Karen Friedrich

Malaria downmodulates mRNA expression and catalytic activities of CYP1A2, 2E1 and 3A11 in mouse liver

It has been reported that malaria reduces cytochrome-P450 (CYP) content and monooxygenase activities in the mammalian host liver. The mechanism by which malaria modulates CYP activities, however, remains unclear. In this study we found that activities of ethoxy- and benzyloxy-resorufin-O-dealkylases, p-nitrophenol-hydroxylase and erythromycin-N-demethylase (mediated by CYP1A, 2B, 2E1 and 3A, respectively) were depressed, while uridine-glucuronosyl-transferase (a phase 2 enzyme) was unaltered in liver microsomes of Plasmodium berghei-infected (parasitemia >20%) male Swiss Webster mice. Prolongation of midazolam sleeping time and a slower clearance of chlorzoxazone were also noted in infected mice. Reductions of hepatic levels of CYP1A2, 2E1 and 3A11 mRNAs indicated that malaria downregulated these CYP-mediated activities at a pre-translational level.

Disposition of Antimony in Rhesus Monkeys Infected with Leishmania braziliensis and Treated with Meglumine Antimoniate

Antimony (Sb) disposition and toxicity was evaluated in Leishmania braziliensis-infected monkeys (Macaca mulatta) treated with a 21-d course of low (LOW) or standard (STD) meglumine antimoniate (MA) dosage regimens (5 or 20 mg SbV/kg body weight/d im). Antimony levels in biological matrices were determined by inductively coupled plasma mass spectrometry (ICPMS), while on-line ion chromatography coupled to ICPMS was used to separate and quantify Sb species in plasma. Nadir Sb levels rose steadily from 19.6 ± 4 and 65.1 ± 17.4 ng/g, 24 h after the first injection, up to 27.4 ± 5.8 and 95.7 ± 6.6 ng/g, 24 h after the 21st dose in LOW and SDT groups, respectively. Subsequently, Sb plasma levels gradually declined with a terminal elimination phase half-life of 35.8 d. Antimony speciation in plasma on posttreatment days 1–9 indicated that as total Sb levels declined, proportion of SbV remained nearly constant (11–20%), while proportion of SbIII rose from 5% (d 1) to 50% (d 9). Plasma [Sb]/erythrocyte [Sb] ratio was >1 until 12 h after dosing and reversed thereafter. Tissue Sb concentrations (posttreatment days 55 and 95) were as follows: >1000 ng/g in thyroid, nails, liver, gall bladder and spleen; >200 and <1000 ng/g in lymph nodes, kidneys, adrenals, bones, skeletal muscles, heart and skin; and <200 ng/g in various brain structures, thymus, stomach, colon, pancreas. and teeth. Results from this study are therefore consistent with view that SbV is reduced to SbIII, the active form, within cells from where it is slowly eliminated. Localization of Sb active forms in the thyroid gland and liver and the pathophysiological consequences of marked Sb accumulation in these tissues warrant further studies.

Use of genetically modified crops and pesticides in Brazil: growing hazards

Genetically modified (GM) crops were officially authorized in Brazil in 2003. In this documentary study, we aimed to identify possible changes in the patterns of pesticide use after the adoption of this technology over a span of 13 years (2000 to 2012). The following variables were analyzed: Pesticide use (kg), Pesticide use per capita (kg/inhab), Pesticide and herbicide use per area (kg/ha) and productivity (kg/ha). Contrary to the initial expectations of decreasing pesticide use following the adoption of GM crops, overall pesticide use in Brazil increased 1.6-fold between the years 2000 and 2012. During the same period, pesticide use for soybean increased 3-fold. This study shows that the adoption of GM crops in Brazil has led to an increase in pesticide use with possible increases in environmental and human exposure and associated negative impacts.

Exposição ambiental e ocupacional a agrotóxicos e o linfoma não Hodgkin

RESUMO Este ensaio versa sobre a exposicao a agrotoxicos e o risco de desenvolvimento de linfoma nao Hodgkin (LNH), um tipo de câncer hematologico que teve aumento progressivo nas ultimas decadas no Brasil e no mundo. Foi realizada uma revisao integrativa para avaliar a associacao de agrotoxicos com a inducao de LNH. A pesquisa mostrou que os agrotoxicos acido diclorofenoxiacetico (2,4-D), diazinona, glifosato e malationa estao associados a essa neoplasia e compartilham alguns mecanismos de carcinogenicidade. Essas informacoes podem subsidiar medidas regulatorias mais restritivas e que contemplem a realidade da exposicao a misturas de agrotoxicos, amplamente utilizados no meio rural e urbano.

Adverse events and technical complaints related to central venous catheters marketed in Brazil.

Aim The objective of this study was to critically analyze data of the National Notification System for Adverse Events and Technical Complaints (Notivisa) related to central venous catheters, through an evaluation of the description of notifications recorded between 2006 and 2009. Methods Notifications were categorized and evaluated to: (i) determine the number of adverse events and technical complaints, (ii) verify compliance with the classification criteria defined by the legislation, (iii) reclassify notifications, when necessary, in order for them to fit in with the legal definitions, (iv) verify registered companies in Brazil, (v) quantify the notifications according to the registered company and product lot, and (vi) identify the country of original of the notified product. Microsoft Excel(r) 2010 was used to categorize and systematize the data. Results Some conceptual errors and incomplete records were found. Altogether, 228 notifications of technical complaints and 119 of adverse events were identified. Some notifications on guidewires and broken catheters were reported which led to the necessity of duplicating some medical procedures and to the occurrence of lesions/lacerations of vessels and tissue injury. Forty-seven percent of companies presented at least one notification in Notivisa and in all, 38 product lots had more than one notification. Conclusion These data support a necessity for cooperation between all entities of the National Health Surveillance System to check compliance of this type of product and to properly report adverse events and technical complaints. It is also important to incorporate minimum standards for the management of technologies in health services, including in the acquisition of products and training of staff.

Vigilância sanitária em postos de revenda de combustíveis: aplicação de um modelo para integrar ações e promover a saúde do trabalhador

Introduction: benzene, a compound found in gasoline, is recognized as a carcinogen, and it has been controlled worldwide because of its acute and chronic effects to human health. In Brazil, gas station (GS) attendants are exposed to benzene during their occupational activities. Health Surveillance, when monitoring the workers’ exposure to benzene, can assess the risks and implement strategies to establish a safer working environment. Objective: to evoke the discussion about Health Surveillance actions in gas stations based on the application of the Driving Force/Pressure/State/Exposure/Effects/Action (DPSEEA) model. Method: we developed the matrix proposed by the DPSEEA model using information from literature review. Discussion: we were able to identify the existing shortcomings in the different institutional levels that have actions directed to workers’ health protection. We also proposed actions for enhancing the discussion on the development model, modes of production, and resources exploitation. We also identified the possible Health Surveillance actions to be applied in the GS occupational environment to eliminate or reduce the health risks to which workers are exposed.