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ANDRADE JUNIOR, Heitor Franco de
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Id: lil-782098
Autor: Borborema, Samanta Etel Treiger; Osso Junior, João Alberto; Andrade Junior, Heitor Franco de; Nascimento, Nanci do.
Título: Antimonial drugs entrapped into phosphatidylserine liposomes: physicochemical evaluation and antileishmanial activity
Fonte: Rev. Soc. Bras. Med. Trop;49(2):196-203, Mar.-Apr. 2016. tab, graf.
Idioma: en.
Projeto: Conselho Nacional de Desenvolvimento Científico e Tecnológico.
Resumo: Abstract: INTRODUCTION: Leishmaniasis is a disease caused by the protozoan Leishmania that resides mainly in mononuclear phagocytic system tissues. Pentavalent antimonials are the main treatment option, although these drugs have toxic side effects and high resistance rates. A potentially alternative and more effective therapeutic strategy is to use liposomes as carriers of the antileishmanial agents. The aims of this study were to develop antimonial drugs entrapped into phosphatidylserine liposomes and to analyze their biological and physicochemical characteristics. METHODS: Liposomes containing meglumine antimoniate (MA) or pentavalent antimony salt (Sb) were obtained through filter extrusion (FEL) and characterized by transmission electron microscopy. Promastigotes of Leishmania infantum were incubated with the drugs and the viability was determined with a tetrazolium dye (MTT assay). The effects of these drugs against intracellular amastigotes were also evaluated by optical microscopy, and mammalian cytotoxicity was determined by an MTT assay. RESULTS: Liposomes had an average diameter of 162nm. MA-FEL showed inhibitory activity against intracellular L. infantum amastigotes, with a 50% inhibitory concentration (IC50) of 0.9μg/mL, whereas that of MA was 60μg/mL. Sb-FEL showed an IC50 value of 0.2μg/mL, whereas that of free Sb was 9μg/mL. MA-FEL and Sb-FEL had strong in vitro activity that was 63-fold and 39-fold more effective than their respective free drugs. MA-FEL tested at a ten-times higher concentration than Sb-FEL did not show cytotoxicity to mammalian cells, resulting in a higher selectivity index. CONCLUSIONS: Antimonial drug-containing liposomes are more effective against Leishmania-infected macrophages than the non-liposomal drugs.
Descritores: Compostos Organometálicos/farmacologia
Fosfatidilserinas/farmacologia
Macrófagos Peritoneais/parasitologia
Leishmania infantum/efeitos dos fármacos
Gluconato de Antimônio e Sódio/farmacologia
Meglumina/farmacologia
Antiprotozoários/farmacologia
-Compostos Organometálicos/química
Fosfatidilserinas/química
Cricetinae
Gluconato de Antimônio e Sódio/química
Concentração Inibidora 50
Testes de Sensibilidade Parasitária
Relação Dose-Resposta a Droga
Antimoniato de Meglumina
Lipossomos
Meglumina/química
Camundongos
Camundongos Endogâmicos BALB C
Antiprotozoários/química
Limites: Animais
Responsável: BR1.1 - BIREME


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Id: lil-798117
Autor: Correia, Vanessa Carolina de Sena; Lima, Nathália Oliveira; Oliveira, Flávio Augusto de Souza; Santos, Ana Paula de Azevedo dos; Teles, Carolina Bioni Garcia; Oliveira Júnior, Waldesse Piragé de; Pimenta, and Raphael Sanzio.
Título: Evaluation of the antiplasmodial and leishmanicidal potential of Myrciaria dubia (Myrtaceae) extract
Fonte: Rev. Soc. Bras. Med. Trop;49(5):586-592, Sept.-Oct. 2016. tab, graf.
Idioma: en.
Projeto: Coordenação de Aperfeiçoamento de Pessoal de Nível Superior.
Resumo: Abstract INTRODUCTION: Malaria and leishmaniasis are prevalent in tropical regions, which have environmental characteristics that are highly favorable to protozoa and vectors of these diseases; the transmission of these infections in sub-tropical regions, although recognized, represents only a small fraction of cases. Plants are constantly being used in the search for and acquisition of new drugs, and many compounds derived from them have been used to combat various diseases. In this study, we evaluated the action of the dichloromethanolic extract of Myrciaria dubia leaves against the protozoa Plasmodium falciparum, Leishmania amazonensis, Leishmania braziliensis, and Leishmania chagasi through bioassays. METHODS The extract from M. dubia was tested for its anti-P. falciparum activity in an anti-histidine-rich protein II immunosorbent assay. The antileishmanial assays were performed using the resazurin method, while cytotoxicity against human hepatoma (HepG2) strain was determined using the colorimetric MTT [3-(4, 5-dimethyl-2- thiazolyl)-2, 5-diphenyl-2H tetrazolium bromide] method. RESULTS The M. dubia extract presented a half-maximal inhibitory concentration equal to 2.35 (1.05)μg/mL for P. falciparum, 190.73 (6.41) μg/mL for L. amazonensis, and greater than equal to 200µg/mL for L. chagasi and L. braziliensis strains. The cytotoxic concentration for 50% of the cells was above 500μg/mL for HepG2, indicating no toxicity and greater selectivity against parasites. CONCLUSIONS The results obtained indicate the presence of antiplasmodial and leishmanicidal bioactive compounds in the dichloromethanolic extracts of M. dubia leaves, and point towards future studies to elucidate the mechanism of action for each physiological effect.
Descritores: Plasmodium falciparum/efeitos dos fármacos
Extratos Vegetais/farmacologia
Myrtaceae/química
Leishmania/efeitos dos fármacos
Antimaláricos/farmacologia
Antiprotozoários/farmacologia
-Extratos Vegetais/toxicidade
Técnicas Imunoenzimáticas
Colorimetria
Concentração Inibidora 50
Testes de Sensibilidade Parasitária
Células Hep G2/efeitos dos fármacos
Leishmania/classificação
Antimaláricos/isolamento & purificação
Antimaláricos/toxicidade
Antiprotozoários/isolamento & purificação
Antiprotozoários/toxicidade
Limites: Humanos
Responsável: BR1.1 - BIREME


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Id: lil-798123
Autor: Meneguetti, Dionatas Ulises de Oliveira; Lima, Renato Abreu; Hurtado, Fernanda Bay; Passarini, Guilherme Matos; Macedo, Sharon Rose Aragão; Barros, Neuza Biguinati de; Oliveira, Flávio Augusto de Souza; Medeiros, Patrícia Soares de Maria de; Militão, Júlio Sancho Linhares Teixeira; Nicolete, Roberto; Facundo, Valdir Alves.
Título: Screening of the in vitro antileishmanial activities of compounds and secondary metabolites isolated from Maytenus guianensis Klotzsch ex Reissek (Celastraceae) chichuá Amazon
Fonte: Rev. Soc. Bras. Med. Trop;49(5):579-585, Sept.-Oct. 2016. tab, graf.
Idioma: en.
Resumo: Abstract INTRODUCTION Maytenus guianensis is a member of the Celastraceae family that is used in traditional medicine, particularly for its anti-parasitic and anti-cancer effects. To explore the ethnopharmacological potential of this plant, the present study was designed to screen the in vitro antileishmanial activities of extracts and compounds isolated from M. guianensis. METHODS Maytenus guianensis stems and leaves were extracted in acetone, followed by the preparation of eluates and isolation of secondary metabolites using chromatography on a glass column with silica gel as the fixed phase. The chemical components were identified using spectroscopic methods, including one- and two-dimensional nuclear magnetic resonance of hydrogen-1 and carbon-13, mass spectroscopy, and infrared spectroscopy. The anti-Leishmania amazonensis activities of these eluates and compounds were evaluated by direct promastigote counting and viability assays. RESULTS It was found that the hexane bark eluate produced the strongest anti-L. amazonensis effect, with 90-100% inhibition of the promastigote form. The isolated metabolite that produced the best result was tingenone B, followed by a compound formed by the union of tingenone and tingenone B (80-90% inhibition). CONCLUSIONS Maytenus guianensis shows anti-parasite activity that warrants further investigation to determine the mechanisms underlying this antileishmanial effect and to evaluate the pharmacological potential of these eluates and isolated secondary metabolites, while minimizing any adverse effects.
Descritores: Leishmania braziliensis/efeitos dos fármacos
Extratos Vegetais/farmacologia
Maytenus/química
Antiprotozoários/farmacologia
-Testes de Sensibilidade Parasitária
Antiprotozoários/isolamento & purificação
Responsável: BR1.1 - BIREME


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Marzochi, Mauro Célio de Almeida
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Id: biblio-1041383
Autor: Duque, Maria Cristina de Oliveira; Vasconcellos, Érica de Camargo Ferreira e; Pimentel, Maria Inês Fernandes; Lyra, Marcelo Rosandiski; Pacheco, Sandro Javier Bedoya; Marzochi, Mauro Celio de Almeida; Rosalino, Cláudia Maria Valete; Schubach, Armando de Oliveira.
Título: Standardization of intralesional meglumine antimoniate treatment for cutaneous leishmaniasis
Fonte: Rev. Soc. Bras. Med. Trop;49(6):774-776, Dec. 2016. graf.
Idioma: en.
Resumo: Abstract INTRODUCTION: Intralesional treatment for cutaneous leishmaniasis has been applied for over 30 years at the Oswaldo Cruz Foundation, Rio de Janeiro, with good therapeutic results and without relevant systemic toxicity. METHODS Meglumine antimoniate was injected subcutaneously, using a long medium-caliber needle (for example, 30mm × 0.8mm); patients received 1-3 injections, with 15-day intervals. RESULTS The technique is described in detail sufficient to enable replication. CONCLUSIONS: The treatment of cutaneous leishmaniasis with intralesional meglumine antimoniate is a simple, effective, and safe technique, which may be used in basic healthcare settings.
Descritores: Compostos Organometálicos/administração & dosagem
Leishmaniose Cutânea/tratamento farmacológico
Meglumina/administração & dosagem
Antiprotozoários/administração & dosagem
-Injeções Intralesionais/normas
Antimoniato de Meglumina
Limites: Humanos
Responsável: BR1.1 - BIREME


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Id: biblio-896990
Autor: Assis, Tália Santana Machado de; Rosa, Dian Carlos Pinheiro; Teixeira, Eliane de Morais; Cota, Gláucia; Azeredo-da-Silva, André Luís Ferreira; Werneck, Guilherme; Rabello, Ana.
Título: The direct costs of treating human visceral leishmaniasis in Brazil
Fonte: Rev. Soc. Bras. Med. Trop;50(4):478-482, July-Aug. 2017. tab.
Idioma: en.
Projeto: Conselho Nacional de Desenvolvimento Científico e Tecnológico.
Resumo: Abstract INTRODUCTION: The drugs available for visceral leishmaniasis (VL) treatment in Brazil have specific characteristics in terms of operability, effectiveness, toxicity, and cost. The aim of this study was to estimate the direct costs of therapies recommended by the Ministry of Health (MH) for VL treatment in Brazil. METHODS: The analytical perspective used was that adopted by the Brazilian Public Health System. Three drugs and four regimens were included: 1) N-methyl glucamine antimoniate intramuscularly at 20mg per kg per day for 30 days; 2) N-methyl glucamine antimoniate intravenously at 20mg per kg per day for 30 days; 3) amphotericin B deoxycholate at 1mg per kg per day for 21 days; and 4) liposomal amphotericin B at 3mg per kg per day for a 7 days treatment. RESULTS: The estimated direct costs of treatment for an adult patient using N-methylglucamine antimoniate administered via the intramuscular and intravenous routes were USD 418.52 and USD 669.40, respectively. The estimated cost of treatment with amphotericin B deoxycholate was USD 1,522.70. Finally, the estimated costs of treatment with liposomal amphotericin B were USD 659.79, and USD 11,559.15 using the price adopted by the WHO and the Drug Regulation Board, respectively. CONCLUSIONS: This analysis indicates the economic feasibility of replacing N-methyl glucamine antimoniate with liposomal amphotericin B, which allows a shorter treatment period with less toxicity compared with other treatments, provided that the purchase value used by the WHO and transferred to the MH is maintained.
Descritores: Custos de Cuidados de Saúde/estatística & dados numéricos
Leishmaniose Visceral/tratamento farmacológico
Antiprotozoários/economia
-Compostos Organometálicos/economia
Compostos Organometálicos/uso terapêutico
Brasil
Anfotericina B/economia
Anfotericina B/uso terapêutico
Protocolos Clínicos
Ácido Desoxicólico/economia
Ácido Desoxicólico/uso terapêutico
Combinação de Medicamentos
Antimoniato de Meglumina
Leishmaniose Visceral/economia
Meglumina/economia
Meglumina/uso terapêutico
Antiprotozoários/uso terapêutico
Limites: Humanos
Responsável: BR1.1 - BIREME


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Id: biblio-842839
Autor: Pimentel, Maria Inês Fernandes; Vasconcellos, Érica de Camargo Ferreira e; Ribeiro, Carla de Oliveira; Lyra, Marcelo Rosandiski; Saheki, Mauricio Naoto; Salgueiro, Mariza de Matos; Antonio, Liliane de Fátima; Schubach, Armando de Oliveira.
Título: Intralesional treatment with meglumine antimoniate in three patients with New World cutaneous leishmaniasis and large periarticular lesions with comorbidities
Fonte: Rev. Soc. Bras. Med. Trop;50(2):269-272, Mar.-Apr. 2017. tab, graf.
Idioma: en.
Resumo: Abstract Although New World cutaneous leishmaniasis is not itself a life-threatening disease, its treatment with systemic antimonials can cause toxicity that can be dangerous to some patients. Intralesional meglumine antimoniate provides a viable, less toxic alternative. Herein, we describe an alternative treatment with subcutaneous intralesional injections of meglumine antimoniate into large periarticular lesions of three patients with cutaneous leishmaniasis and comorbidities. This treatment was safe, successful, and well tolerated. This case series suggests that intralesional meglumine antimoniate is an effective therapy for cutaneous leishmaniasis, even with periarticular lesions. This hypothesis should be tested in controlled clinical trials.
Descritores: Compostos Organometálicos/administração & dosagem
Leishmaniose Cutânea/tratamento farmacológico
Meglumina/administração & dosagem
Antiprotozoários/administração & dosagem
-Fatores de Tempo
Índice de Gravidade de Doença
Injeções Intralesionais
Resultado do Tratamento
Meglumina
Pessoa de Meia-Idade
Limites: Humanos
Masculino
Feminino
Idoso
Tipo de Publ: Relatos de Casos
Responsável: BR1.1 - BIREME


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Romero, Gustavo Adolfo Sierra
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Id: biblio-842815
Autor: Borges, Myrlena Mescouto; Pranchevicius, Maria Cristina da Silva; Noronha, Elza Ferreira; Romero, Gustavo Adolfo Sierra; Carranza-Tamayo, César Omar.
Título: Efficacy and safety of amphotericin B deoxycholate versus N-methylglucamine antimoniate in pediatric visceral leishmaniasis: an open-label, randomized, and controlled pilot trial in Brazil
Fonte: Rev. Soc. Bras. Med. Trop;50(1):67-74, Jan.-Feb. 2017. tab, graf.
Idioma: en.
Resumo: ABSTRACT INTRODUCTION Despite their high toxicity, antimonials and amphotericin B deoxycholate are commonly used for treating visceral leishmaniasis (VL). Few studies showing conflictive data about their efficacy and adverse events in pediatric population are available. This study aimed to evaluate efficacy and safety of amphotericin B deoxycholate vs. that of N-methylglucamine antimoniate in treating pediatric VL in Brazil. METHODS This was a randomized, open-label, 2-arm and controlled pilot clinical trial. Treatment naïve children and adolescents with VL without signs of severe illness were treated with N-methylglucamine antimoniate (20mg/kg/day for 20 days) or amphotericin B deoxycholate (1 mg/kg/day for 14 days). All patients were diagnosed with positive direct examination and/or positive PCR for Leishmania spp. performed in bone marrow samples. The primary efficacy end-point was VL cure determined after 180 days of completion of treatment. The analysis was performed using intention-to-treat (ITT) and per protocol (PP) analyses. RESULTS In total, 101 volunteers were assessed. Efficacy was similar for both groups. The antimonial (n=51) and amphotericin B groups (n=50) had a cure rate of 94.1% and 100%, and 94% and 97.9% according to ITT and PP analyses, respectively. All patients reported adverse events (AE). Serious AE incidence was similar in both groups. Five individuals were excluded from the study because of severe adverse events. CONCLUSIONS N-methylglucamine antimoniate and amphotericin B deoxycholate have similar efficacy and adverse events rate in pediatric patients with VL.
Descritores: Compostos Organometálicos/uso terapêutico
Anfotericina B/uso terapêutico
Ácido Desoxicólico/uso terapêutico
Leishmaniose Visceral/tratamento farmacológico
Meglumina/uso terapêutico
Antiprotozoários/uso terapêutico
-Compostos Organometálicos/efeitos adversos
Projetos Piloto
Anfotericina B/efeitos adversos
Resultado do Tratamento
Ácido Desoxicólico/efeitos adversos
Combinação de Medicamentos
Antimoniato de Meglumina
Meglumina/efeitos adversos
Antiprotozoários/efeitos adversos
Limites: Humanos
Masculino
Feminino
Pré-Escolar
Criança
Tipo de Publ: Estudo Comparativo
Ensaio Clínico Controlado Aleatório
Ensaio Clínico Fase IV
Responsável: BR1.1 - BIREME


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Id: biblio-842826
Autor: Mesa, Luz Estella; Vasquez, Daniel; Lutgen, Pierre; Vélez, Iván Darío; Restrepo, Adriana María; Ortiz, Isabel; Robledo, Sara María.
Título: In vitro and in vivo antileishmanial activity of Artemisia annua L. leaf powder and its potential usefulness in the treatment of uncomplicated cutaneous leishmaniasis in humans
Fonte: Rev. Soc. Bras. Med. Trop;50(1):52-60, Jan.-Feb. 2017. tab, graf.
Idioma: en.
Projeto: Departamento Administrativo de Ciencia, Tecnología e Innovación-COLCIENCIAS.
Resumo: ABSTRACT INTRODUCTION: Cutaneous leishmaniasis (CL) is a tropical disease that affects millions of individuals worldwide. The current drugs for CL may be effective but have serious side effects; hence, alternatives are urgently needed. Although plant-derived materials are used for the treatment of various diseases in 80% of the global population, the validation of these products is essential. Gelatin capsules containing dried Artemisia annua leaf powder were recently developed as a new herbal formulation (totum) for the oral treatment of malaria and other parasitic diseases. Here, we aimed to determine the usefulness of A. annua gel capsules in CL. METHODS: The antileishmanial activity and cytotoxicity of A. annua L. capsules was determined via in vitro and in vivo studies. Moreover, a preliminary evaluation of its therapeutic potential as antileishmanial treatment in humans was conducted in 2 patients with uncomplicated CL. RESULTS: Artemisia annua capsules showed moderate in vitro activity in amastigotes of Leishmania (Viannia) panamensis; no cytotoxicity in U-937 macrophages or genotoxicity in human lymphocytes was observed. Five of 6 (83.3%) hamsters treated with A. annua capsules (500mg/kg/day) for 30 days were cured, and the 2 examined patients were cured 45 days after initiation of treatment with 30g of A. annua capsules, without any adverse reactions. Both patients remained disease-free 26 and 24 months after treatment completion. CONCLUSION: Capsules of A. annua L. represent an effective treatment for uncomplicated CL, although further randomized controlled trials are needed to validate its efficacy and safety.
Descritores: Extratos Vegetais/uso terapêutico
Extratos Vegetais/farmacologia
Leishmaniose Cutânea/tratamento farmacológico
Artemisia annua/química
Antiprotozoários/uso terapêutico
Antiprotozoários/farmacologia
-Cricetinae
Resultado do Tratamento
Folhas de Planta/química
Testes de Sensibilidade Parasitária
Leishmania/efeitos dos fármacos
Limites: Humanos
Animais
Masculino
Feminino
Adulto
Tipo de Publ: Relatos de Casos
Responsável: BR1.1 - BIREME


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Id: biblio-957424
Autor: Pedras, Mariana Junqueira; Carvalho, Janaína de Pina; Silva, Rosiana Estéfane da; Ramalho, Dario Brock; Senna, Maria Camilo Ribeiro de; Moreira, Hugo Silva Assis; Martinho, Lorena Zaine Matos; Rabello, Ana; Cota, Gláucia.
Título: Mucosal leishmaniasis: the experience of a Brazilian referral center
Fonte: Rev. Soc. Bras. Med. Trop;51(3):318-323, Apr.-June 2018. tab, graf.
Idioma: en.
Resumo: Abstract INTRODUCTION Pentavalent antimonials (Sbv) are the most commonly used drugs for the treatment of mucosal leishmaniasis (ML), despite their high toxicity and only moderate efficacy. The aim of this study was to report therapeutic responses with different available options for ML. METHODS This study was based on a review of clinical records of 35 patients (24 men and 11 women) treated between 2009 and 2015. RESULTS The median age of patients was 63 years, and the median duration of the disease was 24 months. Seventeen patients received Sbv, while nine patients were treated with liposomal amphotericin B (AmB), and another nine patients were treated with fluconazole. Patients treated with AmB received a total median accumulated dose of 2550mg. The mean duration of azole use was 120 days, and the daily dose ranged from 450 to 900mg. At the three-month follow-up visit, the cure rate was 35%, 67%, and 22% for Sbv, AmB, and azole groups, respectively. At the six-month follow-up visit, the cure rates for Sbv, AmB, and azole groups were 71%, 78%, and 33%, respectively. CONCLUSIONS There is a scarcity of effective ML treatment alternatives, and based on our observations, fluconazole is not a valid treatment option.
Descritores: Leishmaniose Mucocutânea/tratamento farmacológico
Fluconazol/uso terapêutico
Anfotericina B/uso terapêutico
Antimônio/uso terapêutico
Antiprotozoários/uso terapêutico
-Índice de Gravidade de Doença
Resultado do Tratamento
Pessoa de Meia-Idade
Limites: Humanos
Masculino
Feminino
Adulto
Idoso
Idoso de 80 Anos ou mais
Responsável: BR1.1 - BIREME


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Id: biblio-957422
Autor: Gomes, Maria Antonia Ferreira; Medeiros, Lana Lira Cantidio de; Lobo, Fernanda Paula Dantas; Wanderley, Nathália Rayane Silva; Matos, Ana Paula Rodrigues; Jácome, Tácito do Nascimento; Monteiro, Maria Goretti Lins; Luz, Kleber Giovanni.
Título: Combination therapy with liposomal amphotericin b (ambisome), n-methylglucamine antimoniate (glucantime), and pentamidine isethionate in a refractory visceral leishmaniasis case
Fonte: Rev. Soc. Bras. Med. Trop;51(3):393-396, Apr.-June 2018. tab, graf.
Idioma: en.
Resumo: Abstract Visceral leishmaniasis is a systemic disease that is potentially severe and endemic in Brazil. It clinically manifests as fever, weight loss, swelling, hepatosplenomegaly, paleness, and edema. In this study, we discuss a case of a 1-year-old child diagnosed with refractory visceral leishmaniasis after being treated with liposomal amphotericin B in two distinct occasions. Considering the persistent clinical features and weak response to conventional treatment, a combination therapy with liposomal amphotericin B (ambisome), n-methylglucamine antimoniate (glucantime), and pentamidine isethionate was initiated, and response to treatment was good.
Descritores: Compostos Organometálicos/administração & dosagem
Pentamidina/administração & dosagem
Anfotericina B/administração & dosagem
Leishmaniose Visceral/tratamento farmacológico
Meglumina/administração & dosagem
Antiprotozoários/administração & dosagem
-Quimioterapia Combinada
Antimoniato de Meglumina
Limites: Humanos
Masculino
Lactente
Tipo de Publ: Relatos de Casos
Responsável: BR1.1 - BIREME



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