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Pesquisa : D27.505.954.122.250.100.115 [Categoria DeCS]
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[PMID]:28662966
[Au] Autor:Kutsumura N; Koyama Y; Nagumo Y; Nakajima R; Miyata Y; Yamamoto N; Saitoh T; Yoshida N; Iwata S; Nagase H
[Ad] Endereço:International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
[Ti] Título:Antitrichomonal activity of δ opioid receptor antagonists, 7-benzylidenenaltrexone derivatives.
[So] Source:Bioorg Med Chem;25(16):4375-4383, 2017 Aug 15.
[Is] ISSN:1464-3391
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The 7-benzylidenenaltrexone (BNTX) derivatives 2a-v, 3a-c, 13a-c, and 14a were synthesized from naltrexone (1) and evaluated for their antitrichomonal activity. The structure-activity-relationship studies found that 4-iodo-BNTX (2g) showed the highest activity (IC =10.5µM) and the affinity for the opioid receptor was less important for antitrichomonal activity against Trichomonas vaginalis. The morphinan skeleton bearing both the double bond for a Michael acceptor and the phenolic hydroxy group would be a specific template for development of antitrichomonal agents. In addition, the mechanism of the antitrichomonal activity of the BNTX derivatives may differ from that of the standard drug, metronidazole.
[Mh] Termos MeSH primário: Antitricômonas/farmacologia
Compostos de Benzilideno/farmacologia
Naltrexona/análogos & derivados
Receptores Opioides delta/antagonistas & inibidores
Trichomonas vaginalis/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Antitricômonas/síntese química
Antitricômonas/química
Compostos de Benzilideno/síntese química
Compostos de Benzilideno/química
Células CHO
Cricetulus
Relação Dose-Resposta a Droga
Estrutura Molecular
Naltrexona/síntese química
Naltrexona/química
Naltrexona/farmacologia
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antitrichomonal Agents); 0 (Benzylidene Compounds); 0 (Receptors, Opioid, delta); 129468-28-6 (7-benzylidenenaltrexone); 5S6W795CQM (Naltrexone)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170814
[Lr] Data última revisão:
170814
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170701
[St] Status:MEDLINE


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[PMID]:28100059
[Au] Autor:Peixoto A; Silva M; Vilas-Boas F; Macedo G
[Ad] Endereço:Gastrenterologia, Centro Hospitalar de São João, Portugal.
[Ti] Título:All that glitters is not gold. A different cause for an "ulcerative colitis".
[So] Source:Rev Esp Enferm Dig;109(1):64-65, 2017 Jan.
[Is] ISSN:1130-0108
[Cp] País de publicação:Spain
[La] Idioma:eng
[Ab] Resumo:The authors present the case of a 32-year-old Caucasian male, engineer, who was submitted to a colonoscopy after a presumptive diagnosis of ulcerative colitis. The patient referred an acute bloody and mucous diarrhea, lasting for three weeks, with no fever or rectal tenesmus. Stool studies were negative. During the procedure, colonic segments with continuous hyperemic and exudative mucosa, with small papules with apical ulcers and erosions, were observed.
[Mh] Termos MeSH primário: Colite Ulcerativa/etiologia
Entamoeba histolytica
Entamebíase/complicações
[Mh] Termos MeSH secundário: Adulto
Antitricômonas/uso terapêutico
Colite Ulcerativa/psicologia
Entamebíase/tratamento farmacológico
Entamebíase/parasitologia
Seres Humanos
Masculino
Metronidazol/uso terapêutico
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antitrichomonal Agents); 140QMO216E (Metronidazole)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171102
[Lr] Data última revisão:
171102
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170120
[St] Status:MEDLINE


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[PMID]:27956086
[Au] Autor:de Brum Vieira P; Feijó Silva NL; Silva DB; Lopes NP; da Silva AG; da Silva MV; Bastida J; Macedo AJ; Tasca T
[Ad] Endereço:Laboratório de Pesquisa em Parasitologia, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil; Programa de Pós-graduação em Ciências Biológicas, Universidade Federal do Pampa, São Gabriel, RS, Brazil. Electronic address: patriciasbrum@yahoo.com.br.
[Ti] Título:The Caatinga endemic Manilkara rufula possesses remarkable activity against Trichomonas vaginalis and Tritrichomonas foetus.
[So] Source:Exp Parasitol;173:18-28, 2017 Feb.
[Is] ISSN:1090-2449
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Tritrichomonas foetus infects the bovine urogenital tract, causing bovine trichomoniasis. Significant economic losses may occur due to infertility and abortion among cattle. Trichomonas vaginalis is the causative agent of trichomoniasis; the most common but overlooked non-viral sexually transmitted disease worldwide. Human and bovine trichomoniasis present treatment restrictions and efforts to identify new alternatives are essential. The present study evaluated the anti-trichomonads activities of seven fractions from northwest endemic plant Manilkara rufula. Flavonoids and condensed tannins were identified from these fractions by LC-DAD-MS/MS and MALDI-MS/MS. Altogether, the results demonstrated for the first time the structural description of tannins from leaves of M. rufula and the relation of these compounds with anti-T. vaginalis and anti-T. foetus activities. Overall, this report reveals the potential of M. rufula fractions against both parasites and shows new alternatives to treat the infection caused by trichomonads.
[Mh] Termos MeSH primário: Antitricômonas/farmacologia
Flavonoides/farmacologia
Manilkara/química
Extratos Vegetais/farmacologia
Taninos/farmacologia
Trichomonas vaginalis/efeitos dos fármacos
Tritrichomonas foetus/efeitos dos fármacos
[Mh] Termos MeSH secundário: Antitricômonas/química
Antitricômonas/isolamento & purificação
Brasil
Linhagem Celular
Sobrevivência Celular
Cromatografia Líquida
Células Epiteliais/efeitos dos fármacos
Flavonoides/química
Flavonoides/isolamento & purificação
Células HeLa
Seres Humanos
Estrutura Molecular
Extratos Vegetais/química
Extratos Vegetais/isolamento & purificação
Folhas de Planta/química
Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
Taninos/química
Taninos/isolamento & purificação
Trichomonas vaginalis/fisiologia
Tritrichomonas foetus/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antitrichomonal Agents); 0 (Flavonoids); 0 (Plant Extracts); 0 (Tannins)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170313
[Lr] Data última revisão:
170313
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161214
[St] Status:MEDLINE


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[PMID]:28099544
[Au] Autor:Singh R; Ramachandra SS; Dayakara JK
[Ad] Endereço:Department of Dental Care, Sri Guru Harkrishan Sahib Charitable Eye Hospital, Ludhiana, Punjab, India.
[Ti] Título:Oral fixed drug eruption due to tinidazole.
[So] Source:Cutis;98(6):E1-E2, 2016 Dec.
[Is] ISSN:2326-6929
[Cp] País de publicação:United States
[La] Idioma:eng
[Mh] Termos MeSH primário: Erupção por Droga/etiologia
Mucosa Bucal/efeitos dos fármacos
Tinidazol/efeitos adversos
[Mh] Termos MeSH secundário: Antitricômonas/efeitos adversos
Erupção por Droga/diagnóstico
Erupção por Droga/patologia
Seres Humanos
Masculino
Meia-Idade
Mucosa Bucal/patologia
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antitrichomonal Agents); 033KF7V46H (Tinidazole)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170608
[Lr] Data última revisão:
170608
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170119
[St] Status:MEDLINE


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[PMID]:27349003
[Au] Autor:Cakan H; Polat E; Arda O; Cepni I; Dirican A; Sirekbasan S
[Ti] Título:Morphological Changes of Trichomonas vaginalis Treated by Ornidazole: An In-Vitro Study.
[So] Source:Clin Lab;62(5):793-800, 2016.
[Is] ISSN:1433-6510
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Nitroimidazoles, which are drugs that are used to effectively treat Trichomonas vaginalis, alter the structure of the T. vaginalis cell membrane, penetrate into its cytoplasm and nucleus and block cellular metabolism. In this study, we observed the morphological changes that occurred in T. vaginalis during in vitro exposure to 1.3 µg/mL of ornidazole at various time intervals ranging from 10 minutes to 10 hours. METHODS: Vaginal and urethral secretion samples from suspected T. vaginalis cases were inoculated into Cysteine Peptone Liver Maltose medium. In 18 sterile tubes, 9.5 mL of this solution were mixed with 0.5 mL of ornidazole. The periods of contact between ornidazole and T. vaginalis ranged from 10 minutes to 10 hours. RESULTS: The first change was vacuolization, which started in the 10th minute of exposure. The glycogen particles started to diminish in the 20th minute. CONCLUSIONS: During exposure to 1.3 mg/L of ornidazole, cell lysis began in the 30th minute and accelerated towards the 60th minute (p < 0.001). Cytoplasmic matrix integrity was impaired in the 60th minute (p < 0.001).
[Mh] Termos MeSH primário: Antitricômonas/farmacologia
Ornidazol/farmacologia
Trichomonas vaginalis/efeitos dos fármacos
[Mh] Termos MeSH secundário: Fatores de Tempo
Trichomonas vaginalis/ultraestrutura
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antitrichomonal Agents); 62XCK0G93T (Ornidazole)
[Em] Mês de entrada:1607
[Cu] Atualização por classe:160628
[Lr] Data última revisão:
160628
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160629
[St] Status:MEDLINE


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[PMID]:27058337
[Au] Autor:Aksoy Gökmen A; Girginkardesler N; Kilimcioglu AA; Sirin MC; Özbilgin A
[Ad] Endereço:Katip Celebi University Faculty of Medicine, Department of Medical Microbiology, Izmir, Turkey. aaksoygokmen@hotmail.com.
[Ti] Título:[In vitro susceptibility of Trichomonas vaginalis to metronidazole, ornidazole and proton pump inhibitors pantoprazole and esomeprazole].
[Ti] Título:Trichomonas vaginalis'in metronidazol, ornidazol ve proton pompa inhibitörleri pantoprazol ve esomeprazole karsi in vitro duyarliligi..
[So] Source:Mikrobiyol Bul;50(1):133-9, 2016 Jan.
[Is] ISSN:0374-9096
[Cp] País de publicação:Turkey
[La] Idioma:tur
[Ab] Resumo:The current treatment of trichomoniasis is based on the use of 5-nitroimidazole derivatives. Although metronidazole is reliable, inexpensive and highly effective against anaerobic microorganisms and protozoa, the development of metronidazole-resistant T.vaginalis strains pose to an increasing problem. Nitroimidazoles are compounds having azomycin (2-nitroimidazole) chemical structure and are obtained from Streptomyces strains. Benzimidazole, which is found in the structure of proton pump inhibitors, is also present in the other components that have antiprotozoal activity. In this study, the in vitro susceptibility of T.vaginalis against metronidazole, ornidazole, and the proton pump inhibitors which are tested recently as antiprotozoal agents; pantoprazole and esomeprazole was investigated. For this purpose a clinical T.vaginalis strain which was formerly isolated and stored after cryopreservation process in our laboratory was used. Minimum inhibitory concentration (MIC) and minimum lethal concentration (MLC) values of those agents against to this strain were determined in vitro by dilution method in 24-well cell culture plates. Trypticase yeast extract maltose medium, horse serum and antibiotic (penicillin + streptomycin) were distributed to each well of cell culture plates and after metronidazole, ornidazole, pantoprazole and esomeprazole solutions were added to two wells for each as 800, 400, 200, 100, 50 and 25 µg/ml, followed by the addition of 1 ml 5x10(3) T.vaginalis trophozoites into each well. Plates were incubated at 37°C, and viability and motility of the trophozoites were evaluated under light microscope at 24, 48 and 72 hours after incubation. MIC and MLC values of metronidazole/ornidazole in the 72(th) hour were found as 50 µg/ml and 100 µg/ml, respectively. MIC and MLC values for pantoprazole in the 72th hour were 200 µg/ml and 400 µg/ml, while the values for esomeprazole were 400 µg/ml ve 800 µg/ml, respectively. As a result, T.vaginalis strain used in the study was susceptible to metronidazole and ornidazole, besides, it was considered that pantoprazole and esomeprazole were also effective to the parasite and could be used as alternative drugs. However, further in vitro and clinical studies are clearly needed on the antiprotozoal effects of proton pump inhibitors. To our knowledge, this study was the first in literature, which esomeprazole's susceptibility on T.vaginalis was investigated in vitro.
[Mh] Termos MeSH primário: Antitricômonas/farmacologia
Metronidazol/farmacologia
Ornidazol/farmacologia
Inibidores da Bomba de Prótons/farmacologia
Trichomonas vaginalis/efeitos dos fármacos
[Mh] Termos MeSH secundário: 2-Piridinilmetilsulfinilbenzimidazóis/farmacologia
Criopreservação
Resistência a Medicamentos
Esomeprazol/farmacologia
Seres Humanos
Testes de Sensibilidade Parasitária
Fatores de Tempo
[Pt] Tipo de publicação:ENGLISH ABSTRACT; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (2-Pyridinylmethylsulfinylbenzimidazoles); 0 (Antitrichomonal Agents); 0 (Proton Pump Inhibitors); 140QMO216E (Metronidazole); 62XCK0G93T (Ornidazole); D8TST4O562 (pantoprazole); N3PA6559FT (Esomeprazole)
[Em] Mês de entrada:1607
[Cu] Atualização por classe:160409
[Lr] Data última revisão:
160409
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160409
[St] Status:MEDLINE


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[PMID]:26525913
[Au] Autor:Ibáñez-Escribano A; Nogal-Ruiz JJ; Gómez-Barrio A; Arán VJ; Escario JA
[Ad] Endereço:Moncloa Campus of International Excellence,UCM-UPM & CSIC,Madrid,Spain.
[Ti] Título:In vitro trichomonacidal activity and preliminary in silico chemometric studies of 5-nitroindazolin-3-one and 3-alkoxy-5-nitroindazole derivatives.
[So] Source:Parasitology;143(1):34-40, 2016 Jan.
[Is] ISSN:1469-8161
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:A selection of 1,2-disubstituted 5-nitroindazolin-3-ones (1-19) and 3-alkoxy-5-nitroindazoles substituted at positions 1 (20-24) or 2 (25-39) from our in-house compound library were screened in vitro against the most common curable sexually transmitted pathogen, Trichomonas vaginalis. A total of 41% of the studied molecules (16/39) achieved a significant activity of more than 85% growth inhibition at the highest concentration assayed (100 µg mL(-1)). Among these compounds, 3-alkoxy-5-nitroindazole derivatives 23, 24, 25 and 27 inhibited parasite growth by more than 50% at 10 µg mL(-1). In addition, the first two compounds (23, 24) still showed remarkable activity at the lowest dose tested (1 µg mL(-1)), inhibiting parasite growth by nearly 40%. Their specific activity towards the parasite was corroborated by the determination of their non-specific cytotoxicity against mammalian cells. The four mentioned compounds exhibited non-cytotoxic profiles at all of the concentrations assayed, showing a fair antiparasitic selectivity index (SI > 7·5). In silico studies were performed to predict pharmacokinetic properties, toxicity and drug-score using Molinspiration and OSIRIS computational tools. The current in vitro results supported by the virtual screening suggest 2-substituted and, especially, 1-substituted 3-alkoxy-5-nitroindazoles as promising starting scaffolds for further development of novel chemical compounds with the main aim of promoting highly selective trichomonacidal lead-like drugs with adequate pharmacokinetic and toxicological profiles.
[Mh] Termos MeSH primário: Antitricômonas/farmacologia
Indazóis/farmacologia
Tricomoníase/tratamento farmacológico
Trichomonas vaginalis/efeitos dos fármacos
[Mh] Termos MeSH secundário: Álcoois/química
Animais
Antitricômonas/efeitos adversos
Antitricômonas/química
Sobrevivência Celular
Cercopithecus aethiops
Simulação por Computador
Indazóis/efeitos adversos
Indazóis/química
Testes de Sensibilidade Parasitária
Relação Estrutura-Atividade
Células Vero
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Alcohols); 0 (Antitrichomonal Agents); 0 (Indazoles); 0 (alkoxyl radical); 235Y7P37ZD (5-nitroindazole)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151104
[St] Status:MEDLINE
[do] DOI:10.1017/S0031182015001419


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[PMID]:26384945
[Au] Autor:Forbes GL; Drayton R; Forbes GD
[Ad] Endereço:Department of Sexual Health, Cardiff Royal Infirmary, Cardiff, UK georgina.forbes@wales.nhs.uk.
[Ti] Título:A case of metronidazole-resistant Trichomonas vaginalis in pregnancy.
[So] Source:Int J STD AIDS;27(10):906-8, 2016 Sep.
[Is] ISSN:1758-1052
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Trichomonas vaginalis is a sexually transmitted protozoan infection resulting in vulvo-vaginitis and altered vaginal discharge in symptomatic women. Trichomoniasis has been implicated in causing adverse pregnancy outcomes such as low birth weight and pre-term labour. Metronidazole is the recommended first-line treatment for trichomonal infection. Other nitroimidazoles, such as tinidazole, are used as alternative regimens with similar activity but at a greater expense. Treatment failure usually represents patient non-compliance or re-infection, although metronidazole resistance has previously been documented. Antimicrobial susceptibility testing for T. vaginalis is currently not available in the UK. Patients with disease unresponsive to first-line treatments pose a major challenge, as therapeutic options are limited. We present the case of a patient with presumed resistant infection during pregnancy, and the additional treatment issues that this presented.
[Mh] Termos MeSH primário: Antitricômonas/uso terapêutico
Metronidazol/uso terapêutico
Complicações Parasitárias na Gravidez/tratamento farmacológico
Tinidazol/uso terapêutico
Vaginite por Trichomonas/tratamento farmacológico
Trichomonas vaginalis/isolamento & purificação
[Mh] Termos MeSH secundário: Resistência a Medicamentos
Feminino
Seres Humanos
Gravidez
Complicações Parasitárias na Gravidez/diagnóstico
Resultado da Gravidez
Resultado do Tratamento
Vaginite por Trichomonas/diagnóstico
Trichomonas vaginalis/efeitos dos fármacos
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antitrichomonal Agents); 033KF7V46H (Tinidazole); 140QMO216E (Metronidazole)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170630
[Lr] Data última revisão:
170630
[Sb] Subgrupo de revista:IM; X
[Da] Data de entrada para processamento:150920
[St] Status:MEDLINE
[do] DOI:10.1177/0956462415601295


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[PMID]:26592812
[Au] Autor:Beck S; Muellers SN; Benzie AL; Parkin DW; Stockman BJ
[Ad] Endereço:Department of Chemistry, Adelphi University, 1 South Avenue, Garden City, NY 11530, United States.
[Ti] Título:Adenosine/guanosine preferring nucleoside ribohydrolase is a distinct, druggable antitrichomonal target.
[So] Source:Bioorg Med Chem Lett;25(22):5036-9, 2015 Nov 15.
[Is] ISSN:1464-3405
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Nucleoside salvage pathway enzymes used by Trichomonas vaginalis are distinct from the pathway involved in activation of existing 5-nitroimidazole drugs. They thus represent excellent targets for developing novel, mechanism-based antitrichomonal agents. The purine-specific adenosine/guanosine preferring ribohydrolase (AGNH) was screened against the NIH Clinical Collection to assess its druggability. Eight compounds, including five flavonoids, were identified with IC50 values ⩽10 µM and confirmed in counter screens run in the presence of detergent. The inhibitors are structurally distinct from inhibitors of the pyrimidine-specific uridine ribohydrolase (UNH) thus indicating that AGNH is a distinct, druggable target from UNH.
[Mh] Termos MeSH primário: Antitricômonas/química
Flavonoides/química
N-Glicosil Hidrolases/antagonistas & inibidores
[Mh] Termos MeSH secundário: Adenosina/análogos & derivados
Adenosina/química
Ensaios de Triagem em Larga Escala
Quercetina/análogos & derivados
Quercetina/química
Bibliotecas de Moléculas Pequenas/química
Estereoisomerismo
Trichomonas vaginalis
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antitrichomonal Agents); 0 (Flavonoids); 0 (Small Molecule Libraries); 37739-05-2 (2-chloro-N(6)cyclopentyladenosine); 9025-47-2 (uridine nucleosidase); 9IKM0I5T1E (Quercetin); 9SOB9E3987 (taxifolin); EC 3.2.2.- (N-Glycosyl Hydrolases); EC 3.2.2.1 (purine nucleosidase); K72T3FS567 (Adenosine)
[Em] Mês de entrada:1608
[Cu] Atualização por classe:151123
[Lr] Data última revisão:
151123
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151124
[St] Status:MEDLINE


  10 / 880 MEDLINE  
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[PMID]:26303799
[Au] Autor:Huang KY; Ku FM; Cheng WH; Lee CC; Huang PJ; Chu LJ; Cheng CC; Fang YK; Wu HH; Tang P
[Ad] Endereço:Molecular Regulation and Bioinformatics Laboratory, Department of Parasitology, Chang Gung University, Taoyuan, Taiwan Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan.
[Ti] Título:Novel insights into the molecular events linking to cell death induced by tetracycline in the amitochondriate protozoan Trichomonas vaginalis.
[So] Source:Antimicrob Agents Chemother;59(11):6891-903, 2015 Nov.
[Is] ISSN:1098-6596
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Trichomonas vaginalis colonizes the human urogenital tract and causes trichomoniasis, the most common nonviral sexually transmitted disease. Currently, 5-nitroimidazoles are the only recommended drugs for treating trichomoniasis. However, increased resistance of the parasite to 5-nitroimidazoles has emerged as a highly problematic public health issue. Hence, it is essential to identify alternative chemotherapeutic agents against refractory trichomoniasis. Tetracycline (TET) is a broad-spectrum antibiotic with activity against several protozoan parasites, but the mode of action of TET in parasites remains poorly understood. The in vitro effect of TET on the growth of T. vaginalis was examined, and the mode of cell death was verified by various apoptosis-related assays. Next-generation sequencing-based RNA sequencing (RNA-seq) was employed to elucidate the transcriptome of T. vaginalis in response to TET. We show that TET has a cytotoxic effect on both metronidazole (MTZ)-sensitive and -resistant T. vaginalis isolates, inducing some features resembling apoptosis. RNA-seq data reveal that TET significantly alters the transcriptome via activation of specific pathways, such as aminoacyl-tRNA synthetases and carbohydrate metabolism. Functional analyses demonstrate that TET disrupts the hydrogenosomal membrane potential and antioxidant system, which concomitantly elicits a metabolic shift toward glycolysis, suggesting that the hydrogenosomal function is impaired and triggers cell death. Collectively, we provide in vitro evidence that TET is a potential alternative therapeutic choice for treating MTZ-resistant T. vaginalis. The in-depth transcriptomic signatures in T. vaginalis upon TET treatment presented here will shed light on the signaling pathways linking to cell death in amitochondriate organisms.
[Mh] Termos MeSH primário: Antitricômonas/farmacologia
Tetraciclina/farmacologia
Trichomonas vaginalis/efeitos dos fármacos
[Mh] Termos MeSH secundário: Morte Celular/efeitos dos fármacos
Glicólise/efeitos dos fármacos
Sequenciamento de Nucleotídeos em Larga Escala
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antitrichomonal Agents); F8VB5M810T (Tetracycline)
[Em] Mês de entrada:1608
[Cu] Atualização por classe:160501
[Lr] Data última revisão:
160501
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150826
[St] Status:MEDLINE
[do] DOI:10.1128/AAC.01779-15



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