcinogenesis induced by the chemical 4-nitroquinoline 1-oxide (4NQO) is one of the most frequent in the study of squamous cell carcinoma of the oral cavity (CCEC). The clear advantage is that the model is very similar to the physiological process of malignancy. The model has clear benefits by and is suitable for applications in therapeutic research.

La carcinogénesis oral experimental inducida por el químico 4-nitroquinolina 1-óxido (4NQO) es uno de los métodos más frecuentes en el estudio del carcinoma de células escamosas de la cavidad oral (CCECO). La clara ventaja del modelo radica en el gran parecido al proceso fisiológico de la neoplasia maligna. El modelo tiene beneficios claros y es adecuado para las aplicaciones de la investigación terapéutica.