Eduardo M. De Capitani

Influence of p53 codon 72 exon 4, GSTM1, GSTT1 and GSTP1{*}B polymorphisms in lung cancer risk in a Brazilian population

PURPOSE Glutathione S-transferases (GST) modulates the effects of various cytotoxic and genotoxic agents, particularly those derived from benzo[a]pyrene, which is one of the main tobacco carcinogens. Both the mu 1 (GSTM1) and theta 1 (GSTT1) genes have a null variant allele in which the entire gene is absent. The GSTP1*B allele has an A to G transition at nucleotide 313 (codon 105) in exon 5, causing a change of isoleucine (Ile) to valine (Val), which affects the electrophile binding site of GSTP1 and results in an enzyme with reduced activity. Polymorphisms in these metabolizing enzymes may alter the response to benzo[a]pirene-induced DNA damage. Polymorphisms in p53 may also modulate the risk of lung cancer (LC) carcinogenesis. The aim of our study was to measure the frequency of GSTM1, GSTT1, GSTP1*B and p53 gene polymorphisms in a Brazilian population and determine the possible contribution of these genetic variations to LC risk. PATIENTS AND METHODS Genomic DNA was obtained from 200 Brazilian patients with LC and 264 blood donors (control group). All samples were analyzed by PCR and PCR-RFLP to determine GSTM1, GSTT1, GSTP1*B and p53 codon 72 genotypes. Multiple logistic regressions were used to adjust for confounding factors in this case-control study. RESULTS No statistical significance was observed between GSTM1, GSTT1 and GSTP1*B genetic polymorphisms, either isolated or combined, with LC incidence in the studied population. However, our data showed a higher frequency of p53 codon 72 A/P plus P/P genotype in African-Brazilian than Caucasian-Brazilian patients with LC, and we also found a higher frequency of the P/P genotype of the p53 gene in non-smokers compared to smokers with LC. CONCLUSIONS Genetic polymorphisms of GST and p53 codon 72 did not increase the risk of LC in Brazilian patients. The A/P plus P/P genotype of p53 codon 72 is more common in LC patients with African ethnical background and the P/P genotype more prevalent in non-smoking related LC.

Abnormal antioxidant system in erythrocytes of mercury-exposed workers

To investigate the effects of chronic exposure to mercury we studied the red cell antioxidant system in mercury-exposed workers through the evaluation of reduced glutathione, catalase and superoxide dismutase systems. Oftheseworkers, somewerebeingexposedatthetimeand had presented urinary mercury levels considered safe for occupational exposure for at least 3 months prior to the initiation of this study, and others had been on leave for at least 6 months because of intoxication symptoms. Reduced glutathione levels were lower and catalase activity was higher in the workers which were still being exposed, compared to those on leave and controls. No differences were observed between the workers on leave and controls.

Environmental Contamination and Human Exposure to Lead in Brazil

Adverse effects caused by environmental lead pollution are well recognized. Being a widespread agent in the environment and a major harmful element to organic systems, mostly to children, lead has been investigated all over the world, aiming to improve measures regarding its control. The purpose of this chapter is to present a review of the situation of production, uses, assessment of exposure, and adverse effects from environmental lead contamination in Brazil. It also presents aspects of Brazilian legislation setting up maximum permissible levels of lead in several environmental compartments such as surface and drinking water, soils, sediment, urban air, and also in commercially sold food, vegetables, fish, and meat, in an effort to control industrial emissions. Epidemiological investigations on childrens lead exposure around industrial and mining areas are revised, showing that many situations where lead contamination is potentially present still need to be addressed by governmental agencies. In Brazil, lead was withdrawn from gasoline by the end of the 1980s, and the last lead mining and primary smelting plant was closed in 1995, leaving residual environmental lead contamination, which has recently been investigated using a multidisciplinary approach. Nevertheless, there are hundreds of small secondary battery recycling plants all over the country, running smelting facilities that produce local urban areas of lead contamination.

Acute dapsone exposure and methemoglobinemia in children: treatment with multiple doses

OBJECTIVE: To study the changes in methemoglobinemia of 17 children admitted with acute exposure to dapsone complicated by a methemoglobin concentration greater than 20% of the total hemoglobin. The children were treated with multiple doses of activated charcoal with or without the administration of methylene blue.PATIENTS AND METHODS: Seventeen patients (ages 1-13 y, median 3 y), were admitted 1-72 h after the ingestion of 100-1200 mg (median 350 mg, 10 patients) or an unknown amount of dapsone (7 patients). The methemoglobin blood concentrations upon admission ranged from 23.5%-49.7% (median 37.8%), and the main clinical features were cyanosis (17), tachycardia (17), vomiting (11) and tachypnea (8). All of the children received multiple doses of activated charcoal orally or via nasogastric tube (1g/kg, 10% solution, 4-6 times/day, 3-16 doses with a median of 8 doses). Twelve of the 14 patients with methemoglobin levels greater than 30% were also treated with a single dose of methylene blue (1-2% solution, 1-2 mg/kg) infused IV over 5 min.RESULTS: There was a progressive decrease in the methemoglobin levels after the beginning of both treatments (multiple doses of activated charcoal alone or associated with methylene blue), and only one dose of methylene blue was necessary. There were no significant statistical differences between the results of the two treatments according to the time-course decrease in methemoglobinemia (p=0.49 Wilcoxon test).CONCLUSIONS: Multiple doses of activated charcoal given when methemoglobin levels were greater than 20% can be considered as a possible treatment for pediatric patients, with or without the administration of methylene blue, after acute dapsone exposure.

Fatal ischemic stroke following Tityus serrulatus scorpion sting in a patient with essential thrombocythemia

Abstract Context: Stroke following scorpion stings is rare. We report a fatal envenomation involving multiple, extensive brain infarcts in a patient with a previous diagnosis of essential thrombocythemia (ET) who was stung by Tityus serrulatus (T. serrulatus). Case details: A 44-year-old woman with a diagnosis of low-risk ET (platelets <1,000,000/mm3, age <60 years and no history of thrombosis; positive JAK2V617F mutation) was admitted to a local ED 1 h after being stung by T. serrulatus on the left foot. She developed signs of severe envenomation, including several episodes of profuse vomiting, pallor and confusion soon after the sting, followed by shock (BP: 90/60 to 60/40 mmHg) and was treated with scorpion antivenom, vasopressors and mechanical ventilation. A brain computed tomography (CT) scan (54-h poststing) revealed diffuse bilateral cerebellar hypodensity, with partial involvement of both occipital lobes and thalamus, obstructive hydrocephaly with signs of cerebrospinal fluid extravasation, and ascending transtentorial herniation, suggestive of bilateral ischemia involving the posterior cerebral circulation. External ventricular drainage resulted in no improvement and brain death was confirmed on day 10. Discussion: Several mechanisms have been proposed to explain stroke following scorpion stings, such as sympathetic stimulation, myocardial dysfunction, hypotension/shock, arrhythmias and coagulopathy. Ischemic stroke is one of the most serious complications of ET. The risk factors for thrombotic/ischemic events in patients with ET include age (≥60 years) and previous vascular events. Severe scorpion envenomation resulting in myocardial dysfunction and systemic inflammatory response syndrome may increase the overall risk of arterial thrombosis in this patient.

Medical Geology Studies in South America

“Earth and Health” or medical geology has been promoted worldwide as one of the fundamental themes of the International Year of Planet Earth (2007–2009). This was in response to relevant achievements noted in this new field of applied science from the time of the IGCP 454 project which led to foundation of the International Medical Geology Association (IMGA) in 2004. In association with international movements, several academic, professional, and student groups in South America began to study medical geology which started with scientific meetings held in Chile, Brazil, and Uruguay in 2002 and 2003. In this chapter, an attempt is made to describe South American scientists’ relevant contributions to various subjects such as arsenic, lead, mercury, and selenium as well as fluorine and environmental problems affecting different parts of the continent. Some societal issues arising from medical geology studies are also highlighted from the point of view of the international risk communication and risk governance debate and the pioneering ethnographic descriptions of geophagy in the Andean and Amazonian countries. Finally, some ongoing medical geology projects in South America are identified as inspiring initiatives that may encourage future educational and research activities in this science field.

Antídotos e medicamentos utilizados para tratar intoxicações no Brasil: necessidades, disponibilidade e oportunidades

Antidotes and certain other drugs are essential for treating some types of poisoning. Failures in their supply can jeopardize the populations health and safety. The current study aimed to assess the availability of antidotes and other drugs used in the treatment of poisonings in Brazil. International guidelines were used as the basis for selecting 41 antidotes for analysis, none of which currently protected by patents. Of these, 27 are registered in Brazil, but 11 of these are available in inadequate forms for treating poisoning, leaving 16 commercially available antidotes. Only one-third of the drugs needed for treating poisoning are included in the countrys list of essential drugs. The article also presents a proposal for supplying the demand for one of the antidotes, anti-digoxin antibody, considering Brazils domestic capacity for manufacturing immunobiologicals. The studys results show the limitations to adequate treatment for poison victims in Brazil and reinforce the urgent need to strengthen public policies in this area.Antidotos e determinados medicamentos sao essenciais ao tratamento de algumas intoxicacoes e nao podem sofrer falhas no abastecimento, sob o risco de prejudicar a saude e a seguranca da populacao. O objetivo deste trabalho foi avaliar a disponibilidade de antidotos e medicamentos recomendados para o tratamento de intoxicacoes no Brasil. A partir de consensos internacionais, foram selecionados 41 antidotos para analise, todos sem patente em vigencia. Desses, 27 sao registrados, porem 11 estao disponiveis em formas inadequadas ao tratamento de intoxicacoes, restando 16 medicamentos comercialmente disponiveis. Somente um terco dos medicamentos necessarios para o tratamento de intoxicacoes esta incluido na relacao de medicamentos essenciais do pais. Em adicao, e apresentada proposta de suprimento das demandas a um dos antidotos, anticorpo antidigoxina, considerando a capacidade de producao nacional de imunobiologicos. Os resultados demonstram limitacao da assistencia adequada aos pacientes intoxicados no pais e reforcam a necessidade urgente de politicas publicas na area.

[Antidotes and medicines used to treat poisoning in Brazil: needs, availability and opportunities].

Antidotes and certain other drugs are essential for treating some types of poisoning. Failures in their supply can jeopardize the populations health and safety. The current study aimed to assess the availability of antidotes and other drugs used in the treatment of poisonings in Brazil. International guidelines were used as the basis for selecting 41 antidotes for analysis, none of which currently protected by patents. Of these, 27 are registered in Brazil, but 11 of these are available in inadequate forms for treating poisoning, leaving 16 commercially available antidotes. Only one-third of the drugs needed for treating poisoning are included in the countrys list of essential drugs. The article also presents a proposal for supplying the demand for one of the antidotes, anti-digoxin antibody, considering Brazils domestic capacity for manufacturing immunobiologicals. The studys results show the limitations to adequate treatment for poison victims in Brazil and reinforce the urgent need to strengthen public policies in this area.Antidotos e determinados medicamentos sao essenciais ao tratamento de algumas intoxicacoes e nao podem sofrer falhas no abastecimento, sob o risco de prejudicar a saude e a seguranca da populacao. O objetivo deste trabalho foi avaliar a disponibilidade de antidotos e medicamentos recomendados para o tratamento de intoxicacoes no Brasil. A partir de consensos internacionais, foram selecionados 41 antidotos para analise, todos sem patente em vigencia. Desses, 27 sao registrados, porem 11 estao disponiveis em formas inadequadas ao tratamento de intoxicacoes, restando 16 medicamentos comercialmente disponiveis. Somente um terco dos medicamentos necessarios para o tratamento de intoxicacoes esta incluido na relacao de medicamentos essenciais do pais. Em adicao, e apresentada proposta de suprimento das demandas a um dos antidotos, anticorpo antidigoxina, considerando a capacidade de producao nacional de imunobiologicos. Os resultados demonstram limitacao da assistencia adequada aos pacientes intoxicados no pais e reforcam a necessidade urgente de politicas publicas na area.

Antídotos y medicamentos utilizados para tratar intoxicaciones en Brasil: necesidades, disponibilidad y oportunidades

Antidotes and certain other drugs are essential for treating some types of poisoning. Failures in their supply can jeopardize the populations health and safety. The current study aimed to assess the availability of antidotes and other drugs used in the treatment of poisonings in Brazil. International guidelines were used as the basis for selecting 41 antidotes for analysis, none of which currently protected by patents. Of these, 27 are registered in Brazil, but 11 of these are available in inadequate forms for treating poisoning, leaving 16 commercially available antidotes. Only one-third of the drugs needed for treating poisoning are included in the countrys list of essential drugs. The article also presents a proposal for supplying the demand for one of the antidotes, anti-digoxin antibody, considering Brazils domestic capacity for manufacturing immunobiologicals. The studys results show the limitations to adequate treatment for poison victims in Brazil and reinforce the urgent need to strengthen public policies in this area.Antidotos e determinados medicamentos sao essenciais ao tratamento de algumas intoxicacoes e nao podem sofrer falhas no abastecimento, sob o risco de prejudicar a saude e a seguranca da populacao. O objetivo deste trabalho foi avaliar a disponibilidade de antidotos e medicamentos recomendados para o tratamento de intoxicacoes no Brasil. A partir de consensos internacionais, foram selecionados 41 antidotos para analise, todos sem patente em vigencia. Desses, 27 sao registrados, porem 11 estao disponiveis em formas inadequadas ao tratamento de intoxicacoes, restando 16 medicamentos comercialmente disponiveis. Somente um terco dos medicamentos necessarios para o tratamento de intoxicacoes esta incluido na relacao de medicamentos essenciais do pais. Em adicao, e apresentada proposta de suprimento das demandas a um dos antidotos, anticorpo antidigoxina, considerando a capacidade de producao nacional de imunobiologicos. Os resultados demonstram limitacao da assistencia adequada aos pacientes intoxicados no pais e reforcam a necessidade urgente de politicas publicas na area.