RESUMO
BACKGROUND: Intra-abdominal adhesions and their complications following abdominal surgery are serious problems, with an incidence of 67-93%. Prevention of peritoneal adhesion formation may eliminate the need for surgical intervention, decreasing complications, morbidity, and cost. Bevacizumab is a recombinant monoclonal antibody which specifically binds vascular endothelial growth factor, an important cytokine in adhesion formation, and neutralizes its biological activity. We developed an experimental model in rats to determine the effect of bevacizumab in preventing adhesion formation and analyzed its effect both micro- and macroscopically. METHODS: We used 32. Wistar rats randomly divided into two groups: Group A (control) and Group B (bevacizumab), with 16 rats each. A modified cecum abrasion model was developed; 0.9% NaCl solution was administered intraperitoneally to Group A and bevacizumab to Group B. On day 15, adhesion formation was evaluated both macro- and microscopically. RESULTS: Both micro- and macroscopic adhesion grades in Group B were significantly lower than those of control Group A; macroscopic grades were 2.69 ± 0.95 and 0.69 ± 0.8, and microscopic grades were 2.25 ± 1.06 and 0.5 ± 0.52 for Groups A and B, respectively. CONCLUSIONS: Bevacizumab was effective in preventing intraperitoneal adhesion formation in our study; however, its inhibitory effects on embryogenesis and the hematopoietic, endocrine, and immune systems may limit its clinical use.
Assuntos
Inibidores da Angiogênese/administração & dosagem , Bevacizumab/administração & dosagem , Complicações Pós-Operatórias/prevenção & controle , Aderências Teciduais/prevenção & controle , Inibidores da Angiogênese/farmacologia , Animais , Bevacizumab/farmacologia , Modelos Animais de Doenças , Feminino , Injeções Intraperitoneais , Ratos , Ratos Wistar , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
ABSTRACT BACKGROUND: Increased angiogenetic activity in inflammatory bowel disease (IBD) has been shown in previous studies. The aim of this study was to evaluate the relationship of serum vascular endothelial growth factor (VEGF) and endostatin levels with clinical features and mucosal expression in patients with ulcerative colitis (UC). DESIGN AND SETTING: Cross-sectional analytical study conducted in a tertiary-level public hospital. METHODS: Serum VEGF and endostatin levels were determined in 82 individuals: 39 with UC, 28 with irritable bowel syndrome (IBS) and 15 healthy controls (HCs), using enzyme-linked immunosorbent assays (ELISA). VEGF and endostatin expressions were studied using immunohistochemistry (IHC). RESULTS: Mean serum VEGF and endostatin levels were significantly higher in patients with UC than in patients with IBS and in HCs (511.9 ± 377.5 pg/ml, 305.0 ± 121.42 pg/ml and 36.1 ± 40.6 pg/ml; P = 0.001 for VEGF; and 155.50 ± 59.8 ng/ml, 116.9 ± 23.8 ng/ml and 102.2 ± 22.4 ng/ml; P < 0.001 for endostatin, respectively). There was a positive correlation between serum VEGF and endostatin levels (r = 0.422; P < 0.01). Mean H-scores for VEGF expression were higher in the active UC group than in the inactive UC and IBS groups, in the stroma, endothelium and epithelium. Mean H-scores for endostatin expression were higher in the active UC group than in the inactive UC and IBS groups, in the stroma and endothelium. There was no endostatin expression in the epithelium. CONCLUSION: Increased endostatin appears to be a defensive reaction to increased VEGF in patients with UC.
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Colite Ulcerativa/sangue , Síndrome do Intestino Irritável/sangue , Endostatinas/sangue , Fatores de Crescimento do Endotélio Vascular/metabolismo , Mucosa Intestinal/irrigação sanguínea , Ensaio de Imunoadsorção Enzimática , Colite Ulcerativa/patologia , Estudos de Casos e Controles , Estudos Transversais , Síndrome do Intestino Irritável/patologia , Fatores de Crescimento do Endotélio Vascular/sangue , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologiaRESUMO
BACKGROUND: Increased angiogenetic activity in inflammatory bowel disease (IBD) has been shown in previous studies. The aim of this study was to evaluate the relationship of serum vascular endothelial growth factor (VEGF) and endostatin levels with clinical features and mucosal expression in patients with ulcerative colitis (UC). DESIGN AND SETTING: Cross-sectional analytical study conducted in a tertiary-level public hospital. METHODS: Serum VEGF and endostatin levels were determined in 82 individuals: 39 with UC, 28 with irritable bowel syndrome (IBS) and 15 healthy controls (HCs), using enzyme-linked immunosorbent assays (ELISA). VEGF and endostatin expressions were studied using immunohistochemistry (IHC). RESULTS: Mean serum VEGF and endostatin levels were significantly higher in patients with UC than in patients with IBS and in HCs (511.9 ± 377.5 pg/ml, 305.0 ± 121.42 pg/ml and 36.1 ± 40.6 pg/ml; P = 0.001 for VEGF; and 155.50 ± 59.8 ng/ml, 116.9 ± 23.8 ng/ml and 102.2 ± 22.4 ng/ml; P < 0.001 for endostatin, respectively). There was a positive correlation between serum VEGF and endostatin levels (r = 0.422; P < 0.01). Mean H-scores for VEGF expression were higher in the active UC group than in the inactive UC and IBS groups, in the stroma, endothelium and epithelium. Mean H-scores for endostatin expression were higher in the active UC group than in the inactive UC and IBS groups, in the stroma and endothelium. There was no endostatin expression in the epithelium. CONCLUSION: Increased endostatin appears to be a defensive reaction to increased VEGF in patients with UC.