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[PMID]:28910299
[Au] Autor:Alpern JD; Lopez-Velez R; Stauffer WM
[Ad] Endereço:Division of Infectious Disease & International Medicine, Department of Internal Medicine, University of Minnesota, Minneapolis, Minnesota, United States of America.
[Ti] Título:Access to benznidazole for Chagas disease in the United States-Cautious optimism?
[So] Source:PLoS Negl Trop Dis;11(9):e0005794, 2017 Sep.
[Is] ISSN:1935-2735
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Drugs for neglected tropical diseases (NTD) are being excessively priced in the United States. Benznidazole, the first-line drug for Chagas disease, may become approved by the Food and Drug Administration (FDA) and manufactured by a private company in the US, thus placing it at risk of similar pricing. Chagas disease is an NTD caused by Trypanosoma cruzi; it is endemic to Latin America, infecting 8 million individuals. Human migration has changed the epidemiology causing nonendemic countries to face increased challenges in diagnosing and managing patients with Chagas disease. Only 2 drugs exist with proven efficacy: benznidazole and nifurtimox. Benznidazole has historically faced supply problems and drug shortages, limiting accessibility. In the US, it is currently only available under an investigational new drug (IND) protocol from the CDC and is provided free of charge to patients. However, 2 companies have stated that they intend to submit a New Drug Application (NDA) for FDA approval. Based on recent history of companies acquiring licensing rights for NTD drugs in the US with limited availability, it is likely that benznidazole will become excessively priced by the manufacturer-paradoxically making it less accessible. However, if the companies can be taken at their word, there may be reason for optimism.
[Mh] Termos MeSH primário: Doença de Chagas/tratamento farmacológico
Nitroimidazóis/economia
Nitroimidazóis/provisão & distribuição
Tripanossomicidas/economia
Tripanossomicidas/provisão & distribuição
[Mh] Termos MeSH secundário: Centers for Disease Control and Prevention (U.S.)
Doença de Chagas/epidemiologia
Custos de Medicamentos
Drogas em Investigação/economia
Seres Humanos
Nifurtimox/uso terapêutico
Nitroimidazóis/uso terapêutico
Tripanossomicidas/uso terapêutico
Estados Unidos
United States Food and Drug Administration
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Drugs, Investigational); 0 (Nitroimidazoles); 0 (Trypanocidal Agents); M84I3K7C2O (Nifurtimox); YC42NRJ1ZD (benzonidazole)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170924
[Lr] Data última revisão:
170924
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170915
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pntd.0005794


  2 / 410 MEDLINE  
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Texto completo SciELO Brasil
[PMID]:28902285
[Au] Autor:Santeliz S; Caicedo P; Giraldo E; Alvarez C; Yustiz MD; Rodríguez-Bonfante C; Bonfante-Rodríguez R; Bonfante-Cabarcas R
[Ad] Endereço:Decanato de Ciencias Veterinarias, Unidad de Biomedicina, Departamento de Medicina y Cirugía, Barquisimeto, Estado Lara, Venezuela.
[Ti] Título:Dipyridamole potentiated the trypanocidal effect of nifurtimox and improved the cardiac function in NMRI mice with acute chagasic myocarditis.
[So] Source:Mem Inst Oswaldo Cruz;112(9):596-608, 2017 Sep.
[Is] ISSN:1678-8060
[Cp] País de publicação:Brazil
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: As chronic Chagas disease does not have a definitive treatment, the development of alternative therapeutic protocols is a priority. Dipyridamole (DPY) is an alternative to counteract the pathophysiological phenomena involved in Chagas cardiomyopathy. OBJECTIVE: To evaluate the therapeutic efficacy of DPY associated with nifurtimox (Nfx) in epimastigote axenic cultures and in mice with acute Chagas disease. METHODS: NMRI adult male mice were divided into nine groups: three healthy and six Trypanosoma cruzi-infected groups. Mice received vehicle, Nfx or DPY, alone or combined. The doses assayed were Nfx 10 and 40 mg/kg and DPY 30 mg/kg. The treatment efficacy was evaluated by clinical, electrocardiographic, parasitological, biochemical and histopathological methods. FINDINGS: In vitro, DPY and Nfx had a trypanocidal effect with IC50 values of 372 ± 52 and 21.53 ± 2.13 µM, respectively; DPY potentiated the Nfx effect. In vivo, Nfx (40 mg/kg) with or without DPY had a therapeutic effect, which was reflected in the 84-92% survival rate and elimination of parasitaemia and heart tissue amastigotes. Nfx (10 mg/kg) had a subtherapeutic effect with no survival and persistence of amastigotes, inflammation and fibrosis in heart tissue; adding DPY increased the survival rate to 85%, and all tested parameters were significantly improved. MAIN CONCLUSION: DPY has a trypanocidal effect in vitro and enhances the Nfx therapeutic effect in an in vivo murine model.
[Mh] Termos MeSH primário: Cardiomiopatia Chagásica/tratamento farmacológico
Dipiridamol/uso terapêutico
Nifurtimox/uso terapêutico
Tripanossomicidas/uso terapêutico
[Mh] Termos MeSH secundário: Doença Aguda
Animais
Modelos Animais de Doenças
Sinergismo Farmacológico
Quimioterapia Combinada
Masculino
Camundongos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Trypanocidal Agents); 64ALC7F90C (Dipyridamole); M84I3K7C2O (Nifurtimox)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171109
[Lr] Data última revisão:
171109
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170914
[St] Status:MEDLINE


  3 / 410 MEDLINE  
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Texto completo SciELO Chile
[PMID]:28394984
[Au] Autor:Muñoz Casas Del Valle P
[Ti] Título:[Treatment and follow up of Chagas Disease in immunocompromised hosts].
[Ti] Título:Tratamiento y seguimiento de la enfermedad de Chagas en pacientes inmunocomprometidos..
[So] Source:Rev Chilena Infectol;34(1):67-68, 2017 02.
[Is] ISSN:0717-6341
[Cp] País de publicação:Chile
[La] Idioma:spa
[Mh] Termos MeSH primário: Doença de Chagas/tratamento farmacológico
Doença de Chagas/imunologia
Hospedeiro Imunocomprometido
Tripanossomicidas/uso terapêutico
[Mh] Termos MeSH secundário: Seguimentos
Infecções por HIV/complicações
Seres Humanos
Imunocompetência
Nifurtimox/uso terapêutico
Nitroimidazóis/uso terapêutico
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Nitroimidazoles); 0 (Trypanocidal Agents); M84I3K7C2O (Nifurtimox); YC42NRJ1ZD (benzonidazole)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170914
[Lr] Data última revisão:
170914
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170411
[St] Status:MEDLINE


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[PMID]:28302040
[Au] Autor:Vázquez K; Paulino M; Salas CO; Zarate-Ramos JJ; Vera B; Rivera G
[Ad] Endereço:Facultad de Medicina Veterinaria y Zootecnia, Universidad Autónoma de Nuevo León, Escobedo, 66050, Mexico.
[Ti] Título:Trypanothione Reductase: A Target for the Development of Anti- Trypanosoma cruzi Drugs.
[So] Source:Mini Rev Med Chem;17(11):939-946, 2017.
[Is] ISSN:1875-5607
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:BACKGROUND & OBJECTIVE: Chagas disease or American trypanosomiasis is a major parasitic disease in Latin America with restricted available treatment: nifurtimox and benznidazole. These two drugs are ineffective in the chronic phase of the disease; therefore, there is a need for the development of new, efficient and safe drugs for the treatment of this pathology. With this goal, one of the promising targets is trypanothione reductase (TR), a key enzyme in the metabolism of Trypanosoma cruzi. CONCLUSION: In this review, we analyse the importance of TR as a drug target, as well as the well-known and new inhibitors reported in the last decade as potential therapeutic agents for Chagas disease.
[Mh] Termos MeSH primário: Doença de Chagas/tratamento farmacológico
Sistemas de Liberação de Medicamentos
NADH NADPH Oxirredutases/metabolismo
Tripanossomicidas/química
Tripanossomicidas/uso terapêutico
Trypanosoma cruzi/enzimologia
[Mh] Termos MeSH secundário: Animais
Inibidores Enzimáticos/química
Inibidores Enzimáticos/farmacologia
Seres Humanos
Estrutura Molecular
Nifurtimox/química
Nifurtimox/farmacologia
Tripanossomicidas/farmacologia
Trypanosoma cruzi/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Enzyme Inhibitors); 0 (Trypanocidal Agents); EC 1.6.- (NADH, NADPH Oxidoreductases); EC 1.8.1.12 (trypanothione reductase); M84I3K7C2O (Nifurtimox)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170928
[Lr] Data última revisão:
170928
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170318
[St] Status:MEDLINE
[do] DOI:10.2174/1389557517666170315145410


  5 / 410 MEDLINE  
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Reis, Alexandre Barbosa
Lana, Marta de
Texto completo
[PMID]:27908747
[Au] Autor:Oliveira MT; Branquinho RT; Alessio GD; Mello CG; Nogueira-de-Paiva NC; Carneiro CM; Toledo MJ; Reis AB; Martins-Filho OA; Lana M
[Ad] Endereço:Núcleo de Pesquisas em Ciências Biológicas (NUPEB), Campus Universitário Morro do Cruzeiro, Universidade Federal de Ouro Preto, CEP: 35400-000 Ouro Preto, MG, Brazil.
[Ti] Título:TcI, TcII and TcVI Trypanosoma cruzi samples from Chagas disease patients with distinct clinical forms and critical analysis of in vitro and in vivo behavior, response to treatment and infection evolution in murine model.
[So] Source:Acta Trop;167:108-120, 2017 Mar.
[Is] ISSN:1873-6254
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:The clonal evolution of Trypanosoma cruzi sustains scientifically the hypothesis of association between parasite's genetic, biological behavior and possibly the clinical aspects of Chagas disease in patients from whom they were isolated. This study intended to characterize a range of biological properties of TcI, TcII and TcVI T. cruzi samples in order to verify the existence of these associations. Several biological features were evaluated, including in vitro epimastigote-growth, "Vero"cells infectivity and growth, along with in vivo studies of parasitemia, polymorphism of trypomastigotes, cardiac inflammation, fibrosis and response to treatment by nifurtimox during the acute and chronic murine infection. The global results showed that the in vitro essays (acellular and cellular cultures) TcII parasites showed higher values for all parameters (growth and infectivity) than TcVI, followed by TcI. In vivo TcII parasites were more virulent and originated from patients with severe disease. Two TcII isolates from patients with severe pathology were virulent in mice, while the isolate from a patient with the indeterminate form of the disease caused mild infection. The only TcVI sample, which displayed low values in all parameters evaluated, was also originated of an indeterminate case of Chagas disease. Response to nifurtimox was not associated to parasite genetic and biology, as well as to clinical aspects of human disease. Although few number of T. cruzi samples have been analyzed, a discreet correlation between parasite genetics, biological behavior in vitro and in vivo (murine model) and the clinical form of human disease from whom the samples were isolated was verified.
[Mh] Termos MeSH primário: Doença de Chagas/parasitologia
Nifurtimox/farmacologia
Tripanossomicidas/farmacologia
Trypanosoma cruzi/efeitos dos fármacos
Trypanosoma cruzi/patogenicidade
[Mh] Termos MeSH secundário: Animais
Células Cultivadas
Modelos Animais de Doenças
Seres Humanos
Camundongos
Trypanosoma cruzi/isolamento & purificação
Virulência
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Trypanocidal Agents); M84I3K7C2O (Nifurtimox)
[Em] Mês de entrada:1702
[Cu] Atualização por classe:170817
[Lr] Data última revisão:
170817
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161203
[St] Status:MEDLINE


  6 / 410 MEDLINE  
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[PMID]:28031550
[Au] Autor:Navarrete-Sandoval RH; Servín-Rojas M
[Ad] Endereço:Department of Infectious Diseases, Hospital General de Cuernavaca "Dr. José G. Parres", Cuernavaca, Mexico.
[Ti] Título:Bug Smash, Bug Splash: A Case Report of an Unusual Transmission of American Trypanosomiasis with a Brief Review of the Literature.
[So] Source:Am J Case Rep;17:993-996, 2016 Dec 29.
[Is] ISSN:1941-5923
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND Chagas disease is a chronic parasitosis transmitted by the inoculation of infected triatomine feces into wounds or conjunctival sac, transfusion, congenitally, organ transplantation, and ingestion of contaminated food. The disease is classified into an acute and chronic phase; the latter is a life-long infection that can be asymptomatic or progress to cardiac or digestive complications. CASE REPORT We report a case of acute-phase Chagas disease, transmitted by the splash of gut content from an infected triatomine into the conjunctival mucosa. CONCLUSIONS The diagnosis of Chagas disease is made by the direct visualization of the parasite in blood smears during the acute phase of the disease; during the chronic phase of the disease the diagnosis is made by the detection of IgG antibodies. Parasitological cure can be achieved in up to 80% of the cases in acute phase of the disease, in contrast with less than 30% during the chronic phase.
[Mh] Termos MeSH primário: Doença de Chagas/diagnóstico
Doença de Chagas/transmissão
Nifurtimox/uso terapêutico
Tripanossomicidas/uso terapêutico
Trypanosoma cruzi/parasitologia
[Mh] Termos MeSH secundário: Adulto
Animais
Doença de Chagas/parasitologia
Edema/parasitologia
Febre/parasitologia
Cefaleia/parasitologia
Seres Humanos
Masculino
Doenças Negligenciadas
Resultado do Tratamento
Triatominae/parasitologia
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Trypanocidal Agents); M84I3K7C2O (Nifurtimox)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170320
[Lr] Data última revisão:
170320
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161230
[St] Status:MEDLINE


  7 / 410 MEDLINE  
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[PMID]:27855164
[Au] Autor:Dauchy FA; Bonhivers M; Landrein N; Dacheux D; Courtois P; Lauruol F; Daulouède S; Vincendeau P; Robinson DR
[Ad] Endereço:University of Bordeaux, laboratoire de parasitologie, France.
[Ti] Título:Trypanosoma brucei CYP51: Essentiality and Targeting Therapy in an Experimental Model.
[So] Source:PLoS Negl Trop Dis;10(11):e0005125, 2016 Nov.
[Is] ISSN:1935-2735
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Trypanosoma brucei gambiense is the main causative agent of Human African Trypanosomiasis (HAT), also known as sleeping sickness. Because of limited alternatives and treatment toxicities, new therapeutic options are urgently needed for patients with HAT. Sterol 14alpha-demethylase (CYP51) is a potential drug target but its essentiality has not been determined in T. brucei. We used a tetracycline-inducible RNAi system to assess the essentiality of CYP51 in T. brucei bloodstream form (BSF) cells and we evaluated the effect of posaconazole, a well-tolerated triazole drug, within a panel of virulent strains in vitro and in a murine model. Expression of CYP51 in several T. brucei cell lines was demonstrated by western blot and its essentiality was demonstrated by RNA interference (CYP51RNAi) in vitro. Following reduction of TbCYP51 expression by RNAi, cell growth was reduced and eventually stopped compared to WT or non-induced cells, showing the requirement of CYP51 in T. brucei. These phenotypes were rescued by addition of ergosterol. Additionally, CYP51RNAi induction caused morphological defects with multiflagellated cells (p<0.05), suggesting cytokinesis dysfunction. The survival of CYP51RNAi Doxycycline-treated mice (p = 0.053) and of CYP51RNAi 5-day pre-induced Doxycycline-treated mice (p = 0.008) were improved compared to WT showing a CYP51 RNAi effect on trypanosomal virulence in mice. The posaconazole concentrations that inhibited parasite growth by 50% (IC50) were 8.5, 2.7, 1.6 and 0.12 µM for T. b. brucei 427 90-13, T. b. brucei Antat 1.1, T. b. gambiense Feo (Feo/ITMAP/1893) and T. b. gambiense Biyamina (MHOM/SD/82), respectively. During infection with these last three virulent strains, posaconazole-eflornithine and nifurtimox-eflornithine combinations showed similar improvement in mice survival (p≤0.001). Our results provide support for a CYP51 targeting based treatment in HAT. Thus posaconazole used in combination may represent a therapeutic alternative for trypanosomiasis.
[Mh] Termos MeSH primário: Inibidores de 14-alfa Desmetilase/farmacologia
Nifurtimox/uso terapêutico
Esterol 14-Desmetilase/metabolismo
Tripanossomicidas/uso terapêutico
Trypanosoma brucei brucei/efeitos dos fármacos
Trypanosoma brucei brucei/enzimologia
Tripanossomíase Africana/tratamento farmacológico
[Mh] Termos MeSH secundário: Animais
Antibacterianos/uso terapêutico
Citocinese
Modelos Animais de Doenças
Doxiciclina/uso terapêutico
Eflornitina/uso terapêutico
Ergosterol/farmacologia
Seres Humanos
Camundongos
Fenótipo
Interferência de RNA
Esterol 14-Desmetilase/genética
Triazóis/farmacologia
Triazóis/uso terapêutico
Trypanosoma brucei brucei/crescimento & desenvolvimento
Trypanosoma brucei brucei/patogenicidade
Tripanossomíase Africana/parasitologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (14-alpha Demethylase Inhibitors); 0 (Anti-Bacterial Agents); 0 (Triazoles); 0 (Trypanocidal Agents); 6TK1G07BHZ (posaconazole); EC 1.14.13.70 (Sterol 14-Demethylase); M84I3K7C2O (Nifurtimox); N12000U13O (Doxycycline); Z30RAY509F (Ergosterol); ZQN1G5V6SR (Eflornithine)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170605
[Lr] Data última revisão:
170605
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161118
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pntd.0005125


  8 / 410 MEDLINE  
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[PMID]:27723399
[Au] Autor:Hedley L; Fink D; Sparkes D; Chiodini PL
[Ad] Endereço:Senior Clinical Pharmacist in HIV and Infectious Diseases in the Department of Pharmacy, University College London Hospitals NHS Foundation Trust, London NW1 2BU.
[Ti] Título:African sleeping sickness.
[So] Source:Br J Hosp Med (Lond);77(10):C157-C160, 2016 Oct.
[Is] ISSN:1750-8460
[Cp] País de publicação:England
[La] Idioma:eng
[Mh] Termos MeSH primário: Tripanossomicidas/uso terapêutico
Tripanossomíase Africana/tratamento farmacológico
[Mh] Termos MeSH secundário: Animais
Eflornitina/uso terapêutico
Seres Humanos
Insetos Vetores/parasitologia
Nifurtimox/uso terapêutico
Pentamidina/uso terapêutico
Suramina/uso terapêutico
Trypanosoma brucei gambiense/fisiologia
Trypanosoma brucei rhodesiense/fisiologia
Tripanossomíase Africana/diagnóstico
Tripanossomíase Africana/fisiopatologia
Tripanossomíase Africana/transmissão
Moscas Tsé-Tsé/parasitologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Trypanocidal Agents); 6032D45BEM (Suramin); 673LC5J4LQ (Pentamidine); M84I3K7C2O (Nifurtimox); ZQN1G5V6SR (Eflornithine)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170309
[Lr] Data última revisão:
170309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161011
[St] Status:MEDLINE


  9 / 410 MEDLINE  
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PubMed Central Texto completo
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[PMID]:27551855
[Au] Autor:Brunoro GV; Faça VM; Caminha MA; Ferreira AT; Trugilho M; de Moura KC; Perales J; Valente RH; Menna-Barreto RF
[Ad] Endereço:Laboratório de Toxinologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.
[Ti] Título:Differential Gel Electrophoresis (DIGE) Evaluation of Naphthoimidazoles Mode of Action: A Study in Trypanosoma cruzi Bloodstream Trypomastigotes.
[So] Source:PLoS Negl Trop Dis;10(8):e0004951, 2016 Aug.
[Is] ISSN:1935-2735
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: The obligate intracellular protozoan Trypanosoma cruzi is the causative agent of Chagas disease, a neglected illness affecting millions of people in Latin America that recently entered non-endemic countries through immigration, as a consequence of globalization. The chemotherapy for this disease is based mainly on benznidazole and nifurtimox, which are very efficient nitroderivatives against the acute stage but present limited efficacy during the chronic phase. Our group has been studying the trypanocidal effects of naturally occurring quinones and their derivatives, and naphthoimidazoles derived from ß-lapachone N1, N2 and N3 were the most active. To assess the molecular mechanisms of action of these compounds, we applied proteomic techniques to analyze treated bloodstream trypomastigotes, which are the clinically relevant stage of the parasite. METHODOLOGY/PRINCIPAL FINDINGS: The approach consisted of quantification by 2D-DIGE followed by MALDI-TOF/TOF protein identification. A total of 61 differentially abundant protein spots were detected when comparing the control with each N1, N2 or N3 treatment, for 34 identified spots. Among the differentially abundant proteins were activated protein kinase C receptor, tubulin isoforms, asparagine synthetase, arginine kinase, elongation factor 2, enolase, guanine deaminase, heat shock proteins, hypothetical proteins, paraflagellar rod components, RAB GDP dissociation inhibitor, succinyl-CoA ligase, ATP synthase subunit B and methionine sulfoxide reductase. CONCLUSION/SIGNIFICANCE: Our results point to different modes of action for N1, N2 and N3, which indicate a great variety of metabolic pathways involved and allow for novel perspectives on the development of trypanocidal agents.
[Mh] Termos MeSH primário: Naftoquinonas/farmacologia
Proteínas de Protozoários/análise
Tripanossomicidas/farmacologia
Trypanosoma cruzi/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Doença de Chagas/tratamento farmacológico
Eletroforese em Gel Bidimensional
Camundongos
Nifurtimox/farmacologia
Nitroimidazóis/farmacologia
Proteômica
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Naphthoquinones); 0 (Nitroimidazoles); 0 (Protozoan Proteins); 0 (Trypanocidal Agents); 4707-32-8 (beta-lapachone); M84I3K7C2O (Nifurtimox); YC42NRJ1ZD (benzonidazole)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170614
[Lr] Data última revisão:
170614
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160824
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pntd.0004951


  10 / 410 MEDLINE  
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[PMID]:27356544
[Au] Autor:Paucar R; Moreno-Viguri E; Pérez-Silanes S
[Ti] Título:Challenges in Chagas Disease Drug Discovery: A Review.
[So] Source:Curr Med Chem;23(28):3154-3170, 2016.
[Is] ISSN:1875-533X
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Chagas disease or American trypanosomiasis is a neglected tropical disease caused by the parasite Trypanosoma cruzi. Although the number of infected individuals has decreased, about 6-7 million people are infected worldwide. The chemotherapy drugs currently used are limited to benznidazole and nifurtimox. They are effective in acute phase, congenital transmission and children with chronic infection; however, recent clinical trials have shown limitations in adults with chronic infection, presenting drawbacks during the treatment. Thus, there is an urgent need for new effective, safe and affordable drugs to fight against this complex disease. There were high expectations for azole derivatives as they appeared to be the most promising drugs for the treatment of Chagas disease during the last decade; however, the disappointing results obtained so far in clinical trials evidenced the lack of correlation between preclinical and clinical development. Therefore, the feedback obtained from these studies should define the starting point for addressing a roadmap for the drug discovery process in the fight against this disease. To tackle this challenge, it is important to keep in mind the drug target profile, already defined by panels of experts, and the coordinated work involving multi-disciplinary networks focusing not only on the discovery of new drugs but also on the standardization of the protocols that would allow acceleration in the Chagas disease drug discovery process.
[Mh] Termos MeSH primário: Doença de Chagas/tratamento farmacológico
Tripanossomicidas/uso terapêutico
[Mh] Termos MeSH secundário: Doença de Chagas/diagnóstico
Doença de Chagas/parasitologia
Ensaios Clínicos como Assunto
Descoberta de Drogas
Seres Humanos
Nifurtimox/química
Nifurtimox/farmacologia
Nifurtimox/uso terapêutico
Nitroimidazóis/química
Nitroimidazóis/farmacologia
Nitroimidazóis/uso terapêutico
RNA de Protozoário/metabolismo
Reação em Cadeia da Polimerase em Tempo Real
Tripanossomicidas/química
Tripanossomicidas/farmacologia
Trypanosoma cruzi/efeitos dos fármacos
Trypanosoma cruzi/genética
Trypanosoma cruzi/patogenicidade
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Nitroimidazoles); 0 (RNA, Protozoan); 0 (Trypanocidal Agents); M84I3K7C2O (Nifurtimox); YC42NRJ1ZD (benzonidazole)
[Em] Mês de entrada:1702
[Cu] Atualização por classe:170207
[Lr] Data última revisão:
170207
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160701
[St] Status:MEDLINE



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