Introduction The skin barrier usually refers to the physical barrier formed by the cuticle and sebum membrane of the skin.This barrier not only protects against the onslaught of microorganisms and percutaneous penetra...Introduction The skin barrier usually refers to the physical barrier formed by the cuticle and sebum membrane of the skin.This barrier not only protects against the onslaught of microorganisms and percutaneous penetration of chemicals and allergens but also prevents the loss of nutrients and moisture from the body.Corneodesmosomes play an important role in maintaining the function of the keraphyllous skin barrier.Desmogleins,desmocollin,and corneodesmosin are examples of corneodesmosomes.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
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
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 physiological skin surface pH is just below 5. With age the skin surface pH increases up to 6. An increased pH correlates with reduced barrier integrity/cohesion. The present pilot study assesses possible normaliz...The physiological skin surface pH is just below 5. With age the skin surface pH increases up to 6. An increased pH correlates with reduced barrier integrity/cohesion. The present pilot study assesses possible normalization of an increased skin surface pH of the elderly and improvement of barrier function via application of ≈pH 4.0 skin care products. Baseline skin surface pH was determined in elderly (80+ years old;n = 15) compared to middle aged adults (31 - 50 years old;n = 15). The effect of o/w emulsions at pH-values of 3.5, 4.0, 4.5 and 5.5 on the skin surface pH was determined in both groups. Further, the effect of a 4-week treatment with a pH 4.0 skin care product on the skin surface pH, skin hydration and barrier integrity was assessed. Thirteen elderly females were involved in this home-in-use test. Increased baseline skin surface pH of the elderly normalizes to the physiological pH of 4.5 - 5.0 over 7 hours after single application of o/w-emulsions with a given pH of 3.5 or 4.0. A 4 week treatment employing the pH 4.0 skin care product improves the epidermal barrier integrity of the elderly significantly (p = 0.005). Reduction of the increased baseline skin surface pH of the elderly is accompanied by improved epidermal barrier integrity. Skin care products for the elderly have to be adjusted in the pH range of 3.5 to 4.0.展开更多
BACKGROUND The intestinal mucosal barrier is the first line of defense against numerous harmful substances,and it contributes to the maintenance of intestinal homeostasis.Recent studies reported that structural and fu...BACKGROUND The intestinal mucosal barrier is the first line of defense against numerous harmful substances,and it contributes to the maintenance of intestinal homeostasis.Recent studies reported that structural and functional changes in the intestinal mucosal barrier were involved in the pathogenesis of several intestinal diseases.However,no study thoroughly evaluated this barrier in patients with functional constipation(FC).AIM To investigate the intestinal mucosal barrier in FC,including the mucus barrier,intercellular junctions,mucosal immunity and gut permeability.METHODS Forty FC patients who fulfilled the Rome IV criteria and 24 healthy controls were recruited in the Department of Gastroenterology of China-Japan Friendship Hospital.The colonic mucus barrier,intercellular junctions in the colonic epithelium,mucosal immune state and gut permeability in FC patients were comprehensively examined.Goblet cells were stained with Alcian Blue/Periodic acid Schiff(AB/PAS)and counted.The ultrastructure of intercellular junctional complexes was observed under an electron microscope.Occludin and zonula occludens-1(ZO-1)in the colonic mucosa were located and quantified using immunohistochemistry and quantitative real-time polymerase chain reaction.Colonic CD3+intraepithelial lymphocytes(IELs)and CD3+lymphocytes in the lamina propria were identified and counted using immunofluorescence.The serum levels of D-lactic acid and zonulin were detected using enzyme-linked immunosorbent assay.RESULTS Compared to healthy controls,the staining of mucus secreted by goblet cells was darker in FC patients,and the number of goblet cells per upper crypt in the colonic mucosa was significantly increased in FC patients(control,18.67±2.99;FC,22.42±4.09;P=0.001).The intercellular junctional complexes in the colonic epithelium were integral in FC patients.The distribution of mucosal occludin and ZO-1 was not altered in FC patients.No significant differences were found in occludin(control,5.76E-2±1.62E-2;FC,5.17E-2±1.80E-2;P=0.240)and ZO-1(control,2.29E-2±0.93E-2;FC,2.68E-2±1.60E-2;P=0.333)protein expression between the two groups.The mRNA levels in occludin and ZO-1 were not modified in FC patients compared to healthy controls(P=0.145,P=0.451,respectively).No significant differences were observed in the number of CD3+IELs per 100 epithelial cells(control,5.62±2.06;FC,4.50±2.16;P=0.070)and CD3+lamina propria lymphocytes(control,19.69±6.04/mm^(2);FC,22.70±11.38/mm^(2);P=0.273).There were no significant differences in serum D-lactic acid[control,5.21(4.46,5.49)mmol/L;FC,4.63(4.31,5.42)mmol/L;P=0.112]or zonulin[control,1.36(0.53,2.15)ng/mL;FC,0.94(0.47,1.56)ng/mL;P=0.185]levels between FC patients and healthy controls.CONCLUSION The intestinal mucosal barrier in FC patients exhibits a compensatory increase in goblet cells and integral intercellular junctions without activation of mucosal immunity or increased gut permeability.展开更多
AIM: To investigate the effects of lubiprostone and Polyethylene Glycol 3350 (PEG) on mucosal barrier repair in ischernic-injured porcine intestine. METHODS: Ileum from 6 piglets (approximately 15 kg body weight...AIM: To investigate the effects of lubiprostone and Polyethylene Glycol 3350 (PEG) on mucosal barrier repair in ischernic-injured porcine intestine. METHODS: Ileum from 6 piglets (approximately 15 kg body weight) was subjected to ischemic conditions by occluding the local rnesenteric circulation for 45 min in vivo. Ileal tissues from each pig were then harvested and mounted in Ussing chambers and bathed in oxygenated Ringer's solution in vitro. Intestinal barrier function was assessed by measuring transepithelial electrical resistance (TER) and mucosal-to-serosal fluxes of ^3H-rnannitol and ^14C-inulin. Statistical analyses of data collected over a 120-min time course included 2-way ANOVA for the effects of time and treatment on indices of barrier function. RESULTS: Application of 1μmol/L lubiprostone to the rnucosal surface of ischemic-injured ileum in vitro induced significant elevations in TER compared to nontreated tissue. Lubiprostone also reduced mucosal-toserosal fluxes of ^3H-rnannitol and ^14C-inulin. Alternatively, application of a polyethylene laxative (PEG, 20 rnmol/L) to the mucosal surface of ischernic tissues significantly increased flux of ^3H-rnannitol and ^14C-inulin. CONCLUSION: This experiment demonstrates that lubiprostone stimulates recovery of barrier function in ischemic intestinal tissues whereas the PEG laxative had deleterious effects on mucosal repair. These results suggest that, unlike osmotic laxatives, lubiprostone stimulates repair of the injured intestinal barrier.展开更多
AIM: To evaluate methods measuring the intestinal permeability in chronic kidney disease (CKD) and clarify whether there is an increased intestinal permeability in CKD.METHODS: We reviewed the literature in accord...AIM: To evaluate methods measuring the intestinal permeability in chronic kidney disease (CKD) and clarify whether there is an increased intestinal permeability in CKD.METHODS: We reviewed the literature in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) protocol and performed a systematic literature search through MEDline and EMBASE. All controlled trials and cohort studies using non-invasive methods to assess intestinal permeability in CKD patients were included. Excluded were: Conference abstracts and studies including patients younger than 18 years or animals. From the included studies we summarized the used methods and their advantages and disadvantages. For the comparison of their results we divided the included studies in two categories based on their included patient population, either assessing the intestinal permeability in mild to moderate CKD patients or in end stage renal disease (ESRD) patients. Results were graphically displayed in two plots, one comparing the intestinal permeability in mild to moderate CKD patients to healthy controls and one comparing the intestinal permeability in ESRD patients to healthy controls. RESULTS: From the 480 identifed reports, 15 met our inclusion criteria. Methods that were used to assess the intestinal permeability varied from markers measured in plasma to methods based on calculating the urinary excretion of an orally administered test substance. None of the applied methods has been validated in CKD patients and the infuence of decreased renal function on the different methods remains unclear to a certain extent. Methods that seem the least likely to be influenced by decreased renal function are the quantitative PCR (qPCR) for bacterial DNA in blood and D-lactate. Considering the results published by the included studies; the studiesincluding patients with mild to moderate CKD conductedconflicting results. Some studies did report an increasein intestinal permeability whilst other did not find asignificant increased permeability. However, despite thevariety in used methods among the different studies, allstudies measuring the intestinal permeability in ESRDpoint out a significant increased intestinal permeability.Results should nevertheless be interpreted with cautiondue to the possible infuence of a decreased glomerularfltration rate on test results.CONCLUSION: The intestinal permeability in CKD: (1) could be measured by qPCR for bacterial DNA in blood and D-lactate; and (2) seems to be increased in ESRD.展开更多
目的观察针刺配合通络益气汤治疗脑小血管病致认知功能障碍的临床疗效及其对患者脑微循环、步态平衡和血清神经元PAS结构域蛋白4(neuronal PAS domain protein 4,NPAS4)、P-选择素(CD62P)表达的影响。方法将98例脑小血管病致认知功能障...目的观察针刺配合通络益气汤治疗脑小血管病致认知功能障碍的临床疗效及其对患者脑微循环、步态平衡和血清神经元PAS结构域蛋白4(neuronal PAS domain protein 4,NPAS4)、P-选择素(CD62P)表达的影响。方法将98例脑小血管病致认知功能障碍患者随机分为治疗组和对照组,每组49例。治疗组采用针刺配合通络益气汤治疗,对照组采用单纯通络益气汤治疗。观察两组治疗前后各项实验室指标[谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-Px)、晚期糖基化终末产物(advanced glycation end products,AGEs)、NPAS4、CD62P、一氧化氮(NO)、亲环素A(cyclophilin A,CyPA)、脂蛋白相关磷脂酶A2(lipoprotein-associated phospholipase A2,Lp-PLA2)、血管性血友病因子(von Willebrand factor,vFW)水平]、脑微循环指标[血脑屏障通透性、血管差压、临界压力(critical pressure,CP)、脑血管动态阻力(dynamic resistance,DR)]及各量表[Berg平衡量表(Berg balance scale,BBS)、Tinetti平衡与步态量表、蒙特利尔认知评估量表(Montreal cognitive assessment,MoCA]评分的变化情况,并比较两组临床疗效。结果两组治疗后GSH-Px、NO水平及CP、各量表评分均较同组治疗前显著上升,AGEs、NPAS4、CD62P、CyPA、Lp-PLA2、vFW水平及血脑屏障通透性、血管差压、DR显著下降,差异均具有统计学意义(P<0.05)。治疗组治疗后GSH-Px、NO水平及CP、各量表评分均明显高于对照组,AGEs、NPAS4、CD62P、CyPA、Lp-PLA2、vFW水平及血脑屏障通透性、血管差压、DR均明显低于对照组,两组比较差异均具有统计学意义(P<0.05)。治疗组总有效率为98.0%,明显高于对照组的87.8%,两组比较差异具有统计学意义(P<0.05)。结论针刺配合通络益气汤治疗脑小血管病致认知功能障碍疗效确切,可减少氧化应激反应及炎症反应,降低NPAS4、CD62P水平,减少血管内皮功能及认知功能损伤,改善血脑屏障通透性、脑微循环及步态平衡。展开更多
文摘Introduction The skin barrier usually refers to the physical barrier formed by the cuticle and sebum membrane of the skin.This barrier not only protects against the onslaught of microorganisms and percutaneous penetration of chemicals and allergens but also prevents the loss of nutrients and moisture from the body.Corneodesmosomes play an important role in maintaining the function of the keraphyllous skin barrier.Desmogleins,desmocollin,and corneodesmosin are examples of corneodesmosomes.
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.
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 physiological skin surface pH is just below 5. With age the skin surface pH increases up to 6. An increased pH correlates with reduced barrier integrity/cohesion. The present pilot study assesses possible normalization of an increased skin surface pH of the elderly and improvement of barrier function via application of ≈pH 4.0 skin care products. Baseline skin surface pH was determined in elderly (80+ years old;n = 15) compared to middle aged adults (31 - 50 years old;n = 15). The effect of o/w emulsions at pH-values of 3.5, 4.0, 4.5 and 5.5 on the skin surface pH was determined in both groups. Further, the effect of a 4-week treatment with a pH 4.0 skin care product on the skin surface pH, skin hydration and barrier integrity was assessed. Thirteen elderly females were involved in this home-in-use test. Increased baseline skin surface pH of the elderly normalizes to the physiological pH of 4.5 - 5.0 over 7 hours after single application of o/w-emulsions with a given pH of 3.5 or 4.0. A 4 week treatment employing the pH 4.0 skin care product improves the epidermal barrier integrity of the elderly significantly (p = 0.005). Reduction of the increased baseline skin surface pH of the elderly is accompanied by improved epidermal barrier integrity. Skin care products for the elderly have to be adjusted in the pH range of 3.5 to 4.0.
基金the National Key Technology Support Program during“12th Five-Year Plan”Period of China,No.2014BAI08B00the Project“The role of the gut microbiota and metabolites in the pathogenesis of diarrheapredominant irritable bowel syndrome”of China-Japan Friendship Hospital,No.2019-64-K44.
文摘BACKGROUND The intestinal mucosal barrier is the first line of defense against numerous harmful substances,and it contributes to the maintenance of intestinal homeostasis.Recent studies reported that structural and functional changes in the intestinal mucosal barrier were involved in the pathogenesis of several intestinal diseases.However,no study thoroughly evaluated this barrier in patients with functional constipation(FC).AIM To investigate the intestinal mucosal barrier in FC,including the mucus barrier,intercellular junctions,mucosal immunity and gut permeability.METHODS Forty FC patients who fulfilled the Rome IV criteria and 24 healthy controls were recruited in the Department of Gastroenterology of China-Japan Friendship Hospital.The colonic mucus barrier,intercellular junctions in the colonic epithelium,mucosal immune state and gut permeability in FC patients were comprehensively examined.Goblet cells were stained with Alcian Blue/Periodic acid Schiff(AB/PAS)and counted.The ultrastructure of intercellular junctional complexes was observed under an electron microscope.Occludin and zonula occludens-1(ZO-1)in the colonic mucosa were located and quantified using immunohistochemistry and quantitative real-time polymerase chain reaction.Colonic CD3+intraepithelial lymphocytes(IELs)and CD3+lymphocytes in the lamina propria were identified and counted using immunofluorescence.The serum levels of D-lactic acid and zonulin were detected using enzyme-linked immunosorbent assay.RESULTS Compared to healthy controls,the staining of mucus secreted by goblet cells was darker in FC patients,and the number of goblet cells per upper crypt in the colonic mucosa was significantly increased in FC patients(control,18.67±2.99;FC,22.42±4.09;P=0.001).The intercellular junctional complexes in the colonic epithelium were integral in FC patients.The distribution of mucosal occludin and ZO-1 was not altered in FC patients.No significant differences were found in occludin(control,5.76E-2±1.62E-2;FC,5.17E-2±1.80E-2;P=0.240)and ZO-1(control,2.29E-2±0.93E-2;FC,2.68E-2±1.60E-2;P=0.333)protein expression between the two groups.The mRNA levels in occludin and ZO-1 were not modified in FC patients compared to healthy controls(P=0.145,P=0.451,respectively).No significant differences were observed in the number of CD3+IELs per 100 epithelial cells(control,5.62±2.06;FC,4.50±2.16;P=0.070)and CD3+lamina propria lymphocytes(control,19.69±6.04/mm^(2);FC,22.70±11.38/mm^(2);P=0.273).There were no significant differences in serum D-lactic acid[control,5.21(4.46,5.49)mmol/L;FC,4.63(4.31,5.42)mmol/L;P=0.112]or zonulin[control,1.36(0.53,2.15)ng/mL;FC,0.94(0.47,1.56)ng/mL;P=0.185]levels between FC patients and healthy controls.CONCLUSION The intestinal mucosal barrier in FC patients exhibits a compensatory increase in goblet cells and integral intercellular junctions without activation of mucosal immunity or increased gut permeability.
文摘AIM: To investigate the effects of lubiprostone and Polyethylene Glycol 3350 (PEG) on mucosal barrier repair in ischernic-injured porcine intestine. METHODS: Ileum from 6 piglets (approximately 15 kg body weight) was subjected to ischemic conditions by occluding the local rnesenteric circulation for 45 min in vivo. Ileal tissues from each pig were then harvested and mounted in Ussing chambers and bathed in oxygenated Ringer's solution in vitro. Intestinal barrier function was assessed by measuring transepithelial electrical resistance (TER) and mucosal-to-serosal fluxes of ^3H-rnannitol and ^14C-inulin. Statistical analyses of data collected over a 120-min time course included 2-way ANOVA for the effects of time and treatment on indices of barrier function. RESULTS: Application of 1μmol/L lubiprostone to the rnucosal surface of ischemic-injured ileum in vitro induced significant elevations in TER compared to nontreated tissue. Lubiprostone also reduced mucosal-toserosal fluxes of ^3H-rnannitol and ^14C-inulin. Alternatively, application of a polyethylene laxative (PEG, 20 rnmol/L) to the mucosal surface of ischernic tissues significantly increased flux of ^3H-rnannitol and ^14C-inulin. CONCLUSION: This experiment demonstrates that lubiprostone stimulates recovery of barrier function in ischemic intestinal tissues whereas the PEG laxative had deleterious effects on mucosal repair. These results suggest that, unlike osmotic laxatives, lubiprostone stimulates repair of the injured intestinal barrier.
文摘AIM: To evaluate methods measuring the intestinal permeability in chronic kidney disease (CKD) and clarify whether there is an increased intestinal permeability in CKD.METHODS: We reviewed the literature in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) protocol and performed a systematic literature search through MEDline and EMBASE. All controlled trials and cohort studies using non-invasive methods to assess intestinal permeability in CKD patients were included. Excluded were: Conference abstracts and studies including patients younger than 18 years or animals. From the included studies we summarized the used methods and their advantages and disadvantages. For the comparison of their results we divided the included studies in two categories based on their included patient population, either assessing the intestinal permeability in mild to moderate CKD patients or in end stage renal disease (ESRD) patients. Results were graphically displayed in two plots, one comparing the intestinal permeability in mild to moderate CKD patients to healthy controls and one comparing the intestinal permeability in ESRD patients to healthy controls. RESULTS: From the 480 identifed reports, 15 met our inclusion criteria. Methods that were used to assess the intestinal permeability varied from markers measured in plasma to methods based on calculating the urinary excretion of an orally administered test substance. None of the applied methods has been validated in CKD patients and the infuence of decreased renal function on the different methods remains unclear to a certain extent. Methods that seem the least likely to be influenced by decreased renal function are the quantitative PCR (qPCR) for bacterial DNA in blood and D-lactate. Considering the results published by the included studies; the studiesincluding patients with mild to moderate CKD conductedconflicting results. Some studies did report an increasein intestinal permeability whilst other did not find asignificant increased permeability. However, despite thevariety in used methods among the different studies, allstudies measuring the intestinal permeability in ESRDpoint out a significant increased intestinal permeability.Results should nevertheless be interpreted with cautiondue to the possible infuence of a decreased glomerularfltration rate on test results.CONCLUSION: The intestinal permeability in CKD: (1) could be measured by qPCR for bacterial DNA in blood and D-lactate; and (2) seems to be increased in ESRD.