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The motor response to intestinal resection: motor activity in the canine small intestine following distal resection.

BACKGROUND: The mucosal response to intestinal resection has been extensively studied; little is known of the motor response. Our aim was to evaluate motility in the intestinal remnant following distal resection. METHODS: Motor activity, duodenocecal transit, nutrition, and absorption were studied over a 3-month period in control animals (n = 9) and in groups of dogs who had undergone 25% (n = 6), 50% (n = 5), and 75% (n = 5) distal resection. RESULTS: Diarrhea and steatorrhea developed in each resection group, and the 75% group alone developed true short bowel syndrome. Resection did not affect migrating motor complex frequency or periodicity; phase 1 duration was shorter in the 75% group (control vs. 75%: 22 +/- 4 vs. 6 +/- 2 minutes, P < 0.03). The most striking motor effect was the development of prominent cluster activity in the distal part of the remnant in 25% and 50% resection animals and throughout the remaining intestine in the 75% group. Duodenocecal transit slowed during the study period from 13 +/- 1 to 20 +/- 2 minutes in the 50% and from 10 +/- 2 to 14 +/- 2 minutes in the 75% group (P < 0.05). CONCLUSIONS: The initial motor response to major resections of the distal small intestine is dominated by the development of abnormal patterns. This motor disruption may contribute to the symptomatology and clinical features of the short bowel syndrome.

Animals↗

The effect of intestinal hypoperfusion on intestinal absorption and permeability during cardiopulmonary bypass.

BACKGROUND/AIMS: Mean arterial pressure is reduced during hypothermic cardiopulmonary bypass. The aim of this study was to assess whether this was associated with intestinal hypoperfusion and whether it affected intestinal absorption and permeability. METHODS: Twenty-six patients undergoing coronary artery bypass grafting underwent an intestinal absorption-permeability test involving ingestion of 3-O-methyl-D-glucose, D-xylose, L-rhamnose, and lactulose. Ingestion took place 2 days before, within 3 hours, and 5 days after hypothermic cardiopulmonary bypass. Hemodynamic parameters and gastric mucosal laser Doppler blood flow were measured perioperatively in eight patients. RESULTS: Hypothermic (28 degrees C), nonpulsatile cardiopulmonary bypass resulted in a 25% reduction in mean blood pressure, 10% reduction in cardiac index, and a 46% reduction in gastric mucosal laser Doppler blood flow. There was 85.4%, 85.5%, and 73.6% reduction (P < 0.01) in active (3-O-methyl-D-glucose) and passive (D-xylose) carrier-mediated transport and passive, nonmediated transcellular (L-rhamnose) transport in the immediate postoperative period, respectively. The differential urine excretion of lactulose/L-rhamnose increased sixfold. All parameters returned to control levels by the fifth postoperative day. CONCLUSIONS: Cardiopulmonary bypass, while maintaining generally acceptable levels of hemodynamic performance, is associated with significant intestinal hypoperfusion and malabsorption of monosaccharides, which may have implications for enteral drug treatment in the immediate postoperative period.

Adult↗

Opioid action of the intestine: the importance of the intestinal mucosa.

Drug effects on the intestine are traditionally explained in terms of action on the muscle layers and the nerves that control them. This is particularly true in the case of the opioids but research starting two decades ago has identified the intestinal mucosa as the site of action of the antidiarrhoeal opioids. Continued research using the intestinal mucosa offers a fresh approach to solving some old problems. For example it could lead to more confident predictions to be made about the wanted and unwanted effects of opioid drugs on the intestine and may help to find better drug treatments for alleviating withdrawal diarrhoea in addicts. Eventually it may help to explain how the general process of opioid dependence occurs at a cellular level.

Antidiarrheals↗

Intestinal uptake and retention of copper in the suckling rat, Rattus rattus--IV. Mechanisms of intestinal copper accumulation.

Copper-67, administered either parenterally or via the maternal milk, accumulates principally in the intestine and liver of the 6-day-old pup. Most of the 67Cu in the soluble fraction of the intestine is associated with the heterogeneous Cu-complex, which is located predominantly in the ileum. The rates of uptake and loss of 67Cu in the liver and intestine indicate that enterohepatic circulation of Cu in the neonate is appreciable. Whilst the concentration of Cu in the bile of the 13-day-old pup is high (16-fold greater than that in the adult male rat), translocation of Cu from both the liver and duodenum to the ileum probably occurs via the blood, rather than by the reabsorption of biliary Cu. Although the Cu-complex normally seems to be retained within the distal intestine until the enterocytes are desquamated, Cu in this form is utilized when the Cu-intake of the neonate is restricted.

Animals↗

Lipid-soluble and water-soluble antioxidant activities of the avian intestinal mucosa at different sites along the intestinal tract.

The antioxidant capacity of the avian intestinal mucosa is potentially important in protecting the gut wall from the harmful actions of reactive oxygen species originating from the diet, mucosal metabolism and the inflammatory response to enteric microbes. To assess this capacity, we determined the total lipid-soluble and water-soluble antioxidant activities of mucosal extracts, using tissue from different parts of the intestinal tract of the chicken. The lipid-soluble antioxidants, vitamin E and carotenoids, were also measured in the same samples. Total lipid-soluble antioxidant activity was highest in mucosa from the duodenum followed by the jejunum, with much lower activities in the ileum, ceca and colon. Total water-soluble antioxidant activity of the mucosa was at least an order of magnitude greater than the lipid-soluble activity under the assay conditions and did not differ significantly among the different parts of the intestinal tract. High concentrations of vitamin E were present in the mucosa of the duodenum and jejunum, with a trend to lower levels in the ileum and ceca, and significantly less in the colon. Similarly, the mucosa of the duodenum and jejunum contained the highest concentrations of carotenoids, with much lower levels in the ileum and colon. The different isoforms of vitamin E were absorbed from the digesta by the mucosa without any major selectivity. However, the liver was greatly enriched with alpha-tocopherol over the other isoforms, indicating a high degree of discrimination by this tissue. The results indicate major differences in the relative contributions of lipid- and water-soluble antioxidants in the mucosa along the different parts of the intestinal tract, most likely reflecting the sites of vitamin E and carotenoid absorption.

Animals↗

Effects of Trichinella spiralis infection on intestinal pathology in mice lacking interleukin-4 (IL-4) or intestinal trefoil factor (ITF/TFF3).

The nematode Trichinella spiralis induces pathological changes in the small intestine of the host, which are known to be controlled by immune and inflammatory mediators. The detail of this control has still to be completely understood. Mice deficient in interleukin 4 (IL-4) or in intestinal trefoil factor/trefoil family factor 3 (ITF/TFF3) were infected with T. spiralis and the resultant changes in the intestinal mucosa followed by quantifying numbers of mucosal mast cells, goblet cells, Paneth cells and by monitoring structural changes in villus length and crypt depth. Mice lacking IL-4 were unable to mount a normal protective response to infection, such that worm survival was increased. These mice failed to mount a mucosal mast cell response, but did make goblet cell and Paneth cell responses comparable to normal controls. Mice lacking ITF/TFF3 similarly made normal levels of goblet cell and Paneth cell responses. They also underwent profound changes in mucosal architecture, with marked villus atrophy and crypt hyperplasia. These results are discussed in relation to known patterns of T cell and cytokine control of protective immunity to T. spiralis. They suggest that increased numbers of goblet cell and Paneth cell are not, by themselves, required for protective immunity. ITF/TFF3 appears not to influence cellular responses and does not alter parasite-induced pathological changes in the small intestine.

Animals↗

PACAP-(6-38) inhibits the effects of vasoactive intestinal polypeptide, but not PACAP, on the small intestinal circular muscle.

Vasoactive intestinal polypeptide (VIP) and pituitary adenylate cyclase-activating peptide-(1-38) (PACAP) have been found to stimulate distension-induced peristaltic motility in the guinea-pig isolated small intestine. In this study, we tested whether the putative VIP/PACAP receptor antagonist PACAP-(6-38) counteracts the properistaltic effect of VIP and PACAP in isolated segments of the guinea-pig small intestine. VIP (100 nM) and PACAP (30 nM) had a stimulatory effect, i.e., lowered the peristaltic pressure threshold at which peristaltic waves were triggered and enhanced the frequency of peristaltic waves. PACAP-(6-38) (3 microM) was per se without effect on peristalsis but prevented or reversed the peristaltic motor stimulation caused by VIP, when it was given before or after the agonist, respectively. PACAP-(6-38), however, failed to antagonize the properistaltic effect of PACAP. In ileal circular strips treated with tetrodotoxin (1 microM) and indomethacin (3 microM), spontaneous myogenic activity was inhibited by VIP (5-30 nM). This effect was significantly reduced by a pretreatment with PACAP-(6-38) (3 microM). A similar inhibition by PACAP-(1-38) (10-500 nM) was not influenced by the antagonist. It is concluded that PACAP-(6-38) is a VIP receptor antagonist, both in the peristaltic motor pathways and at the level of the circular muscle of the guinea-pig small intestine. The lack of a motor effect of PACAP-(6-38) on its own indicates that VIP acting on PACAP-(6-38)-sensitive receptors (located on neurons and/or the smooth muscle) is unlikely to participate in peristaltic motor regulation.

Animals↗

Abnormal distribution of intestinal pacemaker (C-KIT-positive) cells in an infant with chronic idiopathic intestinal pseudoobstruction.

BACKGROUND: Chronic idiopathic intestinal pseudoobstruction (CIIPO) is a rare syndrome with an obscure pathogenesis. The proto-oncogene c-kit encodes a transmembrane tyrosine kinase receptor C-KIT that is critical for the development of the interstitial cells of Cajal, cells that are regarded as being the pacemaker cells of the gut. Thus, C-KIT immunopositive (C-KIT-) cells in the muscle layers of the bowel are considered to be intestinal pacemaker cells. METHODS: In this study, the distribution of intestinal pacemaker cells was examined for the first time using C-KIT immunohistochemistry in an infant with CIIPO. RESULTS: C-KIT+ cells were found lying on either side of the border between the two muscle layers (longitudinal and circular) of the bowel and dispersed unevenly throughout both muscle layers. Myenteric plexuses were not demarcated by C-KIT+ cells. In contrast, in controls, C-KIT+ cells were located distinctly between the two muscle layers of the small bowel and dispersed evenly throughout the muscle layers of the colon. Myenteric plexuses were clearly demarcated by C-KIT+ cells. CONCLUSIONS: This case demonstrates for the first time that there is abnormal distribution of intestinal pacemaker cells in CIIPO and provides new evidence that abnormal c-kit gene expression may be responsible for autonomic gut dysmotility. C-KIT immunohistochemistry may be an indispensable tool for diagnosing CIIPO.

Chronic Disease↗

Intestinal metaplasia with adherent Helicobacter pylori: a hybrid epithelium with both gastric and intestinal features.

Helicobacter pylori seem to avoid areas of intestinal metaplasia in the gastric mucosa, but attachment of these bacteria to epithelium with the appearance of incomplete intestinal metaplasia has been documented. To characterize the nature of the epithelium to which H pylori was attached, we carried out an immunohistochemical study using monoclonal antibodies against gastric surface mucous cell mucins (M1), blood group-related carbohydrates antigens (Le(a), sialyl Le(a), Le(b), type 1H, and type 2H) and sialyl Tn antigen. The results of this study suggest that these areas of H pylori attachment represent a hybrid epithelium whose cells share characteristics of both gastric surface mucous cells and intestinal metaplastic cells. Whether all areas of incomplete intestinal metaplasia represent an intermediate stage between the normal gastric epithelium and the fully developed complete type of metaplasia remains to be determined.

ABO Blood-Group System↗

A modified device for the differentiated study of intestinal transfer in isolated intestinal segments from mice and suckling rats in vitro.

An increasing number of mice with genetic variation of intestinal transfer properties is becoming available. A luminal perfusion system for small intestinal segments, therefore, was adapted for the use in mice and rat pups to investigate longitudinal differences in intestinal drug and toxin transfer and to explore the adaptation of transfer properties during maturation under standardized conditions in vitro. At present, cell cultures are inadequate for this goal. The perfusator consists of an upper reservoir and a lower moist chamber to accommodate the intestinal segment. The luminal perfusion fluid is oxygenized and circulated by a gas lift. It is directed through the segment by two three-way taps. For safe and easy decontamination of radioactive substrates, the system is made entirely of glass. To perfuse fragile segments from small animals such as mice and rat pups in vitro, the perfusion pressure had to be reduced to 15 cm H2O column. Therefore, the design of the perfusator was changed, and the gas lift and the three-way taps were moved to the side. With segments from adult rats, the modified perfusor yielded the same transfer data for 59Fe, glucose, and water as did the standard device. Experiments with proximal and distal segments from mice and rat pups showed a longitudinal pattern of adaptation during maturation as well as due to iron deficiency that was in accordance with expectations extrapolated from literature.

Aging↗

Intestinal absorption of drugs. III. The influence of taurocholate on the disappearance kinetics of hydrophilic and lipophilic drugs from the small intestine of the rat.

The influence of sodium taurocholate (TC) on the intestinal absorption of drugs was studied in vivo in a chronically isolated internal loop in the rat. The hydrophilic drugs paracetamol (PA) and theophylline (TP) and the lipophilic drugs griseofulvin (GF) and ketoconazole (KE) were used as model drugs. The drug concentrations were kept below the saturation concentration. Absorption kinetics of the drugs were evaluated on the basis of disappearance rates of the drug from luminal solutions in the intestinal loop. Concentrations of TC above the critical micelle concentration (CMC) did not affect the absorption rate of the hydrophilic drugs PA and TP; the barrier function of the intestinal wall for PA and TP was not altered in the presence of taurocholate. The addition of concentrations of TC above the CMC in the perfusion solution resulted in a reduction of the absorption rate of GF and KE. The reduction in the absorption kinetics of GF in the presence of TC correlated well with the reduction of the drug-free fraction in solution due to micellar solubilization. For KE this relation was less clear. It was not possible to determine, on the basis of the phase-separation model, to what extent the fraction of the drug incorporated in TC micelles contributes to the overall diffusion of GF and KE across the preepithelial diffusion barrier. It was concluded that TC exhibits only a minor, if not negligible, effect on the barrier function of the aqueous diffusion barrier adjacent to the intestinal wall.

Acetaminophen↗

Glycosphingolipid (GSL) microdomains as attachment platforms for host pathogens and their toxins on intestinal epithelial cells: activation of signal transduction pathways and perturbations of intestinal absorption and secretion.

Glycosphingolipid (GSL)-enriched microdomains are used as cellular binding sites for various pathogens including viruses and bacteria. These attachment platforms are specifically associated with transducer molecules, so that the binding of host pathogens (or their toxins) to the cell surface may result in the activation of signal transduction pathways. In the intestinal epithelium, such pathogen-induced dysregulations of signal transduction can elicit a severe impairment of enterocytic functions. In this study, we demonstrate that the interaction of a bacterial toxin (cholera toxin) and a viral envelope glycoprotein (HIV-1 gp120) with the apical plasma membrane of intestinal cells is mediated by GSL-enriched microdomains that are associated with G regulatory proteins. These microbial proteins induce a GSL-dependent increase of intestinal fluid secretion by two mechanisms: activation of chloride secretion and inhibition of Na+ -dependent glucose absorption. Taken together, these data support the view that GSL-enriched microdomains in the apical plasma membrane of enterocytes are involved in the regulation of intestinal functions.

Calcium↗

Sphingomyelin content of intestinal cell membranes regulates cholesterol absorption. Evidence for pancreatic and intestinal cell sphingomyelinase activity.

Micellar cholesterol uptake and secretion were investigated in the human intestinal cell line CaCo-2 following depletion of apical membrane sphingomyelin. The addition of exogenous sphingomyelinase, which hydrolysed 60% of prelabelled sphingomyelin, resulted in a 50% decrease in the uptake of cholesterol from bile salt micelles. The flux of membrane cholesterol into the cell by the hydrolysis of membrane sphingomyelin decreased the rate of cholesterol synthesis by 43% and inhibited hydroxymethylglutaryl-CoA reductase activity by 54%. Moreover, the rate of cholesterol esterification was increased 4-fold. Total cellular cholesterol mass was unchanged by the addition of sphingomyelinase; however, cholesteryl esters increased by 50% and the amount of unesterified cholesterol decreased significantly. The basolateral secretion of cholesterol mass was also decreased following sphingomyelin hydrolysis. Human pancreatic juice was found to contain neutral sphingomyelinase activity which required taurocholate for full expression. The presence of neutral sphingomyelinase activity was also documented in membranes prepared from CaCo-2 cells and in whole homogenates from human duodenal biopsies. The data suggest that the amount of sphingomyelin present in the apical membrane of the intestinal absorptive cell regulates cholesterol uptake from bile salt micelles. Sphingomyelinase activity within intestinal cells and in pancreatic juice could alter the sphingomyelin content of brush-border membranes of small intestinal absorptive cells and thus regulate the amount of cholesterol absorbed by the gut.

Cells, Cultured↗

[Ileus of the small intestine in intestinal marginal-zone B-cell lymphoma of mucoid-associated lymphoid tissue (MALT)].

HISTORY AND ADMISSION FINDINGS: A 67-year-old man had complained of diffuse abdominal pain and constipation for 4 days without indication of any underlying disease. On admission there was no evidence of weight loss, fever or nocturnal sweating. INVESTIGATIONS: Physical examination revealed signs of an acute abdomen with high-pitched bowel sounds and diffuse abdominal guarding. The X-ray showed ileus of the small intestine which required emergency laparotomy. An obstructing conglomerate tumour was present in the area of the ileum, ca. 80 cm proximal to the caecum. It was removed by partial resection of the small intestine. DIAGNOSIS: Ileus of the small intestine with a low-malignant marginal zone B-cell (non-Hodgkin) lymphoma of MALT type (mucoid-associated lymphoid tissue). TREATMENT AND COURSE: Postoperative staging indicated no further manifestation of the lymphoma. As no radical operation in resecting the tumour had been performed, combined radio- and chemotherapy was undertaken. CONCLUSION: Marginal B-cell lymphomas of the small intestine are only rarely seen in central Europe. Despite its usually slow growth this non-Hodgkin lymphoma of low malignancy can produce an acute mechanical ileus without prodromal symptoms. A multimodal therapeutic approach is often employed, but there are no established treatment strategies.

Abdominal Pain↗

Studies of the large intestine of sheep. 1. Fermentation and absorption in sections of the large intestine.

1. Fermentation and absorption of constituents of digesta in segments of the large intestine of sheep given different diets were studied by analysis of gut contents obtained at slaughter after a period during which the sheep had been administered a non-absorbable gut marker. 2. In sheep given chopped, dried lucerne (Medicago sativa) there was net absorption of water throughout the large intestine with concomitant increases in the proportion of dry matter (DM) and organic matter (OM). There was net disappearance of 62 g OM, 1.66 g non-urea non-ammonia-nitrogen (NU-NAN) and 0.6 g (urea + NH3(-N in the caecum and proximal colon. There was no significant change in OM and NU-NAN flow through the remainder of the large intestine but there was a net disappearance of 0.3 g NH3-N. There was also net appearance of volatile fatty acids (VFA) in the caecum, most of which was apparently absorbed before the rectum. 3. Metabolism in the caecum was also studied in sheep grazing fresh pasture or consuming one of three sugar cane-bagasse-based diets, or barley pellets. In the lucerne- and pasture-fed sheep there was a net disappearance of approximately 0.5 g NH3-N/d from the caecum, while in sheep fed on bagasse plus urea, 1.4 g NH3-N/d was apparently absorbed from this region. The addition of fish meal to this latter diet resulted in apparent disappearance of 5.3 g NH3-N/d from the caecum and proximal colon. 4. There was apparent loss of NU-NAN from the caecum of sheep on all diets except the barley diet. With the latter diet there was a net gain of 1 g NU-NAN/d which was associated with relatively high VFA concentration and production; taken together these results indicate that microbial fermentation in the caecum was more extensive in the sheep fed on the barley diet than in those fed on the other diets. 5. The proportions of individual VFA in digesta from the rumen and caecum of lucerne-fed and pasture-fed sheep and in digesta from the caecum of sheep given the bagasse-based or barley diets are also reported and discussed. 6. In general the results indicate that the caecum and to a lesser extent the proximal colon were the major regions of fermentation and absorption of the components of the digesta in the large intestine.

Ammonia↗

Plasma enterolactone or intestinal Bifidobacterium levels do not explain adenoma formation in multiple intestinal neoplasia (Min) mice fed with two different types of rye-bran fractions.

The study was designed to evaluate whether two types of rye-bran fractions result in distinct bifidogenic effect or enterolactone production in multiple intestinal neoplasia (Min) mice and whether these parameters are associated with intestinal tumorigenesis in this animal model. The experimental diets were a non-fibre diet (control), a rye-bran diet, and diets containing either the soluble extract or the insoluble fraction prepared from rye bran. The main result on adenoma formation in these experiments was the observation that the soluble extract increased number (P=0.012) and size (P=0.008) of adenomas in the distal small intestine when compared with the non-fibre group. All rye-supplemented diets supported similarly the in vivo growth of Bifidobacterium (10(8)-10(9) colony forming units/g) in Min mice, whereas the non-fibre diet lowered intestinal Bifidobacterium below the level of detection. The results show that water solubility does not affect the bifidogenicity of rye bran. Mean plasma enterolactone concentration was highest in the rye-bran group (30.0 nmol/l; P=0.002), which along with the soluble-extract group (16.2 nmol/l; P=0.024) differed significantly from the non-fibre diet group (7.5 nmol/l). Thus, the mice fed with the rye bran were the best enterolactone producers. In conclusion, rye bran and rye fractions influence adenoma formation in Min mice to a varying degree but plasma enterolactone levels or the production of bifidogenic bacteria do not mediate the effect.

4-Butyrolactone↗

Morphology of the small intestinal mucosal surface of broilers in relation to age, diet formulation, small intestinal microflora and performance.

1. Three experiments were performed to relate morphological characteristics of the small intestinal mucosal surface to age, dietary factors, small intenstinal microflora and performance of broilers. Characterisation of the small intestinal mucosal surface using a dissecting microscope was based on the orientation of the villi, villus shape and the presence of convoluted villi. 2. In Trial 1, the morphological changes of the mucosal surface were studied weekly in the period from 7 to 28 d of age. At d 7 mainly tongue- and leaf-shaped villi together with some ridge-shaped ones were observed in the middle section of the small intestine, displaying a regular zigzag pattern on 53% of the mucosal surface. During the period from d 7 to 14, the area with ridge-shaped villi increased from 7 to 63% and did not change significantly over the next 2 weeks. 3. In Trial 2, three protein sources, soy isolate (SI), wheat gluten (WG), hydrolysed wheat gluten (HWG) and SI with added L-glutamine (SI + Gln), were studied with respect to their effect as dietary components on villus morphology in the mid-small intestine and performance. Diets were fed with (0 to 14 d) and without pectin (14 to 21 d). Feed conversion ratio on the HWG diet improved in comparison to the native WG diet. During the period 0 to 14 d of age the mucosal area with zigzag-oriented villi increased when the pectin diet was supplemented with Gln. Moreover, weight gain of birds fed the SI + Gln diet increased in the period 41 to 21 d. 4. In Trial 3, a study was made of the morphological response of the villi to a stimulation of microbial activity in the digesta after addition of highly methylated pectin to the soybean meal (SBM) diet. This was performed with and without inoculation of a non-virulent Salmonella typhimurium on d 7. By d 21 the birds fed the pectin diet showed impaired weight gain and higher feed conversion. The pectin affected the mucosal surface by decreasing the area with the zigzag pattern and increasing the area with convoluted, mainly ridge-shaped villi. The Salmonella typhimurium infection increased the effects of pectin on performance and mucosal morphology.

Animal Feed↗

CD3 cells in the intestine of broilers inoculated with intestinal homogenate.

1. Reactivity of polyclonal rabbit CD3 antiserum to human T cells and density of CD3 cells in chicken intestine were studied after the inoculation of 1-d-old broilers with intestinal homogenate to develop the Runting and Stunting Syndrome. 2. Reactivity of CD3 antiserum in chicken intestine was very good. 3. Increased numbers of epithelial lymphocytes as well as infiltration of CD3 cells into the lamina propria were demonstrated. 4. Intestinal homogenate caused impaired growth and bad feathering in broiler chickens until 21 d of age.

Animals↗