To evaluate the effect of proteolytic enzymes on the absorption of insulin in the buccal mucosa, the trichloroacetic acid (TCA) method was used to estimate the degradation of insulin under different conditions in the ...To evaluate the effect of proteolytic enzymes on the absorption of insulin in the buccal mucosa, the trichloroacetic acid (TCA) method was used to estimate the degradation of insulin under different conditions in the buccal mucosal homogenates. In vivo experiments estimating the enhancement of hypoglycaemic effect by enzyme inhibitors were also conducted. The results showed that proteolytic enzymes in the buccal mucosa were less active than in the intestine. Bacitracin, aprotinin and sodium deoxycholate could inhibit the degradation of insulin in the buccal mucosal homogenates. The degradation of insulin in buccal mucosal homogenates of normal hamsters was smaller than that of diabetic hamsters. In vivo experiments of hypoglycaemia supported the in vitro results. When given buccally, bacitracin, aprotinin and sodium deoxycholate could increase the relative pharmacological bioavailability of insulin. When co-administered with aprotinin(0.1%), bacitracin(0.5%) and sodium deoxycholate(5%), the relative pharmacological bioavailabilities of insulin were 4.84%, 6.60% and 14.95% respectively. The in vitro and in vivo results suggest that proteolytic enzymes are present in the buccal mucosa, which limit absorption of insulin. Co-administration with some enzyme inhibitors can improve the bioavailability of insulin via buccal delivery and sodium deoxycholte is more efficient than some enzyme inhibitors used for improving buccal absorption.展开更多
AIM: Ischemia/reperfusion (I/R) injury is one of the major obstacles for intestinal transplantation (ITx). Urinary trypsin inhibitor (Ulinastatin, UTI) suppresses proteases and stabilizes lysosomal membranes. We suppo...AIM: Ischemia/reperfusion (I/R) injury is one of the major obstacles for intestinal transplantation (ITx). Urinary trypsin inhibitor (Ulinastatin, UTI) suppresses proteases and stabilizes lysosomal membranes. We supposed that Ulinastatin would diminish I/R injury of intestinal graft.METHODS: UTI- treated group and untreated control group were investigated by histological assessment at 1.5, 4, 24, and 72 h after ITx. Myeloperoxidase (MPO)activity was used as the activity of neutrophils, and malondialdehyde (MDA) was used as an index of lipid peroxidation. TNFα and i-NOS mRNA expression in graft tissue were measured by semi-quantitative RT-PCR.CD11b+ Gr1+ cells in graft lamina propria were analyzed by flow cytometry.RESULTS: Histological scores of the graft showed that the tissue injury was markedly attenuated by UTI treatment at different time points after ITx, with reduced MPO and MDA value in the grafts. The expression of TNFα and i-NOS mRNA was profoundly inhibited, while the infiltration of CD11b+ Gr1+ cells into the intestinal graft was decreased in UTI group.CONCLUSION: Urinary trypsin inhibitor attenuates I/R injury in mouse intestinal transplantation by reducing monocytes infiltration and down-regulation of TNFα and i-NOS mRNA expression.展开更多
目的评估尿金属蛋白酶组织抑数因子-2(TIMP-2)与胰岛素样生长因子结合蛋白-7(IGFB-P7)的乘积对心脏手术患者术后急性肾损伤(AKI)的早期预测价值。方法检索EMBASE、Pubmed、Cochrane、Web of Science、CNKI、Sinomed、万方数据库。限定...目的评估尿金属蛋白酶组织抑数因子-2(TIMP-2)与胰岛素样生长因子结合蛋白-7(IGFB-P7)的乘积对心脏手术患者术后急性肾损伤(AKI)的早期预测价值。方法检索EMBASE、Pubmed、Cochrane、Web of Science、CNKI、Sinomed、万方数据库。限定时间为2014年2月1日年至2018年2月1日。检索得到相关文献共138篇,经过严格的纳入排除,筛选文献并提取所需数据。按QUADAS-2质量评价标准评估文献。使用Meta-DiSc1.4软件进行数据分析,利用Stata12.0进行发表偏倚的检测。通过亚组分析、Meta回归、敏感性分析识别及处理异质性来源。结果最终筛选出文献10篇,总病例数659例,共发生AKI202例,未发生AKI457例。行异质性检测,发现Spearman相关系数为0.067(P=0.855),提示阈值效应所致异质性不明显。合并诊断比值比I2<25%,提示研究间非阈值效应不存在异质性。合并效应量显示尿[TIMP-2]×[IGFBP-7]预测心脏术后患者早期AKI的合并灵敏度为0.72(95%CI0.66~0.78)、特异度0.72(95%CI0.68~0.76)、诊断比值比8.12(95%CI5.46~12.08)、汇总AUC=0.8021,表明尿[TIMP-2]×[IGFBP-7]对心脏术后患者早期AKI有较好的预测价值。检测发表偏倚,提示发表偏倚不明显。行亚组分析显示样本量大小可能是异质性来源。Meta回归结果未提示明显异质性,敏感性分析显示本分析的稳健性尚可。结论尿[TIMP-2]×[IGFBP-7]对早期预测心脏术后患者AKI具有重要的临床价值,但仍需要进一步大样本临床实验证实。展开更多
文摘To evaluate the effect of proteolytic enzymes on the absorption of insulin in the buccal mucosa, the trichloroacetic acid (TCA) method was used to estimate the degradation of insulin under different conditions in the buccal mucosal homogenates. In vivo experiments estimating the enhancement of hypoglycaemic effect by enzyme inhibitors were also conducted. The results showed that proteolytic enzymes in the buccal mucosa were less active than in the intestine. Bacitracin, aprotinin and sodium deoxycholate could inhibit the degradation of insulin in the buccal mucosal homogenates. The degradation of insulin in buccal mucosal homogenates of normal hamsters was smaller than that of diabetic hamsters. In vivo experiments of hypoglycaemia supported the in vitro results. When given buccally, bacitracin, aprotinin and sodium deoxycholate could increase the relative pharmacological bioavailability of insulin. When co-administered with aprotinin(0.1%), bacitracin(0.5%) and sodium deoxycholate(5%), the relative pharmacological bioavailabilities of insulin were 4.84%, 6.60% and 14.95% respectively. The in vitro and in vivo results suggest that proteolytic enzymes are present in the buccal mucosa, which limit absorption of insulin. Co-administration with some enzyme inhibitors can improve the bioavailability of insulin via buccal delivery and sodium deoxycholte is more efficient than some enzyme inhibitors used for improving buccal absorption.
基金Supported by the Health Scientific Grant 2002 of Zhejiang Province,China. No. 2002ZX021
文摘AIM: Ischemia/reperfusion (I/R) injury is one of the major obstacles for intestinal transplantation (ITx). Urinary trypsin inhibitor (Ulinastatin, UTI) suppresses proteases and stabilizes lysosomal membranes. We supposed that Ulinastatin would diminish I/R injury of intestinal graft.METHODS: UTI- treated group and untreated control group were investigated by histological assessment at 1.5, 4, 24, and 72 h after ITx. Myeloperoxidase (MPO)activity was used as the activity of neutrophils, and malondialdehyde (MDA) was used as an index of lipid peroxidation. TNFα and i-NOS mRNA expression in graft tissue were measured by semi-quantitative RT-PCR.CD11b+ Gr1+ cells in graft lamina propria were analyzed by flow cytometry.RESULTS: Histological scores of the graft showed that the tissue injury was markedly attenuated by UTI treatment at different time points after ITx, with reduced MPO and MDA value in the grafts. The expression of TNFα and i-NOS mRNA was profoundly inhibited, while the infiltration of CD11b+ Gr1+ cells into the intestinal graft was decreased in UTI group.CONCLUSION: Urinary trypsin inhibitor attenuates I/R injury in mouse intestinal transplantation by reducing monocytes infiltration and down-regulation of TNFα and i-NOS mRNA expression.
文摘目的评估尿金属蛋白酶组织抑数因子-2(TIMP-2)与胰岛素样生长因子结合蛋白-7(IGFB-P7)的乘积对心脏手术患者术后急性肾损伤(AKI)的早期预测价值。方法检索EMBASE、Pubmed、Cochrane、Web of Science、CNKI、Sinomed、万方数据库。限定时间为2014年2月1日年至2018年2月1日。检索得到相关文献共138篇,经过严格的纳入排除,筛选文献并提取所需数据。按QUADAS-2质量评价标准评估文献。使用Meta-DiSc1.4软件进行数据分析,利用Stata12.0进行发表偏倚的检测。通过亚组分析、Meta回归、敏感性分析识别及处理异质性来源。结果最终筛选出文献10篇,总病例数659例,共发生AKI202例,未发生AKI457例。行异质性检测,发现Spearman相关系数为0.067(P=0.855),提示阈值效应所致异质性不明显。合并诊断比值比I2<25%,提示研究间非阈值效应不存在异质性。合并效应量显示尿[TIMP-2]×[IGFBP-7]预测心脏术后患者早期AKI的合并灵敏度为0.72(95%CI0.66~0.78)、特异度0.72(95%CI0.68~0.76)、诊断比值比8.12(95%CI5.46~12.08)、汇总AUC=0.8021,表明尿[TIMP-2]×[IGFBP-7]对心脏术后患者早期AKI有较好的预测价值。检测发表偏倚,提示发表偏倚不明显。行亚组分析显示样本量大小可能是异质性来源。Meta回归结果未提示明显异质性,敏感性分析显示本分析的稳健性尚可。结论尿[TIMP-2]×[IGFBP-7]对早期预测心脏术后患者AKI具有重要的临床价值,但仍需要进一步大样本临床实验证实。
