关于肠黏膜屏障功能衰竭临床分期标准的初步探讨

目的:初步建立肠黏膜屏障功能衰竭(IBF)的临床分期标准。方法:选取消化系统恶性肿瘤、肝硬化、炎性肠病等患者共50例作为病例组,选取25例健康志愿者作为对照组,均口服双糖探针后检测样本尿液中乳果糖/甘露醇(L/M)含量以评价肠道通透性,同时采集其新鲜粪便行菌群分析,记录其临床指标及实验室指标,分析病例组与对照组的临床表现、肠道通透性、肠菌群及免疫指标间的关系。结果:与对照组(0.02938±0.00725)相比,病例组尿L/M比值(0.06694±0.02343)显著增高,差异有统计学意义(t=9.874,P<0.01)。不同程度菌群失调患者肠道通透性差异无显著性(F=2.285,P=0.113)。随着患者腹胀及腹泻程度的增高,肠道通透性增高及中重度菌群失调的比例也增加。病例组C反应蛋白[(47.8±33.5)mg/Lvs(3.2±2.6)mg/L]、血浆内毒素[(5.806±4.219)EU/mLvs(0.018±0.056)EU/mL]及血清白细胞介素-6(22.19±8.45)pg/mLvs(6.24±0.13)pg/mL]水平较之对照组均有显著升高(均P<0.01)。结论:根据患者的临床症状、肠黏膜通透性、肠菌群状态及免疫指标间的关系,可初步建立IBF的临床分期标准。     

急性重症胰腺炎大鼠肠粘膜内pH及氧代谢的改变

目的探讨肠粘膜内pH值及氧代谢改变在急性重症胰腺炎(ASP)肠粘膜屏障功能障碍中的作用。方法用胰胆管内注射甘脱氧胆酸结合静脉输注蛙皮素方法复制大鼠ASP模型,分别对ASP及假手术组(SO组)大鼠于术后6、12、24小时取门静脉,腹主动脉血行血气分析,据此计算回肠粘膜内pH值及其氧摄取率,同时取门静脉血测定门静脉血乳酸会计师。结果ASP组大鼠12及24小时肠道氧摄取率[分别为（45.88±6.05）%及(41.31±4.18)%]均较SO组[分别为(24.82±4.28)%和(23.08±3.44)%]显著增加(P均<0.001)以12小时最为显著,而ASP组制模后12及24小时肠粘膜内pH(分别为7.301±0.036及7.165±0.066)显著低于SO组(分别为7.410±0.047及7.390±0.044),P均<0.001,以24小时为最显著以24小时为最显著。门静脉血乳酸含量在12及24小时分别为(3.58±1.06)mmol/L及(7.97±1.05)mmol/L,均较SO组〔分别为(1.16±0.98)mmol/L及(1.24±0.29)mmol/L〕显著增加,门静脉血乳酸含量与粘膜内pH值呈负相关（r=0.868,P<0.001）。结论ASP时肠粘膜氧供减少,氧代谢障碍,肠粘膜内pH值降低,是肠粘膜屏障功能障碍的主要机制之一。     

地塞米松联合盐酸氨溴索对分泌性中耳炎患者血管通透性及免疫功能的影响

目的 探究在分泌性中耳炎（SOM）患者中联合采用地塞米松+盐酸氨溴索治疗对血管通透性及免疫功能的影响。方法 纳入我院2020年3月至2022年3月收治的78例SOM患者，按照随机数字表法分为39例对照组和39例观察组。对照组采用地塞米松治疗，观察组加用盐酸氨溴索，以7d为1个治疗周期，若未痊愈则继续治疗，最多治疗4个周期。比较两组临床疗效、血管通透性、炎症反应、免疫功能、不良反应。结果 与对照组（79.49%）治疗总有效率相比，观察组（97.44%）较高，有统计学差异（P＜0.05）；对比两组治疗前血管通透性、免疫功能、炎症反应，无统计学差异（P＞0.05）；观察组治疗后纤维连接蛋白（Fn）[（195.30±22.46）mg/L]高于对照组，透明质酸（HA）[（54.62±3.26）μg/L]、血小板活化因子（PAF）[（92.49±15.72）ng/L]低于对照组，白介素-2（IL-2）[（13.66±2.12）pg/ml]、白介素-6（IL-6）[（13.66±2.12）pg/ml]水平均低于对照组，CD4+[（44.89±4.52）%]、CD4+/CD8+（1.94±0.15）较对照组高，有统计学差异（P＜0.05）；对比两组不良反应，无统计学差异（P＞0.05）。结论 地塞米松+盐酸氨溴索治疗SOM效果确切，能够改善血管通透性，减轻炎症反应，增强免疫功能，且安全性高。     

经皮经肝胆囊穿刺置管引流联合腹腔镜手术治疗急性胆囊炎的临床疗效观察

目的：探讨经皮经肝胆囊穿刺置管引流（PTGD）联合腹腔镜手术治疗急性胆囊炎的临床效果。方法：选取2018年5月至2020年5月88例进行治疗的急性胆囊炎患者,按随机数字表法分为对照组和观察组,各44例。对照组进行单纯腹腔镜手术治疗,观察组加用PTGD治疗。比较两组手术情况、炎症介质水平[白介素-6（IL-6）、白介素-4（IL-4）、肿瘤坏死因子-α（TNF-α）及C反应蛋白（CRP）]、肝功能指标[胆红素（TBil）、间接胆红素（IBil）、碱性磷脂酶（ALP）及淀粉酶（AMY）]和并发症发生状况。结果：观察组术后引流量、术中出血量分别为（16.85±3.25） ml、（70.13±6.51） ml,少于对照组的（23.68±4.37） ml、（81.47±7.95） ml,手术时间、术后卧床时间和术后排气时间分别为（89.85±7.79） min、（3.75±0.89） d、（19.33±2.58） h,短于对照组的（104.36±8.74） min、（5.28±1.02） d、（23.65±3.17） h,差异有统计学意义（P＜0.05）;两组炎症介质水平术前相比,差异无统计学意义（P＞0.05）;两组IL-6、IL-4、TNF-α、CRP水平术后均低于术前,差异有统计学意义（P＜0.05）;观察组术后IL-6、IL-4、TNF-α、CRP水平为（28.13±3.65） pg/ml、（25.14±3.08） pg/ml、（14.33±2.29） pg/ml、（10.33±2.04） mg/L,低于对照组的（34.58±4.12） pg/ml、（31.25±3.53） pg/ml、（20.17±2.86） pg/ml、（14.53±2.31） mg/L,差异有统计学意义（P＜0.05）;两组肝功能指标术前相比,差异无统计学意义（P＞0.05）;两组TBil、IBil、ALP、AMY水平术后均低于术前,差异有统计学意义（P＜0.05）;观察组术后TBil、IBil、ALP、AMY水平为（13.21±2.25） μmol/L、（10.13±2.02） μmol/L、（89.63±6.52） U/L、（114.85±12.34） U/L,低于对照组的（16.15±2.36） μmol/L、（13.41±2.15） μmol/L、（97.85±7.43） U/L、（133.52±15.35） U/L,差异有统计学意义（P＜0.05）;观察组并发症发生率为4.55%,较对照组的18.18%低,差异有统计学意义（P＜0.05）。结论：PTGD联合腹腔镜手术可减轻急性胆囊炎患者炎症反应,加快TBil、IBil、ALP、AMY水平复常,减少术中出血量,加速手术进程,降低并发症风险,利于患者病情康复。     

大黄对大鼠肠粘膜及肠血管通透性的影响

目的：研究大黄对肠粘膜及肠血管通透性的影响。方法：选用低血容量性休克和内毒素性休克大鼠动物模型，以荧光标记白蛋白和小肠湿／干重比值检测内毒素性休克肠血管通透性，以血浆内毒素含量来衡量肠粘膜通透性。结果：内毒素能引起小肠组织明显水肿，其湿／干重比值显著增高，同时明显提高肠血管壁对荧光标记白蛋白的通透性；而大黄能减轻肠壁水肿和湿／干重比值（内毒素组为３．７５±０．６８，大黄组为１．６６±０．３３，Ｐ＜０．０１），降低肠血管通透性〔小肠组织荧光标记白蛋白含量：内毒素组为（１．２５４±０．１１７）μｍｏｌ／ｇ，大黄组为（０．９００±０．０７１）μｍｏｌ／ｇ，Ｐ＜０．０１〕。低血容量性休克能破坏肠粘膜屏障，提高肠粘膜对内毒素的通透性，而大黄可明显降低低血容量性休克大鼠肠粘膜通透性，抑制肠道内毒素的吸收〔血浆内毒素含量：休克组为（０．５５７±０．０６９）ＥＵ／ｍｌ，大黄组为（０．３４５±０．０５５）ＥＵ／ｍｌ，Ｐ＜０．０１〕。结论：大黄能保护肠粘膜屏障，抑制肠道内毒素吸收，降低肠粘膜及肠毛细血管通透性。     

血液灌流对维持性血透患者血清甲状旁腺素的清除作用

[摘要] 目的 观察血液透析(HD)和血液透析串联血液灌流(HD+HP)对维持性血液透析患者血清甲状旁腺素(PTH)的清除效果。方法 将20例稳定的维持性血液透析患者随机分为2组：HD组及HD+HP组，治疗前、后分别抽静脉血测定血清肌酐（Scr）、尿素氮（BuN）血清磷及PTH。结果 HD组治疗后PTH及血清磷分别由 987.86±445.31pg/ml，2.40±0.31mmol/L降至973.29±424.36pg/ml, 1.87±0.10mmol/L，PTH清除率为 7.33±2.89%，治疗前后无明显差异（P＞0.05），血清磷治疗前后差异显著（P＜0.05）；HD+HP组治疗后PTH由 998.38±431.96pg/ml降至749.13±543.13pg/ml，单次治疗清除率为39.73±27.53% ，治疗前后差异显著(P＜0.05)，血清磷由治疗前2.39±0.37mmol/L降至1.34±0.12mmol/L，差异显著并明显高于HD组（P＜0.05）。结论 HD+HP可以有效清除PTH及磷，HD可以有效清除血清磷但不能有效清除PTH。     

L-精氨酸对严重腹腔感染大鼠肠屏障功能的影响

目的　探讨L 精氨酸对严重腹腔感染大鼠肠屏障功能的影响。方法　SD大鼠 90只 ,随机分成对照组、感染组和精氨酸组 ,每组 30只。对照组仅行单纯剖腹手术 ;感染组采用盲肠结扎加穿孔 (CLP)手术制作严重腹腔感染模型 ;精氨酸组行CLP后每天添加L 精氨酸饮食 [0 2 6 4g/ (kg·d) ]。各组术后 1、2、 4d分别取肠黏膜行病理学观察、增殖细胞核抗原 (PCNA)指数测定、血细菌培养和血浆内毒素水平测定。结果　精氨酸组较感染组小肠黏膜病理性损害明显减轻。感染组术后 2、 4d血浆内毒素水平明显高于精氨酸组 ,分别是 (1 4 2± 0 10 )EU/mlvs (1 14± 0 11)EU/ml,(1 94± 0 0 7)EU mlvs (1 5 8± 0 14 )EU/ml,P <0 0 1。精氨酸组术后 2d血细菌阳性率明显低于感染组 (10 %vs 30 % ,P <0 0 1)。感染组PCNA指数先升高 ,后下降 ,而精氨酸组 4d内下降不明显。结论　当严重腹腔感染导致肠屏障功能障碍时 ,L 精氨酸有促进肠黏膜损伤修复、维护肠屏障功能的作用     

乳酸菌对肠粘膜通透性及中小分子尿毒素清除的影响

目的研究乳酸菌对慢性肾衰竭大鼠的肠粘膜通透性及中小分子尿毒素清除的影响。方法40只SD大鼠分为正常对照组（10只）行假手术,30只作5/6肾切除后分为肾衰竭病理对照组、双歧杆菌治疗组和乳酸杆菌治疗组。喂养1周后处死动物留取血粪标本。用紫外线吸收法测定血/粪中分子物质（MMS）。尿素（UN）和肌酐（Cr）;用酶偶联紫外分光度法检测血D-乳酸。结果病理对照组血、粪MMS和UN、Cr均升高（P〈0.01）;血浆D-乳酸含量增高（P〈0.01）。双歧杆菌治疗组和乳酸杆菌治疗组较病理对照组的血浆D-乳酸含量降低（P〈0.01）;BUN、SCr均降低（P〈0.01）;而粪UN、Cr均增加（P〈0.01）。结论双歧杆菌和乳酸杆菌均可维持慢性肾衰竭大鼠肠粘膜正常通透性,加速肠道清除MMS,分解肠道内尿素和肌酐降低其血中的浓度。     

居家有氧运动对肝癌介入治疗患者负性情绪及血清BDNF、5-HT、NT-3水平的影响

摘要 目的：探讨居家有氧运动对行肝动脉栓塞化疗术（TACE）治疗的肝癌患者焦虑及抑郁情绪和血清BDNF、5-HT、NT-3的影响。 方法：选取2018年1月—2019年12月行TACE治疗的183例肝癌患者,分为运动组91例和对照组92例。对照组接受常规介入科护理教育,运动组在此基础上接受3个月个性化的居家有氧运动。采用医院焦虑抑郁量表评估焦虑及抑郁程度,采用ELISA法检测患者血清BDNF、5-HT、NT-3含量。 结果：运动组82例,对照组85例顺利完成研究。干预前,运动组与对照组焦虑和抑郁评分及血清BDNF、5-HT、NT-3含量无显著性差异（P>0.05）。干预后,运动组焦虑和抑郁评分为（8.46±3.34）和（9.95±2.67）分,显著低于对照组（10.08±4.33）和（12.26±3.09）分;运动组血清BDNF、5-HT和NT-3含量为（23428.74±9885.53）pg/ml、（3987.48±2297.55）ng/ml和（11325.43±3253.96）pg/ml,显著高于对照组（18887.79±8404.10）pg/ml、（3191.08±2163.46）ng/ml和（9235.05±3820.01）pg/ml。 结论：居家有氧运动能够改善肝癌行TACE治疗患者的负性情绪,增加患者血清BDNF、5-HT、NT-3含量。     

呼吸道感染患儿肠道菌群紊乱与Th17/Treg及其分泌炎性细胞因子免疫平衡的相关性研究

目的　探讨呼吸道感染患儿肠道菌群紊乱与Th17/Treg免疫平衡及炎性细胞因子的关系。方法　前瞻性选取2019年5月～2020年11月西北妇女儿童医院收治的呼吸道感染患儿135例作为研究观察组,根据肠道菌群紊乱情况分为菌群失调组（n=60）和非菌群失调组（n=75）。另选取同期健康体检儿童100例作为对照。对比各组肠道菌群数量,检测外周血Th17,Treg细胞百分比及血清炎性因子表达水平。Pearson相关性分析肠道菌群与Th17,Treg细胞及炎性因子表达的相关性。结果　菌群失调组乳酸杆菌、双歧杆菌数量及B/E值较非菌群失调组和对照组明显降低,肠球菌、大肠埃希菌数量明显升高,差异有统计学意义（F=13.849~42.449,均 P<0.05）;与对照组相比,非菌群失调组各菌群变化不显著（P>0.05）。与对照组相比,菌群失调组和非菌群失调组Th17%及IL-2,IL-6,IL-17水平明显升高,Treg%及IL-10水平明显降低,其中菌群失调组变化更显著,差异有统计学意义（F=30.483~92.328,均P＜0.05）。Pearson 相关性分析显示,呼吸道感染患儿Th17%及IL-2,IL-6,IL-17水平与乳酸杆菌、双歧杆菌、B/E值呈负相关（r=0.989~0.586,均P＜0.05）,与肠球菌、大肠埃希菌呈正相关（r=-0.599~0.800,均P＜0.05）;Treg%及IL-10水平与乳酸杆菌、双歧杆菌、B/E值呈正相关（r =0.672~0.756,均P＜0.05）,与肠球菌、大肠埃希菌呈负相关（r= -0.774~-0.684,均P＜0.05）。结论　呼吸道感染患儿肠道菌群紊乱表现为肠道有益菌数量减少,致病菌数量增多;肠道菌群紊乱可能通过诱导机体Th17 /Treg免疫失衡,调控炎性介质分泌,进而参与儿童呼吸道感染的发生发展。     

中药合剂胃肠术后一号对严重腹腔感染大鼠肠黏膜屏障的保护作用

目的观察中药合剂胃肠术后一号对严重腹腔感染大鼠肠黏膜屏障功能的影响。方法90只SD大鼠完全随机分成3组(每组30只):假手术对照组:仅行单纯剖腹手术;腹腔感染组:采用盲肠结扎加穿孔法(CLP)手术制作严重腹腔感染模型;中药治疗组:行CLP后每天灌胃胃肠术后一号〔剂量10 ml/(kg.d)〕;分别于成模后1 d、3 d、7 d 3个时相点各观察大鼠10只。检测血浆二胺氧化酶(DAO)、D乳酸、白介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、内毒素(LPS)和尿甘露醇与乳果糖比值(L/M)的变化。结果腹腔感染组大鼠各个时相的DAO、D乳酸、L/M、IL-6、TNF-α和LPS与假手术组比较,均有显著性增高(P<0.05);胃肠术后一号治疗组与腹腔感染组比较,1 d时上述观测指标无明显下降,3 d和7 d时DAO、D乳酸、IL-6、TNF-α和LPS水平显著性降低(P<0.05),7 d时L/M亦明显下降(P<0.05)。结论腹腔感染时肠黏膜通透性增加,肠黏膜屏障损害;胃肠术后一号可减少腹腔感染时炎性介质和内毒素的释放,降低肠黏膜通透性,对肠黏膜屏障具有保护作用。     

益生菌在胃肠外科术后患者中的应用

目的：探讨益生菌联合营养支持对胃肠外科术后患者肠功能和肠道菌群的影响。方法：36例胃肠道中等以上手术的患者,随机分为研究组和对照组,每组18例。两组术后均接受等氮等能量的营养支持,研究组患者于术后第3天开始每天加用益生菌制剂（6.6×10^7colony forming units）,共7天。监测治疗期间患者的胃肠道症状、生命体征、腹泻情况和菌群比例等。结果：两组患者术后腹痛、腹胀、肠鸣音异常等胃肠道症状均无显著差异（P〉0.05）,两组患者在术后第8和9天的腹泻比例和腹泻评分差异有显著性意义（P〈0.05）。治疗结束后,研究组患者肠道双歧杆菌和乳酸杆菌计数均较对照组高,两组间差异有显著性意义（P〈0.05）。结论：在胃肠外科术后患者中应用益生菌可改善胃肠道症状、减轻腹泻程度和纠正肠道菌群失调。     

TLR ligand decreases mesenteric ischemia and reperfusion injury-induced gut damage through TNF-alpha signaling

Ischemic gut contributes to the development of sepsis and organ failure in critically ill patients. Toll-like receptors (TLRs) have been reported to mediate the pathophysiology of organ damage following ischemia/reperfusion (I/R) injury. We hypothesize that LPS, a ligand for TLR4, decreases mesenteric I/R injury-induced gut damage through tumor necrosis factor alpha (TNF-alpha) signaling. First, wild-type (WT) mice were fed with oral antibiotics for 4 weeks to deplete the intestinal commensal microflora. At week 3, drinking water was supplemented with LPS (10 microg/microL) to trigger TLRs. The intestinal mucosa was harvested for TLR4 protein, caspase 3 activity, and terminal deoxynucleotide transferase labeling assay. Second, WT and Tnfrsf1a mice received 30-min ischemia and 30-min reperfusion (30I-30R) or 30I-180R of the intestine; intestinal permeability and lipid peroxidation of the intestine were examined. Third, WT and Tnfrsf1a mice were fed with oral antibiotics with or without LPS and received 30I-180R of the intestine. The intestinal mucosa was harvested for lipid peroxidation; glutathione (GSH) level; nuclear factor kappaB (NF-kappaB) and AP-1 DNA-binding activity; Bcl-w, TNF-alpha, and CXCR2 mRNA expression; and HSP70 protein assay. Commensal depletion increased caspase 3 activity as well as villi apoptosis and decreased TLR4 expression of the intestinal mucosa. LPS increased TLR4 expression and decreased villi apoptosis. Commensal depletion augmented 30I-180R-induced intestine permeability as well as lipid peroxidation and decreased GSH level in WT mice but not in Tnfrsf1a mice. LPS decreased 30I-180R-induced intestinal permeability as well as lipid peroxidation and increased GSH level of the intestinal mucosa in WT mice but not in Tnfrsf1a mice. Commensal depletion with 30I-180R increased NF-kappaB and AP-1 DNA-binding activity, HSP70 protein expression, and decreased Bcl-w and TNF-alpha mRNA expression of the intestinal mucosa in WT mice but not in Tnfrsf1a mice. Collectively, commensal microflora induces TLR4 expression and decreases apoptosis of the intestinal mucosa. Commensal depletion enhances I/R-induced gut damage. LPS prevents I/R-induced intestinal permeability, lipid peroxidation, and decrease in GSH level. Given that the preventive effect of LPS on I/R-induced gut damage and NF-kappaB activity of the intestine is abolished in Tnfrsf1a mice, we conclude that TLR ligand decreases mesenteric I/R injury-induced gut damage through TNF-alpha signaling.     

异基因造血干细胞移植过程中患者艰难梭菌感染与肠道微生态失调关系的临床研究

本研究探讨异基因造血干细胞移植（allogeneic hematopoietic stem cell transplantation,allo-HSCT）过程中患者艰难梭菌相关性腹泻（clostridium difficile associated diarrhea,CDAD）与肠道微生态的关系,了解肠道微生态失衡的临床特征,寻找有效防治措施,保护肠道菌群,减少细菌易位及感染的发生。对44例allo-HSCT后腹泻患者采用艰难梭菌毒素A＆B检测试剂盒进行毒素检测,采用厌氧培养方法进行艰难梭菌的分离、鉴定。对患者粪便标本进行肠道微生态研究;采用光冈复合式法对目的菌群（双歧杆菌、乳酸杆菌、类杆菌、消化链球菌、产气荚膜梭菌、肠杆菌、肠球菌、酵母菌）进行定性定量分析。结果表明：44例腹泻患者中共检测出12例艰难梭菌阳性,阳性率为27.27%;CDAD的发生与使用抗生素或化疗药物有关;CDAD患者的肠道微生态发生了明显变化,表现为乳酸杆菌、双歧杆菌、类杆菌、肠杆菌等细菌数量明显下降;对CDAD用万古霉素、甲硝唑等药物并配合给予益生菌治疗效果好,但有一定复发率（16.67%）。结论：allo-HSCT并发CDAD与肠道微生态的改变有关,应用敏感抗生素治疗的同时应积极扶植肠道菌群,这样的治疗有利于改善病情和减少复发。     

肠道水疗对急性胰腺炎重症转化的防治作用

目的评价肠道水疗对防止急性胰腺炎重症(SAP)转变的作用,分析其作用机制.方法将62例急性胰腺炎(AP)患者随机分为治疗组、对照组;并将32例健康献血者作为正常对照;治疗组除行常规治疗外,同时给予每日1次的肠道水疗,对所有实验对象同时检测血清内毒素(ET)、C-反应蛋白(CRP)、白细胞介素-6(IL-6)和血淀粉酶(AMS);观察腹痛缓解时间及统计住院时间.结果 AP患者ET、CRP和IL-6均显著高于正常对照组(P<0.05);治疗组ET、CRP和IL-6的下降幅度显著比对照组大(P<0.05):治疗组腹痛缓解时间、AMS降至正常时间比对照组快(P<0.05);治疗组有1例转变为重症,占3.57%(1/28),对照组有7例转变为重症,占20.59%(7/34),两者比较差异有统计学意义(P<0.05).结论肠道水疗可防止AP向SAP转变;促进肠蠕动,加速肠腔内毒素排除是其主要机制.     

烧伤早期大面积切痂术后肠道菌群变化的初步临床研究

目的；探讨烧伤早期大面积切痂术后肠道菌群变化规律及其意义。方法：采用定量和微生物分析法对大面积切痂术后29例患者（手术组）的血浆内毒素和肠道6种常见菌群（肠杆菌、葡萄球菌、双歧杆菌、类杆菌、梭杆菌和酵母菌）进行检测，并与20名正常人进行对照分析。结果：手术组的肠杆菌、酵母菌数量明显高于正常对照组，厌氧菌中类杆菌、梭杆菌、双歧杆菌数量及双歧杆菌／肠杆菌明显低于正常对照组（P均＜0．05或P＜0．01），血浆内毒素水平显著高于正常对照组（P均＜0．01）。29例患者中24例出现不成形软便或稀便等肠道菌群失调症状。结论：肠道菌群失调存在于大面积切痂术后早期，主要是以双歧杆菌为代表的厌氧菌群失调，这是大面积切痂术后肠道感染的主要因素。     

Irritable bowel syndrome--criteria, sub-classification, etiology]

The irritable bowel syndrome (IBS) is a very common condition in gastroenterology clinics, but yet it is one of the pooly understood. A international working team in Rome, 1988, proposed that IBS is a functional intestinal disorder with chronic or recurrent gastrointestinal symptoms without structural or biochemical abnormalities. IBS was sub-classified into 3 groups; abdominal pain as the prominent feature with diarrhea, with constipation, with both while painless diarrhea and simple constipation without pain were excluded from IBS. There is a lot of data suggesting that IBS has a gut dysmotility, which is influenced by many stimuli (food, hormone, drug, menses, mechanical dilatation), including psychological stress. Moreover, currently available evidences implicate that IBS is a more generalized disorder of smooth muscle function not only in the intestine but also outside of the intestine.     

Lipopolysaccharide-induced enterocyte-derived nitric oxide induces intestinal monolayer permeability in an autocrine fashion

Studies indicate that endotoxin (LPS) causes intestinal injury, increases inducible nitric oxide synthase (iNOS) activity, leads to increased NO production, and promotes bacterial translocation (BT). To investigate the mechanism by which LPS causes gut injury and to test the hypothesis that NO produced by enterocytes promotes gut injury in an autocrine fashion, rat intestinal epithelial cell (IEC-6) monolayers were tested. IEC-6 monolayers grown in a bicameral system were incubated with media or with LPS (25 microg/mL) and tested for permeability to phenol red, BT, and nitrate/nitrite (NO2/NO3) production. To determine the direct effect of NO on permeability, monolayers were incubated with the NO donor S-nitroso-acetylpenicillinamide (SNAP; 1 mM) and tested for permeability. Next, the protective effects of two NOS inhibitors (L-NMMA and L-NIL) were tested. Finally, to determine if LPS-induced permeability occurs via a poly (ADP-ribose) synthetase- (PARS) dependent pathway, monolayers incubated with LPS alone or with the PARS inhibitor, INH2BP (100 microM) were tested. LPS significantly increased IEC-6 permeability to phenol red, as well as increased NO2/NO3 by 20-fold (P < 0.001) and increased BT 10-fold (P < 0.001). SNAP mimicked the effect of LPS and significantly increased both permeability to phenol red and BT. Inhibition of iNOS significantly decreased the LPS-induced increase in monolayer permeability and BT (P < 0.05). Monolayers incubated with INH2BP had significantly decreased permeability to phenol red and BT, suggesting that LPS-induced NO production increases monolayer permeability at least in part via a PARS-dependent mechanism. In summary, LPS-induced disruption of monolayer barrier function appears to be related, at least in part, to enterocyte produced NO. This supports the hypothesis that NO produced by LPS-stimulated enterocytes promotes injury in an autocrine fashion and highlights the fact that enterocytes can be a target as well as a producer of NO.     

Co-administration of the health food supplement, bovine colostrum, reduces the acute non-steroidal anti-inflammatory drug-induced increase in intestinal permeability

Non-steroidal anti-inflammatory drugs (NSAIDs) are effective analgesics but cause gastrointestinal injury. Present prophylactic measures are suboptimal and novel therapies are required. Bovine colostrum is a cheap, readily available source of growth factors, which reduces gastrointestinal injury in rats and mice. We therefore examined whether spray-dried, defatted colostrum could reduce the rise in gut permeability (a non-invasive marker of intestinal injury) caused by NSAIDs in volunteers and patients taking NSAIDs for clinical reasons. Healthy male volunteers (n=7) participated in a randomized crossover trial comparing changes in gut permeability (lactulose/rhamnose ratios) before and after 5 days of 50 mg of indomethacin three times daily (tds) per oral with colostrum (125 ml, tds) or whey protein (control) co-administration. A second study examined the effect of colostral and control solutions (125 ml, tds for 7 days) on gut permeability in patients (n=15) taking a substantial, regular dose of an NSAID for clinical reasons. For both studies, there was a 2 week washout period between treatment arms. In volunteers, indomethacin caused a 3-fold increase in gut permeability in the control arm (lactulose/rhamnose ratio 0.36+/-0.07 prior to indomethacin and 1.17+/-0.25 on day 5, P<0.01), whereas no significant increase in permeability was seen when colostrum was co-administered. In patients taking long-term NSAID treatment, initial permeability ratios were low (0.13+/-0.02), despite continuing on the drug, and permeability was not influenced by co-administration of test solutions. These studies provide preliminary evidence that bovine colostrum, which is already currently available as an over-the-counter preparation, may provide a novel approach to the prevention of NSAID-induced gastrointestinal damage in humans.     

Increased gut permeability early after burns correlates with the extent of burn injury.

OBJECTIVE: To determine if increased gut permeability within 48 hrs after burn injury correlates with the extent of injury, before sepsis and pulmonary disorders have complicated the clinical course. DESIGN: Nonrandomized, controlled study. PATIENTS: Consecutive patients admitted with burn injuries on > 20% of body surface area. INTERVENTIONS: Intestinal absorption and renal excretion of polyethylene glycol 3350 was used as the macromolecule to determine gut permeability; polyethylene glycol 400 intestinal absorption was used as an internal control for abnormal motility and malabsorption. Polyethylene glycol 3350 (40 g) and polyethylene glycol 400 (5 g) were administered enterally. MEASUREMENTS AND MAIN RESULTS: Gut permeability was significantly increased early after the injury. The patients excreted 0.56 +/- 0.34% (n = 11) of polyethylene glycol 3350, compared with the amount (0.12 +/- 0.04%) (p < .05) previously reported in normal volunteers. There was no significant difference in the excretion of polyethylene glycol 400 in the patients (27.0 +/- 4.6%, n = 11) vs. the normal volunteers previously reported (26.3 +/- 5.1%, n = 12), suggesting normal intestinal motility and absorption. The percentage of excretion of polyethylene glycol 3350 correlated with the percentage body surface burned; patients with smaller injuries excreted 0.32 +/- 0.17% (n = 6), which was greater than normal and less than those values from patients with larger injuries, 0.84 +/- 0.25% (n = 5) (p < .001 by Turkey test). CONCLUSIONS: Using our newly developed method to separate and quantify polyethylene glycols in urine, gut permeability was found to be increased early after burn injury, which confirms a previous study using lactulose as the permeability probe. Furthermore, this increased gut permeability to polyethylene glycol 3350 correlated with the extent of the burn injury.