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At least 577 records · Page 32Linked to original sources
PubMed2006

Deoxynivalenol transport across human intestinal Caco-2 cells and its effects on cellular metabolism at realistic intestinal concentrations.

Deoxynivalenol (DON) is a mycotoxin of the trichothecenes family to which human exposure levels can be high. Epidemiological studies suggest a link between DON and gastrointestinal illness. We investigated the interaction of DON with Caco-2 cells, a widely used in vitro model of the human intestinal barrier. The apical to basolateral (absorption) and basolateral to apical (excretion) transports of DON were found strictly proportional to both the initial concentration and the duration of the incubation. The absorption and excretion mean rates were similar to those of mannitol and were increased in the presence of EGTA, a calcium chelator. These data suggest that DON crosses the intestinal mucosa by a paracellular pathway through the tight junctions although some passive transcellular diffusion may not be ruled out. The DON transport was not affected by P-glycoprotein (PgP) or multidrug resistance-associated proteins (MRPs) inhibitors. A prolonged exposure to DON provokes the phosphorylation of the mitogen-activated protein kinases (MAPKs) Erk1/2, p38 and SAPK/JNK, as well as a decrease of the transepithelial resistance, suggesting that DON could trigger intestinal inflammation. These data imply that a chronic exposure to DON contaminated foods may negatively affect human health by altering the intestinal mucosa integrity and by inducing the MAPKs implicated in inflammation.

Biological Transport↗
PubMed2000

Structure-activity studies including a Psi(CH(2)-NH) scan of peptide YY (PYY) active site, PYY(22-36), for interaction with rat intestinal PYY receptors: development of analogues with potent in vivo activity in the intestine.

Peptide YY (PYY) is a gut hormone that inhibits secretion and promotes absorption and growth in the intestinal epithelium. We have performed structure-activity studies with the active site, N-alpha-Ac-PYY(22-36)-NH(2), for interaction with intestinal PYY receptors. Investigation of aromatic substitutions at position 27 resulted in analogues that exhibited potent in vitro antisecretory potencies with N-alpha-Ac-[Trp(27)]PYY(22-36)-NH(2) exhibiting even greater potency than intact PYY. In vivo studies in dogs revealed that this analogue also promoted intestinal absorption of water and electrolytes during continuous intravenous and intraluminal infusion. Investigations carried out to identify features that would enhance stability revealed that incorporation of Trp(30) increased affinity for PYY receptors. A "CH(2)-NH" scan revealed that incorporation of reduced bonds at position 28-29 or 35-36 imparted greater receptor affinity. In general, disubstituted analogues designed based on the results of single substitutions exhibited good receptor affinity with N-alpha-Ac-[Trp(27),CH(2)-NH(35-36)]PYY(22-36)-NH(2) having the greatest affinity (IC(50) = 0.28 nM). Conservative multiple substitutions with Nle-->Leu and Nva-->Val also imparted good affinity. An analogue designed to encompass most of the favored substitutions, N-alpha-Ac-[Nle(24,28),Trp(30),Nva(31), CH(2)-NH(35-36)]PYY(22-36)-NH(2), exhibited a proabsorptive effect in dogs comparable to, but longer lasting than, that of intact hormone. Selected analogues also exhibited good antisecretory potencies in rats with N-alpha-Ac-[Trp(30)]PYY(22-36)-NH(2) being even more potent than PYY. However, the potencies did not correlate well with the PYY receptor affinity or the proabsorptive potencies in dogs. These differences could be due to species effects and/or the involvement of multiple receptors and neuronal elements in controlling the in vivo activity of PYY compounds. PYY(22-36) analogues exhibited good affinity for neuronal Y2 receptors but poor affinity for Y1 receptors. Also, crucial analogues in this series hardly bound to Y4 and Y5 receptors. In summary, we have developed PYY(22-36) analogues which, via interacting with intestinal PYY receptors, promoted potent and long-lasting proabsorptive and antisecretory effects in in vivo models. These compounds or analogues based on them may have useful clinical application in treating malabsorptive disorders observed under a variety of conditions.

Animals↗
PubMed1998

Small intestinal dysmotility following abdominal irradiation in the rat small intestine.

Abdominal symptoms such as diarrhoea, abdominal cramps and vomiting are common during and after abdominal radiotherapy for gynaecological and pelvic malignancy. It has recently been recognized that small intestinal dysmotility may contribute to these symptoms but the underlying mechanisms are unclear in part because of the technical difficulties inherent in performing studies in irradiated small intestine. The aim of the current study was to evaluate small intestinal motor activity using perfused micromanometric techniques in 6-8-cm segments of ileum during arterial perfusion with isotonic oxygenated fluorocarbon solution. Intestinal segments from six rats were studied 4 days after treatment with 10 Gy abdominal irradiation. Ileal segments from nine nonirradiated animals acted as controls. For each experiment the total number of pressure waves, high-amplitude (> 20 mmHg, long-duration > 6 sec) pressure waves, and long (> 20 associated) bursts of pressure waves were determined. Irradiation had no effect on the overall number of pressure waves, but increased high-amplitude long-duration (HALD) pressure waves (248 vs 7, P < 0.01). In control animals HALD waves were localized to a single recording site but after radiotherapy 74% of HALD waves were temporally associated with similar pressure waves in other manometric channels. Forty-seven per cent of associated HALD waves migrated aborally. Retrograde migration of HALD waves was seen in five segments following irradiation. Irradiation abolished bursts of > 20 pressure waves.

Abdomen↗
PubMed1999

The characteristics of intestinal injury peripheral to strangulating obstruction lesions in the equine small intestine.

Recent studies suggest that horses requiring surgical correction of strangulating intestinal obstruction may develop post operative complications as a result of ischaemia/reperfusion injury. Therefore, the mucosal and serosal margins of resected small intestine from 9 horses with small intestinal strangulating lesions were examined for evidence of ischaemia/reperfusion injury. Severe mucosal injury and marked elevations in myeloperoxidase activity were detected at ileal resection margins (n = 4), whereas the mucosa from proximal jejunal (n = 9) and distal jejunal (n = 5) resection margins was normal. However, the serosa from jejunal resection margins had evidence of haemorrhage and oedema, and the proximal jejunal serosa had significantly increased numbers of neutrophils. Histological injury in ileal stumps is indicative of the inability fully to resect the ileum in horses with distal small intestinal strangulations. One of 4 horses subjected to ileal resection was subjected to euthanasia and found to have a necrotic ileal stump. Evidence of serosal injury and neutrophil infiltration in the proximal jejunal resection margins may predispose horses to post operative adhesions. Four of 8 horses discharged from the hospital suffered from recurrent colic in the post operative period.

Anastomosis, Surgical↗
PubMed1984

A possible role of intestinal mucin in the pathophysiology of intestinal strangulation obstruction. Consequences of tracing a clinical observation.

In intestinal strangulation obstruction, the pathophysiology is created by factors deriving from the host as well as from the intestinal flora. This article has focused upon the importance of one host-derived factor, i.e. intestinal mucin. Based upon a long series of in vitro and in vivo experiments utilizing germfree as well as conventional animals, it is concluded that intestinal mucin plays a major role in triggering a pathological plasma proteolysis, thereby interacting with microbial products (as endotoxin) in creating the whole variety of serious symptoms found in this situation.

Animals↗
PubMedDate not supplied

Neonatal intestinal perforation caused by congenital defect of the small intestinal musculature: report of one case.

Congenital defect of the small intestinal musculature is a rare cause of neonatal spontaneous intestinal obstruction or perforation. Its etiology and pathogenesis are still controversial. A male infant presented with intestinal obstruction at two days of age and rapidly progressed to perforation and septic shock. He died at seven days of age. Autopsy finding revealed a perforation hole at twenty-five cm proximal to ileocecal valve. Histology examination demonstrates multifocal deficiency of the inner circular muscle layer three cm around the perforation site. The clinical and histological characteristics are reviewed and discussed. We propose that the muscle defect of small intestine, especially ileum, is secondary to ischemic injury rather than an embryological malformation.

Diseases in Twins↗
PubMed1975

[State of the mucus membrane of the small intestine in upper intestinal fistulas].

In modeled experiments of 23 polyfistulous dogs with a reproduced high complete small-intestine fistula it was established that enteral compensation of water-electrolyte losses by means of a saline solution, isotonic and isoionic to the chyme, contributed to the maintenance of the water-salt balance for a prolonged period of time, kept up the animals' life and ensured the return to normalcy following the closure of the fistula. Preservation of the function of absorption by the small intestine was confirmed by the data of morphological investigations of 403 bioptic specimens of the mucosa from various parts of the small intestine repitedly taken in the course of the experiments. The data obtained testify to the absence of atrophy of villi and nakedness of their stroma, despite the intravital detachment of the epithelium into the lumen of the intestine, as well as to hyperproduction of the mucus, dilatation of the vessels of the circulatory and lymphatic systems, to retention of the mitotic activity.

Animals↗
PubMed2006

[Effects of enteral nutrition on intestinal intraepithelial lymphocytes of intestinal mucosal and the barrier of mucus in patients with stomal type enteric fistula].

OBJECTIVE: To investigate the effects of enteral nutrition on intestinal intraepithelial lymphocytes and the barrier of mucus in patients with stomal type enteric fistulas. METHODS: Ten patients with stomal type enteric fistulas after long-term fasting were observed. They received enteral nutrition of 146 kJ.kg(-1).d(-1) non-protein calorie and 0.25 g.kg(-1).d(-1) nitrogen per day. Intestinal mucosa were taken by endoscope through stoma of fistula before, 5 and 10 days after enteral nutrition support. Hematoxylin-eosin stain and immunohistochemical stain were performed to count the cell counts of intestinal intraepithelial lymphocytes (iIELs) and mucin-2 (MUC2) positive cells, specific stain (Alcian Blue) was performed to test the thickness of mucus. RESULTS: Five days after enteral nutrition, MUC2 positive cells and the thickness of mucus were significantly higher than that before enteral nutrition support (P<0.05). Ten days after enteral nutrition, iIEL cell and CD8 counts were also significantly higher than that before enteral nutrition support (P<0.05), MUC2 positive cells and the thickness of mucus showed a significant increase (P<0.01). CONCLUSION: Enteral nutrition is effective in protecting the gut mucosal and improving the immune function of the intestinal intraepithelial in patients with stomal type fistula.

Adolescent↗
PubMed1977

Studies on translocation of immunoglobulins across intestinal epithelium. IV. Evidence for binding of IgA and IgM to secretory component in intestinal epithelium.

We conducted studies concerning the issue of whether secretory component (SC) is a specific receptor on intestinal epithelial cells for IgA and IgM. Initially, frozen sections of human intestinal mucosa were incubated with dimeric monoclonal human IgA, conjugated to horseradish peroxidase; adjacent sections were reacted with peroxidase-conjugated antibodies to SC. The conjugated IgA and anti-SC bound to similar sites in the epithelium, that is to basolateral margins and supranuclear cytoplasm of columnar epithelial cells, principally in gland crypts. In subsequent tests of binding specificity, binding of the dimeric IgA conjugate was inhibited by pretreating the tissues with unconjugated dimeric IgA or 19S IgM, pretreating the tissues with unconjugated antibodies to SC, or preincubating the dimeric IgA conjugate with free SC. Binding was not inhibited or only partially inhibited by pretreating the tissues with monomeric IgA or IgG, pretreating the tissues with antibodies to human or heterologous immunoglobulins, or preincubating the dimeric IgA conjugate with 11S secretory colostral IgA. The findings indicate that dimeric IgA and 19S IgM are capable of binding in vitro to specific sites on intestinal epithelial cells, most likely to SC. This supports the hypothesis that transport of these immunoglobulins into intestinal fluids involves their combination with SC in the epithelium.

Binding Sites, Antibody↗
PubMed1994

[Chronic idiopathic intestinal pseudo-obstruction associated with volvulus of the transverse colon. The identical mode of clinical presentation and of the intestinal manometric pattern in monozygotic twins].

Two monozygotic female twins with chronic idiopathic intestinal pseudo-obstruction associated with transverse colon volvulus are described. Quite similar clinical events and temporal coincidences characterized the symptoms which has preceded and followed right colectomy undergone by both of them due to intestinal volvulus. The esophageal, gastroduodenal, colonic and anorectal manometric investigation revealed very similar alterations in both girls. Increased amplitude of distal contractions of the esophagus, a depressed fasting antro-duodenal motility, with absence into antrum and oro-aboral non-propagation in the duodenum of the phase III activity of the interdigestive motor complex were the main findings along with a state of pronounced colonic hypomotility and an hypoesthesia of the rectal ampulla to the volumetric stimulus. This report indicates the association between chronic intestinal pseudo-obstruction and transverse colon volvulus in monozygotic female twins, and it points out the rarity both of the specific symptomatic coincidences and the similar clinical events and of the almost absolute identity of the intestinal motor patterns.

Adult↗
PubMed1998

[Intestinal transplantation. The first Swedish transplantation of the small intestine in an adult patient with pseudoobstruction].

Recent advances, first and foremost the development of new immunosuppressive agents, have markedly improved the outcome of intestinal transplantation, which is a treatment option for patients with serious intestinal diseases who have become dependent on total parenteral nutrition. The first small bowel transplantation in Sweden was performed at Huddinge Hospital in 1997, in the adult patient with intestinal pseudo-obstruction. The article reports the course of this patient and an update of international progress in intestinal transplantation.

Abdominal Pain↗
PubMed1998

Role of vasoactive intestinal polypeptide in the adaptation of intestinal smooth muscle cells to mechanical distension.

Distension of the small intestine can play a role in the pathogenesis of various functional intestinal disorders. This study determined the role of vasoactive intestinal polypeptide (VIP) in the adaptative response of intestinal smooth muscle to acute and chronic distension of the ileum in vivo. Several in vitro experiments were performed to identify the mechanism of receptor regulation. Distension was applied by a balloon inflated with air in the ileum either during a single episode in anesthetized or repeatedly in conscious guinea pigs. Then, muscle cells were isolated by enzymatic digestion from the distended and nondistended adjacent ileal segments. In addition, in vitro experiments were performed on freshly dispersed cells for determination of mechanisms. Control cells maximally relaxed (Cmax) at 1 microM VIP (EC50 = 50 pM) and 100 microM isoproterenol (EC50 = 7 nM). Both acute and chronic distensions triggered a right-ward shift of the concentration-response curves for VIP (Cmax = 100 microM, EC50 = 10 nM). A desensitization of the relaxing effect of VIP receptors was also observed when cells were preincubated for 30 min in vitro with VIP. By contrast, the relaxing effect of isoproterenol was affected neither by in vivo distension nor by in vitro incubation with isoproterenol. Desensitization of VIP receptors was prevented by in vitro incubation of cells with VIP plus a VIP antagonist [(D-P-Cl-Phe6,Leu17)VIP] and by intraluminal perfusion of the VIP antagonist during acute distention in vivo. Moreover, desensitization of VIP receptors did not occur after 30 min preincubation with either forskolin or 8-Bromo-cyclic AMP. These results indicate that mechanical distension of the ileum induces a homologous desensitization of VIP receptors on circular smooth muscle cells, which requires the occupation of its receptors by VIP.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed2005

Differentiation of organ availability by sequential and simultaneous analyses: intestinal conjugative metabolism impacts on intestinal availability in humans.

The impact of intestinal conjugative metabolism on oral bioavailability was assessed by sequential and simultaneous analyses of the reported data in humans. The data were retrieved from reports on drugs that are metabolized by sulfate conjugation, and the organ availabilities affecting oral bioavailability were differentiated. Sequential analysis gave the following results. The intestinal availability (Fg) of salbutamol was 0.700, whereas hepatic availability (Fh) and bioavailability (F) were 0.893 and 0.493, respectively. Fg of (+)-terbutaline, (-)-terbutaline, and (+/-)-terbutaline was 0.128, 0.254, and 0.250, respectively. In contrast, Fh of (+)-terbutaline, (-)-terbutaline, and (+/-)-terbutaline was 0.979, 0.971, and 0.946, respectively. Fg and Fh of ethynylestradiol were 0.536 and 0.780, respectively. Simultaneous analysis also gave similar results, although the sequential analysis overestimated the intestinal availability. These results indicate that intestinal sulfation metabolism has more impact on intestinal availability than on hepatic availability, resulting in low bioavailability in humans.

Albuterol↗
PubMed2003

Expression of intestine-specific transcription factors, CDX1 and CDX2, in intestinal metaplasia and gastric carcinomas.

Intestinal metaplasia (IM) is part of a stepwise sequence of alterations of the gastric mucosa, leading ultimately to gastric cancer, and is strongly associated with chronic Helicobacter pylori infection. The molecular mechanisms underlying the onset of IM remain elusive. The aim of this study was to assess the putative involvement of two intestine-specific transcription factors, CDX1 and CDX2, in the pathogenesis of gastric IM and gastric carcinoma. Eighteen foci of IM and 46 cases of gastric carcinoma were evaluated by immunohistochemistry for CDX1 and CDX2 expression. CDX1 was expressed in all foci of IM and in 41% of gastric carcinomas; CDX2 was expressed in 17/18 foci of IM and in 54% of gastric carcinomas. In gastric carcinomas, a strong association was observed between the expression of CDX1 and CDX2, as well as between the intestinal mucin MUC2 and CDX1 and CDX2. No association was observed between the expression of CDX1 and CDX2 and the histological type of gastric carcinoma. In conclusion, these results show that aberrant expression of CDX1 and CDX2 is consistently observed in IM and in a subset of gastric carcinomas. The association of CDX1 and CDX2 with expression of the intestinal mucin MUC2, both in IM and in gastric carcinoma, indirectly implies that CDX1 and CDX2 may be involved in intestinal differentiation along the gastric carcinogenesis pathway.

Biomarkers, Tumor↗
PubMed1990

[Intestinal angiodysplasia as a cause of severe intestinal hemorrhage--report of 4 cases].

Angiodysplasia of the small intestine alone cannot be differentiated histologically from hereditary hemorrhagic telangiectasia (Morbus Rendu-Osler-Weber). Isolated localisation in the small intestine is rare and requires surgery in the event of massive bleeding. Four cases of bleeding from angiodysplasias of the small intestine in patients having undergone surgery at our institution over a ten-year period are presented. In three patients the particular intestine was resected. Two of these patients had an uneventful follow-up of even and ten years, one patient relapsed and was rehospitalized for surgical treatment. The fourth patient, who showed angiodysplasias scattered over the entire small intestine, had no further bleeding over a three-year period after transmural ligations of the lesions found by intraoperative endoscopical diaphany.

Adult↗
PubMed1997

Effects of alanyl-glutamine on intestinal adaptation and bacterial translocation in rats after 60% intestinal resection.

The effects of alanyl-glutamine dipeptide (Ala-Gln)-enriched parenteral nutrition on intestinal mucosa and gut barrier function were investigated. Wistar rats were studied. After moderate surgical stress was induced by 60% resection of the small intestine, the rats were randomized to three groups: the chow group was given standard rat chow; the PN group received standard parenteral nutrition (PN); and the Ala-Gln group received glutamine dipeptide-enriched parenteral nutrition (3% Ala-Gln). Rats were maintained on their respective diets for 8 days. The chow and Ala-Gln groups maintained serum glutamine concentrations, intestinal mucosal thickness and villus height. Bacterial translocation rates in the chow and Ala-Gln groups were 20%, which was significantly less than that in the PN group (70%, P < 0.05). The results indicated that Ala-Gln-enriched parenteral nutrition maintains intestinal adaptation and gut barrier function after massive intestinal resection and parenteral nutrition.

Journal Article↗
PubMed1980

[Investigations of the metabolism of colostomised laying hens with 15N-labelled wheat. 5. Incorporation and distribution of 15N in the contents of the intestinal tract, the tissue of stomachs and the segments of the intestines].

In an experiement with 3 colostomised laying hybrids each animal received 80 g pelleted mixed feed and 40 g 15N-labelled wheat with 20.13 atom-% 15N-excess (15N') over a period of four days. On the following four days the hens received rations composed in the same way with uulabelled wheat, however. Of the individual tissues and organs extracted from the slaughtered hens 15N' was determined in the total N and the amino acids lysine, histidine and arginine in the individual segments both of the gasto-intestinal tract and in its contents. On a average, the amount of 15N' in the stomachs, the small intestines and the colon was 43.7%, 27.2% and 29.1%. The tissue of the small intestines contained, on an average, the highest 15N' in lysine of all the basic amino acids. It amounts to 0.82 atom-% 15N' for lysine, O.55% for histidine and 0.63 atom-% 15N' for arginine. On an average, the percentage of the 15N' of the basic amino acids from the corresponding total 15N'-amount of the charges is in the contents of the gasto-intestinal tract 20.5%, in the stomach tissue 28.0% and in the tissue of the small intestines 24.4%, of the caecum 21.5% and of the rectum 25.7%.

Amino Acids↗
PubMed2003

Stem cells and gastric cancer: role of gastric and intestinal mixed intestinal metaplasia.

All of the different types of stomach epithelial cells are known to be derived from a single progenitor cell in each gland. Similarly, cancers develop from single cells, based on data from clonality analysis in C3H/HeN<-->BALB/c chimeric mice. Using gastric and intestinal epithelial cell markers, intestinal metaplasia (IM) can be divided into two major types: a gastric and intestinal (GI) mixed type, and a solely intestinal (I) type. Ectopic expression of Cdx genes and down-regulation of Sox2 in isolated single GI mixed IM glands suggests abnormal differentiation of stem cells that can produce both gastric (G) and I type cells. Similarly, phenotypic expression of gastric cancer cells of each histological type can be clearly classified into G and I type epithelial cells. The heterogeneity of phenotypic expression of gastric cancer cells in individual cancers is assumed to reflect this intrinsic potential for differentiation in two directions. Gastric cancers at early stages, independent of the histological type, mainly consist of G type cells, and phenotypic shift from G to I type expression is clearly observed with progression. The data thus suggest IM may not be a preneoplastic change in gastric carcinoma, but rather that cells of the I type may appear independently in the gastric mucosa in IM and in gastric cancers. Intestinalization of gastric mucosa and cancer cells may represent a kind of homeotic transformation. Whether disturbance of the regulation of Sox2 and Cdx genes may be of importance to the biological behavior of gastric cancers should therefore be clarified in future studies.

Animals↗