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[PMID]:29318278
[Au] Autor:Atri A; Frölich L; Ballard C; Tariot PN; Molinuevo JL; Boneva N; Windfeld K; Raket LL; Cummings JL
[Ad] Endereço:Ray Dolby Brain Health Center, California Pacific Medical Center, San Francisco.
[Ti] Título:Effect of Idalopirdine as Adjunct to Cholinesterase Inhibitors on Change in Cognition in Patients With Alzheimer Disease: Three Randomized Clinical Trials.
[So] Source:JAMA;319(2):130-142, 2018 01 09.
[Is] ISSN:1538-3598
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Importance: New therapeutic approaches for Alzheimer disease (AD) are needed. Objective: To assess whether idalopirdine, a selective 5-hydroxytryptamine-6 receptor antagonist, is effective for symptomatic treatment of mild to moderate AD. Design, Setting, and Participants: Three randomized clinical trials that included 2525 patients aged 50 years or older with mild to moderate AD (study 1: n = 933 patients at 119 sites; study 2: n = 858 at 158 sites; and study 3: n = 734 at 126 sites). The 24-week studies were conducted from October 2013 to January 2017; final follow-up on January 12, 2017. Interventions: Idalopirdine (10, 30, or 60 mg/d) or placebo added to cholinesterase inhibitor treatment (donepezil in studies 1 and 2; donepezil, rivastigmine, or galantamine in study 3). Main Outcomes and Measures: Primary end point in all 3 studies: change in cognition total score (range, 0-70; a lower score indicates less impairment) from baseline to 24 weeks measured by the 11-item cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-Cog); key secondary end points: Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change Scale and 23-item Activities of Daily Living Inventory scores. Dose group efficacy required a significant benefit over placebo for the primary end point and 1 or more key secondary end points. Safety data and adverse event profiles were recorded. Results: Among 2525 patients randomized in the 3 trials (mean age, 74 years; mean baseline ADAS-Cog total score, 26; between 62% and 65% of participants were women), 2254 (89%) completed the studies. In study 1, the mean change in ADAS-Cog total score between baseline and 24 weeks was 0.37 for the 60-mg dose of idalopirdine group, 0.61 for the 30-mg dose group, and 0.41 for the placebo group (adjusted mean difference vs placebo, 0.05 [95% CI, -0.88 to 0.98] for the 60-mg dose group and 0.33 [95% CI, -0.59 to 1.26] for the 30-mg dose group). In study 2, the mean change in ADAS-Cog total score between baseline and 24 weeks was 1.01 for the 30-mg dose of idalopirdine group, 0.53 for the 10-mg dose group, and 0.56 for the placebo group (adjusted mean difference vs placebo, 0.63 [95% CI, -0.38 to 1.65] for the 30-mg dose group; given the gated testing strategy and the null findings at the 30-mg dose, statistical comparison of the 10-mg dose was not performed). In study 3, the mean change in ADAS-Cog total score between baseline and 24 weeks was 0.38 for the 60-mg dose of idalopirdine group and 0.82 for the placebo group (adjusted mean difference vs placebo, -0.55 [95% CI, -1.45 to 0.36]). Treatment-emergent adverse events occurred in between 55.4% and 69.7% of participants in the idalopirdine groups vs between 56.7% and 61.4% of participants in the placebo groups. Conclusions and Relevance: In patients with mild to moderate AD, the use of idalopirdine compared with placebo did not improve cognition over 24 weeks of treatment. These findings do not support the use of idalopirdine for the treatment of AD. Trial Registration: clinicaltrials.gov Identifiers: NCT01955161, NCT02006641, and NCT02006654.
[Mh] Termos MeSH primário: Doença de Alzheimer/tratamento farmacológico
Benzilaminas/uso terapêutico
Inibidores da Colinesterase/uso terapêutico
Indóis/uso terapêutico
Antagonistas da Serotonina/uso terapêutico
[Mh] Termos MeSH secundário: Acidentes por Quedas
Idoso
Idoso de 80 Anos ou mais
Doença de Alzheimer/psicologia
Benzilaminas/administração & dosagem
Benzilaminas/efeitos adversos
Inibidores da Colinesterase/efeitos adversos
Cognição/efeitos dos fármacos
Relação Dose-Resposta a Droga
Método Duplo-Cego
Quimioterapia Combinada
Feminino
Galantamina/uso terapêutico
Seres Humanos
Indanos/uso terapêutico
Indóis/administração & dosagem
Indóis/efeitos adversos
Masculino
Meia-Idade
Piperidinas/uso terapêutico
Rivastigmina/uso terapêutico
Antagonistas da Serotonina/administração & dosagem
Antagonistas da Serotonina/efeitos adversos
Falha de Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE; MULTICENTER STUDY; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 ((2-(6-fluoro-1H-indol-3-yl)-ethyl)-(3-(2,2,3,3-tetrafluoropropoxy)benzyl)amine); 0 (Benzylamines); 0 (Cholinesterase Inhibitors); 0 (Indans); 0 (Indoles); 0 (Piperidines); 0 (Serotonin Antagonists); 0D3Q044KCA (Galantamine); 8SSC91326P (donepezil); PKI06M3IW0 (Rivastigmine)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180311
[Lr] Data última revisão:
180311
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180111
[Cl] Clinical Trial:ClinicalTrial
[St] Status:MEDLINE
[do] DOI:10.1001/jama.2017.20373


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[PMID]:29482394
[Au] Autor:Marcinkowska M; Kotanska M; Zagórska A; Sniecikowska J; Kubacka M; Siwek A; Bucki A; Pawlowski M; Bednarski M; Sapa J; Starek M; Dabrowska M; Kolaczkowski M
[Ad] Endereço:a Department of Medicinal Chemistry , Jagiellonian University Medical College , Kraków , Poland.
[Ti] Título:Synthesis and biological evaluation of N-arylpiperazine derivatives of 4,4-dimethylisoquinoline-1,3(2H,4H)-dione as potential antiplatelet agents.
[So] Source:J Enzyme Inhib Med Chem;33(1):536-545, 2018 Dec.
[Is] ISSN:1475-6374
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Despite the substantial clinical success of aspirin and clopidogrel in secondary prevention of ischemic stroke, up to 40% of patients remain resistant to the available antiplatelet treatment. Therefore, there is an urgent clinical need to develop novel antiplatelet agents with a novel mechanism of action. Recent studies revealed that potent alpha 2B-adrenergic receptor (alpha 2B-ARs) antagonists could constitute alternative antiplatelet therapy. We have synthesized a series of N-arylpiperazine derivatives of 4,4-dimethylisoquinoline-1,3(2H,4H)-dione as potential alpha 2B receptor antagonists. The most potent compound 3, effectively inhibited the platelet-aggregation induced both by collagen and ADP/adrenaline with IC of 26.9 µM and 20.5 µM respectively. Our study confirmed that the alpha 2B-AR antagonists remain an interesting target for the development of novel antiplatelet agents with an alternative mechanism of action.
[Mh] Termos MeSH primário: Isoquinolinas/farmacologia
Piperazinas/farmacologia
Inibidores da Agregação de Plaquetas/farmacologia
Receptores Adrenérgicos alfa 2/metabolismo
[Mh] Termos MeSH secundário: Relação Dose-Resposta a Droga
Seres Humanos
Isoquinolinas/síntese química
Isoquinolinas/química
Modelos Moleculares
Estrutura Molecular
Piperazinas/síntese química
Piperazinas/química
Agregação Plaquetária/efeitos dos fármacos
Inibidores da Agregação de Plaquetas/síntese química
Inibidores da Agregação de Plaquetas/química
Testes de Função Plaquetária
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (ADRA2B protein, human); 0 (Isoquinolines); 0 (Piperazines); 0 (Platelet Aggregation Inhibitors); 0 (Receptors, Adrenergic, alpha-2); 1RTM4PAL0V (piperazine)
[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:180228
[St] Status:MEDLINE
[do] DOI:10.1080/14756366.2018.1437155


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[PMID]:29482389
[Au] Autor:Elzahabi HSA; Nossier ES; Khalifa NM; Alasfoury RA; El-Manawaty MA
[Ad] Endereço:a Department of Pharmaceutical Chemistry , Faculty of Pharmacy (Girls), Al-Azhar University , Cairo , Egypt.
[Ti] Título:Anticancer evaluation and molecular modeling of multi-targeted kinase inhibitors based pyrido[2,3-d]pyrimidine scaffold.
[So] Source:J Enzyme Inhib Med Chem;33(1):546-557, 2018 Dec.
[Is] ISSN:1475-6374
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:An efficient synthesis of substituted pyrido[2,3-d]pyrimidines was carried out and evaluated for in vitro anticancer activity against five cancer cell lines, namely hepatic cancer (HepG-2), prostate cancer (PC-3), colon cancer (HCT-116), breast cancer (MCF-7), and lung cancer (A-549) cell lines. Regarding HepG-2, PC-3, HCT-116 cancer cell lines, 7-(4-chlorophenyl)-2-(3-methyl-5-oxo-2,3-dihydro-1H-pyrazol-1-yl)-5-(p-tolyl)- pyrido[2,3-d]pyrimidin-4(3H)-one (5a) exhibited strong, more potent anticancer (IC : 0.3, 6.6 and 7 µM) relative to the standard doxorubicin (IC : 0.6, 6.8 and 12.8 µM), respectively. Kinase inhibitory assessment of 5a showed promising inhibitory activity against three kinases namely PDGFR ß, EGFR, and CDK4/cyclin D1 at two concentrations 50 and 100 µM in single measurements. Further, a molecular docking study for compound 5a was performed to verify the binding mode towards the EGFR and CDK4/cyclin D1 kinases.
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Quinase 4 Dependente de Ciclina/antagonistas & inibidores
Inibidores de Proteínas Quinases/farmacologia
Piridinas/farmacologia
Pirimidinas/farmacologia
Receptor do Fator de Crescimento Epidérmico/antagonistas & inibidores
Receptor beta de Fator de Crescimento Derivado de Plaquetas/antagonistas & inibidores
[Mh] Termos MeSH secundário: Antineoplásicos/síntese química
Antineoplásicos/química
Linhagem Celular Tumoral
Proliferação Celular/efeitos dos fármacos
Quinase 4 Dependente de Ciclina/metabolismo
Relação Dose-Resposta a Droga
Ensaios de Seleção de Medicamentos Antitumorais
Seres Humanos
Modelos Moleculares
Estrutura Molecular
Inibidores de Proteínas Quinases/síntese química
Inibidores de Proteínas Quinases/química
Piridinas/síntese química
Piridinas/química
Pirimidinas/síntese química
Pirimidinas/química
Receptor do Fator de Crescimento Epidérmico/metabolismo
Receptor beta de Fator de Crescimento Derivado de Plaquetas/metabolismo
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Protein Kinase Inhibitors); 0 (Pyridines); 0 (Pyrimidines); 0 (pyrido(3,2-d)pyrimidine); EC 2.7.10.1 (Receptor, Epidermal Growth Factor); EC 2.7.10.1 (Receptor, Platelet-Derived Growth Factor beta); EC 2.7.11.22 (CDK4 protein, human); EC 2.7.11.22 (Cyclin-Dependent Kinase 4)
[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:180228
[St] Status:MEDLINE
[do] DOI:10.1080/14756366.2018.1437729


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[PMID]:29439603
[Au] Autor:Doggrell SA
[Ad] Endereço:a Faculty of Health , Queensland University of Technology , Brisbane , Australia.
[Ti] Título:Sgemaglutide in type 2 diabetes - is it the best glucagon-like peptide 1 receptor agonist (GLP-1R agonist)?
[So] Source:Expert Opin Drug Metab Toxicol;14(3):371-377, 2018 Mar.
[Is] ISSN:1744-7607
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:INTRODUCTION: Glucagon-like peptide-1 (GLP-1) is produced by the gut, and in a glucose-dependent manner stimulates insulin secretion while inhibiting glucagon secretion, reduces appetite and energy intake, and delays gastric emptying. The GLP-1R agonist semaglutide has recently been registered to treat type 2 diabetes. Area covered: This review is of semaglutide in type 2 diabetes, and considers which properties of this GLP-1R agonist, may be responsible for its clinical outcome benefits . Expert opinion: The pharmacokinetics of semaglutide make it ideal for once-weekly dosing. SUSTAIN 6 (Trial to Evaluate Cardiovascular and Other Long-term Outcomes With Semaglutide in Subjects With Type 2 Diabetes) showed that semaglutide 0.5 or 1 mg subcutaneously once-weekly reduced cardiovascular outcomes in subjects with type 2 diabetes and cardiovascular disease or risk, mean age 65 years, baseline HbA1c 8.7% and mean body weight of 92 kg. Although, semaglutide may be a useful drug in this population, it increased retinopathy to a small extent and this needs further investigation. Also, it is not known whether semaglutide will improve cardiovascular outcomes in other populations including those with lower ages, HbA1c values, and body weights similar to those included in the unsuccessful clinical outcome trials with the GLP-1R agonists, lixisenatide and exenatide.
[Mh] Termos MeSH primário: Diabetes Mellitus Tipo 2/tratamento farmacológico
Peptídeos Semelhantes ao Glucagon/administração & dosagem
Hipoglicemiantes/administração & dosagem
[Mh] Termos MeSH secundário: Idoso
Doenças Cardiovasculares/prevenção & controle
Diabetes Mellitus Tipo 2/fisiopatologia
Relação Dose-Resposta a Droga
Esquema de Medicação
Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas
Peptídeos Semelhantes ao Glucagon/farmacocinética
Peptídeos Semelhantes ao Glucagon/farmacologia
Seres Humanos
Hipoglicemiantes/farmacocinética
Hipoglicemiantes/farmacologia
Insulina/secreção
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Glucagon-Like Peptide-1 Receptor); 0 (Hypoglycemic Agents); 0 (Insulin); 53AXN4NNHX (semaglutide); 62340-29-8 (Glucagon-Like Peptides)
[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:180215
[St] Status:MEDLINE
[do] DOI:10.1080/17425255.2018.1441286


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[PMID]:29431542
[Au] Autor:Smit C; De Hoogd S; Brüggemann RJM; Knibbe CAJ
[Ad] Endereço:a Department of Clinical Pharmacy , St. Antonius Hospital , Nieuwegein , The Netherlands.
[Ti] Título:Obesity and drug pharmacology: a review of the influence of obesity on pharmacokinetic and pharmacodynamic parameters.
[So] Source:Expert Opin Drug Metab Toxicol;14(3):275-285, 2018 Mar.
[Is] ISSN:1744-7607
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:INTRODUCTION: The rising prevalence of obesity confronts clinicians with dosing problems in the (extreme) overweight population. Obesity has a great impact on key organs that play a role in the pharmacokinetics (PK) and pharmacodynamics (PD) of drugs, however the ultimate impact of these changes on how to adapt the dose may not always be known. Areas covered: In this review, physiological changes associated with obesity are discussed. An overview is provided on the alterations in absorption, distribution, drug metabolism and clearance in (morbid) obesity focusing on general principles that can be extracted from pharmacokinetic studies. Also, relevant pharmacodynamic considerations in obesity are discussed. Expert opinion: Over the last two decades, increased knowledge is generated on PK and PD in obesity. Future research should focus on filling in the knowledge gaps that remain, especially in connecting obesity-related physiological changes with changes in PK and/or PD and vice versa. Ultimately, this knowledge can be used to develop physiologically based PK and PD models on the basis of quantitative systems pharmacology principles. Moreover, efforts should focus on thorough prospective evaluation of developed model-based doses with subsequent implementation of these dosing recommendations in clinical practice.
[Mh] Termos MeSH primário: Obesidade Mórbida/metabolismo
Obesidade/metabolismo
Preparações Farmacêuticas/metabolismo
[Mh] Termos MeSH secundário: Animais
Relação Dose-Resposta a Droga
Seres Humanos
Modelos Biológicos
Preparações Farmacêuticas/administração & dosagem
Farmacocinética
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Pharmaceutical Preparations)
[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:180213
[St] Status:MEDLINE
[do] DOI:10.1080/17425255.2018.1440287


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[PMID]:29373935
[Au] Autor:Falcone M; Viale P; Tiseo G; Pai M
[Ad] Endereço:a Department of Public Health and Infectious Diseases , "Sapienza" University of Rome , Rome , Italy.
[Ti] Título:Pharmacokinetic drug evaluation of avibactam + ceftazidime for the treatment of hospital-acquired pneumonia.
[So] Source:Expert Opin Drug Metab Toxicol;14(3):331-340, 2018 Mar.
[Is] ISSN:1744-7607
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:INTRODUCTION: Ceftazidime-avibactam (CAZ-AVI) is a combination of a third-generation cephalosporin and a non-ß-lactam, ß-lactamase inhibitor, recently approved for urinary tract infections and complicated abdominal infections. Moreover, it represents a treatment option for patients with hospital acquired pneumonia (HAP), especially when caused by multidrug-resistant (MDR) bacteria. Areas covered: The review focuses on the pharmacokinetics (PK) of CAZ-AVI in HAP and on preclinical and clinical studies evaluating PK/pharmacodynamics (PD) in this field. Expert opinion: In vitro and in vivo data about PK/PD of CAZ-AVI confirm that penetration of CAZ-AVI in the epithelial lining fluid (ELF) represents approximately 30% of the plasma concentrations. Clinical studies documented that CAZ-AVI 2000 mg/500 mg every 8 h is the optimal dose regimen to achieve the PK/PD target attainment in patients with HAP. Thus, CAZ-AVI could represent an option both to treat HAP caused by Gram-negative bacilli (GNB) displaying resistance to most of the antibiotics and to reduce the use of carbapenems, limiting the onset of resistance profiles among GNB. Additional information about specific patients populations, such as critically-ill subjects or pediatric patients, are needed for a more individualized use of CAZ-AVI.
[Mh] Termos MeSH primário: Antibacterianos/administração & dosagem
Compostos Azabicíclicos/administração & dosagem
Ceftazidima/administração & dosagem
Pneumonia Bacteriana/tratamento farmacológico
[Mh] Termos MeSH secundário: Animais
Antibacterianos/farmacocinética
Compostos Azabicíclicos/farmacocinética
Ceftazidima/farmacocinética
Infecção Hospitalar/tratamento farmacológico
Infecção Hospitalar/microbiologia
Relação Dose-Resposta a Droga
Farmacorresistência Bacteriana Múltipla
Seres Humanos
Pneumonia Bacteriana/microbiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Azabicyclo Compounds); 0 (avibactam, ceftazidime drug combination); 9M416Z9QNR (Ceftazidime)
[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:180128
[St] Status:MEDLINE
[do] DOI:10.1080/17425255.2018.1434142


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[PMID]:29367486
[Au] Autor:Miyazawa N; Yoshimoto H; Kurihara S; Hamaya T; Eguchi F
[Ad] Endereço:Faculty of Regional Environment Science, Tokyo University of Agriculture.
[Ti] Título:Improvement of Diet-induced Obesity by Ingestion of Mushroom Chitosan Prepared from Flammulina velutipes.
[So] Source:J Oleo Sci;67(2):245-254, 2018 Feb 01.
[Is] ISSN:1347-3352
[Cp] País de publicação:Japan
[La] Idioma:eng
[Ab] Resumo:The anti-obesity effects of mushroom chitosan prepared from Flammulina velutipes were investigated using an animal model with diet-induced obesity. In this study, 5-week-old imprinting control region (ICR) mice were divided into six groups of 10 mice each and fed different diets based on the MF powdered diet (standard diet) for 6 weeks: standard diet control group, high-fat diet control group (induced dietary obesity) consisting of the standard diet and 20% lard, and mushroom chitosan groups consisting of the high-fat diet with mushroom chitosan added at 100, 500, 1,000, and 2,000 mg/kg body weight. On the final day of the experiment, mean body weight was 39.1 g in the high-fat control group and 36.3 g in the 2,000 mg/kg mushroom chitosan group, compared to 35.8 g in the standard diet control group. In the mushroom chitosan groups, a dose-dependent suppression of weight gain and marked improvements in serum triglycerides, total cholesterol, LDL-cholesterol, and HDL-cholesterol were found. The mushroom chitosan groups showed fewer and smaller fat deposits in liver cells than the high-fat diet control group, and liver weight was significantly reduced. Glutamic oxaloacetic transaminase (GOT) and glutamate pyruvic transaminase (GPT), which are indices of the hepatic function, all showed dose-dependent improvement with mushroom chitosan administration. These results suggested that mushroom chitosan acts to suppress enlargement of the liver from fat deposition resulting from a high-fat diet and to restore hepatic function. The lipid content of feces showed a marked increase correlated with the mushroom chitosan dose. These findings suggest the potential use of mushroom chitosan as a functional food ingredient that contributes to the prevention or improvement of dietary obesity by inhibiting digestion and absorption of fats in the digestive tract and simultaneously promotes lipolysis in adipocytes.
[Mh] Termos MeSH primário: Quitosana/administração & dosagem
Quitosana/isolamento & purificação
Dieta Hiperlipídica/efeitos adversos
Flammulina/química
Obesidade/prevenção & controle
Fitoterapia
[Mh] Termos MeSH secundário: Adipócitos/metabolismo
Administração Oral
Animais
Fármacos Antiobesidade
Quitosana/farmacologia
Modelos Animais de Doenças
Relação Dose-Resposta a Droga
Lipólise/efeitos dos fármacos
Masculino
Camundongos Endogâmicos ICR
Hepatopatia Gordurosa não Alcoólica/prevenção & controle
Obesidade/etiologia
Obesidade/metabolismo
Ganho de Peso/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Obesity Agents); 9012-76-4 (Chitosan)
[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:180126
[St] Status:MEDLINE
[do] DOI:10.5650/jos.ess17159


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[PMID]:29367485
[Au] Autor:Umigai N; Murakami K; Shimizu R; Takeda R; Azuma T
[Ad] Endereço:Riken Vitamin Co., Ltd.
[Ti] Título:Safety Evaluation and Plasma Carotenoid Accumulation in Healthy Adult Subjects after 12 Weeks of Paprika Oleoresin Supplementation.
[So] Source:J Oleo Sci;67(2):225-234, 2018 Feb 01.
[Is] ISSN:1347-3352
[Cp] País de publicação:Japan
[La] Idioma:eng
[Ab] Resumo:Paprika oleoresin is obtained by solvent extraction from Capsicum annuum L. fruits and contains multiple carotenoids, such as capsanthin, ß-carotene, zeaxanthin, and ß-cryptoxanthin, which are considered protective against various diseases. Herein, we investigated the effect of paprika oleoresin supplementation on plasma carotenoid accumulation and evaluated the safety of the oleoresin. We used a double-blinded, placebo-controlled comparative clinical study design and tested the effects of varying doses in healthy adult subjects. In total, 33 subjects were randomly divided into three groups to take capsules containing 0, 20, or 100 mg of paprika oleoresin daily for 12 consecutive weeks. Plasma carotenoid concentrations were measured at 0, 4, 8, and 12 weeks, and the safety of paprika oleoresin capsules was investigated using analyses of blood biochemistry, hematology, and urine contents. In these experiments, ß-cryptoxanthin and zeaxanthin dose-dependently accumulated in plasma within the dose range of the study over 12 consecutive weeks of paprika oleoresin supplementation. Moreover, ß-cryptoxanthin accumulated to higher levels than the other paprika oleoresin carotenoids. In contrast, capsanthin was not detected in plasma before or during the 12-week treatment period. Finally, no adverse events were associated with intake of paprika oleoresin (20 and 100 mg/day) in safety evaluations. Paprika oleoresin is a suitable source of carotenoids, especially ß-cryptoxanthin.
[Mh] Termos MeSH primário: Capsicum/química
Carotenoides/sangue
Suplementos Nutricionais
Extratos Vegetais/administração & dosagem
Extratos Vegetais/isolamento & purificação
[Mh] Termos MeSH secundário: beta-Criptoxantina/sangue
Suplementos Nutricionais/efeitos adversos
Relação Dose-Resposta a Droga
Método Duplo-Cego
Extratos Vegetais/efeitos adversos
Distribuição Aleatória
Segurança
Solventes
Fatores de Tempo
Zeaxantinas/sangue
[Pt] Tipo de publicação:CLINICAL STUDY; COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Beta-Cryptoxanthin); 0 (Plant Extracts); 0 (Solvents); 0 (Zeaxanthins); 0 (oleoresins); 36-88-4 (Carotenoids)
[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:180126
[St] Status:MEDLINE
[do] DOI:10.5650/jos.ess17155


  9 / 376405 MEDLINE  
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[PMID]:29363349
[Au] Autor:Van Donge T; Mian P; Tibboel D; Van Den Anker J; Allegaert K
[Ad] Endereço:a Intensive Care and Department of Paediatric Surgery , Erasmus MC-Sophia Children's Hospital , Rotterdam , The Netherlands.
[Ti] Título:Drug metabolism in early infancy: opioids as an illustration.
[So] Source:Expert Opin Drug Metab Toxicol;14(3):287-301, 2018 Mar.
[Is] ISSN:1744-7607
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:INTRODUCTION: Drug dosing in infants frequently depends on body weight as a crude indicator for maturation. Fentanyl (metabolized by Cytochrome P450 3A4) and morphine (glucuronidated by UDP-glucuronosyltransferase-2B7) served as model drugs to provide insight in maturation patterns of these enzymes and provide understanding of the impact of non-maturational factors to optimize dosing in infants. Areas covered: Systematic searches on metabolism and population pharmacokinetic (Pop-PK) models for fentanyl and morphine were performed. Pre- and post-model selection criteria were applied to assess and evaluate the validity of these models. It was observed that maturational changes have been rather well investigated, be it with variability in the maturational function estimates. The same holds true for Pop-PK models, where non-maturational covariates have also been reported (pharmacogenetics, disease state or external influences), although less incorporated in the PK models and with limited knowledge on mechanisms involved. Expert opinion: PK models for fentanyl and morphine are currently available. Consequently, we suggest that researchers should not continue to develop new models, but should investigate whether collected data fit in already existing models and provide additional value concerning the impact of (non)-maturational factors like drug-drug interactions or pharmacogenetics.
[Mh] Termos MeSH primário: Analgésicos Opioides/administração & dosagem
Fentanila/administração & dosagem
Morfina/administração & dosagem
[Mh] Termos MeSH secundário: Fatores Etários
Analgésicos Opioides/farmacocinética
Peso Corporal
Citocromo P-450 CYP3A/metabolismo
Relação Dose-Resposta a Droga
Fentanila/farmacocinética
Glucuronosiltransferase/metabolismo
Seres Humanos
Lactente
Modelos Biológicos
Morfina/farmacocinética
Farmacogenética
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Analgesics, Opioid); 76I7G6D29C (Morphine); EC 1.14.13.67 (CYP3A4 protein, human); EC 1.14.14.1 (Cytochrome P-450 CYP3A); EC 2.4.1.- (UGT2B7 protein, human); EC 2.4.1.17 (Glucuronosyltransferase); UF599785JZ (Fentanyl)
[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:180125
[St] Status:MEDLINE
[do] DOI:10.1080/17425255.2018.1432595


  10 / 376405 MEDLINE  
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[PMID]:29363337
[Au] Autor:Patti F; Chisari CG; D'Amico E; Zappia M
[Ad] Endereço:a Department "GF Ingrassia", Section of Neurosciences, Multiple Sclerosis Center , University of Catania , Catania , Italy.
[Ti] Título:Pharmacokinetic drug evaluation of daclizumab for the treatment of relapsing-remitting multiple sclerosis.
[So] Source:Expert Opin Drug Metab Toxicol;14(3):341-352, 2018 Mar.
[Is] ISSN:1744-7607
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:INTRODUCTION: Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system. Despite the availability of several disease-modifying therapies for relapsing MS, there is a need for highly efficacious targeted therapy with a favorable benefit-risk profile and a high level of treatment adherence. Daclizumab is a humanized monoclonal antibody directed against CD25, the α subunit of the high-affinity interleukin 2 (IL-2) receptor, that reversibly modulates IL-2 signaling. Areas covered: Daclizumab blocks the activation and expansion of autoreactive T cells that plays a role in the immune pathogenesis of MS. As its modulatory effects on the immune system, daclizumab's potential for use in MS was tested extensively showing a high efficacy in reducing relapse rate, disability progression and the number and volume of gadolinium-enhancing lesions on brain magnetic resonance imaging. Moreover, phase II and III trials showed a favorable pharmacokinetic (PK) profile with slow clearance, linear pharmacokinetics at doses above 100 mg and high subcutaneous bioavailability, not influenced by age, sex or other clinical parameters. Expert opinion: Among the new emerging drugs for MS, daclizumab also, thanks to a favorable PK profile, may represent an interesting and promising therapeutic option in the wide MS therapies armamentarium.
[Mh] Termos MeSH primário: Anticorpos Monoclonais Humanizados/administração & dosagem
Imunoglobulina G/administração & dosagem
Imunossupressores/administração & dosagem
Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico
[Mh] Termos MeSH secundário: Animais
Anticorpos Monoclonais Humanizados/farmacocinética
Anticorpos Monoclonais Humanizados/farmacologia
Disponibilidade Biológica
Relação Dose-Resposta a Droga
Seres Humanos
Imunoglobulina G/farmacologia
Imunossupressores/farmacocinética
Imunossupressores/farmacologia
Subunidade alfa de Receptor de Interleucina-2/imunologia
Imagem por Ressonância Magnética
Adesão à Medicação
Esclerose Múltipla Recidivante-Remitente/fisiopatologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Antibodies, Monoclonal, Humanized); 0 (IL2RA protein, human); 0 (Immunoglobulin G); 0 (Immunosuppressive Agents); 0 (Interleukin-2 Receptor alpha Subunit); CUJ2MVI71Y (daclizumab)
[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:180125
[St] Status:MEDLINE
[do] DOI:10.1080/17425255.2018.1432594



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