The effect of granulocyte macrophage-colony stimulating factor on bacterial translocation after administration of 5-fluorouracil in rats

BACKGROUND: After surgical resection for colorectal carcinoma there is a high recurrence rate and, therefore, adjuvant chemotherapy may be useful in some patients. 5-Fluorouracil (5-FU) is the most commonly used chemotherapeutic agent in the management of patients with colorectal cancer. However, gastrointestinal injury induced by chemotherapeutic agents may result in bacterial translocation from the gut into the systemic circulation. Granulocyte macrophage-colony stimulating factor (GM-CSF) may be used to prevent this side effect by means of macrophage activity stimulation. MATERIALS AND METHODS: A total of 45 rats were divided into three groups. Control group received intraperitoneal saline solution, 5-FU and GM-CSF groups received 50 mg/kg/day 5-FU intravenous infusion and GM-CSF group also received 200 ng/day GM-CSF subcutaneously for 6 days. Intestinal tissue was also sampled for pathological examination at day 7. Plasma levels of tumor necrosis factor-alpha and interleukin-6 were determined, bacterial translocation was quantified by lymph node, liver and spleen culture, and plasma endotoxin content was measured. RESULTS: White blood cell counts of the 5-FU rats were significantly lower than in the control and GM-CSF groups (P < 0.01). The plasma endotoxin, tumor necrosis factor-alpha and interleukin-6 levels in the 5-FU and GM-CSF groups were significantly increased at day 7 compared with the control groups (P < 0.01), but these levels were significantly lower in the GM-CSF group compared to the 5-FU group (P < 0.01). 5-FU intervention caused significant increase in the frequencies of bacterial translocation at liver, spleen, mesenteric lymph node, and portal blood. Compared with 5-FU group, GM-CSF decreased the bacterial translocation (P < 0.01). CONCLUSIONS: This study observed that the administration of 5-FU resulted in bacterial translocation. Activation of inflammatory response with GM-CSF is highly effective in prevention of bacterial translocation in 5-FU interventions.     

The effect of mesenteric lymphadenectomy and Kupffer cell depletion on bacterial translocation.

BACKGROUND: Infectious complications are associated with high morbidity in patients with short bowel syndrome and after small bowel transplantation. Bacterial translocation from the intestine is probably an essential factor in the genesis of these infections. In a model for bacterial translocation in the rat we examined the consequence of mesenteric lymphadenectomy and the depletion of Kupffer cells. MATERIALS AND METHODS: The effect of mesenteric lymphadenectomy was studied in two different models; in rats where a Thiry-Vella loop had been created from small bowel and in rats that had received a syngeneic small bowel transplant. To study the role of the Kupffer cells, rats with Thiry-Vella loops were treated intravenously with the Kupffer cell inhibitor gadolinium chloride. All animals were sacrificed on Day 3 postoperatively and the bacterial translocation to the mesenteric lymph nodes, liver, spleen, lung, and blood was evaluated. RESULTS: Removal of the mesenteric lymph nodes did not result in any increased bacterial translocation in animals with a Thiry-Vella loop. However, the inactivation of Kupffer cells with gadolinium chloride produced a more severe translocation to the liver, spleen, and lungs. After small bowel transplantation the bacterial translocation to the spleen was increased in animals without mesenteric lymph nodes. CONCLUSIONS: In the model of bacterial translocation from a defunctionalized loop of small bowel the inhibition of Kupffer cells will promote the systemic spread of the translocating bacteria. This indicates an important protective function of the Kupffer cells against translocating microbes.     

The effect of surgical trauma on the bacterial translocation from the gut.

Bacterial translocation is the passage of viable bacteria from the lumen of the gastrointestinal tract through the intestinal mucosa to other sites. It is believed that bacterial translocation may lead to infection and septicemia. The purpose of this study was to determine what factors in experimental surgical trauma lead to bacterial translocation. Two-month-old Wistar albino rats were divided into five groups: (A) control; (B) anesthesia (ether inhalation); (C) anesthesia and surgery (median laparotomy and transient compression of the intestines); (D) fasting only; and (E) anesthesia, surgery, and fasting. After 48 hours, ileum, mesenteric lymph nodes, and blood were cultured for aerobic and anaerobic organisms. In each group the number of animals with bacteria overgrowth was calculated. The incidence of bacterial translocation to mesenteric lymph nodes and blood in groups B and D were similar to the controls (P greater than .01). There was a significant increase in the number of animals with bacterial translocation in groups C and E (P less than .001). The majority of translocating bacteria were E coli.     

The effect of L-tryptophan on hemorrhagic shock induced bacterial translocation

Hemorrhagic shock causes mucosal damage in intestine and it results in translocation of bacteria to distant organs. In this study, effects of various doses of L-Tryptophan on the prevention of bacterial translocation in hemorrhagic shock induced rabbits were investigated. This study was carried out on six groups, each was consisting of 10 rabbits. While any procedure was conducted on the rabbits in group 1 (as a control group), 1 x 10(10)Escherichia coli isolate were administered rabbits in the other groups by gavage. In groups 3, 4, 5, and 6, hemorrhagic shock was induced. After induction of hemorrhagic shock, 10, 50, and 200 mg/kg L-Tryptophan were intragastrically administered to animals in groups 4, 5, and 6, respectively. Blood and terminal ileum samples were taken to detect bacterial translocation by polymerase chain reaction and mucosal damage by histopathological examination at 24 h after hemorrhagic shock. The occurrence of bacterial translocation increased as well when intestinal bacterial intensity was increased (P < 0.05). The most intensive bacterial translocation was formed in group 3 as a result of the additive effect of hemorrhagic shock to bacterial augmentation. It was observed that bacterial translocation was significantly reduced in groups 5 and 6 that are 50 and 200 mg/kg L-Tryptophan were administered (P < 0.01). Histopathological changes on mucosa and submucosa support these results. As a result, we concluded that augmentation of intestinal bacterial intensity induces bacterial translocation, the addition of hemorrhagic shock to bacterial augmentation makes more excessive translocation and mucosal changes have effective roles in these events. L-Tryptophan decreased the intestinal mucosal damage and bacterial translocation induced by hemorrhagic shock, in a dose-dependent manner.     

The effect of dexamethasone and endotoxin administration on biliary IgA and bacterial adherence.

Adherence of bacteria to the intestinal epithelial cell may be the crucial initiating event for invasion and translocation and is normally prevented by both immune (IgA) and nonimmune (mucus, peristalsis, desquamation) mucosal defense mechanisms. The purpose of the present study was to examine the effect of endotoxin administration on mucosal immunity and to define the role of glucocorticoids, commonly released during endotoxicosis, in this process. Thirty female Fisher rats were randomly assigned to three groups of 10 animals each. Group I (CONT), was fed rat chow and H2O ad lib., Group II (DEX) was administered 0.8 mg/kg subcutaneously of dexamethasone, and Group III (ETX) was given 1 mg/kg of endotoxin. Twenty-four hours later animals were sacrificed and mesenteric lymph nodes and vigorously washed stool-free ceca were collected and cultured. Bile was collected and assayed for IgA from 5 animals in each group. A significant decrease (P < 0.05) in secretory IgA was noted in animals treated with either dexamethasone or endotoxin (CONT = 332 +/- 42, DEX = 78 +/- 24, ETX = 68 +/- 16 micrograms/mg protein +/- SEM). No difference in S-IgA between animals in the dexamethasone-treated group and the endotoxin-treated group was noted (P = NS). A statistically significant increase (P < 0.001) in bacteria adherent to the cecal wall in both the dexamethasone-treated rats and the endotoxin-treated rats over that in = 7.5 +/- 0.8, CONT = 6.4 +/- 0.6 cfu/g(log10) +/- SD). Our results suggest that endotoxin or glucocorticoid administration results in significant bacterial adherence to the cecal mucosa and a decrease in IgA.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of interleukin-1alpha administration on intestinal ischemia and reperfusion injury,mucosal permeability,and bacterial translocation in burn and sepsis

OBJECTIVE: To evaluate the effect of interleukin-1alpha (IL-1alpha) on the mesenteric circulation, intestinal mucosal integrity, and bacterial translocation in a burn/endotoxemia chronic porcine model. SUMMARY BACKGROUND DATA: Major burn and sepsis are associated with a high mortality, ischemia/reperfusion injury to the intestine, and an increased rate of bacterial translocation. Pathologic alterations of IL-1 synthesis, degradation, and binding to receptors have been reported. Manipulation of IL-1-mediated effects might be of therapeutic utility. METHODS: Twenty-one female pigs were instrumented with an ultrasonic flow probe on the superior mesenteric artery and a catheter into the superior mesenteric vein. After 5 days, all animals were anesthetized, and 14 received 40% total body surface area third-degree burn. IL-1alpha was administered intravenously at 1,000 ng/kg to seven pigs immediately after burn. Eighteen hours after burn, 100 microg/kg lipopolysaccharide (LPS) was administered intravenously. Systemic and splanchnic hemodynamics were measured and blood samples were drawn for blood gas analysis. Intestinal permeability was assessed every 6 hours by measuring the lactulose/mannitol (L/M) excretion ratio. At the end of the study (42 hours), tissue samples were harvested for bacteriologic cultures. RESULTS: Mesenteric blood flow was significantly decreased after burn and endotoxin. Administration of IL-1alpha significantly improved mesenteric blood flow postburn and post-LPS. Mesenteric oxygen supply and consumption showed a significant reduction after burn. In contrast, animals treated with IL-1alpha showed an increase in postburn mesenteric oxygen supply and consumption. LPS-induced mesenteric hypoxia was also ameliorated by IL-1alpha treatment. Intestinal permeability, as assessed by the L/M ratio, showed a 7- and 10-fold elevation after thermal injury and LPS, respectively. In contrast, IL-1alpha-treated animals showed an increase of only three- and fourfold in the L/M ratio, respectively. Bacterial translocation was significantly increased in the burn/endotoxin group. IL-1alpha significantly reduced the rates of bacterial translocation. CONCLUSIONS: IL-1alpha treatment attenuates mesenteric ischemia and reperfusion injury induced by thermal injury and endotoxemia by improving mesenteric blood flow and oxygenation. Subsequently, IL-1alpha reduces intestinal permeability and bacterial translocation after burn and sepsis.     

早期肠内营养对肝移植术后肠屏障及细菌移位的影响

目的探讨早期肠内营养对肝移植术后病人肠屏障功能和细菌移位的影响。方法40名肝移植病人被随机分成早期肠内营养（EN）组、胃肠外营养（PN）组。术前、术后第1天及术后第8天检测血浆内毒素水平、D-乳酸水平及二胺氧化酶（DAO）水平，术前及术后第1～7天每日行外周血细菌聚合酶链反应（PCR）检测及血细菌培养。结果（1）术后第8天EN组内毒素、D-乳酸及DAO水平显著低于PN组（P〈0．01）。（2）术后第1天两组内毒素、D-乳酸及DAO水平显著高于术前（P〈0．05），两组之间无统计学差异。术后第8天EN组内毒素、D-乳酸及DAO水平显著低于术后第1天水平（P〈0．05），低于术前水平（P〈0．05）。PN组内毒素、D-乳酸及DAO水平显著高于术前水平（P〈0．05），和术后第1天水平无统计学差异（P〉0．05）。（3）40例肝移植病人PCR检测外周血细菌DNA片段阳性总数为25例，阳性率62．5％，术后第4天起两组有显著差异。（4）PCR大肠杆菌检出占所有细菌检出的60％。（5）40名肝移植病人27例出现全身炎症反应综合征（SIRS），其中EN组12例，PN组15例，PCR阳性组SIRS发生率为96％，PCR阴性组SIRS发生率为20％，SIRS发生组PCR阳性率为88．89％，SIRS阴性组PCR阳性率为7．69％。（6）术后血细菌培养阳性率27．5％，显著低于PCR的62．5％（P〈0．01）；培养阳性者，PCR均呈阳性。（7）PCR阳性组感染并发症发生率为64％（16／25），阴性组均未发生感染（0／15），二者差异有显著性（P〈0．01）。结论肝移植术后施行早期肠内营养能有效的维护肠黏膜屏障功能、防止细菌及内毒素移位，减少术后感染的发生。     

严重烫伤小鼠肠黏膜相关淋巴细胞变化与肠道细菌移位

目的探讨小鼠烫伤后肠黏膜相关淋巴细胞变化与肠道细菌移位的关系。方法将40只BALB/c小鼠随机分为正常对照组及烫伤后12、24、72 h组,每组10只。正常对照组不致伤, 其余各组小鼠背部造成20％TBSAⅢ度烫伤后,按时相点处死并留取标本。计数全段小肠集合淋巴结 (PP结)个数及淋巴细胞总数。应用流式细胞仪检测小鼠PP结CD3+、CD4+、CD19+淋巴细胞比例和绝对数,并检测主要脏器肠道细菌移位率。结果烫伤后12、24、72 h组PP结淋巴细胞总数分别为 (4．05±0．28)×106、(2．64±0．39)×106、(2．83±0．46)×106个,均少于正常对照组的(4．54±0．58)× 106个(P<0．05或0．01)。与正常对照组比较,烫伤后72 h组PP结淋巴细胞悬液中CD3+、CD4+百分比明显降低(P<0．05)。伤后各组小鼠CD3+、CD4+、CD19+淋巴细胞绝对数明显减少。各烫伤组肠道细菌移位率分别为16％、52％、30％,均高于正常对照组(4％),其中烫伤后24、72 h组与正常对照组比较,差异有统计学意义(P<0．05)。结论烫伤后肠黏膜相关淋巴细胞减少是肠源性感染的重要因素。     

The effect of hypertonic saline resuscitation on bacterial translocation after hemorrhagic shock in rats

Translocation of enteric bacteria occurs in rats after hemorrhagic shock. A proposed mechanism involves intestinal mucosal injury by hypoperfusion. Recent work suggests that moderate hypovolemia causes gut arteriolar constriction, which is ameliorated by hypertonic saline resuscitation. Bacterial translocation should, therefore, be reduced when hypertonic saline (HS) is used as the resuscitative fluid. Seventy-eight Sprague-Dawley rats were anesthetized and subjected to 30 minutes of hemorrhagic shock (systolic blood pressure 30 to 50 mm Hg) through a modified Wigger's model. Resuscitation was performed with either shed blood (B), 3% HS + 1/2B (1:1), or with 7.5% HS + 1/2B (1:1). Spleen, liver, and mesenteric lymph nodes were sent for quantitative culture 24 hours later. Translocation occurred if enteric organisms were cultured from at least one organ. Statistical analysis used the Fisher exact test. Compared to autotransfusion, hemodilutional resuscitation from hemorrhagic shock with hypertonic saline resulted in a significant reduction in bacterial translocation (p values were 0.03 and 0.04 for 3% and 7.5% hypertonic saline, respectively). The reduction in translocation after hypertonic saline resuscitation may be the consequence of microcirculatory alterations preventing gut hypoperfusion.     

The effect of albumin or crystalloid resuscitation on bacterial translocation and endotoxin absorption following experimental burn injury.

Burn injury induces immune suppression and increases susceptibility to infection. Hypoalbuminemia is an early and consistent finding following thermal injury and is independently associated with gastrointestinal dysfunction and increased rates of infectious morbidity. This study assessed the effects of albumin resuscitation on burn-induced immunosuppression, bacterial translocation, and absorption of gut endotoxin. Male Sprague-Dawley rats, presensitized to keyhole limpet hemocyanin (KLH), underwent a 20% dorsal scald burn injury, followed by laparotomy and IVC catheterization for fluid resuscitation. Animals were randomized to one of three resuscitative regimens: Ringer's lactate 3 ml/kg/% burn, Ringer's lactate 9 ml/kg/% burn, or 5% human albumin 3 ml/kg/% burn. Delayed hypersensitivity (DTH) responses to KLH were depressed 24 hr following injury (preburn 8.9 +/- 0.2 mm, post-burn 3.1 +/- 0.3 mm, P less than 0.001) and were significantly lower in animals in whom gram-negative bacterial translocation had occurred (2.3 +/- 0.4 vs 3.6 +/- 0.2 mm, P less than 0.005). Serum albumin levels were lower and rates of gram-negative bacterial translocation higher for those animals receiving low volume crystalloid resuscitation; animals resuscitated with albumin or high volume crystalloid experienced similar degrees of postinjury hypoalbuminemia and bacterial translocation. Uptake of radiolabeled endotoxin was maximal in animals resuscitated with albumin. Bacterial translocation is believed to be responsible for a significant number of late nosocomial infections following trauma. These data suggest that the adequacy of early resuscitation rather than the type of resuscitative solution is the more important factor in minimizing translocation.     

头孢噻甲羧肟对烧伤后肠源性感染的预防作用

采用30%TBSA Ⅲ度烫伤大鼠模型,分不同时相(伤后3、6和12h)腹腔注射头孢噻甲羧肟,并通过血液、内脏和肠系膜淋巴结中细菌的定性和定量分析,评价头孢噻甲羧肟对预防烫伤大鼠绿脓杆菌肠源性感染的效果。结果表明,伤后3h 和6h 开始用药组,肠源性感染的发生率明显下降(分别为 P<0.001和 P<0.05),而伤后12h 开始用药组则无明显降低(P>0.05),但其肝、肾组织中的菌量也明显减少(P<0.01)。同时我们还动态观察了烫伤大鼠血液和内脏组织中药物的浓度,结果表明,用药后血、肝和小肠粘膜中能迅速达到有效药浓度,并维持4h 以上,但肠系膜淋巴结中未检测到药物。提示:大面积烧伤病人早期,短程使用有针对性的抗生素,对预防肠源性感染可能是有益的。     

头孢噻甲羧肟对烧伤后肠源性感染的预防作用

采用３０％ＴＢＳＡⅢ度烫伤大鼠模型，分不同时相（伤后３、６和１２ｈ）腹腔注射头孢噻甲羧肟，并通过血液、内脏和肠系膜淋巴结中细菌的定性和定量分析，评价头孢噻甲羧肟对预防烫伤大鼠绿脓杆菌肠源性感染的效果。结果表明，伤后３ｈ和６ｈ开始用药组，肠源性感染的发生率明显下降（分别为Ｐ＜０．００１和Ｐ＜０．０５），而伤后１２ｈ开始用药组则无明显降低（Ｐ＞０．０５），但其肝、肾组织中的菌量也明显减少（Ｐ＜０．０１）。同时我们还动态观察了烫伤大鼠血液和内脏组织中药物的浓度，结果表明，用药后血、肝和小肠粘膜中能迅速达到有效药浓度，并维持４ｈ以上，但肠系膜淋巴结中未检测到药物。提示：大面积烧伤病人早期，短程使用有针对性的抗生素，对预防肠源性感染可能是有益的。     

Elemental diet and IV-TPN-induced bacterial translocation is associated with loss of intestinal mucosal barrier function against bacteria.

OBJECTIVE: The goal of the current study was to directly assess the role of loss of mucosal barrier function in nutritionally induced bacterial translocation. BACKGROUND: Parenteral and certain elemental enteral diets have been shown to promote bacterial translocation. The mechanisms underlying this observation, especially the question of whether nutritionally induced bacterial translocation is primarily related to loss of intestinal barrier function, versus an impaired immune system, remain to be fully elucidated. METHODS: Bacterial translocation was measured in vivo, ileal mucosal membranes were harvested, and their electrophysiologic properties and barrier function were measured ex vivo in the Ussing chamber system 7 days after receiving total parenteral nutrition solution parenterally (IV-TPN) or enterally (elemental diet). Chow-fed rats served as control subjects. RESULTS: The incidence of bacterial translocation was significantly increased both to the mesenteric lymph nodes in vivo and across the in vitro Ussing chamber-mounted ileal mucosal membranes of the elemental diet-fed and IV-TPN-fed rats. The magnitude of Escherichia coli and phenol red transmucosal passage in the Ussing chamber was significantly higher in the IV-TPN-fed rats than in the elemental diet-fed or chow-fed animals. The potential differences across the ileal membrane were similar between the three groups at all time points. However, the specific resistances of the ileal membranes of the IV-TPN and elemental diet groups were significantly less than the chow-fed animals, indicating increased membrane permeability. CONCLUSIONS: Loss of intestinal barrier function plays a major role in nutritionally induced bacterial translocation, and the loss of mucosal barrier function to both E. coli and phenol red appeared greater in the IV-TPN than the elemental diet-fed rats.     

Oxygen as an antibiotic. The effect of inspired oxygen on bacterial clearance

Previous experimentation with the guinea pig skin injection model showed that altering the fraction of inspired oxygen had a significant effect on infectious necrosis. Using the same model, we performed quantitative bacterial cultures to determine the number of viable injected bacteria 24 and 48 hours after injection. Animals were randomized to receive 12%, 21%, and 45% inspired oxygen. A significant decrease in bacterial number was seen at 45% inspired oxygen between 24 and 48 hours, and a significant decrease occurred at 48 hours between 12% and 45% inspired oxygen. These results demonstrated a prominent role for oxygen in bacterial clearance and host defense.     

The effect of N-acetylcysteine on oxidative stress in intestine and bacterial translocation after thermal injury

Ischemia due to transient splanchnic vasoconstriction following major burns causes oxidative and/or nitrosative damage in intestinal tissue followed by reperfusion injury. Thus, burn injury leads to breakdown in the intestinal mucosal barrier which can induce bacterial translocation (BT). As an antioxidant and anti-inflammatory agent the protective effects of N-acetylcysteine (NAC) are documented in several studies. This study was designed to determine the effect of NAC treatment on the oxidative stress in the intestine and BT after burn injury. To evaluate this, 32 Wistar rats were randomly divided into four groups as sham (n = 8), burn (n = 8), pre-burn, NAC injection (150 mg kg⁻¹, intraperitoneally) 15 min before thermal injury (n = 8), post-burn, NAC injection (150 mg kg⁻¹, intraperitoneally) 2 h after thermal injury. Under anesthesia, the shaved dorsal skin of rats was exposed to boiling water for 12 s to induce burn injury in a standardized manner. Twenty-four hours later, tissue samples from mesenteric lymph nodes (MLN), spleen, and liver were obtained under sterile conditions for microbiological analysis and ileum samples were harvested for biochemical analysis. In the burn group, the incidence of isolating bacteria in MLN, spleen, and liver specimens was significantly higher than other groups. NAC treatment prevented burn-induced BT in both pre- and post-burn groups. Thermal injury caused a significant decrease in glutathione (GSH) level, significant increases in malondialdehyde (MDA) and myeloperoxidase (MPO) activity at post-burn 24th hour. Treatment of rats with NAC significantly elevated the reduced GSH levels while decreasing MDA levels and MPO activity. These data suggested that NAC has a crucial cytoprotective role in intestinal mucosal barrier and preventive effects against burn injury-induced BT.     

The effects of hemodynamic shock and increased intra-abdominal pressure on bacterial translocation.

BACKGROUND: We hypothesized that hemorrhagic shock followed by the abdominal compartment syndrome (ACS) resulted in bacterial translocation (BT) from the gastrointestinal (GI) tract. METHODS: Nineteen Yorkshire swine (20-30 kg) were divided into two groups. In the experimental group, group 1 (n = 10), animals were hemorrhaged to a mean arterial pressure (MAP) of 25-30 mm Hg for a period of 30 minutes and resuscitated to baseline MAP. Subsequently, intra-abdominal pressure (IAP) was increased to 30 mm Hg above baseline by instilling sterile normal saline into the peritoneal cavity. The IAP was maintained at this level for 60 minutes. Acid/base status, gastric mucosal ph (pHi), superior mesenteric artery (SMA) blood flow, and hemodynamic parameters were measured and recorded. Blood samples were analyzed by polymerase chain reaction (PCR) for the presence of bacteria. Spleen, lymph node, and portal venous blood cultures were obtained at 24 hours. Results were analyzed by ANOVA and are reported as mean +/- SEM. The second group was the control. These animals did not have the hemorrhage, resuscitation, or intra-abdominal hypertension (IAH) but were otherwise similar to the experimental group in terms of laparotomy and measured parameters. RESULTS: SMA blood flow in group 1 (baseline of 0.87 +/- 0.10 l/min) decreased in response to hemorrhage (0.53 +/- 0.10 l/min, p = 0.0001) and remained decreased with IAH (0.63 l/min +/- 0.10, p = 0.0006) as compared to control and returned towards baseline (1.01 +/- 0.5 l/min) on relief of IAH. pHi (baseline of 7.21 +/- 0.03) was significantly decreased with hemorrhage (7.04 +/- 0.03, p = 0.0003) and decreased further after IAH (6.99 +/- 0.03, p = 0.0001) in group 1 compared to control, but returned toward baseline at 24 hours (7.28 +/- 0.04). The mean arterial pH decreased significantly from 7.43 +/- 0.01 at baseline to 7.27 +/- 0.01 at its nadir within group 1 (p = 0.0001) as well as when compared to control (p = 0.0001). Base excess was also significantly decreased between groups 1 and 2 during hemorrhage (3.30 +/- 0.71 vs. 0.06 +/- 0.60, p = 0.001) and IAH (3.08 +/- 0.71 vs. -1.17 +/- 0.60, p = 0.0001). In group 1, 8 of the 10 animals had positive lymph node cultures, 2 of the 10 had positive spleen cultures, and 2 of the 10 had positive portal venous blood cultures for gram-negative enteric bacteria. Only 2 of the 10 animals had a positive PCR. In group 2, five of the nine animals had positive lymph node cultures, zero of the nine had positive spleen cultures, and one of the nine had positive portal venous blood cultures. Two of the nine animals had positive PCRs. There was no significant difference in cultures or PCR results between the two groups (Fisher's exact test, p = 0.3). CONCLUSION: In this study, hemorrhage followed by reperfusion and a subsequent insult of IAH caused significant GI mucosal acidosis, hypoperfusion, as well as systemic acidosis. These changes did not appear to be associated with a significant bacterial translocation as judged by PCR measurements, tissue, or blood cultures.     

Secretory immunoglobulin A, intestinal mucin, and mucosal permeability in nutritionally induced bacterial translocation in rats.

OBJECTIVE. The authors investigated the role of mucin and secretory immunoglobulin A (slgA) in a model of nutritionally induced bacterial translocation. BACKGROUND. Parenteral and certain elemental diets have been shown to impair intestinal barrier function, whereas fiber has been shown to protect against nutritionally induced bacterial translocation. However, the factors responsible for these phenomenon have not been fully determined. METHODS. Intestinal mucin levels, mucosal protein content, slgA, intestinal morphology, and permeability to horseradish peroxidase, bacterial translocation, and intestinal bacterial population levels were measured in rats 7 days after receiving total parenteral nutrition (TPN) solution (28% glucose, 4.25% amino acids; 307 kcal/kg/day) enterally (ORAL-TPN) or parenterally (IV-TPN) with or without enteral bulk fiber supplementation. Chow-fed rats served as control subjects. RESULTS. The incidence of bacterial translocation in the ORAL-TPN and IV-TPN groups was reduced significantly by the provision of fiber (p < 0.05). Mucosal protein, slgA, and insoluble mucin levels were decreased in the jejunum of the ORAL-TPN and IV-TPN groups, with mucosal protein levels being decreased to a greater extent than slgA or mucin. Although similar decreases in these parameters were observed in the fiber-fed groups, fiber appeared to improve intestinal barrier function as measured by horseradish peroxidase permeability. CONCLUSIONS. The provision of bulk-forming fiber improves intestinal barrier function as measured by peroxidase permeability and bacterial translocation, but does not restore mucosal protein content, intestinal mucin, or slgA levels to normal.     

The effect of glucagon-like peptide 2 on intestinal permeability and bacterial translocation in acute necrotizing pancreatitis

BACKGROUND: Acute pancreatitis (AP) initiates a generalized inflammatory response that increases intestinal permeability and promotes bacterial translocation (BT). Impairment of the intestinal epithelial barrier is known to promote BT. Glucagon-like peptide 2 (GLP-2), a 33 residue peptide hormone, is a key regulator of the intestinal mucosa by stimulating epithelial growth. The purpose of this study was to determine whether GLP-2 decreases intestinal permeability and BT in AP. METHODS: To examine whether GLP-2 can decrease intestinal permeability and thereby decrease BT in acute necrotizing pancreatitis, 34 male Sprague-Dawley rats (200 to 300 g) were studied. AP was induced in group I and group II by pressure injection of 3% taurocholate and trypsin into the common biliopancreatic duct (1 mg/kg of body weight). The potent analog to GLP-2 called ALX-0600 was utilized. Group I rats received GLP-2 analog (0.1 mg/kg, SQ, BID) and group II rats received a similar volume of normal saline as a placebo postoperatively for 3 days. Group III and group IV received GLP-2 analog and placebo, respectively. At 72 hours postoperatively, blood was drawn for culture of gram-negative organisms. Specimens from mesenteric lymph nodes (MLN), pancreas and peritoneum were harvested for culture of gram-negative bacteria. Intestinal resistance as defined by Ohm's law was determined using a modified Ussing chamber to measure transepithelial current at a fixed voltage. A point scoring system for five histologic features that include intestinal edema, inflammatory cellular infiltration, fat necrosis, parenchymal necrosis, and hemorrhage was used to evaluate the severity of pancreatitis. Specimens from MLN, pancreas, jejunum, and ileum were taken for pathology. RESULTS: All group I and group II rats had AP. The average transepithelial resistance in group I was 82.8 Omega/cm(2) compared with 55.9 Omega/cm(2) in group II (P <0.01). Gram-negative BT to MLN, pancreas, and peritoneum was 80%, 0%, and 0%, respectively in group I compared with 100%, 30%, and 20% translocation in group II. CONCLUSION: GLP-2 treatment significantly decreases intestinal permeability in acute pancreatitis.