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  1 / 1895 MEDLINE  
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[PMID]:29034805
[Au] Autor:Vural K; Kosova F; Kurt FÖ; Tuglu I
[Ad] Endereço:1 Department of Medical Pharmacology, Faculty of Medicine, Celal Bayar University, Manisa, Turkey.
[Ti] Título:In vitro investigation of the effect of matrix molecules on the behavior of colon cancer cells under the effect of geldanamycin derivative.
[So] Source:Tumour Biol;39(10):1010428317720569, 2017 Oct.
[Is] ISSN:1423-0380
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The chaperone-binding drug, 17-allylamino-17-demethoxygeldanamycin, has recently come into clinical use. It is a derivative of geldanamycin, an ansamycin benzoquinone antibiotic with anti-carcinogenic effect. Understanding the effect of this drug on the cancer cells and their niche is important for treatment. We applied 17-allylamino-17-demethoxygeldanamycin to colon cancer cell line (Colo 205) on matrix molecules to investigate the relationship of apoptosis with terminal deoxynucleotidyl transferase dUTP nick end labeling immunocytochemistry and related gene expression. We used laminin and collagen I for matrix molecules and vascular endothelial growth factor for angiogenic structure. We also examined apoptosis-related signaling pathway including mitochondrial proteins, cytochrome c, Bcl-2, caspase-9, Apaf-1 expression using real-time polymerase chain reaction. There was clear effect of 17-allylamino-17-demethoxygeldanamycin that killed more cells on tissue culture plastic compared to matrix molecules. The IC value was 0.58 µg/mL for tissue culture plastic compared with 0.64 µg/mL for laminin and 0.75 µg/mL for collagen I. The analyses showed that more cells on matrix molecules underwent apoptosis compared to that on tissue culture plastic. Apoptosis-related gene expression was similar in which Bcl-2 expression decreased and proapoptotic gene expression of the cells on matrix molecules increased compared to that on tissue culture plastic. However, the application of 17-allylamino-17-demethoxygeldanamycin was more effective for the cells on collagen I compared to the cells on laminin. There was also a decrease in angiogenesis as shown by the vascular endothelial growth factor staining. This was more pronounced by coating of the tissue culture plastic with matrix molecules. Our results supported the anti-cancer effect of 17-allylamino-17-demethoxygeldanamycin, and this effect depended on matrix molecules. This effect occurs through apoptosis, and related genes were also altered. All these genes may serve for novel target under the effect of matrix substrate. However, correct interpretation of the results requires further studies.
[Mh] Termos MeSH primário: Anticarcinógenos/farmacologia
Benzoquinonas/farmacologia
Neoplasias do Colo/tratamento farmacológico
Neoplasias do Colo/metabolismo
Lactamas Macrocíclicas/farmacologia
[Mh] Termos MeSH secundário: Apoptose/efeitos dos fármacos
Fator Apoptótico 1 Ativador de Proteases/metabolismo
Caspase 9/metabolismo
Linhagem Celular Tumoral
Colágeno/metabolismo
Colo/efeitos dos fármacos
Colo/metabolismo
DNA Nucleotidilexotransferase/metabolismo
Seres Humanos
Proteínas Proto-Oncogênicas c-bcl-2/metabolismo
Rifabutina/farmacologia
Transdução de Sinais/efeitos dos fármacos
Fator A de Crescimento do Endotélio Vascular/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anticarcinogenic Agents); 0 (Apoptotic Protease-Activating Factor 1); 0 (Benzoquinones); 0 (Lactams, Macrocyclic); 0 (Proto-Oncogene Proteins c-bcl-2); 0 (Vascular Endothelial Growth Factor A); 1W306TDA6S (Rifabutin); 3T006GV98U (quinone); 4GY0AVT3L4 (tanespimycin); 9007-34-5 (Collagen); EC 2.7.7.31 (DNA Nucleotidylexotransferase); EC 3.4.22.- (Caspase 9); Z3K3VJ16KU (geldanamycin)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171020
[Lr] Data última revisão:
171020
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171017
[St] Status:MEDLINE
[do] DOI:10.1177/1010428317720569


  2 / 1895 MEDLINE  
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[PMID]:28239079
[Au] Autor:Sung J; Kim N; Park YH; Hwang YJ; Kwon S; Na G; Choi JY; Kang JB; Kim HR; Kim JW; Lee DH
[Ad] Endereço:Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
[Ti] Título:Rifabutin-based Fourth and Fifth-line Rescue Therapy in Patients with for Eradication Failure.
[So] Source:Korean J Gastroenterol;69(2):109-118, 2017 Feb 25.
[Is] ISSN:2233-6869
[Cp] País de publicação:Korea (South)
[La] Idioma:eng
[Ab] Resumo:Background/Aims: Optimized regimen has not yet been established for failures of multiple ( ) eradication. Hence, we aimed to evaluate the efficacy of rifabutin-based rescue therapy, at least after three eradication failures. Methods: Twelve patients, who failed in the treatment for eradication at least three times, were consecutively enrolled between 2007 and 2015 at Seoul National University Bundang Hospital. The rifabutin-based rescue regimen was consisted of proton pump inhibitor (PPI), rifabutin (150 mg b.i.d.), and amoxicillin (1 g b.i.d.), given for 7 or 14 days. MIC concentration test by the agar dilution method was performed on six patients prior to rifabutin-based rescue therapy. Results: One patient did not take this regimen, and per-protocol (PP) analysis was performed in 11 patients. The overall eradication rate by intention-to-treat and PP analysis with rifabutin-based rescue therapy was 50.0% (6/12 patients) and 54.5% (6/11 patients), respectively. There was no difference of the eradication rate depending on the underlying disease, smoking, alcohol, number of previous eradication failures, and CYP2C19 genotype. All of the six patients were susceptible to rifabutin, but only three of them succeeded in eradicating with . Side effects occurred in two patients (18.2%), and compliance was 90.9%. Conclusions: Even the eradication rate of rifabutin-based rescue therapy was not very good. Rifabutin-based rescue therapy could be considered as a rescue therapy, perhaps as the fourth or the fifth-line treatment option. No correlation of rifabutin sensitivity with eradication success rate of suggests that frequent administration of high dose PPI and amoxicillin might be important.
[Mh] Termos MeSH primário: Antibacterianos/uso terapêutico
Infecções por Helicobacter/tratamento farmacológico
Rifabutina/uso terapêutico
[Mh] Termos MeSH secundário: Amoxicilina/uso terapêutico
Citocromo P-450 CYP2C19/genética
Farmacorresistência Bacteriana/efeitos dos fármacos
Quimioterapia Combinada
Feminino
Genótipo
Infecções por Helicobacter/microbiologia
Helicobacter pylori/efeitos dos fármacos
Helicobacter pylori/isolamento & purificação
Seres Humanos
Masculino
Testes de Sensibilidade Microbiana
Inibidores da Bomba de Prótons/uso terapêutico
Rifabutina/farmacologia
Falha de Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Proton Pump Inhibitors); 1W306TDA6S (Rifabutin); 804826J2HU (Amoxicillin); EC 1.14.14.1 (CYP2C19 protein, human); EC 1.14.14.1 (Cytochrome P-450 CYP2C19)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170524
[Lr] Data última revisão:
170524
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170228
[St] Status:MEDLINE
[do] DOI:10.4166/kjg.2017.69.2.109


  3 / 1895 MEDLINE  
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[PMID]:28222358
[Au] Autor:El-Shazly AE; Roncarati P; Lejeune M; Lefebvre PP; Delvenne P
[Ad] Endereço:Department of Otolaryngology and Head and Neck Surgery, Liege University Hospital-CHU, Liege, Belgium; Department of Pathology, Laboratory of Experimental Pathology, University of Liege, Liege, Belgium. Electronic address: amrel_shazly@hotmail.com.
[Ti] Título:Tyrosine kinase inhibition is an important factor for gene expression of CRTH2 in human eosinophils and lymphocytes: A novel mechanism for explaining eosinophils recruitment by the neuro-immune axis in allergic rhinitis.
[So] Source:Int Immunopharmacol;45:180-186, 2017 Apr.
[Is] ISSN:1878-1705
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:We recently shown a novel neuro-immune competition between vasoactive intestinal peptide (VIP) and PGD2 for CRTH2 receptor, and that genistein augmented VIP and PGD2-induced eosinophil chemotaxis. However, there are neither studies on the CRTH2 gene expression in allergic rhinitis (AR) nor in the effect of tyrosine kinase inhibitors in CRTH2 gene regulation. Our Objectives were to study the gene expression modulation of CRTH2 receptor in AR patients and the effect of tyrosine kinase inhibitors (TKIs) on CRTH2 gene modulation. Nasal provocation tests, ELISA, qRT-PCR, western blot, flow cytometry and chemotaxis assays in modified micro-Boyden chambers, were all used, to achieve our objectives. Herein we show that AR patients increased the amounts of VIP and PGD2 in their nasal secretions in the early phase reaction, however CRTH2 gene expression from leukocytes recovered in their nasal secretions was upregulated only during the late phase reaction. The TKIs; Genistein, Erbstatin and Herbimycin A, induced the gene expression of CRTH2 and increased the protein content of CRTH2 in both human lymphocytes and eosinophils. This was functional as PGD2/VIP-induced eosinophil chemotaxis was augmented by the TKIs and inhibited by pervanadate, the tyrosine phosphatase inhibitor. These results open channels for therapeutic modalities targeting CRTH2 molecules in AR.
[Mh] Termos MeSH primário: Movimento Celular/efeitos dos fármacos
Eosinófilos/efeitos dos fármacos
Linfócitos/efeitos dos fármacos
Mucosa Nasal/patologia
Inibidores de Proteínas Quinases/uso terapêutico
Receptores Imunológicos/metabolismo
Receptores de Prostaglandina/metabolismo
Rinite Alérgica/tratamento farmacológico
[Mh] Termos MeSH secundário: Adulto
Antígenos de Dermatophagoides/imunologia
Células Cultivadas
Eosinófilos/imunologia
Feminino
Regulação da Expressão Gênica/efeitos dos fármacos
Genisteína/uso terapêutico
Seres Humanos
Hidroquinonas/uso terapêutico
Linfócitos/imunologia
Masculino
Neuroimunomodulação
Prostaglandina D2/metabolismo
Receptores Imunológicos/genética
Receptores de Prostaglandina/genética
Rinite Alérgica/imunologia
Rifabutina/análogos & derivados
Rifabutina/uso terapêutico
Peptídeo Intestinal Vasoativo/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, Dermatophagoides); 0 (Hydroquinones); 0 (Protein Kinase Inhibitors); 0 (Receptors, Immunologic); 0 (Receptors, Prostaglandin); 0 (prostaglandin D2 receptor); 1W306TDA6S (Rifabutin); 37221-79-7 (Vasoactive Intestinal Peptide); 70563-58-5 (herbimycin); DH2M523P0H (Genistein); RXY07S6CZ2 (Prostaglandin D2); WDH83K6T5P (erbstatin)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170601
[Lr] Data última revisão:
170601
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170222
[St] Status:MEDLINE


  4 / 1895 MEDLINE  
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[PMID]:27350276
[Au] Autor:Nirbhavane P; Vemuri N; Kumar N; Khuller GK
[Ad] Endereço:Lifecare Innovations Pvt Ltd, Laboratory for Translational Research in Nanomedicine, Biotech Park, Janakipuram, Lucknow, 226021, India.
[Ti] Título:Lipid Nanocarrier-Mediated Drug Delivery System to Enhance the Oral Bioavailability of Rifabutin.
[So] Source:AAPS PharmSciTech;18(3):829-837, 2017 Apr.
[Is] ISSN:1530-9932
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Rifabutin (RFB) is prescribed for the treatment of tuberculosis infections as well as Mycobacterium avium complex (MAC) infection in immunocompromised individuals and HIV patients. With a view to develop a sustained release oral solid lipid nanoformulation (SLN), RFB was encapsulated in glyceryl monostearate (GMS) nanoparticles. The rifabutin solid lipid nanoparticles (RFB-SLNs), prepared by the solvent diffusion evaporation method, had a size of 345 ± 17.96 nm and PDI of 0.321 ± 0.09. The stability of RFB-SLNs was investigated in simulated gastric fluid (SGF) pH 2.0, simulated intestinal fluid (SIF) pH 6.8 and physiological buffer (PBS) pH 7.4. The gastric medium did not affect the SLNs and were found to be stable, while a sustained release was observed in SIF up to 48 h and in PBS up to 7 days. The pharmacokinetic profile of a single oral administration of RFB-SLNs in mice showed maintenance of therapeutic drug concentrations in plasma for 4 days and in the tissues (lungs, liver and spleen) for 7 days. Oral administration of free RFB showed clearance from plasma within 24 h. The relative bioavailability of RFB from SLNs was five fold higher as compared to administration with free RFB. The intent of using lipid nanocarriers is primarily to enhance the oral bioavailability of rifabutin and eventually decrease the dose and dosing frequency for successful management of MAC infection.
[Mh] Termos MeSH primário: Portadores de Fármacos/química
Lipídeos/química
Nanopartículas/química
Rifabutina/química
Rifabutina/farmacocinética
[Mh] Termos MeSH secundário: Administração Oral
Animais
Disponibilidade Biológica
Sistemas de Liberação de Medicamentos/métodos
Masculino
Camundongos
Tamanho da Partícula
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Drug Carriers); 0 (Lipids); 1W306TDA6S (Rifabutin)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170713
[Lr] Data última revisão:
170713
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160629
[St] Status:MEDLINE
[do] DOI:10.1208/s12249-016-0559-2


  5 / 1895 MEDLINE  
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[PMID]:27622258
[Au] Autor:Peart JM; Klein RS; Xu X; Stewart C; Rosenbach M
[Ad] Endereço:Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA.
[Ti] Título:Sporotrichoid fluctuant nodules.
[So] Source:Cutis;98(2):82;96, 2016 Aug.
[Is] ISSN:2326-6929
[Cp] País de publicação:United States
[La] Idioma:eng
[Mh] Termos MeSH primário: Abscesso/etiologia
Imunossupressores/efeitos adversos
Doenças Pulmonares Intersticiais/tratamento farmacológico
Infecção por Mycobacterium avium-intracellulare/etiologia
Ácido Micofenólico/efeitos adversos
Polimiosite/tratamento farmacológico
Prednisona/efeitos adversos
Dermatopatias Bacterianas/etiologia
[Mh] Termos MeSH secundário: Abscesso/diagnóstico
Abscesso/tratamento farmacológico
Abscesso/patologia
Antibacterianos/uso terapêutico
Azitromicina/uso terapêutico
Etambutol/uso terapêutico
Feminino
Seres Humanos
Hospedeiro Imunocomprometido
Perna (Membro)
Meia-Idade
Infecção por Mycobacterium avium-intracellulare/diagnóstico
Infecção por Mycobacterium avium-intracellulare/tratamento farmacológico
Infecção por Mycobacterium avium-intracellulare/patologia
Rifabutina/uso terapêutico
Dermatopatias Bacterianas/diagnóstico
Dermatopatias Bacterianas/tratamento farmacológico
Dermatopatias Bacterianas/patologia
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Immunosuppressive Agents); 1W306TDA6S (Rifabutin); 83905-01-5 (Azithromycin); 8G167061QZ (Ethambutol); HU9DX48N0T (Mycophenolic Acid); VB0R961HZT (Prednisone)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170425
[Lr] Data última revisão:
170425
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160914
[St] Status:MEDLINE


  6 / 1895 MEDLINE  
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[PMID]:27550354
[Au] Autor:Parvez MM; Kaisar N; Shin HJ; Jung JA; Shin JG
[Ad] Endereço:Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine, Busan, Republic of Korea.
[Ti] Título:Inhibitory Interaction Potential of 22 Antituberculosis Drugs on Organic Anion and Cation Transporters of the SLC22A Family.
[So] Source:Antimicrob Agents Chemother;60(11):6558-6567, 2016 Nov.
[Is] ISSN:1098-6596
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Twenty-two currently marketed antituberculosis drugs were comprehensively evaluated for their inhibitory effect on organic anionic transporter (OAT)- and organic cation transporter (OCT)-mediated uptake using stably transfected HEK293 cells in vitro We observed moderate to strong inhibitory effects on OAT1- and OAT3-mediated para-aminohippurate (PAH) uptake and OCT1- and OCT2-mediated N-methyl-4-phenylpylidinium acetate (MPP ) uptake. Ciprofloxacin, linezolid, para-aminosalicylic acid (PAS), and rifampin were observed to have strong inhibitory effects, with the concentrations for a 50% inhibitory effect (IC s) being 35.1, 31.1, 37.6, and 48.1 µM, respectively, for OAT1 and >100, 21.9, 24.6, and 30.2 µM, respectively, for OAT3. Similarly, pyrazinamide, rifabutin, and levofloxacin were observed to have inhibitory effects, with IC values being 36.5, 42.7, and 30.3 µM, respectively, for OCT1 and with the IC value for PAS being 94.2 µM for OCT2. In addition, we used zidovudine and metformin as clinically prescribed substrates of OATs and OCTs, respectively, and zidovudine and metformin uptake was also strongly inhibited by the antituberculosis drugs. Among the tested drugs, the highest drug-drug interaction (DDI) indexes were found for PAS, which were 9.3 to 13.9 for OAT1 and 12.0 to 17.7 for OAT3, and linezolid, which were 1.18 to 2.15 for OAT1 and 1.7 to 3.01 for OAT3. Similarly, the DDI indexes of pyrazinamide and levofloxacin were 0.57 and 0.30, respectively, for OCT1, and the DDI index of PAS was 3.8 for OCT2, suggesting a stronger possibility (DDI index value cutoff, >0.1) of in vivo DDIs. This is the first comprehensive report of the inhibitory potential of anti-TB drugs on OAT- and OCT-mediated uptake of prototype and clinically prescribed substrate drugs in vitro, providing an ability to predict DDIs between anti-TB drugs and other coprescribed drugs in clinical studies in vivo.
[Mh] Termos MeSH primário: Antituberculosos/farmacologia
Fator 1 de Transcrição de Octâmero/antagonistas & inibidores
Proteína 1 Transportadora de Ânions Orgânicos/antagonistas & inibidores
Transportadores de Ânions Orgânicos Sódio-Independentes/antagonistas & inibidores
Proteínas de Transporte de Cátions Orgânicos/antagonistas & inibidores
[Mh] Termos MeSH secundário: 1-Metil-4-fenilpiridínio/metabolismo
Ácido Aminossalicílico/farmacologia
Animais
Ciprofloxacino/farmacologia
Células HEK293
Seres Humanos
Concentração Inibidora 50
Transporte de Íons/efeitos dos fármacos
Cinética
Levofloxacino/farmacologia
Linezolida/farmacologia
Metformina/antagonistas & inibidores
Metformina/farmacologia
Fator 1 de Transcrição de Octâmero/metabolismo
Proteína 1 Transportadora de Ânions Orgânicos/metabolismo
Transportadores de Ânions Orgânicos Sódio-Independentes/metabolismo
Proteínas de Transporte de Cátions Orgânicos/metabolismo
Transportador 2 de Cátion Orgânico
Pirazinamida/farmacologia
Rifabutina/farmacologia
Rifampina/farmacologia
Zidovudina/antagonistas & inibidores
Zidovudina/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antitubercular Agents); 0 (Octamer Transcription Factor-1); 0 (Organic Anion Transport Protein 1); 0 (Organic Anion Transporters, Sodium-Independent); 0 (Organic Cation Transport Proteins); 0 (Organic Cation Transporter 2); 0 (POU2F1 protein, human); 0 (SLC22A2 protein, human); 0 (organic anion transport protein 3); 1W306TDA6S (Rifabutin); 2KNI5N06TI (Pyrazinamide); 4B9XT59T7S (Zidovudine); 5B2658E0N2 (Aminosalicylic Acid); 5E8K9I0O4U (Ciprofloxacin); 6GNT3Y5LMF (Levofloxacin); 9100L32L2N (Metformin); ISQ9I6J12J (Linezolid); R865A5OY8J (1-Methyl-4-phenylpyridinium); VJT6J7R4TR (Rifampin)
[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:160824
[St] Status:MEDLINE
[do] DOI:10.1128/AAC.01151-16


  7 / 1895 MEDLINE  
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[PMID]:27536067
[Au] Autor:Pinheiro M; Ribeiro R; Vieira A; Andrade F; Reis S
[Ad] Endereço:IUCIBIO, REQUIMTE, Chemistry Department, Faculty of Pharmacy.
[Ti] Título:Design of a nanostructured lipid carrier intended to improve the treatment of tuberculosis.
[So] Source:Drug Des Devel Ther;10:2467-75, 2016.
[Is] ISSN:1177-8881
[Cp] País de publicação:New Zealand
[La] Idioma:eng
[Ab] Resumo:This work aimed to design, develop, and characterize a lipid nanocarrier system for the selective delivery of rifabutin (RFB) to alveolar macrophages. Lipid nanoparticles, specifically nanostructured lipid carriers (NLC), were synthetized by the high-shear homogenization and ultrasonication techniques. These nanoparticles were designed to exhibit both passive and active targeting strategies to be efficiently internalized by the alveolar macrophages, traffic to the acidified phagosomes and phagolysosomes, and release bactericidal concentrations of the antituberculosis drug intracellularly. NLC that could entrap RFB were prepared, characterized, and further functionalized with mannose. Particles' diameter, zeta potential, morphology, drug% entrapping efficiency, and drug release kinetics were evaluated. The mannose coating process was confirmed by Fourier transform infrared. Further, the cytotoxicity of the formulations was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) assay in A549, Calu-3, and Raw 264.7 cells. The diameter of NLC formulations was found to be in the range of 175-213 nm, and drug entrapping efficiency was found to be above 80%. In addition, high storage stability for the formulations was expected since they maintained the initial characteristics for 6 months. Moreover, the drug release was pH-sensitive, with a faster drug release at acidic pH than at neutral pH. These results pose a strong argument that the developed nanocarrier can be explored as a promising carrier for safer and more efficient management of tuberculosis by exploiting the pulmonary route of administration.
[Mh] Termos MeSH primário: Antibióticos Antituberculose/química
Portadores de Fármacos
Lipídeos/química
Nanopartículas
Rifabutina/química
[Mh] Termos MeSH secundário: Animais
Antibióticos Antituberculose/administração & dosagem
Antibióticos Antituberculose/metabolismo
Antibióticos Antituberculose/toxicidade
Linhagem Celular Tumoral
Sobrevivência Celular/efeitos dos fármacos
Composição de Medicamentos
Estabilidade de Medicamentos
Seres Humanos
Concentração de Íons de Hidrogênio
Cinética
Lectinas Tipo C/metabolismo
Ligantes
Lipídeos/toxicidade
Macrófagos Alveolares/metabolismo
Manose/química
Manose/metabolismo
Lectinas de Ligação a Manose/metabolismo
Camundongos
Nanotecnologia
Tamanho da Partícula
Fagocitose
Células RAW 264.7
Receptores de Superfície Celular/metabolismo
Rifabutina/administração & dosagem
Rifabutina/metabolismo
Rifabutina/toxicidade
Solubilidade
Espectroscopia de Infravermelho com Transformada de Fourier
Tecnologia Farmacêutica/métodos
Ultrassom
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibiotics, Antitubercular); 0 (Drug Carriers); 0 (Lectins, C-Type); 0 (Ligands); 0 (Lipids); 0 (Mannose-Binding Lectins); 0 (Receptors, Cell Surface); 0 (mannose receptor); 1W306TDA6S (Rifabutin); PHA4727WTP (Mannose)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170328
[Lr] Data última revisão:
170328
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160819
[St] Status:MEDLINE
[do] DOI:10.2147/DDDT.S104395


  8 / 1895 MEDLINE  
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[PMID]:27476419
[Au] Autor:Zhang Z; Xue N; Bian C; Yan R; Jin L; Chen X; Yu X
[Ad] Endereço:State Key Laboratory of Bioactive Substance and Function of Natural Medicine, Institute of Materia Medica, Peking Union Medical College & Chinese Academy of Medical Sciences, No. 1 Xiannongtan Street, Beijing 100050, China.
[Ti] Título:C15-methoxyphenylated 18-deoxy-herbimycin A analogues, their in vitro anticancer activity and heat shock protein 90 binding affinity.
[So] Source:Bioorg Med Chem Lett;26(17):4287-91, 2016 09 01.
[Is] ISSN:1464-3405
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Benzoquinone ansamycins are important leads for the discovery of novel inhibitors of heat shock protein 90 (Hsp90), a promising target of cancer chemotherapeutics. Intrinsic hepatotoxicity caused by the benzoquinone moiety appeared to be a serious limitation to the development of these compounds. To solve this problem by rational structure optimization, a short series of C18-deoxy analogues of herbimycin A were designed based on putative interactions between the compound and the protein. Chemical synthesis of the target molecules were attempted by following the established synthetic route to the natural product, but resulted in the isolation of four serendipitous C15 phenylated final products. In vitro antiproliferative activity and Hsp90 binding affinity of the compounds were determined, suggesting the C18-oxygen of herbimycin A is removable and bulky lipophilic groups can be accommodated at C15 without loss of activity.
[Mh] Termos MeSH primário: Antineoplásicos/metabolismo
Antineoplásicos/farmacologia
Proteínas de Choque Térmico HSP90/metabolismo
Rifabutina/análogos & derivados
[Mh] Termos MeSH secundário: Antineoplásicos/síntese química
Antineoplásicos/química
Linhagem Celular Tumoral
Proliferação Celular/efeitos dos fármacos
Seres Humanos
Concentração Inibidora 50
Modelos Moleculares
Ligação Proteica
Rifabutina/síntese química
Rifabutina/química
Rifabutina/metabolismo
Rifabutina/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (HSP90 Heat-Shock Proteins); 1W306TDA6S (Rifabutin); 70563-58-5 (herbimycin)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171122
[Lr] Data última revisão:
171122
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160802
[St] Status:MEDLINE


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[PMID]:27463245
[Au] Autor:Gupta A; Meena J; Sharma D; Gupta P; Gupta UD; Kumar S; Sharma S; Panda AK; Misra A
[Ad] Endereço:CSIR-Central Drug Research Institute , Lucknow 226031, India.
[Ti] Título:Inhalable Particles for "Pincer Therapeutics" Targeting Nitazoxanide as Bactericidal and Host-Directed Agent to Macrophages in a Mouse Model of Tuberculosis.
[So] Source:Mol Pharm;13(9):3247-55, 2016 Sep 06.
[Is] ISSN:1543-8392
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Nitazoxanide (NTZ) has moderate mycobactericidal activity and is also an inducer of autophagy in mammalian cells. High-payload (40-50% w/w) inhalable particles containing NTZ alone or in combination with antituberculosis (TB) agents isoniazid (INH) and rifabutin (RFB) were prepared with high incorporation efficiency of 92%. In vitro drug release was corrected for drug degradation during the course of study and revealed first-order controlled release. Particles were efficiently taken up in vitro by macrophages and maintained intracellular drug concentrations at one order of magnitude higher than NTZ in solution for 6 h. Dose-dependent killing of Mtb and restoration of lung and spleen architecture were observed in experimentally infected mice treated with inhalations containing NTZ. Adjunct NTZ with INH and RFB cleared culturable bacteria from the lung and spleen and markedly healed tissue architecture. NTZ can be used in combination with INH-RFB to kill the pathogen and heal the host.
[Mh] Termos MeSH primário: Antituberculosos/uso terapêutico
Macrófagos/efeitos dos fármacos
Tiazóis/uso terapêutico
Tuberculose/tratamento farmacológico
[Mh] Termos MeSH secundário: Administração por Inalação
Animais
Antituberculosos/administração & dosagem
Autofagia/efeitos dos fármacos
Linhagem Celular
Seres Humanos
Isoniazida/administração & dosagem
Isoniazida/uso terapêutico
Masculino
Camundongos
Planejamento da Radioterapia Assistida por Computador
Rifabutina/administração & dosagem
Rifabutina/uso terapêutico
Tiazóis/administração & dosagem
Tuberculose/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antitubercular Agents); 0 (Thiazoles); 1W306TDA6S (Rifabutin); SOA12P041N (nitazoxanide); V83O1VOZ8L (Isoniazid)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171024
[Lr] Data última revisão:
171024
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160728
[St] Status:MEDLINE
[do] DOI:10.1021/acs.molpharmaceut.6b00459


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[PMID]:27444319
[Au] Autor:Patton PH; Parker CE; MacDonald JK; Chande N
[Ad] Endereço:Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON, Canada.
[Ti] Título:Anti-tuberculous therapy for maintenance of remission in Crohn's disease.
[So] Source:Cochrane Database Syst Rev;7:CD000299, 2016 Jul 22.
[Is] ISSN:1469-493X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: There have been a number of studies with conflicting results which have examined the effect of anti-tuberculous therapy in Crohn's disease. A meta-analysis was performed to evaluate the use of anti-tuberculous therapy for the maintenance of remission in Crohn's disease. OBJECTIVES: To evaluate the effects of anti-tuberculous therapy for the maintenance of remission in patients with Crohn's disease. SEARCH METHODS: We searched MEDLINE, EMBASE, the Cochrane LIbrary, and the Cochrane IBD Group Specialized Register from inception to June 22, 2015. SELECTION CRITERIA: Randomized controlled trials (RCTs) of anti-tuberculous therapy compared to placebo or another active therapy in patients with quiescent Crohn's disease were considered for inclusion. DATA COLLECTION AND ANALYSIS: At least two authors independently extracted data and assessed the quality of included studies using the Cochrane risk of bias tool. We calculated the risk ratio (RR) and corresponding 95% confidence interval (CI) for dichotomous outcomes.. The primary outcome was relapse. Secondary outcomes included adverse events, withdrawals due to adverse events and serious adverse events. All data were analyzed on an intention-to-treat basis. The overall quality of the evidence supporting the primary and secondary outcomes was evaluated using the GRADE criteria. MAIN RESULTS: Four placebo-controlled RCTs including 206 participants were included. Three trials included an 8 to 16 week induction phase with tapering corticosteroids (prednisone, prednisolone or methylprednisolone) as induction therapy. Anti-tuberculous therapy included monotherapy with clofazimine, combination therapy with clofazimine, rifampin, ethambutol, and dapsone or combination therapy with clarithromycin, rifabutin and clofazimine. All of the studies were rated as unclear risk of bias for allocation concealment, three were rated as unclear risk of bias for random sequence generation and two were rated as unclear risk of bias for blinding or participants and personnel. There was a statistically significant difference in relapse rates favoring anti-tuberculous therapy over placebo. Thirty-nine per cent (44/112) of patients in the anti-tuberculous therapy group relapsed at 9 months to 2 years compared to 67% (63/94) of placebo patients (RR 0.58, 95% CI 0.45 to 0.75, I(2) = 47%). A GRADE analysis indicates that the overall quality of the evidence supporting this outcome was very low due to unknown risk of bias and sparse data. Adverse events occurred more frequently in the anti-tuberculous therapy group (37/159) compared to the placebo group (14/163) with a pooled RR of 2.57 (95% CI 1.45 to 4.55; N=322; studies=4, I(2)=64%). A GRADE analysis indicates that the overall quality of the evidence supporting this outcome was very low due to unknown risk of bias, unexplained heterogeneity and sparse data. There was no difference in withdrawals due to adverse events. Nine per cent (14/159) of anti-tuberculous therapy patients withdrew due to adverse events compared to 7% (11/163) of placebo patients (RR 1.29, 95% CI 0.60 to 2.77, I(2) = 0%). Common adverse events included increased skin pigmentation and rashes. No serious adverse events were reported in any of the included studies. AUTHORS' CONCLUSIONS: Anti-tuberculous therapy may provide a benefit over placebo for the prevention of relapse in participants with Crohn's disease in remission. However, this result is very uncertain due to unclear study quality and the small numbers of patients assessed. Further studies are needed to provide better quality evidence for the use of anti-tuberculous therapy for maintaining remission in people with quiescent Crohn's disease.
[Mh] Termos MeSH primário: Antituberculosos/uso terapêutico
Doença de Crohn/prevenção & controle
Quimioterapia de Manutenção/métodos
Prevenção Secundária
[Mh] Termos MeSH secundário: Antituberculosos/efeitos adversos
Claritromicina/uso terapêutico
Clofazimina/uso terapêutico
Doença de Crohn/tratamento farmacológico
Etambutol/uso terapêutico
Glucocorticoides/uso terapêutico
Seres Humanos
Metilprednisolona/uso terapêutico
Prednisona/uso terapêutico
Ensaios Clínicos Controlados Aleatórios como Assunto
Recidiva
Indução de Remissão
Rifabutina/uso terapêutico
Rifampina/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE; META-ANALYSIS; REVIEW
[Nm] Nome de substância:
0 (Antitubercular Agents); 0 (Glucocorticoids); 1W306TDA6S (Rifabutin); 8G167061QZ (Ethambutol); D959AE5USF (Clofazimine); H1250JIK0A (Clarithromycin); VB0R961HZT (Prednisone); VJT6J7R4TR (Rifampin); X4W7ZR7023 (Methylprednisolone)
[Em] Mês de entrada:1609
[Cu] Atualização por classe:160802
[Lr] Data última revisão:
160802
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160723
[St] Status:MEDLINE
[do] DOI:10.1002/14651858.CD000299.pub3



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