Effect of Probiotic Supplementation on Bacterial Translocation in Thermal Injury

Purpose To examine the effects of probiotic supplementation and enteral solutions containing glutamine and arginine on bacterial translocation (BT) and intestinal villous atrophy in thermal injury.Methods Forty male Sprague-Dawley rats weighing 200–250 g were divided into four groups of ten. Group 1 served as control group without thermal injury and was fed standard chow. Thermal injury was inflicted as a 30% scald burn in the other three groups. Group 2 was fed standard chow and group 3 was fed standard chow supplemented with a probiotic (Acidophilus plus) containing Bifidobacterium bifidum, Lactobacillus acidophilus, and Lactobacillus bulgaricus (2 × 10⁹ CFU/day) via an orogastric tube. Group 4 was fed only an enteral diet (Stresson multifiber) containing glutamine, arginine, and medium chain triglyceride, at 1 g/kg per day amino acid and 230 kcal/kg, for 7 days before thermal injury. All the animals were killed 24 h after thermal injury, and ileal segments were resected and examined histopathologically. To evaluate BT, samples from blood, mesenteric lymph nodes, and cecal content were cultured under aerobic and anaerobic conditions. Terminal ileum specimens were histologically examined to evaluate mucosal integrity.Results Significantly less BT was seen in groups 3 and 4 than in group 2 (P < 0.001). No significant difference was found between groups 3 and 4. Histological evaluation showed significant reduction in villous atrophy in groups 3 and 4.Conclusion Probiotic supplementation seems to reduce bacterial translocation and decrease intestinal mucosal atrophy in rats with thermal injury, as do enteral solutions with arginine and glutamine.     

Effect of Glutamine and Bile Acid on Hepatocyte Apoptosis after Bile Duct Ligation in the Rat

Apoptosis is an important process in a wide variety of biologic systems. Cholestasis, or impaired bile formation, occurs in a wide variety of human liver diseases. Retention and accumulation of toxic hydrophobic bile salts in hepatocytes may cause hepatocyte toxicity by inducing apoptosis. In addition, the translocation of bacteria and endotoxin, well documented in patients with obstructive jaundice, contribute to the induction of hepatocyte apoptosis. We hypothesized that oral bile acid replacement, glutamine administration, or both can attenuate or abolish hepatocyte apoptosis. Male Sprague-Dawley rats weighing 250 to 300 g were randomized to four groups (10 in each group). Group 1 underwent a sham operation and was simultaneously treated with normal saline. Group 2 underwent common bile duct (CBD) ligation and was simultaneously treated with normal saline. Group 3 underwent CBD ligation and was simultaneously treated with oral glutamine. Group 4 underwent CBD ligation and was simultaneously treated with oral bile acid replacement. After 3 days (n = 5) and 7 days (n = 5), liver tissues were harvested for histopathologic analysis and apoptosis measurements. When compared with the sham operation group, significantly increased hepatocyte apoptosis and ductular proliferation occurred after CBD ligation for either 3 or 7 days. After administration of either glutamine or bile acid, the increased hepatocyte apoptosis and ductular proliferation after CBD ligation for 3 days were significantly diminished. However, both failed to diminish the changes after CBD ligation for 7 days. Significantly increased hepatocyte apoptosis and ductular proliferation occurred after CBD ligation. The administration of either glutamine or bile acid effectively diminished the hepatocyte apoptosis and ductular proliferation after CBD ligation for 3 days, whereas both failed to show the same effect after CBD ligation for 7 days.     

Prostaglandin E1 maintains structural integrity of intestinal mucosa and prevents bacterial translocation during experimental obstructive jaundice.

The absence of bile in the gut lumen induces mucosal injury and promotes bacterial translocation (BT). Prostaglandin E (PGE) has a protective effect on the mucosal layer of the alimentary tract. We hypothesize that PGE1 may prevent BT by its beneficial action on the mucosa of the small bowel. Thirty Wistar albino rats were divided equally into 3 groups; Group 1 (control) underwent sham laparotomy, group 2 obstructive jaundice (OJ) and group 3 (OJ + PGE1) underwent common bile duct (CBD) ligation and transection. Groups 1 and 2 received; 1 mL normal saline and group 3 received 40 mg of the PGE1 analogue misoprostol dissolved in 1 mL normal saline administered by orogastric tube once daily. After 7 days, laparotomy and collection of samples for laboratory analyses were performed, including bacteriological analysis of intestine, mesenteric lymph nodes (MLNs), and blood, and histopathologic examination of intestinal mucosa to determine mucosal thickness and structural damage. Serum bilirubin and alkaline phosphatase levels confirmed OJ in all animals with CBD transection. The mucosal damage score was significantly reduced in jaundiced animals receiving PGE1 compared to jaundiced controls (2.15 +/- 0.74 vs 5.3 +/- 0.59; p < .00001) and mucosal thickness was greater (607 +/- 59.1 microm vs. 393 +/- 40.3 microm; p < .00001). The incidence of BT to MLNs decreased from 90% to 30% (p < .02) when jaundiced rats received PGE1. PGE1 treatment reduced the detection rate of viable enteric bacteria in the blood from 60% to 10% (p < .057). We conclude that administration of PGE1 provides protection against OJ-induced atrophy and damage of intestinal mucosa, and thereby prevents translocation of enteric bacteria to underlying tissues.     

Obstructive Jaundice Alters Proliferating Cell Nuclear Antigen Expression in Rat Small Intestine

Translocation of bacteria and endotoxin has long been documented in obstructive jaundice, and altered intestinal barrier function is considered to be one of the important mechanisms for this phenomenon. Proliferating cell nuclear antigen (PCNA), also known as cyclin, is an auxiliary protein of DNA polymerase-, and the level of synthesis correlates directly with rates of cellular proliferation and DNA synthesis. This study was designed with the aim of evaluating the effect of obstructive jaundice on PCNA expression in small bowel epithelium. Male Sprague-Dawley rats were randomized to four groups. Group A (n = 10, control group) underwent a sham operation. Group B (n = 9, obstructive jaundice group for 1 week) underwent common bile duct ligation. Group C (n = 8, obstructive jaundice group for 2 weeks) underwent common bile duct ligation. Group D (n = 8, obstructive jaundice group for 2 weeks) underwent common bile duct ligation with oral glutamine intake. After periods of 7 days and 2 weeks, segments of small bowel were harvested from groups A & B and groups C & D, respectively. Nuclear immunohistochemical expression of PCNA in small bowel was evaluated. The PCNA-labeling index [(PCNA-positive cells/500 cells) × 100] was quantified. Comparisons among the four groups were performed. The PCNA-labeling index in small bowel of group B was significantly higher than that of group A (29.0% vs 21.2%, p = 0.001). After 2 weeks of common bile duct ligation, the PCNA-labeling index in small bowel of group C was significantly lower than that of group A (19.4% vs 21.2%, p = 0.045). With oral glutamine intake daily, the PCNA-labeling index in small bowel of Group D was restored and was significantly higher than that of group A (24.5% vs 21.2%, p = 0.002). Obstructive jaundice for 1 week upgraded PCNA expression in rat small intestine. PCNA expression in rat small intestine later became depressed after obstructive jaundice for 2 weeks. Oral glutamine intake daily could effectively restore the PCNA expression in small bowel of rats subjected to obstructive jaundice for 2 weeks.     

Altered Serum Transforming Growth Factor-ß1 and Monocyte Chemoattractant Protein-1 Levels in Obstructive Jaundice

Impaired immune function has long been documented in patients with obstructive jaundice, and those with jaundice due to extrahepatic biliary obstruction still experience a high rate of postoperative complications and death. Transforming growth factor-ß1 (TGFß1) appears to be an important regulator of both normal and pathologic conditions in the liver. Monocyte chemoattractant protein-1 (MCP-1) is an important mediator of monocyte recruitment to inflammatory sites. We hypothesize that obstructive jaundice may alter serum TGFß1 and MCP-1 expressions in the rat and that oral bile acid or glutamine (or both) can restore the altered serum TGFß1 and MCP-1 expression in rats with obstructive jaundice. Male Sprague-Dawley rats weighing 250 to 300 g were randomized to four groups (n = 10 in each group). Group 1 underwent a sham operation with oral normal saline administration. Group 2 underwent common bile duct ligation (CBDL) with oral normal saline administration. Group 3 underwent CBDL with oral bile acid replacement. Group 4 underwent CBDL with oral glutamine administration. Animals were sacrificed after 3 days (n = 5) and 7 days (n = 5), and blood samples were collected. Serum was obtained after centrifugation for measurement of TGFß1 and MCP-1 levels by an enzyme-linked immunosorbent assay. The serum TGFß1 level was significantly elevated (p = 0.006) 3 days after CBDL. Oral glutamine administration prevented this elevation, but oral bile acid replacement did not. The serum MCP-1 level showed similar changes. After 3 days of obstructive jaundice, the TGFß1 and MCP-1 levels were altered in the rat. Oral glutamine administration, not oral bile acid replacement, was able to prevent these alterations.     

肠道缺血再灌注损伤时淋巴干结扎及谷氨酰胺营养干预的作用

目的研究肠道缺血再灌注损伤时肠淋巴干结扎和含谷氨酰胺的肠内营养对肠道及远隔组织的影响。方法 40只SD大鼠胃造瘘后随机分为:假手术组、普通肠内营养组、普通肠内营养+肠淋巴干结扎组、谷氨酰胺组及谷氨酰胺+肠淋巴干结扎组,每组8只。除假手术组外,其余4组大鼠行7 d肠内营养干预后开腹夹闭肠系膜上动脉60 min,2个结扎组同时进行淋巴干结扎;假手术组行普通饮食7 d后开腹60 min后关腹。所有大鼠术后继续原营养3 d。于再灌注前1 d、再灌注后1 d及3 d测定肠道通透性,在再灌注后3 d观察肠壁形态学改变,检测血清中内毒素、D-乳酸、二胺氧化酶水平及肺组织细胞凋亡指数。结果再灌注后1 d时,各组肠道通透性均比再灌注前明显增加(P0.05);再灌注后3 d时与再灌注后1 d比较,2个结扎组的肠道通透性均明显降低(P0.05)。谷氨酰胺+肠淋巴干结扎组回肠和空肠的黏膜厚度及回肠的绒毛高度明显高于其余4组(P0.05),谷氨酰胺组回肠的绒毛高度明显高于普通肠内营养组(P0.05);普通肠内营养+肠淋巴干结扎组肠壁各形态学指标均高于普通肠内营养组,但差异无统计学意义(P0.05)。肠淋巴干结扎组的肺组织细胞凋亡指数明显低于未结扎组(P0.05),内毒素、D-乳酸及二胺氧化酶水平较未结扎组有下降趋势,但差异无统计学意义(P0.05)。结论大鼠肠道缺血再灌注损伤引起肠道通透性增加、细菌内毒素移位和系统炎症反应,肠淋巴管结扎和谷氨酰胺肠内营养干预可以弱化肺组织损伤,增加肠黏膜的厚度,维护肠屏障功能,减少内毒素移位,降低血中内毒素水平,减轻系统炎症反应。含谷氨酰胺的肠内营养效果优于普通肠内营养。     

The prophylactic and therapeutic effects of glutamine- and arginine-enriched diets on radiation-induced enteritis in rats

BACKGROUND: Recent studies indicated that glutamine and arginine support the mucosal barrier in several ways. This experimental study hypothesized that administration of glutamine- and arginine-enriched diets before abdominal radiation therapy would provide a radioprotective effect on intestinal mucosa, and this would augment the therapeutic effectiveness provided by postirradiation administration. MATERIALS AND METHODS: A rat model of radiation enteritis was designed with a single dose of 1100 cGy to the abdomen. Thirty-five rats were randomized into five groups of seven. A 7-day glutamine-enriched diet for Group I and a 7-day arginine-enriched diet for Group II were administered both pre- and postradiation. For Groups III and IV, the same glutamine and arginine diets were given, respectively, postradiation only. Group V was fed a glutamine- and arginine-free diet and was the control group. The rats underwent laparotomy for culture of mesenteric lymph nodes and removal of segments of ileum, jejenum, and colon for microscopic examination. RESULTS: Bacterial translocation was significantly higher in Group V (P < 0.05), while intestinal villus count and villus height were significantly higher in all of the groups fed glutamine and arginine when compared with the control group (P < 0.0001 and P < 0.05, respectively). CONCLUSION: Both arginine- and glutamine-enriched diets have protective effects on gut mucosa in the postirradiation state; however, pre- and postirradiation administration together does not provide superior protection versus postradiation administration alone.     

Effect of Oral Glutamine Administration on Bacterial Tanslocation, Endotoxemia, Liver and Ileal Morphology, and Apoptosis in Rats with Obstructive Jaundice

Postoperative complications in patients with obstructive jaundice remain increased when associated with endotoxemia and the inflammatory response due to gut barrier failure. Administration of glutamine has been proposed to maintain the integrity of the gut mucosa and thus reduce bacterial translocation (BT), but the effects of this pretreatment on apoptosis and histologic morphology of various organs affected by BT in obstructive jaundice have not been studied. We therefore studied the effects of oral glutamine supplementation on endotoxemia, BT, liver and terminal ileal morphology, and apoptosis in an experimental model of obstructive jaundice. A total of 60 male Wistar rats were randomly divided into four groups of 15 each: I, controls; II, sham-operated; III, bile duct ligation (BDL); IV, BDL + glutamine (4.5 g/kg/day in drinking water). Ileal samples for histology, DNA and protein content, liver biopsies, mesenteric lymph nodes (MLNs) for culture, and portal and systemic blood samples for endotoxin measurements were obtained 10 days later. Compared to the controls, a significant increase in contaminated MLN and liver samples and increased endotoxemia were noted in group III (p < 0.01) but were significantly reduced in group IV (p < 0.05). Group IV also had a significantly higher number of mitoses per crypt (M/c) (p < 0.05), less apoptotic body counts (ABCs) (p < 0.05), and a higher DNA content than did group III (p < 0.05). Liver biopsies from group III displayed typical changes of large duct obstruction that significantly improved after glutamine treatment, with decreased ductular proliferation. We concluded that supplementation of oral glutamine in the presence of obstructive jaundice ameliorates BT, endotoxemia, and apoptosis and improves the ileal and liver histology.     

Effects of ursodeoxycholic acid,glutamine and polyclonal immunoglobulins on bacterial translocation in common bile duct ligated rats

Background: The present study was conducted to investigate the effects of ursodeoxycholic acid (UDCA), glutamine and i.v. polyclonal immunoglobulins (IVIG) on the bacterial translocation (BT) and intestinal integrity of obstructive jaundice (OJ) in an animal model. Methods: Fifty rats were randomized into five groups containing 10 rats each. All procedures were performed aseptically under general anaesthesia using intramuscular ketamine (25 mg/kg). The abdomen was opened and the common bile duct was identified, mobilized, doubly ligated using 5−0 silk and divided. In group 1 (the ‘sham’ group), the rats had a similar incision followed by mobilization of the common bile duct (CBD), without ligation or division. In group 2 rats, only common bile duct ligation (CBDL) was performed. In group 3, CBDL was performed and UDCA was administered by orogastric intubation once daily. In group 4 rats, CBDL was performed and glutamine was given by orogastric intubation once daily. Therapeutic substances were started orally on the day CBDL was fulfilled and were continued for 7 days. In group 5, IVIG was administrated via a femoral vein catheter just before CBDL. The animals were killed at the end of the 7th day, and serum levels of total bilirubin (TB), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and gamma-glutamyl transpeptidase (GGT) were measured. Mesenteric lymph nodes (MLN), liver, spleen and blood were cultured. The terminal ileum specimens were examined histopathologically. Results: Bacterial translocation significantly increased in the MLN and spleen of rats in group 2 as compared to groups 3, 4 and 5 (P < 0.05, P = 0.001, P = 0.001, respectively). The BT of the liver in group 2 was significantly higher than that of group 5 (P < 0.05). In the blood, the BT was significantly higher in group 2 than groups 3, 4 and 5 (P < 0.05). The bacterial counts, colony-forming units per gram tissue (cfu/g), were found significantly higher in MLN, liver and spleen of rats in group 2 than those of groups 3, 4 and 5 (P = 0.000). The average villus height in the group 4 was significantly higher than that of groups 2, 3 and 5 (P = 0.000). Conclusion: The present experimental study has demonstrated that the administration of glutamine, UDCA and IVIG reduce the incidence of BT and additionally glutamine preserves intestinal mucosal integrity.     

Improvement of portal flow and hepatic microcirculatory tissue flow with N-acetylcysteine in dogs with obstructive jaundice produced by bile duct ligation.

OBJECTIVE: To find out if N-acetylcysteine (NAC) would improve hepatic circulation in dogs with obstructive jaundice. DESIGN: Open laboratory study. SETTING: University hospitals, Japan and France. MATERIALS: 14 male beagle dogs and 10 male Wistar rats. INTERVENTIONS: Obstructive jaundice was produced by ligation of the common bile duct (CBD) for 7 days in both dogs and rats. Either 5% dextrose (control group, n = 7) or NAC (NAC group, n = 7) was given to dogs. Sinusoidal endothelial cells were obtained from rats after ligation by elutriation, and varying amounts of NAC were given. MAIN OUTCOME MEASURES: The volumes of portal blood flow and hepatic microcirculatory tissue flow were reduced after ligation of the CBD, but those increased after NAC had been given to dogs with obstructive jaundice. NAC increased the concentrations of plasma cyclic 3',5'-guanosine monophosphate (cGMP). It also increased concentrations of serum and hepatic-reduced glutathione, and hepatic adenosine triphosphate (ATP) in cholestatic dogs, and secretion of cGMP from sinusoidal endothelial cells from rats with obstructive jaundice. CONCLUSION: These results suggest that NAC given intravenously effectively improves hepatic circulation and hepatic function in dogs with obstructive jaundice.     

Growth failure and decreased levels of insulin-like growth factor I in obstructive jaundice are reversed by bile diversion

Insulin-like growth factor I (IGF-I) is one of the principal stimuli of linear growth. Growth failure in children with chronic cholestatic jaundice may be related to decreased hepatic synthesis of IGF-I. It was hypothesized that (1) biliary obstruction would lead to growth retardation and decreased circulating IGF-I levels; and (2) surgical drainage of the obstructed biliary system would reverse these effects. To test this hypothesis, the following study of male Sprague-Dawley rats (135 g; 10 animals per group) was performed. Group I underwent common bile duct ligation (CDL); group II underwent choledochoduodenostomy 2 weeks following CDL; group III were sham-operated and fed with CDL rats; and group IV were sham-operated and fed ad libitum. Daily food intake and weekly body weight were recorded. Statistical analysis was by repeated-measures analysis of variance and individual comparisons were evaluated by Student's t test. Biliary obstruction results in decreased food intake, rate of weight gain, and IGF-I levels. A significant reduction in IGF-I levels was also noted in the pair-fed sham-operated rats (group III). Relief of obstructive jaundice by surgical drainage results in a reversal of these changes. It is concluded that the growth failure and decreased IGF-I levels associated with obstructive jaundice can be reversed by surgical drainage of the obstructed biliary system and, in part, are due to inadequate nutrition.     

Experimental Obstructive Jaundice Results in Oxidized Low-Density-Lipoprotein Accumulation in Surgical Wound of Rats

Introduction : Mounting evidence suggests that impaired wound healing is a well-defined consequence in obstructive jaundice and, as redox-regulated processes are relevant to wound healing, it is not unreasonable to suppose that oxidative stress associated with lipid peroxidation in cholestasis might be a systemic phenomenon probably comprising all tissues and organs, including wounds. The aim of the present investigation was to analyse the lipid peroxidation status of surgical wounds, in terms of oxidized low-density-lipoprotein (oxLDL) accumulation in experimental obstructive jaundice.

Methods : Sixteen Wistar-Albino rats weighing 200–230 gr were randomly divided into two groups. Group I (n = 8) was designed as the prolonged obstructive jaundice group and was subjected to bile duct ligation. Group II (Sham-control, n = 8) rats underwent laparotomy alone and bile duct was just dissected from the surrounding tissue. Histopathological evaluation, immunohistochemical screening and immunoflourescent staining of the surgical wound was conducted to the bile-duct ligated rats and control group on the 21^st postoperative day.

Results : Wound healing was found to be impaired in jaundiced rats histopathologically. When compared with the control group, significant positive oxLDL staining and intracellular accumulation of TNF-a, IL-2 and iL-6 was detected in the wound sections of the prolonged obstructive jaundice group.

Conclusion : Our present data is the first in the literature, indicating significant oxLDL accumulation in surgical wounds of cholestatic rats, which might be one of the results of systemic oxidative stress leading to deficient healing capacity as a consequence of persistent inflammation.     

Glutamine ameliorates mechanical obstruction-induced intestinal injury

BACKGROUND: Glutamine has been shown to be an important dietary component for the maintenance of gut integrity. Although considered a nonessential amino acid in normal circumstances, glutamine may become conditionally essential for the bowel during episodes of severe illness and malnutrition. In this study, we employed an animal model simulating mechanical intestinal obstruction to explore the beneficial effects of glutamine on the intestine in response to obstruction-induced injury. MATERIALS AND METHODS: Rats were on three feeding regimens-standard diet and water (control group), diet and water containing 2% glutamine (glutamine group), or diet and water containing 2% arginine (arginine group)-for 3 days prior to surgical preparation of intestinal obstruction. The bowel distension, fluid accumulation, and histological alterations in the intestinal mucosa were measured 40 h after ileal ligation. RESULTS: After 3 days of drinking water intervention, the plasma glutamine levels in the glutamine group (677 +/- 12 microM) were higher than those in the control (451 +/- 27 microM) and arginine (379 +/- 25 microM) groups. The distension ratio measured 40 h after ileal ligation was significantly lower in the glutamine group (30.9 +/- 4.2%) than in the control and arginine groups (45.9 +/- 1.7 and 46.1 +/- 3.4%, respectively). Also, glutamine markedly decreased the fluid accumulation in the obstructed bowel segment (control group, 178.41 +/- 18.60 mg/cm; glutamine group, 104.97 +/- 13.17 mg/cm; arginine group, 141.4 +/- 12.85 mg/cm). Furthermore, the obstruction-induced mucosal injury was substantially improved in glutamine-fed rats. CONCLUSIONS: Our findings indicate that glutamine can significantly reduce the degree of those physiological derangements induced by mechanical intestinal obstruction.     

Effect of Bile Acid Replacement on Endotoxin-induced Tumor Necrosis Factor-a Production in Obstructive Jaundice

There is a high incidence of perioperative morbidity and mortality in patients with obstructive jaundice due to sepsis. Tumor necrosis factor-a (TNF-a) is considered a crucial mediator in inducing and processing the inflammatory cascade. We hypothesize that obstructive jaundice leads to an increased endotoxin-induced TNF-a production and that intestinal bile acid replacement can prevent this phenomenon. Sprague-Dawley rats were randomized to three groups of 12 animals each. Group 1 underwent common bile duct ligation (CBDL) with oral intestinal bile acid (deoxycholic acid 5 mg/100 g body weight/3 times daily) replacement (CBDL + bile acid); group 2 underwent common bile duct ligation with the same amount of normal saline replacement orally (CBDL + saline); and group 3 underwent a sham operation (sham control). After 2 days, endotoxin was given to the animals, and after 90 minutes, tissues (liver and lung) and blood were collected for checking the TNF-a levels and biochemical analyses. Comparisons among these three groups were performed and recorded. While serum and tissue (liver and lung) TNF-a levels of group 2 (CBDL + saline) were significantly increased after endotoxin challenge, these elevations were reduced to control levels (sham control) following oral replacement of intestinal bile acid (CBDL + bile acid). Obstructive jaundice leads to an increased endotoxin-induced TNF-a production and intestinal bile acid replacement can inhibit this phenomenon.     

The Effect of Calcium Dobesilate on Liver Damage in Experimental Obstructive Jaundice

Purpose/Aim of the study: Inflammation and oxidative stress are two significant factors affecting the degree of liver damage in obstructive jaundice. The aim of this study was to evaluate the effect of calcium dobesilate (CaDob), an effective antioxidant and anti-inflammatory drug, on damage to liver caused by experimental obstructive jaundice. Materials and Methods: 30 rats in total were randomly placed into three groups, each group consisting of 10 rats. The sham group (Group 1) only received solely laparotomy. In the control group (Group 2), ligation was applied to the biliary tract and no treatment was implemented. In the CaDob group (Group 3), following ligation of the biliary tract, 100 mg/kg/day CaDob was implemented via an orogastric tube for a 10–day period. Liver tissue and blood samples were taken for histopathological and biochemical examination. Results: The CaDob group had significantly lower test values for serum liver functions when compared to the control group. Statistically lower levels of tissue malondialdehyde (MDA) and fluorescent oxidation products (FOP) were detected in the CaDob group, and the CaDob group had significantly higher levels of sulfydryl (SH) than the control group. Histopathological scores in the CaDob group were found out to be statistically less than the scores the control group received (p < 0.05). Conclusions: CaDob treatment repaired the histpatological changes induced by bile duct ligation. The hepatoprotective effects of CaDob can be associated with its antioxidant properties of the drug.     

大鼠门静脉高压症及梗阻性黄疸时细菌移位与黄嘌呤脱氢酶和黄嘌呤氧化酶的关系

目的探讨大鼠门静脉高压症（porta; ju[ertemsopm,PH）及梗阻性黄疸（obstructive jaundioe,OJ）时,细菌移位（bacterial translocation,BT）与黄嘌呤氧化酶（xanthine oxidase,XO）、黄嘌呤脱氢酶（xanthine dehydrogenase,XD）之间的关系。方法将雄性SD大鼠60只随机分为对照组（A组）,胆总管结扎组（B组）和门静脉缩窄组（C组）,每组20只。术后第3周取肠系膜淋巴结、脾、肝组织及门静脉、腔静脉血细菌培养,测定门静脉压力（free portal pressure,FPP）,及肠XO,XD活性水平。结果B组及C组细菌移位率明显高于对照组（P〈0．01）,对照组为12％,B组和C组分别为28％和54％;B组和C组空肠XO水平活性明显高于对照组（P〈0．01）,B组和C组门静脉压力也较对照组升高。细菌移位率与XO活性成正相关（r=0．603）。XD活性水平无显著差异。结论门静脉高压症及梗阻性黄疸时可发生细菌移位,可能与肠黏膜屏障被破坏通透性增强有关,肠壁XO水平活性增强引起肠黏膜屏障通透性增高有助于细菌移位发生。     

Enteral glutamine supplementation impairs intestinal blood flow in rats

Background

Clinical studies have shown that enteral immune-enhancing diets (IEDs) containing l-glutamine decrease septic complications and length of stay in some patient populations. Animal studies suggest IED benefits might include augmented gut blood flow. We hypothesized that enteral glutamine supplementation modulates gastrointestinal blood flow.

Methods

Blood flow was measured in male Sprague-Dawley rats via the colorimetric microsphere technique at baseline, 60, and 120 minutes. Four groups were studied: (1) control diet (CD) + enteral glutamine; (2) CD + enteral glycine; (3) CD + enteral saline; and (4) CD + intravenous glutamine.

Results

There were no differences in blood pressure or heart rate in any group. Group 1 blood flow was decreased at 120 minutes compared with controls (groups 2 and 3) in small intestine, colon, spleen, and pancreas, whereas the intravenous glutamine group (group 4) had no effect on blood flow.

Conclusions

Enteral glutamine supplementation (as in IEDs) appears to impair gastrointestinal blood flow. Because glutamine provides energy directly to active enterocytes, enteral glutamine availability might diminish metabolic stimuli of absorptive hyperemia. This finding might partially explain the benefits observed with parenteral versus enteral glutamine supplementation in clinical studies (such as bone-marrow-transplant patients).     

The influence of biliary obstruction and sepsis on reticuloendothelial function in rats.

Obstructive jaundice is frequently associated with septic complications and renal impairment. The present study was performed in order to evaluate reticuloendothelial system (RES) function in obstructive jaundice and the influence of a septic challenge. Male Sprague-Dawley rats were allocated into four groups (laparotomy alone, caecal ligation and puncture (CLP), ligation of the common bile duct (CBD) alone and CBD+CLP, respectively). Mortality, blood clearance and organ distribution of 125I labelled Escherichia coli were determined. Mortality in sepsis (CLP) significantly increased in jaundiced animals (p less than 0.033). Blood clearance of radiolabelled E. coli was significantly impaired in both jaundiced groups. In jaundiced animals, hepatic localisation and renal uptake of E. coli significantly increased (p less than 0.001), while radioactive counts in bile significantly decreased (p less than 0.01). Changes in organ distribution of bacteria did not depend on alterations in blood flow. Thus, RES function was impaired in jaundiced animals and mortality increased in a concomitant septic challenge in jaundiced animals.     

Effect of granulocyte-macrophage colony stimulating factor on bacterial translocation after experimental obstructive jaundice.

OBJECTIVE: To investigate the effects of granulocyte-macrophage colony stimulating factor (GM-CSF) on bacterial translocation promoted by obstructive jaundice. DESIGN: Controlled animal study. SETTING: University hospital, Turkey. ANIMALS: 30 male Wistar albino rats. INTERVENTIONS: The first group (n = 10) was the sham operation (control) group, and the second and the third (n = 10 each) had common bile duct (CBD) ligation and division under sterile conditions. The third group were also treated with GM-CSF 200 ng subcutaneously daily between the fifth and ninth postoperative days. All animals were killed on the tenth day, and evaluated biochemically and histopathologically. Mesenteric lymph nodes were cultured under aerobic conditions. MAIN OUTCOME MEASURES: Biochemical analysis, histopathological evaluation, and aerobic cultures. RESULTS: There was no bacterial translocation in either the control or GM-CSF groups, whereas Escherichia coli and Salmonella typhimurium were found in 4 and 2 animals, respectively in the ligation group. Although no aerobic bacteria was found in controls and the GM-CSF groups, bacterial translocation was 6/10 in the ligation alone group (p <0.01). CONCLUSION: Activation of inflammatory response with GM-CSF is highly effective in prevention of bacterial translocation in obstructive jaundice.     

Effects of oral arginine and glutamine on radiation-induced injury in the rat

BACKGROUND: Exposure of the abdominal region to ionizing radiation is associated with serious untoward symptoms of intestinal dysfunction and some reports indicate that nutrient supplements may reduce these adverse effects. This study was designed to investigate the possible beneficial effects of oral arginine or glutamine supplementation on the radiation-induced tissue injury. MATERIALS AND METHODS: Rats were given one of three feeding regimens: standard diet and water (control group), diet and water containing 2% arginine (arginine group), diet and water containing 2% glutamine (glutamine group) for 3 days prior to radiation. All rats were then subjected to a single does of 1100 cGy to the abdomen. Several serum biochemical parameters and the histologic alterations in different segments of gastrointestinal tract and liver were measured 4 days after irradiation. RESULTS: All the arginine-fed rats developed diarrhea on Day 4 postirradiation, compared to 71% incidence in control rats and 86% in glutamine-fed rats. Serum levels of aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) in the arginine group were markedly higher than those in other groups. On histological examination, radiation caused more serious damage to various segments of intestine in the arginine-fed rats compared to rats on other feeding regimens. CONCLUSION: These observations seriously question the beneficial effects of arginine and glutamine supplementations on radiation-induced tissue injury.