RESUMO
Chagas disease is a tropical neglected disease that affects millions of people worldwide, still demanding a more effective and safer therapy, especially in its chronic phase which lacks a treatment that promotes substantial parasitological cure. The technical note of Romanha and collaborators published in 2010 aimed establish a guideline with the set of minimum criteria and decision gates for the development of new agents against Trypanosoma cruzi with the focus on developing new antichagasic drugs. In this sense, the present review aims to update this technical note, bringing the state of the art and new advances on this topic in recent years.
Assuntos
Doença de Chagas , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Tripanossomicidas , Trypanosoma cruzi , Doença de Chagas/tratamento farmacológico , Tripanossomicidas/farmacologia , Tripanossomicidas/uso terapêutico , Animais , Trypanosoma cruzi/efeitos dos fármacos , Humanos , Desenvolvimento de MedicamentosRESUMO
Chagas disease is a neglected tropical parasitic disease caused by the protozoan Trypanosoma cruzi. Worldwide, an estimated 8 million people are infected with T. cruzi, causing more than 10,000 deaths per year. Currently, only two drugs, nifurtimox and benznidazole (BNZ), are approved for its treatment. However, both are ineffective during the chronic phase, show toxicity, and produce serious side effects. This work aimed to obtain and evaluate novel 2-nitroimidazole-N-acylhydrazone derivatives analogous to BNZ. The design of these compounds used the two important pharmacophoric subunits of the BNZ prototype, the 2-nitroimidazole nucleus and the benzene ring, and the bioisosterism among the amide group of BNZ and N-acylhydrazone. The 27 compounds were obtained by a three-step route in 57%-98% yields. The biological results demonstrated the potential of this new class of compounds, since eight compounds were potent and selective in the in vitro assay against T. cruzi amastigotes and trypomastigotes using a drug-susceptible strain of T. cruzi (Tulahuen) (IC50 = 4.3-6.25 µM) and proved to be highly selective with low cytotoxicity on L929 cells. The type I nitroreductase (TcNTR) assay suggests that the new compounds may act as substrates for this enzyme.
Assuntos
Hidrazonas , Nitroimidazóis , Testes de Sensibilidade Parasitária , Tripanossomicidas , Trypanosoma cruzi , Trypanosoma cruzi/efeitos dos fármacos , Tripanossomicidas/farmacologia , Tripanossomicidas/síntese química , Tripanossomicidas/química , Nitroimidazóis/farmacologia , Nitroimidazóis/química , Nitroimidazóis/síntese química , Relação Estrutura-Atividade , Animais , Hidrazonas/farmacologia , Hidrazonas/síntese química , Hidrazonas/química , Doença de Chagas/tratamento farmacológico , Doença de Chagas/parasitologia , Camundongos , Estrutura Molecular , Relação Dose-Resposta a Droga , HumanosRESUMO
Chagas disease (CD), caused by the flagellated protozoan Trypanosoma cruzi (T. cruzi), affects approximately 7 million people worldwide and is endemic in Latin America, especially among socioeconomically disadvantaged populations. Since the 1960s, only two drugs have been commercially available for treating this illness: nifurtimox (NFX) and benznidazole (BZN). Although these drugs are effective in the acute phase (AP) of the disease, in which parasitemia is usually high, their cure rates in the chronic phase (CP) are low and often associated with several side effects. The CP is characterized by a subpatent parasitaemia and absence of clinical symptoms in the great majority of infected individuals. However, at least 30 % of the individuals will develop potentially lethal symptomatic forms, including cardiac and digestive manifestations. For such reason, in the CP the treatment is usually symptomatic and typically focuses on managing complications such as arrhythmias, heart failure, or digestive problems. Therefore, the need for new drugs or therapeutic approaches using BZN or NFX is extremely urgent. This review presents the main clinical trials, especially in the CP, which involve BZN and NFX in different treatment regimens. Additionally, other therapies using combinations of these drugs with other substances such as allopurinol, itraconazole, ravuconazole, ketoconazole, posaconazole and amiodarone are also reported. The importance of early diagnosis, especially in pediatric patients, is also discussed, emphasizing the need to identify the disease in its early stages to improve the chances of successful treatment.
Assuntos
Doença de Chagas , Nifurtimox , Nitroimidazóis , Tripanossomicidas , Trypanosoma cruzi , Doença de Chagas/tratamento farmacológico , Humanos , Nitroimidazóis/uso terapêutico , Trypanosoma cruzi/efeitos dos fármacos , Tripanossomicidas/uso terapêutico , Nifurtimox/uso terapêutico , Doença CrônicaRESUMO
Chagas disease is a tropical neglected disease that affects millions of people worldwide, still demanding a more effective and safer therapy, especially in its chronic phase which lacks a treatment that promotes substantial parasitological cure. The technical note of Romanha and collaborators published in 2010 aimed establish a guideline with the set of minimum criteria and decision gates for the development of new agents against Trypanosoma cruzi with the focus on developing new antichagasic drugs. In this sense, the present review aims to update this technical note, bringing the state of the art and new advances on this topic in recent years.
RESUMO
ABSTRACT Purpose We aimed to characterize surgeons opinion about the vaginal extraction of the kidney after transperitoneal laparoscopic nephrectomy. Matherial and Methods A 9-item questionnaire was published online (Survey Monkey TM) and publicized via email to a multidisciplinary pool of surgeons in Portugal. Data was collected and statistical analysis was performed using IBM SPSS Statistics, Version 21.0. Results Three hundred and fifty nine inquiries were sent, 154 surgeons completed the questionnaires (response rate of 43.0%). Fifty five point eight percent of the participants would choose the transvaginal approach for themselves or for a close relative. The most stated arguments were a better cosmesis (29.0%) expectancy of lower post operative pain (26.0%) and lower rate of incisional hernias (23.0%). Defenders of the transabdominal procedure justified with an expectancy of lower complication rate (39%), namely impairment of sexual function and fertility (22%). The female gender and the familiarity with transvaginal surgery were the stronger predictors of the option for this approach (70.6% vs 48.5%; p=0,016 and 85.3% vs 46.6%; p <0.001 respectively). Conclusions Contrasting with similar surveys published on transvaginal NOTES, the vaginal specimen extraction after conventional laparoscopic nephrectomy was fairly accepted by the inquired surgeons.
Assuntos
Humanos , Masculino , Feminino , Adulto , Vagina , Cirurgia Endoscópica por Orifício Natural/métodos , Nefrectomia/métodos , Complicações Pós-Operatórias , Padrões de Prática Médica/estatística & dados numéricos , Fatores Sexuais , Inquéritos e Questionários , Reprodutibilidade dos Testes , Resultado do Tratamento , Laparoscopia/métodos , Cirurgiões/estatística & dados numéricos , Pessoa de Meia-IdadeRESUMO
O objetivo desse trabalho foi construir equações para predição da FC máxima (FC máx.) e da FC de treino (FC Tr) em corredores de fundo, além de comparar a validade da aplicação de predições generalizadas da FC máx. e da FC Tr no grupo estudado. 14 corredores foram submetidos a teste progressivo na esteira ergométrica que consistia basicamente em incrementos de 1 Km/h a cada minuto até a exaustão, sendo a velocidade inicial de 8 Km/h. Foram medidos FC e consumo de oxigênio (VO2). Comparou-se a FC máx. observada com a predita por diversas equações generalizadas e foram propostas duas equações específicas para corredores: FC máx.= 204,8 0,7 * idade ; %FC máx. = 0,58 * %VO2 máx. + 42,45. Esta última foi comparada à proposta de Marion et al. (10). A FC máx. observada nos corredores foi menor que a predita pelas equações, mas apresentou declínio relacionado à idade semelhante. A equação para predição da FC Tr apresentou baixo erro padrão de estimativa (3,8%) e alto índice de determinação (R2 = 0,90), sugerindo que a intensidade de treino pode ser determinada com razoável precisão pela FC. A equação de Marion difere da dos corredores, sobretudo em cargas baixas.
The objective of this study was to construct equations to predict maximal heart rate (MRH) and training heart rate (THR). In addition it was studied the validity of utilization of existing generalized equation in prescribing training for runners. Fourteen male runners were submitted to a treadmill graded test according the protocol: adptative phase with 4 km/h and 1% of slope followed by 1 min stage with 8 km/h and thereafter the speed was increased by 1 km/h each min until exhaustion. HR and oxygen up-take (VO2) were measured. Observed and predicted MHR and THR were compared and were constructed specifics equations: MHR = 204.8 0,7 * age and %MHR = 0.58 * %VO2max + 42.45. The majority of generalized equation super estimated runners MHR, that also showed to decreased due to aging. The equation to predict THR showed small standard error of the mean (3.8 %) and high coefficient of determination (.90). the results suggests that the training intensity can be estimated accurately by either the specific equation or by Marion et alii (1994)mainly in high intensity.
Assuntos
Humanos , Masculino , Adulto , Limiar Anaeróbio , Frequência Cardíaca , Consumo de Oxigênio , Corrida , EsportesRESUMO
A calibração dinâmica de cicloergômetros de frenagem mecânica (Ciclo-Mec) exige a aplicação de um torquímetro, durante o acionamento do Ciclo-Mec a velocidades conhecidas, para cada um dos ajustes de carga. Na maioria dos centros de avaliação física é feita apenas a calibração, em separado, da velocidade da roda e da resistência aplicada sobre ela. Como a calibração dinâmica exige aparelhos sofisticados, e a fragmentada pode levar a erros, o objetivo deste trabalho foi propor a calibração dinâmica indireta que consiste na comparação do consumo de oxigênio (VO2), medido em diversas cargas, com valores preditos por equação de regressão amplamente utilizada. Após a calibração da velocidade e da carga resistiva do Ciclo-Mec, sete indivíduos do gênero masculino (70,6 ± 4,3 kg, 177,3 ± 5,0 cm, 25,9 ± 7,7 anos) pedalaram a 50 rpm, com carga resistiva inicial de 0,95 kg (286,9 kgm.min-1) e incrementos de 1,0 kg a cada 3 min (302 kgm.min-1), até a carga de 4,95 kg (1494,9 kgm.min-1). Para controle das rotações do pedal, cada sujeito seguia o ritmo marcado por um metrônomo digital. O VO2 era medido continuamente pelo Analisador Metabólico Aerosport modelo Teem 100. Para cálculo do VO2 Predito para carga, aplicou-se à potência nominal a equação: VO2 predito = potência nominal x2 + (3,5 X peso corporal). A potência nominal foi corrigida pela equação: potência corrigida = [VO2 medido - (3,5 X peso corporal)] / 2. Comparando-se a potência nominal e a corrigida observou-se que o erro de medida da Ciclo-Mec estudado é maior à medida que aumenta a Potência Nominal aplicada. Corrigiu-se a potência nominal aplicada pela equação: potência corrigida = 0,53 x potência nominal + 55,12.
Usually, mechanical cycle ergometers (Cycle-Mec) are calibrated in a fragmented way: speed of the wheel and the applied resistance are calibrated independently. For more accurate calibration, it should be performed the dynamic calibration, using a torquimeter while the Cycle-Mec works at different speeds for each possible load, calibrating the system in the real test situation. As the dynamic calibration demands sophisticated equipments, inaccessible to most of the evaluation centers, the objective of this work was to experiment the indirect dynamic calibration of a Cycle-Mec by comparing the oxygen consumption (VO2), in several loads, with the VO2 predicted by regression equation used in aerobic assessment. After speed and resistive load calibration, 7 male individuals (70.6 ± 4.3 kg, 177.3 ± 5.0 cm, 25.9 ± 7.7 years) pedaled at 50 rpm, with initial resistive load of 0.95 kg (286.9 kgm.min-1) and increments of 1.0 kg each 3 min (302 kgm.min-1), until 4.95 kg (1494.9 kgm.min-1). The cadence was marked by digital metronome. Metabolic Analyzer Aerosport Teem 100 measured VO2. For Predicted VO2 calculation it was applied the equation: Predicted VO2 = Nominal power x 2 + (3,5 X corporal weight). Nominal Power was corrected by the equation: Corrected Power = / 2. Comparing nominal and corrected power it was possible to observe that the error of the studied Cycle-Mec was larger as nominal power increases. Correction of nominal power is obtained by the equation: Corrected power = 0.53 x Nominal Power + 55.12.
Assuntos
Humanos , Masculino , Limiar Anaeróbio , Calibragem , Teste de Esforço , Consumo de OxigênioRESUMO
Dos cinco casos de ameloblastoma analisados, predominou o sexo feminino, raça preta, faixa etária entre 17 e 65 anos. As manifestaçöes clínicas observadas foram de: dor de dente e infecçäo na cavidade oral (dois casos), massa tumoral na regiäo mentoniana (um caso), massa tumoral na regiäo mandibular esquerda de crescimento progressivo. O início dos sinais e sintomas variaram de dois a nove anos. Os aspectos radiológicos observados foram de: lesäo lítica multiloculada; lesäo lítica insuflante multiloculada; lesäo cística multiloculada com destruiçäo da cortical; massa com densidade de partes moles e destruiçäo óssea (molar, palato, fossa nasal e seio maxilar); lesäo osteodestrutiva, multiloculada, com aumento de volume de partes moles adjacentes e calcificaçöes tipo "bolha de sabäo" de permeio. Houve predomínio do tipo multicístico (três casos). A recidiva ocorreu em três casos, cujo reinício demorou de seis a doze meses