Poliquistosis renal autosómica dominante: ¿quiénes se benefician del tratamiento con tolvaptán?. Estado del arte / Autosomal dominant polycystic kidney disease. Who can benefit from tolvaptan therapy? State of the art / Doença renal policística autossômica dominante: quem se beneficia do tratamento com tolvaptano? Estado da arte

Resumen: La poliquistosis renal autosómica dominante es la enfermedad renal hereditaria más frecuente. Se caracteriza por la progresiva aparición de quistes renales que suelen conducir a la enfermedad renal crónica extrema en la edad adulta. La aprobación del uso de tolvaptán (antagonista del receptor V2 de la vasopresina) ha marcado un cambio significativo en el tratamiento de esta enfermedad. En los últimos años apareció evidencia que demuestra el beneficio en iniciar tratamiento con tolvaptán en pacientes que presentan una enfermedad con rápida evolución. Se realiza una revisión descriptiva de los principales estudios clínicos publicados en el periodo 2012-2022 y se sugiere un esquema de utilidad para seleccionar aquellos pacientes que pueden beneficiarse del inicio de tratamiento.

Abstract: Autosomal dominant polycystic kidney disease is the most common hereditary kidney disease. It is characterized by the progressive appearance of renal cysts that usually lead to extreme chronic kidney disease in adulthood. The approval of the use of tolvaptán (V2 vasopressin receptor antagonist) has meant a significant change in the treatment of this disease. In recent years, evidence has proved the benefits of initiating treatment with tolvaptán in patients with a rapidly evolving disease. A descriptive review of the main clinical studies published in 2012-2022 period is carried out and a useful scheme is suggested to select those patients who can benefit from the start of treatment.

Resumo: A doença renal policística autossômica dominante é a doença renal hereditária mais comum. Caracteriza-se pelo aparecimento progressivo de cistos renais que geralmente levam à doença renal crônica extrema na idade adulta. A aprovação do uso do tolvaptano (antagonista do receptor de vasopressina V2) marcou uma mudança significativa no tratamento dessa doença. Nos últimos anos, surgiram evidências que demonstram o benefício de iniciar o tratamento com tolvaptano em pacientes com doença de evolução rápida. Faz-se uma revisão descritiva dos principais estudos clínicos publicados no período 2012-2022 e sugere-se um esquema útil para selecionar aqueles pacientes que podem se beneficiar do início do tratamento.

Engagement in primary health care nurses: A cross-sectional study in a Brazilian city.

OBJECTIVE: Professional engagement is an indicator of the relationship between a nurse and the work environment and is an important factor in performance and productivity. The goal of this study was to evaluate levels of engagement among nurses in primary health care units. METHODS: Cross-sectional study in a city of São Paulo state, Brazil, in 2017, using an instrument containing sociodemographic variables and the Utrecht Work Engagement Scale (UWES). RESULTS: In the sample of 75 nurses, the majority were female (94.7%), aged between 29 and 39 (52.0%), specialists (81.3%), married (57.3%), permanent employees (68.0%), working 40 hr per week (98.7%), and working in primary health care for 3-10 years (42.7%). Engagement levels were classified as high in all dimensions. Nurses who worked as managers presented a very high level of dedication; professionals aged 40 years or older presented very high levels in all dimensions (Dedication: 5.2; Absorption: 5.0; Vigor: 5.3; and Overall score: 5.1); and professionals with more than 10 years of experience in primary health care had very high levels in all dimensions (Dedication: 5.0; Absorption: 5.0; Vigor: 5.0; and Overall score: 5.0). CONCLUSIONS: Nurses working in Brazil's primary health care system have high engagement and ability to act; they enhance team performance and quality and effectiveness of care provided.

Zika detection: comparison of methodologies

ABSTRACT Many countries in the Americas have detected local transmission of multiple arboviruses that cause febrile illnesses. Therefore, laboratory testing has become an important tool for confirming the etiology of these diseases. The present study aimed to compare the sensitivity and specificity of three different Zika virus detection assays. One hundred serum samples from patients presenting with acute febrile symptoms were tested using a previously reported TaqMan® RT-qPCR assay. We used a SYBR® Green RT-qPCR and a conventional PCR methodologies to compare the results. Of the samples that were determined to be negative by the TaqMan® RT-qPCR assay, 100% (Kappa = 0.670) were also found to be negative by SYBR® Green RT-qPCR based on Tm comparison; however, 14% (Kappa = 0.035) were found to be positive by conventional PCR followed by agarose gel electrophoresis. The differences between the ZIKV strains circulating worldwide and the low viremia period can compromise diagnostic accuracy and thereby the accuracy of outbreak data. Therefore, improved assays are required to improve the diagnosis and surveillance of arbovirus.

Zika detection: comparison of methodologies.

Many countries in the Americas have detected local transmission of multiple arboviruses that cause febrile illnesses. Therefore, laboratory testing has become an important tool for confirming the etiology of these diseases. The present study aimed to compare the sensitivity and specificity of three different Zika virus detection assays. One hundred serum samples from patients presenting with acute febrile symptoms were tested using a previously reported TaqMan® RT-qPCR assay. We used a SYBR® Green RT-qPCR and a conventional PCR methodologies to compare the results. Of the samples that were determined to be negative by the TaqMan® RT-qPCR assay, 100% (Kappa=0.670) were also found to be negative by SYBR® Green RT-qPCR based on Tm comparison; however, 14% (Kappa=0.035) were found to be positive by conventional PCR followed by agarose gel electrophoresis. The differences between the ZIKV strains circulating worldwide and the low viremia period can compromise diagnostic accuracy and thereby the accuracy of outbreak data. Therefore, improved assays are required to improve the diagnosis and surveillance of arbovirus.

Clinical, laboratory and virological data from suspected ZIKV patients in an endemic arbovirus area.

BACKGROUND: The emergence of Zika virus (ZIKV) presents new challenges to both clinicians and public health authorities. Overlapping clinical features between the diseases caused by ZIKV, dengue (DENV) and chikungunya (CHIKV) and the lack of validated serological assays for ZIKV make accurate diagnosis difficult. Brazilian authorities largely rely on clinical and epidemiological data for the epidemiological and clinical classifications of most ZIKV cases. OBJECTIVE: To report the laboratory and clinical profiles of patients diagnosed with Zika fever based only on clinical and epidemiological data. STUDY DESIGN: We analyzed 433 suspected cases of ZIKV identified by the attending physician based on proposed clinical criteria. The samples were also screened for ZIKV, DENV and CHIKV using PCR. RESULTS: Of the 433 patients analyzed, 168 (38.8%) were laboratory-confirmed for arboviruses: 96 were positive for ZIKV, 67 were positive for DENV (56 for DENV-2, 9 for DENV-1, and 2 for DENV-4), four were positive for co-infection with ZIKV/DENV-2, and one was positive for CHIKV. The most common signs or symptoms in the patients with laboratory-confirmed ZIKV were rash (100%), arthralgia (77.1%), fever (74.0%), myalgia (74.0%) and non-purulent conjunctivitis (69.8%). In patients with laboratory-confirmed DENV infections, the most frequently observed symptoms were rash (100%), fever (79.1%), myalgia (74.6%), headache (73.1%) and arthralgia (70.1%). The measure of association between clinical manifestations and laboratory manifestations among patients with ZIKV and DENV detected a statistically significant difference only in abdominal pain (p=0.04), leukopenia (p=0.003), and thrombocytopenia (p=0.01). CONCLUSION: Our data suggests that clinical and epidemiological criteria alone are not a good tool for ZIKV and DENV differentiation, and that laboratory diagnosis should be mandatory.

Dengue virus surveillance: Detection of DENV-4 in the city of São José do Rio Preto, SP, Brazil.

Dengue viruses are the most common arbovirus infection worldwide and are caused by four distinct serotypes of the dengue virus (DENV). In the present study, we assessed DENV transmission in São José do Rio Preto (SJRP) from 2010 to 2014. We analyzed blood samples from febrile patients who were attended at health care centers in SJRP. DENV detection was performed using multiplex RT-PCR, using flavivirus generic primers, based on the genes of the non-structural protein (NS5), followed by nested-PCR assay with species-specific primers. We analyzed 1549 samples, of which 1389 were positive for NS1 by rapid test. One thousand and eight-seven samples (78%) were confirmed as positive by multiplex RT-PCR: DENV-4, 48.5% (528/1087); DENV-1, 41.5% (449/1087); DENV-2, 9.5% (104/1087); and co-infection (5 DENV-1/DENV-4, 1 DENV-1/DENV-2), 0.5% (6/1087). Phylogenetic analysis of the DENV-4 grouped the isolates identified in this study with the American genotype and the showed a relationship between isolates from SJRP and isolates from the northern region of South America. Taken together, our data shows the detection and emergence of new dengue genotype in a new region and reiterate the importance of surveillance programs to detect and trace the evolution of DENV.

Ambulatório de psiquiatria infantil: prevalência de transtornos mentais em crianças e adolescentes / Children’s psychiatric outpatient clinic: prevalence of mental disorders among children and adolescents / Ambulatorio de psiquiatría infantil: prevalencia de los trastornos mentales en niños y adolescentes

Este estudo teve como objetivo identificar a prevalência de transtornos mentais em pacientes atendidos em ambulatório de psiquiatria infantil, a partir da análise do livro de registros de atendimento (anos de 2009 e 2010) preenchido por médicos residentes e docentes. Foram analisados dados de 109 pacientes, com idade entre 4 e 20 anos (média: 11,08 ± 3,24), sendo 85 do sexo masculino (77,98%). Transtorno de déficit de atenção/hiperatividade (n = 59; 54,12%), retardo mental (n = 55; 50,45%) e transtorno de conduta (n = 34; 31,19%) foram os mais prevalentes. Para o sexo masculino, o mais prevalente foi transtorno de déficit de atenção e hiperatividade, e, para o feminino, retardo mental. As comorbidades mais prevalentes foram retardo mental, transtorno de conduta, transtorno desafiador e de oposição, episódio depressivo e transtorno da ansiedade. A maioria dos pacientes era do sexo masculino, com transtornos externalizantes e comorbidades. Os dados reafirmam a relevância de programas preventivos na atenção primária, na comunidade e nas escolas.

The objective of the study was to identify prevalence of mental disorders among patients served by a children’s psychiatric outpatient unity based on the analysis of the register book of the unity (years: 2009 and 2010), filled by psychiatry residents and professors. Data from 109 patients, ages 4 to 20 (11.08 ± 3.24) was analyzed; 85 were male (77.98%). Most prevalent disorders were attention‑ deficit/hyperactivity disorder (n = 59; 54.12%), mental retardation (n = 55; 50.45%) and conduct disorder (n = 34; 31.19%). For males the most prevalent disorder was attention deficit/hyperactivity and for females the most prevalent was mental retardation. The most prevalent comorbidities were mental retardation, conduct disorder, oppositional defiant disorder, depressive episode, and anxiety disorders. The majority of patients were male, had externalizing disorders and comorbidities. Data confirms the relevance of prevention programs in primary health care, community and schools.

Este estudio investigó la prevalencia de trastornos mentales entre pacientes atendidos en un ambulatorio de psiquiatría infantil mediante levantamiento de datos en el libro de registro de médicos residentes y profesores de psiquiatría (años 2009 y 2010). El estudio incluyó 109 pacientes con edad entre 4 y 20 años (media de 11,08 ± 3,24), 85 niños (77,98%). Los trastornos más prevalentes fueron trastorno de déficit de atención con hiperactividad (n = 59; 54,12%), retardo mental (n = 55; 50,45%) y trastorno de conducta (n = 34; 31,19%). Para los niños el más prevaleciente fue el trastorno de déficit de atención con hiperactividad y para las niñas el retardo mental. Las comorbilidades más prevalecientes fueron retardo mental, trastorno de conducta, trastorno de oposición y desafio, depresión y ansiedad. La mayor parte de los pacientes fueron niños con trastornos externalizantes y otras comorbilidades. Los dados confirman la relevancia de los programas preventivos en la salud primaria, en la comunidad y en las escuelas.

[Vaccines inquiry of enrolled medical and nursing students at School of Medicine of São José do Rio Preto (SP, Brazil), in the years of 2006 and 2007, and the possible involvements at pupil acting]. / Inquérito vacinal de alunos da graduação em medicina e enfermagem da Faculdade de Medicina de São José do Rio Preto (SP, Brasil) nos anos de 2006 e 2007 e suas possíveis implicações na atuação discente.

According to their susceptibility, health workers have higher risk to vaccine-preventable diseases (intramural transmission in hospitals), and can also be a source of infection to others professionals and patients. The aim of this article is to get and describe the vaccination status of the student population at Famerp (São José do Rio Preto, São Paulo, Brazil); to show the importance of keeping a vaccine protocol inquiry and immunization with recommended vaccines for students at Famerp, and others susceptible institutions. The methodology used was a population census of the enrolled medical and nursing students at Famerp, in 2006 and 2007, with application of a closed questionnaire to establish bio-psycho-socio-cultural characteristics of vaccinal relevance. It could be perceived that there isn't a specific immunization program for students at Famerp. We verified that among the 375 interviewed students (59.8%), the majority (59.7%) had related to know the possible adverse reactions, and 66.9% weren't afraid of adverse reactions. Only 69 students (11.0%) presented the vaccine register spontaneously. None of the students presented the vaccines of the adult or health professional routine. It's imperative to work in health planning and regulation, standardized at Famerp and higher education institutions, to protect the susceptible population.

Inquérito vacinal de alunos da graduação em medicina e enfermagem da Faculdade de Medicina de São José do Rio Preto (SP, Brasil) nos anos de 2006 e 2007 e suas possíveis implicações na atuação discente / Vaccines inquiry of enrolled medical and nursing students at School of Medicine of São José do Rio Preto (SP, Brazil), in the years of 2006 and 2007, and the possible involvements at pupil acting

Profissionais da saúde têm risco aumentado para doenças imunopreveníveis (transmissão intra-hospitalar), conforme sua suscetibilidade, e podem ser fonte de infecção a outros profissionais e a pacientes. Este artigo tem como objetivos levantar e descrever o estado vacinal da população dos estudantes da Faculdade de Medicina de São José do Rio Preto; mostrar a necessidade de manutenção de protocolo de inquérito vacinal e imunização, por vacinas recomendadas, do aluno da Famerp e de outras instituições. Utilizou-se o censo populacional dos estudantes de medicina e enfermagem da Famerp matriculados em 2006 e 2007, com aplicação de questionário fechado com caracterização biopsicossociocultural, relevante à vacinação. Não há um programa específico de imunização do corpo discente da Famerp. Pudemos verificar que dos 375 alunos (59,8 por cento) entrevistados, a maioria referiu conhecer as possíveis reações adversas (59,7 por cento) e também não ter medo dessas reações (66,9 por cento). Apenas 69 alunos (11,0 por cento) apresentaram espontaneamente a carteira vacinal. Nenhuma das carteiras apresentou-se em dia com as vacinas de rotina do adulto e dos profissionais de saúde. São imperativos planejamento e ação em saúde regular, normatizada na Famerp e em instituições de ensino superior, para proteção da população suscetível.

According to their susceptibility, health workers have higher risk to vaccine-preventable diseases (intramural transmission in hospitals), and can also be a source of infection to others professionals and patients. The aim of this article is to get and describe the vaccination status of the student population at Famerp (São José do Rio Preto, São Paulo, Brazil); to show the importance of keeping a vaccine protocol inquiry and immunization with recommended vaccines for students at Famerp, and others susceptible institutions. The methodology used was a population census of the enrolled medical and nursing students at Famerp, in 2006 and 2007, with application of a closed questionnaire to establish bio-psycho-socio-cultural characteristics of vaccinal relevance. It could be perceived that there isn't a specific immunization program for students at Famerp. We verified that among the 375 interviewed students (59.8 percent), the majority (59.7 percent) had related to know the possible adverse reactions, and 66.9 percent weren't afraid of adverse reactions. Only 69 students (11.0 percent) presented the vaccine register spontaneously. None of the students presented the vaccines of the adult or health professional routine. It's imperative to work in health planning and regulation, standardized at Famerp and higher education institutions, to protect the susceptible population.

Detection of Saint Louis encephalitis virus in dengue-suspected cases during a dengue 3 outbreak.

Arboviruses are frequently associated with outbreaks in humans and represent a serious public health problem. Among the Brazilian arboviruses, Mayaro virus, Dengue virus (DENV), Yellow Fever virus, Rocio virus, Saint Louis Encephalitis virus (SLEV), and Oropouche virus are responsible for most of human cases. All these arboviruses usually produce undistinguishable acute febrile illness, especially in the acute phase of infection. In this study we investigated the presence of arboviruses in sera of 519 patients presenting acute febrile illness, during a dengue outbreak in São José do Rio Preto City (São Paulo, Brazil). A multiplex-nested RT-polymerase chain reaction assay was applied to detect and identify the main Brazilian arboviruses (Flavivirus, Alphavirus, and Orthobunyavirus genera). The molecular analysis showed that 365 samples were positive to DENV-3, 5 to DENV-2, and 8 to SLEV. Among the positive samples, one coinfection was detected between DENV-2 and DENV-3. The phylogenetic analysis of the SLEV envelope gene indicated that the virus circulating in city is related to lineage V strains. These results indicated that during that large DENV-3 outbreak in 2006, different arboviruses cocirculated causing human disease. Thus, it is necessary to have an efficient surveillance system to control the dissemination of these arboviruses in the population.

The article of the future.

Technological advances and the Internet have contributed to the increased disclosure and updating of knowledge and science. Scientific papers are considered the best form of disclosure of information and have been undergoing many changes, not on their way of development, but on the structure of publication. The Future paper, a name for this new structure, uses hypermediatic resources, allowing a quick, easy and organized access to these items online. The exchange of information, comments and criticisms can be performed in real time, providing agility in science disclosure. The trend for the future of documents, both from professionals or enterprises, is the "cloud computing", in which all documents will be developed and updated with the use of various equipments: computer, palm, netbook, ipad, without need to have the software installed on your computer, requiring only an Internet connection.

Artigo do futuro / The article of the future

Os avanços tecnológicos e a Internet contribuíram para o aumento da divulgação e atualização do conhecimento e da ciência. Os artigos científicos considerados a forma de divulgação dessas informações estão passando por varias modificações, não em sua forma de desenvolvimento, mas sim na estrutura de publicação. O artigo do Futuro, nome dado a essa nova estrutura, utiliza os recursos hipermidiáticos, permitindo um acesso rápido, fácil e organizado destes artigos online. A troca de informações, comentários e críticas, pode ser feita em tempo real, proporcionando agilidade na divulgação da ciência. A tendência para o futuro dos documentos tanto de profissionais quanto das empresas, é o "cloud computing" - nuvem computacional, no qual todos os documentos poderão ser desenvolvidos e atualizados com a utilização de vários equipamentos: computador, palm, netbook, ipad, sem necessidade de possuir o programa instalado em seu computador, necessitando somente de conexão à Internet.

Technological advances and the Internet have contributed to the increased disclosure and updating of knowledge and science. Scientific papers are considered the best form of disclosure of information and have been undergoing many changes, not on their way of development, but on the structure of publication. The Future paper, a name for this new structure, uses hypermediatic resources, allowing a quick, easy and organized access to these items online. The exchange of information, comments and criticisms can be performed in real time, providing agility in science disclosure. The trend for the future of documents, both from professionals or enterprises, is the "cloud computing", in which all documents will be developed and updated with the use of various equipments: computer, palm, netbook, ipad, without need to have the software installed on your computer, requiring only an Internet connection.

5-Nitro-2-furyl derivative actives against Trypanosoma cruzi: preliminary in vivo studies.

Ten 5-nitro-2-furyl derivatives, with good to excellent in vitro anti-Trypanosoma cruzi activity, and nifurtimox were tested oral and intraperitoneally on healthy animals for its acute toxicity on murine models. According to animals' survival percentage, organ histological results, biochemical and haematological findings, three new derivatives, with toxicity like nifurtimox, were selected to test in vivo as antichagasic agents. Clearly, dependences between chemical structure and both acute toxicity and in vivo anti-T. cruzi activity were observed. 4-Hexyl-1-[3-(5-nitro-2-furyl)-2-propenylidene]semicarbazide displayed good profile as anti-T. cruzi agent and better acute toxicity profile than nifurtimox.

New potent 5-nitrofuryl derivatives as inhibitors of Trypanosoma cruzi growth. 3D-QSAR (CoMFA) studies.

Growth inhibitory activity in vitro of sixteen new 5-nitrofuryl derivatives against the protozoan parasite Trypanosoma cruzi, the causative agent of American trypanosomiasis, was studied. The designed compounds combine in the same molecule the recognized 5-nitrofuryl group, an oxidative stress promoter, and lateral chains that could interact with biomolecules such as trypanothione reductase. Some of the derivatives were found to be very active against the epimastigote form of the parasite, being near to 3.0-fold more active than the reference compound, nifurtimox. Moreover, three-dimensional requirements for activity were clearly observed using a 3D-QSAR study based on a comparative molecular field analysis (CoMFA). The best CoMFA model, r(2) = 0.970 and q(2) = 0.725, points to the importance of a specific hydrogen-bonding pattern around the carbonyl or thiocarbonyl moieties, as well as the requirement for hydrophobic lateral chains. Theoretical pharmacokinetics (Lipinski's rule, PSA) supports further in vivo studies.

Investigação de casos de varicela no Hospital Universitário da Faculdade de Medicina de São José do Rio Preto (SP), 2005 / Varicella investigation in the academial hospital of São José do Rio Preto College of Medicine (SP) 2005

A varicela é uma doença infectocontagiosa altamente transmissível causada pelo vírus varicela-zoster. Assume maior importância quando acomete imunodeprimidos e pacientes internados, que podem desenvolver doença grave ou fatal. Em agosto de 2005, um hospital universitário de grande porte de São José do Rio Preto (SP) notificou um provável surto de varicela intra-hospitalar com três óbitos. O objetivo dessa investigação foi conhecer a real magnitude da varicela nesse hospital, confirmar um possível surto intra-hospitalar e estabelecer medidas de controle. As fontes de informação foram: busca ativa de prontuários, entrevistas de funcionários, contato com pacientes após a alta e investigação das unidades de emergência por onde passaram os casos de varicela. Após extensa investigação das fontes de infecção de 31 casos no período de 2 de julho até 8 de outubro de 2005, evidenciou-se a transmissão intra-hospitalar da doença, acometendo quatro pacientes e oito funcionários. Tal fato pode ter sido um reflexo do aumento de casos da doença na comunidade, aliado a uma alta taxa de suscetíveis entre os profissionais de saúde. A partir da detecção dos primeiros casos, diversas medidas foram desencadeadas: notificação e investigação oportuna de novos casos, vacinação contra a varicela ou imunoglobulina, quando indicada, reforço às normas de isolamento, afastamento dos funcionários infectados, divulgação ampla do surto aos profissionais de saúde e integração entre as equipes hospitalares, municipais, regionais e estaduais. Tais medidas viabilizaram o controle da transmissão da varicela num hospital de referência regional.

Uso de drogas entre os estudantes de medicina da Faculdade de Medicina de São José do Rio Preto, SP, no ano de 2002 / Drug use among the students of the Medical School of São José do Rio Preto, SP, in 2002

Objetivos: Avaliar o consumo de álcool e outras drogas e o perfil dos estudantes de medicina, fornecendo subsídios para implementação de medidas preventivas na Instituição. Metodologia: Aplicação de um questionário fechado, de autopreenchimento, anônimo, a todos os alunos do curso de medicina da Famerp. Resultados: Foram analisados 297 questionários (77%), nos quais 51% são homens, média 21,7 anos, renda familiar 11 a 25 salários mínimos, 58% moram com amigos e 94% não trabalham. Cerca de 86% dos alunos usaram álcool na vida, 42% tabaco, 30% inalantes, 25% maconha, 22% anfetaminas, 13,7% ansiolíticos. Destes, 16% iniciaram o uso de álcool após o início do curso de medicina, 22% tabaco, 61% anfetaminas, 30% ansiolíticos, 27% inalantes, 25% maconha. Houve um aumento do consumo de anfetaminas diretamente proporcional às séries. Os homens foram responsáveis pelo maior consumo das drogas, exceto ansiolíticos.Cerca de 69% dos alunos já beberam até se embriagar, sendo 32% no mês anterior. As bebidas mais consumidas são cerveja e vinho e os locais de consumo mais freqüentes são festas de faculdade (46%) e bares (36%) e 74% costumam beber com amigos. Depois de beber, 61% dos alunos já faltaram às aulas, 45% dirigiram e 15% brigaram. Cerca de 35% dos alunos usaram álcool associado a outra droga no último ano. Os homens consomem mais álcool e com mais freqüência que as mulheres. Em relação ao cigarro, 82% dos alunos fumam menos que 10 cigarros por dia, 75% tentaram parar de fumar e 52% conseguiram. As principais razões para o uso de drogas são diversão/prazer e curiosidade. Para 80% dos alunos, a escola médica deve aconselhar o usuário ocasional e para 87% deve tratar e 25% afastar o usuário dependente. Conclusão: há uma freqüência elevada no consumo de drogas, principalmente lícitas, com uso concomitante entre elas, sendo necessárias medidas educativas e de prevenção mais efetivas pela instituição.

Design, synthesis and biological evaluation of new potent 5-nitrofuryl derivatives as anti-Trypanosoma cruzi agents. Studies of trypanothione binding site of trypanothione reductase as target for rational design.

Design, using force-field calculations on the catalytic site of trypanothione reductase from Trypanosoma cruzi, has led to the development of new 5-nitrofuryl derivatives as potential anti-trypanosomal agents. The synthesized compounds were tested in vitro against T. cruzi and more than 75% of the prepared derivatives showed higher activity than nifurtimox. Compounds 5 and 11, hexyl 4-(5-nitrofurfurylidene)carbazate and N-hexyl 3-(5-nitrofuryl)propenamide, showed the highest in vitro trypanocidal effect reported to date for members of the nitrofuran family. Partition coefficients and energies for the single-electron reduction of compounds were theoretically determined. These properties could be not the major cause of the activities' differences. The physicochemical environment around E19, W22, C53 and Y111 residues within the trypanothione binding site of trypanothione reductase resulted a valuable target for the rational design of anti-trypanosomal drugs.

Ruthenium (II) nitrofurylsemicarbazone complexes: new DNA binding agents.

Complexes of the type [Ru(II)Cl(2)(DMSO)(2)L], where L are 5-nitrofurylsemicarbazone derivatives, were prepared in an effort to combine the potential anti-tumor activity of the metal and the free ligands. The new complexes are excellent DNA binding agents for calf thymus DNA. So, their in vitro anti-tumor activity was tested in cellular models and the complexes were found to be non-cytotoxic on the tumor cell lines assayed, neither in aerobic conditions nor in the bio-reductive assay performed. Redox behavior, lipophilicity and stability were studied in order to explain the lack of cellular cytotoxic effects. The complexes resulted 10-100 times more hydrophilic than the parent ligands thus the bio-activity of these compounds would be compromised by their inadequate lipophilic properties.

ESR spin trapping studies of free radicals generated from nitrofuran derivative analogues of nifurtimox by electrochemical and Trypanosoma cruzi reduction.

Electron spin resonance (ESR) spectra of radicals obtained from two analogues of the antiprotozoal drug nifurtimox by electrolytic and Trypanosoma cruzi reduction were analyzed. The electrochemistry of these compounds was studied using cyclic voltammetry. STO 3-21G ab initio and INDO molecular orbital calculations were performed to obtain the optimized geometries and spin distribution, respectively. The antioxidant effect of glutathione on the nitroheterocycle radical was evaluated. DMPO spin trapping was used to investigate the possible formation of free radicals in the trypanosome microsomal system. Nitro1 and Nitro2 nitrofuran analogues showed better antiparasitic activity than nifurtimox. Nitro2 produced oxygen redox cycling in T. cruzi epimastigotes. The ESR signal intensities were consistent with the trapping of either the hydroxyl radical or the Nitro2 analogue radicals. These results are in agreement with the biological observation that Nitro2 showed anti-Chagas activity by an oxidative stress mechanism.