Adherence and/or discontinuation of imatinib mesylate in patients with chronic myeloid leukemia

Adherence to imatinib mesylate improves clinical outcomes and promotes a reduction in health expenditure. However, treatment duration and lack of efficacy decrease adherence to pharmacotherapy, resulting in increased mortality associated with Chronic Myeloid Leukemia. This study aimed to evaluate and compare adherence and/or discontinuation of imatinib mesylate in different studies from the literature. An integrative review of original articles published between the years of 2004 and 2014 was performed using the databases PubMed/MEDLINE, Scopus and SciELO. The descriptor "imatinib" was used in two combinations employing the connector AND between terms: "medication adherence'' AND ''imatinib" AND "leukemia'' and ''patient compliance'' AND "imatinib" AND "leukemia". We identified 476 studies, being 14 included in the study. The rates of adherence and discontinuation were diverse, ranging from 19.0 to 97.0% and from 1.8 and 41.0%, respectively, and a high number of longitudinal studies was observed (71.4%). Most studies used questionnaires as an indirect method to assess adherence and factors related to poor adherence were adverse drug reactions, dose changes and unavailability of the medication. Patient education associated with follow up by pharmacists and other health professionals can improve patient adherence and minimize the pharmacotherapy discontinuation

Cost-effectiveness of insulin analogs from the perspective of the Brazilian public health system

Human insulin is provided by the Brazilian Public Health System (BPHS) for the treatment of diabetes, however, legal proceedings to acquire insulin analogs have burdened the BPHS health system. The aim of this study was to perform a cost-effectiveness analysis to compare insulin analogs and human insulins. This is a pharmacoeconomic study of cost-effectiveness. The direct medical cost related to insulin extracted from the Ministry of Health drug price list was considered. The clinical results, i.e. reduction in glycated hemoglobin (HbA1c), were extracted by meta-analysis. Different scenarios were structured to measure the uncertainties regarding the costs and reduction in HbA1c. Decision tree was developed for sensitivity of Incremental Cost Effectiveness Ratio (ICER). A total of fifteen scenarios were structured. Given the best-case scenario for the insulin analogs, the insulins aspart, lispro, glargine and detemir showed an ICER of R$1,768.59; R$ 3,308.54; R$11,718.75 and R$ 2,685.22, respectively. In all scenarios in which the minimum effectiveness was proposed, lispro, glargine and detemir were dominant strategies. Sensitivity analysis showed that the aspart had R$3,066.98 [95$ 6,163.97 [95% CI: 3919.29; 11401.57] for incremental costs. We concluded there was evidence that the insulin aspart is the most cost-effective

Pharmacists in dispensing drugs (PharmDisp): protocol for a clinical trial to test the effectiveness of distance education in training pharmacists for dispensing drugs

Dispensing drug is a moment in which the pharmacist is able to analyze pharmacotherapy and contribute to its rational use. However, research has shown that some pharmacists lack adequate knowledge to perform this service. This study aims to describe a research protocol for a clinical trial to test the effectiveness of a distance learning program to train pharmacists in dispensing drugs. This is a protocol for an open diagnostic, non-randomized, single group clinical trial. A 12-week duration distance learning course was structured on the Moodle platform for training community pharmacists who are registered in the Regional Board of Pharmacy and work as employees or owners in Brazilian community pharmacies. The course curricula involves concepts and practice of dispensing drugs applied to the treatment of hypertension, diabetes mellitus, dyslipidemia and asthma. Pharmacists are divided randomly into groups, to which previously selected tutors give directions to the discussion and clarify questions. A validated questionnaire is being used before and after the course to measure participants’ knowledge. Participant satisfaction with the course is also being measured. Pharmacists who work in the study headquarters municipality receive two visits from a mystery shopper, before and after the course, to evaluate their performance in dispensing drugs. The virtual platform and the content of the course material were evaluated by judges. The study has been approved by the Research Ethics Committee of the School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo. The sample size was estimated to provide desired power for testing the significance of the difference between baseline-to-endpoint change scores. Information about the course is being released through channels such as social networks. The results will be submitted for publication in scientific journals, but information enabling the identification of the study subjects will be kept confidential. The trial has been registered in The Brazilian Clinical Trials Registry with number RBR7mbrp3 on January 15th, 2015

Pharmacoepidemiological profile and polypharmacy indicators in elderly outpatients

This cross-sectional study was carried out with 1000 elderly outpatients assisted by a Basic Health District Unit (UBDS) from the Brazilian Public Health System (SUS) in the municipality of Ribeirão Preto. We analyzed the clinical, socioeconomic and pharmacoepidemiological profile of the elderly patients in order to identify factors associated with polypharmacy amongst this population. We used a truncated negative binomial model to examine the association of polypharmacy with the independent variables of the study. The software SAS was used for the statistical analysis and the significance level adopted was 0.05. The most prevalent drugs were those for the cardiovascular system (83.4%). There was a mean use of seven drugs per patient and 47.9% of the interviewees used &gt;7 drugs. The variables that showed association with polypharmacy (P value < 0.01) were female gender, age &gt;75 years, self-medication, number of health problems, number of medical appointments, presence of adverse drug events, use of over-the-counter drugs, use of psychotropic drugs, lack of physical exercise and use of sweeteners. The exposition to all these factors justified the high prevalence of polypharmacy amongst the interviewees. These results showed the need to adopt clinical intervention and educational and managerial measures to analyze and promote rationality in the use of drugs amongst the elderly users of SUS.Este estudo transversal foi realizado por meio de entrevistas com 1000 idosos atendidos em uma Unidade Básica Distrital de Saúde (UBDS) do Sistema Único de Saúde (SUS) no município de Ribeirão Preto. Analisou-se o perfil clínico, socioeconômico e farmacoepidemiológico a fim de identificar os fatores associados à polifarmácia nessa população. Utilizou-se um modelo binomial negativo truncado para análise da associação da polifarmácia com as variáveis independentes do estudo. O software SAS foi utilizado para a análise estatística. O nível de significância adotado foi de 0,05. Os fármacos com maior prevalência de uso foram do sistema cardiovascular (83,4%). Observou-se média de, aproximadamente, sete fármacos por paciente e 47,9% dos entrevistados usavam &gt;7 fármacos. As variáveis que apresentaram associação com a polifarmácia (p< 0,01) foram: mulheres, idade (&gt;75 anos), automedicação, quantidade de problemas de saúde, número de consultas médicas, uso de medicamentos isentos de prescrição médica, uso de psicotrópicos, não realização de exercícios físicos e uso de adoçante. A exposição a todos esses fatores justifica a alta prevalência de polifarmácia entre os entrevistados. Os resultados mostraram a necessidade de adotar medidas de intervenção clínica e educacional e gerencial para analisar e promover a racionalização do uso de fármacos entre os idosos usuários do SUS

Studies of micronuclei and other nuclear abnormalities in red blood cells of Colossoma macropomum exposed to methylmercury

The frequencies of micronuclei (MN) and morphological nuclear abnormalities (NA) in erythrocytes in the peripheral blood of tambaqui (Colossoma macropomum), treated with 2 mg.L−1 methylmercury (MeHg), were analyzed. Two groups (nine specimens in each) were exposed to MeHg for different periods (group A - 24 h; group B - 120 h). A third group served as negative control (group C, untreated; n = 9). Although, when compared to the control group there were no significant differences in MN frequency in the treated groups, for NA, the differences between the frequencies of group B (treated for 120 h) and the control group were extremely significant (p < 0.02), thus demonstrating the potentially adverse effects of MeHg on C. macropomum erythrocytes after prolonged exposure

Cost-effectiveness of insulin analogs from the perspective of the Brazilian public health system

ABSTRACT Human insulin is provided by the Brazilian Public Health System (BPHS) for the treatment of diabetes, however, legal proceedings to acquire insulin analogs have burdened the BPHS health system. The aim of this study was to perform a cost-effectiveness analysis to compare insulin analogs and human insulins. This is a pharmacoeconomic study of cost-effectiveness. The direct medical cost related to insulin extracted from the Ministry of Health drug price list was considered. The clinical results, i.e. reduction in glycated hemoglobin (HbA1c), were extracted by meta-analysis. Different scenarios were structured to measure the uncertainties regarding the costs and reduction in HbA1c. Decision tree was developed for sensitivity of Incremental Cost Effectiveness Ratio (ICER). A total of fifteen scenarios were structured. Given the best-case scenario for the insulin analogs, the insulins aspart, lispro, glargine and detemir showed an ICER of R$1,768.59; R$ 3,308.54; R$11,718.75 and R$ 2,685.22, respectively. In all scenarios in which the minimum effectiveness was proposed, lispro, glargine and detemir were dominant strategies. Sensitivity analysis showed that the aspart had R$3,066.98 [95$ 6,163.97 [95% CI: 3919.29; 11401.57] for incremental costs. We concluded there was evidence that the insulin aspart is the most cost-effective

A influência da síndrome de ovários policísticos e síndrome metabólica na escolha do tipo de parto: revisão de literatura

Introduction: Polycystic Ovary Syndrome (PCOS) and Metabolic Syndrome (MS) are interconnected through various physiological pathways, and their coexistence may have significant implications, especially during pregnancy and the childbirth process. During pregnancy, women with PCOS and MS may face an increased risk of obstetric complications. Regarding the impact on childbirth, PCOS and MS can influence the choice of the type of delivery. Methodology: This work constitutes a literature review, following the systematization with the five pillars described below. 1) Problem statement: "What is the influence of PCOS and MS on the choice of the type of delivery?". 2) Relevant studies were identified using the PUBMED platform with the descriptors "Metabolic Syndrome, Polycystic Ovary Syndrome, Parturition, Pregnancy," PUBMED all in accordance with MESH. 3) Initially, 11 studies were selected; 4 were discarded after a thorough reading as they did not contribute to the problem statement. 4) Data extraction was performed using a text editing program. 5) Experts were consulted. Results: The studies revealed that PCOS and MS are associated with a clinically significant increase in the risk of complications during pregnancy compared to control groups. Additionally, there is a 3 to 4 times higher likelihood of developing pregnancy-induced hypertension and preeclampsia, a threefold increase in the risk of gestational diabetes, and a twofold likelihood of premature birth. The elevated obstetric risk for women with PCOS is reflected in a higher rate of spontaneous abortion. Moreover, it was observed that, compared to the general population, PCOS and MS are more associated with cesarean delivery. Conclusion: Cesarean delivery is predominant in patients with PCOS and MS. Furthermore, there is a higher risk of developing pregnancy-induced hypertension, preeclampsia, and premature birth.Introdução: A síndrome dos ovários policísticos (SOP) e a síndrome metabólica (SM) estão interligadas por várias vias físicas, e sua coexistência pode ter implicações significativas, especialmente durante a gravidez e no processo de parto. Durante a gravidez, as mulheres SOP e SM podem enfrentar um risco aumentado de complicações obstétricas. Quanto ao impacto no parto, a SOP e a SM podem influenciar a escolha do tipo de parto Metodologia: Este trabalho trata-se de uma revisão de literatura, de acordo com a sistematização com os 5 pilares descritos a seguir. 1) Questão problema: “Qual a influência da SOP e SM na escolha do tipo de parto?”. 2) Estudos relevantes foram identificados utilizando na plataforma PUBMED os descritores “Metabolic Syndrome, Polycystic Ovary Syndrome, Parturition, Pregnancy”, na PUBMED, todos de acordo com MESH. 3) 11 estudos foram selecionados inicialmente, 4 foram descartados mediante leitura completa por não contribuir com a questão problema. 4) A extração de dados foi realizada em um programa de edição de texto. 5) Especialistas foram consultados.&nbsp; Resultado: Os estudos revelaram que a SOP e SM estão associadas a um aumento clinicamente significativo no risco de complicações durante a gravidez, em comparação com os grupos de controle. Além disso, há uma probabilidade de 3 a 4 vezes maior de desenvolver hipertensão causada pela gravidez e pré-eclâmpsia, um aumento de 3 vezes sem risco de diabetes gestacional e uma probabilidade duas vezes maior de parto prematuro. O risco obstétrico elevado para mulheres com SOP se reflete em uma maior taxa de aborto espontâneo. Diante disso, observou-se que em relação a população em geral, SOP e SM associam-se mais com o parto cesariano. Conclusão: O parto cesariano é predominante em pacientes com SOP e SM. Além disso, há maior risco de desenvolver hipertensão causada pela gravidez, pré-eclâmpsia e parto prematuro

Trastuzumab use for the treatment of women with HER2-positive breast cancer: a pharmacoepidemiological study

Introdução: O câncer de mama é o segundo tipo de câncer mais frequente no mundo, com cerca de 1,67 milhões de casos novos e 521 mil mortes a cada ano. O câncer de mama pode ser classificado em diferentes grupos, sendo o subtipo HER2 positivo um dos mais agressivos e relacionado a um mal prognóstico. No entanto novas terapias, tendo como alvo o receptor HER2, vem sendo desenvolvidas com a finalidade de melhorar as condições das pacientes. Dentre elas encontra-se o trastuzumabe, um anticorpo monoclonal recombinante humanizado do tipo IgG1, o qual se liga com alta afinidade ao domínio extracelular do receptor HER2. O uso do trastuzumabe está associado a um aumento da taxa de sobrevida de mulheres com câncer de mama HER2 positivo. O trastuzumabe é geralmente bem tolerado, porém pode apresentar alguns eventos adversos dentre eles, a cardiotoxicidade, a qual pode levar à interrupção do tratamento, fazendo com que as pacientes se privem dos benefícios desta terapia medicamentosa. Além desse efeito, outros podem afetar a satisfação da paciente tais como as reações imunes relacionadas à infusão do trastuzumabe, eventos gastrointestinais, fadiga, dentre outros. Com a finalidade de aprimorar os cuidados à saúde, faz-se necessário avaliar os eventos adversos ao tratamento, bem como a qualidade de vida (QV) das mulheres com câncer de mama HER2 positivo que fazem uso do trastuzumabe visando contribuir para o aumento do seu bem-estar e garantir melhores resultados terapêuticos. Objetivo: Avaliar o perfil farmacoepidemiológico das mulheres com câncer de mama HER2 positivo que utilizaram o trastuzumabe atendidas pelo Sistema Único de Saúde, junto ao Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo. Casuística e métodos: O presente trabalho é um estudo observacional, descritivo e quantitativo, o qual foi realizado em duas partes. Parte A: restrospectiva, na qual se avaliou os eventos adversos ao trastuzumabe em monoterapia e/ou combinado com a quimioterapia descritos nos prontuários e por meio de exames laboratoriais e dos resultados do ecocardiograma. Foram utilizados modelos de regressão logística para estimar odds ratios e seus respectivos intervalos de confiança de 95%, com a finalidade de verificar a associação dos eventos adversos mais frequentes e uma série de variáveis sociodemográficas e clínicas das mulheres. Parte B: prospectiva, na qual, além da avaliação dos eventos adversos, foi também avaliada a QV das pacientes por meio do questionário específico para câncer QLQ-C30 e seu módulo de câncer de mama BR-23 da European Organization for Research and Treatment of Cancer (EORTC) em quatro momentos: antes do início da quimioterapia, após o término da quimioterapia, durante o uso do trastuzumabe e após o término do uso trastuzumabe. Análise de variância (ANOVA) para medidas repetidas foi utilizada para as comparações entre os escores médios obtidos das escalas e itens individuais dos questionários. Resultados Parte A: Foram analisados os prontuários de 79 pacientes que iniciaram o trastuzumabe entre 2007 e 2011. A incidência de reações imunes relacionadas a infusão do trastuzumabe aconteceu em 16 (20,3%) pacientes. A cardiotoxicidade ocorreu em 26 (32,9%) pacientes, sendo que treze (16,4%) destas interromperam permanentemente o tratamento, três (3,8%) interromperam temporariamente e 10 xi (12,6%) terminaram o tratamento sem interrupção. Com relação aos outros eventos adversos, os mais frequentes apresentados com o uso da quimioterapia combinada com o trastuzumabe foram dor (20,4%), náusea e vômito (15,9%), febre (9,7%), e neutropenia (7,1%), sendo apresentados por 55,7% das mulheres. Com relação ao uso do trastuzumabe em monoterapia, os mais frequentes foram: dor (19,6%), fadiga (10,8%), náusea e vômito (9,8%), e cefaleia (8,8%) apresentados por 49,4% das mulheres. Com exceção da cardiotoxicidade, nenhum outro evento adverso levou à descontinuação do tratamento. Não foram encontradas associações entre os eventos adversos mais frequentes e as variáveis sociodemográficas e clínicas das pacientes pelos modelos de regressão logística. Resultados Parte B: Dez pacientes foram incluídas no estudo, no período de outubro de 2011 a julho de 2012. Durante o uso do trastuzumabe e após o seu término foi observada uma melhora significativa da QV das pacientes nos parâmetros fadiga e efeitos colaterais sistêmicos, em comparação com o momento em que estavam utilizando os quimioterápicos. Entretanto estudos mais extensos com uma maior população são necessários para que possa ser avaliada a existência de associação entre os dados clínicos e sociodemográficos das pacientes como os resultados de QV. Conclusão: Embora o trastuzumabe seja um medicamento relativamente seguro para o tratamento do câncer de mama HER2 positivo, este pode causas alguns eventos adversos. Na população estudada, o único evento que levou à interrupção do tratamento foi a cardiotoxicidade, entretanto outros estudos mostraram que outros eventos adversos também foram capazes de ocasionar a descontinuação do tratamento. Para tanto são necessários que sejam tomados alguns cuidados para a prevenção e manejo desses eventos adversos, como um acompanhamento mais regular da função cardíaca e monitoramento constante das pacientes durante a infusão do trastuzumabe. Além disso, o trastuzumabe mostrou ter efeito positivo sobre a QV das pacientes. A avaliação da QV é importante, pois fornece informações clínica úteis em relação ao real impacto do tratamento proposto sobre a saúde e bem-estar das pacientes e pode também orientar na busca de estratégicas para minimizar os eventos adversos ao tratamento.Introduction: Breast cancer is the second most common cancer in the world, with about 1.67 million new cases and 521,000 deaths each year. Breast cancer can be classified into different groups, being the HER2 positive subtype one of the most aggressive and related to a poor prognosis. However, new therapies that target the HER2 receptor have been developed in order to improve the conditions of patients. Among them is trastuzumab, a recombinant humanized monoclonal antibody of the IgG1 type, which binds with high affinity to the extracellular domain of the HER2 receptor. The use of trastuzumab is associated with an increase in the survival rate of women with HER2 positive breast cancer. Trastuzumab is generally well tolerated, but may have some adverse events, among them the cardiotoxicity, which can lead to treatment discontinuation, depriving patients of the benefits of this therapy. In addition to this effect, others may affect patient satisfaction such as immune reactions related to the infusion of trastuzumab, gastrointestinal events, fatigue, among others. In order to improve health care, it is necessary to assess treatment adverse events and quality of life (QoL) of women with HER2-positive breast cancer that uses trastuzumab to contribute to the increase in their welfare and ensure better treatment results. Objective: To evaluate the pharmacoepidemiological profile of women with HER2-positive breast cancer that used trastuzumab attended by Brazilian public health system, in the General Hospital of Ribeirão Preto Medical School, University of São Paulo. Patients and methods: This is an observational, descriptive and quantitative study, which was conducted in two parts. Part A: retrospective, in which it was evaluated the adverse events to trastuzumab alone and / or combined with chemotherapy described in the medical records and by laboratory tests and echocardiogram results. We used logistic regression models to estimate odds ratios and their 95% confidence intervals to verify the association of the most frequent adverse events and a number of sociodemographic and clinical variables. Part B: prospective, in which besides the evaluation of adverse events it was also evaluated the QoL of patients through the specific questionnaire QLQ-C30 cancer and its breast cancer module BR-23 from the European Organization for Research and Treatment of Cancer (EORTC) in four moments: before the start of chemotherapy, after the end of chemotherapy, during the use of trastuzumab and after the trastuzumab use. Results Part A: The medical records of 79 patients who started the trastuzumab between 2007 and 2011 were analysed. The incidence of immune reactions related to the infusion of trastuzumab occurred in 16 (20.3%) patients. Cardiotoxicity occurred in 26 (32.9%) patients, and 13 (16.4%) of these permanently discontinued the treatment, three (3.8%) discontinued temporarily and 10 (12.6%) completed treatment without interruption. In relation to the other adverse events, the most common events described with the use of trastuzumab combined with chemotherapy were pain (20.4%), nausea and vomiting (15.9%), fever (9.7%), and neutropenia (7.1%), being presented by 55.7% of women. Regarding the use of trastuzumab in monotherapy, the most common were pain (19.6%), fatigue (10.8%), nausea and vomiting (9.8%) and headache (8.8%) presented by 49.4% of women. Except for cardiotoxicity, no other adverse events led to treatment discontinuation. xiii No associations were found between the most frequent adverse events and the sociodemographic and clinical variables of the patients by logistic regression models. Results Part B: Ten patients were included in the study from October 2011 to July 2012. During the use of trastuzumab and after its completion, a significant improvement in QoL of patients on the parameters fatigue and systemic side effects were observed in comparison with the moment they were using chemotherapy. Nevertheless, larger studies with a larger population are needed in order to evaluate if there is an association between clinical and social demographic data of the patients with the results of QoL. Conclusion: Although trastuzumab is a relatively safe medication for the treatment of HER2 positive breast cancer, it may cause some adverse events. In this population, the only event that led to treatment interruption was cardiotoxicity, although other studies have shown that other adverse events were also able to cause treatment discontinuation. Therefore, some precaution needs to be taken for the prevention and management of those adverse events, such as a more regular monitoring of cardiac function and constant monitoring of patients during trastuzumab infusion. Furthermore, trastuzumab has shown to have a positive effect on patients QoL. The assessment of QoL is important as it provides useful clinical information regarding the real impact of the proposed treatment on the health and welfare of patients and can also guide the search for strategies to minimize treatment adverse events

Modulation of events of humoral and cellular immunity by crude venom and components of Bothrops jararacussu and Bothrops pirajai

Serpentes do gênero Bothrops são responsáveis por 90% dos acidentes ofídicos no Brasil. Seus venenos provocam efeitos locais em humanos e animais, como hemorragia, edema, dor e necrose, caracterizando uma resposta inflamatória, cujo mecanismo não está bem definido. Esses efeitos estão relacionados com a ação combinada de proteases, substâncias que induzem hemorragia e fosfolipases, bem como a liberação de mediadores endógenos gerados pelos venenos. Considerando que a ativação do sistema complemento (SC) e de funções celulares, como quimiotaxia, ativação, proliferação e citotoxicidade podem desempenhar papel importante nos processos inflamatórios e de lesão tecidual subsequentes ao envenenamento, o estudo propõe: a) investigar a capacidade dos venenos brutos de serpentes Bothrops jararacussu e Bothrops pirajai e das toxinas purificadas, serinoprotease de B. jararacussu (SPBj) e L-aminoácido oxidase de B. pirajai (LAAOBp), em modular a atividade do SC; b) avaliar a contribuição do efeito sobre o SC no recrutamento de leucócitos polimorfonucleares humanos (PMN); c) avaliar o potencial citotóxico direto dos venenos e toxinas sobre células mononucleares do sangue periférico humano (PBMC); d) analisar o efeito dos venenos sobre a modulação da expressão dos marcadores de ativação CD69, CD25 e HLA-DR em células T, B e natural killer (NK). Os resultados do ensaio de citotoxicidade mostraram que o veneno bruto de B. jararacussu foi citotóxico para PBMC apenas nas concentrações maiores, de 50 e 100g/mL, não apresentando citotoxicidade nas outras concentrações testadas. A serinoprotease apresentou baixa citotoxicidade para essas células, o que sugere a necessidade de maiores investigações quanto aos mecanismos que levam a essa morte celular. O aumento da viabilidade celular encontrado nas amostras incubadas com veneno bruto e LAAO de B. pirajai sugere possível indução de proliferação celular, que necessita de maiores estudos. Os resultados obtidos sugerem que os venenos brutos de B. jararacussu e B. pirajai são capazes de ativar o SC como observado nos ensaios cinéticos da VCVL e VA e de quimiotaxia de neutrófilos, onde ficou evidenciado que a migração celular foi devida a liberação dos fatores quimiotáticos do SC, C3a e C5a. e que suas respectivas toxinas, serinoprotease e LAAO apresentam efeitos moduladores sobre o SC humano, e estimulam investigações mais aprofundadas com a finalidade de se esclarecer os mecanismos de ação e identificar os componentes responsáveis pelos efeitos observados. Houve expressão aumentada de CD69, CD25 e HLA-DR nas células T CD4+ e CD8+, especialmente quando incubadas com veneno bruto de B. jararacussu e LAAO de B. pirajai, o que reflete ativação da resposta imune celular, e pode sugerir que este tipo de resposta desempenhe papel relevante na indução e/ou controle dos processos imunopatológicos decorrentes de envenenamentos por B. jararacussu e B. pirajai. Esta investigação visa fornecer subsídios para a possível utilização das toxinas para fins terapêuticos e como ferramentas para investigação dos mecanismos envolvidos nos processos fisiopatológicos que ocorrem em decorrência de picadas e também em outras doenças de caráter inflamatório.Snakes of the genus Bothrops are responsible for 90% of snakebites in Brazil. Their venoms cause local effects in humans and animals, such as hemorrhage, edema, pain and necrosis, characteristic of an inflammatory response. The mechanism is not well defined. These effects are related to the combined action of proteases, substances that induce bleeding and phospholipases, as well as release of endogenous mediators generated by the venoms. Considering that activation of the complement system (CS) and cellular functions such as chemotaxis, activation, proliferation and cytotoxicity, may play a role in inflammatory processes and tissue injury following envenomation, the study proposes: a) to investigate the ability of crude venom of B. jararacussu and B. pirajai and the purified toxins, serineprotease of B. jararacussu and L-amino acid oxidase (LAAO) of B pirajai in modulating the activity of the CS, b) to assess the contribution of the effect on CS in the recruitment of human polymorphonuclear leukocytes (PMN), c) to assess the direct cytotoxic potential of venoms and toxins on human peripheral blood mononuclear cells (PBMC), d) to analyse the effect of venoms on the modulation of the expression of activation markers CD69, CD25 and HLA-DR on T, B and natural killer (NK) cells. The results of cytotoxicity assay showed that the crude venom of B. jararacussu was cytotoxic to PBMC only at higher concentrations, 50 and 100g/mL, showing no cytotoxicity in the other concentrations. The serineprotease showed low cytotoxicity to the cells, suggesting the need for further investigations about the mechanisms that lead to this cell death. The increase in cell viability found in samples incubated with crude venom of B. pirajai and LAAO suggests the possibility of induction of cell proliferation, which needs further study. The results suggest that the crude venom of B. jararacussu and B. pirajai are capable of activating the CS as observed in kinetic assays of classical pathwaylectin pathway and alternative pathway and neutrophil chemotaxis assay, where it was shown that cell migration was due to release of CS chemotactic factors, C3a and C5a, and that their respective toxins, serineprotease and LAAO have modulatory effects on human CS, and stimulate further research in order to clarify the mechanisms of action and identify the components responsible for the observed effects. There was increased expression of CD69, CD25 and HLA-DR on CD4+ and CD8+, especially when incubated with crude venom of B. jararacussu and LAAO of B. pirajai. It reflects activation of cellular immune response and may suggest that this type of response play an important role in the induction and/or control of immunopathological processes arising from envenomation by B. jararacussu and B. pirajai. This research aims to provide subsidies to the possible use of the toxin for therapeutic purposes and as tools for investigating mechanisms involved in pathophysiological processes that occur as a result of snakebites and also in other diseases of inflammatory nature