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PubMed1995

Epithelial barrier and ion transport in coeliac sprue: electrical measurements on intestinal aspiration biopsy specimens.

Epithelial barrier function and ion transport was studied in coeliac sprue using a miniaturised Ussing device for measurements on diagnostic aspiration biopsy specimens from the jejunum of untreated or gluten free nourished sprue patients, or from healthy controls. Pure epithelial resistance (Re) indicating epithelial barrier function was determined by transmural alternating current impedance analysis. It was reduced by 56% in acute sprue mean (SEM) (9 (1) omega.cm2) compared with controls (20(2) omega.cm2). In gluten free nourished sprue patients Re was only partly recovered (15 (1) omega.cm2). Subepithelial resistance (Rsub) was also changed from 28 (1) omega.cm2- in control to 17 (1) omega.cm2 in acute sprue because of the change in mucosal architecture, but was unchanged in gluten free nourished sprue patients (29 (4) omega.cm2). In acute sprue, unidirectional Na+ and Cl- fluxes were increased in both directions as a consequence of the decreased resistance. However, short circuit current (ISC) as well as Na+ and Cl- net fluxes were not significantly different from control. Subsequently, the electrogenic Cl- secretory system was investigated. After maximal stimulation with theophylline and prostaglandin E1, a Cl(-)-dependent increase in ISC was obtained in the sprue mucosa and control jejunum. It showed saturation characteristics and was blockable by serosal bumetanide. When compared with control, neither Km nor Vmax of this electrogenic Cl- secretion was significantly changed in coeliac sprue. In conclusion, a miniaturised Ussing device was used for transport measurements on intestinal biopsy specimens. In acute coeliac disease, the epithelial barrier of the jejunum was seriously disturbed. The active electrogenic Cl- secretory transport system was present in the sprue mucosa, but was not activated in the Ussing chamber in vitro when compared with control jejunum.

Acute Disease↗

PubMed2005

Bacterial translocation (BT) in cirrhosis.

Gut flora and bacterial translocation (BT) play an important role in the pathogenesis of the complications of cirrhosis. Research on the pathogenesis of BT and its clinical significance transcends established boundaries between microbiology, cell biology, intestinal pathophysiology, and immunology. This review delineates multiple mechanisms involved in the process of BT, with an emphasis on alterations in intestinal flora and mucosal barrier function, particularly immunological defense mechanisms. Current knowledge on the innate and adaptive immune response that allows a "friendly" communication between bacteria and host is summarized, and alterations occurring in cirrhosis that may facilitate BT are discussed. In addition, definition of a "pathological" BT is proposed together with an analysis of the anatomical site and route of BT. Finally, therapeutic approaches for the prevention of BT in experimental and human cirrhosis are reviewed. Future research in the field of BT in cirrhosis will allow the development of new therapeutic targets in the prevention of infections and other complications of cirrhosis.

Bacterial Translocation↗

PubMed2005

Leaky guts and lipid rafts.

The intestinal epithelium functions as a physical barrier separating luminal microorganisms from the underlying immune system. There is compelling evidence that several intestinal diseases are associated with the translocation of commensal bacteria across the epithelial barrier. Recent work has identified a novel mechanism by which normally non-invasive enteric bacteria breach the intestinal epithelium during periods of inflammation.

Bacterial Infections↗

PubMed2006

Vasoactive drugs and the gut: is there anything new?

PURPOSE OF REVIEW: Systemic changes in blood pressure and cardiac output induced by pressors and inotropes do not always correlate to improvements in regional perfusion. Since the gut is often referred to as the 'motor' of the systemic inflammatory response syndrome, the impact of vasoactive agents on splanchnic perfusion has theoretical importance. This review will highlight recent studies examining secondary effects of vasoactive agents on intestinal perfusion, metabolism, and barrier function. RECENT FINDINGS: Norepinephrine has minimal impact on mesenteric blood flow although the combination of norepinephrine and dobutamine increases splanchnic blood flow in sepsis. Dopamine also increases mesenteric blood flow although this may be associated with negative hepatic energy balance at high does. Vasopressin and epinephrine both have negative effects on splanchnic blood flow. Newer inodilators levosimendan and olprinone preferentially improve mesenteric perfusion in animal models. SUMMARY: Secondary effects of norepinephrine and dopamine on splanchnic perfusion are minor compared with their systemic effects. While vasopressin usage is increasing in the intensive care unit, caution should be used because of its adverse effects on gut perfusion. Experimental agents for the treatment of heart failure have beneficial gut-specific effects although the clinical significance of this is currently limited by their availability.

Adrenergic beta-Agonists↗

PubMed2002

Intestinal epithelial pathobiology: past, present and future.

The intestinal epithelium serves as one of man's primary interfaces with the outside world. Its importance is illustrated by the fact that the proper functioning of this interface is absolutely essential for human health, and even modest perturbations in its function may lead to diarrhoea, constipation, malnutrition, dehydration, infectious disease or chronic intestinal inflammatory diseases such as Crohn's disease and ulcerative colitis, collectively referred to as inflammatory bowel disease. Both pathogen-induced intestinal inflammation and the active flares of inflammatory bowel disease are histopathologically defined, their sequellae being mediated by neutrophils that migrate across the intestinal epithelium, forming a crypt abscess. Classically, the intestinal epithelium has been thought of primarily as a barrier, and indeed this is a very important aspect of its function, but the intestinal epithelium is also a highly interactive barrier. This chapter will summarize some of the basic research conducted over the past 15 years that has revealed basic insights into how the epithelium participates in the formation of a crypt abscess and how it plays a role in causing the characteristic clinical manifestations that ensue. In addition, the chapter will discuss how this research has resurrected the 'old', yet newly emerging, concept that physiological malfunction of the intestinal epithelium can be the primary defect that leads to the innate and adaptive immune dysregulation mediating inflammatory bowel disease.

Cell Movement↗

PubMed1996

Increased gastric absorption of polyethylene glycols in atrophic gastritis.

Atrophic gastritis increases the risk of developing gastro-intestinal tumours. An impaired barrier function of the gastric mucosa could contribute to this risk. The absorption of polyethylene glycols (molecular weights 414-766), expressed as recovery in 6-hour urine, was studied both after oral and duodenal loads in patients with atrophic gastritis (n = 18) and compared with controls without gastritis (n = 9). The patients had a higher absorption after oral than after duodenal load for molecular weights 502-546. The differences in absorption after oral and duodenal loads were correlated with the severity of the atrophy in the antrum. No differences were found in the controls. Absorption after the duodenal load did not differ between the study groups. The increased gastric absorption of polyethylene glycols in patients with atrophic gastritis may be caused by a permeability disturbance of the gastric mucosa.

Administration, Oral↗

PubMed1992

The effect of hemorrhagic shock on intestinal amino acid absorption in vivo.

Hemorrhagic shock causes a disproportionate decrease in portal blood flow which may adversely affect the barrier and absorptive functions of the intestine. The absorptive capacity of the small intestine was studied during shock induced by mild and severe hemorrhage in the rat by measurement of the uptake of a radiolabelled amino acid analog (aminoisobutyric acid: AIB). Hemorrhage resulted in a significant reduction in systemic blood pressure, portal blood flow, and the absorption of AIB from the small intestine. Resuscitation restored both blood pressure and portal blood flow. But a significant reduction in absorption of AIB persisted. This suggests that hemorrhage results in an inhibition of amino acid intestinal active transport which is not dependent on the mesenteric circulation. The reduced intestinal absorptive function has important implications for the route of administration of nutrition following hemorrhage and trauma.

Aminoisobutyric Acids↗

PubMed1990

Obstructed intestine as a reservoir for systemic infection.

Intestinal motility, absorption, and secretion are altered after intestinal obstruction, but at what point the normal bacterial barrier function of the viable gut fails after intestinal obstruction is unclear. Thus, we tested whether after simple intestinal obstruction bacteria would translocate across the viable intestinal wall to cause systemic infection. Within 6 hours of intestinal ligation 1 cm proximal or distal to the ileocecal valve, bacteria had translocated to the mesenteric lymph nodes, and by 24 hours after intestinal obstruction, bacteria had spread to the liver, spleen, and blood stream. Bacterial translocation rarely occurred in the animals undergoing laparotomy and sham intestinal ligation, indicating that bacterial translocation was not due to surgical stress. Based on the results of these studies, bacterial translocation induced by intestinal obstruction appears to be due to disruption of the ecology of the normal gut microflora, leading to intestinal overgrowth with certain enteric bacilli and mucosal damage. Although the exact mechanism(s) by which simple mechanical obstruction injures the intestine is not known, the fact that mucosal injury did not occur in germ-free mice suggests that bacteria may play a role in the pathogenesis of obstruction-induced intestinal injury.

Animals↗

PubMed2000

Trans/paracellular, surface/crypt, and epithelial/subepithelial resistances of mammalian colonic epithelia.

The epithelial barrier function of the large intestine resides in the trans- and paracellular pathways of the surface epithelium and crypts. Conventional transmural resistance and permeability measurements, however, yield only the resistance of the whole tissue and not that of its individual components. Combining conductance scanning techniques and impedance analysis, we determined the resistance of epithelial and subepithelial tissues, crypts and surface epithelium, and trans- and paracellular pathways of the mouse distal colon. The subepithelial tissue contributed 15% to the transmural resistance of 118+/-9 omega x cm2. In the epithelium proper the resistance of crypts (429+/-86 omega x cm2) exceeded that of the surface epithelium (132+/-15 omega x cm2). The paracellular resistance (3.2+/-0.4 k omega x cm2) of the surface epithelium was 23-fold higher than the transcellular resistance (137+/-16 omega x cm2), and thus the epithelium was classified as "medium tight". In order to investigate the trans- and paracellular resistances of the crypt epithelium as well, flat monolayers of HT-29/B6 cultured colon crypt cells were studied, which had a transepithelial resistance of 349+/-32 omega x cm2. With transcellular resistance (377+/-41 omega x cm2) tenfold lower than the paracellular resistance (3.9+/-1.3 k omega x cm2), this cryptal monolayer was also classified as "medium tight". Hence, considering the 1.2 times larger area of the crypt epithelium, the surface epithelium has a 4 times larger ion permeability than the crypt epithelium. However, the paracellular resistances are not different. Thus the lower transcellular resistance of the surface compared to the crypt epithelium suggests a higher density of ion channels in the apical membrane of surface cells.

Amiloride↗

PubMed1996

Radionuclide studies in intestinal transplantation. Diagnosis of rejection and assessment of permeability.

Three patients who received intestinal allografts were studied using two distinct radionuclide investigations. In the first, 111In or 99mTc-labeled leukocyte scanning was performed to assist in the diagnosis of rejection. It was able to demonstrate the occurrence of rejection in the transplanted intestine, and the response to antirejection therapy. In 1 case, the abnormality on the scan preceded the histological confirmation of rejection. The second technique studied mucosal integrity by serial 51Cr-EDTA/14C-mannitol permeability tests. These studies demonstrated the initial marked impairment and the slow return to normal function of the intestinal mucosal barrier. In 1 patient, this occurred by 91 days; in another, it took 232 days. A single assay performed in the third patient at the time of allograft rejection was also abnormal. Both radionuclide tests were helpful in the care of these complicated cases.

Adult↗

PubMed2003

Intestinal mucosal oxidative damage and bacterial translocation in cirrhotic rats.

BACKGROUND: Bacterial translocation plays an important role in the pathogenesis of spontaneous bacterial peritonitis mainly due to intestinal bacterial overgrowth. Alterations in the functional integrity of the intestinal barrier caused by an increased production of free radical metabolites as a consequence of portal hypertension could also facilitate bacterial translocation in cirrhotic rats. OBJECTIVE: The aim of the study was to determine intestinal mucosal lipid peroxidation and neutrophil infiltration and their relationship with portal hypertension and bacterial translocation in cirrhotic rats. DESIGN: Eighteen male Sprague-Dawley rats with cirrhosis induced by carbon tetrachloride, administered by gavage, and eight control rats were included in the study. METHODS: Samples of jejunum, ileum and caecum were obtained by laparotomy for the determination of malondialdehyde and myeloperoxidase as indexes of lipid peroxidation and neutrophil infiltration, respectively. Samples of ascitic and pleural fluids, mesenteric lymph nodes and ileal stools were obtained for the culture of microoganisms. RESULTS: The concentration of malondialdehyde was significantly higher in ileal and caecal, but not in jejunal mucosa, in cirrhotic rats, mainly in those with ascites (P< 0.01), as compared to control rats (P< 0.01), and in cirrhotic rats with bacterial translocation compared to those without bacterial translocation (P< 0.01). No differences between groups were observed in the concentrations of myeloperoxidase in jejunum, ileum or caecum. A direct correlation between ileal malondialdehyde and portal pressure was observed (P< 0.01). CONCLUSIONS: Cirrhotic rats, particularly those with ascites and bacterial translocation, show increased malondialdehyde levels in ileal and caecal mucosa. These results suggest that mucosal oxidative damage in ileum and caecum could favour bacterial translocation in cirrhotic rats.

Animals↗

PubMed1994

Strategies for attenuating protein-catabolic responses in the critically ill.

Specialized enteral and parenteral nutrition are now a standard components of care in critically ill patients. This adjunctive therapy corrects and prevents nutrient deficiencies, attenuates the loss of body protein, and improves clinical outcomes in malnourished patients. Several novel strategies designed to improve the metabolic and clinical effects of specialized nutrition are under vigorous clinical investigation. These new approaches include increased emphasis on enteral feeding to maintain intestinal absorptive, immune, and barrier function; administration of conditionally essential amino acids (glutamine, arginine); use of specialized lipid products and antioxidants; and administration of growth factors such as human growth hormone. Randomized, controlled clinical trials will define the clinical and metabolic efficacy and cost-effectiveness of these therapies in specialized nutrition support.

Arginine↗

PubMed2003

Real-time reverse transcription-PCR expression profiling of the complete human ATP-binding cassette transporter superfamily in various tissues.

BACKGROUND: ATP-binding cassette (ABC) transporters are involved in many physiologic processes, such as lipid transport, sterol homeostasis, immune mechanisms, and drug transport, and cause various human inherited diseases. Thus, the analysis of ABC transporter mRNA expression profiles for basic research, especially in the field of lipid metabolism, for clinical diagnosis, and for monitoring of drug effects is of great interest. METHODS: We have developed a rapid, accurate, and highly sensitive real-time reverse transcription-PCR (RT-PCR) method for detection and quantification of all 47 currently known members of the ABC transporter superfamily. Our expression analysis is based on relative quantification using a calibration curve method. With our assay, expression monitoring of a large number of RNA samples in a 384-well format with only 50 ng of total RNA is possible. RESULTS: In contrast to previous expression analyses of single ABC genes, our method allows the rapid and complete analysis of all ABC transporters in given RNA samples. We used our newly established expression panel to study the gene expression of all human ABC transporters in 20 different human tissues. As a result, we identified tissues with high transcriptional activity for ABC transporters. These organs are mainly involved in secretory function (adrenal gland), metabolic function (liver), barrier function (lung, trachea, small intestine), and tropic function (placenta, uterus). CONCLUSIONS: Our RT-PCR assay allows rapid, high-throughput transcriptional profiling of the complete ABC transporter superfamily and thus provides a new enabling tool for research, clinical diagnosis of disease, and drug testing and development.

ATP-Binding Cassette Transporters↗

PubMed1975

[Experimental studies on the pathogenesis of coli enterotoxemia in swine. I. Comparison of toxin effect of 2 different E. coli serotypes following parenteral toxin administration].

Broth culture filtrate containing endotoxin, prepared from serotype O 139:K82(?):H1 was given by the intra-enteric route with and without dimethyl sulphoxide, and with or without blockade of the RES by intravenous injection of trypan blue, using about five piglets for each of the four combinations. Clinical signs, blood pressure, ECG, respiration, temperature, haematology and pathological findings were recorded. Coli enterotoxaemia manifested by fatal endotoxin shock developed in all ten piglets given toxin plus dimethyl sulphoxide, and in 4 of 5 similarly treated after RES blockade. The sondrmoe did not develop in piglets given large amounts of toxin without dimethyl sulphoxide, whether the RES was blocked or not. When enteric absorption of toxin was promoted by dimethyl sulphoxide, RES blockade increased the sensitivity of the animal to toxin (shortening of the time till death). The results show that there are two functional barriers to endotoxin: - the intestinal barrier, which normally prevents large amounts of toxin from entering the circulation; and RES, which plays a part in detoxifying and eliminating endotoxin which has been absorbed. Application of these findings to the pathogenesis of coli, enterotoxaemia is discussed.

Animals↗

PubMed2002

[Enteral tube feeding early after surgery on the stomach and the duodenum].

Experience in enteral tube feeding (ETF) early after stomach resection, gastrectomy, reconstructive surgeries for chronic duodenal obstructions and postgastroresection disorders in 1716 patients is presented. Irrigators were installed in the jejunum during surgery, more rarely--through gastroscope below distal anastomosis. During the first day saline solutions were administered, further--nutritional cocktails. Period of ETF was 5.8 +/- 0.8 days in uncomplicated postoperative period and from 9 to 73 days in postoperative complications. ETF stimulates motor, resorption, synthetic, barrier functions of the small intestine. ETF permits to improve immediate results of stomach and duodenum surgery and to reduce cost of treatment.

Duodenal Obstruction↗

PubMed2006

Spontaneous bacterial peritonitis: pathogenesis, diagnosis, treatment.

Due to inadequate defence mechanisms, cirrhotic patients with ascites have an increased susceptibility to infections, the most frequent and the most severe one being spontaneous bacterial peritonitis (SBP). SBP diagnosis is based on testing of the ascitic fluid obtained by paracentesis. A polymorphonuclear cell count of more than 250 cells/mm3 of ascitic fluid is considered diagnostic and from cultures of ascitic fluid only one germ should be isolated. 60% of the SBP episodes are produced by gram negative enteric bacilli - E. coli and Klebsiella spp. being the most frequent isolated microorganisms. The most important pathogenic mechanism for SBP is bacterial translocation. In liver cirrhosis, three mechanisms are proposed for the pathogenesis of SBP: intestinal bacterial overgrowth, the alterations (structural and functional) of the intestinal mucosal barrier and the deficiencies of the local immune response. The most appropriate antibiotic treatment is a third generation cephalosporin (Cefotaxim or Ceftriaxon) which should be administrated for 5 days. With early start of the antibiotic treatment, the short-term prognosis of cirrhotic patients with SBP has improved significantly. Unfortunately, the long term prognosis remains extremely poor due to the severity of subjacent liver disease.

Anti-Bacterial Agents↗

PubMedDate not supplied

[Phospholipid composition of mucous membrane tissue in the gastrointestinal tract of rabbits in simulated Salmonella infections].

The paper deals with the phospholipid composition in the mucosa tissue of different areas of gastrointestinal tract and in membranes of the villous margin of small intestine enterocytes under conditions of experimental salmonellosis infection. A decreased relative content of cardiolipin is observed in all periods of the infection process in the stomach mucosal tissue and in the period of the disease height and convalescence--in the sigmoid colon. Phosphatidyl choline appears in the tissue of duodenum and jejunum during the height of the infection process. An increase in a relative content of lysophosphatidyl choline and phosphatidyl serine and a decrease in that of phosphatidyl ethanolamine are revealed in membranes of enterocyte villous margin when modelling the diarrhea process by the intraperitoneal administration of the lipopolysaccharide complex of salmonellas. The found changes in the composition of phospholipids in the mucous membrane tissue and membranes of the enterocytes villous margin are supposed to reflect alterations in the functional state of the intestine barrier and play a definite role in development of the diarrhea syndrome.

Animals↗

PubMed1995

Small intestinal absorption of polyethylene glycol 400 to 1,000 in the portacaval shunted rat.

Functional changes of the intestinal barrier that may occur after the creation of a portacaval shunt (PCS) were investigated. After chronic PCS in the rat, the intestinal absorption of and the jejunal permeability to the inert polymer marker polyethylene glycol (PEG) with molecular weight (Mw) ranging from 400 to 1,000 g/mol were investigated. The PEG mixture was orally fed to PCS and sham-operated rats, and urine was collected for 24 hours to obtain the urinary recovery of the different PEG polymers as a measure of intestinal absorption. To study the intestinal permeability, segments from the proximal small intestine were incubated in diffusion chambers with the PEG mixture on the mucosal side, and samples were withdrawn from the serosal side for analysis. The urinary recovery for the PEGs increased (P < .01) while the tissue permeability decreased (P < .001) in the PCS group rats in comparison with Sham-operated rats. The increased absorption in vivo was caused neither by altered renal clearance, nor by changed portal blood pressure. The decreased jejunal permeability in the PCS rats could be explained by a reduction of the mucosal area by shortening of the microvilli. This discrepancy indicates that changes in permeability and absorption may not be parallel during PCS. It is possible that these changes also may be affected by nutritional factors, drug therapy, as well as toxic substances.

Animals↗