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PubMed1982

Sodium movements across the vascularly perfused anuran small intestine and colon.

Values of unidirectional Na fluxes measured across the vascularly perfused small intestine of three anuran species are higher than those found in other preparations in vitro. In Rana ridibunda and R. pipiens no net movement of Na across the small intestine can be detected. In contrast, the unidirectional fluxes of Na across the colon of R. ridibunda and R. pipiens are lower than across the small intestine and a significant net absorption is found. Apparent loading and unloading pools for Na within the small intestine, as measured with tracer Na under standard experimental conditions, consist largely of extracellular Na presumably within the bulk phase of the lumen. The size of these pools can be greatly reduced by the rapid addition to or removal from the lumen of tracer. The loading pool appears to occupy not more than about 9% of the total tissue water, equivalent to about 20% of the extracellular water of the tissue. The washout of tracer Na from preloaded small intestine into the vascular bed is bi-exponential and appears from a pool, or pools, of apparent greater size than that of the loading pool. The results show that Na can move very rapidly across the small intestine and suggest that a high proportion of this movement occurs possibly via paracellular shunt pathways.

Animals↗
PubMed1985

Expression of ornithine transcarbamylase deficiency in the small intestine and colon of sparse-fur mutant mice.

Sparse-fur mutant mice have an X-linked deficiency of liver ornithine transcarbamylase (OTC), similar to congenital hyperammonemia type II seen in children. The purpose of the present study was to see whether the expression of enzyme deficiency in the small intestine and colon was similar to that in the liver. Our results show that the level of residual OTC activity in duodenal, jejunal, and ileal mucosa is not significantly different from that of the liver, both in mutant heterozygous female and hemizygous male mice. A highly significant (p less than 0.001) positive correlation was seen between the enzyme activity from all segments of the normal and mutant intestine and that of the liver. pH dependence of mucosal OTC was similar to liver enzyme, when compared within normal or hemizygous mutant mice. Apparent Km (ornithine) of the enzyme from normal or mutant small intestine did not show any significant differences when compared with OTC from normal or mutant livers, respectively. Apparent Km (carbamyl phosphate) from both organs of normal mice was also similar. However, Km (carbamyl phosphate) of mutant intestine and liver gave variable results on statistical comparisons. The specific activity in the proximal and distal colon of mutant mice was significantly lower (p less than 0.001) than normal mice, and showed a similar expression of enzyme deficiency as seen in the small intestine. The similarity of OTC deficiency in the intestine and liver of sparse-fur mice would provide a basis for investigating the use of mucosal biopsies in the confirmation and characterization of human disease.

Animals↗
PubMed1997

Suppressor and activator functions mediated by a repeated heptad sequence in the liver fatty acid-binding protein gene (Fabpl). Effects on renal, small intestinal, and colonic epithelial cell gene expression in transgenic mice.

A 35-nucleotide sequence in the liver fatty acid-binding protein gene (Fabpl) has been identified that interacts with nuclear proteins present in adult mouse liver, kidney, stomach, small intestine, and colon. The binding site consists of a direct heptad repeat (TTCTGNNTT) separated by five nucleotides. Both heptads are required for formation of stable complexes with nuclear proteins in gel mobility shift assays. The in vivo functions mediated by the repeats were determined by comparing the expression of four Fabpl/human growth hormone fusion genes in multiple pedigrees of adult transgenic mice. The transgenes contained (i) nucleotides -596 to +21 of Fabpl linked to the human growth hormone reporter, (ii) 4 additional copies of the 35-base pair element placed at nucleotide -596 of Fabpl, (iii) 4 additional copies of the sequence placed just upstream of its endogenous site at nucleotide -132, and (iv) a sequence identical to (iii) but with all heptad repeats mutated within each of the 4 additional copies of the 35-base pair element. Transgene expression was defined by RNA blot hybridizations and by light and electron microscopic immunohistochemistry. The heptad repeat functions to suppress expression in tubular epithelial cells of the proximal nephron, in hepatocytes, in the mucus-producing pit cells of the gastric epithelium, and in absorptive enterocytes located in the proximal small intestine. There is a gradient of escape from enterocytic suppression as one moves from the proximal to distal small intestine. This escape progresses to involve successively less differentiated cells located closer and closer to the stem cell zone in crypts of Lieberkühn. The heptad repeat activates gene expression in the colonic epithelium so that all proliferating and nonproliferating cells in colonic crypts distributed from the cecum to the rectum support transgene expression. The heptad has no obvious sequence similarities to known transcription factor binding sites, suggesting that mediators of its in vivo activities are likely to be novel. One candidate factor is a 90-kDa protein identified in Southwestern blots. The 90-kDa protein also binds to an element in the matrix metalloproteinase-2 gene that functions as an enhancer in renal cells, shares sequence homology with the heptad, and generates similar-sized complexes in gel mobility shift assays as the Fabpl repeat. The heptad repeat represents a target for identifying transcription factors that regulate gene expression between gut and renal epithelia and that also regulate the differentiation program of the intestine's principal epithelial lineage as a function of its location along the duodenal-colonic axis. Finally, the Fabpl regulatory elements described in this report should be useful for delivering a variety of gene products throughout the colonic epithelium of transgenic mice.

Animals↗
PubMed1990

Results of a combination treatment with natamycin and butylscopolamine in cases of intestinal Candida colonization.

The findings described show that Candida species can be found in the feces of approximately half a population of nonselected test persons and in the mouths of approximately a third. Intestinal Candida colonization was found in most of these persons after one feces examination, and in practically all of them after a second examination. 10 d of therapy with 400 mg natamycin per day in sugar-coated tablet form and 40 mg natamycin in the form of tablets for sucking produced a negative fungus test for the feces in only 20% of the cases. Although a combination of this therapy with 3 x 10 mg butylscopolamine per day improved short-term results significantly, the long-term results were hardly influenced at all. Typifying results according to the Warnock method showed that we are dealing with recurrences in practically all cases and not with new infections. Minimal inhibition concentrations (MIC) of natamycin showed no marked changes as a consequence of the natamycin treatment.

Adult↗
PubMed2006

Labetalol absorption kinetics: rat small intestine and colon studies.

Labetalol is a widely used drug for the management of hypertension, which is preferably administered by the oral route despite its low bioavailability. The objective of this study is to ascertain the mechanisms underlying its absorption as an approach to help in predicting the influence of dosage changes, possible drug-drug and drug-fruit juice interactions. Perfusion experiments have been performed in rats in two sites of absorption: the intestine and the colon. The nonlinearity of the process has been established by means of the assay of a wide range of concentrations (2-2000 microM). Fitting of the concentration versus time data allows the estimation of passive diffusion constant in the intestine (1.42 +/- 0.05/h) and the colon (1.13 +/- 0.06/h), V(m) and K(m) of the input process (9.85 +/- 4.98 microM/h, and 10.44 +/- 26.16 microM, respectively) and K(m) of an efflux system (0.53 +/- 1.16 microM) and V(m) in both intestinal segments (2.60 +/- 11.37 microM . /h in the intestine and 0.66 +/- 1.38 microM . /h in the colon). The efflux carrier implicated is identified by means of several inhibition experiments, whose inhibition ability is mathematically estimated. Results suggest the p-glycoprotein as responsible for the efflux of labetalol.

Animals↗
PubMedDate not supplied

Colonic vasoactive intestinal polypeptide (VIP) in ulcerative colitis--a radioimmunoassay and immunohistochemical study.

BACKGROUND/AIMS: In this study, we present radioimmunoassay data describing the concentration of Vasoactive Intestinal Polypeptide (VIP) in both plasma and colonic biopsies, as well as immunostaining of VIPergic innervation in mucosal biopsies of normal subjects and patients with ulcerative colitis (UC). PATIENTS AND METHODS: Thirty three patients with UC and 17 healthy subjects were investigated. All UC patients suffered from active disease. Fasting circulating levels of VIP in plasma as well as tissue concentrations were measured by radioimmunoassay. For the immunohistochemistry, polyclonal antibody against VIP and the streptavidin-biotin peroxidase complex technique were carried out. RESULTS: Overall plasma VIP concentrations in the UC patients were similar to those in the controls. Significantly decreased concentrations of VIP were found in UC of rectum compared to the normal tissue. However, both plasma VIP values and tissue concentrations were found to be significantly lower in patients expressing minimal or mild active disease according to clinical activity index (AI) and histological activity index (HAI), but marked increase of plasma VIP was clear in UC patients with moderate or severe AI and HAI. There was a trend towards increased tissue concentrations of VIP in the group of patients with moderate or severe AI and HAI. Our immunohistochemical analysis of VIP fibers and nerve cell bodies revealed consistently weaker VIP-immunoreactivity in the rectum in UC patients with minimal or mild HAI. Simultaneously, in the rectal biopsies from UC patients with moderate and severe disease, the fibers in the lamina propria and ganglion cells in the submucous plexus were markedly increased in density and in degree of immunostaining. Very strong immunoreactivity was also found in inflammatory cells of the lamina propria as well as in the epithelial layer of the biopsies from UC patients with obvious disease. CONCLUSIONS: Our study shows clearly the heterogeneity in the response of VIP plasma level as well as rectum concentration and distribution in UC patients at different stages of the active disease. The possible role of VIP in the colon suggests that further studies of the alterations of this gut peptide may be useful in the understanding of UC pathophysiology.

Adult↗
PubMed1986

Immunoelectron microscopic localization of HLA-DR antigen in control small intestine and colon and in inflammatory bowel disease.

We have elucidated the distribution of I2 (HLA-DR) antigen in control and inflammatory bowel disease specimens, using immunoelectron microscopic methods. Control small intestinal epithelium and inflammatory bowel disease epithelium expressed 12 antigen, while control colonic epithelium did not. I2 expression by enterocytes was more frequent on the lateral and basal surface than on the microvillus surface. Two of three M cells in control ileum expressed I2 antigen. I2-positive intraepithelial lymphocytes were rarely detected in both control and disease specimens. I2-positive lamina propria lymphocytes were significantly increased in inflammatory bowel disease, while I2-positive lamina propria lymphocytes were virtually absent in control specimens. I2-positive mononuclear cells in the intestinal lamina propria were largely macrophages and monocytes in both control and inflammatory bowel disease specimens. I2-positive mononuclear cells resembling dendritic cells were not detected in control or disease specimens. Furthermore, there were no significant morphological differences in I2-positive or -negative macrophages and monocytes in control and disease specimens. The expression of I2 antigen on Schwann cells was detected more frequently in disease specimens than in control specimens. Capillary endothelia of both control and disease specimens expressed I2 antigen. We demonstrate that I2 expression is present on surface membranes of both immune and nonimmune cells of the intestine and colon and show that this expression is more prominent in inflammatory bowel disease than in control intestine and colon. Further studies are required to determine whether this finding is meaningful in terms of antigen presentation and whether this apparent "immune activation" is involved in the pathogenesis of inflammatory bowel disease.

Antibodies, Monoclonal↗
PubMed2001

Intestinal and colonic motor alterations associated with irradiation-induced diarrhoea in rats.

Localized application of ionizing radiation to the gastrointestinal tract frequently elicits responses, which include diarrhoea. The origin of this symptom is not clear but has been attributed to loss of epithelial integrity, together with alterations in motility and increased secretion. The purpose of this study was to examine whether a 10 Gy abdominal gamma irradiation leads to an inflammatory reaction, and to compare intestinal and colonic motility in controls and abdominally irradiated rats 1, 3 and 7 days after irradiation, using an electromyographic technique. The motility parameters analysed were the frequency and velocity of propagation of migrating myoelectric complexes (MMC) in the jejunum and colonic spike activity (long spike bursts; LSB) per 10 min in fasted rats. The MMC frequency was significantly reduced on days 1 and 7 after irradiation and the MMC pattern was markedly disrupted on day 3. The frequency of colonic LSB was significantly reduced on days 1, 3 and 7. Mouth to anus transit was significantly accelerated on day 3 only and diarrhoea was observed at this time. Myeloperoxidase activity in the jejunum and colon was also increased on this day only. It is concluded that irradiation-induced diarrhoea occurs contemporaneously with disruption of MMC in the small intestine.

Animals↗
PubMed1990

[Diagnosis of tumors of the large intestine by colonic ultrasound].

Retrograde instillation of liquid into the colon allows a specific, percutaneous sonographic examination of the colon to be performed. As part of a prospective study of the diagnosis of colonic tumors in 260 patients, this form of colon sonography was examined together with colonoscopy. Sonographically, colonic polyps and carcinomas of the colon manifested as echogenic, parietal masses. Using colonic sonography, it was possible to identify 96% of the carcinomas that had been diagnosed colonoscopically. The sonographic diagnosis of polyps was insufficient if they were smaller than 6 mm: if they were larger than 7 mm, however, diagnostic sensitivity was 91%. The results of this study show that colon sonography is a new, sensitive method in the diagnosis of colonic tumors.

Cecal Neoplasms↗