Evaluation of the cytogenetic effects of I-131 preceded by recombinant human thyrotropin (rhTSH) in peripheral lymphocytes of Wistar rats

The present study was carried out to investigate the cytogenetic effects of therapeutic exposure to radioiodine preceded by rhTSH in an animal model. Three groups of Wistar rats (n = 6) were used: one group was treated only with I-131 (11.1 MBq/animal); the other two groups received rhTSH (1.2 mu g/rat of either Thyrogen or rhTSH-IPEN, respectively) 24 h before administration of radioiodine. The percentage of lymphocytes with chromosome aberrations and the average number of aberrations and of dicentrics per cell were determined on blood samples collected 24 h, 7 and 30 days after administration of I-131. The data show that the treatment with radioiodine alone or associated with rhTSH resulted in a greater quantity of chromosome alterations in relation to basal values after 24 h, with a gradual decline after 7 and 30 days of treatment. An increase in chromosome alterations was also seen after rhTSH treatment alone. Neither of the treatments, i.e., with I-131 alone or associated with hormone, resulted in an aneugenic effect or influenced the kinetics of cellular proliferation in rat blood lymphocytes. There was no significant difference between the cytogenetic effects of Thyrogen and rhTSH-IPEN treatment. These data suggest that the treatment with radioiodine, associated or not with rhTSH, affects to a limited extent a relatively small number of cells although the occurrence of late stochastic effects could not be discarded.

Mechanisms mediating the diuretic and natriuretic actions of the incretin hormone glucagon-like peptide-1

Crajoinas RO, Oricchio FT, Pessoa TD, Pacheco BP, Lessa LM, Malnic G, Girardi AC. Mechanisms mediating the diuretic and natriuretic actions of the incretin hormone glucagon-like peptide-1. Am J Physiol Renal Physiol 301: F355-F363, 2011. First published May 18, 2011; doi: 10.1152/ajprenal.00729.2010.-Glucagon-like peptide-1 (GLP-1) is a gut incretin hormone considered a promising therapeutic agent for type 2 diabetes because it stimulates beta cell proliferation and insulin secretion in a glucose-dependent manner. Cumulative evidence supports a role for GLP-1 in modulating renal function; however, the mechanisms by which GLP-1 induces diuresis and natriuresis have not been completely established. This study aimed to define the cellular and molecular mechanisms mediating the renal effects of GLP-1. GLP-1 (1 mu g.kg(-1).min(-1)) was intravenously administered in rats for the period of 60 min. GLP-1-infused rats displayed increased urine flow, fractional excretion of sodium, potassium, and bicarbonate compared with those rats that received vehicle (1% BSA/saline). GLP-1-induced diuresis and natriuresis were also accompanied by increases in renal plasma flow and glomerular filtration rate. Real-time RT-PCR in microdissected rat nephron segments revealed that GLP-1 receptor-mRNA expression was restricted to glomerulus and proximal convoluted tubule. In rat renal proximal tubule, GLP-1 significantly reduced Na(+)/H(+) exchanger isoform 3 (NHE3)-mediated bicarbonate reabsorption via a protein kinase A (PKA)-dependent mechanism. Reduced proximal tubular bicarbonate flux rate was associated with a significant increase of NHE3 phosphorylation at the PKA consensus sites in microvillus membrane vesicles. Taken together, these data suggest that GLP-1 has diuretic and natriuretic effects that are mediated by changes in renal hemodynamics and by downregulation of NHE3 activity in the renal proximal tubule. Moreover, our findings support the view that GLP-1-based agents may have a potential therapeutic use not only as antidiabetic drugs but also in hypertension and other disorders of sodium retention.

A randomized, comparative study of formoterol and terbutaline dry powder inhalers in the treatment of mild to moderate asthma exacerbations in the pediatric acute care setting

Background: Formoterol is a fast-acting, long-acting beta-agonist. Its on-demand use by outpatients has been beneficial in controlling asthma. Objective: To evaluate the efficacy of formoterol as rescue medication for pediatric asthma exacerbation. Methods: A randomized, double-blind study was conducted on parallel groups involving 79 pediatric patients (mean [SD] age, 9.92 [2.5] years) with mild to moderate asthma exacerbations. They were treated with up to 3 doses of formoterol aerolizer, 12 mu g, or terbutaline Turbuhaler, 0.5 mg (dry powder inhalers). Respiratory rate, clinical score, pulse oximetry, and spirometry were analyzed at baseline and 15 minutes after administration of each bronchodilator dose. All the patients received oral prednisolone, 1 mg/kg, at study entry, followed by a single daily dose for 4 days. Forty-one patients were treated with formoterol and 38 with terbutaline. The groups were comparable in age and in severity of asthma exacerbation. Results: Both treatments resulted in similar clinical and functional improvement; 37 patients (47%) required 1 bronchodilator dose. Increases of 19.5% and 1.5.3% occurred in forced expiratory volume in 1 second in the formoterol and terbutaline groups, respectively. Therapeutic failures occurred in 2 patients. No adverse effects were observed. At 1-week follow-up, patients were stable, with pulmonary function close to normal. Conclusion: Formoterol therapy was at least as effective as terbutaline therapy in children and adolescents with mild and moderate asthma exacerbations. Ann Allergy Asthma Immunol. 2009; 103:248-253.

Early rise in blood pressure following administration of adrenocorticotropic hormone-[1-24] in humans

1. An elevation in blood pressure has been consistently observed 24 h after adrenocorticotropic hormone (ACTH) administration and is caused by increased ACTH-stimulated cortisol secretion, in association with increased cardiac output. The aim of the present study was to investigate the previously undefined time of onset of this increase in blood pressure in normal humans. 2. Ten normal healthy volunteers received 250 mug ACTH-[1-24], in 500 mL normal saline, infused at a constant rate over 8 h. Six subjects also received a placebo infusion (normal saline only). Blood pressure, heart rate and cortisol levels were determined hourly. Adrenocorticotropic hormone (ACTH-[1-24] plus native ACTH) was measured at 0, 1, 7 and 8 h. 3. Infusion of ACTH-[1-24] produced maximal secretion rates of cortisol, resulting in a mean peak plasma level of 985 +/- 46 nmol/L at 8 h. In response, blood pressure and heart rate rose significantly by 2 h and remained generally elevated for the duration of the infusion. 4. The early onset of haemodynamic responses is consistent with classical steroid receptor-mediated genomic mechanisms, but could be due non-genomic mechanisms. 5. The cardiovascular consequences of therapeutic use of ACTH are well recognized. This results of the present study suggest that even diagnostic administration of ACTH, delivered over a few hours, may raise blood pressure.

Recoverable reserves and support effects when optimizing open pit mine designs

Orebody modelling, support effects and the estimation of recoverable reserves are key parts of open pit optimization studies. A case study is presented on the estimation of recoverable reserves using an implementation of indicator kriging where metal quantity is used to select cutoffs, and support corrections founded on a conditional simulation approach. Mining selectivity is explored in the subsequent optimization study to compare results from indicator kriging of grade estimates on a regular size blocks and indicator kriging estimates on small size blocks. The use of indicator kriging models adjusted for a given selectivity and the use of grade proportions in each block for the optimization study, provide a presentation of the expected ore recovery for a predefined level of selectivity. The case study shows that indicator kriging estimation with full accounting of block grade distributions generates substantially better results in the pit optimization study. In addition, the adverse effects of small blocks and over-smoothing on optimization results are illustrated.

Modulation of osteoclastogenesis by antihypertensive drugs

Despite its rigid structure, bone is a dynamic tissue that is in constant remodeling. This process requires the action of the bone-resorbing osteoclasts and the bone-synthesing osteoblasts. One of the adverse effects attributed to some antihypertensive agents is the ability to alter normal bone metabolism. However, their effective actions on human bone cells remain to be clarified. In this work, the effects of five calcium channel blockers, a class of antihypertensive drugs (AHDs), were investigated on osteoclastic differentiation. Osteoclastic cell cultures were established from precursor cells isolated from human peripheral blood, and were maintained in the absence (control) or in the presence of 10-8-10-4 M of different AHDs (amlodipine, felodipine, diltiazem, lercanidipine and nifedipine). Cell cultures were characterized throughout a 21 day period for tartrate-resistant acid phosphatase (TRAP) activity, number of TRAP+ multinucleated cells, presence of cells with actin rings and expressing vitronectin and calcitonin receptors, and apoptosis rate. Also, the involvement of several signaling pathways on the cellular response was addressed. It was observed that the tested AHDs had the ability to differentially affect osteoclastogenesis. At low doses, amlodipine and felodipine caused an increase on osteoclastic differentiation, while the other drugs inhibited it. At higher doses, all the molecules caused a decrease on the process. The tested AHDs also showed different effects on the analysed signaling pathways. In conclusion, AHDs appeared to have a direct effect on human osteoclast precursor cells, affecting their differentiation. Interestingly, some of them increased while others inhibited the process. Unraveling the mechanisms beneath these observations might help to explain the adverse effects on bone tissue described for this drug class.

Low prevalence of hypertension with pharmacological treatments and associated factors

OBJECTIVE: To assess the determinants of the lack of pharmacological treatment for hypertension. METHODS: In 2005, 3,323 Mozambicans aged 25-64 years old were evaluated. Blood pressure, weight, height and smoking status were assessed following the Stepwise Approach to Chronic Disease Risk Factor Surveillance. Hypertensives (systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg and/or antihypertensive drug therapy) were evaluated for awareness of their condition, pharmacological and non-pharmacological management, as well as use of herbal or traditional remedies. Prevalence ratios (PR) were calculated, adjusted for sociodemographic characteristics, cardiovascular risk factors and non-pharmacological treatment. RESULTS: Most of the hypertensive subjects (92.3%), and nearly half of those aware of their condition were not treated pharmacologically. Among the aware, the prevalence of untreated hypertension was higher in men {PR = 1.61; 95% confidence interval (95%CI 1.10;2.36)} and was lower in subjects under non-pharmacological treatment (PR = 0.58; 95%CI 0.42;0.79); there was no significant association with traditional treatments (PR = 0.75; 95%CI 0.44;1.26). CONCLUSIONS: The lack of pharmacological treatment for hypertension was more frequent in men, and was not influenced by the presence of other cardiovascular risk factors; it could not be explained by the use of alternative treatments as herbal/traditional medicines or non-pharmacological management. It is important to understand the reasons behind the lack of management of diagnosed hypertension and to implement appropriate corrective actions to reduce the gap in the access to healthcare between developed and developing countries.

Environmental data management in the Sado Estuary

Estuaries are perhaps the most threatened environments in the coastal fringe; the coincidence of high natural value and attractiveness for human use has led to conflicts between conservation and development. These conflicts occur in the Sado Estuary since its location is near the industrialised zone of Peninsula of Setúbal and at the same time, a great part of the Estuary is classified as a Natural Reserve due to its high biodiversity. These facts led us to the need of implementing a model of environmental management and quality assessment, based on methodologies that enable the assessment of the Sado Estuary quality and evaluation of the human pressures in the estuary. These methodologies are based on indicators that can better depict the state of the environment and not necessarily all that could be measured or analysed. Sediments have always been considered as an important temporary source of some compounds or a sink for other type of materials or an interface where a great diversity of biogeochemical transformations occur. For all this they are of great importance in the formulation of coastal management system. Many authors have been using sediments to monitor aquatic contamination, showing great advantages when compared to the sampling of the traditional water column. The main objective of this thesis was to develop an estuary environmental management framework applied to Sado Estuary using the DPSIR Model (EMMSado), including data collection, data processing and data analysis. The support infrastructure of EMMSado were a set of spatially contiguous and homogeneous regions of sediment structure (management units). The environmental quality of the estuary was assessed through the sediment quality assessment and integrated in a preliminary stage with the human pressure for development. Besides the earlier explained advantages, studying the quality of the estuary mainly based on the indicators and indexes of the sediment compartment also turns this methodology easier, faster and human and financial resource saving. These are essential factors to an efficient environmental management of coastal areas. Data management, visualization, processing and analysis was obtained through the combined use of indicators and indices, sampling optimization techniques, Geographical Information Systems, remote sensing, statistics for spatial data, Global Positioning Systems and best expert judgments. As a global conclusion, from the nineteen management units delineated and analyzed three showed no ecological risk (18.5 % of the study area). The areas of more concern (5.6 % of the study area) are located in the North Channel and are under strong human pressure mainly due to industrial activities. These areas have also low hydrodynamics and are, thus associated with high levels of deposition. In particular the areas near Lisnave and Eurominas industries can also accumulate the contamination coming from Águas de Moura Channel, since particles coming from that channel can settle down in that area due to residual flow. In these areas the contaminants of concern, from those analyzed, are the heavy metals and metalloids (Cd, Cu, Zn and As exceeded the PEL guidelines) and the pesticides BHC isomers, heptachlor, isodrin, DDT and metabolits, endosulfan and endrin. In the remain management units (76 % of the study area) there is a moderate impact potential of occurrence of adverse ecological effects and in some of these areas no stress agents could be identified. This emphasizes the need for further research, since unmeasured chemicals may be causing or contributing to these adverse effects. Special attention must be taken to the units with moderate impact potential of occurrence of adverse ecological effects, located inside the natural reserve. Non-point source pollution coming from agriculture and aquaculture activities also seem to contribute with important pollution load into the estuary entering from Águas de Moura Channel. This pressure is expressed in a moderate impact potential for ecological risk existent in the areas near the entrance of this Channel. Pressures may also came from Alcácer Channel although they were not quantified in this study. The management framework presented here, including all the methodological tools may be applied and tested in other estuarine ecosystems, which will also allow a comparison between estuarine ecosystems in other parts of the globe.

Attention performance among Brazilian truck drivers and its association with amphetamine use: pilot study

The aim of this article was to describe the attention functioning of twenty-two truck drivers and its relationship with amphetamine use. Those drivers who reported using amphetamines in the twelve months previous to the interview had the best performance in a test evaluating sustained attention functioning. Although amphetamine use may initially seem advantageous to the drivers, it may actually impair safe driving. The findings suggest the importance of monitoring the laws regarding amphetamine use in this country.

Biological drugs for the treatment of psoriasis in a public health system

OBJECTIVE To analyze the access and utilization profile of biological medications for psoriasis provided by the judicial system in Brazil.METHODSThis is a cross-sectional study. We interviewed a total of 203 patients with psoriasis who were on biological medications obtained by the judicial system of the State of Sao Paulo, from 2004 to 2010. Sociodemographics, medical, and political-administrative characteristics were complemented with data obtained from dispensation orders that included biological medications to treat psoriasis and the legal actions involved. The data was analyzed using an electronic data base and shown as simple variable frequencies. The prescriptions contained in the lawsuits were analyzed according to legal provisions.RESULTS A total of 190 lawsuits requesting several biological drugs (adalimumab, efalizumab, etanercept, and infliximab) were analyzed. Patients obtained these medications as a result of injunctions (59.5%) or without having ever demanded biological medication from any health institution (86.2%), i.e., public or private health services. They used the prerogative of free legal aid (72.6%), even though they were represented by private lawyers (91.1%) and treated in private facilities (69.5%). Most of the patients used a biological medication for more than 13 months (66.0%), and some patients were undergoing treatment with this medication when interviewed (44.9%). Approximately one third of the patients discontinued treatment due to worsening of their illness (26.6%), adverse drug reactions (20.5%), lack of efficacy, or because the doctor discontinued this medication (13.8%). None of the analyzed medical prescriptions matched the legal prescribing requirements. Clinical monitoring results showed that 70.3% of the patients had not undergone laboratory examinations (blood work, liver and kidney function tests) for treatment control purposes.CONCLUSIONS The plaintiffs resorted to legal action to get access to biological medications because they were either unaware or had difficulty in accessing them through institutional public health system procedures. Access by means of legal action facilitated long-term use of this type of medication through irregular prescriptions and led to a high rate of adverse drug reactions as well as inappropriate clinical monitoring.

Trends in the use of antidepressants among older adults: Bambuí Project

OBJECTIVE To analyze the trends and factors associated with the antidepressant use among older adults. METHODS This population-based study evaluated older adults in 1997 (n = 351, baseline) and the survivors at the 15th follow-up year (n = 462, in 2012) among the aging cohort of Bambuí. The prevalence of antidepressant use was estimated, and the most commonly used antidepressants each year were identified. Prevalence ratios with 95% confidence intervals were estimated using Poisson regression with robust variance to investigate differences in the prevalence of use between 1997 and 2012. RESULTS The overall consumption of antidepressants (PR = 2.87, 95%CI 1.94;4.25) and of selective serotonin reuptake inhibitors (PR = 7.50, 95%CI 3.74;15.02) was significantly higher in 2012. However, no significant difference was observed in the use of tricyclic antidepressants between the two cohorts (PR = 0.89, 95%CI 0.49;1.62). In the 2012 cohort, antidepressant use was associated with females, increased age, increased income (≥ 4 minimum wages), self-assessment of health as reasonable, and attending ≥ 5 medical consultations in the last 12 months. CONCLUSIONS The increased consumption of antidepressants in the period due to increased use of selective serotonin reuptake inhibitors was consistent with results observed in international studies of different population groups and contexts. The positive correlation observed between antidepressant use and family income may be a warning of possible inequalities in access to mental health services.

Cyclosporine versus tacrolimus: cost-effectiveness analysis for renal transplantation in Brazil

OBJECTIVE To analyze the cost-effectiveness of treatment regimens with cyclosporine or tacrolimus, five years after renal transplantation.METHODS This cost-effectiveness analysis was based on historical cohort data obtained between 2000 and 2004 and involved 2,022 patients treated with cyclosporine or tacrolimus, matched 1:1 for gender, age, and type and year of transplantation. Graft survival and the direct costs of medical care obtained from the National Health System (SUS) databases were used as outcome results.RESULTS Most of the patients were women, with a mean age of 36.6 years. The most frequent diagnosis of chronic renal failure was glomerulonephritis/nephritis (27.7%). In five years, the tacrolimus group had an average life expectancy gain of 3.96 years at an annual cost of R$78,360.57 compared with the cyclosporine group with a gain of 4.05 years and an annual cost of R$61,350.44.CONCLUSIONS After matching, the study indicated better survival of patients treated with regimens using tacrolimus. However, regimens containing cyclosporine were more cost-effective.

Exposição profissional a chumbo : utilização da protoporfirina-zinco (PPZ) na vigilância de saúde de trabalhadores ex

Resumo Uma estratégia de avaliação e prevenção de riscos na exposição a agentes químicos deve ter sempre em conta que a vigilância do ambiente de trabalho e a da saúde dos trabalhadores são aspectos complementares de uma mesma realidade – os riscos resultantes da interacção entre um agente químico e os trabalhadores a ele expostos. Se à Vigilância Ambiental compete apreciar o risco, pela caracterização do agente no ambiente de trabalho, a Vigilância Biológica pronuncia-se sobre a interacção entre o tóxico e o organismo, avaliando a resposta à agressão química e a evolução das reacções de adaptação ou de desajuste face à absorção do tóxico. Os Indicadores Biológicos, deste modo, assumem um estatuto de instrumento privilegiado na vigilância da saúde dos trabalhadores expostos, na medida em que medem a quantidade de tóxico que efectivamente penetrou e foi absorvido, ou o resultado (efeito) determinado por essa mesma dose. O presente estudo procura contribuir para a definição de um quadro metodológico de utilização dos Indicadores Biológicos na avaliação/gestão da exposição profissional ao chumbo, designadamente apreciando a variação da protoporfirina-zinco (PPZ), indicador até ao presente ainda não utilizado em Portugal. O chumbo é um metal de ocorrência natural, cujos níveis nos diversos ecossistemas resultam, principalmente, das actividades antropogénicas de natureza doméstica e industrial. A sua capacidade poluente é assinalável, representando uma fonte de exposição permanente para o homem, demonstrável pela sua constante presença no organismo apesar de não desempenhar qualquer tipo de função fisiológica. São actualmente inúmeras as suas aplicações, tornando a exposição profissional ao chumbo uma realidade vasta: indústrias de acumuladores eléctricos, de vidros, de plásticos e de munições, construção civil, manutenção e reparação automóvel e de navios, fabrico de tintas, indústrias electrónicas, fundições e actividades de soldadura são, entre outras, situações onde é uma realidade a ter em conta. A penetração dos compostos inorgânicos de chumbo no organismo efectua-se principalmente por via respiratória, não sendo, no entanto, desprezável, a sua penetração por via digestiva. As partículas absorvidas são transportadas pelo sangue principalmente ligadas aos eritrocitos (95%), distribuem-se pelos tecidos moles e depositam-se essencialmente no tecido ósseo, onde representam mais de 90% da carga corporal do total absorvido e tendo aí um elevado tempo de semi-vida (mais de 20 anos). Não é metabolizado no organismo e a sua eliminação efectua-se essencialmente por via renal,sendo igualmente excretado, em menor escala, através das fezes, do suor, da saliva, das faneras e do leite materno. O conhecimento científico evidencia que concentrações sanguíneas de chumbo entre 20 e 50 mg/dL são susceptíveis de determinar efeitos adversos no homem, podendo ser afectados o sistema hematopoiético, o sistema nervoso, o sistema cardiovascular, o sistema reprodutor e o sistema imunitário. Contudo, ainda muito há a clarificar no âmbito da toxicidade do chumbo. Os níveis de exposição a que correspondem as alterações nos diversos órgãos e sistemas continuam a ser motivo de alguma controvérsia. As características carcinogénicas e mutagénicas do chumbo são, ainda, um campo de vasta exigência de investigação. A intoxicação por chumbo e seus sais (Saturnismo) de origem ocupacional é reconhecida em Portugal como doença profissional (grupo 1 - Doenças Provocadas por Agentes Químicos, da Lista das Doenças Profissionais). É uma intoxicação do tipo crónico, fruto da absorção contínua de doses relativamente pequenas durante longo período, evidenciando-se no seu início por sinais e sintomas vagos e difusos de grande inespecificidade, que podem incluir, nomeadamente, perda de apetite, sabor metálico na boca, palidez, mal-estar e fadiga, cefaleias, mialgias e artralgias, irritabilidade, tremores finos, obstipação, cólicas abdominais, insónias, déficit da memória de curto prazo e da capacidade de concentração. Um importante conjunto de indicadores biológicos pode ser utilizado na vigilância periódica da saúde de trabalhadores nestas condições de exposição. Tais indicadores (de dose ou de efeito), encerram diferentes significados e comportam distintas exigências, competindo ao Médico do Trabalho, no âmbito dos programas de prevenção dos efeitos adversos relacionados com a exposição profissional a chumbo, seleccionar a sua utilização e interpretar a sua informação, de modo a avaliar a interacção do tóxico com o organismo numa fase de reversibilidade. O presente estudo envolveu 180 trabalhadores dos quais 110 apresentavam plumbémias (Pb-S) iguais ou superiores a 40 mg/dL. Além da Pb-S, a todos foi doseada a protoporfirina-zinco (PPZ) e efectuado o Hemograma e a cerca de 25% foi determinada a concentração do ácido d-aminolevulínico urinário (ALA-U). Os doseamentos da PPZ efectuados em amostra de sangue capilar através de um hematofluorímetro portátil revelaram-se de total fiabilidade, dando significado a uma técnica de fácil execução e baixo custo. A avaliação do tipo de colheita urinária para doseamento do ALA-U concluiu pela necessidade de recurso a urinas de 24 horas.Os resultados do estudo evidenciaram uma elevada associação entre a PPZ e a Pb-S, com uma maior magnitude e de início mais precoce do que o que registado na associação da Pb-S com o ALA-U. Revelaram, ainda, fracos níveis de associação da hemoglobina (e outros parâmetros hematológicos) com a Pb-S. E demonstraram para um cut-off de 100 mg/ dL de PPZ, taxa de falsos negativos e falsos positivos, para plumbémias a partir de 70 mg/dL, inferiores a 20%. Assim, concluiu-se que, nos protocolos de vigilância de saúde de trabalhadores expostos a chumbo, o doseamento da PPZ por hematofluorímetro, em sangue de colheita capilar, é adequado, fiável e de realização preferencial em relação ao do ALA-U. Concluiu-se, também, que a realização do hemograma apenas se justifica em situações individuais que clinicamente o tornem aconselhável. E que estes protocolos devem incluir a realização da Pb-S e da PPZ, podendo, em situações de controlo rigoroso (ambiental, biológico e clínico), basear-se apenas na determinação da PPZ reservando os outros indicadores para aprofundar a investigação médica nos casos de taxas elevadas desta ou de situações limitantes. ■ Résumée Une stratégie d’évaluation et de prévention des risques d’exposition aux agents chimiques doit toujours tenir en considération que la vigilance du lieu de travail et de la santé des travailleurs sont des aspects complémentaires d’une même réalité – les risques résultant d’une interaction entre l’agent chimique et les travailleurs exposés. Si c’est à la Vigilance Ambiantale de juger le risque, par la caractérisation de l’agent dans le lieu de travail, la Vigilance Biologique, elle, se prononce sur l’interaction entre le toxique et l’organisme, évaluant la réponse à l’agression chimique et l’évolution des réactions d’adaptation ou de rupture face à l’absorption du toxique. Les Indicateurs Biologiques assument ainsi un statut d’instrument privilégié de vigilance de la santé des travailleurs exposés, dans la mesure où ils déterminent la quantité de toxique qui a effectivement été pénétré et absorbé, ou le résultat (effet) déterminé par cette dose. Cette étude-ci cherche à contribuer à la définition d’un cadre méthodologique d’utilisation des Indicateurs Biologiques dans l’évaluation/ gestion de l’exposition professionnelle au plomb inorganique, évaluant spécialement le comportement de la protoporphirine-zinc (PPZ), indicateur pas encore utilisé au Portugal.Le plomb est un métal d’occurrence naturelle dont les niveaux dans les différents écosystèmes en résultent, principalement, des activités anthropogéniques de nature domestique et industrielle. Sa capacité polluante peut être signalée, représentant une source d’exposition permanente pour l’homme, celle-ci démontrable par sa présence continue dans l’organisme, même si elle n’y accomplit aucune fonction physiologique. Actuellement ses applications sont innombrables, faisant de l’exposition professionnelle au plomb une réalité de grande ampleur : industries d’accumulateurs électriques, de verre, de plastique et de munitions, bâtiments, manutention et réparation automobile et navale, fabrication d’encres, industries électroniques, fontes et activités de soudure sont, entre autres, des situations réelles a en tenir compte. La pénétration du plomb inorganique dans l’organisme se fait principalement par voie respiratoire, pouvant se faire également par voie digestive. Les particules absorbées sont transportées par le sang, surtout liées aux érythrocytes (95%), se repartent à travers les tissus mous et se déposent essentiellement dans le tissu osseux, où elles représentent plus de 90% de la charge corporelle de ce qui a été absorbé et ont un temps de demi-vie élevé (plus de 20 ans). Le plomb n’est pas métabolisé dans l’organisme et son élimination se fait essentiellement par voie rénale, pouvant tout de même, à une moindre échelle, être excrété dans les fèces, de la sueur, de la salive, des ongles, des cheveux et du lait maternel. La connaissance scientifique met en évidence que des concentrations sanguines de plomb entre 20 et 50 mg/dL sont susceptibles de déterminer des effets adverses dans l’homme, pouvant les systèmes hématopoïétique, nerveux, cardiovasculaire, reproducteur et immunitaire en être affectés. Cependant, il en reste beaucoup à éclaircir dans le domaine de la toxicité du plomb. Les niveaux d’exposition auxquels correspondent les modifications des divers organes et systèmes, demeurent toujours sujet de quelque controverse. Les caractéristiques carcinogèniques et mutagèniques du plomb restent toujours un champ d’investigation d’une grande exigence. L’intoxication par le plomb et ses sels (Saturnisme) d’origine occupationnelle est reconnue, au Portugal, comme une maladie professionnelle (groupe 1- Maladies Provoquées par des Agents Chimiques, de la Liste des Maladies Professionnelles). C’est une intoxication du tipe chronique, due à l’absorption continue de doses relativement petites pendant une longue période, mise en évidence à travers des signes et des symptômes vagues et diffus sans grande spécificité, lesquels peuvent inclure, particulièrement, le manque d’appétit, goût métallique dans la bouche, pâleur, malaise et fatigue, céphalées, myalgies et arthralgies, irritabilité, tremblements fins, constipation, coliques abdominales, insomnies, déficit de la mémoire à court terme et de la capacité de concentration.Un ensemble important d’indicateurs biologiques peut être employé dans la vigilance périodique de la santé des travailleurs dans ces conditions d’exposition. Ces indicateurs (de dose ou d’effet) renferment différentes significations et comportent diverses exigences, devant le Médecin de Travail, dans le domaine des programmes de prévention des effets adverses qui sont en relation avec l’exposition professionnelle au plomb, sélectionner son utilisation et interpréter son information de façon à évaluer l’interaction de l’élément toxique avec l’organisme à un stade de réversibilité. L’étude ci-présent engloba 180 travailleurs desquels 110 présentaient des plombémies (Pb-S) égales ou supérieures à 40 mg/dL. À part la Pb-S, la protoporphyrine-zinc (PPZ) leur a été prise en dosage et un Hémogramme fut effectué et fut déterminé l’acide d- aminolévulinique urinaire (ALA-U) sur environ 25% des travailleurs. Le dosage de la PPZ efectué en échantillon de sang capillaire par un fluorimètre portable, s’est accomplit d’une fiabilité total, donnant du sgnificat à une téchnique de facile execution et bas prix. L’évaluation de la prise urinaire par dosage du ALA-U conclut au besoin d’un recours aux urines de 24 heures Les résultats de l’étude ont mis en évidence une association élevée entre la PPZ et la Pb- S, avec une intensité majeure et de début plus précoce par rapport à celui qui fut registré lors de l’association de la Pb-S avec la ALA-U. Ces résultats ont également montré de faibles niveaux d’association entre l’hémoglobine (et autres paramètres hématologiques) et la Pb-S. Ils ont démontré aussi, une valeur de cut-off de 100 mg/dL de PPZ, des taux de faux négatifs et faux positifs, pour des plombémies de 70 mg/dL, inférieurs à 20%. On peut donc conclure que dans les protocoles de vigilance de la santé des travailleurs exposés au plomb, le dosage de la PPZ par fluorimetrie dans le sang capillaire est adéquat, fiable et de réalisation préférentielle par rapport à celui du ALA-U. On peut également conclure que la réalisation de l’hémogramme ne se justifie que dans les cas individuels où, cliniquement, celui-ci est conseillé. De plus, ces protocoles doivent inclure la réalisation de la Pb-S et de la PPZ, pouvant, en cas de contrôle rigoureux (ambiantal, biologique et clinique), s’appuyer que dans la détermination de la PPZ réservant les autres indicateurs pour approfondir l’investigation médicale dans les cas où les taux de celle-ci sont élevés ou dans les cas de situations limitantes. ■ Summary Any strategy to evaluate and prevent the risks of chemical agents exposure must always regard the work environment and workers health as complementary aspects of one reality - the resulting risks from the interaction between the chemical agent and the exposed workers. It is the responsibility of Environmental Monitoring to evaluate the risks of exposure by the characterization of the chemical agent in the work environment. Biological Monitoring, on the other hand, pronounces itself over the toxin and body interaction, evaluating human response to the chemical aggression and the body adaptations to the toxic absorption. Biological Exposure Indices (BEI) assume, therefore, a privileged status among exposed workers' health monitoring instruments, as they measure the actual penetrated and absorbed toxic quantity and the effect it produces. This research study aims to contribute to the definition of a methodological strategy on the utilization of BEI’s in evaluating inorganic lead's occupational exposure, more specifically appreciating the zinc protoporphyrin (ZPP) variation, an index that has never been taken under consideration in Portugal until now. Lead is a natural metal whose ecosystem’s levels are mainly due to domestic and industrial anthropogenic activities. Its pollutant capacity is notable, representing a permanent exposure risk shown by its constant presence in the human body, although it has no physiologic function. Nowadays, lead's applications are countless, turning its professional exposure a huge reality: storage batteries industries, glass industries, plasterers and munitions industries, building construction, ships and motor car maintenance and repairing, ink manufacture, electronics industries, foundries and other soldering activities are, among so many other, realities to attend to. Respiration is the main cause of human body's inorganic lead absorption, although digestive pathway must not to be ignored. The absorbed particles are transported by blood, essentially bounded to erythrocytes (95%). It is distributed by soft tissues and settled mainly on bone tissues, where it represents approximately 90% of the total body charge and has a high half-life time (more than 20 years). It is not metabolized by the organism, its elimination being effectuated by renal activity and, in smaller scale, through lees, sweat, saliva, nails, hair and maternal milk.Scientific knowledge shows that concentrations of lead in blood between 20 e 50 mg/dL are susceptible to determine adverse effects in man and able to affect the hematopoietic system, the nervous system, the cardiovascular system, the reproductive system and the immunological system. Nevertheless, there's still much to be learned and clarified about lead's toxicity. The correlation between exposure levels and human's systems and organs alteration levels continues to be a centre of controversies. Still, lead's carcinogenic and mutagenic characteristics continue to be a high demanding research field. Intoxication by lead and its compounds (saturnism), from occupational origin, is recognized in Portugal as an occupational disease, included in Group 1 - Chemical Agents Caused Diseases, on the Occupational Diseases List. It is a chronic intoxication caused by a continuous absorption of small doses, throughout a long period of time. Its signs and symptoms are diffuse and imprecise, of great unspecificity, such as loss of appetite, metallic flavor in the mouth, paleness, ailment and fatigue, headaches, myalgia and arthralgia, irritability, thin tremors, constipation, abdominal pain, insomnias, short memory loses and inability to concentrate. A considered number of BEI’s can be used in Periodic Health Monitoring of workers in such exposure conditions. Such BEI (dose indices or effect indices) provide different meanings and imply different procedures, being Occupational Doctors responsibility, in the context of lead related adverse effects preventive programmes, to select and interpret its information, in order to evaluate the interaction between toxic and organism in a reversible phase of the toxic action. The present research study involved 180 workers, 110 of which presented blood lead levels (PbB) above or equal to 40 mg/dL. Besides PbB, all workers has been evaluated for zinc protoporphyrin levels (PPZ) and submitted to a haemogram. About 25% of the workers were selected for d-aminolevulinic urinary acid (ALA-U) determination. The evaluation of PPZ, by a portable hematofluorometer using capillary blood samples, turned out to be an easy procedure with low costs and total warrantability. As in regard for ALA- U procedure, it was concluded the necessity of 24 hours urine samples. This research results underlined a strong connection between ZPP and PbB, which was found to to be stringer and to begin earlier than it was registered for PbB and ALA-U association. The same study also revealed a low association level between PbB and hemoglobin or other hematological indices. It was also verified less than 20% of false negatives and false positives cases when admitted a ZPP 100 mg/dL cut off value for PbB³ 70 mg/dL. As in result it was concluded that in Health Monit

Characterization of the Toxicological Effects of Aminocarb on Rats: Hematological, Biochemical, and Histological Analyses

Aminocarb is a widely applied carbamate insecticide with action of controlling pests such as Lepidoptera and Coleoptera. In this study, subchronic effects on Wistar rats were investigated using hematological, biochemical, and histological techniques. Rats were exposed orally at sublethal levels of 10, 20, or 40 mg/kg body weight (groups A, B, and C, respectively) for 14 d. Hematological results revealed no statistical differences after 1 d of exposure but significant reduction in white blood cells detected after 7 d of exposure in group C, as well as, in all treated groups after 14 d of exposure. Biochemical data showed a decrease of acetylcholinesterase activity in all groups after 1 d of exposure with a return to normal after 7 and 14 d. Significant increase in alkaline phosphatase activity of rats exposed to aminocarb was noted after 7 d of treatment. The levels of triglycerides were also significantly decreased. The present investigation also showed a significant increase in content of serum urea and creatinine in animals from group A (14 d), and from groups B and C (7 and 14 d). Histological results demonstrated hemorrhagic focus on hepatic and renal parenchyma in all exposed groups. Taken together, the attained results were dose dependent and indicated adverse effects of aminocarb on hepatic and renal functions, as well as on immune responsiveness at sublethal tested doses.

Utilização de PAM's e Medicamentos e/ou Produtos à base de Plantas pela População do Concelho de Bragança

Introdução: Entende-se por fitoterapia a terapêutica caracterizada pelo uso de plantas medicinais nas diferentes formas farmacêuticas com finalidade terapêutica, usada assim para prevenir, atenuar ou curar um estado patológico. Objetivos: Caracterizar a utilização de plantas aromáticas e medicinais (PAM´s), medicamentos e produtos à base de plantas pela população do concelho de Bragança, conhecer a fonte de indicação deste tipo de produtos, apurar a relação entre a fonte de indicação e o estado de saúde após a utilização, verificar a sua correta utilização relativa à indicação terapêutica, modo e frequência de utilização, identificar potenciais interacções medicamentosas, averiguar se os utentes informam o médico do seu uso, investigar a ocorrência de efeitos adversos e apurar a relação entre os efeitos adversos ocorridos e o género dos inquiridos. Métodos: Trata-se de um estudo observacional analítico-transversal. Nele participaram 404 indivíduos de ambos os géneros e com idades compreendidas entre os 18 e os 89 anos. A recolha de dados foi realizada entre os meses de abril e junho de 2014, através de um questionário estruturado de autopreenchimento, formado por 30 perguntas. Após a recolha dos dados procedeu-se à leitura óptica dos questionários, sendo os dados posteriormente exportados para SPSS permitindo assim o tratamento dos mesmos. Para análise estatística utilizou-se o teste do qui-quadrado considerando o nível de significância p <0,05. Resultados: Verificou-se que 53,7% dos inquiridos recorre terapeuticamente a PAM´s que inclui principalmente o uso de cidreira e camomila enquanto 33,8% faz uso de medicamentos e/ou produtos àbase de plantas nomeadamente Valdispert e Daflon. A utilização de PAM,s é motivada por autoconhecimento e indicação de familiares, amigos e vizinhos. Já os medicamentos e/ou produtos à base de plantas são utilizados maioritariamente por prescrição médica e indicação na farmácia. A ocorrência de efeitos indesejáveis foi sentida unicamente com a utilização de PAM´s e em pequena escala. Conclusão: O recurso a este tipo de produtos é uma prática bastante comum entre os moradores do concelho de Bragança, que utilizam uma grande diversidade de plantas e produtos à base de plantas para um variado leque de indicações terapêuticas, apontando a percentagem de respostas para um conhecimento dos seus efeitos terapêuticos.