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At least 721 records · Page 40Linked to original sources
PubMed1998

Intestinal fibroblasts regulate intestinal epithelial cell proliferation via hepatocyte growth factor.

Although the presence of subepithelial intestinal fibroblasts has been well recognized, the effects of fibroblasts on intestinal epithelial cell (IEC) growth are incompletely understood. In vitro studies were undertaken to evaluate the effects of fibroblasts on the proliferation of model IEC lines. IECs (Caco-2, T84, and IEC-6) were grown alone or in the presence of human intestinal (CCD-18), lung (CCD-37), or skin explant-derived fibroblasts. Cocultures were carried out directly on irradiated fibroblasts or by Transwell coculture technique with fibroblasts and epithelial cells separated by a porous filter. Cell proliferation was assessed by [3H]thymidine incorporation and cell counts. Hepatocyte growth factor (HGF) and c-met transcript expression in IECs and fibroblasts was examined by RT-PCR and Northern blotting; protein expression was evaluated by immunoblotting. Intestinal as well as lung and skin fibroblasts substantially stimulated proliferation of Caco-2, T84, and IEC-6 cells in both direct and Transwell cocultures. In addition, fibroblast-conditioned medium stimulated IEC proliferation, suggesting a paracrine mechanism. Anti-human HGF-neutralizing antibodies blocked the growth-promoting effects in both fibroblasts and fibroblast-conditioned medium. Recombinant human HGF dose dependently promoted IEC proliferation. HGF mRNA and protein expression was restricted to fibroblasts. High levels of c-met expression were found in Caco-2 and T84 cells; in contrast, expression in fibroblasts was weak. In summary, fibroblasts stimulate IEC proliferation through a paracrine mechanism mediated predominantly by HGF.

Cell Division↗
PubMed2003

Intestinal heat shock protein 110 regulates expression of CD1d on intestinal epithelial cells.

CD1d is expressed on the surface of professional and nonprofessional APCs, including intestinal epithelial cells (IECs), for a role in the presentation of glycolipid-based antigens to subsets of T cells. The mechanisms that regulate CD1d expression in any cell type are unknown. To investigate the possibility that expression of CD1d is influenced by exogenous factors present within the intestinal lumen, CD1d expression was analyzed in several IEC lines after culturing in the presence of lumenal contents (LC) of the normal human intestine. Exposure of the colon-derived cell lines T84, HT-29, and Caco-2 to soluble LC resulted in a marked induction of CD1d expression as determined by RT-PCR, confocal microscopy, cell surface ELISA, and Western blot analysis. Similarly, exposure of human IECs to LC isolated from mice bred in both specific pathogen-free and germfree conditions also resulted in the induction of CD1d expression, with the maximum CD1d-inducing activity observed in the small intestine. Biochemical and biophysical characterization of the human CD1d-inducing activity identified heat shock protein 110 (Hsp110) as a major functional component of the LC that contributes to CD1d surface regulation, and immunolocalization studies revealed Hsp110 expression in subsets of human IECs in vivo. These data support the presence of a novel autocrine pathway of CD1d regulation by Hsp110.

Amino Acid Sequence↗
PubMed2000

Relationship of intestinal calcium absorption to 1,25-dihydroxyvitamin D [1,25(OH)2D] levels in young versus elderly women: evidence for age-related intestinal resistance to 1,25(OH)2D action.

Intestinal calcium absorption decreases with aging, but it is unclear whether this is attributable to an age-related intestinal resistance to 1,25-dihydroxyvitamin D [1,25(OH)2D] action. Thus, we assessed the in vivo dose response of active intestinal calcium absorption to a broad range of circulating 1,25(OH)2D levels in elderly [age (mean +/- SD), 72.5+/-3.0 yr] vs. young women (age, 28.7+/-5.3 yr; n = 20 per group), who were stratified into 5 subgroups: group 1 was given a high calcium intake of 75 mmol/day, suppressing 1,25(OH)2D levels; group 2 was given a normal calcium diet of 15-30 mmol/day, representing basal 1,25(OH)2D levels; group 3 was given a low-calcium diet of 5 mmol/day to stimulate endogenous 1,25(OH)2D production; group 4 was given the low-calcium diet plus 1 microg/day 1,25(OH)2D; and group 5 was given a low-calcium diet plus 2 microg/day 1,25(OH)2D. After 7 days of diet and/or 1,25(OH)2D treatment, fasting fractional calcium absorption (FCA) was assessed by a double-tracer method using stable calcium isotopes. Serum 1,25(OH)2D and vitamin D-binding protein levels were measured concurrently, and the free 1,25(OH)2D index [molar ratio of 1,25(OH)2D to DBP] was calculated. FCA was significantly correlated with the free 1,25(OH)2D index in the young (R = 0.63, P = 0.003) but not in the elderly women (R = 0.27, P = 0.25). Moreover, the slope of the relationship between FCA and free 1,25(OH)2D index (representing intestinal sensitivity to 1,25(OH)2D) was significantly greater in the young (compared with the elderly) women [mean +/- SEM, 0.15+/-0.04 (young) vs. 0.03+/-0.02, elderly, P = 0.03]. Thus, using an experimental design that allowed us to assess FCA over a wide range of 1,25(OH)2D levels, we demonstrate that elderly women have a resistance to 1,25(OH)2D action that may contribute to their negative calcium balance, secondary hyperparathyroidism, and bone loss.

Adult↗
PubMed1994

A potent stimulator of small intestinal cell proliferation extracted by simple diffusion from intact irradiated intestine: in vitro studies.

The epithelium lining the small intestine is one of the most rapidly proliferating body tissues yet it rarely develops cancers. The proliferation, migration and differentiation of the stem cell progeny appears to be under very strict control. After 8 Gy gamma irradiation the murine epithelium contains surviving stem cells from which the epithelium rapidly and effectively regenerates, presumably in response to stimulatory signals, and then returns to steady state conditions after overshoots in proliferation. Here we describe the isolation and preliminary characterisation in vitro of a potent stimulatory extract obtained by diffusion from intact murine small intestine, post-irradiation. In addition to in vivo responses the extract stimulates intestinal epithelial lines very effectively, most notably the rat IEC 18 line where it can replace the serum requirement. The extent of the induced increase in proliferation could not be reproduced by any other single growth factor tested. Preliminary evidence suggests the extract contains either a potent stimulatory cocktail of factors or a novel intestinal growth factor(s).

Animals↗
PubMed1995

Intestinal alkaline phosphatase can transphosphorylate thiamin to thiamin monophosphate during intestinal transport in the rat.

Intestinal alkaline phosphatase (IAP) purified from calf intestine and IAP present in the brush border membrane of rat small intestine effectively transphosphorylated thiamin (T) to thiamin monophosphate (TMP) using Na2-beta-glycerophosphate or Na2-creatine phosphate as phosphate donors at pH 8.5. TMP production in the brush border membrane was very small and corresponded to 0.001-0.01 percent of the total inorganic phosphate simultaneously released by the enzyme activity. This reaction, however, could account for TMP formation independently from that much more important due to the hydrolysis of thiamin pyrophosphate during T intestinal absorption.

Alkaline Phosphatase↗
PubMed2000

Dnmt1N/+ reduces the net growth rate and multiplicity of intestinal adenomas in C57BL/6-multiple intestinal neoplasia (Min)/+ mice independently of p53 but demonstrates strong synergy with the modifier of Min 1(AKR) resistance allele.

Altered patterns of the 5-cytosine methylation of genomic DNA are associated with the development of a wide range of human cancers. We have studied the mechanisms and genetic pathways by which a targeted heterozygous deficiency in the murine 5-cytosine DNA methyltransferase gene (Dnmt1(N/+)) diminishes intestinal tumorigenesis in C57BL/6-multiple intestinal neoplasia (Min)/+ mice. We found that Dnmt1(N/+) retards the net growth rate of intestinal adenomas and reduces tumor multiplicity by approximately 50%. This tumor resistance affects the entire intestinal tract and is independent of the status of modifier of Min 1 and p53, two loci that have been found to confer strong resistance to Min-induced neoplasia Interestingly, Dnmt/(N/+) and modifier of Min 1 resistance interact synergistically, together virtually eliminating tumor incidence. This finding may provide an insight into potential combinatorial therapeutic approaches for treating human colon cancer.

Adenoma↗
PubMed2001

Intestinal inflammation enhances the inhibitory effects of opioids on intestinal permeability in mice.

The inhibitory effects of central and peripherally acting opioid agonists on intestinal permeability (PER) were evaluated during acute and chronic intestinal inflammation in mice. Inflammation was induced by the intragastric (p.o.) administration of one (acute) or two (chronic) doses of croton oil (CO), whereas controls received saline (SS). Intestinal PER was assessed by the blood-to-lumen transfer of 51Cr-ethylenediaminetetraacetate (51Cr-EDTA). CO significantly increased PER during acute (2.5 times) and chronic (3.2 times) inflammation. The potency of s.c. morphine-inhibiting PER was enhanced 3.8 and 8.7 times in acute and chronic CO, whereas that of s.c. fentanyl was increased 2.0 and 4.3 times, respectively, compared with SS. Similarly, s.c. [D-Pen(2,5)]-enkephalin was 4.7 and 11.1 times more potent during acute and chronic CO, and the E(max) values of the dose-response curves increased 35% during inflammation. The potency of s.c. U50,488H was 5.6 (acute) and 6.7 times (chronic) greater compared with SS. All effects were reversed by specific antagonists. The i.p. administration of beta-funaltrexamine differentially blocked morphine effects during acute and chronic CO, suggesting that the effects are mediated by different populations of functional mu-opioid receptors (OR). The increase in potencies of s.c. PL017 and ICI-204,448 during CO were comparable to those observed with fentanyl and U50,488H and their effects were antagonized by s.c. naloxone methiodide. Moreover, the potency of the agonists during inflammation was unaltered when administered i.c.v. The results show that intestinal inflammation enhances the effects of delta- > mu- > kappa-opioid agonists on PER by activation of peripheral OR.

Analgesics, Opioid↗
PubMed2000

Inhibitory effects of intestinal mucus on bacterial adherence to cultured intestinal epithelial cells after surface burns.

OBJECTIVE: To investigate the relationship between intestinal mucus IgA content and mucus barrier function after surface burns. METHODS: Detection of IgA content in mucus was performed by enzyme linked immunosorbent assay (ELISA) at different time points after burns. Bacterial adherence to cultured epithelial cells (IEC-6) in vitro using E. coli was assessed for each group. RESULTS: The intestinal mucus barrier function declined, parallel to a decrease in IgA content after surface burn in mice. In the normal control group, mucus IgA content was 2.32 D lambda, and 2.51, 1.76, 1.49, 1.06 D lambda at 0.5 h, 1 h, 6 h and 24 h after burn, respectively. Bacterial adherence rate was 0.53 in control group, and 0.46, 0.69, 0.58, 0.81 at 0.5 h, 1 h, 6 h, 24 h after burn, respectively. CONCLUSION: The decrease of intestinal mucus IgA contents is one of the reasons why intestinal mucus barrier function declines after burns.

Animals↗
PubMedDate not supplied

Effect of prokinetic agents, cisapride and metoclopramide, on the bioavailability in humans and intestinal permeability in rats of ranitidine, and intestinal charcoal transit in rats.

To investigate the effect of two prokinetic drugs, cisapride and metoclopramide, on the bioavailability of drugs, a marker drug, ranitidine, was administered to healthy volunteers following pre-treatments with or without the prokinetic agents. Cisapride or metoclopramide HCl (a respective dose of 10 mg) was administered orally 30 min prior to an oral administration of ranitidine (300 mg). Serum samples were collected for a 12 h period after the administration of ranitidine and the concentration of ranitidine was determined by an HPLC method. The bioavailability parameters of the groups with the prokinetic agent pretreatment were compared with those of the control group. In addition, the effects of these prokinetic drugs on the in vitro apparent permeability of ranitidine across the rat jejunum in the Ussing chamber, and on the in vivo intestinal transit of charcoal meals in rats were also examined. The Tmax of ranitidine in human subjects was shortened significantly by the either of the pretreatments (i.e., with cisapride and metoclopramide). The AUC(inf) of ranitidine in human subjects was also decreased significantly in the case of cisapride pretreatment. However, no changes were observed for the values of Cmax and T(1/2) by the pretreatments. Rat studies revealed that cisapride and metoclopramide had no influence on the in vitro permeability of ranitidine or the in vivo intestinal transit of charcoal meals. Therefore, these data indicated that the changes in the bioavailability parameters (i.e., Tmax and AUC(inf)) in humans are not related with the intestinal permeability or intestinal transit of ranitidine. The shortened Tmax of ranitidine appears to be due to accelerated gastric emptying of the drug. However, underlying mechanisms for the decreased AUC(inf) of ranitidine in the case of cisapride pretreatment are currently unclear.

Adult↗
PubMed1992

Small intestinal bacterial overgrowth and enhanced intestinal permeability in healthy beagles.

The small intestine of healthy adult Beagles was examined to determine whether subclinical abnormalities might exist that would be relevant to the use of Beagles in pharmacologic studies. Duodenal juice was obtained for qualitative and quantitative bacteriologic examinations; jejunal mucosa was taken for morphologic and biochemical investigation, and intestinal permeability was assessed by quantification of 24-hour urinary excretion of 51Cr-labeled EDTA after its oral administration. Comparisons were made with findings in healthy adult dogs of other breeds that served as controls. Small intestinal bacterial overgrowth was found in 14 of the 21 Beagles examined, and represented a mixed flora that included obligate anaerobic bacteria in 8 dogs and exclusively aerobic bacteria in 6 dogs. Intestinal permeability (percentage urinary recovery of 51Cr-labeled EDTA; mean +/- SEM) was considerably higher (P < 0.01) in Beagles with anaerobic overgrowth (37.6 +/- 3.2%) or aerobic overgrowth (30.5 +/- 4.8%), compared with Beagles with no overgrowth (17.3 +/- 1.6%) and with controls (11.1 +/- 1.0%). In Beagles, significant (r = 0.54, P = 0.03) correlation was observed between 24-hour urinary recovery of 51Cr-labeled EDTA and bacterial numbers in duodenal juice. Morphologic changes in jejunal mucosa were minimal, and specific activities of brush border enzymes were not significantly decreased, apart from aminopeptidase N, but activities of lysosomal and endoplasmic reticular marker enzymes were higher in the 3 groups of Beagles with anaerobic, aerobic, or no overgrowth, compared with controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1978

[Applications of electromyography in the study of changes in intestinal motility following surgery on the small intestine].

Changes in the intestinal motility were studied in dogs after different surgical operations performed on the small bowel. Electrodes were implanted on the intestine and the electrical activity of the bowel was recorded after transection of the bowel and after jejunoileal shunt. The results showed that the transection of the bowel provoked a slowing of the propagation of the intestinal contractions. This phenomenon was particularly important at the level of the ileum. The jejunoileal shunt was followed by a strong increase of the level of the motor activity, probably related with an increase of the intraluminal content at the level of the ileum. These results gave an explanation for the slowing of the intestinal transit which is observed after some operations which involve a transection of the small bowel.

Animals↗
PubMed1991

Intestinal absorption of aluminium: studies in the isolated perfused rat intestinal preparation.

Aluminium (Al) absorption was studied using an isolated in vitro vascularly perfused rat intestinal preparation. Al was introduced into the lumen as AlCl3, Al(NO3)3 or Al lactate to give final concentrations equivalent to 0.625, 1.25, 2.50, 5.00, or 10.00 g/L of Al. The intestinal tissue remained viable up to 5.0 g/L of Al. The amount of Al associated with intestinal tissue after 90 min increased with the concentration up to 5 g/L of Al for chloride and nitrate and 10 g/L of Al for lactate. The time course of Al disappearance from the lumen followed a single exponential decay when the intestinal lumen was perfused with 0.625 g/L of Al as the chloride salt. The total amount of Al appearing in the vascular perfusate after 90 min was always small. Absorption quotes ranged between 0.005-3.2% depending on the salt and concentration used. Addition of transferrin to the VM caused a 2-fold increase in the amount of Al appearing in the vascular effluent in comparison with controls when 1.25 g/L of Al as AlCl3 was introduced into the lumen. Al tissue content was not affected.

Aluminum↗
PubMed1989

Intestinal immunity to Trichinella spiralis is a property of OX8- OX22- T-helper cells that are generated in the intestine.

The phenotype of T-helper cells conferring protection against Trichinella spiralis (Ts) was studied using adoptive transfer procedures and T-helper cell subsets isolated by monoclonal antibodies. With these techniques OX8- OX22+ and OX8- OX22- T-helper cell populations were isolated from thoracic duct lymph (TDL) of infected rats three-five-fold more concentrated than in unfractionated lymph. The OX8- OX22- cell subset alone transferred enhanced rejection of adult worms from the intestine. The origin of protective OX8- OX22- cells was examined in mesenteric lymphadenectomized (MX) rats. After MX, protective cells were found in the cell population draining directly from the intestine on Days 2-3 after infection. Protective cells first appeared in the mesenteric lymph node (MLN) and efferent lymph at Day 3. MX rats rejected T. spiralis at the same time as intact controls and showed enhanced rejection when immune TDL were transfused. No evidence was found for a direct role of the MLN in the generation or expression of parasite rejection. Depletion of migrating OX8- OX22- blast cells by 48-hr drainage of TDL did not influence the expression of an anamnestic response to challenge infection. This suggests that an intestinally resident cell population has a substantial role in mediating primary worm rejection and anamnestic immunity. Day 2 OX8- OX22- cells from MX rats proliferated in response to the presentation of adult and muscle larvae antigens in vitro. We conclude that protection resides in the OX8- OX22- T-helper cell subset that is produced and functions in the intestine.

Animals↗
PubMed1989

[Experimental study of injury on the small intestine in acute portal vein occlusion and the following restoration of portal vein flow in rats--free radicals in the small intestine and lipid peroxidation].

Free radicals in the small intestine were quantified by using an electron spin resonance spectrometer, and the amounts of TBA (thiobarbituric acid) reactants in arterial plasma, portal venous plasma and intestinal tissue were determined at the several stages. The effects of allopurinol, alpha-tocopherol, the simultaneous occlusion of superior mesenteric artery or the porto-jugular venous bypass, with the temporary occlusion of the portal vein, were also investigated. 1) Free radical concentration (mostly, semiquinones of CoQ and/or flavin in mitochondria) decreased with portal vein occlusion but showed a temporary increase at 10 sec after reperfusion. Allopurinol suppressed such temporary increase. 2) TBA reactants increased with the temporary occlusion of the portal vein. TBA reactants decreased during the portal vein occlusion with alpha-tocopherol and during reperfusion with allopurinol. Lipid peroxidation in the small intestine was also diminished by using the methods of simultaneous occlusion of the superior mesenteric artery or the porto-jugular venous bypass. In conclusion, there may be three sources for the generation of superoxide: the xanthine oxidase system, semiquinone radicals and paramagnetic metal irons. They may induce lipid a peroxidation, which accelerates the injury on the small intestine, in acute portal vein occlusion and the following restoration of portal vein flow in rats.

Allopurinol↗
PubMed1989

Purification of rat intestinal cinnabarinate synthase and its possible role in hyperplasia of the small intestine in diabetic rats.

Streptozotocin diabetic rats fed ad libitum exhibited hyperplasia of the small intestine. As compared to the control animals, the intestine of experimental animals grew in weight, length and total RNA and DNA contents. Intestinal cinnabarinate synthase activity in diabetic rats was however significantly lower. Developmental studies in albino rats indicated that, attainment of the terminal and highest activity of the enzyme tends to correspond with cessation of further increase in RNA and DNA contents of the intestine, thereby suggesting a possible relationship between cinnabarinate synthase and the hyperplastic changes observed. It was also observed that some properties of this enzyme, such as Km and Vmax are modified in diabetic condition. The enzyme was purified to apparent homogeneity and some of its kinetic and other properties were studied.

Animals↗
PubMed1989

[Variation of C3 in ascitic fluid from cirrhotic patients subjected to intestinal sterilization or selective intestinal decontamination].

Patients with liver cirrhosis with ascites and low levels of C3 and Total Proteins in ascitic fluid show a greater predisposition to the development of spontaneous bacterial peritonitis. The variation of C3 and Total Proteins levels in ascitic fluid in two groups of patients with liver cirrhosis was studied. Group I (n = 14) underwent intestinal sterilization (n = 7) or selective intestinal decontamination (= 7). Group II was a control. A statistically significant increase in C3 (p less than 0.01) and Total Proteins (p less than 0.015) levels in ascitic fluid in Group I patients was found. There were no changes in the control group. The incidence of side effects was higher in those patients who underwent intestinal sterilization. Our results suggest that selective intestinal decontamination may be useful as a prophylactic measure against spontaneous bacterial peritonitis in those patients with liver cirrhosis at high risk of infection by increasing the bactericidal capacity of ascitic fluid.

Adult↗
PubMed1989

Intestinal adaptation during lactation in the mouse. I. Enhanced intestinal uptake of dietary protein antigen.

Small quantities of dietary protein antigens cross the intestinal epithelium of the lactating mouse, enter the circulation, are transferred across the mammary gland into the milk and reach the suckling neonate. In this study, we sought to determine whether intestinal uptake of ovalbumin (OVA) was enhanced in lactating compared to control mice. OVA was administered by gavage under ether anaesthesia. Blood was obtained at 15, 30, 60 and 120 min and immunoreactive OVA (iOVA) measured by enzyme immunoassay. At 30 and 60 min, a three- to four-fold higher concentration of iOVA was detected in lactating compared to control mice. Because this increase in concentration of iOVA might be explained by changes in plasma volume, rate of clearance of OVA from the circulation or altered uptake from the intestine, plasma volume was measured by isotope dilution after i.v. injection of 125I-bovine serum albumin (BSA) and clearance was assessed by measuring elimination of OVA from the circulation after i.v. injection of OVA. In comparison to controls, plasma volume of Day 7-10 lactating mice was increased two-fold and no difference in clearance rate was noted. Because the increase in concentration of iOVA in lactating mice is several-fold greater than in controls, we suggest that increased intestinal uptake of the protein occurs during lactation.

Animals↗
PubMed1977

[Gastro-intestinal electromyography: interest in the study of mechansims of regulation of intestinal motility (author's transl)].

Investigations we carried out in man and animals in order to study the relationships between the electrical and the mechanical activities of the intestine, and to precise the role of BER in the regulation of intestinal motility. In the dog, an intestinal movements transducer allowed to establish that spiking activities were concomitant with circular contractions, and that these two phenomena were rhythmed by the slow waves. Under basal conditions, the longitudinal movements occurred independently; under stimulation longitudinal movements occurred independently; under stimulation longitudinal relaxations were observed to correspond to circular contractions. In man, the post-laparotomy paralytic ileus provoked abnormalities in the BER which seemed to be related to a disturbance of the coordination of the motility, resulting in the absence of intraluminal propulsion. Administration of coherin, a postpituitary extract, was followed by a regularization of the BER and by a decrease of paralytic ileus duration. This confirms the important role of the BER in the myogenic regulation of the intestinal motility.

Animals↗