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PubMed1993

Selective paracellular permeability in two models of intestinal absorption: cultured monolayers of human intestinal epithelial cells and rat intestinal segments.

New data on the permeabilities of hydrophilic markers in two commonly used in vitro models, i.e., excised intestinal segments from the rat and monolayers of Caco-2 cells, are presented. The results are compared to human in vivo data. Two groups of hydrophilic marker molecules were tested: (1) monodisperse polyethylene glycols of molecular weights ranging from 194 to 502 g/mol and (2) a heterogeneous group of molecules consisting of urea, creatinine, erythritol, and mannitol (60-182 g/mol). The permeabilities of the marker molecules showed a nonlinear dependence on the molecular weight and decreased in the order rat ileum > rat colon > Caco-2 cells. Surprisingly, the polyethylene glycols permeated more easily than the other marker molecules, indicating that characteristics other than molecular weight, e.g., the flexibility of the structure, may also be important for permeation through the membrane. Comparisons with the published permeability profiles of polyethylene glycols in human intestinal segments in vivo (i.e., calculated permeability coefficients as a function of molecular weight) indicate that the human intestine is more permeable than the in vitro models. However, the permeability profiles of the corresponding segments in the human intestine and the in vitro models were comparable. Thus, good correlations were established between permeabilities of the human ileum and rat ileum and between those of human colon, rat colon, and the Caco-2 cells. We conclude that the paracellular absorption in humans can be studied mechanistically in these in vitro models.

Animals↗

PubMed1985

Interaction of vasoactive intestinal peptide with rat small intestinal epithelial cells after intestinal resection.

Specific binding of vasoactive intestinal peptide (VIP) and VIP-stimulated cyclic AMP accumulation were studied in small intestinal epithelial cells (both of crypt and villous levels) 3, 7 and 14 d after a 60% resection of the small intestine. The affinity, but not the binding capacity, of VIP receptors decreased during the adaptive hyperplastic response. Basal cyclic AMP levels were similar in cells of both control and resected rats. Resection induced a decrease of potency, but not of efficiency, of VIP on the stimulation of cyclic AMP accumulation.

Animals↗

PubMed1996

Effectiveness and toxicity screening of various absorption enhancers in the rat small intestine: effects of absorption enhancers on the intestinal absorption of phenol red and the release of protein and phospholipids from the intestinal membrane.

Sodium glycocholate, sodium taurocholate, sodium deoxycholate, EDTA, sodium salicylate, sodium caprate, diethyl maleate, N-lauryl-beta-D-maltopyranoside, linoleic acid polyoxyethylated (60 mol) mixed micelles (all 20 mM) have been ranked in order of their effectiveness as enhancers of the absorption of drugs in the rat small intestine, by use of an in-situ loop model with phenol red as a model drug. Local toxicity in rats was examined by assessing protein and phospholipid release as biological markers. Of the absorption enhancers, sodium deoxycholate, EDTA and N-lauryl-beta-D-maltopyranoside were the most effective; sodium deoxycholate and EDTA, however, caused significant release of protein and phospholipids. N-lauryl-beta-D-maltopyranoside, on the other hand, did not damage the small intestinal membrane. Sodium taurocholate enhanced phenol red absorption from the small intestine and resulted in little or no protein and phospholipids release. Sodium salicylate, diethyl maleate and the mixed micelles had no absorption-promoting effects on phenol red. There was good correlation between the area under the plasma concentration-time curve for phenol red and the amounts of protein and phospholipid released in the presence of absorption enhancers. From these results it might be concluded that N-lauryl-beta-D-maltopyranoside and sodium taurocholate are effective absorption enhancers which have low toxicity levels at a concentration of 20 mM.

Animals↗

PubMed1994

Primary small-intestinal lymphomas in Taiwan: immunoproliferative small-intestinal disease and nonimmunoproliferative small-intestinal disease.

PURPOSE: The clinicopathologic findings in 45 adult Chinese patients with primary small-intestinal lymphoma (PSIL) are described and compared with those in Western countries and in underdeveloped nations. The efficacy of combination chemotherapy is also assessed. PATIENTS AND METHOD: Six patients had immunoproliferative small-intestinal disease (IPSID) indicated by the presence of alpha-heavy chain protein (alpha-CP) in body fluids or tumor tissues. Thirty-nine patients had non-IPSID, including one with postrenal transplant lymphoma. Thirty-three non-IPSID patients received a minimum of four cycles of combination chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP). RESULTS: All IPSID patients presented with the clinical and laboratory features of severe intestinal malabsorption, and all had diffuse lymphoplasmacytic infiltration in the mucosa of the small bowel. Lymphomas were localized mainly in the jejunum and mesenteric nodes. The histologic subtypes were diffuse large cell in two, immunoblastic in three, and diffuse mixed in one. All patients responded poorly to chemotherapy, with a median survival duration of 10.5 months. The common presenting symptoms of the 39 non-IPSID patients included abdominal pain (90%), weight loss (31%), abdominal mass (26%), obstruction (26%), and perforation (23%). Diffuse large-cell and immunoblastic lymphomas constituted 82% of cases. Four patients had stage IE, 19 stage II 1E, and 16 stage 112E disease according to the Musshoff's criteria; 22 had bulky tumors and 19 had multiple tumors. The tumors were completely resected in 14 patients. Of 33 patients treated with combination chemotherapy, 73% achieved a complete remission. With a median follow-up duration of 90 months, there have been four relapses, with only one at the primary tumor site. The overall 5-year survival and disease-free survival rates for non-IPSID patients who were treated with chemotherapy were 59% and 54%, respectively. CONCLUSION: Intensive chemotherapy produces long-term disease-free survival in locally advanced non-IPSID PSIL.

Adult↗

PubMed1988

Villin, intestinal brush border hydrolases and keratin polypeptides in intestinal metaplasia and gastric cancer; an immunohistologic study emphasizing the different degrees of intestinal and gastric differentiation in signet ring cell carcinomas.

Gastric carcinomas have been assayed for the presence of villin and for the small intestinal hydrolases aminopeptidase N and sucrase isomaltase. These proteins seem not to be present in normal stomach epithelium. However intestinal metaplasia in stomach, and tumour cells in the glandular patterns of gastric carcinoma were positive for all three markers, showing characteristic apical positivity. In contrast, in diffuse gastric carcinomas the percentage of signet ring cells positive for these markers varied from 10-100% with each marker showing a similar percentage of positive cells. Testing of gastric carcinomas with antibodies specific for different keratin polypeptides showed that while all 7 tumours were positive for keratins 8 and 18.2 were also positive for keratin 7. In the keratin 7 positive tumours all tumour cells were keratin 7 positive. The keratin 8 antibody also reacted on routinely fixed specimens. Thus gastric carcinomas reveal different degrees of gastric and intestinal differentiation.

Adenocarcinoma, Mucinous↗

PubMed1987

In vitro translation of rat intestinal RNA prepared from isolated villus and crypt cells and from the epithelium-denuded intestine. Synthesis of intestinal basement membrane.

RNA purified from rat intestinal epithelial cells, obtained as isolated cell fractions of a villus-to-crypt gradient, were shown to be capable of directing peptide synthesis in a cell-free system. Analysis of products have demonstrated differences between villus and crypt and between jejunum and ileum. RNA purified from epithelium-denuded intestine was also shown to be capable of directing cell-free protein synthesis. Precipitation of products by antisera to rat IBM showed differences between epithelial and nonepithelial cells. Anti-laminin derived from mouse EHS sarcoma laminin precipitated products synthesized, in vitro, only by nonepithelial intestinal cells. Further studies on the control of the synthesis of rat IBM should provide valuable information on the relative contributions of epithelial and nonepithelial cells to the synthesis of basement membrane components of this organized tissue system.

Animals↗

PubMed1985

Ultrastructure of the epithelial cells of the small intestinal villi, the surface epithelium of the large intestinal mucosa and some elements of the intestinal mucosal lamina propria in rats with acute uraemia.

Electron microscopic studies on the dynamics of changes in the epithelial cells and some elements of the intestinal mucosal lamina propria were performed on rats after bilateral high ureter ligation. Simultaneously, they were referred to blood serum biochemical and electrolyte disturbances. The ultrastructural changes indicate that as early as in the initial period of acute uraemia water-electrolyte disturbances become evident, which are still increasing. In the later period cell organelles alter and bacterial infection sets in. Ultrastructural abnormalities of the intestinal mucous membrane are increasing proportionally to biochemical and electrolyte disturbances of the blood serum.

Animals↗

PubMed1988

[Perforations of the small intestine and intestinal parasitic diseases. Apropos of a case of peritonitis caused by the perforation of the small intestine combined with Taenia saginata infection].

A case is reported of peritonitis from perforation of the small intestine found on operation to be due to Taenia saginata. A review of the relevant literature of the last 20 years failed to find many similar cases, parasites, particularly Taenia being an exceptional direct cause of perforation. In the case reported, however, a direct cause/effect relation is highly probable.

Adult↗

PubMed1996

Effectiveness and toxicity screening of various absorption enhancers in the large intestine: intestinal absorption of phenol red and protein and phospholipid release from the intestinal membrane.

The effectiveness and local toxicity of absorption enhancers on the absorption of phenol red (PR) from the large intestine of rats were examined using an in situ loop method. The absorption enhancers used in this study were sodium glycocholate (GC-Na), sodium taurocholate (TC-Na), sodium deoxycholate (DC-Na), EDTA, sodium salicylate (Sal-Na), sodium caprate (Cap-Na), diethyl maleate (DM), N-lauryl-beta-D-maltopyranoside (LM) and mixed micelles (MM), all used at a concentration of 20 mM. Local toxicity was also investigated by assessing protein and phospholipid release as biological markers. DC-Na and MM were the most effective absorption enhancers, but they caused considerable release of proteins and phospholipids. GC-Na, TC-Na and LM, which caused little or only slight membrane damage, promoted PR absorption. Sal-Na, DM and EDTA did not enhance PR absorption. Overall, a correlation exists between the area under the curve of PR and protein and phospholipid release in the presence of absorption enhancers. However, GC-Na, TC-Na and LM promoted the absorption of PR with low toxicity. From these results, we concluded that GC-Na, TC-Na and LM are effective absorption enhancers which have low levels of toxicity at a concentration of 20 mM.

Animals↗

PubMedDate not supplied