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Cotrim, Paulo Cesar
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[PMID]:28454918
[Au] Autor:Monteiro LM; Löbenberg R; Ferreira EI; Cotrim PC; Kanashiro E; Rocha M; Chung MC; Bou-Chacra N
[Ad] Endereço:Pharmacy Department, Faculty of Pharmaceutical Sciences, University de São Paulo, São Paulo, Brazil.
[Ti] Título:Targeting Leishmania amazonensis amastigotes through macrophage internalisation of a hydroxymethylnitrofurazone nanostructured polymeric system.
[So] Source:Int J Antimicrob Agents;50(1):88-92, 2017 Jul.
[Is] ISSN:1872-7913
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Dextran-coated poly (n-butyl cyanoacrylate) nanoparticles (PBCA-NPs) were prepared and were evaluated for enhanced delivery of a promising anti-Leishmania drug candidate, hydroxymethylnitrofurazone (NFOH), to phagocytic cells. Currently available chemotherapy for leishmaniasis, such as pentavalent antimonials, presents low safety and efficacy. Furthermore, widespread drug resistance in leishmaniasis is rapidly emerging. To overcome these drawbacks, the use of nanosized delivery systems can reduce systemic drug toxicity and increase the drug concentration in infected macrophages, therefore improving treatment of leishmaniasis. PBCA-NPs containing NFOH (PBCA-NFOH-NPs) were prepared by an anionic emulsion polymerisation method. The z-average and polydispersity index (PDI) were determined by photon correlation spectroscopy, the zeta potential by microelectrophoresis and the entrapment efficiency by HPLC. Cytotoxicity was determined using macrophages from BALB/c mice. Efficacy tests were performed using Leishmania amazonensis promastigotes and amastigotes. The z-average of PBCA-NFOH-NPs was 151.5 ± 61.97 nm, with a PDI of 0.104 ± 0.01, a zeta potential of -10.1 ± 6.49 mV and an entrapment efficiency of 64.47 ± 0.43%. Efficacy in amastigotes revealed IC values of 0.33 µM and 31.2 µM for the nanostructured and free NFOH, respectively (95-fold increase). The cytotoxicity study indicated low toxicity of the PBCA-NFOH-NPs to macrophages. The selectivity index was 370.6, which is 49-fold higher than free NFOH (7.6). Such findings indicated that improved efficacy could be due to NP internalisation following site-specific drug delivery and reactivation of immune protective reactions by the NP components. Thus, PBCA-NFOH-NPs have the potential to significantly improve the treatment of leishmaniasis, with reduced systemic side effects.
[Mh] Termos MeSH primário: Antiprotozoários/metabolismo
Leishmania/efeitos dos fármacos
Macrófagos/parasitologia
Nanopartículas/metabolismo
Nitrofurazona/análogos & derivados
[Mh] Termos MeSH secundário: Animais
Sobrevivência Celular/efeitos dos fármacos
Concentração Inibidora 50
Macrófagos/fisiologia
Camundongos Endogâmicos BALB C
Nanopartículas/toxicidade
Nitrofurazona/metabolismo
Testes de Sensibilidade Parasitária
[Pt] Tipo de publicação:JOURNAL ARTICLE; MULTICENTER STUDY
[Nm] Nome de substância:
0 (Antiprotozoal Agents); 0 (hydroxymethylnitrofurazone); X8XI70B5Z6 (Nitrofurazone)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180222
[Lr] Data última revisão:
180222
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170430
[St] Status:MEDLINE


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[PMID]:29443773
[Au] Autor:Cai X; Zhou H; Xie Y; Yu D; Wang Z; Ren H
[Ad] Endereço:Department of Pediatrics, West China Second University Hospital.
[Ti] Título:Anti-N-methyl-D-aspartate receptor encephalitis associated with acute Toxoplasma gondii infection: A case report.
[So] Source:Medicine (Baltimore);97(7):e9924, 2018 Feb.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:RATIONALE: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis has been recognized as the most frequent autoimmune encephalitis in children. Several infectious agents have been implicated in anti-NMDA encephalitis. PATIENT CONCERNS: A previously healthy immunocompetent 9-year-old girl first presented with seizures, headaches and vomiting. Cerebrospinal fluid and brain magnetic resonance imaging were normal. After one week onset, the patient gradually developed unexplained personality and behavior changes, accompanied by fever and seizures again. Repeated CSF analysis revealed a slightly lymphocytic predominant pleocytosis and positive anti-NMDAR antibody. A variety of pathogenic examinations were negative, except for positive toxoplasma IgM and IgG. DIAGNOSES: The patient was diagnoses for anti-NMDA encephalitis associated with acute acquired toxoplasma gondii infection. INTERVENTIONS: The patient received 10 days azithromycin for treatment of acquired toxoplasma infection. The parents refuse immunotherapy because substantial recovery from clinical symptoms. OUTCOMES: The patient was substantially recovered with residual mild agitation after therapy for acquired toxoplasma gondii infection. Two months later, the patient was completely devoid of symptoms, and the levels of serum IgM and IgG of toxoplasma gondii were decreased. LESSONS: Acquired toxoplasma gondii infection may trigger anti-NMDAR encephalitis in children, which has not been reported previously. Clinicians should assess the possibility of toxoplasma gondii infection when evaluating a patient with anti-NMDA encephalitis.
[Mh] Termos MeSH primário: Encefalite Antirreceptor de N-Metil-D-Aspartato/diagnóstico
Encefalite Antirreceptor de N-Metil-D-Aspartato/parasitologia
Toxoplasmose Cerebral/diagnóstico
[Mh] Termos MeSH secundário: Encefalite Antirreceptor de N-Metil-D-Aspartato/tratamento farmacológico
Antiprotozoários/uso terapêutico
Azitromicina/uso terapêutico
Criança
Feminino
Seres Humanos
Imunoglobulina G/sangue
Imunoglobulina M/sangue
Toxoplasma/imunologia
Toxoplasmose Cerebral/tratamento farmacológico
Resultado do Tratamento
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antiprotozoal Agents); 0 (Immunoglobulin G); 0 (Immunoglobulin M); 83905-01-5 (Azithromycin)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180220
[Lr] Data última revisão:
180220
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180215
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000009924


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Texto completo SciELO Brasil
[PMID]:29236929
[Au] Autor:Silva RED; Carvalho JP; Ramalho DB; Senna MCR; Moreira HSA; Rabello A; Cota E; Cota G
[Ad] Endereço:Centro de Referência em Leishmanioses, Pesquisa Clínica e Políticas Públicas em Doenças Infecto-Parasitárias, Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz-Fiocruz, Belo Horizonte, MG, Brasil.
[Ti] Título:Towards a standard protocol for antimony intralesional infiltration technique for cutaneous leishmaniasis treatment.
[So] Source:Mem Inst Oswaldo Cruz;113(2):71-79, 2018 Feb.
[Is] ISSN:1678-8060
[Cp] País de publicação:Brazil
[La] Idioma:eng
[Ab] Resumo:BACKGROUND Despite its recognised toxicity, antimonial therapy continues to be the first-line drug for cutaneous leishmaniasis (CL) treatment. Intralesional administration of meglumine antimoniate (MA) represents an alternative that could reduce the systemic absorption of the drug and its side effects. OBJECTIVES This study aims to validate the standard operational procedure (SOP) for the intralesional infiltration of MA for CL therapy as the first step before the assessment of efficacy and safety related to the procedure. METHODS The SOP was created based on 21 trials retrieved from the literature, direct monitoring of the procedure and consultation with experts. This script was submitted to a formal computer-aided inspection to identify readability, clarity, omission, redundancy and unnecessary information (content validation). For criterion and construct validations, the influence of critical condition changes (compliance with the instructions and professional experience) on outcome conformity (saturation status achievement), tolerability (pain referred) and safety (bleeding) were assessed. FINDINGS The median procedure length was 12 minutes and in 72% of them, patients classified the pain as mild. The bleeding was also classified as mild in 96.6% of the procedures. Full compliance with the SOP was observed in 66% of infiltrations. Despite this, in 100% of the inspected procedures, lesion saturation was observed at the end of infiltration, which means that it tolerates some degree of modification in its execution (robustness) without prejudice to the result. CONCLUSIONS The procedure is reproducible and can be used by professionals without previous training with high success and safety rates.
[Mh] Termos MeSH primário: Antiprotozoários/administração & dosagem
Protocolos Clínicos/normas
Injeções Intralesionais
Leishmaniose Cutânea/tratamento farmacológico
Meglumina/administração & dosagem
Compostos Organometálicos/administração & dosagem
[Mh] Termos MeSH secundário: Seres Humanos
Injeções Intralesionais/efeitos adversos
Injeções Intralesionais/métodos
Reprodutibilidade dos Testes
[Pt] Tipo de publicação:JOURNAL ARTICLE; VALIDATION STUDIES
[Nm] Nome de substância:
0 (Antiprotozoal Agents); 0 (Organometallic Compounds); 6HG8UB2MUY (Meglumine); 75G4TW236W (meglumine antimoniate)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180215
[Lr] Data última revisão:
180215
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171214
[St] Status:MEDLINE


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[PMID]:29326050
[Au] Autor:Nayak A; Akpunarlieva S; Barrett M; Burchmore R
[Ad] Endereço:Institute of Infection, Immunity and Inflammation and Glasgow Polyomics, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
[Ti] Título:A defined medium for Leishmania culture allows definition of essential amino acids.
[So] Source:Exp Parasitol;185:39-52, 2018 Feb.
[Is] ISSN:1090-2449
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Axenic culture of Leishmania is generally performed in rich, serum-supplemented media which sustain robust growth over multiple passages. The use of such undefined media, however, obscures proteomic analyses and confounds the study of metabolism. We have established a simple, defined culture medium that supports the sustained growth of promastigotes over multiple passages and which yields parasites that have similar infectivity to macrophages to parasites grown in a conventional semi-defined medium. We have exploited this medium to investigate the amino acid requirements of promastigotes in culture and have found that phenylalanine, tryptophan, arginine, leucine, lysine and valine are essential for viability in culture. Most of the 20 proteogenic amino acids promote growth of Leishmania promastigotes, with the exception of alanine, asparagine, and glycine. This defined medium will be useful for further studies of promastigote substrate requirements, and will facilitate future proteomic and metabolomic analyses.
[Mh] Termos MeSH primário: Aminoácidos Essenciais/metabolismo
Meios de Cultura/química
Leishmania/crescimento & desenvolvimento
[Mh] Termos MeSH secundário: Anfotericina B/farmacologia
Animais
Antiprotozoários/farmacologia
Concentração Inibidora 50
Leishmania/efeitos dos fármacos
Leishmania donovani/crescimento & desenvolvimento
Leishmania major/crescimento & desenvolvimento
Leishmania mexicana/crescimento & desenvolvimento
Metotrexato/farmacologia
Pentamidina/farmacologia
Inoculações Seriadas
Especificidade da Espécie
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amino Acids, Essential); 0 (Antiprotozoal Agents); 0 (Culture Media); 673LC5J4LQ (Pentamidine); 7XU7A7DROE (Amphotericin B); YL5FZ2Y5U1 (Methotrexate)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180214
[Lr] Data última revisão:
180214
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180113
[St] Status:MEDLINE


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[PMID]:29287089
[Au] Autor:Ortiz D; Guiguemde WA; Hammill JT; Carrillo AK; Chen Y; Connelly M; Stalheim K; Elya C; Johnson A; Min J; Shelat A; Smithson DC; Yang L; Zhu F; Guy RK; Landfear SM
[Ad] Endereço:Department of Molecular Microbiology & Immunology, Oregon Health & Science University, Portland, Oregon, United States of America.
[Ti] Título:Discovery of novel, orally bioavailable, antileishmanial compounds using phenotypic screening.
[So] Source:PLoS Negl Trop Dis;11(12):e0006157, 2017 12.
[Is] ISSN:1935-2735
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Leishmaniasis is a parasitic infection that afflicts approximately 12 million people worldwide. There are several limitations to the approved drug therapies for leishmaniasis, including moderate to severe toxicity, growing drug resistance, and the need for extended dosing. Moreover, miltefosine is currently the only orally available drug therapy for this infection. We addressed the pressing need for new therapies by pursuing a two-step phenotypic screen to discover novel, potent, and orally bioavailable antileishmanials. First, we conducted a high-throughput screen (HTS) of roughly 600,000 small molecules for growth inhibition against the promastigote form of the parasite life cycle using the nucleic acid binding dye SYBR Green I. This screen identified approximately 2,700 compounds that inhibited growth by over 65% at a single point concentration of 10 µM. We next used this 2700 compound focused library to identify compounds that were highly potent against the disease-causing intra-macrophage amastigote form and exhibited limited toxicity toward the host macrophages. This two-step screening strategy uncovered nine unique chemical scaffolds within our collection, including two previously described antileishmanials. We further profiled two of the novel compounds for in vitro absorption, distribution, metabolism, excretion, and in vivo pharmacokinetics. Both compounds proved orally bioavailable, affording plasma exposures above the half-maximal effective concentration (EC50) concentration for at least 12 hours. Both compounds were efficacious when administered orally in a murine model of cutaneous leishmaniasis. One of the two compounds exerted potent activity against trypanosomes, which are kinetoplastid parasites related to Leishmania species. Therefore, this compound could help control multiple parasitic diseases. The promising pharmacokinetic profile and significant in vivo efficacy observed from our HTS hits highlight the utility of our two-step phenotypic screening strategy and strongly suggest that medicinal chemistry optimization of these newly identified scaffolds will lead to promising candidates for an orally available anti-parasitic drug.
[Mh] Termos MeSH primário: Antiprotozoários/farmacocinética
Avaliação Pré-Clínica de Medicamentos/métodos
Leishmania mexicana/efeitos dos fármacos
Leishmaniose Cutânea/tratamento farmacológico
[Mh] Termos MeSH secundário: Administração Oral
Animais
Antiprotozoários/administração & dosagem
Antiprotozoários/efeitos adversos
Antiprotozoários/química
Linhagem Celular
Química Farmacêutica
Descoberta de Drogas
Feminino
Seres Humanos
Leishmania mexicana/crescimento & desenvolvimento
Leishmaniose Cutânea/parasitologia
Macrófagos/parasitologia
Camundongos
Camundongos Endogâmicos BALB C
Fenótipo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antiprotozoal Agents)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180212
[Lr] Data última revisão:
180212
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171230
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pntd.0006157


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[PMID]:29191699
[Au] Autor:Nieto-Meneses R; Castillo R; Hernández-Campos A; Maldonado-Rangel A; Matius-Ruiz JB; Trejo-Soto PJ; Nogueda-Torres B; Dea-Ayuela MA; Bolás-Fernández F; Méndez-Cuesta C; Yépez-Mulia L
[Ad] Endereço:Departamento de Parasitología, ENCB-IPN, 11340 Mexico City, Mexico; Unidad de Investigación Médica en Enfermedades Infecciosas y Parasitarias-Pediatría, Instituto Mexicano del Seguro Social, 06720 Mexico City, Mexico.
[Ti] Título:In vitro activity of new N-benzyl-1H-benzimidazol-2-amine derivatives against cutaneous, mucocutaneous and visceral Leishmania species.
[So] Source:Exp Parasitol;184:82-89, 2018 Jan.
[Is] ISSN:1090-2449
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The identification of specific therapeutic targets and the development of new drugs against leishmaniasis are urgently needed, since chemotherapy currently available for its treatment has several problems including many adverse side effects. In an effort to develop new antileishmanial drugs, in the present study a series of 28 N-benzyl-1H-benzimidazol-2-amine derivatives was synthesized and evaluated in vitro against Leishmania mexicana promastigotes. Compounds 7 and 8 with the highest antileishmanial activity (micromolar) and lower cytotoxicity than miltefosine and amphotericin B were selected to evaluate their activity against L. braziliensis 9and L. donovani, species causative of mucocutaneous and visceral leishmaniasis, respectively. Compound 7 showed significantly higher activity against L. braziliensis promastigotes than compound 8 and slightly lower than miltefosine. Compounds 7 and 8 had IC values in the micromolar range against the amastigote of L. mexicana and L. braziliensis. However, both compounds did not show better activity against L. donovani than miltefosine. Compound 8 showed the highest SI against both parasite stages of L. mexicana. In addition, compound 8 inhibited 68.27% the activity of recombinant L. mexicana arginase (LmARG), a therapeutic target for the treatment of leishmaniasis. Docking studies were also performed in order to establish the possible mechanism of action by which this compound exerts its inhibitory effect. Compound 8 shows promising potential for the development of more potent antileishmanial benzimidazole derivatives.
[Mh] Termos MeSH primário: Antiprotozoários/farmacologia
Benzimidazóis/farmacologia
Leishmania braziliensis/efeitos dos fármacos
Leishmania donovani/efeitos dos fármacos
Leishmania mexicana/efeitos dos fármacos
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Anfotericina B/farmacologia
Animais
Antiprotozoários/toxicidade
Arginase/antagonistas & inibidores
Arginase/química
Benzimidazóis/síntese química
Benzimidazóis/química
Benzimidazóis/toxicidade
Linhagem Celular
Concentração Inibidora 50
Leishmania mexicana/enzimologia
Leishmaniose Cutânea/tratamento farmacológico
Leishmaniose Cutânea/parasitologia
Leishmaniose Mucocutânea/tratamento farmacológico
Leishmaniose Mucocutânea/parasitologia
Leishmaniose Visceral/tratamento farmacológico
Leishmaniose Visceral/parasitologia
Macrófagos/efeitos dos fármacos
Camundongos
Simulação de Acoplamento Molecular
Fosforilcolina/análogos & derivados
Fosforilcolina/farmacologia
Alinhamento de Sequência
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antiprotozoal Agents); 0 (Benzimidazoles); 107-73-3 (Phosphorylcholine); 53EY29W7EC (miltefosine); 7XU7A7DROE (Amphotericin B); EC 3.5.3.1 (Arginase)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180205
[Lr] Data última revisão:
180205
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171202
[St] Status:MEDLINE


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[PMID]:29324838
[Au] Autor:Travi BL; Cordeiro-da-Silva A; Dantas-Torres F; Miró G
[Ad] Endereço:Department of Internal Medicine-Division of Infectious Diseases, University of Texas Medical Branch, Galveston, Texas, United States of America.
[Ti] Título:Canine visceral leishmaniasis: Diagnosis and management of the reservoir living among us.
[So] Source:PLoS Negl Trop Dis;12(1):e0006082, 2018 01.
[Is] ISSN:1935-2735
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:This article reviews essential topics of canine visceral leishmaniasis (CVL) due to Leishmania infantum infection. It focuses on the current serological and molecular diagnostic methods used in epidemiological research and veterinary clinics to diagnose CVL and includes new point-of-care (POC) tests under development. The efficacy of different treatment regimens on the clinical improvement and infectiousness of dogs is also addressed. In the last section, the review provides a critical appraisal of the effectiveness of different control measures that have been implemented to curb disease transmission.
[Mh] Termos MeSH primário: Antiprotozoários/uso terapêutico
Doenças do Cão/diagnóstico
Doenças do Cão/tratamento farmacológico
Leishmaniose Visceral/diagnóstico
Leishmaniose Visceral/veterinária
Técnicas de Diagnóstico Molecular
[Mh] Termos MeSH secundário: Alopurinol/uso terapêutico
Animais
Reservatórios de Doenças/parasitologia
Reservatórios de Doenças/veterinária
Doenças do Cão/parasitologia
Cães
Leishmania infantum/efeitos dos fármacos
Leishmaniose Visceral/parasitologia
Meglumina/uso terapêutico
Compostos Organometálicos/uso terapêutico
Fosforilcolina/análogos & derivados
Fosforilcolina/uso terapêutico
Sistemas Automatizados de Assistência Junto ao Leito
Testes Sorológicos
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Antiprotozoal Agents); 0 (Organometallic Compounds); 107-73-3 (Phosphorylcholine); 53EY29W7EC (miltefosine); 63CZ7GJN5I (Allopurinol); 6HG8UB2MUY (Meglumine); 75G4TW236W (meglumine antimoniate)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180130
[Lr] Data última revisão:
180130
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180112
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pntd.0006082


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[PMID]:29192424
[Au] Autor:Heras-Mosteiro J; Monge-Maillo B; Pinart M; Lopez Pereira P; Reveiz L; Garcia-Carrasco E; Campuzano Cuadrado P; Royuela A; Mendez Roman I; López-Vélez R
[Ad] Endereço:Department of Preventive Medicine and Public Health & Immunology and Microbiology, Rey Juan Carlos University, Avda. Atenas s/n, Alcorcón, Madrid, Spain, 28922.
[Ti] Título:Interventions for Old World cutaneous leishmaniasis.
[So] Source:Cochrane Database Syst Rev;12:CD005067, 2017 12 01.
[Is] ISSN:1469-493X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Cutaneous leishmaniasis, caused by a parasitic infection, is considered one of the most serious skin diseases in many low- and middle-income countries. Old World cutaneous leishmaniasis (OWCL) is caused by species found in Africa, Asia, the Middle East, the Mediterranean, and India. The most commonly prescribed treatments are antimonials, but other drugs have been used with varying success. As OWCL tends to heal spontaneously, it is necessary to justify the use of systemic and topical treatments. This is an update of a Cochrane Review first published in 2008. OBJECTIVES: To assess the effects of therapeutic interventions for the localised form of Old World cutaneous leishmaniasis. SEARCH METHODS: We updated our searches of the following databases to November 2016: the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS. We also searched five trials registers and checked the reference lists of included studies for further references to relevant randomised controlled trials (RCTs). We wrote to national programme managers, general co-ordinators, directors, clinicians, WHO-EMRO regional officers of endemic countries, pharmaceutical companies, tropical medicine centres, and authors of relevant papers for further information about relevant unpublished and ongoing trials. We undertook a separate search for adverse effects of interventions for Old World cutaneous leishmaniasis in September 2015 using MEDLINE. SELECTION CRITERIA: Randomised controlled trials of either single or combination treatments in immunocompetent people with OWCL confirmed by smear, histology, culture, or polymerase chain reaction. The comparators were either no treatment, placebo/vehicle, and/or another active compound. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and risk of bias and extracted data. We only synthesised data when we were able to identify at least two studies investigating similar treatments and reporting data amenable to pooling. We also recorded data about adverse effects from the corresponding search. MAIN RESULTS: We included 89 studies (of which 40 were new to this update) in 10,583 people with OWCL. The studies included were conducted mainly in the Far or Middle East at regional hospitals, local healthcare clinics, and skin disease research centres. Women accounted for 41.5% of the participants (range: 23% to 80%). The overall mean age of participants was 25 years (range 12 to 56). Most studies lasted between two to six months, with the longest lasting two years; average duration was four months. Most studies were at unclear or high risk for most bias domains. A lack of blinding and reporting bias were present in almost 40% of studies. Two trials were at low risk of bias for all domains. Trials reported the causative species poorly.Here we provide results for the two main comparisons identified: itraconazole (200 mg for six to eight weeks) versus placebo; and paromomycin ointment (15% plus 10% urea, twice daily for 14 days) versus vehicle.In the comparison of oral itraconazole versus placebo, at 2.5 months' follow up, 85/125 participants in the itraconazole group achieved complete cure compared to 54/119 in the placebo group (RR 3.70, 95% CI 0.35 to 38.99; 3 studies; 244 participants). In one study, microbiological or histopathological cure of skin lesions only occurred in the itraconazole group after a mean follow-up of 2.5 months (RR 17.00, 95% CI 0.47 to 612.21; 20 participants). However, although the analyses favour oral itraconazole for these outcomes, we cannot be confident in the results due to the very low certainty evidence. More side effects of mild abdominal pain and nausea (RR 2.36, 95% CI 0.74 to 7.47; 3 studies; 204 participants) and mild abnormal liver function (RR 3.08, 95% CI 0.53 to 17.98; 3 studies; 84 participants) occurred in the itraconazole group (as well as reports of headaches and dizziness), compared with the placebo group, but again we rated the certainty of evidence as very low so are unsure of the results.When comparing paromomycin with vehicle, there was no difference in the number of participants who achieved complete cure (RR of 1.00, 95% CI 0.86, 1.17; 383 participants, 2 studies) and microbiological or histopathological cure of skin lesions after a mean follow-up of 2.5 months (RR 1.03, CI 0.88 to 1.20; 383 participants, 2 studies), but the paromomycin group had more skin/local reactions (such as inflammation, vesiculation, pain, redness, or itch) (RR 1.42, 95% CI 0.67 to 3.01; 4 studies; 713 participants). For all of these outcomes, the certainty of evidence was very low, meaning we are unsure about these results.Trial authors did not report the percentage of lesions cured after the end of treatment or speed of healing for either of these key comparisons. AUTHORS' CONCLUSIONS: There was very low-certainty evidence to support the effectiveness of itraconazole and paromomycin ointment for OWCL in terms of cure (i.e. microbiological or histopathological cure and percentage of participants completely cured). Both of these interventions incited more adverse effects, which were mild in nature, than their comparisons, but we could draw no conclusions regarding safety due to the very low certainty of the evidence for this outcome.We downgraded the key outcomes in these two comparisons due to high risk of bias, inconsistency between the results, and imprecision. There is a need for large, well-designed international studies that evaluate long-term effects of current therapies and enable a reliable conclusion about treatments. Future trials should specify the species of leishmaniasis; trials on types caused by Leishmania infantum, L aethiopica, andL donovani are lacking. Research into the effects of treating women of childbearing age, children, people with comorbid conditions, and those who are immunocompromised would also be helpful.It was difficult to evaluate the overall efficacy of any of the numerous treatments due to the variable treatment regimens examined and because RCTs evaluated different Leishmania species and took place in different geographical areas. Some outcomes we looked for but did not find were degree of functional and aesthetic impairment, change in ability to detect Leishmania, quality of life, and emergence of resistance. There were only limited data on prevention of scarring.
[Mh] Termos MeSH primário: Antiprotozoários/uso terapêutico
Itraconazol/uso terapêutico
Leishmaniose Cutânea/terapia
Paromomicina/uso terapêutico
[Mh] Termos MeSH secundário: Adulto
Animais
Anti-Infecciosos/uso terapêutico
Antiprotozoários/administração & dosagem
Terapias Complementares/métodos
Crioterapia/métodos
Extremo Oriente
Feminino
Temperatura Alta/uso terapêutico
Seres Humanos
Itraconazol/administração & dosagem
Terapia a Laser
Leishmania major
Leishmania tropica
Masculino
Meia-Idade
Oriente Médio
Bases para Pomadas/administração & dosagem
Paromomicina/administração & dosagem
Fotoquimioterapia
Ensaios Clínicos Controlados Aleatórios como Assunto
[Pt] Tipo de publicação:JOURNAL ARTICLE; META-ANALYSIS; RESEARCH SUPPORT, NON-U.S. GOV'T; REVIEW
[Nm] Nome de substância:
0 (Anti-Infective Agents); 0 (Antiprotozoal Agents); 0 (Ointment Bases); 304NUG5GF4 (Itraconazole); 61JJC8N5ZK (Paromomycin)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180123
[Lr] Data última revisão:
180123
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171202
[St] Status:MEDLINE
[do] DOI:10.1002/14651858.CD005067.pub5


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[PMID]:29278948
[Au] Autor:Nocentini A; Cadoni R; Dumy P; Supuran CT; Winum JY
[Ad] Endereço:a Institut des Biomolécules Max Mousseron (IBMM), UMR 5247 CNRS, ENSCM, Université de Montpellier , Montpellier Cedex , France.
[Ti] Título:Carbonic anhydrases from Trypanosoma cruzi and Leishmania donovani chagasi are inhibited by benzoxaboroles.
[So] Source:J Enzyme Inhib Med Chem;33(1):286-289, 2018 Dec.
[Is] ISSN:1475-6374
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:A series of 6-substituted ureido- and thioureido-benzoxaboroles were investigated as inhibitors of carbonic anhydrases from Trypanosoma cruzi (TcCA), and Leishmania donovani chagasi (LdcCA). Both enzymes were inhibited by benzoxaboroles in the micromolar range. Preferential inhibitory potency against the ß-CA LdcCA versus the α-CA TcCA was observed with submicromolar inhibitory activities. Some derivatives displayed excellent inhibitory and selectivity profile over the ubiquitous and physiological relevant human off-target hCA II. This study provides a convincing opportunity to study benzoxaborole scaffold for the design of antiprotozoan potential drugs targeting the pathogen's carbonic anhydrases.
[Mh] Termos MeSH primário: Antiprotozoários/farmacologia
Compostos de Boro/farmacologia
Inibidores da Anidrase Carbônica/farmacologia
Anidrases Carbônicas/metabolismo
Compostos Heterocíclicos com 2 Anéis/farmacologia
Leishmania donovani/efeitos dos fármacos
Trypanosoma cruzi/efeitos dos fármacos
[Mh] Termos MeSH secundário: Antiprotozoários/síntese química
Antiprotozoários/química
Compostos de Boro/síntese química
Compostos de Boro/química
Inibidores da Anidrase Carbônica/síntese química
Inibidores da Anidrase Carbônica/química
Relação Dose-Resposta a Droga
Compostos Heterocíclicos com 2 Anéis/síntese química
Compostos Heterocíclicos com 2 Anéis/química
Leishmania donovani/enzimologia
Testes de Sensibilidade Microbiana
Estrutura Molecular
Relação Estrutura-Atividade
Trypanosoma cruzi/enzimologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antiprotozoal Agents); 0 (Boron Compounds); 0 (Carbonic Anhydrase Inhibitors); 0 (Heterocyclic Compounds, 2-Ring); EC 4.2.1.1 (Carbonic Anhydrases)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180105
[Lr] Data última revisão:
180105
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171228
[St] Status:MEDLINE
[do] DOI:10.1080/14756366.2017.1414808


  10 / 9457 MEDLINE  
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[PMID]:29232588
[Au] Autor:Galal Osman A; Elokely KM; Yadav VK; Carvalho P; Radwan M; Slade D; Gul W; Khan S; Dale OR; Husni AS; Klein ML; Cutler SJ; Ross SA; ElSohly MA
[Ad] Endereço:National Center for Natural Products Research, The University of Mississippi, University, MS 38677, United States. Electronic address: amgalalv@yahoo.com.
[Ti] Título:Bioactive products from singlet oxygen photooxygenation of cannabinoids.
[So] Source:Eur J Med Chem;143:983-996, 2018 Jan 01.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:Photooxygenation of Δ tetrahydrocannabinol (Δ -THC), Δ tetrahydrocannabinol (Δ -THC), Δ tetrahydrocannabinolic acid (Δ -THCA) and some derivatives (acetate, tosylate and methyl ether) yielded 24 oxygenated derivatives, 18 of which were new and 6 were previously reported, including allyl alcohols, ethers, quinones, hydroperoxides, and epoxides. Testing these compounds for their modulatory effect on cannabinoid receptors CB and CB led to the identification of 7 and 21 as CB partial agonists with Ki values of 0.043 µM and 0.048 µM, respectively and 23 as a cannabinoid with high binding affinity for CB with Ki value of 0.0095 µM, but much less affinity towards CB (Ki 0.467 µM). The synthesized compounds showed cytotoxic activity against cancer cell lines (SK-MEL, KB, BT-549, and SK-OV-3) with IC values ranging from 4.2 to 8.5 µg/mL. Several of those compounds showed antimicrobial, antimalarial and antileishmanial activities, with compound 14 being the most potent against various pathogens.
[Mh] Termos MeSH primário: Antibacterianos/farmacologia
Antifúngicos/farmacologia
Antimaláricos/farmacologia
Antineoplásicos/farmacologia
Antiprotozoários/farmacologia
Canabinoides/farmacologia
Oxigênio Singlete/química
[Mh] Termos MeSH secundário: Antibacterianos/síntese química
Antibacterianos/química
Antifúngicos/síntese química
Antifúngicos/química
Antimaláricos/síntese química
Antimaláricos/química
Antineoplásicos/síntese química
Antineoplásicos/química
Antiprotozoários/síntese química
Antiprotozoários/química
Bactérias/efeitos dos fármacos
Canabinoides/síntese química
Canabinoides/química
Linhagem Celular Tumoral
Proliferação Celular/efeitos dos fármacos
Ensaios de Seleção de Medicamentos Antitumorais
Fungos/efeitos dos fármacos
Seres Humanos
Leishmania major/efeitos dos fármacos
Testes de Sensibilidade Microbiana
Testes de Sensibilidade Parasitária
Processos Fotoquímicos
Plasmodium falciparum/efeitos dos fármacos
Receptor CB1 de Canabinoide/agonistas
Receptor CB2 de Canabinoide/agonistas
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Antifungal Agents); 0 (Antimalarials); 0 (Antineoplastic Agents); 0 (Antiprotozoal Agents); 0 (Cannabinoids); 0 (Receptor, Cannabinoid, CB1); 0 (Receptor, Cannabinoid, CB2); 17778-80-2 (Singlet Oxygen)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180101
[Lr] Data última revisão:
180101
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171213
[St] Status:MEDLINE



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