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[PMID]:29241231
[Au] Autor:Jansen S; Boor M; Meyer MF; Pracht ED; Volland R; Klünter HD; Hüttenbrink KB; Beutner D; Grosheva M
[Ad] Endereço:Department of Otorhinolaryngology, Head and Neck Surgery, University of Cologne, Medical Faculty, Germany.
[Ti] Título:Influence of repetitive diving in freshwater on pressure equalization and Eustachian tube function in recreational scuba divers.
[So] Source:Diving Hyperb Med;47(4):223-227, 2017 Dec.
[Is] ISSN:1833-3516
[Cp] País de publicação:Australia
[La] Idioma:eng
[Ab] Resumo:INTRODUCTION: We investigated the effect of repetitive pressure exposure during freshwater dives on Eustachian tube function and the middle ear, assessed by the Eustachian tube function test (ETFT). METHODS: This prospective observational cohort study included 23 divers over three consecutive days of diving in freshwater lakes in Nordhausen, Germany. Participants underwent otoscopy and ETFT before the first dive, between each dive and after the last dive. ETFT included regular tympanometry (R-tymp), tympanometry after Valsalva (V-tymp) and after swallowing (S-tymp). The peak pressure difference between the R-tymp and the V-tymp (R-V ) defined effectiveness of pressure equalization after Valsalva manoeuvres. We evaluated the change in compliance and peak pressure and correlated the results to the otoscopic findings and diving experience. RESULTS: Twenty-three divers performed 144 dives. Middle ear barotrauma was assessed using the Edmonds modification of the TEED scoring system. In the ETFT, the R-tymp peak pressure displayed a negative shift from day one to three (P = 0.001) and differed significantly between the experience groups (P = 0.01). R-V did not change significantly on any of the three days of diving (all P > 0.05). Participants without MEBt showed significantly lower R-tymp values than did those with barotrauma (P = 0.019). CONCLUSION: Repetitive pressure exposure during three consecutive days of freshwater diving led to a negative shift of the peak pressure in the middle ear. Less experienced divers showed significantly higher middle ear peak pressure and higher pressure differences after equalization manoeuvres. Higher middle ear peak pressure was also associated with a higher prevalence of barotrauma.
[Mh] Termos MeSH primário: Testes de Impedância Acústica/métodos
Mergulho/fisiologia
Tuba Auditiva/fisiologia
Água Doce
[Mh] Termos MeSH secundário: Adulto
Complacência (Medida de Distensibilidade)
Mergulho/estatística & dados numéricos
Orelha Média/fisiologia
Estudos de Viabilidade
Feminino
Seres Humanos
Masculino
Otoscopia
Pressão
Estudos Prospectivos
Recreação
Fatores de Tempo
Manobra de Valsalva/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180201
[Lr] Data última revisão:
180201
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171215
[St] Status:MEDLINE
[do] DOI:10.28920/dhm47.4.223-227


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Martins, Pedro
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[PMID]:28454911
[Au] Autor:Rynkevic R; Martins P; Hympanova L; Almeida H; Fernandes AA; Deprest J
[Ad] Endereço:University of Porto, Faculty of Engineering, Portugal; INEGI, University of Porto, Faculty of Engineering, Portugal; KU Leuven, Department Development and Regeneration, Biomedical Sciences, Leuven, Belgium; Centre for Surgical Technologies, Group Biomedical Sciences, Belgium. Electronic address: r.r
[Ti] Título:Biomechanical and morphological properties of the multiparous ovine vagina and effect of subsequent pregnancy.
[So] Source:J Biomech;57:94-102, 2017 05 24.
[Is] ISSN:1873-2380
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Pelvic floor soft tissues undergo changes during the pregnancy. However, the degree and nature of this process is not completely characterized. This study investigates the effect of subsequent pregnancy on biomechanical and structural properties of ovine vagina. Vaginal wall from virgin, pregnant (in their third pregnancy) and parous (one year after third vaginal delivery) Swifter sheep (n=5 each) was harvested. Samples for biomechanics and histology, were cut in longitudinal axis (proximal and distal regions). Outcome measurements describing Young's modulus, ultimate stress and elongation were obtained from stress-strain curves. For histology samples were stained with Miller's Elastica staining. Collagen, elastin and muscle cells and myofibroblasts contents were estimated, using image processing techniques. Statistical analyses were performed in order to determine significant differences among experimental groups. Significant regional differences were identified. The proximal vagina was stiffer than distal, irrespective the reproductive status. During the pregnancy proximal vagina become more compliant than in parous (+47.45%) or virgin sheep (+64.35%). This coincided with lower collagen (-15 to -21%), higher elastin (+30 to +60%), and more smooth muscle cells (+17 to +37%). Vaginal tissue from parous ewes was weaker than of virgins, coinciding with lower collagen (-10%), higher elastin (+50%), more smooth muscle cells (+20%). It could be proposed that after pregnancy biomechanical properties of vagina do not recover to those of virgins. Since elastin has a significant influence on the compliance of soft tissues and collagen is the main "actor" regarding strength, histological analysis performed in this study justifies the mechanical behavior observed.
[Mh] Termos MeSH primário: Gravidez/fisiologia
Vagina/fisiologia
[Mh] Termos MeSH secundário: Animais
Fenômenos Biomecânicos
Colágeno/fisiologia
Complacência (Medida de Distensibilidade)
Módulo de Elasticidade
Elastina/fisiologia
Feminino
Processamento de Imagem Assistida por Computador
Miócitos de Músculo Liso/fisiologia
Paridade
Ovinos
Vagina/anatomia & histologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
9007-34-5 (Collagen); 9007-58-3 (Elastin)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:180120
[Lr] Data última revisão:
180120
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170430
[St] Status:MEDLINE


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[PMID]:29176890
[Au] Autor:Ghio S; Crimi G; Pica S; Temporelli PL; Boffini M; Rinaldi M; Raineri C; Scelsi L; Pistono M; Totaro R; Guida S; Oltrona Visconti L
[Ad] Endereço:Division of Cardiology, Fondazione IRCCS Policlinico S. Matteo, Pavia, Italy.
[Ti] Título:Persistent abnormalities in pulmonary arterial compliance after heart transplantation in patients with combined post-capillary and pre-capillary pulmonary hypertension.
[So] Source:PLoS One;12(11):e0188383, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: The hemodynamic definitions of pulmonary hypertension (PH) in left heart disease have recently been refined to better match the characteristics required to reflect the presence of pulmonary vascular disease. Accordingly, we tested the hypothesis that abnormalities in the stiffness of pulmonary circulation would persist after heart transplantation in patients with combined post-capillary and pre-capillary PH (Cpc-PH) in contrast to those with isolated post-capillary PH (Ipc-PH). METHODS: We retrospectively analyzed right heart hemodynamics in a cohort of 295 consecutive patients with heart failure and advanced left ventricular systolic dysfunction (LVSD) before and 1 year after heart transplantation. RESULTS: According to their baseline hemodynamic profile, patients were classified as: 75 Cpc-PH, 111 Ipc-PH, and 98 without PH (no-PH), and 11 pre-capillary PH. One year after heart transplantation, pulmonary artery pressures, pulmonary vascular resistance and cardiac index normalized in all patients regardless of the baseline hemodynamic profile. However, pulmonary arterial compliance remained lower in Cpc-PH patients (from 1.6±1.2 at baseline to 3.7±1.4 ml/mmHg at 1 year) than in Ipc-PH (from 1.2±2.0 to 4.4±2.3 ml/mmHg) and no-PH patients (from 3.7±2.0 to 4.5±1.8 ml/mmHg); (adjusted p = 0.03 Ipc-PH vs. Cpc-PH INT<0.001). CONCLUSIONS: In heart failure patients with advanced LVSD, a hemodynamic profile characterized by Cpc-PH predicts the persistence of a stiffer pulmonary circulation at 1 year after heart transplantation.
[Mh] Termos MeSH primário: Transplante de Coração/efeitos adversos
Hipertensão Pulmonar/etiologia
Hipertensão Pulmonar/fisiopatologia
Artéria Pulmonar/anormalidades
Artéria Pulmonar/fisiopatologia
[Mh] Termos MeSH secundário: Estudos de Coortes
Complacência (Medida de Distensibilidade)
Hemodinâmica
Seres Humanos
Análise de Componente Principal
Resistência Vascular
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171219
[Lr] Data última revisão:
171219
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171128
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0188383


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[PMID]:28538123
[Au] Autor:Phan BAP; Chung P
[Ad] Endereço:University of California, San Francisco, San Francisco binhan.phan@ucsf.edu.
[Ti] Título:Galloping Heart.
[So] Source:N Engl J Med;376(21):e44, 2017 May 25.
[Is] ISSN:1533-4406
[Cp] País de publicação:United States
[La] Idioma:eng
[Mh] Termos MeSH primário: Ruídos Cardíacos
Ventrículos do Coração/fisiopatologia
Hipertensão/fisiopatologia
Contração Miocárdica/fisiologia
[Mh] Termos MeSH secundário: Dor no Peito/etiologia
Complacência (Medida de Distensibilidade)
Seres Humanos
Hipertensão/complicações
Masculino
Meia-Idade
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE; VIDEO-AUDIO MEDIA
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170531
[Lr] Data última revisão:
170531
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170525
[St] Status:MEDLINE
[do] DOI:10.1056/NEJMicm1614250


  5 / 3857 MEDLINE  
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[PMID]:28483208
[Au] Autor:Abou R; Leung M; Tonsbeek AM; Podlesnikar T; Maan AC; Schalij MJ; Ajmone Marsan N; Delgado V; Bax JJ
[Ad] Endereço:Department of Cardiology, Leiden University Medical Centre, Leiden, The Netherlands.
[Ti] Título:Effect of Aging on Left Atrial Compliance and Electromechanical Properties in Subjects Without Structural Heart Disease.
[So] Source:Am J Cardiol;120(1):140-147, 2017 Jul 01.
[Is] ISSN:1879-1913
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Aging is associated with changes in left atrial (LA) structure and function. The present study aimed at describing the effect of aging on LA properties in a large cohort of subjects without structural heart disease. We divided 386 subjects (mean age 58 years [range 16 to 91]; 188 men [49%]) clinically referred for echocardiography according to age groups. The P-wave dispersion (PWD), reflecting total atrial conduction time, was measured on a 12-lead surface electrocardiogram as the difference between maximum and minimum P-wave duration. The PA-TDI duration reflecting the total atrial conduction time was measured on tissue Doppler imaging (TDI) as the time between onset of P wave on surface electrocardiogram to peak A'-wave velocity. Two-dimensional speckle-tracking echocardiography was used to assess LA reservoir function, reflecting LA compliance. In the overall population, mean PWD, PA-TDI, and LA reservoir strain were 43 ± 12 ms, 129 ± 27 ms, and 36 ± 13%, respectively. Increasing age was independently associated with prolonged PWD (ß = 0.161; p <0.001), PA-TDI (ß = 0.476; p <0.001), and reduced LA reservoir strain (ß = -0.259; <0.001), suggesting age-related fibrotic changes of the LA myocardium. The association between age and LA reservoir strain was modulated by body mass index (ß = -0.582; p <0.001) and LA volume index (ß = -0.117; p = 0.014). In conclusion, aging is associated with longer PWD and PA-TDI duration along with a decrease in LA reservoir function. Obesity and larger LA volumes are independently associated with reduced LA compliance.
[Mh] Termos MeSH primário: Envelhecimento/fisiologia
Função do Átrio Esquerdo/fisiologia
Ecocardiografia Doppler/métodos
Eletrocardiografia
Átrios do Coração/diagnóstico por imagem
[Mh] Termos MeSH secundário: Adolescente
Adulto
Idoso
Idoso de 80 Anos ou mais
Complacência (Medida de Distensibilidade)
Feminino
Seres Humanos
Masculino
Meia-Idade
Valores de Referência
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170809
[Lr] Data última revisão:
170809
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170510
[St] Status:MEDLINE


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[PMID]:28379718
[Au] Autor:Kugler MC; Loomis CA; Zhao Z; Cushman JC; Liu L; Munger JS
[Ad] Endereço:1 Division of Pulmonary, Critical Care and Sleep Medicine.
[Ti] Título:Sonic Hedgehog Signaling Regulates Myofibroblast Function during Alveolar Septum Formation in Murine Postnatal Lung.
[So] Source:Am J Respir Cell Mol Biol;57(3):280-293, 2017 Sep.
[Is] ISSN:1535-4989
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Sonic Hedgehog (Shh) signaling regulates mesenchymal proliferation and differentiation during embryonic lung development. In the adult lung, Shh signaling maintains mesenchymal quiescence and is dysregulated in diseases such as idiopathic pulmonary fibrosis and chronic obstructive pulmonary disease. Our previous data implicated a role for Shh in postnatal lung development. Here, we report a detailed analysis of Shh signaling during murine postnatal lung development. We show that Shh pathway expression and activity during alveolarization (postnatal day [P] 0-P14) are distinct from those during maturation (P14-P24). This biphasic pattern is paralleled by the transient presence of Gli1 ;α-smooth muscle actin (α-SMA) myofibroblasts in the growing alveolar septal tips. Carefully timed inhibition of Hedgehog (Hh) signaling during alveolarization defined mechanisms by which Shh influences the mesenchymal compartment. First, interruption of Hh signaling at earlier time points results in increased lung compliance and wall structure defects of increasing severity, ranging from moderately enlarged alveolar airspaces to markedly enlarged airspaces and fewer secondary septa. Second, Shh signaling is required for myofibroblast differentiation: Hh inhibition during early alveolarization almost completely eliminates Gli1 ;α-SMA cells at the septal tips, and Gli1-lineage tracing revealed that Gli1 cells do not undergo apoptosis after Hh inhibition but remain in the alveolar septa and are unable to express α-SMA. Third, Shh signaling is vital to mesenchymal proliferation during alveolarization, as Hh inhibition decreased proliferation of Gli1 cells and their progeny. Our study establishes Shh as a new alveolarization-promoting factor that might be affected in perinatal lung diseases that are associated with impaired alveolarization.
[Mh] Termos MeSH primário: Proteínas Hedgehog/metabolismo
Miofibroblastos/metabolismo
Organogênese
Alvéolos Pulmonares/crescimento & desenvolvimento
Alvéolos Pulmonares/metabolismo
Transdução de Sinais
[Mh] Termos MeSH secundário: Animais
Animais Recém-Nascidos
Diferenciação Celular
Complacência (Medida de Distensibilidade)
Matriz Extracelular/metabolismo
Regulação da Expressão Gênica no Desenvolvimento
Camundongos
Camundongos Endogâmicos C57BL
Versicanas/metabolismo
Proteína GLI1 em Dedos de Zinco/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Gli protein, mouse); 0 (Hedgehog Proteins); 0 (Zinc Finger Protein GLI1); 126968-45-4 (Versicans)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171021
[Lr] Data última revisão:
171021
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170406
[St] Status:MEDLINE
[do] DOI:10.1165/rcmb.2016-0268OC


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[PMID]:28356291
[Au] Autor:Neal CJ; Lin JB; Hurley T; Miner AS; Speich JE; Klausner AP; Ratz PH
[Ad] Endereço:Department of Mechanical and Nuclear Engineering, Virginia Commonwealth University, Richmond, Virginia; and.
[Ti] Título:Slowly cycling Rho kinase-dependent actomyosin cross-bridge "slippage" explains intrinsic high compliance of detrusor smooth muscle.
[So] Source:Am J Physiol Renal Physiol;313(1):F126-F134, 2017 Jul 01.
[Is] ISSN:1522-1466
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Biological soft tissues are viscoelastic because they display time-independent pseudoelasticity and time-dependent viscosity. However, there is evidence that the bladder may also display plasticity, defined as an increase in strain that is unrecoverable unless work is done by the muscle. In the present study, an electronic lever was used to induce controlled changes in stress and strain to determine whether rabbit detrusor smooth muscle (rDSM) is best described as viscoelastic or viscoelastic plastic. Using sequential ramp loading and unloading cycles, stress-strain and stiffness-stress analyses revealed that rDSM displayed reversible viscoelasticity, and that the viscous component was responsible for establishing a high stiffness at low stresses that increased only modestly with increasing stress compared with the large increase produced when the viscosity was absent and only pseudoelasticity governed tissue behavior. The study also revealed that rDSM underwent softening correlating with plastic deformation and creep that was reversed slowly when tissues were incubated in a Ca -containing solution. Together, the data support a model of DSM as a viscoelastic-plastic material, with the plasticity resulting from motor protein activation. This model explains the mechanism of intrinsic bladder compliance as "slipping" cross bridges, predicts that wall tension is dependent not only on vesicle pressure and radius but also on actomyosin cross-bridge activity, and identifies a novel molecular target for compliance regulation, both physiologically and therapeutically.
[Mh] Termos MeSH primário: Actomiosina/metabolismo
Contração Muscular
Músculo Liso/enzimologia
Bexiga Urinária/enzimologia
Quinases Associadas a rho/metabolismo
[Mh] Termos MeSH secundário: Animais
Fenômenos Biomecânicos
Complacência (Medida de Distensibilidade)
Masculino
Modelos Biológicos
Coelhos
Transdução de Sinais
Estresse Mecânico
Fatores de Tempo
Viscosidade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
9013-26-7 (Actomyosin); EC 2.7.11.1 (rho-Associated Kinases)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170918
[Lr] Data última revisão:
170918
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170331
[St] Status:MEDLINE
[do] DOI:10.1152/ajprenal.00633.2016


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[PMID]:28138832
[Au] Autor:Ekas NV; McDonald NM; Pruitt MM; Messinger DS
[Ad] Endereço:Department of Psychology, Texas Christian University, TCU Box 298920, Fort Worth, TX, 76129, USA. naomi.ekas@tcu.edu.
[Ti] Título:Brief Report: The Development of Compliance in Toddlers at-Risk for Autism Spectrum Disorder.
[So] Source:J Autism Dev Disord;47(4):1239-1248, 2017 Apr.
[Is] ISSN:1573-3432
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Parents of children with autism spectrum disorder (ASD) report concerns with child compliance. The development of compliance in 24-, 30-, and 36-month-old high-risk children with ASD outcomes (n = 21), high-risk children without ASD (n = 49), and low-risk children (n = 41) was examined. The High-Risk/ASD group showed greater passive noncompliance at 24-months than the non-ASD groups and a smaller increase in compliance than the High-Risk/No ASD group. The High-Risk/ASD group also showed a smaller decline in active noncompliance than the Low-Risk group. After controlling for receptive language, the passive noncompliance findings were nonsignificant whereas compliance and active noncompliance findings retained significance. The growth of compliance is attenuated in children with ASD, while changes in passive noncompliance are in part associated with language comprehension.
[Mh] Termos MeSH primário: Transtorno do Espectro Autista/diagnóstico
Transtorno do Espectro Autista/psicologia
Complacência (Medida de Distensibilidade)
[Mh] Termos MeSH secundário: Estudos de Casos e Controles
Pré-Escolar
Feminino
Seres Humanos
Lactente
Masculino
Sintomas Prodrômicos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171012
[Lr] Data última revisão:
171012
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170201
[St] Status:MEDLINE
[do] DOI:10.1007/s10803-016-2984-1


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[PMID]:28106664
[Au] Autor:Mokwatsi GG; Schutte AE; Kruger R
[Ad] Endereço:aHypertension in Africa Research Team (HART) bMedical Research Council, Research Unit for Hypertension and Cardiovascular Disease, Faculty of Health Sciences, North-West University, Potchefstroom, South Africa.
[Ti] Título:Ethnic differences regarding arterial stiffness of 6-8-year-old black and white boys.
[So] Source:J Hypertens;35(5):960-967, 2017 May.
[Is] ISSN:1473-5598
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:OBJECTIVES: Vascular deterioration is suggested to occur earlier in black than white populations, thereby increasing their risk for developing hypertension. To establish whether this is the case, we compared different estimates of arterial stiffness in black and white children and investigated the links with body composition and advanced glycation end products (AGEs) as potential contributors. METHODS: We included 40 black and 41 white boys (aged 6-8 years) from similar schools and measured arterial stiffness [pulse wave velocity (PWV) in different arterial sections, systemic arterial compliance and carotid stiffness estimates], anthropometry as well as urinary pentosidine as a marker of AGEs. RESULTS: Black boys displayed increased PWV [carotid-to-radial (P = 0.002), carotid-to-femoral (P < 0.0001) and carotid-to-dorsalis pedis (P = 0.008)], DBP (P = 0.001) and carotid intima-media thickness (P = 0.007) than white boys. Despite higher pentosidine in black boys (P = 0.039), arterial stiffness indices did not correlate with pentosidine in any group. However, only in black boys, pentosidine correlated negatively with BMI (P = 0.015), BSA (P = 0.017), weight (P = 0.018), waist (P = 0.022) and hip circumference (P = 0.010). Arterial stiffness indices related inversely to body composition in white boys, but femoral PWV correlated inversely with BMI (r = -0.32; P = 0.049) in black boys. CONCLUSION: Already at very young ages (6-8 years), with a high proportion of prehypertension, black boys in our study have increased arterial stiffness in all sections of the arterial tree, along with higher DBP, carotid intima-media thickness and AGEs. This phenotype underlines the increasing trend of early-onset vascular aging among black populations.
[Mh] Termos MeSH primário: Grupo com Ancestrais do Continente Africano
Artérias/fisiopatologia
Grupo com Ancestrais do Continente Europeu
Hipertensão/etnologia
Hipertensão/fisiopatologia
Rigidez Vascular
[Mh] Termos MeSH secundário: Arginina/análogos & derivados
Arginina/sangue
Composição Corporal
Índice de Massa Corporal
Peso Corporal/etnologia
Artérias Carótidas/fisiopatologia
Espessura Intima-Media Carotídea
Criança
Complacência (Medida de Distensibilidade)
Produtos Finais de Glicação Avançada/sangue
Seres Humanos
Lisina/análogos & derivados
Lisina/sangue
Masculino
Análise de Onda de Pulso
Circunferência da Cintura/etnologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Glycation End Products, Advanced); 94ZLA3W45F (Arginine); BJ4I2X2CQJ (pentosidine); K3Z4F929H6 (Lysine)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170121
[St] Status:MEDLINE
[do] DOI:10.1097/HJH.0000000000001267


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[PMID]:28060543
[Au] Autor:Organ L; Bacci B; Koumoundouros E; Kimpton WG; Samuel CS; Nowell CJ; Bradding P; Roach KM; Westall G; Jaffar J; Snibson KJ
[Ad] Endereço:1 Faculty of Veterinary and Agricultural Science, The University of Melbourne, Parkville, Victoria, Australia.
[Ti] Título:Inhibition of the K 3.1 Channel Alleviates Established Pulmonary Fibrosis in a Large Animal Model.
[So] Source:Am J Respir Cell Mol Biol;56(4):539-550, 2017 Apr.
[Is] ISSN:1535-4989
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive disease of increasing prevalence marked by poor prognosis and limited treatment options. Ca -activated K 3.1 potassium channels have been shown to play a key role in the aberrant activation and responses to injury in both epithelial cells and fibroblasts, both considered key drivers in the fibrotic process of IPF. Pharmacological inhibition of IPF-derived fibroblasts is able to somewhat prevent TGF-ß- and basic fibroblast growth factor-dependent profibrotic responses. In the current study, we investigated whether blockade of the K 3.1 ion channel in vivo with a selective inhibitor, Senicapoc, was able to attenuate both histological and physiological outcomes of early fibrosis in our large animal (sheep) model for pulmonary fibrosis. We also determined whether treatment was targeting the profibrotic activity of sheep lung fibroblasts. Senicapoc was administered in established fibrosis, at 2 weeks after bleomycin instillation, and drug efficacy was assessed 4 weeks after treatment. Treatment with Senicapoc improved pre-established bleomycin-induced changes compared with vehicle control, leading to improved lung compliance, reduced extracellular matrix and collagen deposition, and a reduction in both α-smooth muscle actin expression and proliferating cells, both in vivo and in vitro. These studies show that inhibiting the K 3.1 ion channel is able to attenuate the early fibrogenic phase of bleomycin-dependent fibrosis and inhibits profibrotic behavior of primary sheep lung fibroblasts. This supports the previous research conducted in human IPF-derived fibroblasts and suggests that inhibiting K 3.1 signaling may provide a novel therapeutic approach for IPF.
[Mh] Termos MeSH primário: Canais de Potássio Ativados por Cálcio de Condutância Intermediária/antagonistas & inibidores
Fibrose Pulmonar/metabolismo
[Mh] Termos MeSH secundário: Acetamidas/farmacologia
Animais
Bleomicina
Complacência (Medida de Distensibilidade)
Modelos Animais de Doenças
Fibroblastos/efeitos dos fármacos
Fibroblastos/metabolismo
Fibroblastos/patologia
Imunofluorescência
Canais de Potássio Ativados por Cálcio de Condutância Intermediária/metabolismo
Pulmão/efeitos dos fármacos
Pulmão/metabolismo
Pulmão/patologia
Pulmão/fisiopatologia
Fibrose Pulmonar/patologia
Fibrose Pulmonar/fisiopatologia
Testes de Função Respiratória
Ovinos
Compostos de Tritil/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Acetamides); 0 (Intermediate-Conductance Calcium-Activated Potassium Channels); 0 (Trityl Compounds); 11056-06-7 (Bleomycin); TS6G201A6Q (senicapoc)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170630
[Lr] Data última revisão:
170630
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170107
[St] Status:MEDLINE
[do] DOI:10.1165/rcmb.2016-0092OC



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