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  1 / 1805 MEDLINE  
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[PMID]:28470520
[Au] Autor:Suganuma K; Molefe NI; Inoue N
[Ad] Endereço:National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada, Obihiro, Hokkaido, 080-8555, Japan. k.suganuma@obihiro.ac.jp.
[Ti] Título:An ATP-Based Luciferase Viability Assay for Animal African Trypanosomes Using a 96-Well Plate.
[So] Source:Methods Mol Biol;1601:89-95, 2017.
[Is] ISSN:1940-6029
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Cell viability assays using multi-well cell culture plates are frequently used for in vitro drug screening. We herein describe an ATP-based luciferase viability assay for animal African trypanosomes using a 96-well plate. This assay could be further applied to the screening of novel compounds for the treatment of animal African trypanosomiasis.
[Mh] Termos MeSH primário: Sobrevivência Celular/efeitos dos fármacos
Tripanossomicidas/farmacologia
Trypanosoma brucei brucei/efeitos dos fármacos
Trypanosoma congolense/efeitos dos fármacos
Tripanossomíase Africana/veterinária
[Mh] Termos MeSH secundário: Trifosfato de Adenosina/análise
Trifosfato de Adenosina/metabolismo
Animais
Diminazena/análogos & derivados
Diminazena/farmacologia
Avaliação Pré-Clínica de Medicamentos/instrumentação
Avaliação Pré-Clínica de Medicamentos/métodos
Seres Humanos
Concentração Inibidora 50
Luciferases/metabolismo
Pentamidina/farmacologia
Tripanossomíase Africana/tratamento farmacológico
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Trypanocidal Agents); 673LC5J4LQ (Pentamidine); 8L70Q75FXE (Adenosine Triphosphate); EC 1.13.12.- (Luciferases); JI8SAD85NO (diminazene aceturate); Y5G36EEA5Z (Diminazene)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180219
[Lr] Data última revisão:
180219
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170505
[St] Status:MEDLINE
[do] DOI:10.1007/978-1-4939-6960-9_8


  2 / 1805 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


  3 / 1805 MEDLINE  
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[PMID]:28470665
[Au] Autor:Zhao E; Ilyas G; Cingolani F; Choi JH; Ravenelle F; Tanaka KE; Czaja MJ
[Ad] Endereço:Department of Medicine and the Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY.
[Ti] Título:Pentamidine blocks hepatotoxic injury in mice.
[So] Source:Hepatology;66(3):922-935, 2017 09.
[Is] ISSN:1527-3350
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Toxin-induced liver diseases lack effective therapies despite increased understanding of the role factors such as an overactive innate immune response play in the pathogenesis of this form of hepatic injury. Pentamidine is an effective antimicrobial agent against several human pathogens, but studies have also suggested that this drug inhibits inflammation. This potential anti-inflammatory mechanism of action, together with the development of a new oral form of pentamidine isethionate VLX103, led to investigations of the effectiveness of this drug in the prevention and treatment of hepatotoxic liver injury. Pretreatment with a single injection of VLX103 in the d-galactosamine (GalN) and lipopolysaccharide (LPS) model of acute, fulminant liver injury dramatically decreased serum alanine aminotransferase levels, histological injury, the number of terminal deoxynucleotide transferase-mediated deoxyuridine triphosphate nick end-labeling (TUNEL)-positive cells and mortality compared with vehicle-injected controls. VLX103 decreased GalN/LPS induction of tumor necrosis factor (TNF) but had no effect on other proinflammatory cytokines. VLX103 prevented the proinflammatory activation of cultured hepatic macrophages and partially blocked liver injury from GalN/TNF. In GalN/LPS-treated mice, VLX103 decreased activation of both the mitochondrial death pathway and downstream effector caspases 3 and 7, which resulted from reduced c-Jun N-terminal kinase activation and initiator caspase 8 cleavage. Delaying VLX103 treatment for up to 3 hours after GalN/LPS administration was still remarkably effective in blocking liver injury in this model. Oral administration of VLX103 also decreased hepatotoxic injury in a second more chronic model of alcohol-induced liver injury, as demonstrated by decreased serum alanine and aspartate aminotransferase levels and numbers of TUNEL-positive cells. CONCLUSION: VLX103 effectively decreases toxin-induced liver injury in mice and may be an effective therapy for this and other forms of human liver disease. (Hepatology 2017;66:922-935).
[Mh] Termos MeSH primário: Galactosamina/toxicidade
Lipopolissacarídeos/toxicidade
Falência Hepática Aguda/prevenção & controle
Pentamidina/farmacologia
[Mh] Termos MeSH secundário: Animais
Biópsia por Agulha
Western Blotting
Citocinas/metabolismo
Modelos Animais de Doenças
Imuno-Histoquímica
Marcação In Situ das Extremidades Cortadas
Falência Hepática Aguda/induzido quimicamente
Falência Hepática Aguda/mortalidade
Testes de Função Hepática
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Distribuição Aleatória
Reação em Cadeia da Polimerase em Tempo Real/métodos
Taxa de Sobrevida
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Cytokines); 0 (Lipopolysaccharides); 673LC5J4LQ (Pentamidine); 7535-00-4 (Galactosamine)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:180122
[Lr] Data última revisão:
180122
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170505
[St] Status:MEDLINE
[do] DOI:10.1002/hep.29244


  4 / 1805 MEDLINE  
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[PMID]:28362799
[Au] Autor:Sekhar GN; Georgian AR; Sanderson L; Vizcay-Barrena G; Brown RC; Muresan P; Fleck RA; Thomas SA
[Ad] Endereço:King's College London, Institute of Pharmaceutical Science, Waterloo, London United Kingdom.
[Ti] Título:Organic cation transporter 1 (OCT1) is involved in pentamidine transport at the human and mouse blood-brain barrier (BBB).
[So] Source:PLoS One;12(3):e0173474, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Pentamidine is an effective trypanocidal drug used against stage 1 Human African Trypanosomiasis (HAT). At the blood-brain barrier (BBB), it accumulates inside the endothelial cells but has limited entry into the brain. This study examined transporters involved in pentamidine transport at the human and mouse BBB using hCMEC/D3 and bEnd.3 cell lines, respectively. Results revealed that both cell lines expressed the organic cation transporters (OCT1, OCT2 and OCT3), however, P-gp was only expressed in hCMEC/D3 cells. Polarised expression of OCT1 was also observed. Functional assays found that ATP depletion significantly increased [3H]pentamidine accumulation in hCMEC/D3 cells (***p<0.001) but not in bEnd.3 cells. Incubation with unlabelled pentamidine significantly decreased accumulation in hCMEC/D3 and bEnd.3 cells after 120 minutes (***p<0.001). Treating both cell lines with haloperidol and amantadine also decreased [3H]pentamidine accumulation significantly (***p<0.001 and **p<0.01 respectively). However, prazosin treatment decreased [3H]pentamidine accumulation only in hCMEC/D3 cells (*p<0.05), and not bEnd.3 cells. Furthermore, the presence of OCTN, MATE, PMAT, ENT or CNT inhibitors/substrates had no significant effect on the accumulation of [3H]pentamidine in both cell lines. From the data, we conclude that pentamidine interacts with multiple transporters, is taken into brain endothelial cells by OCT1 transporter and is extruded into the blood by ATP-dependent mechanisms. These interactions along with the predominant presence of OCT1 in the luminal membrane of the BBB contribute to the limited entry of pentamidine into the brain. This information is of key importance to the development of pentamidine based combination therapies which could be used to treat CNS stage HAT by improving CNS delivery, efficacy against trypanosomes and safety profile of pentamidine.
[Mh] Termos MeSH primário: Barreira Hematoencefálica/metabolismo
Transportador 1 de Cátions Orgânicos/metabolismo
Pentamidina/metabolismo
[Mh] Termos MeSH secundário: Trifosfato de Adenosina/metabolismo
Animais
Transporte Biológico/genética
Transporte Biológico/fisiologia
Western Blotting
Encéfalo/metabolismo
Linhagem Celular
Eletroforese em Gel de Poliacrilamida
Seres Humanos
Camundongos
Microscopia Confocal
Microscopia Eletrônica de Transmissão
Fator 3 de Transcrição de Octâmero/genética
Fator 3 de Transcrição de Octâmero/metabolismo
Proteínas de Transporte de Cátions Orgânicos/genética
Proteínas de Transporte de Cátions Orgânicos/metabolismo
Transportador 1 de Cátions Orgânicos/genética
Transportador 2 de Cátion Orgânico
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Octamer Transcription Factor-3); 0 (Organic Cation Transport Proteins); 0 (Organic Cation Transporter 1); 0 (Organic Cation Transporter 2); 0 (Pou5f1 protein, mouse); 0 (Slc22a2 protein, mouse); 673LC5J4LQ (Pentamidine); 8L70Q75FXE (Adenosine Triphosphate)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170401
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0173474


  5 / 1805 MEDLINE  
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[PMID]:28174101
[Au] Autor:de Araújo MV; David CC; Neto JC; de Oliveira LA; da Silva KC; Dos Santos JM; da Silva JK; de A Brandão VB; Silva TM; Camara CA; Alexandre-Moreira MS
[Ad] Endereço:Laboratory of Pharmacology and Immunity, Institute of Biological Sciences and Health, Federal University of Alagoas, 57020-720, Maceió, AL, Brazil. Electronic address: morgana_vital@hotmail.com.
[Ti] Título:Evaluation on the leishmanicidal activity of 2-N,N'-dialkylamino-1,4-naphthoquinone derivatives.
[So] Source:Exp Parasitol;176:46-51, 2017 May.
[Is] ISSN:1090-2449
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Parasites of the Leishmania genus are the causative agents of leishmaniasis in humans, a disease that affects more than 12 million people worldwide. In this study was evaluated in vitro leishmanicidal activity of 2-N,N'-dialkylamino-1,4-naphthoquinone derivatives, covering a series of fourteen 2-N-morpholino-, 2-N-thiomorpholino, 2-N-piperidino, 2-N-(N -methyl)-piperazino naphthoquinones (1a-n) derived from nor-lapachol and lawsone, belong to some other di-alkyaminoderivatives. At the cytotoxicity assay on peritoneal macrophages, the compounds possessing larger alkyl groups and N-methyl-piperazino moiety (1d, 1h, 1i and 1k), showed toxic effects similar to the standard drug used pentamidine. However, the other compounds of the series showed no deleterious effect on the host cell. Meanwhile, these cytotoxic derivatives (1d, 1h and 1i) had pronounced leishmanicidal activity against L. amazonensis promastigotes, and treatments with six other compounds (1d, 1e, 1f, 1h, 1k and 1n) had significant effect leishmanicidal against L. chagasi promastigotes. In the assay against L. chagasi amastigotes, eight compounds (1a, 1b, 1c, 1d, 1h, 1i, 1k and 1m) showed significant activity. Moreover, the compounds (1a, 1b, 1c, and 1m) showed effect against amastigotes of L. chagasi and not being toxic to the host cell. These data show the derivatives as promising substances for research leishmanicidal activity.
[Mh] Termos MeSH primário: Antiprotozoários/farmacologia
Leishmania mexicana/efeitos dos fármacos
Naftoquinonas/farmacologia
[Mh] Termos MeSH secundário: Animais
Antiprotozoários/química
Antiprotozoários/toxicidade
Concentração Inibidora 50
Macrófagos Peritoneais/efeitos dos fármacos
Macrófagos Peritoneais/parasitologia
Camundongos
Naftoquinonas/química
Naftoquinonas/toxicidade
Pentamidina/farmacologia
Pentamidina/toxicidade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antiprotozoal Agents); 0 (Naphthoquinones); 673LC5J4LQ (Pentamidine)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170411
[Lr] Data última revisão:
170411
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170209
[St] Status:MEDLINE


  6 / 1805 MEDLINE  
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[PMID]:28167598
[Au] Autor:Ginouvès M; Simon S; Nacher M; Demar M; Carme B; Couppié P; Prévot G
[Ad] Endereço:Laboratoire Associé, Centre National de Référence Leishmania, Laboratoire Hospitalo-Universitaire de Parasitologie et Mycologie, General Hospital, Cayenne, French Guiana.
[Ti] Título:In Vitro Sensitivity of Cutaneous Promastigote Isolates Circulating in French Guiana to a Set of Drugs.
[So] Source:Am J Trop Med Hyg;96(5):1143-1150, 2017 May.
[Is] ISSN:1476-1645
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:AbstractAnti-leishmaniasis drug resistance is a common problem worldwide. The aim of this study was to inventory the general in vitro level of sensitivity of isolates circulating in French Guiana and to highlight potential in vitro pentamidine-resistant isolates. This sensitivity study was conducted on 36 patient-promastigote isolates for seven drugs (amphotericin B, azithromycin, fluconazole, meglumine antimoniate, miltefosine, paromomycin, and pentamidine) using the Cell Counting Kit-8 viability test. The IC values obtained were heterogeneous. One isolate exhibited high IC values for almost all drugs tested. Pentamidine, which is the first-line treatment in French Guiana, showed efficacy at very low doses (mean of 0.0038 µg/mL). The concordance of the in vitro pentamidine results with the patients' clinical outcomes was 94% ( = 0.82).
[Mh] Termos MeSH primário: Antiprotozoários/farmacologia
Leishmania braziliensis/efeitos dos fármacos
Leishmania guyanensis/efeitos dos fármacos
Leishmaniose Cutânea/tratamento farmacológico
Pentamidina/farmacologia
[Mh] Termos MeSH secundário: Anfotericina B/farmacologia
Azitromicina/farmacologia
Resistência a Medicamentos
Fluconazol/farmacologia
Seres Humanos
Leishmania braziliensis/crescimento & desenvolvimento
Leishmania braziliensis/isolamento & purificação
Leishmania guyanensis/crescimento & desenvolvimento
Leishmania guyanensis/isolamento & purificação
Leishmaniose Cutânea/parasitologia
Meglumina/farmacologia
Compostos Organometálicos/farmacologia
Testes de Sensibilidade Parasitária
Paromomicina/farmacologia
Fosforilcolina/análogos & derivados
Fosforilcolina/farmacologia
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antiprotozoal Agents); 0 (Organometallic Compounds); 107-73-3 (Phosphorylcholine); 53EY29W7EC (miltefosine); 61JJC8N5ZK (Paromomycin); 673LC5J4LQ (Pentamidine); 6HG8UB2MUY (Meglumine); 75G4TW236W (meglumine antimoniate); 7XU7A7DROE (Amphotericin B); 83905-01-5 (Azithromycin); 8VZV102JFY (Fluconazole)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170803
[Lr] Data última revisão:
170803
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170208
[St] Status:MEDLINE
[do] DOI:10.4269/ajtmh.16-0373


  7 / 1805 MEDLINE  
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[PMID]:28087819
[Au] Autor:Hoeker GS; Skarsfeldt MA; Jespersen T; Poelzing S
[Ad] Endereço:Biomedical Engineering and Mechanics, Center for Heart and Regenerative Medicine, Virginia Tech Virginia Tech Carilion Research Institute, Roanoke, Virginia.
[Ti] Título:Electrophysiologic effects of the IK1 inhibitor PA-6 are modulated by extracellular potassium in isolated guinea pig hearts.
[So] Source:Physiol Rep;5(1), 2017 Jan.
[Is] ISSN:2051-817X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The pentamidine analog PA-6 was developed as a specific inward rectifier potassium current (I ) antagonist, because established inhibitors either lack specificity or have side effects that prohibit their use in vivo. We previously demonstrated that BaCl , an established I inhibitor, could prolong action potential duration (APD) and increase cardiac conduction velocity (CV). However, few studies have addressed whether targeted I inhibition similarly affects ventricular electrophysiology. The aim of this study was to determine the effects of PA-6 on cardiac repolarization and conduction in Langendorff-perfused guinea pig hearts. PA-6 (200 nm) or vehicle was perfused into ex-vivo guinea pig hearts for 60 min. Hearts were optically mapped with di-4-ANEPPS to quantify CV and APD at 90% repolarization (APD ). Ventricular APD was significantly prolonged in hearts treated with PA-6 (115 ± 2% of baseline; P < 0.05), but not vehicle (105 ± 2% of baseline). PA-6 slightly, but significantly, increased transverse CV by 7%. PA-6 significantly prolonged APD during hypokalemia (2 mmol/L [K+] ), although to a lesser degree than observed at 4.56 mmol/L [K+] In contrast, the effect of PA-6 on CV was more pronounced during hypokalemia, where transverse CV with PA-6 (24 ± 2 cm/sec) was significantly faster than with vehicle (13 ± 3 cm/sec, P < 0.05). These results show that under normokalemic conditions, PA-6 significantly prolonged APD , whereas its effect on CV was modest. During hypokalemia, PA-6 prolonged APD to a lesser degree, but profoundly increased CV Thus, in intact guinea pig hearts, the electrophysiologic effects of the I inhibitor, PA-6, are [K+] -dependent.
[Mh] Termos MeSH primário: Potenciais de Ação/efeitos dos fármacos
Antraquinonas/farmacologia
Sistema de Condução Cardíaco/efeitos dos fármacos
Ventrículos do Coração/efeitos dos fármacos
Pentamidina/análogos & derivados
Bloqueadores dos Canais de Potássio/farmacologia
Canais de Potássio/efeitos dos fármacos
Potássio/metabolismo
[Mh] Termos MeSH secundário: Potenciais de Ação/fisiologia
Animais
Antraquinonas/administração & dosagem
Compostos de Bário/administração & dosagem
Compostos de Bário/farmacologia
Cloretos/administração & dosagem
Cloretos/farmacologia
Fenômenos Eletrofisiológicos
Cobaias
Coração/fisiologia
Sistema de Condução Cardíaco/fisiologia
Ventrículos do Coração/metabolismo
Ventrículos do Coração/fisiopatologia
Hipopotassemia/fisiopatologia
Masculino
Bloqueadores dos Canais de Potássio/administração & dosagem
Canais de Potássio/metabolismo
Compostos de Piridínio/análise
Compostos de Piridínio/metabolismo
Imagens com Corantes Sensíveis à Voltagem/métodos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anthraquinones); 0 (Barium Compounds); 0 (Chlorides); 0 (Potassium Channel Blockers); 0 (Potassium Channels); 0 (Pyridinium Compounds); 0 (ptilometric acid 6-O-sulfate); 0VK51DA1T2 (barium chloride); 673LC5J4LQ (Pentamidine); 90134-00-2 (1-(3-sulfonatopropyl)-4-(beta)(2-(di-n-butylamino)-6-naphthylvinyl)pyridinium betaine); RWP5GA015D (Potassium)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171106
[Lr] Data última revisão:
171106
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170115
[St] Status:MEDLINE


  8 / 1805 MEDLINE  
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[PMID]:28074607
[Au] Autor:Kruizinga MD; Bresters D; Smiers FJ; Lankester AC; Bredius RGM
[Ad] Endereço:Department of Pediatric Immunology-Infections and Stem Cell Transplantation, Leiden University Medical Center, Leiden, The Netherlands.
[Ti] Título:The use of intravenous pentamidine for the prophylaxis of Pneumocystis pneumonia in pediatric patients.
[So] Source:Pediatr Blood Cancer;64(8), 2017 Aug.
[Is] ISSN:1545-5017
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Pneumocystis jiroveci pneumonia was common in the immunocompromised host before the widespread use of prophylaxis. When trimethoprim-sulfamethoxazole is not tolerated, prophylaxis with intravenous pentamidine (IVP) may be initiated. We performed a retrospective analysis of all pediatric patients who received IVP regarding efficacy, safety, and reason for initiation. Of 106 patients included in our analysis, one patient tested positive for Pneumocystis DNA. Adverse events were reported in 18% of IVP courses, and main reason for initiation was cytopenia (59%). We found IVP to be effective and safe, and recommend the use of IVP in pediatric patients in whom first-line prophylaxis is contraindicated.
[Mh] Termos MeSH primário: Antifúngicos/uso terapêutico
Hospedeiro Imunocomprometido/efeitos dos fármacos
Pentamidina/uso terapêutico
Pneumonia por Pneumocystis/prevenção & controle
[Mh] Termos MeSH secundário: Criança
Feminino
Seres Humanos
Masculino
Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia
Estudos Retrospectivos
Transplante de Células-Tronco
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antifungal Agents); 673LC5J4LQ (Pentamidine)
[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:170112
[St] Status:MEDLINE
[do] DOI:10.1002/pbc.26453


  9 / 1805 MEDLINE  
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[PMID]:27976958
[Au] Autor:Plate A; Vallelian F; Herfs G
[Ad] Endereço:1 Klinik und Poliklinik für Innere Medizin, Universitätsspital Zürich.
[Ti] Título:Der Zytokinsturm ­ eine Komplikation des adulten Morbus Still..
[So] Source:Praxis (Bern 1994);105(25):1503-1506, 2016.
[Is] ISSN:1661-8157
[Cp] País de publicação:Switzerland
[La] Idioma:ger
[Mh] Termos MeSH primário: Citocinas/sangue
Doença de Still de Início Tardio/complicações
[Mh] Termos MeSH secundário: Administração por Inalação
Adulto
Anticorpos Monoclonais Humanizados/uso terapêutico
Ciclosporina/uso terapêutico
Relação Dose-Resposta a Droga
Hipersensibilidade a Drogas/imunologia
Quimioterapia Combinada
Feminino
Ferritinas/sangue
Seres Humanos
Ativação Linfocitária/efeitos dos fármacos
Ativação Linfocitária/imunologia
Síndrome de Ativação Macrofágica/diagnóstico
Síndrome de Ativação Macrofágica/tratamento farmacológico
Síndrome de Ativação Macrofágica/imunologia
Pentamidina/uso terapêutico
Prednisona/uso terapêutico
Recidiva
Doença de Still de Início Tardio/diagnóstico
Doença de Still de Início Tardio/tratamento farmacológico
Doença de Still de Início Tardio/imunologia
Linfócitos T/efeitos dos fármacos
Combinação Trimetoprima e Sulfametoxazol/efeitos adversos
Combinação Trimetoprima e Sulfametoxazol/uso terapêutico
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Monoclonal, Humanized); 0 (Cytokines); 673LC5J4LQ (Pentamidine); 8064-90-2 (Trimethoprim, Sulfamethoxazole Drug Combination); 83HN0GTJ6D (Cyclosporine); 9007-73-2 (Ferritins); I031V2H011 (tocilizumab); VB0R961HZT (Prednisone)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170621
[Lr] Data última revisão:
170621
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161216
[St] Status:MEDLINE


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[PMID]:27729250
[Au] Autor:Seguel V; Castro L; Reigada C; Cortes L; Díaz MV; Miranda MR; Pereira CA; Lapier M; Campos-Estrada C; Morello A; Kemmerling U; Maya JD; López-Muñoz R
[Ad] Endereço:Programa de Farmacología Molecular y Clínica, ICBM, Facultad de Medicina, Universidad de Chile, Santiago, Chile.
[Ti] Título:Pentamidine antagonizes the benznidazole's effect in vitro, and lacks of synergy in vivo: Implications about the polyamine transport as an anti-Trypanosoma cruzi target.
[So] Source:Exp Parasitol;171:23-32, 2016 Dec.
[Is] ISSN:1090-2449
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Benznidazole is the first-line drug used in treating Chagas disease, which is caused by the parasite Trypanosoma cruzi (T. cruzi). However, benznidazole has limited efficacy and several adverse reactions. Pentamidine is an antiprotozoal drug used in the treatment of leishmaniasis and African trypanosomiasis. In T. cruzi, pentamidine blocks the transport of putrescine, a precursor of trypanothione, which constitutes an essential molecule in the resistance of T. cruzi to benznidazole. In the present study, we describe the effect of the combination of benznidazole and pentamidine on isolated parasites, mammalian cells and in mice infected with T. cruzi. In isolated trypomastigotes, we performed a dose-matrix scheme of combinations, where pentamidine antagonized the effect of benznidazole, mainly at concentrations below the EC of pentamidine. In T. cruzi-infected mammalian cells, pentamidine reversed the effect of benznidazole (measured by qPCR). In comparison, in infected BALB/c mice, pentamidine failed to get synergy with benznidazole, measured on mice survival, parasitemia and amastigote nest quantification. To further explain the in vitro antagonism, we explored whether pentamidine affects intracellular trypanothione levels, however, pentamidine produced no change in trypanothione concentrations. Finally, the T. cruzi polyamine permease (TcPAT12) was overexpressed in epimastigotes, showing that pentamidine has the same trypanocidal effect, independently of transporter expression levels. These results suggest that, in spite of the high potency in the putrescine transport blockade, TcPAT12 permease is not the main target of pentamidine, and could explain the lack of synergism between pentamidine and benznidazole.
[Mh] Termos MeSH primário: Doença de Chagas/tratamento farmacológico
Nitroimidazóis/antagonistas & inibidores
Pentamidina/farmacologia
Tripanossomicidas/farmacologia
Trypanosoma cruzi/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Cercopithecus aethiops
Doença de Chagas/patologia
DNA de Protozoário/análise
DNA de Protozoário/isolamento & purificação
Relação Dose-Resposta a Droga
Glutationa/análogos & derivados
Glutationa/efeitos dos fármacos
Glutationa/metabolismo
Macrófagos/parasitologia
Masculino
Camundongos
Camundongos Endogâmicos BALB C
Miocárdio/patologia
Parasitemia/tratamento farmacológico
Parasitemia/parasitologia
Putrescina/metabolismo
Distribuição Aleatória
Espermidina/análogos & derivados
Espermidina/metabolismo
Timidina/metabolismo
Tripanossomicidas/antagonistas & inibidores
Células Vero
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (DNA, Protozoan); 0 (Nitroimidazoles); 0 (Trypanocidal Agents); 673LC5J4LQ (Pentamidine); 96304-42-6 (trypanothione); GAN16C9B8O (Glutathione); U87FK77H25 (Spermidine); V10TVZ52E4 (Putrescine); VC2W18DGKR (Thymidine); YC42NRJ1ZD (benzonidazole)
[Em] Mês de entrada:1701
[Cu] Atualização por classe:170112
[Lr] Data última revisão:
170112
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161013
[St] Status:MEDLINE



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