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[PMID]:29247859
[Au] Autor:Zhao S; Li K; Jin Y; Lin J
[Ad] Endereço:Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education, School of Chemical Science and Technology, Yunnan University, Kunming 650091, PR China.
[Ti] Título:Synthesis and biological evaluation of novel 1-(aryl-aldehyde-oxime)uracil derivatives as a new class of thymidine phosphorylase inhibitors.
[So] Source:Eur J Med Chem;144:41-51, 2018 Jan 20.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:A novel series of 1-(aryl aldehyd oxime) uracil derivatives were synthesized, characterized and evaluated for its inhibitory activity against thymidine phosphorylase. Among them, the compound 8d, 8e, 8f, 8g and 8l displayed potent thymidine phosphorylase inhibitory activities with the IC values ranging between 0.12 ± 0.05 and 7.2 ± 1.4 µM. And the compounds 8a, 8h, 8i, 8j, 8m, 8n, 8o, 8q, 8s, 8t and 8u (IC is from 10.7 to 39.9 µM) showed a good thymidine phosphorylase inhibition when compared to the standard 7DX and TPI. The most biologically active compound 8l was demonstrated to be a competition mode of enzyme inhibition. The Molecular docking analysis showed the interaction of these newly synthesized compounds at the active binding site of thymidine phosphorylase based on the experimental results. In general, these results indicated these compounds are promising inhibitors of thymidine phosphorylase for the potential treatment of anti-angiogenesis.
[Mh] Termos MeSH primário: Inibidores Enzimáticos/química
Inibidores Enzimáticos/farmacologia
Timidina Fosforilase/antagonistas & inibidores
Uracila/análogos & derivados
Uracila/farmacologia
[Mh] Termos MeSH secundário: Inibidores da Angiogênese/síntese química
Inibidores da Angiogênese/química
Inibidores da Angiogênese/farmacologia
Inibidores Enzimáticos/síntese química
Células Endoteliais da Veia Umbilical Humana
Seres Humanos
Concentração Inibidora 50
Modelos Moleculares
Oximas/síntese química
Oximas/química
Oximas/farmacologia
Relação Estrutura-Atividade
Timidina Fosforilase/metabolismo
Uracila/síntese química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Angiogenesis Inhibitors); 0 (Enzyme Inhibitors); 0 (Oximes); 56HH86ZVCT (Uracil); EC 2.4.2.4 (Thymidine Phosphorylase)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171217
[St] Status:MEDLINE


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[PMID]:28462587
[Au] Autor:Whon TW; Shin NR; Jung MJ; Hyun DW; Kim HS; Kim PS; Bae JW
[Ad] Endereço:Department of Life and Nanopharmaceutical Sciences and Department of Biology, Kyung Hee University , Seoul, Republic of Korea.
[Ti] Título:Conditionally Pathogenic Gut Microbes Promote Larval Growth by Increasing Redox-Dependent Fat Storage in High-Sugar Diet-Fed Drosophila.
[So] Source:Antioxid Redox Signal;27(16):1361-1380, 2017 Dec 01.
[Is] ISSN:1557-7716
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:AIMS: Changes in the composition of the gut microbiota contribute to the development of obesity and subsequent complications that are associated with metabolic syndrome. However, the role of increased numbers of certain bacterial species during the progress of obesity and factor(s) controlling the community structure of gut microbiota remain unclear. Here, we demonstrate the inter-relationship between Drosophila melanogaster and their resident gut microbiota under chronic high-sugar diet (HSD) conditions. RESULTS: Chronic feeding of an HSD to Drosophila resulted in a predominance of resident uracil-secreting bacteria in the gut. Axenic insects mono-associated with uracil-secreting bacteria or supplemented with uracil under HSD conditions promoted larval development. Redox signaling induced by bacterial uracil promoted larval growth by regulating sugar and lipid metabolism via activation of p38a mitogen-activated protein kinase. INNOVATION: The present study identified a new redox-dependent mechanism by which uracil-secreting bacteria (previously regarded as opportunistic pathobionts) protect the host from metabolic perturbation under chronic HSD conditions. CONCLUSION: These results illustrate how Drosophila and gut microbes form a symbiotic relationship under stress conditions, and changes in the gut microbiota play an important role in alleviating deleterious diet-derived effects such as hyperglycemia. Antioxid. Redox Signal. 27, 1361-1380.
[Mh] Termos MeSH primário: Drosophila melanogaster/crescimento & desenvolvimento
Vida Livre de Germes
Obesidade/microbiologia
Sacarose/administração & dosagem
[Mh] Termos MeSH secundário: Animais
Bactérias/classificação
Bactérias/isolamento & purificação
Bactérias/metabolismo
Modelos Animais de Doenças
Drosophila melanogaster/microbiologia
Trato Gastrointestinal/microbiologia
Metabolismo dos Lipídeos
Microbiota
Proteína Quinase 14 Ativada por Mitógeno/metabolismo
Obesidade/induzido quimicamente
Oxirredução
Uracila/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
56HH86ZVCT (Uracil); 57-50-1 (Sucrose); EC 2.7.11.24 (Mitogen-Activated Protein Kinase 14)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE
[do] DOI:10.1089/ars.2016.6790


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[PMID]:28453695
[Au] Autor:Suenaga M; Schirripa M; Cao S; Zhang W; Yang D; Murgioni S; Rossini D; Marmorino F; Mennitto A; Ning Y; Okazaki S; Berger MD; Miyamoto Y; Gopez R; Barzi A; Yamaguchi T; Loupakis F; Lenz HJ
[Ad] Endereço:Department of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, USA.
[Ti] Título:Genetic variants of DNA repair-related genes predict efficacy of TAS-102 in patients with refractory metastatic colorectal cancer.
[So] Source:Ann Oncol;28(5):1015-1022, 2017 05 01.
[Is] ISSN:1569-8041
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Background: Tri-phosphorylated trifluridine (FTD) incorporation into DNA is TAS-102's main anti-tumor action. We tested whether genetic polymorphisms in homologous recombination (HR) and cell cycle checkpoint pathway for DNA repair is associated with outcomes in refractory metastatic colorectal cancer (mCRC) patients treated with TAS-102. Patients and methods: We analyzed genomic DNA extracted from 233 samples of three cohorts: an evaluation cohort of 52 patients receiving TAS-102, a validation cohort of 129 patients receiving TAS-102 and a control cohort of 52 patients receiving regorafenib. Single nucleotide polymorphisms of genes involved in HR (ATM, BRCA1, BRCA2, XRCC3, FANCD2, H2AX, RAD51) and cell cycle checkpoint (ATR, CHEK1, CHEK2, CDKN1A, TP53, CHE1, PIN1, PCNA) were analyzed by PCR-based direct sequencing. Results: In univariate analysis for the evaluation cohort, patients with any G allele in ATM rs609429 had longer overall survival (OS) than those with the C/C variant (8.7 vs. 4.4 months, HR 0.37, 95% CI: 0.14-0.99, P = 0.022). Patients carrying any A allele in XRCC3 rs861539 had significantly longer progression-free survival (PFS) (3.8 vs. 2.3 months, HR 0.44, 95% CI: 0.21-0.92, P = 0.024) and OS (15.6 vs. 6.3 months, HR 0.25, 95% CI: 0.08-0.79, P = 0.012) than those with the G/G variant. In multivariable analysis, ATM rs609429 remained significant for OS (P = 0.020). In the validation cohort, patients having ATM rs609429 with any G allele showed longer OS and PFS; the G/A variant in XRCC3 rs861539 showed longer OS, though without statistical significance. Conclusion: Genetic variants in the HR pathway may predict clinical outcome in mCRC patients receiving TAS-102.
[Mh] Termos MeSH primário: Antineoplásicos/uso terapêutico
Neoplasias Colorretais/genética
Enzimas Reparadoras do DNA/genética
Neoplasias Hepáticas/genética
Trifluridina/uso terapêutico
Uracila/análogos & derivados
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Antineoplásicos/farmacologia
Neoplasias Colorretais/tratamento farmacológico
Neoplasias Colorretais/mortalidade
Neoplasias Colorretais/patologia
Intervalo Livre de Doença
Combinação de Medicamentos
Resistência a Medicamentos Antineoplásicos/genética
Feminino
Estudos de Associação Genética
Seres Humanos
Neoplasias Hepáticas/tratamento farmacológico
Neoplasias Hepáticas/mortalidade
Neoplasias Hepáticas/secundário
Masculino
Meia-Idade
Compostos de Fenilureia/farmacologia
Compostos de Fenilureia/uso terapêutico
Modelos de Riscos Proporcionais
Piridinas/farmacologia
Piridinas/uso terapêutico
Estudos Retrospectivos
Resultado do Tratamento
Trifluridina/farmacologia
Uracila/farmacologia
Uracila/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Drug Combinations); 0 (Phenylurea Compounds); 0 (Pyridines); 0 (TAS 102); 24T2A1DOYB (regorafenib); 56HH86ZVCT (Uracil); EC 6.5.1.- (DNA Repair Enzymes); RMW9V5RW38 (Trifluridine)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE
[do] DOI:10.1093/annonc/mdx035


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[PMID]:29335207
[Au] Autor:Kim SM; Lee M; Lee SY; Lee SM; Kim EJ; Kim JS; Ann J; Lee J; Lee J
[Ad] Endereço:R&D Center, TiumBio Company Ltd., Seongnam-si, Gyeonggi-do, 13493, South Korea.
[Ti] Título:Synthesis and biological evaluation of 3-(2-aminoethyl) uracil derivatives as gonadotropin-releasing hormone (GnRH) receptor antagonists.
[So] Source:Eur J Med Chem;145:413-424, 2018 Feb 10.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:We investigated a series of uracil analogues by introducing various substituents on the phenyl ring of the N-3 aminoethyl side chain and evaluated their antagonistic activity against human gonadotropin-releasing hormone (GnRH) receptors. Analogues with substituents at the ortho or meta position demonstrated potent in vitro antagonistic activity. Specifically, the introduction of a 2-OMe group enhanced nuclear factor of activated T-cells (NFAT) inhibition up to 6-fold compared to the unsubstituted analogue. We identified compound 12c as a highly potent GnRH antagonist with moderate CYP inhibition. Compound 12c showed potent and prolonged LH suppression after a single dose was orally administered in castrated monkeys compared to a known antagonist, Elagolix. We believe that our SAR study offers useful insights to design GnRH antagonists as a potential treatment option for endometriosis.
[Mh] Termos MeSH primário: Inibidores do Citocromo P-450 CYP3A/farmacologia
Citocromo P-450 CYP3A/metabolismo
Receptores LHRH/antagonistas & inibidores
Uracila/farmacologia
[Mh] Termos MeSH secundário: Animais
Inibidores do Citocromo P-450 CYP3A/administração & dosagem
Inibidores do Citocromo P-450 CYP3A/química
Relação Dose-Resposta a Droga
Seres Humanos
Hormônio Luteinizante/antagonistas & inibidores
Hormônio Luteinizante/sangue
Macaca fascicularis
Estrutura Molecular
Relação Estrutura-Atividade
Uracila/análogos & derivados
Uracila/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cytochrome P-450 CYP3A Inhibitors); 0 (Receptors, LHRH); 56HH86ZVCT (Uracil); 9002-67-9 (Luteinizing Hormone); EC 1.14.13.67 (CYP3A4 protein, human); EC 1.14.14.1 (Cytochrome P-450 CYP3A)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180302
[Lr] Data última revisão:
180302
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180117
[St] Status:MEDLINE


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[PMID]:29390377
[Au] Autor:Trifan A; Stanciu C; Gheorghe L; Iacob S; Curescu M; Cijevschi Prelipcean C; Stefanescu G; Girleanu I; Chiriac S; Mihai C; Brisc C; Goldis A; Sporea I; Miftode E; Bataga S; Rogoveanu I; Preda C; Caruntu FA; Singeap AM
[Ad] Endereço:"Grigore T. Popa" University of Medicine and Pharmacy Iasi.
[Ti] Título:Efficacy and safety of paritaprevir/ritonavir, ombitasvir, and dasabuvir with ribavirin for the treatment of HCV genotype 1b compensated cirrhosis in patients aged 70 years or older.
[So] Source:Medicine (Baltimore);96(50):e9271, 2017 Dec.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Advanced age has been a major limitation of interferon-based treatment for chronic hepatitis C virus (HCV) infection because of its poor response and tolerability. Direct-acting antiviral (DAA) drug regimens are safe and highly effective, allowing administration of treatment also in elderly. This study aims to assess the efficacy and safety of paritaprevir/ritonavir, ombitasvir, and dasabuvir (PrOD) with ribavirin for the treatment of patients aged ≥70 years with HCV genotype 1b compensated cirrhosis.A total of 1008 patients with HCV genotype 1b compensated cirrhosis were prospectively treated with PrOD + ribavirin for 12 weeks, between December 2015 and July 2016. Sustained virologic response 12 weeks after the end of treatment (SVR12), adverse effects (AEs), comorbidities, discontinuation, and death rates were recorded. Efficacy and safety of therapy were assessed in patients aged ≥70 years and compared with data from patients <70 years.There were 117 patients aged ≥70 years, preponderantly females (58.9%), mean age 73.3 ±â€Š2.8 years (range 70-82), and 37 (31.6%) were treatment-experienced. Comorbidities were reported in 60.6% of patients ≥70 years and in 39.8% of those <70 years (P < .001). SVR12 rates based on intention-to-treat and per-protocol analyses were 97.4% and 100%, respectively, in patients ≥70 years, compared to 97.8% and 99.6%, respectively, in patients <70 years (P = ns and P = ns). Severe AEs were reported in 4 (3.4%) patients ≥70 years, compared to 23 (2.6%) in those <70 years (P = ns). One death was recorded in a patient aged 79 years (0.9%) and 6 deaths (0.8%) in those <70 years (P = ns).Treatment with PrOD + ribavirin in patients 70 years of age or older with HCV genotype 1b compensated cirrhosis proved as effective, safe, and well tolerated, as it did in younger patients.
[Mh] Termos MeSH primário: Antivirais/uso terapêutico
Hepatite C Crônica/tratamento farmacológico
Cirrose Hepática/tratamento farmacológico
Cirrose Hepática/virologia
[Mh] Termos MeSH secundário: Idoso
Idoso de 80 Anos ou mais
Anilidas/uso terapêutico
Carbamatos/uso terapêutico
Farmacorresistência Viral
Quimioterapia Combinada
Feminino
Genótipo
Seres Humanos
Compostos Macrocíclicos/uso terapêutico
Masculino
Estudos Prospectivos
Ribavirina/uso terapêutico
Ritonavir/uso terapêutico
Sulfonamidas/uso terapêutico
Resposta Viral Sustentada
Uracila/análogos & derivados
Uracila/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (ABT-267); 0 (ABT-333); 0 (ABT-450); 0 (Anilides); 0 (Antiviral Agents); 0 (Carbamates); 0 (Macrocyclic Compounds); 0 (Sulfonamides); 49717AWG6K (Ribavirin); 56HH86ZVCT (Uracil); O3J8G9O825 (Ritonavir)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180301
[Lr] Data última revisão:
180301
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180203
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000009271


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[PMID]:29441996
[Au] Autor:Ayoub BM; Abdel-Aziz O
[Ti] Título:A guide for using experimental design in chromatographic method development: applied to the analysis of selected anti-diabetic pharmaceutical combinations.
[So] Source:Pharmazie;71(12):683-690, 2016 Dec 01.
[Is] ISSN:0031-7144
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:A guide experimental design in chromatographic method development was described and applied successfully to the analysis of different recently approved anti-diabetic pharmaceutical combinations. Enhancement of UHPLC analysis of alogliptin benzoate either with pioglitazone hydrochloride or with metformin hydrochloride was achieved. The optimal chromatographic conditions were not attained by trial and error that requires a large number of experiments. Alternatively, a computer program was used as a systematic optimization strategy for the design of the experiment which accurately predicts the combined effect of different factors simultaneously. Resolution between peaks was studied by the proposed fractional factorial design approach performed by the Minitab® Program using screening and optimization steps. Application of the central composite design was implemented. A Pareto chart was used to exclude the insignificant variables. Linearity ranges were found to be 0.5-40 µg ml-1, 1-20 µg ml-1 and 1-32 µg ml-1 for alogliptin benzoate, pioglitazone hydrochloride and metformin hydrochloride, respectively. The proposed method is applicable for the analysis of six pharmaceutical dosage forms namely, Nesina®, Actos®, Glucophage®, Oseni®, Kazano® and Actoplus MET® tablets.
[Mh] Termos MeSH primário: Cromatografia Líquida de Alta Pressão/métodos
Hipoglicemiantes/análise
[Mh] Termos MeSH secundário: Formas de Dosagem
Combinação de Medicamentos
Desenho de Equipamento
Metformina/análise
Piperidinas/análise
Padrões de Referência
Reprodutibilidade dos Testes
Soluções
Comprimidos/análise
Tiazolidinedionas/análise
Uracila/análogos & derivados
Uracila/análise
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Dosage Forms); 0 (Drug Combinations); 0 (Hypoglycemic Agents); 0 (Piperidines); 0 (Solutions); 0 (Tablets); 0 (Thiazolidinediones); 56HH86ZVCT (Uracil); 9100L32L2N (Metformin); JHC049LO86 (alogliptin); X4OV71U42S (pioglitazone)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180227
[Lr] Data última revisão:
180227
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180215
[St] Status:MEDLINE
[do] DOI:10.1691/ph.2016.6095


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[PMID]:29305327
[Au] Autor:Moraes ACN; Magalhães VF
[Ad] Endereço:Laboratory of Ecophysiology and Toxicology of Cyanobacteria, Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. Electronic address: moraesacn@gmail.com.
[Ti] Título:Renal tubular damage caused by cylindrospermopsin (cyanotoxin) in mice.
[So] Source:Toxicol Lett;286:89-95, 2018 Apr.
[Is] ISSN:1879-3169
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Cylindrospermopsin (CYN) is a cyanotoxin and a hydrophilic alkaloid of 415 Da. The principal effect of CYN is the inhibition of protein synthesis, and it can damage various organs. Studies have demonstrated that the kidney is the most affected organ. CYN has played roles in at least two poisoning cases, i.e., the mysterious Palm Island disease in Australia and the event at Caruaru in Brazil. Therefore, we aimed to determine how CYN disrupts the renal tissue. Dose-response curves following single intraperitoneal injections of purified CYN (at 0, 16, 32, 64 and 128 µg CYN/kg body weight) were created in 10-week-old male BALB/C mice (n = 4). Renal physiology parameters were analyzed after 7 and 14 days. However, no alterations in the glomerular filtration rate (GFR) or nephrin expression (a crucial protein for glomerular integrity) were observed. We detected low-molecular-weight proteinuria and increased excretions of the tubular enzymes lactate dehydrogenase (LDH) and gamma-glutamyl transferase (GGT) at doses of 16, 32 and 64 µg CYN/kg body weight. Furthermore, we observed increases in the renal interstitial space and collagen deposition that indicated edema and fibrosis. The data seem to indicate that the damage is in the proximal tubule.
[Mh] Termos MeSH primário: Toxinas Bacterianas/toxicidade
Nefropatias/induzido quimicamente
Túbulos Renais Proximais/efeitos dos fármacos
Uracila/análogos & derivados
[Mh] Termos MeSH secundário: Animais
Biomarcadores/urina
Colágeno/metabolismo
Relação Dose-Resposta a Droga
Edema/induzido quimicamente
Fibrose
Nefropatias/enzimologia
Nefropatias/patologia
Nefropatias/urina
Túbulos Renais Proximais/enzimologia
L-Lactato Desidrogenase/urina
Masculino
Camundongos Endogâmicos BALB C
Proteinúria/induzido quimicamente
Proteinúria/urina
Medição de Risco
Fatores de Tempo
Uracila/toxicidade
gama-Glutamiltransferase/urina
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bacterial Toxins); 0 (Biomarkers); 2JIZ556BA3 (cylindrospermopsin); 56HH86ZVCT (Uracil); 9007-34-5 (Collagen); EC 1.1.1.27 (L-Lactate Dehydrogenase); EC 2.3.2.2 (gamma-Glutamyltransferase)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180220
[Lr] Data última revisão:
180220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180107
[St] Status:MEDLINE


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[PMID]:29325476
[Au] Autor:Chamorro-de-Vega E; Gimenez-Manzorro A; Rodriguez-Gonzalez CG; Escudero-Vilaplana V; De Lorenzo-Pinto A; Iglesias-Peinado I; Herranz-Alonso A; Sanjurjo Saez M; GRUviC Study Group
[Ad] Endereço:a Pharmacy Department , Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria del Hospital Gregorio Marañón , Madrid , Spain.
[Ti] Título:Twelve weeks of ombitasvir/paritaprevir/r and dasabuvir without ribavirin is effective and safe in the treatment of patients with HCV genotype 1b infection and compensated cirrhosis: results from a real-world cohort study.
[So] Source:Expert Opin Drug Saf;17(3):235-241, 2018 Mar.
[Is] ISSN:1744-764X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: To explore the effectiveness and safety of ombitasvir/paritaprevir/ritonavir and dasabuvir (OBV/PTV/r+DSV) for 12 weeks without ribavirin in adults with chronic HCV genotype 1b infection and compensated cirrhosis. METHODS: Observational study of a prospective cohort of adult patients with HCV genotype 1b infection and compensated cirrhosis who received 12 weeks of OBV/PTV/r and DSV without ribavirin. Effectiveness was assessed by recording the percentage of patients achieving sustained virological response at week 12 post-treatment (SVR12). Safety outcomes were based on the incidence of adverse events. RESULTS: Seventy-eight patients were included. The SVR12 rate was 96.1% (95%CI 89.2-99.2). Adverse events were recorded in 78.0% of patients. Of these, 97.7% were grade 1/2. One patient discontinued treatment prematurely owing to adverse events. Eighty-six interactions were detected in 43 patients (55.1%). Overall, 81.4% of interactions required close monitoring, alteration of drug dosage, or timing of administration. In 7.0% of cases, the interactions arose from contraindications that required the suspension of the concomitant drug. In 11.6% of cases, medicinal plants or foods were withdrawn. CONCLUSIONS: The simplified regimen of OBV/PTV/r+DSV administered for 12 weeks is effective and safe in patients with chronic HCV genotype 1b infection and compensated cirrhosis. No adverse reactions related to drug-drug interactions were recorded.
[Mh] Termos MeSH primário: Antivirais/administração & dosagem
Hepacivirus/genética
Hepatite C Crônica/tratamento farmacológico
Cirrose Hepática/tratamento farmacológico
[Mh] Termos MeSH secundário: Idoso
Anilidas/administração & dosagem
Anilidas/efeitos adversos
Antivirais/efeitos adversos
Carbamatos/administração & dosagem
Carbamatos/efeitos adversos
Estudos de Coortes
Interações Medicamentosas
Quimioterapia Combinada
Feminino
Genótipo
Hepatite C Crônica/virologia
Seres Humanos
Cirrose Hepática/virologia
Compostos Macrocíclicos/administração & dosagem
Compostos Macrocíclicos/efeitos adversos
Masculino
Meia-Idade
Estudos Prospectivos
Ritonavir/administração & dosagem
Ritonavir/efeitos adversos
Sulfonamidas/administração & dosagem
Sulfonamidas/efeitos adversos
Resultado do Tratamento
Uracila/administração & dosagem
Uracila/efeitos adversos
Uracila/análogos & derivados
[Pt] Tipo de publicação:JOURNAL ARTICLE; OBSERVATIONAL STUDY
[Nm] Nome de substância:
0 (ABT-267); 0 (ABT-333); 0 (ABT-450); 0 (Anilides); 0 (Antiviral Agents); 0 (Carbamates); 0 (Macrocyclic Compounds); 0 (Sulfonamides); 56HH86ZVCT (Uracil); O3J8G9O825 (Ritonavir)
[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:180113
[St] Status:MEDLINE
[do] DOI:10.1080/14740338.2018.1424829


  9 / 9203 MEDLINE  
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[PMID]:29305868
[Au] Autor:Tominaga A; Sato M; Takahashi T; Toyoda E; Toyoda K; Suzuki T; Takahashi M; Watanabe M; Okazaki K
[Ad] Endereço:Department of Orthopaedic Surgery, Tokyo Women's Medical University, 8-1 Kawadacho, Shinjuku-ku, Tokyo, 162-8666, Japan.
[Ti] Título:Quality assessment of cellular and tissue-based products using liquid chromatography-tandem mass spectrometry.
[So] Source:Biochem Biophys Res Commun;496(2):429-435, 2018 02 05.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:We are currently conducting clinical research on cell sheets for cartilage regeneration. One issue with the future use of chondrocyte sheets as cellular and tissue-based products is quality assessment. Currently, chondrocyte sheets are evaluated using invasive methods that cannot be performed on every sheet produced. We report here on our liquid chromatography-tandem mass spectrometry (LC-MS/MS) technique that allows the noninvasive assessment of every sheet using only 50 µl of culture medium. We found that LC-MS/MS could be used to confirm cell sheet viability through the measurement of glucose and glutamine uptake, to estimate extracellular matrix production by measuring serine consumption, to estimate cell kinetics by measuring cytidine and uracil concentrations, and to estimate melanoma inhibitory activity level by measuring pyridoxal concentration. LC-MS/MS may be useful for the noninvasive assessment of products to be used in regenerative medicine.
[Mh] Termos MeSH primário: Cartilagem/metabolismo
Condrócitos/metabolismo
Cromatografia Líquida/normas
Regeneração/fisiologia
Espectrometria de Massas em Tandem/normas
[Mh] Termos MeSH secundário: Transporte Biológico
Cartilagem/patologia
Cartilagem/cirurgia
Citidina/metabolismo
Matriz Extracelular
Glucose/metabolismo
Glutamina/metabolismo
Seres Humanos
Controle de Qualidade
Medicina Regenerativa/métodos
Serina/metabolismo
Uracila/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0RH81L854J (Glutamine); 452VLY9402 (Serine); 56HH86ZVCT (Uracil); 5CSZ8459RP (Cytidine); IY9XDZ35W2 (Glucose)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180213
[Lr] Data última revisão:
180213
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180107
[St] Status:MEDLINE


  10 / 9203 MEDLINE  
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[PMID]:29239718
[Au] Autor:Ordeig L; Garcia-Cehic D; Gregori J; Soria ME; Nieto-Aponte L; Perales C; Llorens M; Chen Q; Riveiro-Barciela M; Buti M; Esteban R; Esteban JI; Rodriguez-Frias F; Quer J
[Ad] Endereço:1​Liver Unit, Liver Disease Laboratory-Viral Hepatitis, Internal Medicine Department, Vall d'Hebron Institut Recerca (VHIR)-Hospital Universitari Vall d'Hebron (HUVH), 08035, Barcelona, Spain.
[Ti] Título:New hepatitis C virus genotype 1 subtype naturally harbouring resistance-associated mutations to NS5A inhibitors.
[So] Source:J Gen Virol;99(1):97-102, 2018 Jan.
[Is] ISSN:1465-2099
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Hepatitis C virus (HCV) is a highly divergent virus currently classified into seven major genotypes and 86 subtypes (ICTV, June 2017), which can have differing responses to therapy. Accurate genotyping/subtyping using high-resolution HCV subtyping enables confident subtype identification, identifies mixed infections and allows detection of new subtypes. During routine genotyping/subtyping, one sample from an Equatorial Guinea patient could not be classified into any of the subtypes. The complete genomic sequence was compared to reference sequences by phylogenetic and sliding window analysis. Resistance-associated substitutions (RASs) were assessed by deep sequencing. The unclassified HCV genome did not belong to any of the existing genotype 1 (G1) subtypes. Sliding window analysis along the complete genome ruled out recombination phenomena suggesting that it belongs to a new HCV G1 subtype. Two NS5A RASs (L31V+Y93H) were found to be naturally combined in the genome which could limit treatment possibilities in patients infected with this subtype.
[Mh] Termos MeSH primário: Farmacorresistência Viral/genética
Genótipo
Hepacivirus/genética
Mutação
Filogenia
Proteínas não Estruturais Virais/genética
[Mh] Termos MeSH secundário: Anilidas/uso terapêutico
Antivirais/uso terapêutico
Benzimidazóis/uso terapêutico
Carbamatos/uso terapêutico
Guiné Equatorial
Feminino
Fluorenos/uso terapêutico
Expressão Gênica
Hepacivirus/classificação
Hepacivirus/efeitos dos fármacos
Hepatite C/tratamento farmacológico
Hepatite C/patologia
Hepatite C/virologia
Seres Humanos
Imidazóis/uso terapêutico
Testes de Sensibilidade Microbiana
Meia-Idade
Análise de Sequência de DNA
Sulfonamidas/uso terapêutico
Uracila/análogos & derivados
Uracila/uso terapêutico
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (ABT-267); 0 (ABT-333); 0 (Anilides); 0 (Antiviral Agents); 0 (BMS-790052); 0 (Benzimidazoles); 0 (Carbamates); 0 (Fluorenes); 0 (Imidazoles); 0 (NS-5 protein, hepatitis C virus); 0 (Sulfonamides); 0 (Viral Nonstructural Proteins); 013TE6E4WV (ledipasvir); 56HH86ZVCT (Uracil)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171229
[Lr] Data última revisão:
171229
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171215
[St] Status:MEDLINE
[do] DOI:10.1099/jgv.0.000996



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