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Machado, Ricardo Luiz Dantas
Banic, Dalma Maria
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Id: biblio-1012675
Autor: Pratt-Riccio, Lilian Rose; Baptista, Bárbara de Oliveira; Torres, Vanessa Rodrigues; Bianco-Junior, Cesare; Perce-Da-Silva, Daiana de Souza; Riccio, Evelyn Kety Pratt; Lima-Junior, Josué da Costa; Totino, Paulo Renato Rivas; Cassiano, Gustavo Capatti; Storti-Melo, Luciane Moreno; Machado, Ricardo Luiz Dantas; de Oliveira-Ferreira, Joseli; Banic, Dalma Maria; Carvalho, Leonardo José de Moura; Daniel-Ribeiro, Cláudio Tadeu.
Título: Chloroquine and mefloquine resistance profiles are not related to the circumsporozoite protein (CSP) VK210 subtypes in field isolates of Plasmodium vivax from Manaus, Brazilian Amazon
Fonte: Mem. Inst. Oswaldo Cruz;114:e190054, 2019. tab, graf.
Idioma: en.
Resumo: BACKGROUND The central repetitive region (CRR) of the Plasmodium vivax circumsporozoite surface protein (CSP) is composed of a repetitive sequence that is characterised by three variants: VK210, VK247 and P. vivax-like. The most important challenge in the treatment of P. vivax infection is the possibility of differential response based on the parasite genotype. OBJECTIVES To characterise the CSP variants in P. vivax isolates from individuals residing in a malaria-endemic region in Brazil and to profile these variants based on sensitivity to chloroquine and mefloquine. METHODS The CSP variants were determined by sequencing and the sensitivity of the P. vivax isolates to chloroquine and mefloquine was determined by Deli-test. FINDINGS Although five different allele sizes were amplified, the sequencing results showed that all of the isolates belonged to the VK210 variant. However, we observed substantial genetic diversity in the CRR, resulting in the identification of 10 different VK210 subtypes. The frequency of isolates that were resistant to chloroquine and mefloquine was 11.8 and 23.8%, respectively. However, we did not observe any difference in the frequency of the resistant isolates belonging to the VK210 subtypes. MAIN CONCLUSION The VK210 variant is the most frequently observed in the studied region and there is significant genetic variability in the CRR of the P. vivax CSP. Moreover, the antimalarial drug sensitivity profiles of the isolates does not seem to be related to the VK210 subtypes.
Descritores: Plasmodium vivax/efeitos dos fármacos
Mefloquina/uso terapêutico
Cloroquina/uso terapêutico
Resistência a Múltiplos Medicamentos/imunologia
-Brasil
Responsável: BR1.1 - BIREME


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Id: lil-787558
Autor: Lobo, Lis; Sousa, Bruno de; Cabral, Lília; Cristiano, Maria LS; Nogueira, Fátima.
Título: Highly active ozonides selected against drug resistant malaria
Fonte: Mem. Inst. Oswaldo Cruz;111(7):450-453tab.
Idioma: en.
Projeto: CAPES; . FCT; . FCT.
Resumo: Ever increasing multi-drug resistance by Plasmodium falciparum is creating new challenges in malaria chemotherapy. In the absence of licensed vaccines, treatment and prevention of malaria is heavily dependent on drugs. Potency, range of activity, safety, low cost and ease of administration are crucial issues in the design and formulation of antimalarials. We have tested three synthetic ozonides NAC89, LC50 and LCD67 in vitro and in vivo against multidrug resistant Plasmodium. In vitro, LC50 was at least 10 times more efficient inhibiting P. falciparum multidrug resistant Dd2 strain than chloroquine and mefloquine and as efficient as artemisinin (ART), artesunate and dihydroartemisinin. All three ozonides showed high efficacy in clearing parasitaemia in mice, caused by multi-drug resistant Plasmodium chabaudi strains, by subcutaneous administration, demonstrating high efficacy in vivo against ART and artesunate resistant parasites.
Descritores: Antimaláricos/farmacologia
Malária Falciparum/parasitologia
Plasmodium falciparum/efeitos dos fármacos
-Artemisininas/farmacologia
Cloroquina/farmacologia
Modelos Animais de Doenças
Mefloquina/farmacologia
Camundongos
Parasitemia/tratamento farmacológico
Limites: Seres Humanos
Animais
Feminino
Responsável: BR1.1 - BIREME


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Id: lil-712406
Autor: Segura, César; Cuesta-Astroz, Yesid; Nunes-Batista, Camila; Zalis, Mariano; von Krüger, Wanda Maria de Almeida; Mascarello Bisch, Paulo.
Título: Partial characterization of Plasmodium falciparum trophozoite proteome under treatment with quinine, mefloquine and the natural antiplasmodial diosgenone / Caracterización parcial del proteoma del trofozoíto de Plasmodium falciparum bajo tratamiento con quinina, mefloquina y el compuesto natural diosgenona
Fonte: Biomédica (Bogotá);34(2):237-249, abr.-jun. 2014. ilus, tab.
Idioma: en.
Resumo: Introduction: Despite efforts to control malaria, around 10% of the world population is at risk of acquiring this disease. Plasmodium falciparum accounts for the majority of severe cases and deaths. Malaria control programs have failed due to the therapeutic failure of first-line antimalarials and to parasite resistance. Thus, new and better therapeutic alternatives are required. Proteomic analysis allows determination of protein expression levels under drug pressure, leading to the identification of new therapeutic drug targets and their mechanisms of action. Objective: The aim of this study was to analyze qualitatively the expression of P.falciparum trophozoite proteins (strain ITG2), after exposure to antimalarial drugs, through a proteomic approach. Materials and methods: In vitro cultured synchronized parasites were treated with quinine, mefloquine and the natural antiplasmodial diosgenone. Protein extracts were prepared and analyzed by two-dimensional electrophoresis. The differentially expressed proteins were selected and identified by MALDI-TOF mass spectrometry. Results: The following proteins were identified among those differentially expressed in the parasite in the presence of the drugs tested: enolase (PF10_0155), calcium-binding protein (PF11_0098), chaperonin (PFL0740c), the host cell invasion protein (PF10_0268) and proteins related to redox processes (MAL8P1.17). These findings are consistent with results of previous studies where the parasite was submitted to pressure with other antimalarial drugs. Conclusion: The observed changes in the P. falciparum trophozoite protein profile induced by antimalarial drugs involved proteins mainly related to the general stress response.

Introducción. A pesar de los esfuerzos para controlar la malaria, esta sigue siendo un problema de salud pública. Plasmodium falciparum es responsable de la mayoría de los casos graves y de las muertes. Los programas de control de la malaria han sido cuestionados debido al fracaso del tratamiento y a la resistencia del parásito a los antipalúdicos de primera línea, por lo que se requieren nuevas y mejores alternativas. El análisis proteómico permite identificar y determinar los niveles de expresión de las proteínas bajo la presión de los medicamentos, lo que posibilita la identificación de nuevos blancos terapéuticos y mecanismos de acción. Objetivo. Analizar cualitativamente la expresión diferencial de proteínas del citosol del trofozoíto de P. falciparum bajo tratamiento con quinina, mefloquina y el compuesto natural diosgenona mediante una aproximación proteómica. Materiales y métodos. Se trataron trofozoítos sincronizados y cultivados in vitro de P. falciparum (cepa ITG2) con quinina, mefloquina y el compuesto natural diosgenona. Los extractos proteicos se prepararon y analizaron por electroforesis bidimensional. Las proteínas con aparente expresión diferencial se seleccionaron e identificaron mediante espectrometría de masas MALDI-TOF. Resultados. Se encontraron las siguientes proteínas diferencialmente expresadas en el trofozoíto: la enolasa (PF10_0155), la proteína de unión a calcio (PF11_0098), la chaperonina (PFL0740c), la proteína de invasión a la célula del huésped (PF10_0268) y la proteína relacionada con procesos de reducción y oxidación (redox) (MAL8P1.17). Estos hallazgos son congruentes con resultados previos de estudios en los que el parásito fue presionado con otros medicamentos antipalúdicos. Conclusión. Los cambios observados en el perfil de proteínas del trofozoíto de P. falciparum tratado con antipalúdicos involucraron preferencialmente proteínas relacionadas con la respuesta al estrés general.
Descritores: Antiprotozoários/farmacologia
Mefloquina/farmacologia
Plasmodium falciparum/efeitos dos fármacos
Proteínas de Protozoários/biossíntese
Quinina/farmacologia
Compostos de Espiro/farmacologia
Triterpenos/farmacologia
-Sequência de Aminoácidos
Eletroforese em Gel Bidimensional
Eritrócitos/parasitologia
Regulação da Expressão Gênica/efeitos dos fármacos
Proteínas de Choque Térmico/biossíntese
Proteínas de Choque Térmico/genética
Proteínas de Choque Térmico/isolamento & purificação
Técnicas In Vitro
INHIBITORY CONCENTRATION ACADEMIES AND INSTITUTES
Dados de Sequência Molecular
Proteoma
Plasmodium falciparum/crescimento & desenvolvimento
Plasmodium falciparum/metabolismo
Proteínas de Protozoários/genética
Proteínas de Protozoários/isolamento & purificação
Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
Limites: Seres Humanos
Tipo de Publ: Research Support, Non-U.S. Gov't
Responsável: CO332 - Facultad de Medicina


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Id: lil-704116
Autor: Nogueira, Fernando Henrique Andrade; Reis, Naialy Fernandes Araújo; Chellini, Paula Rocha; César, Isabela da Costa; Pianetti, Gerson Antônio.
Título: Development and validation of an HPLC method for the simultaneous determination of artesunate and mefloquine hydrochloride in fixed-dose combination tablets
Fonte: Braz. j. pharm. sci;49(4):837-843, Oct.-Dec. 2013. ilus, tab.
Idioma: en.
Resumo: The present study developed and validated an HPLC method for the simultaneous determination of artesunate (AS) and mefloquine hydrochloride (MQ) in fixed-dose combination tablets, according to ICH guidelines. The chromatographic separation was carried out on an XBridge C18 (250 x 4.6 mm i.d., 5 µm particle size, Waters) analytical column. The mobile phase included a 0.05 M monobasic potassium phosphate buffer (pH adjusted to 3.0 with phosphoric acid) and acetonitrile (50 + 50, v/v). The flow rate was 1.0 mL/min, and the run time was 13 minutes. A dual-wavelength approach was employed: AS detection was performed at 210 nm and MQ was detected at 283 nm, using a diode array detector. Stability of sample solutions was evaluated for 8 hours after preparation, during which time the solutions remained stable. Youden's test was employed to evaluate robustness. The method proved to be linear (r²>0.99), precise (RSD<2.0%), accurate, selective, and robust, proving to be appropriate for routine drug quality control analysis.

Um método por cromatografia a líquido de alta eficiência para a determinação simultânea de artesunato (AS) e cloridrato de mefloquina (MQ) em comprimidos em dose fixa combinada foi desenvolvido e validado, de acordo com as normas do ICH. A separação cromatográfica foi realizada com uma coluna analítica XBridge C18 (250 x 4,6 mm d.i., partículas de 5 µm, Waters). A fase móvel foi constituída de tampão fosfato monobásico de potássio 0,05 M (pH ajustado para 3,0 com ácido fosfórico) e acetonitrila (50 + 50, v/v). O fluxo da fase móvel foi de 1,0 mL/min e o tempo de corrida foi de 13 minutos. Utilizaram-se dois comprimentos de onda: a detecção do AS foi realizada em 210 nm e a de MQ foi realizada em 283 nm, utilizando-se um detector de arranjo de diodos. A estabilidade das soluções padrão e amostra foi avaliada por 8 horas após sua preparação e as soluções permaneceram estáveis nesse período. O teste de Youden foi empregado para a avaliação da robustez do método. O método se mostrou linear (r²>0,99), preciso (DPR<2,0%), exato, seletivo e robusto, sendo adequado para análises rotineiras de controle de qualidade dos medicamentos.
Descritores: Cromatografia Líquida de Alta Pressão/métodos
Mefloquina/análise
Comprimidos/análise
-Preparações Farmacêuticas/análise
Responsável: BR1.1 - BIREME


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Id: lil-674944
Autor: Carmona-Fonseca, Jaime; Agudelo-García, Olga María; Arango-Flórez, Eliana.
Título: Eficacia terapéutica y eventos adversos de tratamientos para malaria vivax y malaria falciparum en gestantes en las regiones de Urabá y Alto San Jorge, Colombia, 2008-2011 / Therapeutic efficacy and adverse events of treatments for vivax and falciparum malaria in pregnant women in the regions of Uraba and Alto San Jorge, Colombia, 2008-2011
Fonte: Rev. colomb. obstet. ginecol;64(1):27-37, ene.-mar. 2013. tab.
Idioma: es.
Resumo: Objetivo: evaluar, con el protocolo de la Organización Mundial de la Salud (OMS) de 1998, la respuesta terapéutica antimalárica (RTA) y los eventos adversos (EA) en cuatro esquemas de tratamiento antiplasmodial en gestantes colombianas, con diagnóstico de malaria no complicada por P. vivax o por P. falciparum, según gota gruesa.Materiales y métodos: experimento controlado aleatorizado en paralelo. Se calculó un tamaño muestral de 60 pacientes con P. vivax y 30 con P. falciparum. Se evaluaron cuatro tratamientos: malaria vivax en cualquier trimestre de gestación tratada con cloroquina o con amodiaquina; malaria falciparum en trimestres 2 y 3, terapia tratada con artesunato-mefloquina o arteméter-lumefantrina. Se hizo seguimiento por 28 días. Se midió la proporción de falla terapéutica y de eventos adversos. Los grupos se comparan mediante análisis univariado. El protocolo del estudio fue registrado en el sitio: ClinicalTrials. gov bajo el registro: MGP-02. Resultados: se trataron 90 pacientes. La RTA fue adecuada en 97-100% de los casos de malaria vivax (variación del método de análisis) y en 100% de los casos con malaria falciparum. Los EA más comunes fueron dolor epigástrico, mareo, tinitus y visión borrosa. No hubo eventos adversos graves.Conclusiones: la cloroquina y la amodiaquina tienen igual respuesta terapéutica adecuada. Las combinaciones artesunato-mefloquina y arteméterlumefantrina no mostraron fallas terapéuticas. Se requieren estudios en otros lugares del país con los esquemas evaluados y con otros.

Objective: To assess, using the 1998 WHO protocol, adequate clinical and parasitological response (ACPR) and adverse events (AEs) to 4 antiplasmodial treatment regimens in pregnant Colombian women diagnosed with uncomplicated P. vivax or P. falciparum malaria on the basis of thick blood smear.Materials and methods: Parallel randomized controlled trial. The estimated sample size was 60 patients with P. vivax and 30 with P. falciparum. Four treatments were assessed: vivax malaria in any trimester treated with chloroquine or amodiaquine; falciparum malaria in second and third trimesters treated with artesunate-mefloquine or artemether-lumefantrine. Patients were followed for 28 days. Measurements included the proportion of therapeutic failures and of adverse events. Groups were compared using univariate analysis. The study protocol was registered in ClinicalTrials.gov under the Protocol Record MGP-02. Results: Overall, 90 patients were treated. ACPR was adequate in 97-100% of vivax cases (analytical method variation) and in 100% of falciparum cases. The most common AEs were epigastric pain, dizziness, tinnitus and blurred vision. There were no serious adverse events. Conclusions: Both chloroquine as well as amodiquine have similar adequate responses. No therapeutic failures were found for the combinations of artesunate-mefloquine and artemether-lumefantrine. Studies need to be done in other places of the country using the regimens assessed as well as others.
Descritores: Amodiaquina
Cloroquina
Malária
Mefloquina
Plasmodium
Gravidez
-Colômbia
Limites: Adulto
Feminino
Responsável: CO76


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Id: lil-606644
Autor: El-Lakkany, Naglaa Mohamed; el-Din, Sayed Hassan Seif; Sabra, Abdel-Nasser Abdel-Aal; Hammam, Olfat Ali.
Título: Pharmacodynamics of mefloquine and praziquantel combination therapy in mice harbouring juvenile and adult Schistosoma mansoni
Fonte: Mem. Inst. Oswaldo Cruz;106(7):814-822, Nov. 2011. ilus, tab.
Idioma: en.
Resumo: Praziquantel (PZQ) is currently the only drug widely used for the treatment of schistosomiasis, but the antimalarial drug mefloquine (Mef) possesses interesting antischistosomal properties. Combination therapy with these two drugs has been suggested as a strategy for transmission control, as PZQ is active against adult worms and Mef is active against schistosomula. To examine the efficacy of combination therapy, Schistosoma mansoni-reinfected mice were separated into seven groups: untreated (I), treated with PZQ in doses of 200 mg/kg (II) or 1,000 mg/kg (III), treated with Mef in doses of 200 mg/kg (IV) or 400 mg/kg (V); each dose was divided equally and given on two consecutive days. Group VI was treated with doses of PZQ + Mef as in groups II and IV, respectively, while group VII was treated with PZQ + Mef as in groups III and V, respectively. PZQ + Mef at the reduced doses of 200 mg/kg each enhanced the therapeutic efficacy over the reduced PZQ dose alone as shown by a very high reduction in the total numbers of mature worms (95 percent vs. 49 percent), immature worms (96 percent vs. 29 percent) and the complete eradication of immature females, mature females and immature eggs. The reduction in worm burden was associated with the healing of hepatic granulomatous lesions and the normalisation of all liver enzymes. Therefore, the use of Mef with PZQ is more effective than PZQ alone and should be considered for clinical trials in humans as a potential treatment regimen to prevent treatment failures in areas with high rates of schistosomiasis.
Descritores: Mefloquina/administração & dosagem
Praziquantel/administração & dosagem
Schistosoma mansoni/efeitos dos fármacos
Esquistossomose mansoni/tratamento farmacológico
Esquistossomicidas/administração & dosagem
-Modelos Animais de Doenças
Relação Dose-Resposta a Droga
Quimioterapia Combinada/métodos
Granuloma/parasitologia
Granuloma/patologia
Fígado/parasitologia
Fígado/patologia
Mefloquina/farmacocinética
Contagem de Ovos de Parasitas
Praziquantel/farmacocinética
Esquistossomose mansoni/parasitologia
Esquistossomose mansoni/patologia
Esquistossomicidas/farmacocinética
Limites: Animais
Feminino
Masculino
Camundongos
Tipo de Publ: Research Support, Non-U.S. Gov't
Responsável: BR1.1 - BIREME


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Id: lil-602900
Autor: Nogueira, Fernando Henrique Andrade; Moreira-Campos, Lígia Maria; Santos, Roseli La Corte dos; Pianetti, Gerson Antônio.
Título: Quality of essential drugs in tropical countries: evaluation of antimalarial drugs in the Brazilian Health System / Qualidade de medicamentos essenciais em países tropicais: avaliação de medicamentos antimaláricos no Sistema de Saúde do Brasil
Fonte: Rev. Soc. Bras. Med. Trop;44(5):582-586, Sept.-Oct. 2011.
Idioma: en.
Resumo: INTRODUCTION: The emergence of drug resistance is one of the main problems concerning malaria treatment. The use of counterfeit and/or substandard antimalarial drugs can contribute to the development of parasite resistance. Thus, the aim of this study was to evaluate the quality of antimalarial drugs distributed in Brazil. METHODS: Samples containing chloroquine phosphate, mefloquine hydrochloride, primaquine phosphate, and quinine sulfate tablets were delivered to the Rio de Janeiro central storeroom (CENADI), state storerooms (SS), and Basic Health Units (BHUs) in the north region of Brazil - a total of 10 sample sets. After 5 months of storage, the samples were collected, and in vitro quality control analyses according to official and published methods were performed. RESULTS: Inadequate drug storage conditions were found in two SS and in all BHUs evaluated. There were no quality deviations found in the chloroquine samples. The quinine samples exhibited weight variation above the allowed limits. The primaquine samples were found to have packaging deficiency. The release of mefloquine in samples from some regions showed a statistically significant difference when compared with the CENADI samples. CONCLUSIONS: It is important to periodically evaluate the quality and storage conditions of essential drugs. The quality deviations found with the primaquine and quinine samples are not related to storage conditions and must be addressed urgently. The decreased mefloquine release from tablets is related to formulation problems or influenced by inadequate storage conditions, prompting further investigation. Even with the mentioned problems, the samples would probably not contribute to resistant parasite selection.

INTRODUÇÃO: O aparecimento de resistência aos medicamentos é um dos maiores problemas do tratamento da malária. O uso de medicamentos falsos e/ou de má qualidade pode contribuir para o desenvolvimento de resistência no parasita. Este estudo tem por objetivo avaliar a qualidade dos medicamentos antimaláricos distribuídos no Brasil. MÉTODOS: Amostras contendo comprimidos de difosfato de cloroquina, cloridrato de mefloquina, difosfato de primaquina e sulfato de quinina foram enviadas ao almoxarifado central na Cidade do Rio de Janeiro (CENADI), almoxarifados estaduais (SS) e Unidades Básicas de Saúde (UBS) nos estados da região norte do Brasil, totalizando dez amostras. Após cinco meses de armazenamento, as amostras foram coletadas e analisadas segundo métodos oficiais e da literatura. RESULTADOS: Foram encontradas condições inadequadas de armazenamento de medicamentos em duas SS e em todas as UBS avaliadas. Não foram encontrados problemas de qualidade com as amostras de cloroquina. As amostras de quinina apresentaram variação de peso acima dos limites permitidos. Amostras de primaquina foram encontradas com problemas na embalagem. A cedência de mefloquina de comprimidos, em algumas regiões, apresentou diferença estatisticamente significativa quando comparada com a amostra do CENADI. CONCLUSÕES: É importante avaliar, periodicamente, a qualidade e as condições de armazenamento de medicamentos essenciais. Desvios de qualidade encontrados com as amostras de primaquina e quinina não estão relacionados às condições de armazenamento e devem ser corrigidos urgentemente. O decréscimo na cedência de mefloquina dos comprimidos está relacionado com a formulação ou foi influenciada por condições de armazenamento inadequadas, necessitando de uma investigação posterior. Apesar dos problemas mencionados, as amostras provavelmente não contribuiriam para a seleção de parasitas resistentes.
Descritores: Antimaláricos/normas
Armazenamento de Medicamentos/normas
Medicamentos Essenciais/normas
-Brasil
Cromatografia Líquida de Alta Pressão
Cloroquina/normas
Mefloquina/normas
Primaquina/normas
Controle de Qualidade
Quinina/normas
Limites: Seres Humanos
Tipo de Publ: Estudos de Avaliação
Research Support, Non-U.S. Gov't
Responsável: BR1.1 - BIREME


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Id: lil-554015
Autor: Guzmán, Valentina; Carmona-Fonseca, Jaime; Cuesta, Fanny; Maestre, Amanda; Burgos, Luis C; Uscátegui, Rosa M.
Título: Respuesta terapéutica a mefloquina, estado nutricional y variantes alélicas del gen CYP3A4 en pacientes con malaria falciparum no complicada; Antioquia (Colombia) / Malaria: efficacy of mefloquine according to nutritional status and alellic variations of the CYP3A4 gen
Fonte: Iatreia;22(2):132-142, jun. 2009.
Idioma: es.
Resumo: Introducción: hay poca información sobre las relaciones entre la falla de la terapia antimalárica y algunos factores del hospedero (estado nutricional, fenotipo y genotipo del citocromo CYP450 que metaboliza el medicamento antipalúdico). Objetivo: explorar si la falla terapéutica de la mefloquina dada a pacientes con malaria falciparum no complicada se puede explicar por la influencia del estado nutricional del enfermo y del fenotipo y genotipo de su citocromo CYP3A4. Materiales y métodos: estudio de casos y controles no pareado. Pacientes: hombres y mujeres adultos, de Turbo y El Bagre (Antioquia, Colombia). Resultados: se evaluó la respuesta terapéutica en 46 enfermos; hubo solo tres fallas (6,5%); por la muy baja ocurrencia de falla terapéutica (n = 3/46), los resultados se presentan en forma descriptiva para los 46 pacientes. La relación dextrometorfano/3-metoximorfinano fue 0,39 (mediana); 20% fueron metabolizadores lentos. Las concentraciones sanguíneas medianas de mefloquina a las 24 horas (C24h) y al día 14 (Cd14) fueron 1.363 + 397 ng/mL y 978 + 106 ng/mL, respectivamente. Los 46 pacientes presentaron el alelo CYP3A4*2 (silvestre). Conclusión: no se pudo evaluar con profundidad la relación entre la respuesta a la terapia antimalárica, por una parte y, por otra, la actividad del CYP450 y el estado nutricional, pero hubo hallazgos que justifican la evaluación y control de las características del hospedero en estudios posteriores de farmacocinética antimalárica.

Introduction: Information on the relationship between treatment failure in malaria and factors of the host (nutritional status, phenotype and genotype of cytochrome CYP450) involved in the metabolism of antimalarials is scarce. Objective: To explore whether treatment failure of mefloquine administered to patients with noncomplicated falciparum malaria can be explained in terms of the patient's nutritional status and the CYP3A4 phenotype and genotype. Materials and methods: Non-matched case-control study. Patients were adult males and females, inhabitants of Turbo and El Bagre (Antioquia, Colombia). Results: The therapeutic response was assessed in 46 patients, and there were only three failures (6.5%); due to the rare occurrence of therapeutic failure (n = 3/46), results are presented in a descriptive way for the 46 patients. The dextrometorphan/3-methoxymorphinan ratio was 0.39 (median); 20% of the patients were slow metabolizers. The blood concentrations of mefloquine at 24 hours (C24h) and at day 14 (Cd14) were (median) 1.363 ± 397 ng/mL and 978 ± 106 ng/mL, respectively. All 46 patients had the wild CYP3A4*2 allele. Conclusion: We were unable to assess in depth the relationship between the response to mefloquine, on the one hand and, on the other, CYP450 activity and nutritional status. However, there were findings that justify the assessment and control of the characteristics of the host in subsequent studies of antimalarial pharmacokinetics.
Descritores: Alelos
Ferritinas
Malária
Desnutrição
Mefloquina
Selênio
SISTEMA ENZIMATICO DEL CITOCROMO P-ALDEHYDES
Vitamina A
Responsável: CO56.1 - Biblioteca


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Id: lil-544513
Autor: Vásquez, Ana María; Sanín, Felipe; Álvarez, Luis Gonzalo; Tobón, Alberto; Ríos, Alexandra; Blair, Silvia.
Título: Estudio piloto de la eficacia y de los efectos sobre los gametocitos del esquema artesunato-mefloquina-primaquina para la malaria por Plasmodium falciparum / Therapeutic efficacy of a regimen of artesunate-mefloquine-primaquine treatment for Plasmodium falciparum malaria and treatment effects on gametocytic development
Fonte: Biomédica (Bogotá);29(2):307-319, jun. 2009. tab, graf.
Idioma: es.
Resumo: Introducción. El tratamiento de la malaria por P. falciparum requiere de un esquema seguro, eficaz y de impacto en la transmisión. En 2006, se implementó en Antioquia el esquema artesunato-mefloquina y se adicionó primaquina para eliminar los gametocitos. Objetivo. Evaluar la eficacia y acción gametocida de los esquemas artesunato-mefloquina-primaquina y artesunato-mefloquina en pacientes con malaria no complicada por P. falciparum de Turbo, Antioquia. Materiales y métodos. Ensayo clínico aleatorio; los tratamientos se suministraron de forma supervisada y se realizó seguimiento clínico-parasitológico en los días 1, 2, 3, 7, 14, 21, 28, 35, y 42, para evaluar la respuesta según el protocolo OMS-2003 modificado. Resultados. Entre abril de 2007 y febrero de 2008, 50 pacientes fueron reclutados; los resultados mostraron una eficacia de 100% (IC95% 86,3%-100%) para el esquema artesunato-mefloquina (con/sin primaquina); la parasitemia y la fiebre fueron eliminadas completamente al tercer día de tratamiento en todos los pacientes. La eliminación de gametocitos fue mayor con el uso de primaquina; al tercer día de seguimiento, el 92% (IC95% 74%-99%) de los pacientes que recibieron primaquina no tuvieron gametocitos, en comparación con 78,3% (IC95% 59%-93%) de pacientes del grupo artesunato-mefloquina. Además, el esquema artesunato-mefloquina-primaquina eliminó la gametocitemia una semana antes que el esquema sin primaquina. Conclusión. Se recomienda el uso del esquema artesunato-mefloquina para la malaria por P. falciparum por su alta eficacia y se sugieren futuras evaluaciones del beneficio de la PQ en la reducción de la densidad y prevalencia de gametocitos.

Introduction. The treatment of Plasmodium falciparum malaria requires a safe and effective therapeutic treatment regimen, which in turn has high impact on the transmission. In 2006, an artesunate (AS)-mefloquine (MQ) treatment program was implemented in Antioquia. In addition, primaquine (PQ) was added to eliminate malaria gametocytes in the bloodstream. Objective. The efficacy and gametocytocidal activity was evaluated for two treatment regimens, AS-MQ-PQ and AS-MQ, in patients with uncomplicated P. falciparum malaria. Materials and methods. Between April 2007 and February 2008, 50 patients were recruited for the trial in Turbo, Antioquia. A randomized clinical trial was conducted. Treatment compliance was supervised, with a clinical and parasitological assessment on days 1, 2, 3, 7, 14, 21, 28, 35, and 42 to evaluate response rate according to the WHO 2003 protocol. Results. Clinical response and parasite elimination efficacy of AS-MQ (with or without PQ) was 100% (95% CI 86.3%-100%), and parasitemia and fever were absent on day 3 of treatment in all patients. Gametocyte elimination was superior when PQ was used--92% (95% CI: 74%-99%) of patients who received PQ had no gametocytes on day 3, compared to 78.3% (95% CI: 59%-93%) of patients who only received AS-MQ. Furthermore, circulating gametocytes were eliminated on average one week faster when the AS-MQ-PQ treatment scheme was used compared to the scheme without PQ. Conclusion. These studies recommend the use of AS-MQ to treat P. falciparum malaria given its good therapeutic efficacy. However, further assessment is suggested concerning the benefit of adding PQ to this treatment scheme.
Descritores: Malária
Mefloquina
Plasmodium falciparum
Primaquina
Resultado do Tratamento
Responsável: CO42.1 - Biblioteca Nacional de Salud José Celestino Mutis


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Id: lil-527176
Autor: Svihrova, Viera; Szilagyiova, Maria; Krkoska, Dusan; Simekova, Katarina; Hudeckova, Henrieta; Avdicova, Maria.
Título: Analysis of the direct and indirect costs of treatment of imported malaria in the Slovak Republic / Análise dos custos diretos e indiretos do tratamento da malária importada na República Eslovaca
Fonte: Rev. Soc. Bras. Med. Trop;42(4):377-380, July-Aug. 2009. tab.
Idioma: en.
Resumo: This study analyzed the approximate cost of treatment of patients hospitalized with a diagnosis of imported malaria in Slovakia. Between 2003 and 2007, 15 patients with imported malaria were hospitalized. The mean direct cost of the treatment was 970.75 euros and the mean indirect cost was 53.15 euros. For the patient with the highest cost of treatment, the use of mefloquine prophylaxis would have represented only 0.5 percent of the total direct cost of treating the disease. Despite the partial resistance of plasmodia, malaria chemoprophylaxis is unequivocally a cheaper choice than subsequent treatment of malaria.

Análise do custo aproximado do tratamento dos doentes hospitalizados na Eslováquia com malária importada. Entre 2003 a 2007, foram internados 15 doentes com malária importada. Os custos médios diretos do tratamento foram avaliados em 920,75 euros e indireto em 53,15 euros. No doente com o custo mais elevado de tratamento, a utilização da profilaxia com mefloquina representaria somente 0,5 por cento do total dos custos diretos do tratamento da doença. Apesar da resistência parcial do plasmódio, a quimioprofilaxia da malária é inequivocamente uma opção mais econômica do que o tratamento posterior da malária.
Descritores: Antimaláricos/economia
Custos de Cuidados de Saúde/estatística & dados numéricos
Malária/economia
Mefloquina/economia
-Antimaláricos/uso terapêutico
Análise Custo-Benefício
Malária/tratamento farmacológico
Malária/prevenção & controle
Mefloquina/uso terapêutico
Eslováquia
Adulto Jovem
Limites: Adulto
Animais
Feminino
Seres Humanos
Masculino
Meia-Idade
Adulto Jovem
Tipo de Publ: Research Support, Non-U.S. Gov't
Responsável: BR1.1 - BIREME



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