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[PMID]:29318368
[Au] Autor:Mirlohi MS; Yaghooti H; Shirali S; Aminasnafi A; Olapour S
[Ad] Endereço:Hyperlipidemia Research Center, School of Allied Medical Sciences, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
[Ti] Título:Increased levels of advanced glycation end products positively correlate with iron overload and oxidative stress markers in patients with ß-thalassemia major.
[So] Source:Ann Hematol;97(4):679-684, 2018 Apr.
[Is] ISSN:1432-0584
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:The impaired biosynthesis of the ß-globin chain in ß-thalassemia leads to the accumulation of unpaired alpha globin chains, failure in hemoglobin formation, and iron overload due to frequent blood transfusion. Iron excess causes oxidative stress and massive tissue injuries. Advanced glycation end products (AGEs) are harmful agents, and their production accelerates in oxidative conditions. This study was conducted on 45 patients with major ß-thalassemia who received frequent blood transfusions and chelation therapy and were compared to 40 healthy subjects. Metabolic parameters including glycemic and iron indices, hepatic and renal functions tests, oxidative stress markers, and AGEs (carboxymethyl-lysine and pentosidine) levels were measured. All parameters were significantly increased in ß-thalassemia compared to the control except for glutathione levels. Blood glucose, iron, serum ferritin, non-transferrin-bound iron (NTBI), MDA, soluble form of low-density lipoprotein receptor, glutathione peroxidase, total reactive oxygen species (ROS), and AGE levels were significantly higher in the ß-thalassemia patients. Iron and ferritin showed a significant positive correlation with pentosidine (P < 0.01) but not with carboxymethyl-lysine. The NTBI was markedly increased in the ß-thalassemia patients, and its levels correlated significantly with both carboxymethyl-lysine and pentosidine (P < 0.05). Our findings confirm the oxidative status generated by the iron overload in ß-thalassemia major patients and highlight the enhanced formation of AGEs, which may play an important role in the pathogenesis of ß-thalassemia major.
[Mh] Termos MeSH primário: Transfusão de Sangue
Produtos Finais de Glicação Avançada/sangue
Sobrecarga de Ferro/etiologia
Estresse Oxidativo
Reação Transfusional/fisiopatologia
Talassemia beta/sangue
[Mh] Termos MeSH secundário: Adolescente
Adulto
Biomarcadores/sangue
Terapia por Quelação/efeitos adversos
Terapia Combinada/efeitos adversos
Estudos Transversais
Desferroxamina/uso terapêutico
Feminino
Seres Humanos
Irã (Geográfico)
Sobrecarga de Ferro/prevenção & controle
Masculino
Piridonas/uso terapêutico
Receptores Depuradores Classe E/sangue
Adulto Jovem
Talassemia beta/terapia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers); 0 (Glycation End Products, Advanced); 0 (OLR1 protein, human); 0 (Pyridones); 0 (Scavenger Receptors, Class E); 2BTY8KH53L (deferiprone); J06Y7MXW4D (Deferoxamine)
[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:180111
[St] Status:MEDLINE
[do] DOI:10.1007/s00277-017-3223-3


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[PMID]:29231667
[Au] Autor:Myrstad M; Vandvik I; Engebretsen EH; Tveit A
[Ti] Título:Hjerneslag etter seponering av nye antikoagulasjonsmidler før kirurgi..
[So] Source:Tidsskr Nor Laegeforen;137(23-24), 2017 12 12.
[Is] ISSN:0807-7096
[Cp] País de publicação:Norway
[La] Idioma:nor
[Mh] Termos MeSH primário: Anticoagulantes/administração & dosagem
Antitrombinas/administração & dosagem
Dabigatrana/administração & dosagem
Inibidores do Fator Xa/administração & dosagem
Cuidados Pré-Operatórios/efeitos adversos
Pirazóis/administração & dosagem
Piridonas/administração & dosagem
Acidente Vascular Cerebral/etiologia
[Mh] Termos MeSH secundário: Idoso
Idoso de 80 Anos ou mais
Fibrilação Atrial/tratamento farmacológico
Seres Humanos
Masculino
Meia-Idade
Medição de Risco
Fatores de Risco
Acidente Vascular Cerebral/diagnóstico por imagem
Procedimentos Cirúrgicos Operatórios
Fatores de Tempo
Tomografia Computadorizada por Raios X
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anticoagulants); 0 (Antithrombins); 0 (Factor Xa Inhibitors); 0 (Pyrazoles); 0 (Pyridones); 3Z9Y7UWC1J (apixaban); I0VM4M70GC (Dabigatran)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180306
[Lr] Data última revisão:
180306
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171213
[St] Status:MEDLINE
[do] DOI:10.4045/tidsskr.17.0532


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[PMID]:29317618
[Au] Autor:Kirtane AR; Abouzid O; Minahan D; Bensel T; Hill AL; Selinger C; Bershteyn A; Craig M; Mo SS; Mazdiyasni H; Cleveland C; Rogner J; Lee YL; Booth L; Javid F; Wu SJ; Grant T; Bellinger AM; Nikolic B; Hayward A; Wood L; Eckhoff PA; Nowak MA; Langer R; Traverso G
[Ad] Endereço:Department of Chemical Engineering and David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
[Ti] Título:Development of an oral once-weekly drug delivery system for HIV antiretroviral therapy.
[So] Source:Nat Commun;9(1):2, 2018 01 09.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The efficacy of antiretroviral therapy is significantly compromised by medication non-adherence. Long-acting enteral systems that can ease the burden of daily adherence have not yet been developed. Here we describe an oral dosage form composed of distinct drug-polymer matrices which achieved week-long systemic drug levels of the antiretrovirals dolutegravir, rilpivirine and cabotegravir in a pig. Simulations of viral dynamics and patient adherence patterns indicate that such systems would significantly reduce therapeutic failures and epidemiological modelling suggests that using such an intervention prophylactically could avert hundreds of thousands of new HIV cases. In sum, weekly administration of long-acting antiretrovirals via a novel oral dosage form is a promising intervention to help control the HIV epidemic worldwide.
[Mh] Termos MeSH primário: Fármacos Anti-HIV/administração & dosagem
Sistemas de Liberação de Medicamentos/métodos
Compostos Heterocíclicos com 3 Anéis/administração & dosagem
Piridonas/administração & dosagem
Rilpivirina/administração & dosagem
[Mh] Termos MeSH secundário: Administração Oral
Animais
Fármacos Anti-HIV/farmacocinética
Fármacos Anti-HIV/uso terapêutico
Avaliação Pré-Clínica de Medicamentos
Compostos Heterocíclicos com 3 Anéis/farmacocinética
Compostos Heterocíclicos com 3 Anéis/uso terapêutico
Seres Humanos
Modelos Teóricos
Cooperação do Paciente
Estudo de Prova de Conceito
Piridonas/farmacocinética
Piridonas/uso terapêutico
Rilpivirina/farmacocinética
Rilpivirina/uso terapêutico
Suínos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Anti-HIV Agents); 0 (GSK1265744); 0 (Heterocyclic Compounds, 3-Ring); 0 (Pyridones); DKO1W9H7M1 (dolutegravir); FI96A8X663 (Rilpivirine)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180111
[St] Status:MEDLINE
[do] DOI:10.1038/s41467-017-02294-6


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[PMID]:27775691
[Au] Autor:Hendrix MJ; Kandela I; Mazar AP; Seftor EA; Seftor RE; Margaryan NV; Strizzi L; Murphy GF; Long GV; Scolyer RA
[Ad] Endereço:Department of Biology, Shepherd University, Shepherdstown, WV, USA.
[Ti] Título:Targeting melanoma with front-line therapy does not abrogate Nodal-expressing tumor cells.
[So] Source:Lab Invest;97(2):176-186, 2017 02.
[Is] ISSN:1530-0307
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Metastatic melanoma is a highly aggressive skin cancer with a poor prognosis. It is the leading cause of skin cancer deaths with a median overall survival for advanced-stage metastatic disease of <6 months. Despite advances in the field with conventional and targeted therapies, the heterogeneity of melanoma poses the greatest ongoing challenge, ultimately leading to relapse and progression to a more drug-resistant tumor in most patients. Particularly noteworthy are recent findings, indicating that these therapies exert selective pressure on tumors resulting in the activation of pathways associated with cancer stem cells that are unresponsive to current therapy. Our previous studies have shown how Nodal, an embryonic morphogen of the transforming growth factor-beta superfamily, is one of these critical factors that is reactivated in aggressive melanoma and resistant to conventional chemotherapy, such as dacarbazine. In the current study, we sought to determine whether BRAF inhibitor (BRAFi) therapy targeted Nodal-expressing tumor cells in uniquely matched unresectable stage III and IV melanoma patient samples before and after therapy that preceded their eventual death due to disease. The results demonstrate that BRAFi treatment failed to affect Nodal levels in melanoma tissues. Accompanying experiments in soft agar and in nude mice showed the advantage of using combinatorial treatment with BRAFi plus anti-Nodal monoclonal antibody to suppress tumor growth and metastasis. These data provide a promising new approach using front-line therapy combined with targeting a cancer stem cell-associated molecule-producing a more efficacious response than monotherapy.
[Mh] Termos MeSH primário: Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Melanoma/tratamento farmacológico
Proteína Nodal/antagonistas & inibidores
Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores
Neoplasias Cutâneas/tratamento farmacológico
[Mh] Termos MeSH secundário: Animais
Anticorpos Monoclonais/administração & dosagem
Western Blotting
Linhagem Celular Tumoral
Feminino
Seres Humanos
Imidazóis/administração & dosagem
Imuno-Histoquímica
Neoplasias Pulmonares/prevenção & controle
Neoplasias Pulmonares/secundário
Melanoma/genética
Melanoma/metabolismo
Camundongos Nus
Terapia de Alvo Molecular/métodos
Mutação
Proteína Nodal/imunologia
Proteína Nodal/metabolismo
Oximas/administração & dosagem
Proteínas Proto-Oncogênicas B-raf/genética
Proteínas Proto-Oncogênicas B-raf/metabolismo
Piridonas/administração & dosagem
Pirimidinonas/administração & dosagem
Neoplasias Cutâneas/genética
Neoplasias Cutâneas/metabolismo
Resultado do Tratamento
Ensaios Antitumorais Modelo de Xenoenxerto/métodos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Antibodies, Monoclonal); 0 (Imidazoles); 0 (Nodal Protein); 0 (Oximes); 0 (Pyridones); 0 (Pyrimidinones); 33E86K87QN (trametinib); EC 2.7.11.1 (Proto-Oncogene Proteins B-raf); QGP4HA4G1B (dabrafenib)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:180306
[Lr] Data última revisão:
180306
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161025
[St] Status:MEDLINE
[do] DOI:10.1038/labinvest.2016.107


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[PMID]:29316536
[Au] Autor:Xie W; Wu Y; Zhang J; Mei Q; Zhang Y; Zhu N; Liu R; Zhang H
[Ad] Endereço:School of Chemistry and Chemical Engineering, Hunan University of Science and Technology, Xiangtan 411201, China; Key Laboratory of Theoretical Organic Chemistry and Function Molecule of Ministry of Education, Hunan University of Science and Technology, Xiangtan 411201, China; Hunan Provincal Key La
[Ti] Título:Design, synthesis and biological evaluations of novel pyridone-thiazole hybrid molecules as antitumor agents.
[So] Source:Eur J Med Chem;145:35-40, 2018 Feb 10.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:A hybrid pharmacophore approach was adopted to design and synthesize new series of pyridone-thiazole hybrid compounds. The structures of the compounds were established by IR, H NMR, C NMR, and HRMS. All the newly prepared compounds (3a-3m) were in vitro evaluated for their antiproliferative activity against three human cancer cell lines, namely Colon cancer (HCT-116), gastric carcinoma (MGC803) and hepatocellular cancer (Huh7). Bioassay results demonstrated that most of the tested compounds showed potent anti-tumor activities against various cancer cells in vitro, and some compounds exhibited stronger effects than positive control 5-Fluorouracil (5-FU). Compound 3b showed the best anti-tumor activity with IC values of 8.17 µM and 3.15 µM against HCT116 and MGC803 cell lines, respectively, which was 1.4-8.1 times more potent than 5-Fluorouracil (IC = 11.29 µM and 25.54 µM against HCT116 and MGC803 respectively). These findings suggest that compound 3b may have potential to be developed as a promising lead for the design of novel anticancer small-molecule drugs.
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Desenho de Drogas
Piridonas/farmacologia
Tiazóis/farmacologia
[Mh] Termos MeSH secundário: Antineoplásicos/síntese química
Antineoplásicos/química
Linhagem Celular Tumoral
Proliferação Celular/efeitos dos fármacos
Relação Dose-Resposta a Droga
Ensaios de Seleção de Medicamentos Antitumorais
Seres Humanos
Estrutura Molecular
Piridonas/química
Relação Estrutura-Atividade
Tiazóis/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Pyridones); 0 (Thiazoles)
[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:180110
[St] Status:MEDLINE


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[PMID]:29269690
[Au] Autor:Kikuno M; Koga M; Kume Y; Ohtsuka T; Hayakawa M; Toyoda K
[Ad] Endereço:Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center.
[Ti] Título:[A case of cardiogenic embolism, which occurred under appropriate warfarin use, treated with thoracoscopic left atrial appendectomy].
[So] Source:Rinsho Shinkeigaku;58(1):9-14, 2018 Jan 26.
[Is] ISSN:1882-0654
[Cp] País de publicação:Japan
[La] Idioma:jpn
[Ab] Resumo:A 74-year-old man with a past medical history of bradycardiac atrial fibrillation and an old cerebral infarction presented with dysarthria. He had been treated with warfarin and PT-INR on admission was 2.0. MRI of the head revealed an acute ischemic stroke involving the cerebellum and left occipital lobe. Because transesophageal cardiac echography showed a thrombus in the left atrial appendage, anticoagulant treatment with warfarin and heparin was initiated. The thrombus was enlarging; therefore, we changed the anticoagulant therapy to apixaban with heparin on day 11. On day 17, a hemorrhagic cerebral infarction occurred. After the hemorrhage diminished, we treated him with warfarin aiming for a PT-INR between 3 and 4. The thrombus gradually shrank and disappeared on day 110. Finally, a thoracoscopic left atrial appendectomy was performed as a secondary prevention, with no recurrence till date.
[Mh] Termos MeSH primário: Anticoagulantes/administração & dosagem
Procedimentos Cirúrgicos Cardíacos/métodos
Infarto Cerebral/etiologia
Átrios do Coração/cirurgia
Cardiopatias/etiologia
Toracoscopia/métodos
Trombose/etiologia
Varfarina/administração & dosagem
[Mh] Termos MeSH secundário: Idoso
Quimioterapia Combinada
Cardiopatias/terapia
Heparina/administração & dosagem
Seres Humanos
Coeficiente Internacional Normatizado
Masculino
Pirazóis/administração & dosagem
Piridonas/administração & dosagem
Recidiva
Síndrome do Nó Sinusal/complicações
Trombose/terapia
Resultado do Tratamento
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anticoagulants); 0 (Pyrazoles); 0 (Pyridones); 3Z9Y7UWC1J (apixaban); 5Q7ZVV76EI (Warfarin); 9005-49-6 (Heparin)
[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:171223
[St] Status:MEDLINE
[do] DOI:10.5692/clinicalneurol.cn-001065


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[PMID]:29373602
[Au] Autor:Li X; Keshishian A; Hamilton M; Horblyuk R; Gupta K; Luo X; Mardekian J; Friend K; Nadkarni A; Pan X; Lip GYH; Deitelzweig S
[Ad] Endereço:Worldwide Health Economics and Outcomes Research, Bristol-Myers Squibb Company, Lawrenceville, NJ, United States of America.
[Ti] Título:Apixaban 5 and 2.5 mg twice-daily versus warfarin for stroke prevention in nonvalvular atrial fibrillation patients: Comparative effectiveness and safety evaluated using a propensity-score-matched approach.
[So] Source:PLoS One;13(1):e0191722, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Prior real-world studies have shown that apixaban is associated with a reduced risk of stroke/systemic embolism (stroke/SE) and major bleeding versus warfarin. However, few studies evaluated the effectiveness and safety of apixaban according to its dosage, and most studies contained limited numbers of patients prescribed 2.5 mg twice-daily (BID) apixaban. Using pooled data from 4 American claims database sources, baseline characteristics and outcomes for patients prescribed 5 mg BID and 2.5 mg BID apixaban versus warfarin were compared. After 1:1 propensity-score matching, 31,827 5 mg BID apixaban-matched warfarin patients and 6600 2.5 mg BID apixaban-matched warfarin patients were identified. Patients prescribed 2.5 mg BID apixaban were older, had clinically more severe comorbidities, and were more likely to have a history of stroke and bleeding compared with 5 mg BID apixaban patients. Compared with warfarin, 5 mg BID apixaban was associated with a lower risk of stroke/SE (hazard ratio [HR]: 0.70, 95% confidence interval [CI]: 0.60-0.81) and major bleeding (HR: 0.59, 95% CI: 0.53-0.66). Compared with warfarin, 2.5 mg BID apixaban was also associated with a lower risk of stroke/SE (HR: 0.63, 95% CI: 0.49-0.81) and major bleeding (HR: 0.59, 95% CI: 0.49-0.71). In this real-world study, both apixaban doses were assessed in 2 patient groups differing in age and clinical characteristics. Each apixaban dose was associated with a lower risk of stroke/SE and major bleeding compared with warfarin in the distinct population for which it is being prescribed in United States clinical practice. TRIAL REGISTRATION: Clinicaltrials.Gov Identifier: NCT03087487.
[Mh] Termos MeSH primário: Fibrilação Atrial/complicações
Pirazóis/administração & dosagem
Piridonas/administração & dosagem
Acidente Vascular Cerebral/prevenção & controle
Varfarina/administração & dosagem
[Mh] Termos MeSH secundário: Adolescente
Adulto
Idoso
Esquema de Medicação
Feminino
Seres Humanos
Masculino
Meia-Idade
Estudos Retrospectivos
Acidente Vascular Cerebral/etiologia
Adulto Jovem
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE; OBSERVATIONAL STUDY; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Pyrazoles); 0 (Pyridones); 3Z9Y7UWC1J (apixaban); 5Q7ZVV76EI (Warfarin)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180226
[Lr] Data última revisão:
180226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180127
[Cl] Clinical Trial:ClinicalTrial
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0191722


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[PMID]:29192703
[Au] Autor:Osorio-Nieto U; Vázquez-Amaya LY; Höpfl H; Quintero L; Sartillo-Piscil F
[Ad] Endereço:Centro de Investigación de la Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla (BUAP), 14 Sur Esq. San Claudio, Col. San Manuel, 72570, Puebla, México. fernando.sartillo@correo.buap.mx.
[Ti] Título:The direct and highly diastereoselective synthesis of 3,4-epoxy-2-piperidones. Application to the total synthesis and absolute configurational assignment of 3α,4α-epoxy-5ß-pipermethystine.
[So] Source:Org Biomol Chem;16(1):77-88, 2017 Dec 19.
[Is] ISSN:1477-0539
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The substrate-controlled asymmetric total synthesis and absolute configurational assignment of biologically active 3α,4α-epoxy-5ß-pipermethystine, a minor component in the aerial parts of kava, has been achieved by featuring, as a key step, the environmentally friendly and direct synthesis of 2,3-epoxyamides from allyl amines. By using the chiron approach, first a carbohydrate-derived dehydropiperidine was prepared and subjected to a stereoselective tandem C-H/C[double bond, length as m-dash]C oxidation reaction. In this attempt, the required α,α-trans-epoxy-2-piperidone skeleton of the kava metabolite precursor was not achieved, although the tandem oxidation was highly stereoselective. However, starting from non-carbohydrate 3-hydroxy-4,5-dehydropiperidine, and using the same tandem oxidation, the target intermediate was obtained in high yield and complete unprecedented anti-stereoselectivity. Since the proposed mechanistic course of this tandem oxidation implies the transient formation of an α,ß-unsaturated amide followed by the subsequent epoxidation reaction, this second approach supports the previously established biotransformation proposal of (-)-pipermethystine to (-)-3α,4α-epoxy-5ß-pipermethystine.
[Mh] Termos MeSH primário: Piperidonas/síntese química
Piridonas/síntese química
[Mh] Termos MeSH secundário: Estrutura Molecular
Piperidonas/química
Piridonas/química
Estereoisomerismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Piperidones); 0 (Pyridones); 71627-22-0 (pipermethystine)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180223
[Lr] Data última revisão:
180223
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171202
[St] Status:MEDLINE
[do] DOI:10.1039/c7ob02700a


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[PMID]:29304154
[Au] Autor:Kerrigan D; Mantsios A; Gorgolas M; Montes ML; Pulido F; Brinson C; deVente J; Richmond GJ; Beckham SW; Hammond P; Margolis D; Murray M
[Ad] Endereço:Department of Health, Behavior & Society, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, United States of America.
[Ti] Título:Experiences with long acting injectable ART: A qualitative study among PLHIV participating in a Phase II study of cabotegravir + rilpivirine (LATTE-2) in the United States and Spain.
[So] Source:PLoS One;13(1):e0190487, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Challenges with adherence to daily oral antiretroviral therapy (ART) among people living with HIV (PLHIV) have stimulated development of injectable long-acting (LA) regimens. We conducted 39 in-depth interviews with participants and providers in a Phase IIb study (LATTE-2) evaluating an injectable LA regimen in the U.S. and Spain. Interviews exploring participant and provider attitudes and experiences with LA versus oral ART were audiotaped, transcribed and analyzed using thematic content analysis. Participants described the convenience of LA injections versus daily pills and emotional benefits such as minimized potential for HIV disclosure and eliminating the "daily reminder of living with HIV." Providers recognized benefits but cautioned that LA candidates still need to adhere to clinic visits for injections and raised questions around ongoing clinical management. LA was seen as preferable to daily oral ART among PLHIV. Further research is needed regarding appropriate candidates, including with women and "non-adherent" populations across settings.
[Mh] Termos MeSH primário: Fármacos Anti-HIV/administração & dosagem
Infecções por HIV/tratamento farmacológico
Piridonas/uso terapêutico
Rilpivirina/uso terapêutico
[Mh] Termos MeSH secundário: Seres Humanos
Piridonas/administração & dosagem
Pesquisa Qualitativa
Rilpivirina/administração & dosagem
Espanha
Estados Unidos
[Pt] Tipo de publicação:CLINICAL TRIAL, PHASE II; JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Anti-HIV Agents); 0 (GSK1265744); 0 (Pyridones); FI96A8X663 (Rilpivirine)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180221
[Lr] Data última revisão:
180221
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180106
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0190487


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[PMID]:29384960
[Au] Autor:Martín Algarra S; Soriano V; Fernández-Morales L; Berciano-Guerrero MÁ; Mujika K; Manzano JL; Puértolas Hernández T; Soria A; Rodríguez-Abreu D; Espinosa Arranz E; Medina Martínez J; Márquez-Rodas I; Rubió-Casadevall J; Ortega ME; Jurado García JM; Lecumberri Biurrun MJ; Palacio I; Rodríguez de la Borbolla Artacho M; Altozano JP; Castellón Rubio VE; García A; Luna P; Ballesteros A; Fernández O; López Martín JA; Berrocal A; Arance A
[Ad] Endereço:Medical Oncology, Clínica Universidad de Navarra, Pamplona.
[Ti] Título:Dabrafenib plus trametinib for compassionate use in metastatic melanoma: A STROBE-compliant retrospective observational postauthorization study.
[So] Source:Medicine (Baltimore);96(52):e9523, 2017 Dec.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The main objective of the study was to evaluate the efficacy and safety of dabrafenib alone or combined with trametinib for compassionate use in patients with metastatic melanoma.This retrospective, observational study involved 135 patients with unresectable stage IIIC or stage IV melanoma from an expanded-access program at 30 Spanish centers.Forty-eight patients received dabrafenib monotherapy and 87 received combination dabrafenib and trametinib; 4.4% and 95.6% of the patients had stage IIIC and IV melanoma, respectively. All patients showed BRAF mutations in their primary or metastatic lesions; 3 were positive for V600K while the remainder had V600E or V600+. A positive response to treatment was reported in 89.3% of the patients. Overall survival rates at 12 and 24 months were 59.6% (95% confidence interval [CI], 52.5-68.9%) and 36.4% (95% CI, 27.8-45%), respectively. Progression-free survival rates at 12 and 24 months were 39.3% (95% CI, 31.1-47.5%) and 21.6% (95% CI, 14.5-28.7%), respectively. Fifty-seven patients (42.2%) reported cutaneous toxicity of any type, mainly hyperkeratosis (14.8%) and rash (11.9%). The most frequent adverse events were pyrexia (27.4%), asthenia (19.3%), arthralgia (16.9%), and diarrhoea (13.2%).Our results suggest that both dabrafenib alone or in combination with trametinib are effective for compassionate use in terms of response and/or survival rates. However, differences in patients' prognostic features ought to be considered. No new findings were revealed regarding the safety profiles of either regimen. This is the first study to evaluate the efficacy of these 2 selective BRAF and mitogen-activated extracellular signal-regulated kinase inhibitors in a real-world setting in Spain.
[Mh] Termos MeSH primário: Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Imidazóis/uso terapêutico
Melanoma/tratamento farmacológico
Melanoma/patologia
Oximas/uso terapêutico
Piridonas/uso terapêutico
Pirimidinonas/uso terapêutico
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
Ensaios de Uso Compassivo
Feminino
Seres Humanos
Imidazóis/administração & dosagem
Imidazóis/efeitos adversos
Masculino
Meia-Idade
Metástase Neoplásica
Oximas/administração & dosagem
Oximas/efeitos adversos
Piridonas/administração & dosagem
Piridonas/efeitos adversos
Pirimidinonas/administração & dosagem
Pirimidinonas/efeitos adversos
Estudos Retrospectivos
Espanha
Análise de Sobrevida
[Pt] Tipo de publicação:JOURNAL ARTICLE; OBSERVATIONAL STUDY
[Nm] Nome de substância:
0 (Imidazoles); 0 (Oximes); 0 (Pyridones); 0 (Pyrimidinones); 33E86K87QN (trametinib); QGP4HA4G1B (dabrafenib)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180220
[Lr] Data última revisão:
180220
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180201
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000009523



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