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PubMed1990

Enhanced intestinal permeability to 51Cr-labeled EDTA in dogs with small intestinal disease.

Intestinal permeability in dogs with small intestinal disease was measured by quantitation of 24-hour urinary excretion of 51Cr-labeled EDTA following intragastric administration. Permeability was high in dogs with a variety of naturally acquired small intestinal diseases including wheat-sensitive enteropathy of Irish Setters, small intestinal bacterial over-growth, and giardiasis, and permeability was decreased after successful treatment. These findings indicate that the assessment of intestinal permeability may be a useful technique for detecting small intestinal disease and for monitoring the efficacy of treatment in dogs.

Animals↗
PubMed1986

Immunohistochemical localization of gut peptides in the small intestine of snakes.

The small intestine of Vipera aspis, Natrix natrix and Natrix maura has been investigated for the presence of six gastrointestinal peptides reported to occur in Mammals. Gastrin/CCK and somatostatin were present in endocrine cells of the gut of all the species investigated. The neuropeptide vasoactive intestinal polypeptide was located within nerve terminals and in body cells only in the small intestine of Vipers and was absent in the Natricinae investigated. No immunoreactivity was found with the antisera to glucagon, secretin and motilin.

Animals↗
PubMed1995

Metabolism of [14C]1,3-dinitrobenzene by rat small intestinal mucosa in vitro.

The small intestine can metabolize a variety of substances and can play a role in the presystemic clearance of ingested compounds. Relatively little is known about the ability of small intestine to catalyze the presystemic reductive metabolism of xenobiotics. 1,3-Dinitrobenzene (1,3-DNB), which is known to undergo reductive biotransformation in an intact, oxygenated isolated perfused intestinal preparation, was used as a model substrate for reductive enzymes of the small intestine of the rat. Subcellular fractions from duodenal, jejunal, and ileal regions of rat small intestinal mucosa were used to characterize the enzyme source(s) of those reductive reactions of 1,3-DNB that are relevant in the oxygenated intestinal tissue. 1,3-DNB was reduced to 3-nitroaniline (3-NA) by cytosol from duodenum and jejunum. The rate of reduction was 2 times faster when incubations contained duodenal rather than jejunal cytosol. Jejunal cytosol-catalyzed reduction of 1,3-DNB was supported by hypoxanthine, NADPH, or NADH. Duodenal microsomes catalyzed the reduction of 1,3-DNB to 3-NA in the presence of supplemental NADPH or NADH; however, the reaction was very slow. Jejunal microsomes, ileal microsomes, and ileal cytosol failed to catalyze the reduction of 1,3-DNB. Studies with chemical inhibitors suggested possible roles for DT diaphorase, glutathione reductase, or xanthine oxidase in the jejunal cytosol-catalyzed reaction. Purified, commercially available xanthine oxidase (from buttermilk) catalyzed the reduction of 1,3-DNB to 3-NA when supplemented with NADH or hypoxanthine.

Animals↗
PubMed2005

Chloride channels in the small intestinal cell line IEC-18.

Small intestinal crypt cells play a critical role in modulating Cl- secretion during digestion. The types of Cl- channels mediating Cl- secretion in the small intestine was investigated using the intestinal epithelial cell line, IEC-18, which was derived from rat small intestine crypt cells. In initial radioisotope efflux studies, exposure to forskolin, ionomycin or a decrease in extracellular osmolarity significantly increased 36Cl efflux as compared to control cells. Whole cell patch clamp techniques were subsequently used to examine in more detail the swelling-, Ca2+-, and cAMP-activated Cl- conductance. Decreasing the extracellular osmolarity from 290 to 200 mOsm activated a large outwardly rectifying Cl- current that was voltage-independent and had an anion selectivity of I- > Cl-. Increasing cytosolic Ca2+ by ionomycin activated whole cell Cl- currents, which were also outwardly rectifying but were voltage-dependent. The increase in intracellular Ca2+ levels with ionomycin was confirmed with fura-2 loaded IEC-18 cells. A third type of whole cell Cl- current was observed after increases in intracellular cAMP induced by forskolin. These cAMP-activated Cl- currents have properties consistent with cystic fibrosis transmembrane regulator (CFTR) Cl- channels, as the currents were blocked by glibenclamide or NPPB but insensitive to DIDS. In addition, the current-voltage relationship was linear and had an anion selectivity of Cl- > I-. Confocal immunofluorescence studies and Western blots with two different anti-CFTR antibodies confirmed the expression of CFTR. These results suggest that small intestinal crypt cells express multiple types of Cl- channels, which may all contribute to net Cl- secretion.

Animals↗
PubMed1979

Microflora of the human small intestine.

The human small intestine is normally sterile in nearly one half of North American subjects. In this study the duodenum, jejunum, and ileum were sterile in 82, 69, and 55 per cent of the cases, respectively. Gram-positive cocci were the most frequent finding. E. coli, Enterobacter, and Klebsiella were present in the small bowel in nearly 7, 15, and 35 per cent of duodenal, jejunal, and ileal samples, respecatively. They were present in significant numbers (greater than 1 X 10(5)/ml) in the mid-jejunum in two patients and in the mid-ileum in seven patients (23 per cent). Even with modern anaerobic techniques, anaerobes are scarce in the small bowel; 4 to 6 per cent of persons may have aerotolerant anaerobes like clostridia, but strict anaerobes like bacteroides are rare. Our study provides baseline data for use in interpreting the intestinal bacterial overgrowth associated with certain postoperative disorders.

Abdominal Injuries↗
PubMedDate not supplied

Risk factors for adenocarcinomas and malignant carcinoids of the small intestine: preliminary findings.

Although the small intestine contains 75% of the mucosal surface of the gastrointestinal tract, it is the site of only 2% as many malignancies as the large bowel. The association of Crohn's disease with small intestine adenocarcinoma is well known, but the analytic epidemiology of small intestine malignancies has not received much attention. We reviewed the medical records of 19 patients with adenocarcinoma and 17 with malignant carcinoids identified from the Columbia-Presbyterian Medical Center Tumor Registry in the years 1980-1987. These were compared with 52 controls with nonmalignant conditions from the same time period. Three adenocarcinoma patients but no carcinoid patients or controls had previous Crohn's disease (P < 0.004). Three adenocarcinomas and three carcinoids, but no controls, had previous cholecystectomy (P < 0.004). Previous peptic ulcer disease was recorded for two patients with adenocarcinoma and three with carcinoid but no controls (P < 0.02, P < 0.0002). The age and sex adjusted odds ratio for cigarette smoking was 4.6 (95% confidence interval, 1.0-20.7) for adenocarcinomas and 4.2 (0.8-22.4) for carcinoids. The adjusted odds ratio for alcohol consumption was 4.0 (1.0-15.9) for adenocarcinomas and 3.1 (0.7-13.9) for carcinoids. Further studies are warranted to confirm these associations and to identify potential protective factors in the small intestine.

Adenocarcinoma↗
PubMed1990

Proenkephalin A-derived peptide E and its fragments alter opioid contractility in the small intestine.

The human and canine small intestine exhibit increased contractility when exposed to exogenous or endogenous opioid peptides. The response of the canine small intestine to the proenkephalin A-derived peptide, peptide E and related processing fragments [Met5]enkephalin, BAM-12P, BAM-18P and BAM-22P was investigated by administering each peptide to isolated, small intestine segments which causes a significant increase in intraluminal pressure. Concentration-response curves from intraarterial bolus administration of peptide E, [Met5]enkephalin, BAM-12P, BAM-18P and BAM-22P showed decreasing efficacy with decreasing amino acid chain length while naloxone (305 nM) significantly antagonized the response. Results using the classical guinea pig ileum/myenteric plexus longitudinal muscle and mouse vas deferens bioassays with specific opioid receptor antagonists provide evidence that peptide E and BAM-18P are relatively specific to the mu opioid receptor, [Met5]enkephalin is more delta specific, BAM-22P is both mu and kappa specific and BAM-12P is kappa opioid receptor specific. These studies demonstrate that locally released (and possibly circulating) peptide E and related processing fragments increase contractility in the small intestine and may be active through more than a single receptor mechanism, particularly the mu receptor.

Animals↗
PubMed2003

Microsatellite instability and expression of MLH1 and MSH2 in carcinomas of the small intestine.

BACKGROUND: Carcinomas of the small intestine are rare, but the risk is greatly increased in patients with hereditary nonpolyposis colorectal cancer (HNPCC) due to an inherited mismatch repair (MMR) gene mutation, most commonly affecting the genes MLH1 or MSH2. Defective MMR is characterized by microsatellite instability (MSI) and loss of MMR protein expression in the tumor tissue. However, a subset of several sporadic tumor types, including about 15% of colon cancers, also evolve through defective MMR. METHODS: The authors have assessed the frequency of MSI and analyzed the immunohistochemical expression of MLH1 and MSH2 in a population-based series of 89 adenocarcinomas of the small intestine. To study the contribution of MSI and defective MMR protein expression in young patients, 43 cancers of the small intestine from patients below age 60 years (including 24 tumors from the population-based series and an additional 19 tumors from young individuals) were also analyzed. RESULTS: MSI was detected in 16/89 tumors (18%) in the population-based series, and immunohistochemistry revealed loss of expression for MLH1 in 7/16 MSI tumors and in 2/73 MSS tumors, whereas all tumors showed normal expression for MSH2. Among the young patients, the authors identified MSI in 10/43 tumors (23%), and 6 of these 10 MSI tumors showed immunohistochemical loss of MMR protein expression, which affected MLH1 in 3 cases and MSH2 in 3 cases. CONCLUSIONS: The frequency of MSI (18%) in adenocarcinomas of the small intestine equals that of colon cancer. However, silencing of MLH1 seems to explain the MSI status in only about half of the MSI tumors. Among patients with cancer of the small intestine before age 60 years, MSI is found in 23% of the cases, with MLH1 and MSH2 being affected at equal frequencies, indicating that HNPCC may underly a subset of such cases.

Adaptor Proteins, Signal Transducing↗
PubMed1976

[Perforation of the small intestine in systemic diseases].

Small intestine perforations caused by systemic disorders are, except with M. Crohn, extremely rare. Therefore we report two cases of "spontaneous" small intestine perforations: one with hypersensitivity angiitis and one with Moya-Moya-disease, the latter not yet described in the literature.

Adult↗
PubMed2006

Immunohistochemical investigation of tumorigenic pathways in small intestinal adenocarcinoma: a comparison with colorectal adenocarcinoma.

Small intestinal adenocarcinoma is an uncommon neoplasm morphologically similar to or indistinguishable from colorectal adenocarcinoma. Although much has been learned about genetic pathways critical to colorectal tumorigenesis, little is known about molecular alterations involved in the development of small intestinal adenocarcinoma. In this study, we immunohistochemically compared non-ampullary small intestinal adenocarcinomas with sporadic colorectal adenocarcinomas for the expression of several proteins known to serve pivotal roles in colorectal tumorigenesis. These included adenomatous polyposis coli and beta-catenin involved in the Wnt signaling pathway, and DNA mismatch repair enzymes hMLH1, hMSH2 and hMSH6 involved in the microsatellite instability pathway. The expression of two important tumor suppressors, p53 and RB, was also examined. The results show that complete loss of adenomatous polyposis coli immunoreactivity, presumably resulting from its gene mutations, was observed in eight of 26 (31%) small intestinal adenocarcinomas and 36 of 51 (71%) colorectal adenocarcinomas (P = 0.0008). Nuclear localization of beta-catenin, an indirect evidence of deregulated Wnt signaling pathway, was observed in 5 (19%) small intestinal adenocarcinomas and 36 (71%) colorectal adenocarcinomas (P<0.0001). Total lack of nuclear staining for one or more of the DNA mismatch repair enzymes occurred in a similar low frequency in both small intestinal and colorectal adenocarcinomas, seen in two of 25 (8%) and 10 of 47 (21%) cases, respectively (P = 0.1958). The frequencies of aberrant p53 and RB expression were also similar between small intestinal and colorectal adenocarcinomas. These observations indicate that defects in the Wnt and microsatellite instability pathways occur in over 90% of colorectal adenocarcinomas, but in only 40% of small intestinal adenocarcinomas. Small intestinal tumorigenesis appears to follow a distinct, yet unidentified, molecular pathway(s) from its colorectal counterpart despite their morphologic similarity.

Adaptor Proteins, Signal Transducing↗
PubMed2006

Effect of osmolality on net fluid absorption in non-infected and ETEC-infected piglet small intestinal segments.

In the small intestinal segment perfusion model the effect of osmolality on net fluid absorption in enterotoxigenic Escherichia coli (ETEC)-infected and non-infected small intestinal segments of piglets was investigated. In ETEC-infected segments net fluid absorption was reduced. Lowering the osmolality from 375 to 150 mOsmol/l by reducing sodium chloride concentrations increased net fluid absorption. There was a linear relationship between osmolality and net fluid absorption for both non-infected and ETEC-infected segments. Below 150 mOsmol/l the inverse relationship between osmolality and net fluid absorption disappeared. Substitution of sodium chloride with mannitol decreased net fluid absorption since mannitol cannot be actively absorbed. In ETEC-infected segments perfused with oral rehydration solution net fluid absorption significantly increased compared to a sodium chloride solution of similar osmolality, probably because of the high glucose concentration. Supplying hypotonic sodium chloride fluids to piglets can be beneficial in replenishing water and electrolyte losses in case of infectious diarrhoea.

Animals↗
PubMed1978

Hemodynamic effects of phenoxybenzamine and volume replacement in segmental ischemia of the rat small intestine.

Segmental ischemia of the small intestine in the rat was established by ligating the mesenteric arterial end arcades of 1/4 of the length of the small intestine. Regional and central blood flow was measured with the microsphere technique before and 2 h after induction of the ischemia. In one series of rats an i.v. infusion of 16 ml plasma per kg body weight (b.w.) was given during the experimental period, which maintained the central circulation. However, the impairment of blood supply to the whole small intestine caused by the segmental ischemia was not normalized. Two other series of rats were treated with either phenoxybenzamine alone, 3 mg.kg-1 b.w., or the same dosage of phenoxybenzamine plus plasma infusion (16 ml.kg-1 b.w.). The central circulation was deteriorated and the blood flow to the small intestine reduced in the rats receiving phenoxybenzamine alone. Both the central circulation and the blood supply to the non-ischemic parts of the intestine were maintained in rats treated with both phenoxybenzamine and plasma. Combined treatment with phenoxybenzamine and volume replacement thus seems to be valuable for limiting the secondary hemodynamic changes caused by segmental intestinal ischemia.

Acid-Base Equilibrium↗
PubMed2003

Variable expression of CYP and Pgp genes in the human small intestine.

BACKGROUND: The small intestine is receiving increased attention for its importance in drug metabolism. However, knowledge of the intervariability and regulation of the enzymes involved, cytochrome p450 and P-Glycoproteins (CYP and Pgp), is poor when compared with the corresponding hepatic enzymes. METHODS: The expression of eight different CYP genes and the Pgp were determined by reverse transcription polymerase chain reaction (RT-PCR) in 51 human duodenum biopsies. And the variability and correlation of expression was analyzed. RESULTS: Extensive interindividual variability was found in the expression of most of the genes. Only CYP2C9, CYP3A4 and Pgp were found in all samples. CYP1A2, CYP2A6 and CYP2E1 exhibited the highest interindividual variability. No strong correlation of expression existed between the genes. But a highly significant correlation was found between CYP2D6/1A2, 2D6/2E1, 1A2/2E1 and 2B6/2C9. Acetylsalicylic acid and omeprazole significantly increased the expression of CYPs 2A6, 2E1 and 3A4, respectively. CONCLUSIONS: Extensive interindividual variability is characteristic for the expression of drug-metabolizing CYP and Pgp genes in human duodenum, and external factors such as drugs may further increase the variability. It is possible that the large interindividual variability may lead to variable bioavailability of orally used drugs and hence complicate optimal drug therapy, especially for drugs with a small therapeutic window. Elucidation of factors contributing to clinically important variances warrants further investigation.

Adult↗
PubMed1988

Effects of fractionated doses of ionizing radiation on small intestinal motor activity.

The small intestinal motor effects of fractionated doses of ionizing radiation were studied in 6 conscious dogs. Eight strain-gauge transducers were implanted on the small intestine and a single gauge on the ascending colon, of each dog. After control recordings, an abdominal dose of 250 cGy was administered three times a week on alternate days for 3 successive weeks (total dose, 2250 cGy). Recordings were then made for 4 wk of follow-up. Giant migrating contractions occurred 11 times in 520 h of control recordings in the fasted and fed state, with a mean distance of origin of 55 +/- 16 cm from the ileocolonic junction. Abdominal field irradiation significantly increased the incidence and distance of origin of these giant contractions to 438 in 745 recording hours and 158 +/- 7 cm from the ileocolonic junction, respectively. The incidence of giant migrating contractions peaked after the second dose of radiation. The amplitude ratio of radiation-induced giant migrating contractions to phase III contractions, and their duration and velocity of migration, were similar to the control state. The dogs developed diarrhea and vomiting as early as the first fraction of radiation. Irradiation also increased the incidence of retrograde giant contractions from 8 in 520 h of control recording to 42 in 745 h of recording during the radiation schedule. The radiation-induced retrograde giant contractions peaked in incidence on the day of the first fraction of radiation and were more likely to be associated with a vomiting episode than those occurring in the control period. Migrating motor complex cycling persisted during radiation and its cycle length was not different from the control or postradiation values. Our findings suggest that some of the side effects of radiation such as diarrhea, abdominal cramping, and vomiting may be related to the dramatically increased incidence of giant migrating contractions and retrograde giant contractions.

Animals↗
PubMed1977

Specific inhibition of cell proliferation in the mouse intestine by an aqueous extract of rabbit small intestine.

An aqueous extract was prepared from the mucosa of rabbit small intestine by homogenization and centrifugation at 105,000 g. After precipitation with ammonium sulfate, the 0-50 fraction (F1) and the supernatant (F2) were collected, dialysed against a phosphate buffer and tested on rats in vitro and mice in vivo. The F1 fraction was found to inhibit thymidine incorporation into rat intestinal DNA in vitro, but this effect was not found to be tissue specific (liver, kidney). Two hours after a single injection of F1 (10 mg protein content), the uptake of tritiated thymidine was decreased in jejunal and colonic DNA in mice. This effect was maximal between 2 and 4 hr and totally reversible after 7 hr; this effect was found in neither the kidney nor the testis. A slowing of cellular migration was also noticed in the jejunum and the colon. Conversely, the F2 fraction did not inhibit the synthesis of jejunal and colonic DNA either in vitro or in vivo. Our results suggest that the F1 fraction of the aqueous extract of rabbit small intestine contains one or more substances which may act either on intestinal DNA synthesis or on the GI--S transition of the cellular cycle in the mouse intestine. This reversible and specific intestinal action appears to inhibit cell proliferation and presents several of the characteristics defining a chalone.

Animals↗
PubMed1999

Experimental colitis increases small intestine permeability in the rat.

Small intestine permeability is frequently altered in patients with Crohn's disease and is thought to play a pathogenic role. The aim of this study was to investigate the permeability and structure of small intestine tight junctions (TJ) in an animal model of chronic distal colitis. Seven days after colitis induction with trinitrobenzenesulfonic acid/ethanol, the duodenal and ileal TJ were studied by means of transmission electron microscopy using lanthanum nitrate, freeze fractures, and immunohistochemistry of occludin, ZO-1, and cingulin. Animals treated with intrarectal ethanol alone served as controls. In controls, 7.5% of duodenal and 9.6% of ileal TJ were permeable to lanthanum, whereas in colitis, permeability increased significantly (79.5% and 72.9%, respectively; p < 0.001, both segments compared with controls). In colitis, the percentage of "leaky" junctions in duodena as well as in terminal ilea correlated positively with the macroscopic colon damage score (p < 0.02 and p < 0.005, respectively). Freeze-fracture analysis and immunohistochemistry of cingulin and ZO-1 did not reveal any difference between control and treated animals, whereas the signal of the transmembrane protein occludin was found to be disrupted and irregular in both small intestine segments. Distal colitis induces an increase of TJ permeability throughout the entire small intestine, and the extent of alterations correlates with colonic damage. Alterations in the transmembrane protein occludin seem to be responsible for the observed changes. Further investigation is needed to elucidate the mechanism of TJ alterations by a remote focus of inflammation.

Animals↗
PubMed1990

[Massive hemorrhage in the small intestine].

Haemorrhage into the small intestine accounts only for cca 1% of all haemorrhages into the gastrointestinal tract. Profuse haemorrhage is very rare, it occurs in malignant tumours, sarcomas and also haemangiomas. Preoperative diagnosis is practically impossible not only because the small intestine is not readily accessible for examination but in case of profuse haemorrhage also because of lack of time. Therefore a decision on early laparotomy has to be taken.

Aged↗