RESUMO
According to the three-dimensional (3D) complex structure of (hIL-6â hIL-6Râ gp 130)2 and the binding orientation of hIL-6, three compounds with high affinity to hIL-6R and bioactivity to block hIL-6 in vitro were screened theoretically from the chemical databases, including 3D-Available Chemicals Directory (ACD) and MDL Drug Data Report (MDDR), by means of the computer-guided virtual screening method. Using distance geometry, molecular modeling and molecular dynamics trajectory analysis methods, the binding mode and binding energy of the three compounds were evaluated theoretically. Enzyme-linked immunosorbent assay analysis demonstrated that all the three compounds could block IL-6 binding to IL-6R specifically. However, only compound 1 could effectively antagonize the function of hIL-6 and inhibit the proliferation of XG-7 cells in a dose-dependent manner, whereas it showed no cytotoxicity to SP2/0 or L929 cells. These data demonstrated that the compound 1 could be a promising candidate of hIL-6 antagonist.
Assuntos
Bases de Dados de Compostos Químicos , Avaliação Pré-Clínica de Medicamentos , Interleucina-6/antagonistas & inibidores , Proliferação de Células/efeitos dos fármacos , Humanos , Modelos Moleculares , Estrutura Molecular , Células Tumorais CultivadasRESUMO
BACKGROUND AND OBJECTIVES: To evaluate the effects of subtotal colectomy combined with the modified Duhamel procedure on mixed constipation. METHODS: A total of 16 female patients with mixed constipation were enrolled and underwent subtotal colectomy combined with the modified Duhamel procedure under laparoscopy from April 2010 to April 2012. Before surgery, physical examinations such as the gastrointestinal transit test, barium enema, and defecography were performed for all the patients. After surgical treatment, 2-year follow-up was performed using questionnaires to assess the effect of treatment. RESULTS: All 16 cases were treated successfully, with a mean operation time of 230 minutes (range, 180-290 minutes). No intraoperative or postoperative complications were found, and no deaths occurred. Constipation and relevant symptoms were relieved, and all patients were satisfied with their quality of life. The gastrointestinal quality-of-life score was significantly increased 6 months postoperatively (mean, 102) compared with preoperatively (mean, 75). CONCLUSION: Subtotal colectomy combined with the modified Duhamel procedure under laparoscopy is effective and safe for the treatment of mixed constipation.