Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “INTESTINES”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 217 records · Page 12Linked to original sources
PubMed2004

Intectin, a novel small intestine-specific glycosylphosphatidylinositol-anchored protein, accelerates apoptosis of intestinal epithelial cells.

Intestinal epithelial cells undergo rapid turnover and exfoliation especially at the villus tips. This process is modulated by various nutrients especially fat. Apoptosis is one of the important regulatory mechanisms of this turnover. Therefore, identification of the factors that control epithelial cell apoptosis should help us understand the mechanism of intestinal mucosal turnover. Here, we report the identification of a novel small intestine-specific member of the Ly-6 family, intectin, by signal sequence trap method. Intectin mRNA expression was exclusively identified in the intestine and localized at the villus tips of intestinal mucosa, which is known to undergo apoptosis. Intectin mRNA expression was modulated by nutrition. Intestinal epithelial cells expressing intectin were more sensitive to palmitate-induced apoptosis, compared with control intestinal epithelial cells, and such effect was accompanied by increased activity of caspase-3. Intectin expression also reduced cell-cell adhesion of intestinal epithelial cells.

Amino Acid Sequence↗
PubMed2003

In vitro inhibition of human small intestinal and liver microsomal astemizole O-demethylation: different contribution of CYP2J2 in the small intestine and liver.

1. The effects of chemical agents on the metabolism of the antihistamine drug astemizole were investigated to evaluate drug-drug interactions. 2. Chemical inhibitors of astemizole O-demethylation were screened using the small intestinal and liver microsomes from rabbit as an animal model for the first-pass metabolism of humans. In the rabbit small intestine, astemizole O-demethylation was clearly inhibited by ebastine, arachidonic acid, alpha-naphthoflavone, ketoconazole, tranylcypromine, troglitazone and terfenadine. 3. In humans, these inhibitors also reduced microsomal astemizole O-demethylation in both the small intestine and liver. However, the inhibition rate of almost all these chemicals were clearly greater in the small intestine than in the liver. Thus, a different contribution of cytochrome p450 in each tissue is suggested. 4. All the chemicals inhibited astemizole O-demethylation in recombinant CYP2J2 microsomes. The results suggest that CYP2J2 is involved in astemizole O-demethylation in both the human small intestine and liver; however, the contribution in the liver is lower than in the small intestine. The effects of the CYP2J2 inhibitors during first-pass metabolism may be more important in the small intestine than in the liver. Since all the inhibition profiles of astemizole O-demethylation were different in the liver and small intestine, involvement of another p450 in astemizole O-demethylation in human liver may be speculated. 5. In the rabbit microsomal systems, the same metabolites found in humans were qualitatively detected and the inhibition profiles of the chemical agents in the microsomes resembled that of humans.

Animals↗
PubMed2006

Class 1 integrons and their conjugal transfer with and without virulence-associated genes in extra-intestinal and intestinal Escherichia coli of poultry.

Multiple-drug resistance in enteric bacteria is frequently associated with integrons. To determine whether integrons may play a role in avian pathogenic Escherichia coli, isolates of extra-intestinal (n = 27) and intestinal (n = 40) E. coli from dead chicks and turkey poults were analysed for the presence of class 1 integrons and of the virulence-associated genes iss, tsh and colV. Eleven extra-intestinal strains possessed a 1.0 kb class 1 integron with a variable region of aadA1 and were resistant to tetracycline. These traits were indicative of the presence of the Tn21 transposon, which was confirmed by polymerase chain reaction. All extra-intestinal strains had the colV, iss and tsh genes, but none of these genes were cotransferred with the 1.0 kb integron when conjugal transferability was tested. The integron content of the intestinal strains showed considerable variability: one or two of four different class 1 integrons, which varied from 1.0 to 2.4 kb in size, were detected in the 11 strains. The aadA7 gene of the 1.0 kb integron, the dfrA1-aadA1 genes of the 1.6 kb integron and the folA-catB3-aadA5 genes of the 2.4 kb integron were identical to those described by other workers. However, the orfIN682-dhfrV-orfD gene cassette arrangement of the 1.5 kb integron of an intestinal strain of serogroup O5 had no similarity to any previously reported integrons. Conjugal transfer of the 1.6 and 2.4 kb integrons was successful, and in a serogroup O33 intestinal E. coli strain the iss gene was apparently cotransferred with a 1.6 kb integron. The 1.0 and 1.5 kb integrons were not transferable. Our data suggest that intestinal E. coli strains of poultry may be a reservoir for emerging multiresistant strains of avian pathogenic E. coli.

Animals↗
PubMed2001

Intestinal tumours induced by the food carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine in multiple intestinal neoplasia mice have truncation mutations as well as loss of the wild-type Apc(+) allele.

C57BL/6J-Min/+ (multiple intestinal neoplasia) is a murine model for familial adenomatous polyposis (FAP), where the mice are heterozygous for a nonsense Apc(Min) (adenomatous polyposis coli) mutation, and therefore develop numerous spontaneous adenomas in the small intestine and colon. Neonatal exposure of Min/+ mice to the food carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) (eight subcutaneous injections of 25 or 50 mg/kg PhIP to pups or 50 mg/kg PhIP to lactating dams) markedly increased (2--9-fold) the number of intestinal tumours, especially in the small intestine. We examined whether the Apc gene was affected in small intestinal and colonic tumours induced by PhIP. In spontaneous tumours formed in these mice, the main mechanism for tumour induction is loss of the wild-type Apc(+) allele, i.e. loss of heterozygosity (LOH). Also in the PhIP-induced tumours, this is a major mechanism, since large fractions of PhIP-induced tumours had LOH in APC: However, mechanisms other than LOH must also prevail, since a lower frequency of LOH was found in the small intestinal tumours from male mice exposed to PhIP either via breast milk (65%) or by direct injection (68%), compared with the untreated controls (92%). Tumours that had retained the wild-type Apc(+) allele were further analysed for presence of truncated Apc proteins with in vitro synthesized protein (IVSP) assay. Truncated Apc proteins, indicating truncation mutations in exon 15 of the Apc gene, were detected in 20% (8 of 40) of the tumours not showing LOH from the small intestine after PhIP exposure, all in segment 2 (codons 686--1217). Seventeen percent (2 of 12) of the colonic tumours had a truncated Apc protein in segment 3 (codons 1099--1693). Importantly, no truncated proteins were detected in tumours from unexposed mice with apparently retained wild-type Apc(+) allele. These results show that PhIP induces intestinal tumours in the Min/+ mice both by causing LOH and truncation mutations in the wild-type Apc(+) allele.

Adenoma↗
PubMed2002

Cyclooxygenase-2 expression is increased in early intestinal-type gastric cancer and gastric mucosa with intestinal metaplasia.

OBJECTIVE: Cyclooxygenase-2 (COX-2) expression is increased in gastric cancer. We examined COX-2 expression in early stage gastric cancer and background mucosa to elucidate the role of COX-2 in gastric carcinogenesis. METHODS: Thirty-three early gastric cancers obtained from 30 patients infected with Helicobacter pylori were studied. Twenty-three patients had an intestinal, four patients had a diffuse, and three patients had both an intestinal and a diffuse type cancer. Expression of COX-2 protein was detected by immunohistochemistry by counting the number of positive staining cells per 100 cells. RESULTS: Mean COX-2 expression was 84.1 (SD 11.4) in 26 intestinal type cancers and was significantly higher than that in seven diffuse type cancers (23.1 +/- 9.7) (P < 0.001). In three patients who had both the intestinal and the diffuse type cancer, COX-2 expression was 92, 90 and 83 in the intestinal type cancer and only 25, 24 and 7 in the corresponding diffuse type cancer. In 18 patients who had intestinal metaplasia (15 had incomplete metaplasia), COX-2 expression was 60.2 (24.2) in the crypts with metaplasia while it was only 16.8 (10.7) in the crypts without metaplasia (P < 0.001). CONCLUSIONS: COX-2 expression may be associated with the carcinogenesis of the intestinal type gastric cancer and, speculatively, inhibition of COX-2 might have preventative effects on the intestinal type gastric cancer.

Cyclooxygenase 2↗
PubMed1975

Radioimmunoassay studies of intestinal calcium-binding protein in the pig. I. Identification of intestinal calcium-binding protein in blood and response to a low calcium diet.

We have developed a radioimmunoassay for porcine intestinal calcium-binding protein (CaBP) and have used it to detect CaBP in pig plasma. Plasma CaBP is identical to intestinal CaBP on the basis of immunological activity, molecular size, and molecular charge properties. The plasma CaBP concentration was greater in the portal blood than in mixed venous blood, suggesting that blood CaBP originates in the gut. Two of four 15-week-old littermate pigs were placed on a low calcium diet (0.15% calcium, 0.65% phosphorus) and two on a control diet (0.65% calcium, 0.65% phosphorus). After 2 weeks, the entire small intestine was removed and divided into nine 1.8-m segments. CaBP was assayed in both plasma and intestinal mucosa. When the two pigs on a low calcium diet were compared with two control pigs, there was a general increase in immunoreactive CaBP in both plasma and intestinal mucosa. However, there was no increment in immunoreactive CaBP in the first 1.8-m segment of small intestine. Seventy-one percent of the increment in CaBP occurred distal to the first two segments. The largest fractional low calcium diet effect occurred in the ileum. The mean CaBP concentration for the total small intestine increased by a factor of 1.9. The plasma CaBP concentration increased by a factor of 2.6. In these pigs, plasma CaBP was a more reliable indicator of change in CaBP status than was the measurement in the proximal gut segment which contained the duodenum. The assay of CaBP in blood is convenient and may obviate the sampling errors inherent in intestinal biopsy.

Animals↗
PubMed1996

Do intestinal hyperpermeability and the related food antigens play a role in the progression of IgA nephropathy? I. Study of intestinal permeability.

Intestinal permeability was investigated by using 51Cr-EDTA as a probe molecule in 29 patients with immunoglobulin A nephropathy (IgA NP) and 20 healthy controls in 1990. Intestinal permeability was significantly higher in the IgA NP patients than in the controls (IgA NP, 3.86 +/- 0.29%; controls, 2.72 +/- 0.23%, p < 0.005). There was a significant relation between the manifestations of the disease (proteinuria and/or microhematuria) and the increased intestinal permeability (p < 0.05). By 1994, after an interval of 4 years, average intestinal permeability in the 21 patients available for study had not changed (3.80 +/- 0.36 vs. 4.57 +/- 0.63%) and was significantly higher than in the controls (p < 0.02). In patients with elevated serum IgA levels (serum IgA > 3.2 g/l; n = 15) there was a significant correlation between serum IgA levels and the degree of intestinal permeability (p < 0.02). During the 4-year period, the patients' kidney function deteriorated (n = 25; creatinine clearance in 1990, 92.4 +/- 6.1 ml/min; in 1994, 73.9 +/- 7.6 ml/min; p < 0.0002), the deterioration being greater in patients with increased intestinal permeability. There was no relation between the histologic grade of the biopsy specimen, hypertension and intestinal permeability. These data collected over a 4-year period suggest that in IgA NP increased intestinal permeability may play a role in the pathogenesis of the disease and adversely influence its progression.

Adult↗
PubMed2005

Mixed gastric- and intestinal-type metaplasia is formed by cells with dual intestinal and gastric differentiation.

We have proposed to divide intestinal metaplasia (IM) into two categories, i.e., a mixed gastric and intestinal (GI) type, and a solely intestinal (I) type, based on the residual gastric phenotype cells. The GI-mixed-type IM can be identified by the presence of both cells with either gastric or intestinal phenotypes in a single gland. This study is conducted to elucidate whether cells in the GI-mixed-type IM glands can simultaneously present both gastric and intestinal phenotypes. MUC5AC, MUC2, CD10 and villin expressions were investigated in 20 samples from five gastric cancer cases, directly using either AlexaFluor 488- or 568-labeled specific monoclonal antibodies and observed by fluorescent microscopy and confocal laser-scanning microscopy. GI-mixed IM glands comprise a population expressing MUC5AC and MUC2, MUC5AC and villin, and MUC5AC and CD10. MUC2 and villin expressions were reciprocally increased with decreasing MUC5AC expression, while CD10 expression was limited to cells with only a residual MUC5AC expression or no expression. These results suggest that a heterogeneous cell population with both gastric and intestinal phenotypes would develop into a single intestinal phenotype, as reflected in the progression of intestinal metaplasia from GI-mixed-type- to I-type IM-type glands.

Animals↗
PubMed1997

Effect of aging on the intestinal transport of hydrophilic drugs in the rat small intestine.

The effect of aging on the intestinal transport of hydrophilic drugs (and probe compounds) was investigated in the rat small intestine. Passive transport was suggested to be unchanged with aging from 8 (young) to 54 (old) and further to 101 (very old) weeks old, as shown for D-xylose and urea in single-pass intestinal perfusion (under urethane anesthesia), where steady-state transport across the intestinal membrane into the blood stream was evaluated. The passive transports of cephradine, 5-fluorouracil (5-FU) and L-glucose were also unchanged, though they were compared only between the young and the old. Consistently, the passive uptake in the intestinal everted sacs, where the entry process into the membrane was evaluated for 5-FU, D-xylose, urea and polyethylene glycol (PEG) 900, was unchanged with aging from the young to the very old. The carrier-mediated transport of cephradine was also unchanged with aging from the young to the old in perfusion under anesthesia, though that of D-glucose was declined by about 50% with aging from the young to the old and thereafter remained constant in the very old. In perfusion in unanesthetized rats, age independency in passive transport (examined for cephradine, L-glucose and D-xylose) and an age-dependent decline in D-glucose transport were also observed, suggesting that the findings under anesthesia are not qualitatively distorted. These results suggest that, although carrier-mediated transport may moderately decline with aging, the barrier function of the intestinal membrane to passive permeation of hydrophilic drugs (with molecular weight below 1000) may be unaffected by aging, supporting the suggestion from our previous in vivo studies that age-dependent increases in the orally absorbed fraction may be predicted for incompletely absorbed drugs because of delayed intestinal transit rather than increased intestinal transport (membrane permeability).

Aging↗
PubMed1989

Light and electron microscope study on developing intestinal mucosa in rat fetuses with special reference to the obliteration of the intestinal lumen.

The development of the small intestine in rat fetuses was studied by light and electron microscopy with special reference to morphological events during the stage of obliteration. Prior to this stage, the epithelium lining the intestinal lumen was simple, tall and columnar and consisted of undifferentiated cells mutually joined by the adluminal junctional complex. At the stage of obliteration, the epithelium appeared stratified and the intestinal lumen was identified as a narrow irregular slit. In addition to the junctional complex surrounding the intestinal lumen, secondary junctional complexes were scattered in the more basal parts of the epithelium. The intra-epithelial cavity was formed within the macula occludens of the secondary junctional complex and became larger by division of the surrounding cells. Since the small intestinal epithelium was essentially simple columnar, mitosis occurred facing the lumen. At the stage of obliteration when the number of epithelial cells was rapidly increasing, mitosis occurred facing not only the main intestinal lumen but also the intra-epithelial cavity. As the intra-epithelial cavities fused with the main intestinal lumen, mesenchyme invaded to form villi and the epithelium returned to a simple columnar form. Consequently, the intestinal lumen was enlarged and villi were formed. At the same time, absorptive cells with a brush border appeared in the villous epithelium and immature goblet cells were occasionally seen.

Animals↗
PubMedDate not supplied

Role of organized intestinal lymphoid aggregates in intestinal regeneration.

Intestinal lymphoid tissue has a complex interrelationship with the epithelium. The epithelia of intestinal crypts associated with lymphoid aggregates have an increased proliferation rate. In the present study, the authors tested the hypothesis that organized intestinal lymphoid tissue (Peyer's patches) enhances intestinal regeneration by studying this process with and without an adjacent Peyer's patch. Forty adult male Sprague-Dawley rats had full-thickness ileal defects patched with cecal serosa to allow regeneration of ileal mucosa. Control animals (group I) had the patch constructed adjacent to a Peyer's patch, whereas this Peyer's patch was excised in group II. Intestinal regeneration in both groups was evaluated on the third, fifth, seventh, and ninth days after operation. During the early phase of regeneration, both epithelial cell proliferation and migration were decreased in the patched defect after excision of the Peyer's patch. Crypt cell production rate in the adjacent normal mucosa also was decreased after excision of the Peyer's patch. Excision of the Peyer's patch resulted in less well-developed crypts and villi. Wound contraction, however, was greater in the intestinal defect adjacent to the Peyer's patch until day 7. In conclusion, Peyer's patches have a facilitative effect on the healing of intestinal wounds by promoting both epithelial cell migration on the defect and epithelial cell proliferation in the crypts adjacent to the wound and by decreasing the rate of wound contraction. These findings support a role for intestinal lymphoid tissue in the regulation of epithelial cell maintenance.

Animals↗
PubMedDate not supplied

Intestinal ischemia-reperfusion injury augments intestinal mucosal injury and bacterial translocation in jaundiced rats.

BACKGROUND/AIMS: The aim of this study was to evaluate local effects and degree of bacterial translocation related with intestinal ischemia-reperfusion injury in a rat obstructive jaundice model. METHODOLOGY: Thirty adult Sprague-Dawley rats (200-250 g) were divided into three groups; including Group 1 (jaundice group), Group 2 (jaundice-ischemia group) and Group 3 (ischemia group). All rats had 2 laparotomies. After experimental interventions, tissue samples for translocation; liver and ileum samples for histopathological examination, 25 cm of small intestine for mucosal myeloperoxidase and malondialdehyde levels and blood samples for biochemical analysis were obtained. RESULTS: Jaundiced rats had increased liver enzyme levels and total and direct bilirubin levels (p<0.05). Intestinal mucosal myeloperoxidase and malondialdehyde levels were found to be high in intestinal ischemia-reperfusion groups (p<0.05). Intestinal mucosal damage was more severe in rats with intestinal ischemia-reperfusion after bile duct ligation (p<0.05). Degree of bacterial translocation was also found to be significantly high in these rats (p<0.05). CONCLUSIONS: Intestinal mucosa is disturbed more severely in obstructive jaundice with the development of ischemia and reperfusion. Development of intestinal ischemia-reperfusion in obstructive jaundice increases bacterial translocation.

Animals↗
PubMed1988

[The role of the liver in the intestinal immune system. Origin of specific B-lymphocytes in the liver following intestinal immunization].

After intestinal priming with cholera toxin (CT) the highest number of specific B-cells is found in the liver, whereas after an intestinal booster dose of CT, high numbers of specific B-cells also locate to the intestine. Correspondingly, after priming, 70% of biliary IgA anti-CT are synthesized within the liver and after boosting approximately 30%. To test the hypothesis that the B-cells in the liver are derived from intestinal lymphoid tissue, thoracic duct lymphocytes (TDL) from intestinally primed and boosted donor rats were transferred to syngeneic recipients. TDL from primed donors predominantly homed to the liver of recipients, and TDL from boosted donors in high numbers to the intestine also. High biliary IgA anti-CT titers in both groups of recipients proved that the immune response was transmitted successfully. In the rat, at any rate, the liver is part of the intestinal immune system not only in terms of IgA transport but also as a specific homing organ for intestinal B-cells.

Animals↗
PubMed1983

[Myosin B ATPase activity of the intestinal smooth muscle in intestinal obstruction].

Intestinal smooth myosin B was prepared from muscle layers around the lesion in dogs with experimental colonic stenosis and in patients with congenital intestinal obstruction. Mg2+-ATPase activity of the myosin B was compared between the proximal dilated segment and distal segment to obstruction. Experimental colonic stenosis: In early period after surgery, proximal colons showed higher activity of myosin B ATPase than distal colons, decreasing to less than distal colon as time passed. Congenital intestinal obstruction: In three cases, whose atresia might have occurred at earlier period of gestation, proximal bowels showed less activity of myosin B ATPase than distal bowels. However, in two cases, whose atresia might have occurred at later period of gestation, and two cases with intestinal stenosis, proximal bowels indicated higher activity of myosin B ATPase than distal bowels. These data suggested that the contractibility of the proximal intestine was depending on the duration of obstruction, and it was depressed in the former patients and was accelerated in the latter patients. These results suggested that the extensive resection of dilated proximal bowel in the congenital atresia is not always necessary to obtain good postoperative intestinal dynamics at the operation of the atresial lesions which may be induced at later period of gestation. They also suggested that surgery for intestinal obstruction should be performed before the depression of intestinal contractibility to get good bowel function.

Adenosine Triphosphatases↗
PubMed1981

Effect of intestinal ischemia on diamine oxidase activity in rat intestinal tissue and blood.

This study examines the effect of increasing duration of intestinal ischemia on the mucosal integrity and the release of the enzyme diamine oxidase from the small intestine. Acute ischemia was produced by the occlusion of the superior mesenteric artery, and the subsequent changes in DNA and 125I-albumin content in the lumen were taken as indices of intestinal lesions. Diamine oxidase activity was measured in the intestinal lumen, mucosa, lymph, and serum. Occlusions of the superior mesenteric artery for periods of more than 60 min resulted in significant leakage of 125I-albumin (i.v.) into the lumen. In contrast, luminal DNA content rose significantly after 15 min of ischemia and continued to increase proportionally with the increased duration of the occlusion up to 120 min. Similarly, diamine oxidase activity was augmented in the lumen after 15 min of occlusion and rose sharply as the ischemic period was lengthened up to 60 min, leveling off thereafter. Increases in the diamine oxidase activity were also observed in the intestinal lymph and serum, reaching levels that were 2.6 and 3.6 times that of the control respectively after 60 min of ischemia. These findings suggest that intestinal ischemia reduces the diamine oxidase content in the intestinal mucosa by desquamation of the surface epithelial cells and by releasing the enzyme into the intestinal interstitial fluid, from which at least a portion is transported to the blood via the lymphatics. The early release of diamine oxidase seems to occur before the mucosal barrier is broken.

Albumins↗
PubMed1988

Histology of the intestine in human gastroschisis--relationship to intestinal malfunction: dissolution of the "peel" and its ultrastructural characteristics.

There are conflicting views on the pathogenesis of the intestinal malfunction seen in infants with gastroschisis. It has been variously ascribed to abnormalities of ganglion cells and smooth muscle elements, intestinal ischemia, and the "peel" which invests the serosa of the intestine. Review of the clinical and experimental literature showed only limited information on the histology of the eviscerated human intestine. In order to add to this data base, and to further investigate the pathogenesis of the intestinal malfunction from a histologic standpoint, we reviewed surgical and autopsy material from our experience with 105 neonates with gastroschisis. Ten specimens were satisfactory for evaluation from a standpoint of tissue integrity. The specific mural components of mucosa, submucosa, muscularis, and ganglion cells were examined and found to be either normal, or to show nonspecific abnormalities that varied from case to case, and were related mostly to intestinal infarction due to compromise of the gut at the site of the gastroschisis defect. In six patients, this progressed to atresia formation. The most consistent abnormalities were found in the serosal layer with its peel. Using special stains, the peel was found to be composed largely of fibrin and collagen. Based on this study, we feel that edema and ischemic changes, though often present, are much less prominent than the peel, as the leading histologic abnormality of the intestine of gastroschisis. Squamous epithelial cells were seen in the peel in four cases, suggesting that the peel had been "appliqued" onto the serosa of the herniated fetal gut.

Abdominal Muscles↗
PubMed1997

Intestinal transport and metabolism of analgesic dipeptide, kyotorphin: rate-limiting factor in intestinal absorption of peptide as drug.

Intestinal transport and metabolism of kyotorphin (KTP) were studied in rat everted small intestine. KTP on the mucosal side was metabolized completely within 60 min, and any amounts of KTP were not detected on the serosal side. On the other hand, [D-Arg2]-KTP (D-KTP) was stable on the mucosal side to appear on the serosal side. However, N-t-butoxycarbonyl-KTP (Boc-KTP), which was metabolized on the mucosal side faster than KTP, appeared on the serosal side. In intestinal homogenate, KTP was metabolized, and the metabolic clearance (CL(met)) was decreased by peptidase inhibitors, bestatin, o-phenanthrolin and tryptophan hydroxamate. In the presence of these peptidase inhibitors, the absorption clearance (CL(abs)) of KTP was increased. The less the CL(met) of KTP was, the more the CL(abs) of KTP was. Meanwhile, Boc-KTP in intestinal homogenate was stable even in the absence of peptidase inhibitors. The CL(abs) of Boc-KTP was constant irrespective of the stability on the mucosal side. Kinetic analysis by the metabolic inhibition model indicated that the stabilization of KTP in the intestinal tissue could increase the CL(abs) up to 0.247 microl/min per cm, which was as much as the CL(abs) of stable D-KTP. These results led to the conclusion that rate-limiting process in intestinal absorption of KTP is metabolic degradation in intestinal tissue during the absorption.

Analgesics↗
PubMed2001

A phenotypic change of small intestinal epithelium to colonocytes in small intestinal adenomas and adenocarcinomas.

OBJECTIVE: Using a novel monoclonal antibody (mAb Das-1) that specifically reacts with colon epithelium, we examined if there is a phenotypic change of small intestinal enterocytes toward colonocytes in small intestinal neoplastic tissue. METHODS: Tissue sections of the small intestine consisting of adenomas (n = 20, five with histories of familial polyposis), adenocarcinomas (eight primary and one metastatic from colon). carcinoids (n = 2), and hyperplastic polyps (n = 3) were examined by a sensitive immunoperoxidase assay using mAb Das-1 (IgM isotype). Normal jejunal (n = 10) and colonic (n = 10) biopsy specimens were also included as additional controls. RESULTS: mAb Das-1 reacted with normal colonic epithelium but not with jejunal mucosa. However, mAb Das-1 reacted strongly with each of the five adenomas (100%) from patients with histories of familial polyposis, but only five of 15 (33%) of the adenomas from nonfamilial polyposis patients, and each of the eight (100%) adenocarcinomas of the small intestine (p < 0.001). The reactivity with the adenomas from nonfamilial polyposis patients was very focal, whereas in the adenomas with familial polyposis the reactivity was more extensive. Each of the eight carcinomas reacted strongly with mAb Das-1. Adjacent normal small intestinal mucosa did not react. Hyperplastic polyps and the carcinoids did not react with mAb Das-1. CONCLUSION: These data demonstrate a phenotypic change in small intestinal epithelium toward the colonic phenotype, particularly in familial polyposis and in adenocarcinomas. mAb Das-1 may be clinically useful in identifying small intestinal adenomas with "high risk" for malignancy, such as in familial polyposis.

Adenocarcinoma↗