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Results for “Intestinal Barrier Function”

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PubMed2003

[Clinical and prognostic value of lesions in the gastrointestinal tract in systemic vascular purpura].

AIM: To evaluate clinical peculiarities and prognostic value of abdominal syndrome in adult patients with systemic vascular purpura (SVP). MATERIAL AND METHODS: Incidence, clinical picture, complications of abdominal syndrome, its relations with principal extraintestinal manifestations of SVP were studied in 125 SVP patients. Absorption and barrier functions of the small intestine, their correlations with clinical activity of the disease were investigated in 32 SVP patients with no clinical signs of intestinal affection. Computer-assisted morphometry of duodenal mucosa biopsies was conducted and the results were compared to those of intestinal permiability and clinical activity of SVP. RESULTS: Negative correlation was found between the occurrence of abdominal syndrome and the patients' age. The gastrointestinal tract suffered more frequently in men. 21% patients had abdominal complications, association of abdominal syndrome with higher frequency of glomerulonephritis. In the absence of abdominal symptoms, the barrier function of the small intestine for protein macromolecules was impaired. This correlated with exacerbations of skin purpura. Increased intestinal permeability and activity of skin purpura correlated with severity of inflammation in the duodenal mucosa. CONCLUSION: Abdominal syndrome in SVP is an unfavourable prognostic factor indicating possible severe complications and high risk of glomerulonephritis. Subclinical intestinal involvement presenting as barrier dysfunction may contribute to aggravation of skin vasculitis.

Adolescent↗

PubMed2004

Glutamine supplementation in infants with gastrointestinal disease: a randomized, placebo-controlled pilot trial.

OBJECTIVE: Glutamine (Gln) is a non-essential amino acid that plays an important role in energy metabolism for gastrointestinal epithelia and other cells with rapid turnover. We evaluated the effects of enteral supplementation with Gln in infants undergoing surgery for congenital or acquired gastrointestinal disease. METHODS: This was a randomized, double-masked, controlled clinical trial. RESULTS: Twenty infants were randomly assigned to receive Gln (n = 9) or placebo amino acid (n = 11), with a goal of supplemental amino acid intake of 0.4 g.kg(-1).d(-1). Infants were weaned from parenteral nutrition, and enteral feeds were started according to a standardized feeding protocol. Median (interquartile range) durations of parenteral nutrition were 39 d (12 to 99) in the Gln group and 21 d (6 to 59) in the control group (P = 0.201). Median (interquartile range) durations needed to reach 80% of the US recommended dietary allowance for energy with enteral nutrition were 24 d (8 to 55) in the Gln group and 12.5 d (5 to 32) in the control group (P = 0.313). There were no differences in the occurrence of infections between groups. Among all infants enrolled, significant correlations were found between duration of parenteral nutrition and residual small bowel length, peak concentrations of direct bilirubin, and alanine aminotransferase. Peak direct bilirubin was associated with longer duration of parenteral nutrition, shorter gestation, older age before feeds were started, shorter bowel length, and larger amounts of parenteral energy and protein intake. CONCLUSIONS: In this pilot trial, enteral Gln supplementation was well tolerated among infants with surgical gastrointestinal disease. There was no effect observed on the duration of parenteral nutrition, tolerance of enteral feeds, or intestinal absorptive or barrier function. Larger, multicenter trials in infants with surgical gastrointestinal disease are needed due to the variability in important outcome measurements.

Dietary Supplements↗

PubMed2005

Dexamethasone reduces gut permeability in pediatric cardiac surgery.

OBJECTIVES: Little attention has been paid to the effect of the systemic inflammatory response syndrome on intestinal dysfunction in the postoperative period. Several proinflammatory cytokines have been reported to increase the permeability of intestinal mucosa in vitro. We investigated the effect of dexamethasone on gut permeability in pediatric patients undergoing cardiac surgery by using the dual sugar permeability test and absorption of 2 other saccharides. METHODS: Thirty-four patients scheduled for cardiac surgery with cardiopulmonary bypass were prospectively randomized to either act as control subjects or to receive dexamethasone (1 mg . kg -1) during induction of anesthesia. Intestinal permeability was measured with 3-O-methyl-D-glucose, D-xylose, L-rhamnose, and lactulose administered orally after induction of anesthesia and 12 and 24 hours later. RESULTS: Lactulose/rhamnose ratios were increased from the outset in both groups (mean 0.57 [95% confidence interval, 0.24-0.91] for the control group and 0.76 [95% confidence interval, 0.35-1.17] for patients receiving dexamethasone). Although the ratios decreased 12 hours (0.29 [95% confidence interval, 0.17-0.42]) and 24 hours later (0.17 [95% confidence interval, 0.08-0.15]) in the dexamethasone group, in the control group there was a rise at 12 hours (0.77 [95% confidence interval, 0-1.64]), with a slight reduction 24 hours later (0.46 [95% confidence interval, 0.06-0.85]). CONCLUSIONS: Infants and children undergoing cardiac surgery with cardiopulmonary bypass show a significant reduction in gut permeability when dexamethasone is used during induction of anesthesia. Dexamethasone does not affect the intestinal barrier at the functional level, as assessed on the basis of 3-O-methyl-D-glucose and D-xylose absorption.

Adolescent↗

PubMed2004

The role of probiotics in the clinical management of food allergy and atopic dermatitis.

The probiotics are cultures of potentially beneficial bacteria that positively affects host by enhancing the microbial balance and therefore restore the normal intestinal permeability and gut microecology, improve the intestine's immunologic barrier function and reduce the generation of proinflammatory cycochines characteristics of allergic inflammation. The authors made a survey of the most relevant studies concerning the use of probiotics in the food allergy, atopic dermatitis, and in primary prevention of atopy. On the basis of these trials probiotic therapy alleviates allergic inflammation as demonstrated by the control of clinical symptoms and the reduction of local and systemic inflammatory markers.

Dermatitis, Atopic↗

PubMed2006

Difference in oral absorption of ginsenoside Rg1 between in vitro and in vivo models.

AIM: To clarify the cause of poor oral absorption of ginsenoside Rg1 (Rg1), the active ingredient in Panax notoginseng saponins (PNS) used for treating hemorrhage. METHODS: Caco-2 cell monolayers were used as an in vitro model to study the transport mechanism of Rg1 across the intestinal mucosa. Moreover, the serum concentration-time profiles after peroral (po), intraduodenal (id), portal venous (pv) and tail venous (iv) administration of Rg1 in rats were compared to evaluate the first-pass effects in the stomach, intestine, and liver. RESULTS: Uptake of Rg1 by Caco-2 cell monolayers was temperature-dependent, but was not influenced by cyclosporin A. The change in the apical pH produced no obvious effect on the uptake of Rg1. The uptake and transport of Rg1 was non-saturable; whereas the flux from the apical compartment to the basolateral compartment (A-B) increased in a linear manner with the increase in concentration, indicating passive transport. An apparent permeability coefficient of (2.59+/-0.17)*10(-7) cm/s (C0=1 mg/mL) predicted incomplete absorption. A significant difference was observed between the po (F(po) was 3.29% at a dose of 1500 mg/kg), id (F(id) was 6.60% at a dose of 1200 mg/kg) and pv (F(pv) was 50.56%) administration methods, and the barrier function of the intestine was more significant than those of the stomach and liver in the absorption process. CONCLUSION: Elimination in the stomach, large intestine and liver contributed to the low oral bioavailability of Rg1, but low membrane permeability might be a more important factor in determining the extent of absorption.

Administration, Oral↗

PubMed1997

Effect of aging on the intestinal transport of hydrophilic drugs in the rat small intestine.

The effect of aging on the intestinal transport of hydrophilic drugs (and probe compounds) was investigated in the rat small intestine. Passive transport was suggested to be unchanged with aging from 8 (young) to 54 (old) and further to 101 (very old) weeks old, as shown for D-xylose and urea in single-pass intestinal perfusion (under urethane anesthesia), where steady-state transport across the intestinal membrane into the blood stream was evaluated. The passive transports of cephradine, 5-fluorouracil (5-FU) and L-glucose were also unchanged, though they were compared only between the young and the old. Consistently, the passive uptake in the intestinal everted sacs, where the entry process into the membrane was evaluated for 5-FU, D-xylose, urea and polyethylene glycol (PEG) 900, was unchanged with aging from the young to the very old. The carrier-mediated transport of cephradine was also unchanged with aging from the young to the old in perfusion under anesthesia, though that of D-glucose was declined by about 50% with aging from the young to the old and thereafter remained constant in the very old. In perfusion in unanesthetized rats, age independency in passive transport (examined for cephradine, L-glucose and D-xylose) and an age-dependent decline in D-glucose transport were also observed, suggesting that the findings under anesthesia are not qualitatively distorted. These results suggest that, although carrier-mediated transport may moderately decline with aging, the barrier function of the intestinal membrane to passive permeation of hydrophilic drugs (with molecular weight below 1000) may be unaffected by aging, supporting the suggestion from our previous in vivo studies that age-dependent increases in the orally absorbed fraction may be predicted for incompletely absorbed drugs because of delayed intestinal transit rather than increased intestinal transport (membrane permeability).

Aging↗

PubMed2004

Alcohol and immunology: introduction to and summary of the 2003 Alcohol and Immunology Research Interest Group (AIRIG) meeting.

The 8th Meeting of the Alcohol and Immunology Research Interest Group (AIRIG) was held at Loyola University Medical Center, Maywood, Illinois, USA, on November 21, 2003. Reports from multiple laboratories reveal that the functional integrity of the immune system is of paramount importance to the survival of the individual after infection or injury. Evidence supports the idea that exposure to alcohol causes dysregulation of both the innate and the adaptive arms of the immune system. Gaining a better understanding of how alcohol interferes with normal inflammatory and immunoregulatory processes will aid researchers in the design of therapeutic interventions that can be used to improve these responses to better fight infection and maintain the health of the individual. At this meeting, nine speakers presented a summary of their recent work on the combined effects of ethanol and injury, infection, or inflammatory challenge. Topics were (1) T-cell activation after chronic ethanol ingestion in mice, (2) effect of ethanol consumption on the severity of acute viral-mediated pancreatitis, (3) ethanol and alveolar macrophage dysfunction, (4) impaired intestinal immunity and barrier function: a cause for enhanced bacterial translocation in alcohol intoxication and burn injury, (5) immune consequences of the combined insult of acute ethanol exposure and burn injury, (6) consequences of alcohol-induced dysregulation of immediate hemodynamic and inflammatory responses to trauma/hemorrhage, (7) regulation of tumor necrosis factor-alpha production by Kupffer cells after chronic exposure to ethanol, (8) acute exposure to ethanol and suppression of cytokine responses induced through Toll-like receptors, and (9) inhibition of antigen-presenting cell functions by alcohol: implications for hepatitis C virus infection. We anticipate that the work presented at the 8th Meeting of AIRIG, summarized in this article, and presented in the nine articles to follow in this Special Issue of Alcohol will stimulate ideas that will develop into research projects in these topical areas.

Alcoholism↗

PubMedDate not supplied

Experimental assessment of chemotherapy-induced early intestinal damage in colon cancer the lactulose-mannitol permeability test.

AIMS AND BACKGROUND: Although chemotherapy plays an important role in the management and cure of cancer, it has undesiderable side effects mostly affecting the bone marrow and gastrointestinal tract, which greatly limit patient compliance and treatment efficacy. METHODS: The lactulose-mannitol test was used to assess intestinal mucosa damage 48 hours after the end of the first adjuvant chemotherapy cycle with 5-fluorouracil (5-FU) and levamisole in 12 patients with colon cancer. Fifteen age- and sex-matched subjects were studied as controls. The excreted amount of lactulose and mannitol was expressed as the percentage of the administered doses recovered in the urine as well as their ratio. RESULTS: The percent urinary recovery of lactulose was significantly (P < 0.001) higher in colon cancer patients (1.1 +/- 0.5%) than in the control group (0.3 +/- 0.03%), whereas the mannitol recovery was only slightly reduced in the former. As a result, the lactulose/mannitol excretion ratio was significantly (P < 0.001) higher in colon cancer patients (0.07 +/- 0.03) than in the control group (0.01 +/- 0.01). CONCLUSIONS: As assessed by the lactulose-mannitol test, the combined chemotherapy regimen with 5-FU and levamisole affects mainly the barrier function of the intestinal mucosa rather than its absorption capacity. The toxic effect seems to be attributable to the 5-FU molecule rather than to levamisole. The lactulose-mannitol test is a simple, safe and reliable tool to evaluate chemotherapy-induced early damage to the intestinal epithelium, in particular when new kinds of substances are being administered. Its use in clinical practice seems appropriate to establish the correct timing of drug administration, thereby enhancing treatment efficacy and improving patient compliance.

Administration, Oral↗

PubMed2002

IL-10 is not protective in intestinal ischemia reperfusion injury.

BACKGROUND: Ischemia/reperfusion of the small intestine disrupts gut barrier function, increases bacterial translocation, and activates systemic pro-inflammatory responses. Pharmacological treatment with the anti-inflammatory cytokine interleukin-10 (IL-10) following ischemia to muscle reduces the severity of local and systemic inflammation. While endogenous IL-10 is protective in murine models of acute endotoxemia, its physiological role during direct gut injury is unknown. PATIENTS AND MATERIALS: Mice genetically deficient in IL-10 (IL-10(-/-)) and their normal littermates (IL-10(+/+)) underwent 20 to 50 min of gut ischemia by occlusion of the superior mesenteric artery. RESULTS: Both short- and long-term (>16 h) survival after reperfusion of IL-10(-/-) mice was identical to that of the wild-type littermates, with 50% mortality observed at 35 min of occlusion. The small bowel demonstrated discrete gross areas of hemorrhage and ischemia localized to the jejunum. No significant difference in the extent or time for occurrence of macroscopic or microscopic intestinal damage to the small bowel was observed in IL-10(-/-) or IL-10(+/+) mice, despite the marked elevation in serum IL-6. CONCLUSIONS: The absolute serum concentration of IL-6 in the presence or the absence of IL-10 does not affect local or systemic response to ischemic intestinal injury. These results also demonstrate that the anti-inflammatory cytokine IL-10 does not play a significant local or systemic protective role in this model of ischemia/reperfusion.

Animals↗

PubMed2000

Fish oil-supplemented parenteral diets normalize splanchnic blood flow and improve killing of translocated bacteria in a low-dose endotoxin rat model.

OBJECTIVE: Intestinal ischemia decreases barrier function of the gut and enhances translocation of bacteria and toxins. Several studies indicate that fish oil can modulate prostaglandin formation and thus, regional blood flow and immune function. This study was performed to determine the effects of parenteral diets with omega-3 fatty acids on microcirculation and barrier function of the gut.0 DESIGN: Prospective, randomized, controlled animal study. SETTING: University laboratory. SUBJECTS: A total of 64 male Sprague-Dawley CD rats. INTERVENTIONS AND MEASUREMENTS: For 48 hrs, eight groups of eight rats each received total parenteral nutrition with four different types of lipids. The source of fat in group L was soybean oil only and in group L-M a mixture of soybean oil and medium-chain triglycerides. In groups FO-20 and FO-40, 20% or 40%, respectively, of the soybean oil in group L-M was replaced by fish oil. The other four groups received an additional continuous infusion of endotoxin (0.1 mg/100 g body weight per day) for the last 24 hrs. Blood flow was measured with microspheres, and translocation was determined by microbiological methods and instillation of radioactive-marked bacteria into the gut. MAIN RESULTS: In the animals without fish oil, the endotoxin application reduced the blood flow to the intestine approximately 25%. Animals with fish oil in their diets showed normal values. Translocation of gut bacteria was increased significantly in all endotoxin groups. However, less-viable bacteria could be detected in the animals with fish oil diets in their mesenteric lymph nodes and livers. CONCLUSIONS: In this model, diets enriched with fish oil abolish the endotoxin-induced decrease of nutritive blood flow to the gut and ameliorate the bactericidal defense of the splanchnic region. The lower count of viable bacteria in the fish oil groups is more related to an improved killing of translocated bacteria than a reduction of the translocation rate.

Animals↗

PubMed1994

Intestinal drug absorption during induced net water absorption in man; a mechanistic study using antipyrine, atenolol and enalaprilat.

1. The effect of induced water absorption on the intestinal permeability of antipyrine, atenolol and enalaprilat in the proximal jejunum was studied in eight healthy subjects with a regional intestinal perfusion technique. 2. The mean (+/- s.d.) net water flux changed from a secretory status of 1.2 +/- 1.2 ml h-1 cm-1 to an absorptive status of -3.7 +/- 3.5 ml h-1 cm-1 (P < 0.0025) on the introduction of a hypo-osmolar glucose-containing electrolyte solution. 3. The mean permeability values for the three drugs in the eight subjects were unchanged despite the increase in net water absorption (5.7 +/- 3.0 to 7.0 +/- 3.6 x 10(-4) cm s-1 for antipyrine, 0.1 +/- 0.2 to 0.2 +/- 0.2 x 10(-4) cm s-1 for atenolol and 0.3 +/- 0.3 to 0.1 +/- 0.2 x 10(-4) cm s-1 for enalaprilat). One subject showed a large change in the permeability for antipyrine and atenolol in parallel with a large increase in water absorption, but enalaprilat was unaffected. 4. The luminal recovery of PEG 4000 was similar before (100 +/- 4%) and during (101 +/- 7%) induction of water absorption, which indicates that the barrier function of the intestine appears to be maintained during glucose-stimulated fluid absorption in man. 5. We conclude that induced net water absorption in man does not influence the paracellular permeability of hydrophilic drugs or drugs with high molecular weight to any significant extent.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMedDate not supplied

The interleukin-2-deficient mouse model.

Interleukin-2-deficient (IL-2(-/-)) mice develop colitis with striking clinical and morphological similarities to ulcerative colitis. Since transport and barrier properties are impaired in ulcerative colitis, we studied transport and barrier functions in IL-2(-/-) mice in order to gain insight for the first time into the general pathomechanisms of disturbed transport and barrier function of the intestine during inflammation. Alternating current impedance analysis was used to determine tissue conductance in the inflamed proximal colon of IL-2(-/-) mice and to discriminate between pure epithelial and subepithelial conductance. Surprisingly, epithelial conductance was not increased but diminished in IL-2(-/-) mice compared to controls (20.2 +/- 1.3 versus 28.8 +/- 2.8 mS/cm(2)). Concomitantly, conductance of the subepithelial tissue layers was decreased in IL-2(-/-) mice as a result of edema and infiltration with inflammatory cells. In the distal colon, electrogenic Na(+) transport (J(Na)) mediated by the epithelial Na(+) channel (ENaC) was measured 8 h after stimulation with 3.10(-9) M aldosterone in vitro as the drop in I(SC) (short circuit current) after addition of 10(-4) M amiloride. In controls, J(Na) was 6.9 +/- 0.9 micromol x h(-1) x cm(-2), whereas it was abolished in IL-2(-/-) mice. In conclusion, the inflamed colon of IL-2(-/-) mice exhibits a severe disturbance in Na(+) uptake via the ENaC in the absence of a barrier defect. Thus, reduced expression of active absorptive transport and not a barrier defect is responsible for the diarrhea in this model of intestinal inflammation. This makes this model suitable for studying the general pathomechanisms of the inflammatory downregulation of intestinal transport proteins.

Aldosterone↗

PubMed2003

Implications of hypoxia on mucosal barrier function.

Epithelial cells which line mucosal surfaces (e.g. lung, intestine) critically function as a semi-permeable barrier to the outside world. Mucosal organs are highly vascular with extensive metabolic demands, and for this reason, are particularly susceptible to diminished blood flow and resultant tissue hypoxia. Recent work from a number of groups have defined the critical molecular and cellular determinants of barrier function in hypoxic/ischemic tissues. Here, we will briefly highlight some of these studies from both a basic and clinical viewpoint and provide a perspective on future work related to tigh tjunction function in mucosal hypoxia.

Adherens Junctions↗

PubMed1983

Cadaverine and aminoguanidine potentiate the uptake of histamine in vitro in perfused intestinal segments of rats.

Examination of the serosal fluid following in vitro luminal perfusion of rat intestinal segments with 1 mg/ml [3H]histamine for 2 hr showed that histamine constituted only 22.1% of the total serosal radioactivity. The remainder of the radioactivity was comprised of histamine metabolites. When equimolar amounts of either aminoguanidine and cadaverine were added to the luminal perfusate, the percentage of the serosal radioactivity as histamine increased to 67.0 and 60.4%, respectively. However, when equal amounts of histamine and anserine were added to the luminal perfusate, only 30.6% of the 3H translocated within 2 hr was [3H]histamine. In all cases, the gross translocation rate based on the percentage of total serosal radioactivity for total radioisotope [( 3H]histamine plus [3H]histamine metabolites) was unchanged by the addition of these substances to the luminal perfusate. The results indicate that the potentiation of histamine toxicity by putrefactive amines, such as cadaverine, results from the inhibition of histamine metabolism which leads to increased uptake of unmetabolized histamine. The results do not support the hypothesis that potentiation occurs via an overall increase in the absorption of histamine and its metabolites due to some disruption in the barrier function of the intestine.

Animals↗

PubMed1993

Increased absorption of polyethylene glycol 600 deposited in the colon in active ulcerative colitis.

A defect in the barrier function of the intestinal mucosa has been proposed as important in both the pathogenesis and systemic manifestations of inflammatory bowel disease. After colonoscopy, polymers of polyethylene glycol (PEG) with molecular weights of 414-810 (mean 600), were instilled in the descending colon of patients with ulcerative colitis (n = 17) and in controls without intestinal inflammation (n = 8). The patients with active ulcerative colitis (n = 6) had a significantly increased uptake of PEGs in the molecular weight range 458-810, measured as urinary excretion over the first 6 hours after instillation. The median values for their excretion were 2.85-3.80% of PEGs instilled compared with 0.32-0.94% for patients in remission (n = 11) (p < 0.05-0.01) and 0.17-0.60% for the controls (p < 0.05-0.01). The differences in absorption of PEG 414 did not reach the present level of statistical significance. There was a positive correlation between PEG absorption and the endoscopic and histological grading of inflammatory activity in the sigmoid colon (p < 0.01-0.001). These findings support a correlation between the presence of active inflammation and PEG absorption. There was little evidence to support the presence of a primary defect in the colonic barrier in patients with ulcerative colitis.

Adolescent↗

PubMed2005

Prebiotic ingestion does not improve gastrointestinal barrier function in burn patients.

Prebiotics increase intestinal levels of health-promoting bacteria implicated in decreasing pathogen colonization, stimulating immune functions and stabilizing gut barrier functions, parameters which are altered in burn patients. We propose that regular intake of a prebiotic, oligofructose (OF), might help to improve the altered gastrointestinal (GI) permeability observed in burn patients. A randomized, double-blind, controlled clinical trial was carried out in 41 burn patients (mean burn surface area=17.1+/-8.2%) who ingested daily 6 g of oligofructose (OF group) or sucrose as placebo (Control group) during 15 days. Gastrointestinal permeability to sucrose and lactulose/mannitol (L/M) was evaluated on days 1 (before treatment) 3, 7, 14 and 21. A permeability test was also performed in 18 healthy subjects as controls. Thirty-one patients completed the protocol (dropout rate=24.4%). Healthy subjects had a basal sucrose excretion of 21.3 mg (14.0-32.5 mg) and a basal L/M ratio of 0.017% (0.009-0.022%). Sucrose excretion increased 5-fold and L/M ratio 4.4-fold in burn patients on day 1 and these high levels of marker excretion decreased significantly throughout the study (p=0.016 and 0.000001, respectively). No differences between the OF and Control groups were observed for sucrose excretion or L/M ratio. In conclusion, the normalization of gastrointestinal permeability is not accelerated by prebiotic intake.

Adult↗

PubMed1996

[The digestive barrier functions of the enzymatic systems of the normal small intestine and in pathology].

The fact that the enzymes splitting food nutrients, those of protein nature in particular, not only in the epithelial cells of the small bowel, but in the lower structures of the intestinal wall, i.e. in the stromal and muscle serous layers, is shown for the first time. They are integral parts of the intestinal enzymatic barrier that protects the internal medium of the body from penetration of proteins and peptides. The activities of the enzymes which are present in the epithelial, stromal, and muscle serous layers have been demonstrated to be substantially changed in disorders (immobilization in the presence of starvation, surgical interventions into the small bowel). It is suggested that examining the functions of the postepithelial enzymatic barrier along with those of the epithelial and immunological ones will provide a deeper insight into some certain disorders of the alimentary tract.

Animals↗

PubMed1990

Protein malnutrition predisposes to inflammatory-induced gut-origin septic states.

The development of an uncontrolled inflammatory response has been implicated in the pathogenesis of adult respiratory distress syndrome and multiple-organ failure. Because zymosan activates complement and induces a systemic inflammatory response, the effect of zymosan on intestinal structure and barrier function was measured in normally nourished (NN) and protein malnourished (PM) mice. Normally nourished and protein malnourished (up to 21 days) mice challenged intraperitoneally with zymosan (0.1 mg/g body weight) were killed 24 hours after zymosan challenge and their organs cultured for translocating bacteria. Zymosan-induced bacterial translocation was limited to the mesenteric lymph nodes of the NN mice, whereas translocating bacteria spread from the gut to the liver, spleen, and blood stream (p less than 0.05) in the PM mice. Zymosan-induced bacterial translocation appeared to be related primarily to the combination of mucosal injury and a disruption of the gut flora ecology in the PM mice and to mucosal injury in the NN mice. The extent of mucosal injury was greater the longer the mice were protein malnourished before zymosan challenge. The effect of zymosan on survival was measured in separate groups of mice. At a dose of 0.1 mg/g body weight, no deaths occurred in NN mice or in 7-day PM mice. However 20% of the 14-day PM mice and 80% of the 21-day PM mice receiving zymosan died. Thus PM predisposes to mucosal damage and the development of potentially lethal gut origin septic state during periods of systemic inflammation.

Animals↗