Occurrence of caffeine, fluoxetine, bezafibrate and levothyroxine in surface freshwater of São Paulo State (Brazil) and risk assessment for aquatic life protection.

The prioritization of active pharmaceutical ingredients (APIs) for monitoring programmes and/or environmental risk assessment (ERA) purposes is based on several criteria, including environmental occurrence data. However, data on API occurrence in Brazilian surface freshwaters are still scarce. The Brazilian Unified Health System (SUS) provides several medicines free-of-charge, including medications that have bezafibrate, fluoxetine and levothyroxine as the API. Thus, our objective was to investigate the occurrence of bezafibrate, fluoxetine and levothyroxine in samples collected at sampling sites included in the surface freshwater monitoring program of the São Paulo State Environmental Agency (CETESB); caffeine was also included in the analysis because it is commonly used as an anthropogenic marker of aquatic environment contamination. Monitoring results showed that levothyroxine was not found in any of the analysed samples. Caffeine was ubiquitous in the analysed samples, thus indicating anthropic contamination in the studied water bodies. Caffeine and bezafibrate presented risk quotient (RQ) < 1 for all the sampling sites and periods evaluated in this study. For fluoxetine, RQs > 1 were found in all water samples in which this API was found, indicating a potential risk for freshwater pelagic biota. Thus, fluoxetine should be regulated in São Paulo State in order to protect the aquatic biota. Additional occurrence studies in other Brazilian states are still needed to evaluate if fluoxetine is a nationwide pollutant.

Assessment of the ecotoxicity of the pharmaceuticals bisoprolol, sotalol, and ranitidine using standard and behavioral endpoints.

The pharmaceuticals bisoprolol (BIS), sotalol (SOT), and ranitidine (RAN) are among the most consumed pharmaceuticals worldwide and are frequently detected in different aquatic ecosystems. However, very few ecotoxicity data are available in the literature for them. To help fill these data gaps, toxicity tests with the algae Raphidocelis subcapitata, the macrophyte Lemna minor, the cnidarian Hydra attenuata, the crustacean Daphnia similis, and the fish Danio rerio were performed for assessing the ecotoxicity of these pharmaceuticals. Standard, as well as non-standard endpoint, was evaluated, including the locomotor behavior of D. rerio larvae. Results obtained for SOT and RAN showed that acute adverse effects are not expected to occur on aquatic organisms at the concentrations at which these pharmaceuticals are usually found in fresh surface waters. On the other hand, BIS was classified as hazardous to the environment in the acute III category. Locomotor behavior of D. rerio larvae was not affected by BIS and RAN. A disturbance on the total swimming distance at the dark cycle was observed only for larvae exposed to the highest test concentration of 500 mg L-1 of SOT. D. similis reproduction was affected by BIS with an EC10 of 3.6 (0.1-34.0) mg L-1. A risk quotient (RQ) of 0.04 was calculated for BIS in fresh surface water, considering a worst-case scenario. To the best of our knowledge, this study presents the first chronic toxicity data with BIS on non-target organisms.

Single and mixture toxicity of four pharmaceuticals of environmental concern to aquatic organisms, including a behavioral assessment.

Pharmaceuticals are frequently detected in aquatic environments as mixtures and can cause toxic effects to non-target organisms. We aimed to evaluate the single and mixture effects of the pharmaceuticals metformin, bisoprolol, ranitidine and sotalol using Daphnia similis and Danio rerio. In addition, we aimed to test the predictive accuracy of the mathematical models concentration addition and independent action and to evaluate the nature of the possible toxicological interactions among these pharmaceuticals using the combination index-isobologram model. The acute toxicity of these four pharmaceuticals individually and of their binary mixtures were evaluated using the D. similis tests. Developmental and behavioral effects induced by the pharmaceuticals in quaternary mixtures were evaluated using D. rerio embryos. We observed that most of the binary mixture effects were in the zone between the effects predicted by the concentration addition and the independent action model. The combination index-isobologram model showed to be adequate to describe the nature of possible interactions occurring between the combined pharmaceuticals. Developmental and behavioral acute adverse effects seem not to be induced by the joint action of the quaternary mixture of the evaluated pharmaceuticals on D. rerio embryos, at the concentrations at which they are usually found in surface fresh waters. However, from the results obtained with D. similis, we can conclude that assessing the ecological risk based on the effects of individual pharmaceuticals can underestimate the risk level posed by these environmental contaminants.

Estado nutricional e qualidade de vida em adultos e idosos com depressão / Nutritional status and quality of life in adults and older adults with depression / Estado nutricional y calidad de vida de adultos y mayores con depresión

OBJETIVO: Avaliar o estado nutricional e a qualidade de vida em adultos e idosos com e sem depressão. MÉTODOS: Estudo quantitativo e transversal, com 79 usuários das Unidades Básicas de Saúde de municípios do Vale do Taquari, Rio Grande do Sul. Para determinar os escores dos domínios (físico, psicológico, ambiental e social) de qualidade de vida (QV) foi aplicado o questionário World Health Organization Quality of Life-Bref e um questionário socioeconômico (idade, renda, escolaridade e estado civil). A avaliação antropométrica contemplou peso, estatura, Índice de Massa Corporal, Circunferência da Cintura (CC) e Circunferência do Pescoço (CP). O diagnóstico de depressão foi realizado por psicólogas. O nível de significância máximo assumido foi 5% (p≤0,05), análise realizada através do software SPSS versão 22.0. Utilizaram- se os testes Mann-Whitney, correlação de Pearson e qui-quadrado. RESULTADOS: Verificou-se correlação direta entre idade e domínio físico (p=0,017), psíquico (p<0,01), social (p=0,001) e ambiental (p=0,003). Os homens obtiveram média superior e significativa no domínio ambiental (p=0,009) em relação às mulheres. Os pacientes sem diagnóstico de depressão apresentaram média significativamente superior nos domínios físico (p=0,035) e psicológico (p=0,042). Em relação ao estado nutricional, a magreza e eutrofia apresentaram média superior no domínio físico (p=0,015). CONCLUSÃO: As melhores percepções sobre os domínios de QV foram observadas entre os homens, idosos e participantes sem diagnóstico de depressão. Verificou-se correlação direta entre a idade e todos os domínios e que os participantes depressivos eram, em sua maioria, obesos, com risco cardiovascular e sem risco de excesso de peso.

OBJECTIVE: To assess nutritional status and quality of life in adults and older adults with and without depression. METHODS: This is a quantitative cross-sectional study of 79 users of Primary Health Care Centers located in the municipalities in the Vale do Taquari, Rio Grande do Sul. To determine the scores of the Quality of Life (QoL) domains (physical, psychological, environmental and social) we used the World Health Organization Quality of Life-Bref questionnaire and a socioeconomic questionnaire (age, income, education and marital status). Anthropometric measurement included weight, height, Body Mass Index, Waist Circumference (WC) and Neck Circumference (NC). Diagnosis of depression was given by psychologists. The maximum significance level assumed was 5% (p≤0.05) and the analysis was performed using SPSS version 22.0. The Mann-Whitney test, the Pearson's correlation coefficient and the Chi-squared test were used. RESULTS: There was a direct correlation between age and the physical (p=0.017), psychological (p<0.01), social (p=0.001) and environmental (p=0.003) domains. Men scored significantly higher in the environmental domain (p=0.009) compared with women. Patients without a diagnosis of depression scored significantly higher in the physical (p=0.035) and psychological (p=0.042) domains. As for nutritional status, thinness and normal weight were associated with higher mean scores in the physical domain (p=0.015). CONCLUSION: The best perceptions of QoL domains were observed among men, older adults and participants without a diagnosis of depression. There was a direct correlation between age and all the domains, and depressive participants were mostly obese and presented cardiovascular risk, but without risk of presenting excess weight.

OBJETIVO: Evaluar el estado nutricional y la calidad de vida de adultos y mayores con y sin depresión. MÉTODOS: Estudio cuantitativo y transversal con 79 usuarios de las Unidades Básicas de Salud de los municipios del Vale de Taquari, Rio Grande do Sul. Se ha aplicado el cuestionario World Health Organization Quality of Life-Bref y un cuestionario socioeconómico (edad, renta, escolaridad y estado civil) para determinar las puntuaciones de los dominios (físico, psicológico, ambiental y social) de la calidad de vida (CV). En la evaluación antropométrica se ha incluido el peso, la estatura, el Índice de Masa Corporal, la Circunferencia de la Cintura (CC) e la Circunferencia del Cuello (CC). El diagnóstico de depresión ha sido realizado por psicólogas. El nivel de significación máxima asumido ha sido del 5% (p≤0,05) y el análisis ha sido realizado a través del software SPSS versión 22.0. Se utilizaron las pruebas de Mann-Whitney, la correlación de Pearson y el chi-cuadrado. RESULTADOS: Se verificó la correlación directa entre la edad y el dominio físico (p=0,017), el psíquico (p<0,01), el social (p=0,001) y el ambiental (p=0,003). Los hombres tuvieron la media superior y significativa para el dominio ambiental (p=0,009) en comparación a las mujeres. Los pacientes sin el diagnostico de depresión presentaron la media significativamente superior para los dominios físico (p=0,035) y el psicológico (p=0,042). Respecto el estado nutricional, la delgadez y la eutrofia presentaron media superior para el dominio físico (p=0,015). CONCLUSIÓN: Las mejores percepciones de los dominios de CV han sido observadas entre los hombres, los mayores y los participantes sin el diagnostico de depresión. Se verificó la correlación directa entre la edad y todos los dominios y que los participantes depresivos eran, en su mayoría, obesos, con riesgo cardiovascular y sin riesgo de exceso de peso.

Assessment of the single and mixture ecotoxicity of pharmaceuticals of environmental concern using aquatic test organisms / Avaliação da ecotoxicidade individual e das misturas de fármacos de preocupação ambiental usando organismos-teste aquáticos

Pharmaceuticals are contaminants of emerging concern which have been a target of increasing attention by the scientific community. Pharmaceuticals presenting high consumption, incomplete metabolism and incomplete removal at wastewater treatment plants have been frequently detected in aquatic ecosystems worldwide. This is the case of the pharmaceuticals metformin (MET), bisoprolol (BIS), sotalol (SOT) and ranitidine (RAN). However, ecotoxicity data for these contaminants are scarce, especially regarding behavior effects and chronic toxicity. In addition, the knowledge regarding the joint toxicity of these pharmaceuticals on non-target organisms is still incipient, which makes their environment risk assessment uncertain. This study aimed to fill these knowledge gaps for these four pharmaceuticals, by carrying out toxicity tests using five test organisms from three trophic levels. Different endpoints were assessed in tests with Raphidocelis subcapitata (algae), Lemna minor (macrophyte), Daphnia similis (crustacean), Hydra attenuate (cnidarian) and Danio rerio (fish). The binary and quaternary mixture acute toxicity for these pharmaceuticals were assessed on D. similis and D. rerio embryo tests, respectively. This study also aimed to evaluate the predictive accuracy of the Concentration addition (CA) and the Independent action (IA) classic models. In addition, the nature of the possible toxicological interactions between the pharmaceuticals in binary mixtures were also evaluated, using the Combination Index-isobologram (CI) method. The modelling of the concentration-response curves and the associated statistical analyses were performed using the automated spreadsheet ToxCalcMix v.1.0 and the software OriginPro 2015. The software CompuSyn was used for performing the mixture analyses with the CI method. The experimental planning of the binary mixture tests was performed using the fractioned factorial design, in order to cover several possible ratio and level-dependent effects with a reduced number of test organisms. The results obtained in this study are shown in four articles. In article 1, we provided a critical review and discussed the misunderstandings, deficiencies and data gaps on the ecotoxicity data of pharmaceuticals and personal care products mixtures published in the literature. In the following articles, the results obtained from the single and mixture toxicity tests performed in this study were presented and discussed. The pharmaceuticals MET (article 2) and BIS (article 3) were classified as hazardous to the aquatic environment, in the acute toxicity category. However, an ecological risk is not expected for the pelagic freshwater species exposed to these two pharmaceuticals, based on the chronic data obtained. The results obtained from the mixture toxicity tests (article 4) showed that most of the observed toxicity effects from the binary mixtures were in the zone between the predicted effects by the CA and IA models. The CI model showed to be an useful tool to describe the possible toxicological interactions occurring between the pharmaceuticals in joint action. Even statistically significant non-effect concentrations of the pharmaceuticals added up to induce significant adverse effects in mixtures (something from nothing). It was concluded that ecological risk assessment based on single toxic effects can underestimate the real impact of environmental contaminants on aquatic ecosystems

A contaminação ambiental por fármacos tem sido alvo de crescente preocupação pela comunidade científica. Fármacos de elevado consumo, incompleto metabolismo e remoção incompleta em estações de tratamento de esgoto, como é o caso da metformina (MET), bisoprolol (BIS), sotalol (SOT) e ranitidina (RAN), têm sido frequentemente detectados em matrizes aquáticas do mundo todo. Apesar disso, dados ecotoxicológicos consistentes para esses contaminantes são escassos, principalmente com relação a efeitos comportamentais e oriundos de estudos crônicos. Além disso, o entendimento dos efeitos de suas ações combinadas em organismos não-alvo é ainda incipiente, o que gera incertezas na avaliação dos seus riscos ambientais. Esta pesquisa teve por objetivo preencher essas lacunas de conhecimentos para esses quatro fármacos, por meio da realização de testes com cinco diferentes organismos-teste de três diferentes níveis tróficos. Foram analisados diferentes parâmetros avaliativos em testes com os organismos aquáticos Raphidocelis subcapitata (alga), Lemna minor (macrófita), Daphnia similis (crustáceo), Hydra attenuata (cnidário) e Danio rerio (peixe). As toxicidades agudas das misturas binárias e quaternárias desses quatro fármacos também foram avaliadas em testes com D. similis e embriões de D. rerio, respectivamente. Este trabalho também teve por objetivo avaliar a acurácia preditiva dos modelos de adição de concentração (CA) e ação independente (IA) e analisar a natureza das possíveis interações toxicológicas entre os fármacos, em misturas binárias, usando o modelo do Índice de Combinação (CI). A modelagem das relações concentração-resposta e as análises estatísticas associadas foram realizadas empregando-se a planilha automatizada ToxCalcMix versão 1.0 e o software OriginPro 2015. O software CompuSyn foi utilizado para as análises envolvendo o CI. O planejamento experimental dos testes de misturas binárias foi realizado por meio do design fatorial fracionado, a fim de cobrir diversas possíveis interações em várias proporções e níveis de efeitos, com a redução do número de organismos-teste. Os resultados desta pesquisa estão apresentados em quatro artigos. No artigo 1, realizou-se uma revisão crítica com relação às lacunas de conhecimentos e deficiências identificadas a partir da análise da literatura sobre a ecotoxicologia de misturas de fármacos e de produtos de higiene pessoal. Nos artigos seguintes, foram apresentados e discutidos os resultados oriundos dos testes com os quatro fármacos avaliados neste estudo. Os fármacos MET (artigo 2) e BIS (artigo 3) foram classificados como perigosos para o ambiente aquático, na categoria de toxicidade aguda. Contudo, um risco ecológico não é esperado para as espécies pelágicas de água doce expostas a esses dois fármacos, com base nos dados de toxicidade crônica obtidos. Os resultados dos testes de misturas (artigo 4) permitiram concluir que a maior parte dos efeitos observados das misturas binárias estiveram na zona entre os efeitos preditos pelos modelos clássicos de CA e IA. O modelo do CI mostrou-se uma ferramenta útil para descrever a natureza das possíveis interações toxicológicas que ocorrem entre os fármacos em ações combinadas. Mesmo concentrações de nenhum efeito estatisticamente significativo dos fármacos causaram efeitos adversos significativos quando em misturas (something from nothing). Concluiu-se que avaliações de risco ecológicas baseadas em efeitos tóxicos individuais de contaminantes ambientais podem subestimar o real impacto desses compostos em ecossistemas aquáticos

Ecotoxicological effects, water quality standards and risk assessment for the anti-diabetic metformin.

Metformin (MET) is among the most consumed pharmaceuticals worldwide. This compound has been frequently detected in fresh surface water. However, ecotoxicological information for MET is still too limited, particularly regarding chronic and behavioral data. This study aimed to help filling these knowledge gaps, by carrying out both acute and chronic studies with four different test organisms from three different trophic levels. We assessed different endpoints, including the swimming behavior of Danio rerio larvae. We also derived both short-term and long-term environmental quality standards (EQS) for the protection of freshwater pelagic biota towards MET adverse effects. A risk quotient (RQ) was calculated for MET in fresh surface water, considering a worst-case scenario. Daphnia similis was by far the most sensitive species evaluated. An EC10 of 4.4 mg L-1 was obtained from the reproduction test with D. similis. A long-term EQS of 88 µg L-1 was derived and a RQ of 0.38 was obtained. An ecological risk is not expected for the chronic exposure of pelagic freshwater species to MET, considering the endpoints and the standard bioassays usually recommended in standard protocols. However, endocrine disruptive effects and potential interactive effects of MET with other co-occurring contaminants cannot be ruled out. To the best of our knowledge, this study presents the first data related with MET effects on population endpoints of D. similis and Hydra attenuata, as well as on the locomotor activity of D. rerio.

Lethal and sublethal toxicity of abamectin and difenoconazole (individually and in mixture) to early life stages of zebrafish.

In recent years, the need for the development of alternative test methods for the conventional acute fish toxicity test (AFT) with adult fish has often been discussed. In addition, concerns have been raised on the potential risks related with environmentally realistic pesticide mixtures since risk evaluations have traditionally been based on individual pesticides. The insecticide/acaricide abamectin and the fungicide difenoconazole are the main pesticides that are intensively used in Brazilian strawberry crop and are hence likely to occur simultaneously in edge-of-field waterbodies. The aim of the present study was therefore to evaluate the lethal and sublethal toxicity of single and mixture exposures of these pesticides to zebrafish early life stages (embryos and juveniles). By comparing the derived toxicity data of the individual compounds with that previously determined for zebrafish adults, the order of life stage sensitivity was juvenile > adult > embryo. The pesticide mixture revealed a dose-level dependent deviation of the independent action model, with antagonism at low dose levels and synergism at high dose levels. Sublethal parameters (especially those related with locomotion) were considerably more sensitive than lethality. Subsequently, the inclusion of sublethal parameters may greatly improve the sensitivity of FET tests and hence its suitability as a substitution of adult fish testing in risk assessment evaluations.

Efectiveness of the waveone and ProTaper D systems for removing gutta-percha with or without a solvent.

Endodontic retreatment requires complete removal of the filling material and access to the apical foramen. The purpose of this study was to evaluate the effectiveness of the Wave One reciprocating system and compare it to the ProTaper D rotarysystem, with or without the use of a solvent, in removing filling material from root canals. The time required for each filling removal technique employed was also determined and compared. Forty extracted human mandibular premolars with a single, straight, flattened canal were prepared and filled. They were divided into four groups (n = 10): Group 1: ProTaper D Ni Ti rotary instruments; Group 2: ProTaper D Ni Tirotary instruments, with a solvent; Group 3: Wave One primary instrument; and Group 4: Wave One primary instrument, with a solvent. The teeth were then split along their long axis and photographed using an operating microscope with 5Xmagnification. The amount of remaining filling material was assessed with Image Tool software. The results were compared using the Kruskal Wallis test (p <0.05). There was no significant difference between groups regarding the amount of residual filling material (p > 0.05). Operative time was significantly longer in Group 3 than in groups 1, 2 and 4 (p <0.05). The Wave One system and the ProTaper D system were equally effective, with or without a solvent. The time required to remove the filling material from the canals was significantly longer in Group 3 than in the other groups.

No retratamento endodôntico, a completa remoção do material obturador e o acesso ao forame apical são necessários para permitir a limpeza do sistema de canais. O propósito deste estudo foi avaliar a eficácia do sistema reciprocante WaveOne ecomparálaao sistema rotatório ProTaper Universal, com ousem o uso de solvente, na remoção do material obturador. O tempo necessário a cada técnica empregada foi determinado e comparado. Quarenta pré-molares inferiores humanos extraídoscom canal único, reto e achatado foram preparados e obturados. Foram então divididos em quatro grupos (n = 10) de acordo como sistema utilizado, como segue. Grupo 1: ProTaper D Niti; Grupo 2: Sistema ProTaper D com solvente; Grupo 3: Sistema WaveOne instrumento Primary; e Grupo 4: Sistema WaveOne instrumento Primary com solvente, sendo o tempo registrado. Os dentes foram clivados longitudinalmente e fotografados utilizando microscópio operatório com aumento de 5 vezes. A quantidade de material remanescente foi avaliada com o uso do software Image Tool 3.0. Os resultados foram comparados utilizando o teste de Kruskal Wallis(p < 0.05). Em relação aos resultados, não houve diferença significativa entre os gruposquanto à quantidade de material obturador residual (p > 0.05). O tempo operatório no Grupo 3 foi significativa mente maior do que nos grupos 1, 2 e 4 (p < 0.05). O sistema WaveOne foi tão efetivo quanto o ProTaper D, com ou sem solvente. tempo necessário à des obturação dos canais no Grupo 3 (WaveOne sem solvente) foi significativamente maior do que nos demais grupos.

Effectiveness of the waveone and protaper D systems for removing gutta-percha with or without a solvent / Eficiência dos sistemas waveone e protaper D na remoção de guta-percha com ou sem uso solvente

Endodontic retreatment requires complete removal of the filling material and access to the apical foramen. The purpose of this study was to evaluate the effectiveness of the WaveOne reciprocating system and compare it to the ProTaper D rotary system, with or without the use of a solvent, in removing filling material from root canals. The time required for each filling removal technique employed was also determined and compared. Forty extracted human mandibular premolars with a single, straight, flattened canal were prepared and filled. They were divided into four groups (n = 10): Group 1: ProTaper D NiTi rotary instruments; Group 2: ProTaper D NiTi rotary instruments, with a solvent; Group 3: WaveOne primary instrument; and Group 4: WaveOne primary instrument, with a solvent. The teeth were then split along their long axis and photographed using an operating microscope with 5X magnification. The amount of remaining filling material was assessed with Image Tool software. The results were compared using the KruskalWallis test (p <0.05). There was no significant difference between groups regarding the amount of residual filling material (p > 0.05). Operative time was significantly longer in Group 3 than in groups 1, 2 and 4 (p < 0.05). The WaveOne system and the ProTaper D system were equally effective, with or without a solvent. The time required to remove the filling material from the canals was significantly longer in Group 3 than in the other groups.

No retratamento endodôntico, a completa remoção do material obturador e o acesso ao forame apical são necessários para permitir a limpeza do sistema de canais. O propósito deste estudo foi avaliar a eficácia do sistema reciprocante WaveOne e comparála ao sistema rotatório ProTaper Universal, com ou sem o uso de solvente, na remoção do material obturador.O tempo necessário a cada técnica empregada foi determinado e comparado. Quarenta prémolares inferiores humanos extraídos com canal único, reto e achatado foram preparados e obturados. Foram então divididos em quatro grupos (n = 10) de acordo com o sistema utilizado, como segue. Grupo 1: ProTaper D Niti; Grupo 2: Sistema ProTaper D com solvente; Grupo 3: Sistema WaveOne instrumento Primary; e Grupo 4: Sistema WaveOne instrumento Primary com solvente, sendo o tempo registrado. Os dentes foram clivados longitudinalmente e fotografados utilizando microscópio operatório com aumento de 5 vezes.A quantidade de material remanescente foi avaliada com o uso do software Image Tool 3.0. Os resultados foram comparados utilizando o teste de KruskalWallis( p < 0.05). Em relação aos resultados, não houve diferença significativa entre os grupos quanto à quantidade de material obturador residual (p > 0.05). O tempo operatório no Grupo 3 foi significativa mente maior do que nos grupos 1, 2 e 4 (p < 0.05).O sistema WaveOne foi tão efetivo quanto o ProTaper D, com ou sem solvente.tempo necessário à desobturação dos canais no Grupo 3 (WaveOne sem solvente) foi significativamente maior do que nos demais grupos.

Occurrence, ecotoxicological effects and risk assessment of antihypertensive pharmaceutical residues in the aquatic environment--A review.

This study presents a review of the investigated antihypertensives in different aquatic compartments. It aims to compare these data with those regarding ecotoxicity effects in order to find out ecotoxicological data gaps for these pharmaceuticals and to point out the need for future studies. In addition, part of this article is dedicated to the risk assessment of the parent compounds atenolol, metoprolol, propranolol and verapamil, which are of great environmental concern in terms of contamination levels and for which there are sufficient ecotoxicological data available. 79 articles were retrieved presenting quantization data for 34 different antihypertensives and/or their metabolites. Only 43 articles were found regarding acute and chronic ecotoxicological effects of antihypertensive drugs. The results indicated that the beta-blockers atenolol, metoprolol and propranolol are the antihypertensives most frequently detected in the aquatic environment. They are also the drugs which reached the highest maximum concentrations in surface waters in the data reported in the literature. The highest percentages of ecotoxicity data regarding antihypertensives were also related to these beta-blockers. On the other hand, there is clearly a lack of ecotoxicity data, especially the chronic ones, regarding other antihypertensives. The environmental risk assessment (ERA) showed that all three of the evaluated beta-blockers can pose a potential long-term risk for non-target organisms of both fresh and marine water species. However, more meaningful ecotoxicity data for antihypertensives, including saltwater species, are required to refine and enlarge these results. Additional studies focusing on potential interactions between pharmaceutical mixtures, including antihypertensives, are also an urgent need.

Ecotoxicological evaluation of propranolol hydrochloride and losartan potassium to Lemna minor L. (1753) individually and in binary mixtures.

Antihypertensive pharmaceuticals, including the beta-blockers, are one of the most detected therapeutic classes in the environment. The ecotoxicity of propranolol hydrochloride and losartan potassium was evaluated, both individually and combined in a binary mixture, by using the Lemna minor growth inhibition test. The endpoints evaluated in the single-pharmaceutical tests were frond number, total frond area and fresh weight. For the evaluation of the mixture toxicity, the selected endpoint was frond number. Water quality criteria values (WQC) were derived for the protection of freshwater and saltwater pelagic communities regarding the effects induced by propranolol and losartan using ecotoxicological data from the literature, including our data. The risks associated with both pharmaceutical effects on non-target organisms were quantified through the measured environmental concentration (MEC)/predicted-no-effect concentration (PNEC) ratios. For propranolol, the total frond area was the most sensitive endpoint (EC50 = 77.3 mg L(-1)), while for losartan there was no statistically significant difference between the endpoints. Losartan is only slightly more toxic than propranolol. Both concentration addition and independent action models overestimated the mixture toxicity of the pharmaceuticals at all the effect concentration levels evaluated. The joint action of both pharmaceuticals showed an antagonistic interaction to L. minor. Derived WQC assumed lower values for propranolol than for losartan. The MEC/PNEC ratios showed that propranolol may pose a risk for the most sensitive aquatic species, while acceptable risks posed by losartan were estimated for most of aquatic matrices. To the authors knowledge these are the first data about losartan toxicity for L. minor.

A supervisão como processo educativo: Construindo o paradigma de redução de danos emancipatória com uma equipe de CAPS-AD / Supervision as an educative process: Building Emancipatory Harm Reduction paradigm with a mental health team

Introdução: O consumo contemporâneo de drogas ocupa lugar de destaque nas políticas públicas e na mídia. Diferentes formas de enfrentar a problemática vêm se apresentando, sendo uma delas a Redução de Danos Emancipatória, um movimento social antiproibicionista baseado no desenvolvimento de crítica sobre a realidade a fim de transformá-la. Objetivo: Discutir processo de supervisão em um Centro de Atenção Psicossocial para álcool e outras Drogas, CAPS-AD de uma cidade do estado de São Paulo com a finalidade de transformar as práticas da equipe de saúde, refletindo sobre o processo de produção em saúde e os processos de trabalho. Método: Compreendeu-se a supervisão como processo educativo emancipatório, utilizando-se o referencial teórico da Saúde Coletiva. Seis encontros foram realizados com a equipe do serviço. Resultados: A supervisão configurou-se como processo educativo crítico, visando à emancipação dos usuários e trabalhadores do serviço. Discussão: O processo de supervisão pautado no referencial crítico possibilitou o desenvolvimento de práticas da equipe de saúde fundamentadas na Redução de Danos Emancipatória.(AU)

Introduction: The contemporary drug consumption has been highlighted in the public policies and by the media. Different forms of coping with this issue are being constructed. Emancipatory Harm Reduction, an antiprohibitionist social movement based on the development of critical conscience about the reality in order to transform it, is one of them. Objective: To discuss the supervision process of a public community mental health institution focused on treatment of problematic consumption of drugs in a municipality of the state of San Paulo, aiming to transform the mental health team practices, reflecting about the health production process and their work process. Method: A Collective Health theoretical framework was used to base the supervision in an emancipatory educative process. The process occurred in six meetings with the health care team. Results: The supervision was configured as a critical educative process, and its objective was the emancipation of the institution’s workers and users. Discussion: The supervision process based on critical theoretical framework enhanced the development of the mental health team practices, based on Emancipatory Harm Reduction.(AU)

A supervisão como processo educativo: construindo o paradigma de redução de danos emancipatória com uma equipe de CAPS-AD / Supervision as an educative process: building emancipatory harm reduction paradigm with a mental health team

INTRODUÇÃO: O consumo contemporâneo de drogas ocupa lugar de destaque nas políticas públicas e na mídia. Diferentes formas de enfrentar a problemática vêm se apresentando, sendo uma delas a Redução de Danos Emancipatória, um movimento social antiproibicionista baseado no desenvolvimento de crítica sobre a realidade a fim de transformá-la. OBJETIVO: Discutir processo de supervisão em um Centro de Atenção Psicossocial para Álcool e outras Drogas, CAPS-AD de uma cidade do estado de São Paulo com a finalidade de transformar as práticas da equipe de saúde, refletindo sobre o processo de produção em saúde e os processos de trabalho. MÉTODO: Compreendeu-se a supervisão como processo educativo emancipatório, utilizando-se o referencial teórico da Saúde Coletiva. Seis encontros foram realizados com a equipe do serviço. RESULTADOS: A supervisão configurou-se como processo educativo crítico, visando à emancipação dos usuários e trabalhadores do serviço. DISCUSSÃO: O processo de supervisão pautado no referencial crítico possibilitou o desenvolvimento de práticas da equipe de saúde fundamentadas na Redução de Danos Emancipatória

IINTRODUCTION: The contemporary drug consumption has been highlighted in the public policies and by the media. Different forms of coping with this issue are being constructed. Emancipatory Harm Reduction, an antiprohibitionist social movement based on the development of critical conscience about the reality in order to transform it, is one of them. OBJECTIVE: To discuss the supervision process of a public community mental health institution focused on treatment of problematic consumption of drugs in a municipality of the state of San Paulo, aiming to transform the mental health team practices, reflecting about the health production process and their work process. METHOD: A Collective Health theoretical framework was used to base the supervision in an emancipatory educative process. The process occurred in six meetings with the health care team. RESULTS: The supervision was configured as a critical educative process, and its objective was the emancipation of the institution's workers and users. DISCUSSION: The supervision process based on critical theoretical framework enhanced the development of the mental health team practices, based on Emancipatory Harm Reduction

Linfoma canino: clínica, hematologia e tratamento com o protocolo de Madison-Wisconsin / Canine lymphoma: clinical and hematological aspects and treatment with the Madison-Wisconsin protocol

O linfoma é uma neoplasia de elevada incidência na população canina mundial, e que apresenta sinais clínicos diversos, dependentes da classificação anatômica e da extensão da doença. Este estudo objetivou avaliar as características clínicas e hematológicas de cães com linfoma no momento do diagnóstico, além da evolução clínica dos mesmos ao longo do tratamento com o protocolo de Madison-Wisconsin. Dos 18 cães inseridos no estudo, 50 por cento apresentaram a forma multicêntrica da doença e 33 por cento a forma cutânea. A manifestação clínica mais comum foi a linfadenomegalia superficial, acompanhada dos sinais sistêmicos de hiporexia, apatia e perda de peso. As principais alterações hematólogicas foram anemia normocítica normocrômica, trombocitopenia e leucocitose, associadas às síndromes paraneoplásicas. Vinte e sete por cento dos animais atingiram remissão completa da doença e apenas 22 por cento atingiram sobrevida de um ano. Houve correlação positiva entre o valor do hematócrito e o tempo de sobrevida para os cães que morreram, demonstrando a influência da anemia no prognóstico dos animais. Sugere-se que o estágio avançado da doença no momento do diagnóstico tenha influenciado as baixas taxas de remissão e sobrevida obtidas neste estudo.

Lymphoma is a neoplasm of high incidence in dogs, and has several clinical signs, depending on the tumor anatomical area and the extent of the disease. This study aimed to evaluate the clinical and hematological findings in dogs with lymphoma at diagnosis, and the clinical evolution during Madison-Wisconsin chemotherapy protocol. Of the 18 dogs that underwent the study, 50 percent of the dogs had the multicentric form and 33 percent the cutaneous forms of the disease. The most common clinical sign was superficial lymphadenomegaly, combined to systemic signs of hyporexia, apathy and weight loss. The main hematological changes were anemia, thrombocytopenia and leukocytosis, associated with paraneoplastic syndromes. Complete remission was achieved in 27 percent of the animals and the one-year survival rate was 22 percent. There was a positive correlation between the hematocrit and survival time in dogs that died, which indicates the importance of anemia in the prognosis. It is suggested that the advanced stage of the disease may have contributed to the low remission and survival rates observed in this study.

Quantificação de células CD34+ do sangue do cordão umbilical de cães / Quantification of CD34+ hematopoietic stem cells from the umbilical cord of dogs

As células-tronco promovem a reconstituição hematopoética e de outros tecidos, estando presentes no embrião, no sangue periférico, na medula óssea e no sangue do cordão umbilical (SCU). Os modelos experimentais de células-tronco do sangue periférico e da medula óssea em cães têm propiciado informações relevantes para transplantes de células-tronco em humanos. Entretanto, não existe estudo sobre as células-tronco no SCU canino no Brasil. O objetivo deste ensaio foi quantificar as células nucleadas e as células-tronco CD34+ no SCU de cães para propostas de reconstituição hematológica. No presente protocolo experimental, a coleta de SCU de 40 cães neonatos foi realizada para contagem das células nucleadas no contador automático de células sangüíneas e contagem das células-tronco CD34+ no citômetro de fluxo. O método de coleta do SCU na porção justaplacentária dos vasos umbilicais permitiu a quantificação das células-tronco CD34+. Os valores das células nucleadas do SCU foram reduzidos em relação àqueles do sangue periférico de cães sadios recém-nascidos e adultos. Apesar do volume escasso de SCU (1325µL), a quantidade de células-tronco do cordão umbilical canino (3,38±2,72 CD34+ x10(6) kg-1) é semelhante àquela reportada para medula óssea, bem como para o sangue periférico mobilizado de cães adultos, sendo coincidente com aquela preconizada para reconstituição hematopoética.

Stem cells promote the reconstitution of the hematopoietic and other tissues, and are present in the embryo, peripheral blood, bone marrow and umbilical cord blood (UCB). The experimental models of bone marrow and peripheral blood stem cells in dogs provide important information for stem cells transplants in humans. However, there are no studies on the UCB cells of dogs in Brazil. This experiment aimed at quantifying nucleated and stem cells in the umbilical cord of dogs having as its purpose the hematological recuperation. In this assay, UCB of 40 neonates dogs was collected for nucleated cell count in automatic cell counter and stem cell CD34+ count in flow cytometer. The method of UCB collection at the juxta-placental portion of the umbilical vessels allowed UCB blood and stem cell CD34+ quantification. The nucleated cell values of UCB were reduced as compared to the reference values of the peripheral blood of healthy neonate and adult dogs. Despite the small volume of UCB (1325µL), the quantity of stem cells in the canine umbilical cord (3.38±2.72 CD34+ x10(6) kg-1) is similar to that reported in the bone marrow and mobilized peripheral blood of adult dogs, coinciding with the amount recommend for hematopoetic reconstitution.

Autologous bone marrow transplantation in a dog with lymphoma: a clinical study / Transplante autólogo de medula óssea em um cão com linfoma: ensaio clínico

The objective of this study is to provide the first report of bone marrow transplantation (BMT) in dogs in Brazil. A Rottweiler with cutaneous lymphoma was submitted to a twelve-week Madison-Wisconsin chemotherapy protocol followed by autologous bone marrow transplantation. For this, 10mL kg-1 of bone marrow was collected simultaneously from both iliac crests and cryopreserved in a freezer at -80°C. The conditioning step was performed by administering cyclophosphamide by intravenous route at 400mg m-2. Bone marrow was reinfused after defrosting in a water bath at 37°C. Bone marrow nucleated cell counts before and after freezing, showed a small relative loss of nucleated cells (35.10 and 31.80x10³µL-1 , respectively). Cyclophosphamide induced neutropenia which was reverted by a granulocyte colony-stimulating factor (G-CSF) capable of stimulating hematopoetic reconstitution. On the day 360 after transplant the patient was found to be in complete remission. This study indicates that autologous BMT in a dog with lymphoma submitted to myelosuppressive chemotherapy was potentially safe and effective.

Este estudo teve como objetivo descrever o primeiro relato de transplante de medula óssea (TMO) em cães no Brasil. Para tanto, um rottweiller com linfoma cutâneo foi submetido ao protocolo quimioterápico de Madison-Wisconsin pelo período de 12 semanas, seguido pelo transplante autólogo de medula óssea. Para tanto, 10mL kg-1 de medula óssea foram coletados de ambas as cristas ilíacas do paciente, simultaneamente; sendo o volume final criopreservado em freezer a -80°C. A etapa de condicionamento foi realizada com a administração da ciclofosfamida, por via intravenosa, na dose de 400mg m-2. A reinfusão da medula óssea foi realizada após o descongelamento da bolsa em banho-maria a 37°C. As contagens de células nucleadas de alíquotas obtidas da bolsa de medula óssea antes do congelamento e após o descongelamento demonstram pequena perda relativa de células nucleadas (35,10 e 31,80 x10³µL-1, respectivamente). A neutropenia decorrente da ciclofosfamida foi revertida com a administração de um fator estimulador de colônia de granulócitos (G-CSF), que foi capaz de acelerar a reconstituição hematopoética. O paciente encontra-se no dia + 360 pós-transplante em remissão completa da doença. Este trabalho indicou que o TMO autólogo em um cão com linfoma, submetido à quimioterapia mielossupressora, foi potencialmente seguro e efetivo.

Perfil eletroforético de proteínas séricas do sangue do cordão umbilical de cães / Electrophoretic profile of serum proteins from the umbilical chord blood of dogs

A importância do estudo do sangue do cordão umbilical (SCU) tem sido verificada pela presença de células-tronco hematopoéticas no SCU humano. O modelo experimental em cão tem propiciado informações importantes nos transplantes em humanos. Entretanto, apesar da importância do SCU e do modelo experimental em cães, não existem estudos sobre a eletroforese de proteínas séricas do cordão umbilical canino. No presente protocolo experimental, foi feita a colheita de SCU de 20 neonatos caninos, o qual foi utilizado para o fracionamento eletroforético de suas proteínas. Os valores médios absolutos obtidos para proteínas séricas totais, albumina, alfa, beta e gamaglobulinas no sangue do cordão umbilical de cães ao nascimento foram 3,09±0,59; 1,51±0,38; 0,87±0,17; 0,68±0,12 e 0,03±0,01, respectivamente. Todos os resultados apresentaram-se abaixo dos níveis reportados para animais adultos, devido à passagem das proteínas e suas frações ocorrerem principalmente através do colostro e pela imaturidade hepática. Em todos os traçados eletroforéticos do SCU de cães, foi observada uma pequena curva entre alfaglobulina 2 e betaglobulina 1, não relatada no soro de cães adultos. Portanto, neste experimento, foram observadas diferenças quantitativas no traçado eletroforético das proteínas séricas do SCU de cães, ao nascimento, diferindo-os, neste particular, de cães em diferentes fases da vida pós-colostral.

Characterization and quantification of blood cells from the umbilical cord of dogs.

BACKGROUND: Models for the study of hematopoietic stem cells in dogs provide important information for bone marrow transplantation in humans. Recent studies have reported the importance of human umbilical cord blood (UCB) as an alternative to allogenic bone marrow for hematopoietic reconstitution. However, there are no studies on the UCB cells of dogs. OBJECTIVE: The aim of this experiment was to characterize and quantify the blood cells of the umbilical cord of dogs. METHODS: The blood of the umbilical cord of 20 neonatal dogs, delivered at term, with a median gestation time of 58 days, was collected with a 5-mL syringe containing EDTA. Total RBC, WBC, and platelet counts, HCT, hemoglobin (Hgb) concentration, and RBC indices were determined using an automatic cell counter. The differential leukocyte count was determined manually in blood smears stained with May-Grünwald-Giemsa. Reticulocyte percentages were determined on blood smears stained with brilliant cresyl blue and counterstained with May-Grünwald Giemsa. RESULTS: The MCHC and numbers of RBCs, WBCs, neutrophils, and eosinophils in UCB were lower as compared with reference values for the peripheral blood of healthy neonatal and adult dogs; whereas, the MCV and reticulocyte percentages were higher. CONCLUSION: Erythrocyte macrocytosis and hypochromasia in UCB were consistent with marked reticulocytosis and indicative of high erythropoietic activity. The results of this study are an important first step in the characterization of UCB from neonatal dogs.

Influência do tipo de parto na hematologia do cordão umbilical de cães / Influence of the kind of delivery in the dog umbilical cord hematology

O sangue do cordão umbilical humano tem sido crescentemente utilizado como fonte de células-tronco. Os modelos experimentais de células-tronco da medula óssea, em cães, têm propiciado informações importantes para transplantes medulares em humanos. Vários trabalhos citam a influência do tipo de parto nas características do sangue do cordão umbilical (SCU) humano. Entretanto, não existem relatos sobre a colheita do sangue do cordão umbilical de cães. O objetivo deste ensaio é avaliar a influência do tipo de parto na hematologia do cordão umbilical de cães. No presente protocolo experimental, foram estudados 54 fetos de cães, ao final da vida intra-uterina, provenientes de parto normal (n=24) e cesariana (n=30). A colheita de sangue do cordão umbilical foi realizada com seringa de cinco mL contendo solução anticoagulante EDTA (1mg/1mL sangue). Em seguida, a contagem global de hemácias, leucócitos, plaquetas, a determinação da concentração de hemoglobina, taxa de hematócrito, os índices eritrocitários foram realizados no contador automático de células. A contagem diferencial de leucócitos foi determinada em esfregaços de SCU corados com May-Grunwald-Giemsa (MGG). Com relação ao eritrograma e ao plaquetograma, não houve diferença significativa entre as amostras obtidas em cesarianas e partos normais. Os valores do leucograma do SCU colhido em partos normais foram superiores àqueles obtidos em cesarianas (P<0,05). Portanto, o tipo de parto influencia os valores hematológicos do cordão umbilical de cães.