Activation of matrix metalloproteinase-2 causes peritoneal injury during peritoneal dialysis in rats.

BACKGROUND: Sclerosing peritonitis (SP) and encapsulating peritoneal sclerosis (EPS) are serious complications of continuous ambulatory peritoneal dialysis. Although we have shown previously that matrix metalloproteinase-2 (MMP-2) is increased in peritoneal injury leading to SP/EPS, most of the MMP-2 in the dialysate drained from the peritoneal cavity was the latent form that was lacking activity. In the present study, we investigated whether MMP-2 causes peritoneal injury. METHODS: To create an animal model of peritoneal injury, we administered intraperitoneally chlorhexidine gluconate to rats. Dialysate drained from these rats was analysed by gelatin zymography and MMP-2 activity was analysed by an in situ film zymography method. In vitro myofibroblasts were cultured in collagen three-dimensional culture and then MMP-2 in conditioned medium from the culture was analysed by gelatin zymography. RESULTS: Zymographic analysis revealed that latent form MMP-2 levels were high in the dialysate from peritoneal injury rats, whereas the active form was barely detectable. MMP-2 activity in the peritoneal tissue of the peritoneal injury rats was strongly detected by in situ film zymography. In vitro myofibroblasts were promoted to produce MMP-2 and to activate MMP-2 in collagen three-dimensional culture. CONCLUSIONS: In the present model, most of the MMP-2 was in the latent form, but activation of MMP-2 was promoted in the peritoneum during peritoneal injury. Activated MMP-2 may be associated with the progression of peritoneal injury.     

A survey of perceptions and attitudes among European surgeons towards the clinical impact and management of postoperative ileus

OBJECTIVE: Postoperative ileus (POI) can negatively affect patient recovery and morbidity, yet the lack of an internationally accepted definition and clinical management pathway for this condition suggest POI may be under-recognized as a clinical problem. The purpose of this survey was therefore to assess current attitudes of surgeons towards the clinical impact and management of POI. SUBJECTS AND METHODS: Telephone interviews were conducted with 230 surgeons from hospitals in the UK, France, Germany, Italy and Spain. RESULTS: Across Europe, there are differences in the terms surgeons use to refer to delayed recovery of gastrointestinal (GI) function and the symptoms, concerns and risks they associate with this condition. Furthermore, there is marked variation in the attitudes of European surgeons towards minimizing the risk of delayed recovery of GI function and in the strategies to manage POI. Additionally, some of the measures applied most commonly by European surgeons are in contrast to evidence in the literature indicating that they have no benefit for quicker resolution of GI function. CONCLUSION: The results suggest that there is a need for clearer definition of the factors that constitute POI, increased recognition of the impact of this condition and improved understanding of the most effective peri-/postoperative care for surgical patients.     

Epidural morphine delays gastric emptying and small intestinal transit in volunteers

The influence of a painful stimulus and lumbar epidural morphine on gastric emptying, the orocecal transit time and small intestinal transit were studied in nine healthy volunteers. Acetaminophen absorption was used as a measure of the rate of gastric emptying. Orocecal transit time was determined by measuring the end-expiratory hydrogen concentration. Small intestinal transit was calculated from measurements of the orocecal transit time and gastric emptying. Cold pain stress with intermittent immersion of the feet in ice-cold water was used as a painful stimulus. Each volunteer was investigated on 3 different days: once after receiving 4 mg of epidural morphine and during cold pain; once during cold pain; and once under control conditions without pain and epidural morphine. Immersion of the feet in ice-cold water was always very painful, but was more tolerable during epidural morphine analgesia. The increase in blood pressure which accompanied the cold pain was the same whether this pain was induced without or during epidural morphine analgesia. Gastric emptying, orocecal transit time and small intestinal transit were delayed during epidural morphine analgesia compared with the findings under the control and plain cold pain conditions. Cold pain stress alone did not influence gastric emptying, orocecal transit time or intestinal transit. To conclude, epidural morphine in itself delayed gastric emptying, orocecal transit and transit through the small intestine in healthy volunteers.     

Effect of colonic distention on ileal motor activity with evidence of coloileal reflex

Chyme delivery from the ileum to the colon is controlled by various neurologic and hormonal factors, many of which remain to be identified. In this report we investigated the effect of colonic distention on ileal motility with the aim of identifying the mechanism of chyme delivery from the ileum to the colon. The right colon of 16 healthy volunteers (12 men and 4 women; mean age 36 ± 9 years standard deviation) was distended by a balloon that was filled with saline solution in increments of 20 ml. The pressure response of the terminal ileum to the colonic distention was recorded by a saline-perfused tube. The test was repeated in nine subjects after the colonic segment around the balloon was anesthetized by xylocaine injection into the colonic wall. Twenty and 40 ml colonic distention produced no significant ileal pressure response. Colonic distention with 60 ml produced an increase in colonic pressure (P < 0.05), as measured by intraballoon pressure, and a decrease in ileal pressure (P < 0.05); a similar response was achieved with 80 ml distention. At 100 ml colonic distention, the balloon was dispelled to the transverse colon. Distention up to 100 ml of the anesthetized colonic segment produced no significant colonic or ileal pressure response. The flow of chyme from the small to the large gut appears to be controlled by a reflex mechanism that we call the ‘coloileal reflex.’ Whenever the right colon is distended with a substantial volume of chyme that increases the intraluminal pressure, it is suggested that ileal relaxation occurs, which delays the emptying of chyme from the ileum.     

Effects of endotoxin on intestinal hemodynamics, glutamine metabolism, and function

The purpose of this study was to investigate the intestinal hemodynamics and gut glutamine metabolism during endotoxemia, and their correlation with altered intestinal absorptive capacity and permeability. Seventeen Sprague-Dawley rats were used in the study. The endotoxin group (ENDO) recieved endotoxin (10 mg/kg intraperitoneally,n=9), while the control group (CONT,n=8) received saline injection. Twelve hours later, D-xylose (0.5 g/kg) and fluorescein isothiocyanate-dextran (FITC-dextran, 750 mg/kg) were given by oral gavage. One hour later abdominal aortic (AA) blood flow, superior mesenteric venous (SMV) flow, mean arterial pressure (MAP), central venous pressure (CVP), and SMV pressure (SMVP) were also measured. The MAP, AA, and SMV blood flow decreased (P<0.05), while the CVP and SMVP increased (P<0.05) in the ENDO group as compared with the CONT group. The ENDO group showed significant decreases for both intestinal glutaminase activity and net intestinal glutamine uptake (P<0.05). The D-xylose concentration in SMV decreased significantly (P<0.05) in the ENDO group as compared with the CONT group. However, the plasma FITC-dextran concentration showed no significant difference between the groups. Endotoxin produced a hypodynamic effect in rats 12h after intraperitoneal administration in association with both a decreased intestinal glutamine metabolism and an absorptive capacity.     

Role of Extrinsic and Intrinsic Nerves in Hormonal Induction of the Migrating Motor Complex in the Jejunum

The mechanism of induction of the migrating motor complex (MMC) by neural or humoral agents and their role in the control of fasting motility are not well understood. Our aim was to determine the role of extrinsic und intrinsic nerves in mediating the induction of the MMC by motilin. Three groups of dogs were studied. Group I consisted of neurally intact control dogs. In group II, intrinsic neural continuity between the duodenum and the jejunum was interrupted by transection and reanastomosis of the distal duodenum. Dogs in group III underwent disruption of all intrinsic and extrinsic neural input to the entire jejunoileum. Serosal electrodes were sewn to duodenum and jejunum in all dogs. After a 2-week recovery, fasting myoelectric activity was recorded on four or more occasions. Motilin (0.1 µg/kg iv) was given 30 min after a spontaneous duodenal phase III. In group I (controls), motilin induced a premature MMC, which originated in the duodenum and migrated along the small intestine. In group II (intrinsic neural disruption), motilin induced a premature MMC, which began simultaneously in the proximal duodenum and proximal jejunum. In group III (intrinsic and extrinsic neural disruption), motilin induced a premature MMC in the duodenum but not in the jejunum: rather, a short, nonmigrating burst of spike potentials occurred simultaneously in all jejunal electrodes. These observations suggest that extrinsic innervation is necessary for motilin to induce phase III activity in the jejunum. Extrinsic neural pathways appear to mediate motilin-induced MMC activity in the jejunum.     

Effects of intestinal electrical stimulation on postprandial small-bowel motility and transit in dogs

Background

Intestinal electrical stimulation (IES) with long pulses has been reported to inhibit motility as well as accelerate transit of continuous infusion. However, it is unknown whether there is a correlation between the IES-induced alterations in motility and transit and whether there is a difference in transit during IES between continuous infusion and bolus infusion.

Methods

The study was performed in 2 postprandial sessions (control and stimulation) in dogs with 2 pairs of serosal electrodes and 2 intestinal cannulas. Intestinal motility and transit with and without IES were measured by manometry and phenol red, respectively.

Results

IES significantly decreased intestinal motility and increased transit time. There was a significant correlation between motility index and transit during IES.

Conclusions

IES inhibits both intestinal bolus motility and transit. There is correlation between motility and transit during IES.     

舒芬太尼复合小剂量纳美芬对术后静脉自控镇痛效能的作用

目的：观察舒芬太尼复合小剂量纳美芬用于术后静脉自控镇痛效果和对胃肠动力变化的影响。方法：选择全麻术后静脉自控镇痛患者58例,按照随机数字表法随机分为2组,对照组（舒芬太尼组）镇痛泵配方为舒芬太尼2μg/kg、氟哌利多2.5 mg稀释至100 mL,纳美芬组（纳美芬-舒芬太尼组）在对照组基础上加纳美芬0.5μg/kg。结果：与对照组相比,纳美芬组恶心呕吐发生率明显降低,首次排气时间明显缩短（P＜0.05）。结论：小剂量纳美芬可增强镇痛效果,减少舒芬太尼术后镇痛恶心呕吐发生率,同时促进肠蠕动恢复。     

Effects of Prostaglandin F2α and Cisapride on Small Intestinal Activity During the Early Postoperative Period in Humans

2 α (PGF) and cisapride were investigated during the early postoperative period in 26 patients who underwent abdominal surgery. Records of intestinal motility were made using an infusion catheter. PGF, 0.4 μg/kg per minute, given intravenously over 60 min, and cisapride, 5 mg, given intraintestinally, were administered to 13 patients each, first immediately after the operation, and then after the migrating motor complexes (MMCs) had reappeared following a period of intestinal quiescence. The MMCs were reestablished within the first postoperative day. Both PGF and cisapride stimulated irregular, high-amplitude contractions; however, the MMCs reappeared following these induced contractions only if the drugs were administered just after the postoperative MMCs became evident. These prokinetic drugs did not affect gastrointestinal hormone concentrations, but induced contractile activity even in the early postoperative period. Although the findings of this study demonstrate that these drugs may be useful as prokinetic agents to promote recovery from postoperative ileus just after the reappearance of MMCs in the early postoperative period, their precise mode of action has not been established. (Received for publication on May 7, 1997; accepted on Nov. 6, 1997)     

The effect of lymphatic blockage on the amount of endotoxin in portal circulation, nitric oxide synthesis, and the liver in dogs with peritonitis

P < 0.0001). Bacteria grew in all of the blood cultures from the group 2 animals, but growth was seen only in blood cultures from four of the group 3 animals. The levels of endotoxin, nitrite, and AST levels in group 3 were significantly increased in comparison with those in group 2 (P < 0.0001). Extensive hepatocellular necrosis with hemorrhage was observed in the livers of the group 3 animals, and all of them died within 48 h. The results of this study suggest that the blockage of lymph flow has a negative effect on liver and survival in dogs with peritonitis, and that hepatic damage is directly related to the amount of endotoxin to which the liver is exposed. (Received for publication on Mar. 23, 1998; accepted on Jan. 7, 1999)     

Higher rate and earlier peritonitis in Aboriginal patients compared to non-Aboriginal patients with end-stage renal failure maintained on peritoneal dialysis in Australia: analysis of ANZDATA

BACKGROUND: Aboriginal patients maintained on peritoneal dialysis (PD) have a higher rate of technique failure than any other racial group in Australia. Peritonitis accounts for the bulk of these technique failures, but it is uncertain whether the increased risk of peritonitis in Aboriginal patients was independent of associated comorbid conditions, such as diabetes mellitus. METHODS: Using data collected by the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA), peritonitis rates and time to first peritonitis were compared between Aboriginal (n = 238) and non-Aboriginal patients (n = 2924) commencing PD in Australia between 1 April 1999 and 31 March 2003. RESULTS: Aboriginal PD patients were younger, and had a higher incidence of diabetes than their non-Aboriginal counterparts. Mean peritonitis rates were significantly higher among Aboriginal (1.15 episodes/year; 95% confidence interval (CI): 1.03-1.28) than non-Aboriginal patients (0.60 episodes/year; 95% CI: 0.57-0.62, P < 0.05). Using multivariate negative binomial regression, independent predictors of higher peritonitis rates include Aboriginal racial origin (adjusted odds ratio 1.78; 95% CI: 1.45-2.19), obesity, age and absence of a recorded dialysate : plasma creatinine ratio (D/P creatinine) measurement. Aboriginal racial origin was also associated with a shorter median time to first peritonitis (9.9 vs 19.3 months, P < 0.05), which remained statistically significant in a multivariate Cox proportional hazards model (adjusted hazard ratio 1.76; 95% CI: 1.47-2.11, P < 0.05). CONCLUSION: Aboriginal and obese PD patients have a higher rate of peritonitis and a shorter time to first peritonitis, independent of demographic and comorbid factors. Further investigation of the causes of increased peritonitis risk in Aboriginal patients is needed.     

Free air on CT and the risk of peritonitis in peritoneal dialysis patients: a retrospective study

Background: Intra-abdominal free air is found frequently in patients undergoing peritoneal dialysis (PD). Some studies have investigated an association between intra-abdominal free air and peritonitis in PD patients. However, most used chest X-rays, which are of limited sensitivity, and the association was not made clear. We conducted a retrospective study of the association between peritonitis and intra-abdominal free air using computed tomography. Methods: The presence and volume of free air, and its relationship with other variables, were assessed on review of routine examinations in 108 patients. Correlations between the presence of free air and age, duration of PD, continuous ambulatory versus automated PD, presence or absence of a person who assisted in bag changes, exit-site infection, tunnel infection and peritonitis were assessed. Results: Free air was detected in 29 patients (27.1%). The prevalence of peritonitis was higher in the free air (+) group than in the free air (?) group: 1/40.2 patient-months for free air (+) versus 1/96.9 patient-months for free air (?). The risk ratio of free air for peritonitis was 2.41 (95% confidence interval: 2.28–2.55) and was similar when corrected for age, gender, albumin, diabetes mellitus and body mass index. Conclusion: Free air is an independent risk factor for peritonitis in PD patients. This suggests that bag change procedures should be re-evaluated, and patients re-educated, when necessary.     

内毒素介导的急性肺损伤大鼠白细胞介素13表达及肺组织激活剂蛋白1活性的变化

目的　观察内毒素 /脂多糖 (LPS)致伤大鼠的血浆白细胞介素 (IL)13含量及肺组织激活剂蛋白 1(AP 1)活性的变化 ,探讨AP 1与IL 13表达的关系。　 方法　将 12 0只Wistar大鼠根据注射LPS剂量不同随机分为A(2mg/kg)、B(4mg/kg)、C(6mg/kg)、D(8mg/kg)组 ,并设立相应的等渗盐水对照组 (NS组 ) ,取伤后 1、2、4、6h为观察时相点 ,每组每时相点 6只大鼠。致伤Wistar大鼠 ,复制全身炎症反应综合征 急性肺损伤 (SIRS ALI)模型。在致伤后 1、2、4、6h,采用酶联免疫吸附测定法 (ELISA)检测血浆IL 13含量 ,采用凝胶迁移率分析法 (EMSA)检测肺组织中AP 1活性。　 结果　LPS可使IL 13含量及AP 1活性同步升高。A、B、C、D组与NS组比较 ,差异均有显著性意义及非常显著性意义 (P <0.0 5～ 0.0 1)。C、D组的血浆IL 13含量及肺组织中的AP 1活性均显著增加 ,D组两指标的峰值分别为 (45 .6 2± 5 .78) pg/ml、(177.6 8± 6.81)NII%,均出现在伤后 2h。　 结论　IL 13表达增强时AP 1活性亦升高 ,并与SIRS ALI发生有关。     

Contribution of lactate buffer, glucose and glucose degradation products to peritoneal injury in vivo.

BACKGROUND: Long-term peritoneal dialysis (PD) is associated with the development of functional and structural alterations of the peritoneal membrane. In this study, we investigated the contribution of low pH lactate buffer, high glucose concentration and glucose degradation products to peritoneal injury in a rat peritoneal exposure model. METHODS: Rats received daily 10 ml of either heat-sterilized (3.86% glucose, pH 5.2, n = 8) or filter-sterilized PD fluid (3.86% glucose, pH 5.2, n = 8), or lactate buffer (pH 5.2, n = 8) via a mini vascular access port during a 10 week period. Untreated rats served as controls. RESULTS: The low pH lactate buffer instillation induced pronounced morphological changes including the induction of angiogenesis in various peritoneal tissues and mild damage to the mesothelial cell layer covering the peritoneum. It also evoked a cellular response characterized by an increased mesothelial cell density on the liver, the induction of milky spots and accumulation of omental mast cells in the omentum, and significant changes in the composition of peritoneal leukocytes. The addition of glucose to low pH lactate buffer (filter-sterilized PD fluid) strengthened most, but not all of the responses described above and induced a fibrogenic response. In addition to glucose and low pH lactate buffer, the presence of glucose degradation products (heat-sterilized PD fluid) significantly induced an additional omental milky spot response (P < 0.03) and caused profound mesothelial damage. The vessel density in the omentum and the mesentery was significantly correlated to both the number of tissue mast cells and the hyaluronan content in the peritoneal lavage, which might suggest a role for mast cells and hyaluronan in the induction of angiogenesis. CONCLUSIONS: Instillations of low pH lactate buffer, a high glucose concentration and glucose degradation products contribute differently and often cumulatively to peritoneal injury in vivo.     

Effects of lazaroids on intestinal ischemia and reperfusion injury in experimental models

Mesenteric ischemia occurs in a number of clinically relevant pathophysiologic processes, including sepsis, hemorrhage, intestinal transplantation, severe burns, and mesenteric thrombosis. The readmission of molecular oxygen into an ischemic tissue promotes the oxidation of resuscitated tissue with certain pathophysiologic mechanisms. Depending on the duration and the intensity of ischemia, reoxygenation of the intestine that has been reperfused may further induce tissue injury. Intestinal ischemia and reperfusion injury can accelerate complex processes between the endothelium and different cell types leading to microvascular injury, cellular necrosis, and apoptosis. The injury due to reperfusion is found predominantly in the intestinal mucosa and submucosa, causing endothelial detachment. The 21-aminosteroids (lazaroids) are a family of compounds that inhibit lipid membrane peroxidation. Many of the performed studies show conflicting results, which reflect differences in experimental design, evolving time that (I/R) is induced, total or partial vascular occlusion, dosage of the lazaroid, and the exact period of time that the lazaroid is administered.     

Influence of peritoneal fluid from spontaneous and stimulated cycles on sperm motility in vitro

Summary. Peritoneal fluids ( PF s) from spontaneous ( n = 14) and gonadotrophin-stimulated cycles ( n = 20) were obtained during diagnostic laparoscopy and gamete intrafallopian transfer (GIFT) procedures, respectively. The effects of these fluids on the linear component of sperm motility and on the percentage of motile spermatozoa were studied in vitro by objective motility assessments and compared to a control medium ( B ₂-Ménézo).
Overall, the two types of PFs were found to have rather similar effects on the motility parameters studied. However, the fluids from hormonally-stimulated cycles sustained motility better (i.e., sperm velocity and percentage of motile sperm) and in a rather constant manner as a function of time (narrower range distributions of the motility measurements). Furthermore, it was observed that under identical experimental conditions motility measurements depended not only on the type of PF used but also on the sperm sample.
These results suggest that assisted reproduction procedures in which PF is the medium where the gametes eventually meet and interact, such as direct peritoneal insemination ( DIPI ) or peritoneal oocyte and sperm transfer ( POST ), could have different success rates if performed in spontaneous rather than in stimulated cycles. At the same time, our results may help to explain why different pregnancy rates were reported in different studies using DIP or POST.