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  1 / 14151 MEDLINE  
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[PMID]:29425766
[Au] Autor:Tahara A; Takasu T
[Ad] Endereço:Candidate Discovery Science Laboratories, Astellas Pharma Inc., Ibaraki, Japan. Electronic address: atsuo.tahara@jp.astellas.com.
[Ti] Título:Antidiabetic effects of SGLT2 inhibitor ipragliflozin in type 2 diabetic mice fed diets containing different carbohydrate contents.
[So] Source:Life Sci;197:80-90, 2018 Mar 15.
[Is] ISSN:1879-0631
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:AIMS: Daily intake of carbohydrates differs among individual patients with type 2 diabetes. Here, we investigated whether or not dietary carbohydrate content affects the efficacy of the sodium-glucose cotransporter 2 (SGLT2) inhibitor ipragliflozin in type 2 diabetic mice. MAIN METHODS: Diabetic mice were fed a regular (50% kcal), high (75% kcal)-, or low (25% kcal)-carbohydrate diet. Ipragliflozin was orally administered once a day for 4 weeks. KEY FINDINGS: In all groups, mice exhibited characteristics of type 2 diabetes, including hyperglycemia, hyperinsulinemia, and obesity. Hyperglycemia was more severe in the high-carbohydrate diet group and milder in the low-carbohydrate diet group than in the regular diet group. In all diabetic mice, ipragliflozin significantly increased urinary glucose excretion and improved hyperglycemia, hyperinsulinemia, glucose tolerance, insulin resistance, obesity, and nephropathy. Although these antidiabetic effects of ipragliflozin were more marked in the high-carbohydrate diet group (which showed more severe hyperglycemia) than in the other two groups, no significant differences in effective dose or degree of response were observed among the three groups. SIGNIFICANCE: The antidiabetic effects of ipragliflozin were not greatly affected by dietary carbohydrate content, suggesting that ipragliflozin may have similar efficacy for patients with type 2 diabetes regardless of carbohydrate intake.
[Mh] Termos MeSH primário: Diabetes Mellitus Experimental/tratamento farmacológico
Diabetes Mellitus Tipo 2/tratamento farmacológico
Dieta
Carboidratos da Dieta/farmacologia
Glucosídeos/farmacologia
Hipoglicemiantes/farmacologia
Transportador 2 de Glucose-Sódio/antagonistas & inibidores
Tiofenos/farmacologia
[Mh] Termos MeSH secundário: Animais
Glicemia/metabolismo
Diabetes Mellitus Tipo 2/sangue
Camundongos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Blood Glucose); 0 (Dietary Carbohydrates); 0 (Glucosides); 0 (Hypoglycemic Agents); 0 (Slc5a2 protein, mouse); 0 (Sodium-Glucose Transporter 2); 0 (Thiophenes); 3N2N8OOR7X (ipragliflozin)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180301
[Lr] Data última revisão:
180301
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180210
[St] Status:MEDLINE


  2 / 14151 MEDLINE  
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[PMID]:28456475
[Au] Autor:Molinuevo MS; Fernández JM; Cortizo AM; McCarthy AD; Schurman L; Sedlinsky C
[Ad] Endereço:Laboratorio de Investigación en Osteopatías y Metabolismo Mineral, Facultad de Ciencias Exactas, Universidad Nacional de La Plata. 47 y 115, (1900) La Plata, Argentina.
[Ti] Título:Advanced glycation end products and strontium ranelate promote osteogenic differentiation of vascular smooth muscle cells in vitro: Preventive role of vitamin D.
[So] Source:Mol Cell Endocrinol;450:94-104, 2017 Jul 15.
[Is] ISSN:1872-8057
[Cp] País de publicação:Ireland
[La] Idioma:eng
[Ab] Resumo:Advanced glycation end products (AGE) have been demonstrated to induce the osteogenic trans-differentiation of vascular smooth muscle cells (VSMC). Strontium ranelate (SR) is an anti-osteoporotic agent that has both anti-catabolic and anabolic actions on bone tissue. However, in the last years SR has been associated with an increase of cardiovascular risk. We hypothesize that SR can increase the osteoblastic trans-differentiation of VSMC and the induction of extracellular calcifications, an effect that could be potentiated in the presence of AGE and inhibited by simultaneous administration of vitamin D. The present results of our in vitro experiments demonstrate that AGE and SR alone or in combination, stimulate L-type calcium channels, causing an increase in reactive oxygen species and activation of both ERK and NFkB, with the final effect of promoting the osteogenic shift of VSMC. Importantly, these in vitro effects of AGE and/or SR can be prevented by co-incubation with vitamin D.
[Mh] Termos MeSH primário: Diferenciação Celular/efeitos dos fármacos
Produtos Finais de Glicação Avançada/farmacologia
Músculo Liso Vascular/citologia
Miócitos de Músculo Liso/citologia
Osteogênese/efeitos dos fármacos
Tiofenos/farmacologia
Vitamina D/farmacologia
[Mh] Termos MeSH secundário: Animais
Ácido Ascórbico/farmacologia
Contagem de Células
Movimento Celular/efeitos dos fármacos
Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo
Masculino
Modelos Biológicos
Miócitos de Músculo Liso/efeitos dos fármacos
Miócitos de Músculo Liso/metabolismo
Nifedipino/farmacologia
Estresse Oxidativo/efeitos dos fármacos
Ratos Sprague-Dawley
Espécies Reativas de Oxigênio/metabolismo
Sulfassalazina/farmacologia
Vitamina E/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Core Binding Factor Alpha 1 Subunit); 0 (Glycation End Products, Advanced); 0 (Reactive Oxygen Species); 0 (Thiophenes); 04NQ160FRU (strontium ranelate); 1406-16-2 (Vitamin D); 1406-18-4 (Vitamin E); 3XC8GUZ6CB (Sulfasalazine); I9ZF7L6G2L (Nifedipine); PQ6CK8PD0R (Ascorbic Acid)
[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:170501
[St] Status:MEDLINE


  3 / 14151 MEDLINE  
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[PMID]:29215922
[Au] Autor:Liao X; Huang J; Lin W; Long Z; Xie Y; Ma W
[Ad] Endereço:1 State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology , Macau, China .
[Ti] Título:APTM, a Thiophene Heterocyclic Compound, Inhibits Human Colon Cancer HCT116 Cell Proliferation Through p53-Dependent Induction of Apoptosis.
[So] Source:DNA Cell Biol;37(2):70-77, 2018 Feb.
[Is] ISSN:1557-7430
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:To evaluate the in vitro anticancer activity and to investigate the mechanism of action of a thiophene heterocyclic compound, [3-Amino-5-[(2,6-dimethylphenyl)amino]-4-(phenylsulfonyl)-2-thienyl](4-fluorophenyl)methanone (APTM) against human colon cancer HCT116 cells. Sulforhodamine B assay and colony formation assay for cell proliferation assay; propidium iodide (PI) staining for cell cycle profile analysis; Hoechst staining; annexin V-FITC/PI double staining and Western blotting for apoptosis assay. APTM inhibits the growth of HCT116 cells dose and time dependently. The growth inhibitory effect of APTM on HCT116 cells was associated with induction of apoptosis but not cell cycle arrest. Also, the isogenic cell depletion of p53 was resistant to APTM-induced apoptosis and thus grows relatively better than the wild-type cells. The anticancer effect of APTM resulted from p53-dependent induction of apoptosis. Also, APTM is a promising lead compound for the treatment of human colon cancer.
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Apoptose/efeitos dos fármacos
Proliferação Celular/efeitos dos fármacos
Tiofenos/farmacologia
[Mh] Termos MeSH secundário: Neoplasias do Colo/tratamento farmacológico
Ensaios de Seleção de Medicamentos Antitumorais
Células HCT116
Seres Humanos
Concentração Inibidora 50
Proteína Supressora de Tumor p53/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (3-amino-5-((2,6-dimethylphenyl)amino)-4-(phenylsulfonyl)-2-thienyl)(4-fluorophenyl)methanone)); 0 (Antineoplastic Agents); 0 (TP53 protein, human); 0 (Thiophenes); 0 (Tumor Suppressor Protein p53)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180222
[Lr] Data última revisão:
180222
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171208
[St] Status:MEDLINE
[do] DOI:10.1089/dna.2017.3962


  4 / 14151 MEDLINE  
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[PMID]:29188248
[Au] Autor:Saini KM; Saunthwal RK; Verma AK
[Ad] Endereço:Synthetic Organic Chemistry Research Laboratory, Department of Chemistry, University of Delhi, Delhi, 110007, India. averma@acbr.du.ac.in.
[Ti] Título:Pd-Catalyzed one-pot sequential cross-coupling reactions of tetrabromothiophene.
[So] Source:Org Biomol Chem;15(48):10289-10298, 2017 Dec 13.
[Is] ISSN:1477-0539
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Unsymmetrical one-pot sequential cross-coupling reactions of sterically hindered tetrabromothiophene with arylboronic acid and an alkyne/alkene to afford selective bi-, tri-, and tetrasubstituted aryl/alkynyl-thiophenes with the aid of a palladium catalyst were described. The reaction proceeds via a site-selective Suzuki/Sonogashira coupling, followed by selective Sonogashira, Suzuki and Heck coupling reactions. This methodology has demonstrated an important framework for the synthesis of organic scaffolds.
[Mh] Termos MeSH primário: Hidrocarbonetos Bromados/síntese química
Chumbo/química
Tiofenos/síntese química
[Mh] Termos MeSH secundário: Catálise
Hidrocarbonetos Bromados/química
Estrutura Molecular
Tiofenos/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Hydrocarbons, Brominated); 0 (Thiophenes); 2P299V784P (Lead)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180222
[Lr] Data última revisão:
180222
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171201
[St] Status:MEDLINE
[do] DOI:10.1039/c7ob02601c


  5 / 14151 MEDLINE  
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[PMID]:28744112
[Au] Autor:Pan WL; Chen PL; Lin CY; Pan YC; Ju YR; Chan CP; Hsu RW
[Ad] Endereço:Department of Periodontics, Chang Gung Memorial Hospital, Taipei, Taiwan.
[Ti] Título:Strontium ranelate treatment in a postmenopausal woman with osteonecrosis of the jaw after long-term oral bisphosphonate administration: a case report.
[So] Source:Clin Interv Aging;12:1089-1093, 2017.
[Is] ISSN:1178-1998
[Cp] País de publicação:New Zealand
[La] Idioma:eng
[Ab] Resumo:Bisphosphonates (BPs) suppress bone resorption and increase bone strength, thus reducing the risk of fracture. Oral BPs are widely used for the prevention and treatment of osteoporosis and osteopenia. Here, we describe the case of a postmenopausal woman who took oral alendronate for >3 years for osteoporosis. The patient presented at the clinic with sharp jaw pain and swelling on the left mandible 4 months after extraction of the third molar. Clinical examinations identified an inflamed mucosal opening with pus over an area of necrotic bone. Initial images of cone beam computed tomography revealed a sequestrum at the extracted socket. The condition did not improve after 1 week of antibiotic treatment; therefore, the alendronate treatment was terminated and the patient was prescribed strontium ranelate instead. The patient gradually recovered and, at the 2-year follow-up, the site of BP-related osteonecrosis of the jaw healed completely as determined by both clinical and cone beam computed tomography measures. The bone mineral densities in the femoral neck and lumbar spine improved after 1 year, and were maintained at the 3-year follow-up. The serum C-terminal cross-linking telopeptide values also gradually increased from the initial 130 pg/mL to 320 pg/mL at the 3-year follow-up. Taken together, this case supports the use of strontium ranelate as an alternative treatment for postmenopausal women who receive long-term oral BP treatments and are at risk for serious complications of BP-related osteonecrosis of the jaw.
[Mh] Termos MeSH primário: Alendronato/efeitos adversos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/tratamento farmacológico
Conservadores da Densidade Óssea/efeitos adversos
Osteoporose Pós-Menopausa/tratamento farmacológico
Tiofenos/uso terapêutico
[Mh] Termos MeSH secundário: Idoso de 80 Anos ou mais
Alendronato/uso terapêutico
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/diagnóstico
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/etiologia
Conservadores da Densidade Óssea/uso terapêutico
Difosfonatos/efeitos adversos
Feminino
Seres Humanos
Pós-Menopausa
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bone Density Conservation Agents); 0 (Diphosphonates); 0 (Thiophenes); 04NQ160FRU (strontium ranelate); X1J18R4W8P (Alendronate)
[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:170727
[St] Status:MEDLINE
[do] DOI:10.2147/CIA.S141753


  6 / 14151 MEDLINE  
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[PMID]:29266836
[Au] Autor:Konda M; Maiti S; Jadhav RG; Das AK
[Ad] Endereço:Department of Chemistry, Indian Institute of Technology Indore, Indore, India.
[Ti] Título:Redox-Active Peptide-Functionalized Quinquethiophene-Based Electrochromic π-Gel.
[So] Source:Chem Asian J;13(2):204-209, 2018 Jan 18.
[Is] ISSN:1861-471X
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:An electrochromic system based on a self-assembled dipeptide-appended redox-active quinquethiophene π-gel is reported. The designed peptide-quinquethiophene consists of a symmetric bolaamphiphile that has two segments: a redox-active π-conjugated quinquethiophene core for electrochromism, and peptide motif for the involvement of molecular self-assembly. Investigations reveal that self-assembly and electrochromic properties of the π-gel are strongly dependent on the relative orientation of peptidic and quinquethiophene scaffolds in the self-assembly system. The colors of the π-gel film are very stable with fast and controlled switching speed at room temperature.
[Mh] Termos MeSH primário: Técnicas Eletroquímicas
Peptídeos/química
Tiofenos/química
[Mh] Termos MeSH secundário: Géis/química
Estrutura Molecular
Oxirredução
Tiofenos/síntese química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Gels); 0 (Peptides); 0 (Thiophenes)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180219
[Lr] Data última revisão:
180219
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171222
[St] Status:MEDLINE
[do] DOI:10.1002/asia.201701460


  7 / 14151 MEDLINE  
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[PMID]:29371602
[Au] Autor:Gélinas R; Mailleux F; Dontaine J; Bultot L; Demeulder B; Ginion A; Daskalopoulos EP; Esfahani H; Dubois-Deruy E; Lauzier B; Gauthier C; Olson AK; Bouchard B; Des Rosiers C; Viollet B; Sakamoto K; Balligand JL; Vanoverschelde JL; Beauloye C; Horman S; Bertrand L
[Ad] Endereço:Pole of Cardiovascular Research, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, Brussels, 1200, Belgium.
[Ti] Título:AMPK activation counteracts cardiac hypertrophy by reducing O-GlcNAcylation.
[So] Source:Nat Commun;9(1):374, 2018 01 25.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:AMP-activated protein kinase (AMPK) has been shown to inhibit cardiac hypertrophy. Here, we show that submaximal AMPK activation blocks cardiomyocyte hypertrophy without affecting downstream targets previously suggested to be involved, such as p70 ribosomal S6 protein kinase, calcineurin/nuclear factor of activated T cells (NFAT) and extracellular signal-regulated kinases. Instead, cardiomyocyte hypertrophy is accompanied by increased protein O-GlcNAcylation, which is reversed by AMPK activation. Decreasing O-GlcNAcylation by inhibitors of the glutamine:fructose-6-phosphate aminotransferase (GFAT), blocks cardiomyocyte hypertrophy, mimicking AMPK activation. Conversely, O-GlcNAcylation-inducing agents counteract the anti-hypertrophic effect of AMPK. In vivo, AMPK activation prevents myocardial hypertrophy and the concomitant rise of O-GlcNAcylation in wild-type but not in AMPKα2-deficient mice. Treatment of wild-type mice with O-GlcNAcylation-inducing agents reverses AMPK action. Finally, we demonstrate that AMPK inhibits O-GlcNAcylation by mainly controlling GFAT phosphorylation, thereby reducing O-GlcNAcylation of proteins such as troponin T. We conclude that AMPK activation prevents cardiac hypertrophy predominantly by inhibiting O-GlcNAcylation.
[Mh] Termos MeSH primário: Proteínas Quinases Ativadas por AMP/genética
Acetilglucosamina/metabolismo
Cardiomegalia/genética
Miocárdio/metabolismo
Miócitos Cardíacos/metabolismo
Transferases de Grupos Nitrogenados/genética
[Mh] Termos MeSH secundário: Proteínas Quinases Ativadas por AMP/deficiência
Acetilglucosamina/farmacologia
Acilação/efeitos dos fármacos
Animais
Animais Recém-Nascidos
Azasserina/farmacologia
Compostos Azo/farmacologia
Cardiomegalia/metabolismo
Cardiomegalia/patologia
Ativação Enzimática/efeitos dos fármacos
Ativadores de Enzimas/farmacologia
Regulação da Expressão Gênica
Glicosilação/efeitos dos fármacos
Ventrículos do Coração/efeitos dos fármacos
Ventrículos do Coração/metabolismo
Ventrículos do Coração/patologia
Masculino
Camundongos
Camundongos Knockout
Miocárdio/patologia
Miócitos Cardíacos/efeitos dos fármacos
Miócitos Cardíacos/patologia
Transferases de Grupos Nitrogenados/antagonistas & inibidores
Transferases de Grupos Nitrogenados/metabolismo
Norleucina/análogos & derivados
Norleucina/farmacologia
Fosforilação/efeitos dos fármacos
Cultura Primária de Células
Pironas/farmacologia
Ratos
Ratos Wistar
Transdução de Sinais
Tiofenos/farmacologia
Troponina T/genética
Troponina T/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (6-diazo-5-oxonorleucine); 0 (A 769662); 0 (Azo Compounds); 0 (Enzyme Activators); 0 (Pyrones); 0 (Thiophenes); 0 (Troponin T); 832C8OV84S (Norleucine); 87299V3Q9W (Azaserine); EC 2.6.- (Nitrogenous Group Transferases); EC 2.6.1.16 (Gfpt1 protein, mouse); EC 2.7.11.1 (AMPK alpha2 subunit, mouse); EC 2.7.11.31 (AMP-Activated Protein Kinases); V956696549 (Acetylglucosamine)
[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:180127
[St] Status:MEDLINE
[do] DOI:10.1038/s41467-017-02795-4


  8 / 14151 MEDLINE  
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[PMID]:29175456
[Au] Autor:Gupta A; Kumar A; Kumar D; Singh R; Shankar K; Varshney S; Rajan S; Srivastava A; Gupta S; Narender T; Gaikwad AN
[Ad] Endereço:Division of Pharmacology, CSIR-Central Drug Research Institute, Lucknow 226031, India.
[Ti] Título:Ecliptal, a promising natural lead isolated from Eclipta alba modulates adipocyte function and ameliorates metabolic syndrome.
[So] Source:Toxicol Appl Pharmacol;338:134-147, 2018 01 01.
[Is] ISSN:1096-0333
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:A swift increase has been observed in the number of individuals with metabolic syndrome worldwide. A number of natural compounds have been identified towards combating metabolic syndrome. Adding to this premise, here we report the pleiotropic activities of Ecliptal (EC); a natural compound isolated from the herb Eclipta alba. Administration of EC was shown to have prominent anti-adipogenic effects in 3T3-L1 and hMSC derived adipocytes. It was shown to activate Wnt-pathway and alter AKT signaling. Additionally, it caused cell cycle arrest and inhibited mitotic clonal expansion. EC treatment augmented mitochondrial biogenesis as well as function as estimated by expression of PGC1α, UCP-1, mitochondrial complexes and estimation of oxygen consumption rate. EC also reduced LPS-induced inflammation and tunicamycin induced ER stress. Further, EC enhanced insulin sensitivity by increasing AKT phosphorylation, inhibiting PKCα/ßII phosphorylation and reducing leptin/adiponectin ratio. Finally, EC administration in Syrian golden hamsters was shown to have potent anti-dyslipidemic effects. Cumulatively, encompassing pleiotropic activities of EC, it could prove to be a potential drug candidate against obesity, insulin resistance and related metabolic syndrome.
[Mh] Termos MeSH primário: Adipócitos/efeitos dos fármacos
Eclipta/química
Síndrome Metabólica/tratamento farmacológico
[Mh] Termos MeSH secundário: Células 3T3-L1
Adipócitos/fisiologia
Adipogenia/efeitos dos fármacos
Animais
Diferenciação Celular/efeitos dos fármacos
Estresse do Retículo Endoplasmático/efeitos dos fármacos
Masculino
Mesocricetus
Camundongos
Mitocôndrias/efeitos dos fármacos
Extratos Vegetais/farmacologia
Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores
Tiofenos/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Plant Extracts); 0 (Thiophenes); 0 (ecliptal); EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180213
[Lr] Data última revisão:
180213
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171128
[St] Status:MEDLINE


  9 / 14151 MEDLINE  
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[PMID]:28458353
[Au] Autor:Takasu T; Hayashizaki Y; Hirosumi J; Minoura H; Amino N; Kurosaki E; Takakura S
[Ad] Endereço:Tsukuba Research Center, Drug Discovery Research, Astellas Pharma Inc.
[Ti] Título:The Sodium Glucose Cotransporter 2 Inhibitor Ipragliflozin Promotes Preferential Loss of Fat Mass in Non-obese Diabetic Goto-Kakizaki Rats.
[So] Source:Biol Pharm Bull;40(5):675-680, 2017.
[Is] ISSN:1347-5215
[Cp] País de publicação:Japan
[La] Idioma:eng
[Ab] Resumo:Sodium glucose cotransporter 2 (SGLT2) inhibitors improve hyperglycemia in patients with type 2 diabetes mellitus (T2DM) by increasing urinary glucose excretion. In addition to their antihyperglycemic effect, SGLT2 inhibitors also reduce body weight and fat mass in obese and overweight patients with T2DM. However, whether or not SGLT2 inhibitors similarly affect body composition of non-obese patients with T2DM remains unclear. In this study, we investigated the effect of the SGLT2 inhibitor ipragliflozin on body composition in a Goto-Kakizaki (GK) rat model of non-obese T2DM. GK rats were treated with ipragliflozin once daily for 9 weeks, starting at 23 weeks of age. Body composition was then analyzed using dual-energy X-ray absorptiometry. Treatment with ipragliflozin increased urinary glucose excretion, reduced hemoglobin A1c (HbA1c) levels and suppressed body weight gain as the dose increased. Body composition analysis revealed that body fat mass was lower in the ipragliflozin-treated groups than in the control group, while lean body mass and bone mineral contents were comparable between groups. Thus, an SGLT2 inhibitor ipragliflozin was found to promote preferential loss of fat mass in a rat model of non-obese T2DM. Ipragliflozin might also promote preferential loss of fat in non-obese patients with T2DM.
[Mh] Termos MeSH primário: Tecido Adiposo/efeitos dos fármacos
Diabetes Mellitus Tipo 2/tratamento farmacológico
Glucosídeos/farmacologia
Hipoglicemiantes/farmacologia
Transportador 2 de Glucose-Sódio/antagonistas & inibidores
Tiofenos/farmacologia
[Mh] Termos MeSH secundário: Absorciometria de Fóton
Tecido Adiposo/patologia
Animais
Composição Corporal/efeitos dos fármacos
Diabetes Mellitus Tipo 2/patologia
Dieta Hiperlipídica
Ingestão de Alimentos/efeitos dos fármacos
Glicosúria/metabolismo
Masculino
Ratos
Ratos Wistar
Perda de Peso/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Glucosides); 0 (Hypoglycemic Agents); 0 (Sglt2 protein, rat); 0 (Sodium-Glucose Transporter 2); 0 (Thiophenes); 3N2N8OOR7X (ipragliflozin)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180212
[Lr] Data última revisão:
180212
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170502
[St] Status:MEDLINE
[do] DOI:10.1248/bpb.b16-00964


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Fotocópia
[PMID]:27775102
[Au] Autor:Dent MR; López-Duarte I; Dickson CJ; Chairatana P; Anderson HL; Gould IR; Wylie D; Vysniauskas A; Brooks NJ; Kuimova MK
[Ad] Endereço:Department of Chemistry, Imperial College London, Exhibition Road, London, SW7 2AZ, UK. m.kuimova@imperial.ac.uk n.brooks@imperial.ac.uk.
[Ti] Título:Imaging plasma membrane phase behaviour in live cells using a thiophene-based molecular rotor.
[So] Source:Chem Commun (Camb);52(90):13269-13272, 2016 Nov 03.
[Is] ISSN:1364-548X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Molecular rotors have emerged as versatile probes of microscopic viscosity in lipid bilayers, although it has proved difficult to find probes that stain both phases equally in phase-separated bilayers. Here, we investigate the use of a membrane-targeting viscosity-sensitive fluorophore based on a thiophene moiety with equal affinity for ordered and disordered lipid domains to probe ordering and viscosity within artificial lipid bilayers and live cell plasma membranes.
[Mh] Termos MeSH primário: Membrana Celular/química
Imagem Molecular
Tiofenos/química
[Mh] Termos MeSH secundário: Linhagem Celular
Sobrevivência Celular
Seres Humanos
Bicamadas Lipídicas/química
Fenômenos Mecânicos
Conformação Molecular
Simulação de Dinâmica Molecular
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Lipid Bilayers); 0 (Thiophenes)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180205
[Lr] Data última revisão:
180205
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161104
[St] Status:MEDLINE



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