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PubMed2006

Decreased expression of breast cancer resistance protein in the duodenum in patients with obstructive cholestasis.

BACKGROUND/AIMS: The expression of transporters involved in bile acid homeostasis is differentially regulated during obstructive cholestasis. Since the drug efflux transporter breast cancer resistance protein (BCRP) is known to transport bile acids, we investigated whether duodenal BCRP expression could be altered during cholestasis. METHODS: Using real-time RT-PCR analysis we determined mRNA expression levels in duodenal tissue of 19 cholestatic patients. Expression levels were compared to 14 healthy subjects. BCRP protein staining was determined in biopsies of 6 cholestatic and 6 healthy subjects by immunohistochemistry. RESULTS: We found that in patients with obstructive cholestasis mean duodenal BCRP mRNA levels were significantly reduced to 53% and mean protein staining was reduced to 57%. CONCLUSIONS: BCRP, a transporter for bile acids and numerous drugs, appears to be down-regulated in the human duodenum during cholestasis. The clinical impact of these results has to be investigated in further studies.

ATP Binding Cassette Transporter, Subfamily G, Mem↗
PubMed1981

Healing of incisional wounds in stomach and duodenum. Collagen synthesis.

Collagen synthesis, collagen concentration and collagen content were studied 5, 7, 10, 20 and 40 days postoperatively to elucidate the turnover of collagen in healing incisional wounds in rat stomach and duodenum. Collagen synthesis was elevated relative to total protein synthesis in wound tissues compared to intact tissues and increased throughout the period with peak values at day 5. Also, collagen concentration increased while collagen content remained constant implying equal rates of collagen synthesis and degradation. This shows that the prime tissue response to wounding is changes in collagen metabolism, which correlates with mechanical strength gain.

Animals↗
PubMed1988

Cimetidine and mucosal cell renewal in the duodenum.

Cimetidine may protect gastric and duodenal mucosa by increasing cell turnover. Mucosal cell turnover in the duodenum of 7 control rats receiving intraperitoneal injections of normal saline for 6 days was compared with 8 rats receiving cimetidine for 6 days (500 mg/kg/24 h). Cell proliferation was assessed by autoradiography after injection of tritiated thymidine. The 'leading edge' was defined as the highest tritium-labelled nucleus in the crypt-villus (D/V) column expressed as a percentage of the complete C/V column. Ten C/V columns were measured in each rat. The number of tritium-labelled nuclei in 10 complete C/V columns was also counted in each rat. In the controls the median leading edge was 74.8% (25% quartile 70.6%, 75% quartile 76.2%) and in the rats receiving cimetidine 73.4% (25% quartile 72.1%, 75% quartile 75.9%). The median labelled cell counts were 2,052 (25% quartile 2,008, 75% quartile 2,173) and 1,999 (25% quartile 1,822, 75% quartile 2,041), respectively. These differences were not significant (p greater than 0.1; Mann-Whitney U test). Duodenal mucosal proliferation was assessed in 19 rats 48 h after two subcutaneous injections of 20 mg cysteamine and in another 9 after the same dose of cysteamine plus cimetidine (500 mg/kg/24 h). The median leading edge was 90.1% (25% quartile 84.4%, 75% quartile 92.8%) in cysteamine-treated rats and 76.7% (25% quartile 71%, 75% quartile 79.9%) in rats receiving cysteamine plus cimetidine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1996

Bicarbonate secretion in the guinea pig duodenum: functional characterization of peptide hormone receptors in duodenal enterocytes.

To get information about the peptide hormone receptors involved in duodenal bicarbonate secretion (DBS) and their cellular location, we determined DBS and adenylate cyclase (AC) activity in response to hormones of the vasoactive intestinal polypeptide (VIP)/secretin family of peptides. DBS was determined in an isolated, perfused (24 mmol/1 NaHCO3) loop of the proximal duodenum in urethane- and indometacin-treated guinea pigs. AC stimulation was measured in isolated, homogenized duodenal enterocytes, the histological evaluation of which revealed their villous origin. VIP (10(-9) to 10(-7) mol x kg-1) dose-dependently increased DBS 3.5-fold (p < 0.01); this effect was completely inhibited by the VIP antagonist [D-p-Cl-Phe6,Leu17]VIP (10(-6) mol x kg-1). Glucagon (10(-8) to 10(-6) mol x kg-1) increased DBS 2.1-fold, while secretin (10(-9) to 10(-6) mol x kg-1) had no effect on DBS, but stimulated pancreatic bicarbonate secretion. VIP concentration-dependently increased AC activity 5.6-fold with an EC50 of 1.3 x 10(-9) mol/l. [D-p-Cl-Phe6,Leu17]VIP caused a rightward shift of the VIP concentration-response curve. A Schild plot analysis yielded a slope of 0.85 +/- 0.11, indicating competitive inhibition. While secretin also stimulated AC activity, although 1,000-fold less potent than VIP, glucagon was ineffective. These data indicate that specific VIP receptors, which mediate VIP-stimulated bicarbonate secretion, are present on villous enterocytes. Stimulation of AC by secretin seems to be of pharmacological relevance only and is consistent with the lack of effect of this hormone on DBS. Glucagon likely activates a second transmitter of bicarbonate secretion, or works independently of AC.

Adenylyl Cyclases↗
PubMed1982

A study of two enteroendocrine cells in the duodenum of the gerbil-Meriones unguiculatus.

Gastrin-secreting G cells and enterochromaffin cells have been examined in the duodenum of the gerbil-Meriones unguiculatus. G cells examined by immunoperoxidase and immunofluorescence methods were seen primarily located in the mucosa lining the villi and rarely in the glands of Lieberkühn. They were flask-shaped cells that extended from the basal lamina to the mucosal surface. Immunoreactive gastrin was localized all over in the cytoplasm but was especially concentrated in the juxtanuclear and subnuclear regions. Enterochromaffin cells were identified by a serotonin-specific formaldehyde-induced fluorescence method. These cells were also primarily located in the duodenal villi, were flask-shaped and revealed an intense yellow fluorescence that was especially concentrated in the subnuclear cytoplasm. At the ultrastructural level the enterochromaffin cells showed numerous pleomorphic electron-dense secretory granules especially located in the subnuclear cytoplasm. Microfilament bundles were often observed, especially in the perinuclear region.

Animals↗
PubMed1978

Influence of lanthanum on calcium transport and retention in the rat duodenum.

The present study examined the effects of lanthanum on calcium retention and transport in rat duodenal segments in vitro. Increasing the concentration of lanthanum from 0.1 to 10 mM in both the serosal and mucosal media produced a progressive decrease in tissue calcium retention and calcium transport. The addition of 10 mM lanthanum to the mucosal media alone reduced both calcium retention and transport. The addition of 10 mM lanthanum to the serosal media alone decreased calcium transport but did not alter total calcium retention by the duodenal segments. The results of this study indicate that lanthanum at a concentration of 1--10 mM acts at calcium transport sites in rat duodenum to reduce both calcium uptake and extrusion, with the net result that the addition of lanthanum to either the mucosal media, serosal media or both significantly reduced calcium transport.

Animals↗
PubMed1987

Zinc transfer among proteins in rat duodenum mucosa.

Duodenums from freshly killed stock colony rats were incubated in Krebs buffer containing carrier-free 65ZnCl2 for periods of time between 5 and 60 s. Mucosa cytosol was separated and fractionated by gel filtration on Sephadex G-75. 65Zn was present in two main bands of protein with molecular weights of about 45,000 and 6,500, but the ratio between them rose progressively with time of exposure to the isotope. Addition of metabolic inhibitors greatly lowered the 45,000/6,500 ratio for 65Zn. It is concluded that when zinc enters the mucosal cytoplasm during absorption, it rapidly binds to the 6,500 protein in a passive way and is then transferred to the protein of molecular weight 45,000 by an active process.

Animals↗
PubMed1990

Postprandial release of cholecystokinin after duodenum-preserving total pancreatectomy is independent of intraluminal pancreatic protease activity in dogs.

The effect of meal stimulation, with and without the intraduodenal presence of pancreatic enzymes, on plasma cholecystokinin (CCK) release was studied in order to investigate the role of CCK in the putative feedback mechanism between intraduodenal pancreatic proteases and pancreatic enzyme secretion. Plasma CCK concentrations in response to a semiliquid meal, with and without the supplementation of exocrine pancreatic enzymes, were measured in 8 dogs after duodenum preserving pancreatectomy. With a well-balanced endocrine and exocrine substitution regimen all dogs were kept in good clinical condition, without steatorrhea or significant weight loss, and fasting plasma glucose levels within the normal range. Exocrine supplementation was stopped at least 3 days prior to tests. Basal plasma CCK levels after 3 days without exocrine supplementation (2.5 +/- 0.3 pM) did not significantly differ from the results with supplementation (3.0 +/- 0.5 pM) nor from the preoperative levels (2.3 +/- 0.3 pM). In addition, integrated plasma CCK responses to the meal without exocrine supplementation (330 +/- 37 pM.90 min) were not significantly different from the responses to the meal with exocrine supplementation (303 +/- 49 pM.90 min), or from the postprandial CCK response in the dogs with an intact pancreas preoperatively (390 +/- 100 pM.90 min). It is concluded that the release of CCK in dogs after total pancreatectomy is independent of intraluminal protease activity. It is therefore not likely that CCK mediates the putative feedback mechanism between intraluminal protease activity and pancreatic enzyme secretion in dogs.

Animals↗
PubMed1976

Duodenum-, ileum- and colon-specific antigens.

Antigens specific for discrete segments of the intestinal tract of germ-free rats have been identified. There is at least one duodenum-, one ileum- and one colon-specific antigen. In addition there is an intestine-specific antigen present at all levels of the bowel. The intestine-specific antigens are found in the goblet cell mucus. The intestinal epithelial cell cytoplasm contains antigen which is shared by other tissue.

Absorption↗
PubMed1991

Ontogeny of iron uptake across brush border membrane of guinea pig duodenum and its autoradiographic localisation.

Although the neonatal guinea pig has substantial body iron stores, the rate of duodenal iron absorption is greater than in the mature animal. Here we have used brush border membrane vesicles and biopsy tissue to examine the role of the brush border in changes in Fe2+ and Fe3+ uptake by the duodenum of newborn and adult guinea pigs. We conclude that the brush border membrane is unlikely to be an important site for developmental alterations in iron absorption. Autoradiographic analysis of Fe2+ uptake, however, implies that whilst only the upper villus cells of adult duodenal villi are involved in iron uptake, all enterocytes in the neonate display this function.

Absorption↗
PubMed1986

Identification of progastrin in gastrinomas, antrum, and duodenum by a novel radioimmunoassay.

Recent studies on the gene sequence encoding the human pyloric antral hormone, gastrin, indicate a precursor of 101 residues. We have now raised antibodies to a synthetic analogue corresponding to (Tyr)-human progastrin COOH-terminal pentapeptide. The antibodies could be used in radioimmunoassay to measure this peptide, but they did not react with corresponding fragments of procholecystokinin, porcine progastrin, or other human progastrin-derived peptides, notably heptadecapeptide gastrin (G17), and 34-residue gastrin (G34). Radioimmunoassay of human antral and duodenal extracts revealed a major peak of activity that corresponded to the native COOH-terminal fragment of progastrin, and occurred in approximately equimolar amounts with COOH-terminal G17 immunoreactivity. In addition, there was a minor peak of apparently higher molecular weight material. In some gastrinomas the latter material was the predominant immunoreactive form, and it occurred in higher molar concentrations than any other form of gastrin. Digestion of this material with trypsin liberated peptides that reacted with antibodies specific for the NH2-terminus of G34, and G17. On this basis the high molecular weight component was identified as a form of gastrin that extended from the COOH-terminus of the precursor to a point at least beyond the NH2-terminus of G34, and probably included the entire progastrin sequence. The results suggest differences in posttranslational processing pathways of progastrin in antrum, duodenum, and gastrinomas. They also indicate that the present experimental approach allows the identification of progastrin-like substances, which should open the way to studying the mechanisms of gastrin biosynthesis.

Chromatography, High Pressure Liquid↗
PubMed1998

Intestinal carbamoyl phosphate synthase I in human and rat. Expression during development shows species differences and mosaic expression in duodenum of both species.

The clinical importance of carbamoyl phosphate synthase I (CPSI) relates to its capacity to metabolize ammonia, because CPSI deficiencies cause lethal serum ammonia levels. Although some metabolic parameters concerning liver and intestinal CPSI have been reported, the extent to which enterocytes contribute to ammonia conversion remains unclear without a detailed description of its developmental and spatial expression patterns. Therefore, we determined the patterns of enterocytic CPSI mRNA and protein expression in human and rat intestine during embryonic and postnatal development, using in situ hybridization and immunohistochemistry. CPSI protein appeared during human embryogenesis in liver at 31-35 e. d. (embryonic days) before intestine (59 e.d.), whereas in rat CPSI detection in intestine (at 16 e.d.) preceded liver (20 e.d.). During all stages of development there was a good correlation between the expression of CPSI protein and mRNA in the intestinal epithelium. Strikingly, duodenal enterocytes in both species exhibited mosaic CPSI protein expression despite uniform CPSI mRNA expression in the epithelium and the presence of functional mitochondria in all epithelial cells. Unlike rat, CPSI in human embryos was expressed in liver before intestine. Although CPSI was primarily regulated at the transcriptional level, CPSI protein appeared mosaic in the duodenum of both species, possibly due to post-transcriptional regulation.

Adolescent↗
PubMed1980

Gangliocytic paraganglioma of the duodenum: case report.

A case of gangliocytic paraganglioma of the duodenum, the 25th in world medical literature, is reported. The histologic appearance consists of epithelioid cell nests resembling "Zellballen" of carotid body tumors, together with gangliocyte-like elements. Ultramicroscopically, the cytoplasm of the cells contains round electron-dense granules or a large number of filaments. Occasional cells contain both granules and filaments.

Adult↗
PubMed2005

Long-term prolactin exposure differentially stimulated the transcellular and solvent drag-induced calcium transport in the duodenum of ovariectomized rats.

Prolactin, having been shown to stimulate transcellular active and solvent drag-induced calcium transport in the duodenum of female rats, was postulated to improve duodenal calcium transport in estrogen-deficient rats. The aim of the present study was, therefore, to demonstrate the effects of long-term prolactin exposure produced by anterior pituitary (AP) transplantation on the duodenal calcium transport in young (9-week-old) and adult (22-week-old) ovariectomized rats. We found that ovariectomy did not alter the transcellular active duodenal calcium transport in young and adult rats fed normal calcium diet (1.0% w/w Ca) but decreased the solvent drag-induced duodenal calcium transport from 75.50 +/- 10.12 to 55.75 +/- 4.77 nmol.hr(-1).cm(-2) (P < 0.05) only in adult rats. Long-term prolactin exposure stimulated the transcellular active calcium transport in young and adult AP-grafted ovariectomized rats fed with normal calcium diet by more than 2-fold from 7.56 +/- 0.79 to 16.54 +/- 2.05 (P < 0.001) and 9.78 +/- 0.72 to 15.99 +/- 1.75 (P < 0.001) nmol.hr(-1).cm(-2), respectively. However, only the solvent drag-induced duodenal calcium transport in young rats was enhanced by prolactin from 95.51 +/- 10.64 to 163.20 +/- 18.03 nmol.hr(-1).cm(-2) (P < 0.001) whereas that in adult rats still showed a decreased flux from 75.50 +/- 10.12 to 47.77 +/- 5.42 nmol.hr(-1).cm(-2) (P < 0.05). Because oral calcium supplement has been widely used to improve calcium balance in estrogen-deficient animals, the effect of a high-calcium diet (2.0% w/w Ca) was also investigated. The results showed that stimulatory action of long-term prolactin on the transcellular active duodenal calcium transport in both young and adult rats was diminished after being fed a high-calcium diet. The same diet also abolished prolactin-enhanced solvent drag-induced duodenal calcium transport in young and further decreased that in adult AP-grafted ovariectomized rats. We concluded that the solvent drag-induced duodenal calcium transport in adult rats was decreased after ovariectomy. Long-term prolactin exposure stimulated the transcellular active duodenal calcium transport in both young and adult rats whereas enhancing the solvent drag-induced duodenal calcium transport only in young rats. Effects of prolactin were abolished by a high-calcium diet.

Animals↗
PubMed1981

Immunohistochemical localization of indoleamine 2,3-dioxygenase in the argyrophilic cells of rabbit duodenum and thyroid gland.

To identify the cells containing indoleamine 2,3-dioxygenase, indirect immunofluorescence studies were performed using the monospecific antibody toward the enzyme purified to apparent homogeneity from rabbit small intestine. The antibody precipitated almost 100% of the enzyme activities of various organs or rabbit in a quantitatively similar manner, but did not cross-react with tryptophan 2,3-dioxygenase [L-tryptophan:oxygen 2,3-oxidoreductase (decyclizing), E.C. 1.13.11.11] in the liver. Immunohistochemical localization was studied using rabbit tissue because of the species-specific reactivity of the antibody. In the duodenum, indoleamine 2,3-dioxygenase-immunoreactive cels were found to be sporadically but exclusively localized in the mucosa, a large number being in the basal portion. No staining was seen in the consecutive sections treated with control immunoglobulin. Restaining within the same section using Grimelius' silver technique revealed that the immunoreactive cells coincided with the argyrophilic cells reportedly containing serotonin under physiological conditions. In the thyroid gland, the immunofluorescence was positive in the cluster of the parafollicular cells also shown to be argyrophilic, the cells proposed to have a monoamine-handling capacity specific for serotonin. These results indicate that indoleamine 2,3-dioxygenase is present in those cells rich in serotonin or active in serotonin biosynthesis and further support our previous contention that the enzyme may play an important role in the regulation of the metabolism of indoleamines and their precursors in such cells.

Animals↗
PubMed1986

Cimetropium bromide as a relaxant for the radiological examination of the stomach and duodenum.

A study was carried out to evaluate the efficacy of two different doses of a new hypotonizing agent, cimetropium bromide, as a premedication for X-ray of the stomach and duodenum. Forty consecutive patients were allocated at random to two groups and treated intravenously in double-blind fashion with 5 mg or 10 mg cimetropium bromide. The drug was administered immediately after the first phase of an upper gastro-intestinal series had been completed. Duration of the drug-induced hypokinesia was recorded fluoroscopically. The hypotonizing effect was evaluated by measuring the diameters of the gastric antrum, duodenal bulb and loop on the pre-injection and post-injection radiographs. In both groups, the relaxant effect started promptly (within 1 minute of injection) and lasted for an average of 10 minutes, which was considered adequate for the study. There were no statistically significant differences between the two groups in relaxant activity. The treatments were scored arbitrarily as 'excellent' in 75% of the examinations after the 10 mg dose and in 60% after the 5 mg dose. The difference between the two groups was not significant. Side-effects were few, of mild entity and not dose-related.

Adult↗
PubMed1980

Circadian phase-dependent stimulatory effects of epidermal growth factor on deoxyribonucleic acid synthesis in the duodenum, jejunum, ileum, caecum, colon, and rectum of the adult male mouse.

Epidermal growth factor (EGF) previously isolated from the submandibular salivary glands of mice was injected ip at five different circadian phases into separate sub-groups of adult male CD2F1 mice that had been standardized to 12 h of light alternating with 12 h of darkness. Comparable control groups were injected only with the carrier substance. Four, 8, and 12 h after each of the five injection times, subgroups of five mice were killed. Thirty minutes before sacrifice, each mouse was injected ip with 24 mu Ci tritiated thymidine ([3H]-TdR). Incorporation of [3H]TdR into the DNA of the duodenum, jejunum, ileum, cecum, colon, and rectum was determined. The results demonstrate for the first time that EGF has a stimulatory effect on DNA synthesis in these tissues, particularly in the colon and rectum. Under the conditions of this study, the stimulatory effects of EGF on DNA synthesis in the cecum, colon, and rectum were more dramatic than those in the three regions of the small intestine; in fact, DNA synthesis in the latter was occasionally statistically significantly decreased, particularly for mice killed during the dark phase. Stimulatory effects of EGF on DNA synthesis in the cecum, colon, and rectum were noticed as early as 4 h after injection; however, maximal stimulation occurred 8 and 12 h post injection.

Animals↗