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Métodos Terapêuticos e Terapias MTCI
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1.
2.
Atherosclerosis ; 236(2): 277-85, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25108619

RESUMO

OBJECTIVE: Excessive neointima formation often occurs after arterial injury. Interleukin-1ß (IL-1ß) is a potent pleiotropic cytokine that has been shown to regulate neointimal proliferation. We investigated the effects of the IL-1ß modulator gevokizumab in a rat carotid denudation model. METHODS: Sprague-Dawley rats were subjected to balloon denudation of the right carotid artery and were then randomized to receive a single subcutaneous infusion immediately after balloon injury of saline (control group, n = 13) or gevokizumab (gevokizumab groups, n = 15 in each group: 1, 10 and 50 mg/kg). We evaluated the treatment effects on carotid intima-media thickness (IMT) using ultrasonography, on endothelial regrowth using Evans Blue staining and on inflammatory response using histology. We also assessed the effects of IL-1ß and gevokizumab on human umbilical vein endothelial cells (HUVEC) and rat smooth muscle cells. RESULTS: We found that carotid IMT, in the proximal part of the denuded artery at day 28, was decreased by gevokizumab 1 mg/kg compared with controls. Neointima area and the intima/media area ratio were both reduced in the gevokizumab 1 mg/kg-treated group. Gevokizumab at the 1 mg/kg dose also improved endothelial regrowth. No effect was observed with gevokizumab 10 or 50 mg/kg. Gevokizumab also decreased the inflammatory effect of IL-1ß in in vitro cell experiments and protected HUVECs from IL-1ß's deleterious effects on cell migration, apoptosis and proliferation. CONCLUSION: A single administration of gevokizumab 1 mg/kg improves endothelial regrowth and reduces neointima formation in rats following carotid denudation, at least in part through its beneficial effects on endothelial cells.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Lesões das Artérias Carótidas/tratamento farmacológico , Neointima/prevenção & controle , Animais , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/farmacologia , Aorta/citologia , Apoptose/efeitos dos fármacos , Lesões das Artérias Carótidas/diagnóstico por imagem , Lesões das Artérias Carótidas/patologia , Artéria Carótida Primitiva/diagnóstico por imagem , Artéria Carótida Primitiva/patologia , Espessura Intima-Media Carotídea , Divisão Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/patologia , Endotélio Vascular/fisiopatologia , Perfilação da Expressão Gênica , Células Endoteliais da Veia Umbilical Humana , Humanos , Interleucina-1beta/farmacologia , Interleucina-1beta/fisiologia , Masculino , Miócitos de Músculo Liso/efeitos dos fármacos , Neointima/tratamento farmacológico , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Regeneração , Vasculite/tratamento farmacológico , Vasculite/prevenção & controle
4.
J Surg Res ; 162(1): 26-32, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20421114

RESUMO

OBJECTIVE: This study investigated the effects of ginsenoside Rb1 (Rb1) on injury-induced intimal hyperplasia in ApoE knock out (ApoE -/-) mice. We also examined the value of an ultrasound micro-image system in dynamic monitoring of lumen diameter and flow velocity. METHODS: After guide wire injury of the distal left common carotid artery (CCA), ApoE-/- mice were treated with intraperitoneal infusion of normal saline (NS), homocysteine (Hcy), ginsenoside Rb1 (Rb1), or Hcy+Rb1 for 4 wk. Bilateral CCA luminal diameters and flow velocities were measured with an ultrasound micro-image system before surgery and weekly afterwards. Following the final ultrasound, CCAs were harvested and analyzed for intima-medium thickness ratios. RESULTS: Progressive reduction in luminal diameters and increase in flow velocity of the injured left distal CCA segment were observed using ultrasound micro-imaging system in all groups compared with the relatively stable left proximal CCA and right CCA. The NS and Hcy groups had significantly higher degree of diameter reduction compared with the Rb1 and Rb1+Hcy groups. The ultrasound findings were consistent with histology analyses at 4 wk post-op. CONCLUSIONS: The study suggested that Rb1 attenuated the effects of Hcy on injured carotid arteries of ApoE -/- mice. The study also showed that ultrasound micro-image system was a reliable tool in monitoring luminal reduction after injury in a murine model. This study establishes a fundamental step of in vivo monitoring of the therapeutic effects of agents in a murine model without sacrificing the animals.


Assuntos
Lesões das Artérias Carótidas/tratamento farmacológico , Ginsenosídeos/uso terapêutico , Homocisteína/uso terapêutico , Fitoterapia , Túnica Íntima/efeitos dos fármacos , Animais , Lesões das Artérias Carótidas/diagnóstico por imagem , Lesões das Artérias Carótidas/patologia , Ginsenosídeos/farmacologia , Oclusão de Enxerto Vascular/prevenção & controle , Homocisteína/farmacologia , Hiperplasia/prevenção & controle , Camundongos , Camundongos Knockout , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Túnica Íntima/diagnóstico por imagem , Túnica Íntima/patologia , Ultrassonografia
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