RESUMO
OBJECTIVE: Matrix metalloproteinases are inflammatory biomarkers involved in carotid plaque instability. Our objective was to analyze the inflammatory activity of plasma and carotid plaque MMP-8 and MMP-9 after intravenous administration of hydrocortisone. METHODS: The study included 22 patients with stenosis ≥ 70% in the carotid artery (11 symptomatic and 11 asymptomatic) who underwent carotid endarterectomy. The patients were divided into two groups: Control Group - hydrocortisone was not administered, and Group 1 - 500 mg intravenous hydrocortisone was administered during anesthetic induction. Plasma levels of MMP-8 and MMP-9 were measured preoperatively (24 hours before carotid endarterectomy) and at 1 hour, 6 hours and 24 hours after carotid endarterectomy. In carotid plaque, tissue levels of MMP-8 and MMP-9 were measured. RESULTS: Group 1 showed increased serum levels of MMP- 8 (994.28 pg/ml and 408.54 pg/ml, respectively; P=0.045) and MMP-9 (106,656.34 and 42,807.69 respectively; P=0.014) at 1 hour after carotid endarterectomy compared to the control group. Symptomatic patients in Group 1 exhibited lower tissue concentration of MMP-8 in comparison to the control group (143.89 pg/ml and 1317.36 respectively; P=0.003). There was a correlation between preoperative MMP-9 levels and tissue concentrations of MMP-8 (P=0.042) and MMP-9 (P=0.019) between symptomatic patients in the control group. CONCLUSION: Hydrocortisone reduces the concentration of MMP- 8 in carotid plaque, especially in symptomatic patients. There was an association between systemic and tissue inflammation.
Assuntos
Anti-Inflamatórios/farmacologia , Artéria Carótida Interna/efeitos dos fármacos , Estenose das Carótidas/cirurgia , Hidrocortisona/farmacologia , Metaloproteinase 8 da Matriz/efeitos dos fármacos , Metaloproteinase 9 da Matriz/efeitos dos fármacos , Idoso , Idoso de 80 Anos ou mais , Anti-Inflamatórios/uso terapêutico , Biomarcadores/análise , Artéria Carótida Interna/enzimologia , Estenose das Carótidas/enzimologia , Endarterectomia das Carótidas , Feminino , Humanos , Hidrocortisona/uso terapêutico , Masculino , Metaloproteinase 8 da Matriz/análise , Metaloproteinase 9 da Matriz/análise , Pessoa de Meia-Idade , Período Pós-Operatório , Valores de Referência , Estatísticas não Paramétricas , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Simvastatin is a cholesterol-lowering drug whose pleiotropic effects may have a therapeutic impact on bone. This study evaluates the effect of simvastatin on rats subjected to experimental periodontal disease. METHODS: Periodontitis was induced by ligature placement around the maxillary left second molar of rats for 11 days. Groups of six animals received oral saline or simvastatin (3, 10, and 30 mg/kg/day) until sacrifice on day 11. Alveolar bone loss was determined by macroscopic and histologic examination. The serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total alkaline phosphatase (TAP) were evaluated. Gingival myeloperoxidase activity and gingival levels of interleukin-1ß (IL-1ß), tumor necrosis factor-α, IL-10, reduced glutathione, malonaldehyde, and nitrate/nitrite were analyzed to investigate oxidative stress and inflammation. Expression of inducible nitric oxide synthase (iNOS), matrix metalloproteinases 1 and 8 (MMP-1 and -8), bone morphogenetic protein-2 (BMP-2), receptor activator of nuclear factor κB (RANK), RANK ligand (RANKL), and osteoprotegerin (OPG) were also investigated by immunohistochemistry to assess bone turnover and metabolism. Immunofluorescence microscopy was used to confirm the expression of RANKL in rats' maxillae. RESULTS: Treatment with simvastatin improved alveolar bone loss within all of the parameters studied, thus demonstrating anti-inflammatory and antioxidant activity. Simvastatin reduced expression of iNOS, MMP-1 and -8, RANK, and RANKL and increased BMP-2 and OPG levels in the periodontal tissue. Simvastatin (30 mg/kg) increased TAP activity on day 11 compared with the saline group. No differences were found in the levels of AST and ALT in any of the groups studied. CONCLUSION: The present data suggest that simvastatin prevents inflammatory bone resorption in experimental periodontitis, which may be mediated by its anti-inflammatory and antioxidant properties.
Assuntos
Anti-Inflamatórios/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Periodontite/prevenção & controle , Sinvastatina/uso terapêutico , Alanina Transaminase/efeitos dos fármacos , Fosfatase Alcalina/efeitos dos fármacos , Perda do Osso Alveolar/prevenção & controle , Animais , Antioxidantes/uso terapêutico , Aspartato Aminotransferases/efeitos dos fármacos , Proteína Morfogenética Óssea 2/efeitos dos fármacos , Feminino , Gengiva/efeitos dos fármacos , Glutationa/efeitos dos fármacos , Interleucina-10/análise , Interleucina-1beta/efeitos dos fármacos , Malondialdeído/análise , Metaloproteinase 1 da Matriz/efeitos dos fármacos , Metaloproteinase 8 da Matriz/efeitos dos fármacos , Nitratos/análise , Óxido Nítrico Sintase Tipo II/efeitos dos fármacos , Nitritos/análise , Osteoprotegerina/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Peroxidase/efeitos dos fármacos , Ligante RANK/efeitos dos fármacos , Ratos , Ratos Wistar , Receptor Ativador de Fator Nuclear kappa-B/efeitos dos fármacos , Fator de Necrose Tumoral alfa/efeitos dos fármacosRESUMO
OBJECTIVE: To compare the levels of interleukin (IL)-1beta, IL-6, and matrix metalloproteinase (MMP)-8 in the vaginal secretions of pregnant women with a positive fetal fibronectin (fFN) test result with or without asymptomatic bacterial vaginosis (BV) before and after treatment with oral clindamycin. METHODS: A prospective cohort study was conducted among 43 pregnant women with a positive fFN test result. All patients were treated with clindamycin, and the pre- and post-treatment levels of IL-1beta, IL-6, and MMP-8 were compared. RESULTS: Before treatment, levels of IL-1beta and MMP-8 were significantly higher in women with BV compared with women without BV (P<0.05). Vaginal levels of IL-1beta and IL-6, but not MMP-8, decreased after treatment in pregnant women with BV. CONCLUSIONS: The inability of clindamycin to decrease MMP-8 vaginal levels may explain why it is ineffective in reducing preterm birth in pregnant women with positive fFN and BV.