Over the past decades evidence has been accumulating that intestinal barrier integrity loss plays a key role in the development and perpetuation of a variety of disease states including inflammatory bowel disease and ...Over the past decades evidence has been accumulating that intestinal barrier integrity loss plays a key role in the development and perpetuation of a variety of disease states including inflammatory bowel disease and celiac disease,and is a key player in the onset of sepsis and multiple organ failure in situations of intestinal hypoperfusion,including trauma and major surgery.Insight into gut barrier integrity and function loss is important to improve our knowledge on disease etiology and pathophysiology and contributes to early detection and/or secondary prevention of disease.A variety of tests have been developed to assess intestinal epithelial cell damage,intestinal tight junction status and consequences of intestinal barrier integrity loss,i.e.increased intestinal permeability.This review discusses currently available methods for evaluating loss of human intestinal barrier integrity and function.展开更多
The intestinal barrier is important in preventing translocation of bacteria, toxins and antigens from the lumen of the gut into the body. Enhanced permeability, or gut leakiness, has been associated with different dis...The intestinal barrier is important in preventing translocation of bacteria, toxins and antigens from the lumen of the gut into the body. Enhanced permeability, or gut leakiness, has been associated with different diseases. Probiotics can, strain-specifically, improve the epithelial barrier function. However, so far most researches have used cell lines or animal models due to the difficulty of measuring the effects of products on the epithelial barrier function in vivo in humans. Here a systematic literature search was performed to find articles addressing the effects of probiotics on the barrier function in human trials. The Pubmed database was searched (January 2013) to identify human in vivo studies with probiotic products in which parameters for epithelial barrier function were measured. In total 29 studies were identified, but patients, bacterial characteristics and methods to measure intestinal barrier function caused large heterogeneity among these studies. About half of the studies showed positive results of probiotics on the epithelial barrier function, indicating a clear potential of probiotics in this field. In a case series of 14 patients using Ecologica825, a probiotic food supplement with known effect on epithelial barrier function, different markers of intestinal integrity improved significantly. Further studies in this field should consider strain(s), dose and duration of the probiotic supplementation as well as the markers used to measure epithelial barrier function. Besides the lactulose/mannitol test, zonulin and α1-antitrypsin might be valuable markers to measure epithelial barrier function in future experiments.展开更多
AIM To assess intestinal barrier function during human intestinal ischemia and reperfusion(IR).METHODS In a human experimental model,6 cm of jejunum was selectively exposed to 30 min of ischemia(I) followed by 30 and ...AIM To assess intestinal barrier function during human intestinal ischemia and reperfusion(IR).METHODS In a human experimental model,6 cm of jejunum was selectively exposed to 30 min of ischemia(I) followed by 30 and 120 min of reperfusion(R). A sham procedure was also performed. Blood and tissue was sampled at all-time points. Functional barrier function was assessed using dual-sugar absorption tests with lactulose(L) and rhamnose(R). Plasma concentrations of citrulline,an amino acid described as marker for enterocyte function were measured as marker of metabolic enterocytes restoration. Damage to the epithelial lining was assessed by immunohistochemistry for tight junctions( TJs),by plasma marker for enterocytes damage(I-FABP) and analyzed by electron microscopy(EM) using lanthanum nitrate as an electrondense marker.RESULTS Plasma L/R ratio's were significantly increased after 30 min of ischemia(30 I) followed by 30 min of reperfusion(30 R) compared to control(0.75 ± 0.10 vs 0.20 ± 0.09,P < 0.05). At 120 min of reperfusion(120 R),ratio's normalized(0.17 ± 0.06) and were not significantly different from control. Plasma levels of I-FABP correlated with plasma L/R ratios measured at the same time points(correlation: 0.467,P < 0.01). TJs staining shows distortion of staining at 30 I. An intact lining of TJs was again observed at 30 I120 R. Electron microscopy analysis revealed disrupted TJs after 30 I with paracellular leakage of lanthanum nitrate,which restored after 30 I120 R. Furthermore,citrulline concentrations closely paralleled the histological perturbations during intestinal IR.CONCLUSION This study directly correlates histological data with intestinal permeability tests,revealing that the human gut has the ability of to withstand short episodes of ischemia,with morphological and functional recovery of the intestinal barrier within 120 min of reperfusion.展开更多
目的:通过建立表皮通透屏障功能障碍模型—“血虚风燥型”慢性湿疹样病变豚鼠模型,研究针灸治疗对皮肤表皮通透屏障功能的作用机制。方法:普通级纯白色雄性豚鼠32只,随机分为空白组8只和造模组24只,采用2,4-二硝基氯苯(2,4-dinitrochlor...目的:通过建立表皮通透屏障功能障碍模型—“血虚风燥型”慢性湿疹样病变豚鼠模型,研究针灸治疗对皮肤表皮通透屏障功能的作用机制。方法:普通级纯白色雄性豚鼠32只,随机分为空白组8只和造模组24只,采用2,4-二硝基氯苯(2,4-dinitrochlorobenzene,DNCB)诱导法造模,建立“血虚风燥”湿疹样病变豚鼠模型,随机数字表法分为模型组(8只)、对照组(8只)、针灸组(8只)。针灸组取双肺俞、双脾俞、双膈俞、双曲池、双足三里、双血海,双三阴交,针刺以平补平泻为主,留针15min,治疗疗程为两周。对照组给予氯雷他定片,每日一次,连续灌胃两周。观察豚鼠皮肤组织形态学改变情况、多功能皮肤测试仪检测皮肤角质层含水量(Water content of stratum corneum,WCSC)及经表皮水分流失量(Trans-epidermal water loss,TEWL)、酶联免疫法(Enzyme-Linked ImmunoSorbent Assay,ELISA)测定血清免疫球蛋白E(IgE)、白细胞介素-4(IL-4)、白细胞介素-17(IL-17)浓度。结果:与模型对照组比较,针灸组皮损评分显著降低(P<0.01),皮肤角质层水分含量(WCSC)明显升高(P<0.01),经表皮水分流失量(TEWL)显著降低(P<0.01),血清IgE、IL-17浓度显著降低(P<0.01),IL-4浓度显著升高(P<0.01)。结论:在“血虚风燥型”慢性湿疹样皮炎表皮通透屏障功能障碍豚鼠模型实验中,针灸通过改善表皮水分调节,改善细胞因子表达量,发挥全身免疫作用,修复损伤的表皮通透屏障功能,进一步改善“皮毛微环境”状态。展开更多
文摘Over the past decades evidence has been accumulating that intestinal barrier integrity loss plays a key role in the development and perpetuation of a variety of disease states including inflammatory bowel disease and celiac disease,and is a key player in the onset of sepsis and multiple organ failure in situations of intestinal hypoperfusion,including trauma and major surgery.Insight into gut barrier integrity and function loss is important to improve our knowledge on disease etiology and pathophysiology and contributes to early detection and/or secondary prevention of disease.A variety of tests have been developed to assess intestinal epithelial cell damage,intestinal tight junction status and consequences of intestinal barrier integrity loss,i.e.increased intestinal permeability.This review discusses currently available methods for evaluating loss of human intestinal barrier integrity and function.
文摘The intestinal barrier is important in preventing translocation of bacteria, toxins and antigens from the lumen of the gut into the body. Enhanced permeability, or gut leakiness, has been associated with different diseases. Probiotics can, strain-specifically, improve the epithelial barrier function. However, so far most researches have used cell lines or animal models due to the difficulty of measuring the effects of products on the epithelial barrier function in vivo in humans. Here a systematic literature search was performed to find articles addressing the effects of probiotics on the barrier function in human trials. The Pubmed database was searched (January 2013) to identify human in vivo studies with probiotic products in which parameters for epithelial barrier function were measured. In total 29 studies were identified, but patients, bacterial characteristics and methods to measure intestinal barrier function caused large heterogeneity among these studies. About half of the studies showed positive results of probiotics on the epithelial barrier function, indicating a clear potential of probiotics in this field. In a case series of 14 patients using Ecologica825, a probiotic food supplement with known effect on epithelial barrier function, different markers of intestinal integrity improved significantly. Further studies in this field should consider strain(s), dose and duration of the probiotic supplementation as well as the markers used to measure epithelial barrier function. Besides the lactulose/mannitol test, zonulin and α1-antitrypsin might be valuable markers to measure epithelial barrier function in future experiments.
基金Supported by Dutch Digestive Foundation(MLDS grant WO10-57 to Dejong CHC and Lenaerts K)and MLDS Career development grant CDG13-14 to Derikx JPM)the Netherlands Organisation for Scientific Research(Rubicon grant 2013/07161/ALW to Grootjans J)
文摘AIM To assess intestinal barrier function during human intestinal ischemia and reperfusion(IR).METHODS In a human experimental model,6 cm of jejunum was selectively exposed to 30 min of ischemia(I) followed by 30 and 120 min of reperfusion(R). A sham procedure was also performed. Blood and tissue was sampled at all-time points. Functional barrier function was assessed using dual-sugar absorption tests with lactulose(L) and rhamnose(R). Plasma concentrations of citrulline,an amino acid described as marker for enterocyte function were measured as marker of metabolic enterocytes restoration. Damage to the epithelial lining was assessed by immunohistochemistry for tight junctions( TJs),by plasma marker for enterocytes damage(I-FABP) and analyzed by electron microscopy(EM) using lanthanum nitrate as an electrondense marker.RESULTS Plasma L/R ratio's were significantly increased after 30 min of ischemia(30 I) followed by 30 min of reperfusion(30 R) compared to control(0.75 ± 0.10 vs 0.20 ± 0.09,P < 0.05). At 120 min of reperfusion(120 R),ratio's normalized(0.17 ± 0.06) and were not significantly different from control. Plasma levels of I-FABP correlated with plasma L/R ratios measured at the same time points(correlation: 0.467,P < 0.01). TJs staining shows distortion of staining at 30 I. An intact lining of TJs was again observed at 30 I120 R. Electron microscopy analysis revealed disrupted TJs after 30 I with paracellular leakage of lanthanum nitrate,which restored after 30 I120 R. Furthermore,citrulline concentrations closely paralleled the histological perturbations during intestinal IR.CONCLUSION This study directly correlates histological data with intestinal permeability tests,revealing that the human gut has the ability of to withstand short episodes of ischemia,with morphological and functional recovery of the intestinal barrier within 120 min of reperfusion.
文摘目的:通过建立表皮通透屏障功能障碍模型—“血虚风燥型”慢性湿疹样病变豚鼠模型,研究针灸治疗对皮肤表皮通透屏障功能的作用机制。方法:普通级纯白色雄性豚鼠32只,随机分为空白组8只和造模组24只,采用2,4-二硝基氯苯(2,4-dinitrochlorobenzene,DNCB)诱导法造模,建立“血虚风燥”湿疹样病变豚鼠模型,随机数字表法分为模型组(8只)、对照组(8只)、针灸组(8只)。针灸组取双肺俞、双脾俞、双膈俞、双曲池、双足三里、双血海,双三阴交,针刺以平补平泻为主,留针15min,治疗疗程为两周。对照组给予氯雷他定片,每日一次,连续灌胃两周。观察豚鼠皮肤组织形态学改变情况、多功能皮肤测试仪检测皮肤角质层含水量(Water content of stratum corneum,WCSC)及经表皮水分流失量(Trans-epidermal water loss,TEWL)、酶联免疫法(Enzyme-Linked ImmunoSorbent Assay,ELISA)测定血清免疫球蛋白E(IgE)、白细胞介素-4(IL-4)、白细胞介素-17(IL-17)浓度。结果:与模型对照组比较,针灸组皮损评分显著降低(P<0.01),皮肤角质层水分含量(WCSC)明显升高(P<0.01),经表皮水分流失量(TEWL)显著降低(P<0.01),血清IgE、IL-17浓度显著降低(P<0.01),IL-4浓度显著升高(P<0.01)。结论:在“血虚风燥型”慢性湿疹样皮炎表皮通透屏障功能障碍豚鼠模型实验中,针灸通过改善表皮水分调节,改善细胞因子表达量,发挥全身免疫作用,修复损伤的表皮通透屏障功能,进一步改善“皮毛微环境”状态。