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PubMed1980

IgE levels in intestinal juice.

This investigation was performed to determine the possible significance of the IgE levels in intestinal secretions for the recognition of type I food allergy (immediate hypersensitivity). Four groups of individuals were studied and compared with each other: (1) healthy controls and patients with gastrointestinal disorders not affecting the small intestine; (2) patients with small intestinal disease; (3) patients with various manifestations of allergy but without food intolerance; and (4) patients with atopic sensitivity to foods. Despite the presence of proteolysis in the intestinal fluid, a statistically highly significant increase of the intestinal IgE level was observed in patients of group 4 with type I food allergy and in patients of group 3 as compared with normals. This was associated with an increase in the serum IgE level. An increased synthesis of the IgE in the lamina propria of the small intestine is most probable, but not yet adequately established.

Ancylostomiasis↗
PubMed2006

Stress-induced breakdown of intestinal barrier function in the rat: reversal by wood creosote.

Our previous studies demonstrated that wood creosote (Seirogan) inhibits intestinal secretion and normalizes the transport of electrolytes and water in rats subjected to restraint stress. The goal of the present study was to examine whether wood creosote has a protective effect against stress-induced breakdown of intestinal barrier function. F-344 rats were subjected to 90-min water avoidance stress (WAS) with wood creosote (30 mg/kg) or vehicle administered intragastrically 30 min prior to WAS. Sham stressed rats received wood creosote or vehicle treatment but did not experience the WAS. All rats were euthanized at the end of the WAS or sham-stress and the jejunum and colon were isolated. Epithelial transport was studied in modified Ussing chambers. Spontaneous secretion was assessed by electrophysiological measurement of the short circuit current (I(sc)) while electrical conductance (G) was calculated from the potential difference (PD) and I(sc) using Ohm's law. Intestinal permeability was defined by the mucosal-to-serosal flux of horseradish peroxidase (HRP). WAS significantly elevated basal I(sc) and G and increased epithelial permeability to HRP in the jejunum but not in the colon. Wood creosote resulted in a significant reduction of the stress-induced increase in I(sc), G and the mucosal-to-serosal flux of HRP compared to the vehicle-treated group. Wood creosote caused no significant effects in sham-stressed rats. The results suggest that oral administration of wood creosote may prevent stress-induced diarrhea by preventing aversive effects on small intestinal secretion and barrier function.

Animals↗
PubMed1984

Evidence for cardiac volume-receptor regulation of feline jejunal blood flow and fluid transport.

The aim of the study was to investigate the role of cardiac mechanoreceptors in the reflex regulation of intestinal blood flow and fluid transport. Feline cardiac mechanoreceptor activity was modified with two noninvasive techniques: positive-pressure ventilation (PPV) and inspiratory resistance breathing (IRB). A jejunal segment with intact vascular and nervous supply was isolated and exposed to cholera toxin as a model for intestinal secretion. The results revealed that PPV induced a pronounced intestinal vasoconstriction and a marked inhibition of choleraic secretion. IRB had the opposite effects. The responses were well correlated with changes in central blood volume and either markedly reduced or abolished by vagotomy, intestinal alpha-adrenoreceptor blockade, or postganglionic mesenteric denervation. The results indicate that cardiac mechanoreceptors with vagal afferents may mediate the observed reflex responses, and hence this receptor station may be of importance in the normal reflex control of intestinal hemodynamics and fluid transport.

Animals↗
PubMed1991

Gut lavage fluid proteins as markers of activity of inflammatory bowel disease.

Intestinal secretions may be obtained by gut lavage using a polyethyleneglycol-based electrolyte lavage solution; concentrations of immunoglobulins and other proteins are readily measured in processed gut lavage fluid. As patients with inflammatory bowel disease (IBD) have greatly increased numbers of IgG-producing intestinal immunocytes, we measured gut lavage fluid IgG levels in 44 patients with IBD with various degrees of disease activity to determine whether total IgG in gut lavage fluid reflects disease activity. We also measured levels of albumin in gut lavage fluid, to determine the degree of plasma leakage. Both IgG and albumin levels in the patients with active IBD were significantly higher than those in controls and patients with inactive IBD (all p less than 0.00001). IgG is a more specific index of disease activity than albumin, with no overlap between levels in controls and patients with active IBD. There was a positive correlation (r = 0.68, p less than 0.0001) between IgG and albumin levels, suggesting that gut lavage fluid IgG is mainly plasma-derived.

Adolescent↗
PubMed2004

Serotonin and vasoactive intestinal peptide antagonists attenuate rotavirus diarrhoea.

BACKGROUND AND AIMS: The mechanisms underlying intestinal secretion in rotavirus diarrhoea remain to be established. We previously reported that rotavirus evokes intestinal fluid and electrolyte secretion by activation of the enteric nervous system. We now report that antagonists for the 5-hydroxytryptamine 3 receptor (5-HT(3)) and vasoactive intestinal peptide (VIP) receptor, but not antagonists for 5-hydroxytryptamine 4 receptor or the muscarinic receptor, attenuate rotavirus induced diarrhoea. METHODS: Neurotransmitter antagonists were administered to wild-type or neurokinin 1 receptor knockout mice infected with homologous (EDIM) or heterologous (RRV) rotavirus. RESULTS: While RRV infected mice had diarrhoea for 3.3 (0.2) days (95% confidence interval (CI) 3.04-3.56), the 5-HT(3) receptor antagonist (granisetron) and the VIP receptor antagonist (4Cl-D-Phe(6),Leu(17))-VIP both reduced the total number of days of RRV induced diarrhoea to 2.1 (0.3) (95% CI 1.31-2.9) (p<0.01). EDIM infected mice treated with granisetron had a significantly shorter duration of diarrhoea (5.6 (0.4) days) compared with untreated mice (8.0 (0.4) days; p<0.01). Experiments with neurokinin 1 receptor antagonists suggest that this receptor may possibly be involved in the secretory response to rotavirus. On the other hand, rotavirus diarrhoea was not attenuated in the neurokinin 1 receptor knockout mice. CONCLUSIONS: Our results suggest that the neurotransmitters serotonin and VIP are involved in rotavirus diarrhoea; observations that could imply new principles for treatment of this disease with significant global impact.

Animals↗
PubMed1990

The serum polymeric IgA antibody response to typhoid vaccination; its relationship to the intestinal IgA response.

The relationship between the IgA antibody response in serum (total and polymeric IgA) and intestinal secretions was examined in volunteers subjected to oral and parenteral typhoid vaccination. After oral vaccination (three doses of 10(11) live Ty21a vaccine given at 48-hr intervals), serum pIgA antibody to typhoid lipopolysaccharide (LPS) was detected in seven of the 14 subjects (46.4 +/- 59 U/100 microliters, mean +/- SD). However, all 14 showed a significant intestinal IgA response (993 +/- 2516 and 9349 +/- 6754 U/mg pre- and post-vaccine; t = 5.25, P = 0.0002). The level of pIgA antibody declined rapidly, whereas intestinal IgA antibody levels remained elevated. Serum pIgA antibody was also found after parenteral immunization (two doses of 5 X 10(8) heat-killed bacteria given 14 days apart to six subjects), but an intestinal IgA antibody response was detected in these individuals only after a subsequent course of the oral vaccine given 1 month after initial parenteral immunization. Changes in serum pIgA antibody followed those of total serum IgA antibody rather than those of intestinal antibody. The results indicate that a serum pIgA response can be induced by an antigenic stimulus delivered either orally or parenterally, whereas an intestinal IgA response is induced only by a local antigen stimulus. The regulation of serum pIgA and intestinal IgA appear to be independent.

Adult↗
PubMed1997

Application of intestinal xenografts to the study of enteropathogenic infectious disease.

We have developed, characterized and utilized paired segments of fetal intestine subcutaneously transplanted into heterogenic nude or SCID mice as a model system for the study of viral, bacterial and protozoal pathogens. The xenografted intestine matures in the recipient mouse and is biochemically and anatomically comparable to intestine from age-matched, whole-animal controls. The grafted tissue is free of ingesta, intestinal flora, extra-intestinal secretions and host immune functions. The transplanted intestine is long-lived and easily accessible to manipulation and harvest. Tissue from a single fetal donor can be used to create numerous xenografts allowing for tightly controlled experiments. Xenografts enable the study of species-specific intestinal pathogens in the homologous intestinal tissue thus preserving biological applicability of results. Xenografts can be used to study pathogenesis, pathophysiology and therapeutics of enteric disease in situations where such study might otherwise be prohibitively expensive or confounded by intercurrent variables inherent to whole animals. Xenografts have important advantages over in vitro models that may not approximate the in vivo biology of the intestine in the disease process.

Animals↗
PubMed1983

Influence of bile acids on cholera toxin-induced secretion in mouse jejunum.

The influence of bile acids on intestinal secretion induced by cholera toxin (CT) was studied in mice. The secretion was examined in ligated loops after the bile flow had been stopped by ligation of the common bile duct (CD). Bile depletion was found to inhibit both the secretion induced by CT, the degradation of CT, and the binding of CT to epithelial cells--all of which could be restored to normal by the application, before CT challenge, of bile acids in the loops of CD-ligated mice. Out of the nine bile acids tested, cholic acid, deoxycholic acid and chenodeoxycholic acid were the most potent, their ED50 values being 0.2, 0.2, and 0.6 mM respectively.

Animals↗
PubMed2002

Experimental models of small intestinal transplantation in rats: orthotopic versus heterotopic model.

Two kinds of surgical models of small intestinal transplantation (SITx) in rats, namely heterotopic (HIT) and orthotopic transplantion (OIT), have been reviewed. In OIT, the small intestine of the recipient is removed and the transplanted intestine replaces it in continuity. On the other hand, in the HIT model, the small intestinal grafts are rendered dysfunctional without alimentary tract continuity. Histological evidence showed that acute rejection appeared earlier in HIT as compared to OIT. Hyperplasia and hypertrophy of the muscularis externa produced in the chronic rejection process were more pronounced in HIT allografts. The HIT grafts showed severe mucosal atrophy due to the lack of intraluminal trophic factors, because oral feedings can stimulate tropic hormones for mucosal growth, and provide nutrients for enterocytes. Intestinal permeability was consistently higher after HIT than after OIT. The HIT grafts demonstrated less contractility and less response to chemical stimulation than did OIT grafts. The OIT models are advantageous in studies of intraluminal nutrients, and intestinal secretions in these models might modulate the intestinal immune status and possibly delay rejection. The superior intestinal barrier function and the delayed onset of rejection in OIT rats suggest that nutrients and other factors in the succus entericus are important for the maintenance of intestinal graft function.

Animals↗
PubMed1980

Antibody response of the lactating sow to oral immunization with Escherichia coli.

Oral immunization of the lactating sow with live Escherichia coli (O8:K88) stimulated an IgA anti-K88 antibody response in mammary secretions and significantly enhanced the capacity of whey to inhibit adhesion of the inoculum E. coli strain to isolate pig enterocytes. An increase in agglutinating anti-O8 activity was also evident in jilk and was associated with both the IgA and IgM immunoglobulin classes. These results are consistent with the concept of a gut-mammary link, although measurement of specific antibody in the intestinal secretions of these animals suggested that there may be a difference in response duration at the two secretory sites. Prolonged oral administration of heat-killed organisms also stimulated specific antibody synthesis within the mammary gland, although the response, particularly to the O antigen, was both reduced and delayed in its appearance.

Animals↗
PubMed1982

The effect of intestinal fluid transport of exposing the serosa to hydrochloric acid. A study of mechanisms.

Hydrochloric acid (0.1 M) placed on the serosal surface of a jejunal segment evoked an intestinal secretion (rats) or inhibited a net fluid absorption (cats). In rats it was demonstrated that lidocaine (placed on the serosa of periarterially denervated intestinal segments), hexamethonium (given i.v.; innervated or denervated intestines) and indomethacin (given i.v.; denervated intestines) markedly inhibited the acid induced secretion, while atropine (given i.v.) had no effect. In the cat experiments it was shown that tetrodotoxin (given close i.a. to denervated intestines) returned the rate of net fluid absorption to the control value observed before applying acid. It is concluded that exposing the intestinal serosa to an acid solution evokes a fluid secretion that is nervously mediated. Furthermore, it is proposed that prostaglandins are involved in the induction of the fluid secretion probably via a stimulation of nociceptors. It is also suggested that the results may have pathophysiological implications for some types of paralytic ileus.

Animals↗
PubMed1982

Studies of the antisecretory activity of morphine in rabbit ileum in vitro.

We studied the influence of morphine on intestinal secretion induced by three different secretogogues in an attempt to elucidate the mechanism for its antisecretory activity. In rabbit ileal mucosa in vitro morphine (10(-4) M) did not influence the electrical response to the subsequent administration of prostaglandin E2 or of acetylcholine but did inhibit the net secretion of chloride provoked by both agents and prevented the reduction of sodium adsorption induced by the prostaglandin. Morphine reduced the peak electrical response to cholera toxin and reduced toxin-induced net chloride secretion. The modes of action of morphine appeared to be by both enhancing adsorption, as it does in control, nonsecreting mucosa, and by inhibiting secretogogue activity.

Acetylcholine↗
PubMed1997

Guanosine 3',5'-cyclic monophosphate-dependent protein kinase II mediates heat-stable enterotoxin-provoked chloride secretion in rat intestine.

BACKGROUND & AIMS: Escherichia coli heat-stable enterotoxins (STa) provoke electrogenic Cl- secretion in the intestine through a guanosine 3',5'-cyclic monophosphate (cGMP)-dependent signal transduction pathway. The cGMP receptor involved in the activation of the Cl- channel is not known with certainty but may comprise either adenosine 3',5'-cyclic monophosphate (cAMP)-dependent protein kinase (cAK) or cGMP-dependent protein kinase (cGK) type II. The aim of this study was to discriminate between these possibilities using specific kinase inhibitors. METHODS: Intestinal electrogenic Cl- secretion was determined by measuring short-circuit current (Isc) in a Ussing chamber. RESULTS: The general protein kinase inhibitors staurosporine and H-8 inhibited rat cGK II activity in vitro with 50% inhibitory concentration values of 4 nmol/L and 3 mumol/L, respectively, which are lower than those reported for cAK. Both staurosporine and H-8, when added to rat proximal colon at concentrations that did not affect the Isc response to 8-bromo-cAMPS, inhibited the STa- and 8-bromo-cGMP-provoked Isc response for more than 80%. Furthermore, the relative specific cGK inhibitor Rp isomer of 8-(chlorophenylthio)-cGMP, but not the cAK inhibitor RP isomer of (Rp) 8-bromo-cAMPS, inhibited the Isc response to submaximal levels of STa in rat proximal colon. CONCLUSIONS: These data provide further evidence for an important role of cGK II in STa-mediated Cl- secretion in native rat intestinal epithelium.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1990

IgA subclass antibodies to gliadin in serum and intestinal juice of patients with coeliac disease.

Serum IgA anti-gliadin antibodies (AGA) were positive in 25 (68%) of 37 untreated adults with coeliac disease belonging mostly to IgA1 subclass (88%) and only in a few cases to IgA2 (12%). Antisecretory component IgA AGA were present in serum of seven patients (28%) by immunofluorescence and in nine (36%) by ELISA. The search for IgA AGA in jejunal juice of eight untreated children with coeliac disease was positive in seven cases (88%), with consistent finding of antisecretory component IgA AGA. These antibodies belonged with equal proportion to IgA1 and IgA2 subclasses. This study shows that in intestinal secretions of untreated coeliac disease cases the IgA immune response to gliadin is confined to polymeric anti-secretory component IgA with the same prevalence of IgA1 and IgA2 subclasses, while in serum IgA AGA are largely monomeric, more frequently of IgA1 than of IgA2 subclass, and with a lower proportion of polymeric anti-secretory component IgA (20-36%). The finding of secretory IgA AGA in serum of patients with coeliac disease could result from a spill-over from the intestinal mucosal synthesis into the circulation.

Adolescent↗
PubMed1989

Transport of serum IgA into murine respiratory secretions and its implications for immunization strategies.

Both nonlabeled and radiolabeled IgA mAb with specificity toward Sendai virus, a respiratory pathogen, were used to investigate the transport of serum polymeric and monomeric IgA into murine upper and lower respiratory secretions as well as into the gut. After purification by affinity chromatography, IgA mAb were fractionated into monomers and polymers by gel filtration and radiolabeled with 125I. Mice were injected i.v. with either 125I-monomer and 131I-albumin or 125I-polymer and 161I-albumin. At various times after injection, serum and gut, nasal and bronchoalveolar lavage samples were collected. The TCA precipitable radioactivities were determined and the selective transport indices calculated. The results indicated selective transport of polymeric IgA but not monomeric IgA from serum into upper respiratory and intestinal secretions. The degree of TCA precipitability in nasal lavage and to a lesser extent gut secretions suggested significant degradation of the antibody during or after transport. To investigate further the integrity of the IgA in mucosal secretions, ELISA viral binding activity of nonradiolabeled IgA was determined for both IgA incubated with nasal secretions in vitro and polymeric IgA recovered by nasal lavage 4 h after i.v. injection. Although reconstitution experiments indicated no significant loss of antibody binding activity after incubation of antibody with lavage fluid in vitro, only negligible ELISA binding activity was detected in nasal washes after i.v. injection of antibody. The data overall suggest that although there is a quantitatively small, but selective transport of polymeric IgA into the upper respiratory tract, this transport results in minimal functional antibody activity. Implications of these and other findings for strategies of oral immunization in prophylaxis against respiratory infections are discussed.

Administration, Oral↗
PubMed2002

The high metabolic cost of a functional gut.

BACKGROUND & AIMS: Animal studies have shown that more than half of the dietary protein intake is used by the gut and that a large proportion of this utilization is devoted to (glyco-)protein synthesis. Recycling of these secretions may play a critical role in the regulation of overall dietary amino acid bioavailability. METHODS: Four piglets (age 32 days, 8-10 kg) bearing portal, arterial, and duodenal catheters and a portal flow probe were infused with a complete diet via the duodenum for 12 hours, followed by 12 hours of fasting. The portal balance of glucose and amino acids was measured throughout the 24-hour period. The animals also received duodenal and intravenous infusions of different lysine and threonine tracers. Measurements of intestinal tracer utilization and reappearance in the portal blood were used to calculate intestinal amino acid utilization and recycling. RESULTS: From 0 to 6 hours, one third of the protein intake appeared in the portal blood. As feeding continued, the portal glucose balance (60% of intake) was constant, but the net amino acid portal balance became progressively more positive. Significant net amino acid absorption continued for at least 6 hours after the cessation of feeding. Over 24 hours, 52% of the dietary protein intake appeared in the circulation and one third of this derived from recycled intestinal secretions. CONCLUSIONS: Intestinal recycling of amino acids contributes significantly to their systemic availability and may be a critical factor in amino acid nutrition.

Absorption↗
PubMed1987

Secretory epithelial cell marker on gastrointestinal tumors and in human secretions defined by a monoclonal antibody.

A new marker for human secretory epithelial cell types (Exo-1) has been defined by a mouse monoclonal antibody (Pa-G14). The antibody was raised against a human exocrine pancreatic tumor cell line (Capan-1) and tested against 46 cultured human cell types and 228 freshly frozen human tissue sections. It reacted specifically with 28 normal and 55 secretory neoplastic epithelial tissues tested. Eleven different secretory epithelial cell types expressed this antigen, as well as human fetal tissues of the gut and bronchi. One hundred and twenty samples of normal tissues, cells, and tumors of nonexocrine origin were Exo-1 negative. In normal secretory tissues staining was most pronounced at the apical poles and as shown by immunoelectron microscopy in the case of the duodenum, at the microvilli. In cultured Exo-1 positive tumor cells the antigen was not demonstrable on the cell surface but in the cytoplasm after acetone/methanol fixation only. The antigen was identified biochemically as a polar neutral glycolipid and detected in human salivary, bronchial, pancreatic, and intestinal secretions by an enzyme-linked immunosorbent assay, but was not found in sera of healthy controls or patients with gastrointestinal and other tumors. Antigen Exo-1 represents a novel common antigen for normal and tumorous glandular epithelial cells.

Animals↗