Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Intestinal barrier”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 721 records · Page 40Linked to original sources

The metabolic signal of hunger and satiety, and its pharmacological manipulation.

Hunger is elicited by the depletion of available macronutrients to the cells. The question is how the depletion is sensed and transduced into a biologically meaningful signal of hunger. Accumulating data show that the signal comes not from depletion of carbohydrates alone or from one of the other major macronutrients. Instead, the signal is generated by the overall cellular power production that induces hunger when it decreases and satiety when it increases. As for satiation, i.e. the state that causes the termination of a meal before nutrients cross the intestinal barrier, it is induced by early metabolic events elicited reflexly from orogastric afferences and tuning the preprandial metabolism towards the level of the postprandial metabolism. Neuronal responses from the medial hypothalamus suggest that they may integrate information on the degree of utilization of glucose and of lipids. Some of the pharmacological agents that reduce feeding seem to operate by increasing the metabolic rate in a way similar to that induced by a meal. These pharmacological agents are active because they mobilize endogenous metabolites, such as lipids, so inducing a sort of 'autocanibalic' meal.

Animals↗

Changes of plasma D(-)-lactate, diamine oxidase and endotoxin in patients with liver cirrhosis.

BACKGROUND: Plasma D(-)-lactate and diamine oxidase (DAO) can reflect patients' intestinal mucosal condition. We evaluated the changes of plasma D(-)-lactate, DAO and endotoxin activities and their significance in patients with liver cirrhosis. METHODS: Fifty liver cirrhosis patients were enrolled into experimental group and 30 healthy people into control group. The plasma levels of D(-)-lactate, DAO and endotoxin were detected spectrophotographically. RESULTS: The level of D(-)-lactate was significantly higher in the experimental group than that in the control group (P<0.01). Significant differences of D(-)-lactate levels were observed in Child-Pugh subgroups of the experimental group (P<0.01). The level of DAO was significantly higher in the experimental group than that in the control group (P<0.01), but the level of DAO in Child-Pugh subgroup C was significantly lower than that in Child-Pugh subgroup B (P<0.01). The level of endotoxin was significantly increased in the experimental group except Child-Pugh subgroup A (P<0.01). The plasma levels of D(-)-lactate, DAO and endotoxin were positively correlated with each other (P<0.01). CONCLUSIONS: The data suggest that both plasma D(-)-lactate and DAO activity are sensitive markers for early diagnosis of gut failure and endotoxemia in patients with liver cirrhosis. The impairment of intestinal barrier function may be one of the critical reasons for deterioration of liver cirrhosis.

Adolescent↗

[Immunological aspects of food intolerance in children during first years of life].

A study was made of the morphofunctional status and local defence of the gastrointestinal tract in 122 children aged 4 months to 6 years, suffering from food intolerance showed up by atopic dermatitis in 52 children and by chronic diarrhea in 70 children. Based on the allergological anamnesis, scarification cutaneous tests with food allergens, detection of antibodies to food antigens (RAST, HAIT) food allergy was revealed in all the children. Chronic gastroduodenitis was identified in all the children suffering from atopic dermatitis and in 95% of the children with chronic diarrhea. It should be mentioned that one-third of that group had a graver illness--diffuse duodenitis with sub-atrophy of the villi. The allergic genesis of the impairment of the gastroduodenal mucosa was confirmed. It was more remarkable in atopic dermatitis (tissue eosinophilia and high content of IgE-plasmacytes in the duodenal mucosa). The decrease of local immune defence of the mucous membrane, lactase deficiency, elevated growth of microorganisms in the duodenal contents promote the rise of intestinal barrier permeability for food antigens and enhancement of sensitization.

Age Factors↗

[Nutrition in acute pancreatitis].

Nutritional management during acute pancreatitis has the purpose to avoid a negative influence on the outcome and to preserve the morphofunctional integrity of the gut, preventing bacterial translocation. When the patient would start again normal nutrition after a period shorter than a week, thanks to the resolution of the clinical picture, and when the initial nutritional state of the patient is satisfactory, a particular nutritional support is not necessary. When the course of the disease is longer and the severity is higher, an early artificial nutritional support is advisable. Caloric needs thought to be useful are 25-30 kcal/kg/die; 40-60% of nutrient mixture should consist of carbohydrates and 20-30% of lipids. Proteins should be approximately 1.0-1.5 g/kg/die. On the basis of recent randomised, prospective clinical trials, enteral jejunal feeding is indicated as a first choice nutritional way, because of its ability to maintain the integrity of the intestinal barrier and its minimal effect on pancreatic secretion, acting significantly on inflammatory parameters and on prognostic markers. This procedure is not indicated when ileum is present and when it causes nausea, vomiting, abdominal pain and an increase of hepatic enzymes. In this case, parenteral feeding is an alternative. Hydroly-sated formulas, containing short peptides and a low percentage of long chain fat acids, are recommended.

Acute Disease↗

Perspectives in the design and development of new products for enteral nutrition.

Enteral nutrition is a technique that even though it was used in times immemorial, in the last 25 years has suffered a considerable development, from being considered a secondary therapeutic weapon destined only to feed the patient, to occupying an important status that goes beyond the single act of nourishing. The quantitative composition but overall the qualitative one, is object of an interesting argument in which a profile allowing the modulation of certain aspects of the organism response through the supplementation with different nutrients is searched. That includes from the keeping of the intestinal trophism and of the anti-bacteria intestinal barrier, so important to avoid the frightening multiple organ dysfunction, up to the lessening of the Systemic Response Inflammatory Syndrome (SRIS), going through the immuno-modulative feeding concepts, specific-feeding, pharmaco-nutrient or eco-nutrition. In this new dynamic not only certain nutrients such as glutamine, arginine, nucleotides, omega-3 fatty acids and many antioxidants have acquired importance, but also the manipulation of other molecules of a non- nutritional nature, such as hormones, cytokines and blockers. These aspects that imply passionate ways of investigation for the future are born from the better knowledge that is being acquired from such a severe pathophysiology processes such as sepsis and the organism response before fast and severe aggression; therefore, the modulation of that response through changes in the quantitative and qualitative formulas composition is being attempted.

Enteral Nutrition↗

[Nutritional consequences of gastrointestinal surgery].

The surgery of the Gastrointestinal Tract can damage the absorption and metabolism of the nutrients. We review the most important changes from the nutritional point of view, when any section of the G.I. Tract is removed; also the failure of the intestinal barrier is reviewed in critically ill patients. We discuss and suggest the Nutritional Support needed in G.I. Tract illness or surgical complications.

Digestive System Surgical Procedures↗

The origin and fate of hyaluronan in amniotic fluid.

The mechanisms which regulate the steady-state concentration and molecular weight of hyaluronan in the amniotic fluid of sheep at different gestational ages have been investigated. An attempt to trace the origin of the polysaccharide has been made by analyses of various fetal fluids (amniotic fluid, allantoic fluid, tracheal fluid, urine, and serum). The fate has been studied by injection of radioactively labelled hyaluronan into the amniotic cavity and following the tracer in fetal tissues and fluids. The concentration of hyaluronan in amniotic fluid varies considerably but is in the order of 5 mg/l at mid-pregnancy and decreases to 1 mg/l in late pregnancy. The polysaccharide has a Mr-distribution with a weight-average in the order of 10(6) at 10 to 13 weeks of gestation which decreases to 10(5) closer to term. Calculations show that urine contributes 0.1 and 0.5 mg of low-molecular (Mr = 10(4) hyaluronan per day in mid- and late pregnancy, respectively, and the lung 10-20% of that amount in the form of high-molecular weight polymer (Mr greater than 10(6). The hyaluronan disappears from the amniotic cavity by bulk flow due to fetal swallowing. It is taken up and degraded in the fetal intestine. Molecules of Mr = 10(3) can pass the intestinal barrier. Calculations show that about 0.5 mg and 1.0 mg of hyaluronan is eliminated per day from the amniotic fluid at 12 and 17 weeks of gestation, respectively. Thus, the higher rate of elimination and the relatively high urinary contribution in more mature fetuses explain the low concentration and Mr of amniotic hyaluronan in late gestation, whereas a slower elimination combined with a relatively larger contribution of high molecular weight hyaluronan both from lung and urine and possibly from other sources are responsible for the higher concentration and Mr of the compound in early pregnancy.

Allantois↗

[Organ distribution of bovine serum albumin administered intragastrically in the rat].

Radioimmunoassay was employed to examine distribution of antigenic structures of bovine serum albumin (BSA), absorbed by the gastrointestinal tract, in the blood serum and organs of intact rats. It was shown that 3 h after administering 3H-BSA an appreciable amount of its antigenic structures could be identified in the blood serum, liver, spleen, and carcass of the animals. The total amount of antigenic determinants of BSA which got into the internal environment of the body from the intestine amounted to about 0.2% of the dose administered. The highest specific content of antigenic structures of BSA supplied via the intestinal barrier was detected in the spleen.

Animals↗

Thermotolerance in the murine jejunum.

The heat sensitivity of the murine jejunum from C3H/HeJ mice and its capacity to develop thermotolerance were measured. Exteriorized loops of murine jejunum were heated in water baths at temperatures of 43-46 degrees C for various times. Animal mortality was used to calculate the median lethal dose by day 7 (LD50/7) in minutes as a function of temperature. The LD50/7 value was independent of the length of the intestinal loop, the presence of serum in the heating medium, prior starvation of animals, and fluid replacement post heating. The time-temperature plot for the LD50/7 values had an exponential slope constant of -0.71 degrees C-1, similar to that for other normal tissues. A heat treatment of 5 minutes at 45 degrees C increased the LD50/7 (total time at 45 degrees C) from 5.9 minutes to 13.0 and 15.6 minutes for 1- and 3-day fractionation intervals, respectively. Death after intestinal heating was associated with septicemia and reached a peak on days 2 and 3 post hyperthermia. Gentamicin (0.1 mg/mouse/day) increased the LD50/7 at 45 degrees C from 5.9 to 9.6; however, septicemia was still noted in dying, gentamicin-treated mice. Additional antibiotics did not further increase the LD50/7. Heat fractionation with gentamicin increased the LD50/7 (total time at 45 degrees C) to 23.0 and 12.5 minutes at 45 degrees C for 1- and 3-day intervals, respectively. These data suggest that thermotolerance plays a significant role in the intestinal heat response, but that the heat damage to intestinal barriers against bacterial septicemia may be superimposed on the cellular damage to the crypt-villus system.

Animals↗

Conservative treatment in acute pancreatitis.

In the absence of causative therapy of acute pancreatitis the management of the disease focus on treatment and prevention of complications and symptoms. In mild acute pancreatitis intravenous fluid administration, analgetics and avoidance of oral fluid or food intake is sufficient in most cases. The treatment of severe pancreatitis involves identification of pancreatic and peripancreatic necroses, best demonstrated and evaluated by contrast-enhanced computerized tomography (CT). Infection of such necroses is the most common cause of death from acute pancreatitis. Recent data suggest that antibiotic prophylaxis is worthwhile and it should therefore always be instituted in the severe form of the disease. Careful monitoring of vital functions is mandatory and early treatment with assisted ventilation and renal dialysis is advised. Adequate volume replacement and nutritional support is important. The role of the gut in the development of infected necroses is becoming increasingly obvious. Also, the absence of food in the intestine may increase the intestinal barrier damage. Therefore, enteral nutrition is discussed as a logical step in pancreatitis treatment. However, the food should be delivered below the ligament of Treitz (below the area of the cholecystokinin (CCK) cells) as CCK stimulation probably worsen the course of the disease.

Acute Disease↗

Infection, the gut and the development of the multiple organ dysfunction syndrome.

It has been hypothesised that failure of the gut is an important pathophysiological phenomenon of the generalised inflammatory response that leads to the multiple organ dysfunction syndrome (MODS). Abnormal colonisation, infections of gut origin, bacterial translocation are all signs of gut failure that have been implicated in the pathogenesis of MODS. We have concluded after summarising published experimental and clinical studies that have tried to correlate the occurrence or prevention (by selective decontamination of the digestive tract) of these phenomena with the development of MODS, it seems that in some patients it is clear that loss of intestinal barrier function or the onset of infection precedes the development of MODS. In other patients, however, this relationship is not so clear and it seems that these phenomena may reflect a failure of the host's immune and mechanical defence systems and are epiphenoma of critical illness. The causal relation between those phenomena and the development of MODS are complex and need further clarification.

Animals↗

Bacterial translocation in multiple organ failure: cause or epiphenomenon still unproven.

BACKGROUND: A body of evidence exists for the occurrence of bacterial translocation and its relationship to multiple organ failure (MOF). METHODS: Relevant articles on bacterial translocation (the phenomenon defined as the passage of microbes and endotoxin across the intestinal barrier) in patients prone to develop MOF and in representative animal studies were selected. To interpret and evaluate the evidence for bacterial translocation in current literature, the endpoints generally used are discussed. RESULTS: Fractional data from individual manuscripts were tabulated and assessed for statistical significance with chi 2 analysis. Various clinically relevant stimuli, postulated as important causative factors for the development of MOF, appeared to be interrelated and related to bacterial translocation itself. CONCLUSIONS: Convincing evidence exists that bacterial translocation can occur in humans during various disease processes. However, it remains to be determined whether a causal relationship between bacterial translocation and MOF exists. MOF is probably multifactorial and not uniform in origin; when evaluating translocation as a causative factor in the absence of an infective focus, the type of initiating event and the period of time after which MOF develops should be taken into account. The origin of early MOF is probably a non-bacterial, extensive, inflammatory response resulting in massive generalized endothelial cell activation. Late MOF may be caused primarily by bacterial translocation inducing an imbalance between proinflammatory and anti-inflammatory cytokines.

Animals↗

[Administration of glutamine and its dipeptides in parenteral nutrition. Which patients are candidates?].

Despite the fact that glutamine is not considered to be an essential amino acid, it is the amino acid found in the greatest concentration both in plasma (26%) as in skeletal muscle (75%). These levels may decrease in post-operative, trauma, or critical patients. Glutamine performs many functions in which its demand may be increased, such as: it is a precursor of the synthesis of nucleotides; it is an activator of the protein synthesis and at the same time it inhibits the degradation; it is an activator of glycogen synthesis; it is a metabolic substrate for rapidly replicating cells; it is an energy source for the enterocyte which is so important for maintaining the integrity and the function of the intestinal barrier, and the consumption thereof may be increased under conditions of stress. The administration of glutamine intravenously leads to two physical-chemical problems; the first is its low solubility in water; at 20 degrees C this is only 36 g/l, and the second problem is its low chemical stability in an aqueous solution at 22-24 degrees C, this being 11 days. This problem has led the industry to research two dipeptides of glutamine; L-alanyl-glutamine, and L-glycyl L-glutamine, both of which are much more soluble and much more stable. At present there is still a controversy regarding the dosage of glutamine and its dipeptides, with the dose being 0.19-0.29 g/kg/day of L-glutamine or its dipeptide forms, in surgical post-operative periods or to prevent bacterial translocation, and in patients who are candidates for bone marrow transplants, the administered dose has been 0.37-0.57 g/kg/day. The purpose of this study is to review the existing bibliography regarding the efficacy of L-glutamine or its dipeptides in four possible indications for its application in the daily clinical practice, such as: a) In post-operative surgical patients of major or medium surgery, glutamine or its dipeptides reduces the losses of muscular glutamine and its catabolism, showing a less negative nitrogen balance. b) Whether it avoids bacterial translocation. c) Whether it favors the response of the immunological system. d) Whether in patients who are candidates for bone marrow transplants this decreases the side effects due to chemotherapy and radiotherapy such as mucositis, or whether it decreases the number of days of neutrophil recovery. At present, on the European market there are two commercially available brands of glutamine dipeptides: Dipeptiven, by Fresenius Laboratories, Germany. A 100 ml vial which corresponds to 20 g of L-alanyl L-glutamine (8.2 g of alanine + 13.46 g of L-glutamine). This is added to the standard amino acid solution. Glamin, Pharmacia and Upjohn Laboratory, Sweden. This is an amino acid solution with 13.4% essential and non-essential amino acids which are equivalent to 22.4 g of nitrogen/l, and which contain 30.27 g L-glycyl-L-glutamine (10.27 g of glycine + 20 g of L-glutamine).

Bone Marrow Transplantation↗

[Optimal postoperative nutrition: pro and contra enteral and parenteral feeding].

Malnutrition is correlated with an increased incidence of postoperative complications. As a consequence, preoperative hyperalimentation results in a decrease of postoperative complications in patients with malnutrition. In contrast, the beneficial effects of postoperative nutritional support are still to be proven. The majority of prospective trials have shown limited advantageous effects for patients with delayed nutritional intake after the surgical procedure. In these patients enteral nutrition has been shown to reduce the rate of infectious complications. If enteral nutrition cannot be applied, the addition of glutamine as a dipeptide is beneficial with regard to intestinal barrier function.

Enteral Nutrition↗

Beneficial effects of lexipafant, a PAF antagonist on gut barrier dysfunction caused by intestinal ischemia and reperfusion in rats.

BACKGROUND: Platelet-activating factor (PAF) may play a pivotal role in the pathogenesis of intestinal ischemic injury. METHODS: The potential role of PAF in intestinal ischemia and reperfusion (I/R) and the development of gut endothelial and epithelial barrier dysfunction and distant organ injury were investigated by pretreatment with a PAF antagonist, lexipafant. Bidirectional permeability of the intestinal barrier, enteric bacterial translocation, protease-antiprotease balance and mucosal histology, and also changes in pulmonary and liver endothelial barrier permeability were measured following intestinal ischemia for 40 min with 6 h of reperfusion in rats. RESULTS: Intestinal mucosal endothelial and epithelial permeabilities significantly increased in animals with I/R. Lexipafant prevented the increase in albumin leakage from blood to the mucosal interstitium and the intestinal lumen during reperfusion, and the mucosal albumin leakage from the gut lumen to blood during I/R. Bacterial translocation was frequently noted in animals with I/R, while only a few positive cultures were obtained in animals with I/R administered lexipafant. Less leakage of fluorescein isothiocyanate dextran 70,000 into the interstitial space and gut lumen in I/R animals with lexipafant pretreatment was found under fluorescein microscopy. Lexipafant also partly prevented C1 inhibitor, prekallikrein, and factor X consumption in I/R animals and partly prevented changes in pulmonary and liver albumin leakage. CONCLUSIONS: PAF seems to play an important role in I/R-associated intestinal dysfunction and the development of distant organ dysfunction, probably by triggering endothelial and epithelial barrier dysfunction. Furthermore, PAF seems to be partly involved in activation of the protease-antiprotease system. The use of PAF antagonists may provide a mode of treatment against I/R-associated organ dysfunction.

Animals↗

Morphine-induced degradation of the host defense barrier role of intestinal mucosal injury.

The effect of morphine on intestinal ulcer formation and on the degradation of the host defense barrier was studied. Mice receiving morphine (MRM) showed mucosal ulcer formation in the ileum and in the upper third of the colon. In in vitro studies, morphine enhanced apoptosis of cultured human colonic cells (HCC). Nitric oxide synthase (NOS) inhibitors attenuated the proapoptotic effect of morphine. Moreover, morphine stimulated NO generation by HCCs. MRM also showed a breach in the host defense barrier as well as injury to peritoneal macrophages. Although NOS inhibitors completely prevented morphine-induced intestinal ulcer formation, it provided only partial protection against a breach in the host defense barrier and peritoneal macrophage injury. Propranolol did not inhibit the induction of intestinal ulcer formation in MRM; nevertheless, propranolol prevented a breach in the host defense barrier as well as macrophage injury in MRM, whereas hemin exacerbated macrophage injury as well as the breach in the host defense barrier of MRM. These findings suggest that morphine-induced intestinal injury is mediated through NO generation. However, the degradation of the host defense barrier correlates with macrophage injury, but not intestinal injury.

Animals↗

Molecular mechanism of tumor necrosis factor-alpha modulation of intestinal epithelial tight junction barrier.

A TNF-alpha-induced increase in intestinal epithelial tight junction (TJ) permeability has been proposed to be an important proinflammatory mechanism contributing to intestinal inflammation in Crohn's disease and other inflammatory conditions. Previous studies from our laboratory suggested that the TNF-alpha-induced increase in intestinal TJ permeability was mediated by an increase in myosin light chain kinase (MLCK) protein expression. However, the molecular mechanisms that mediate the TNF-alpha increase in intestinal TJ permeability and MLCK protein expression remain unknown. The purpose of this study was to delineate the intracellular and molecular mechanisms that mediate the TNF-alpha-induced increase in intestinal TJ permeability; using an in vitro intestinal epithelial model system consisting of filter-grown Caco-2 intestinal epithelial monolayers. To examine the molecular mechanisms involved in the TNF-alpha regulation of intestinal TJ barrier, we identified and cloned for the first time a functionally active MLCK promoter region. TNF-alpha treatment of filter-grown Caco-2 monolayers transfected with plasmid vector containing the MLCK promoter region produced an increase in MLCK promoter activity and MLCK transcription. The TNF-alpha-induced increase in MLCK transcription corresponded to a sequential increase in MLCK protein expression, MLCK activity, and Caco-2 TJ permeability. The TNF-alpha-induced increase in MLCK promoter activity was mediated by NF-kappaB activation, and the inhibition of NF-kappaB activation prevented the TNF-alpha-induced increase in promoter activity and the subsequent increase in MLCK protein expression and Caco-2 TJ permeability. The TNF-alpha-induced activation of MLCK promoter was mediated by binding of the activated NF-kappaB p50/p65 dimer to the downstream kappaB binding site (-84 to -75) on the MLCK promoter region; deletion of the kappaB binding site prevented the TNF-alpha increase in promoter activity. Additionally, siRNA silencing of NF-kappaB p65 also prevented the TNF-alpha increase in MLCK promoter activity. In conclusion, our findings indicated that the TNF-alpha-induced increase in intestinal epithelial TJ permeability was mediated by NF-kappaB p50/p65 binding and activation of the MLCK promoter. NF-kappaB p50/p65 activation of the MLCK promoter then leads to a stepwise increase in MLCK transcription, expression and activity, and MLCK-mediated opening of the intestinal TJ barrier.

Caco-2 Cells↗