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Effect of carbachol on luminal release of somatostatin from isolated perfused rat duodenum.

The dynamic release of somatostatin-like immunoreactivity (SLI) from duodenum into the lumen was studied in the isolated, vascularly perfused rat duodenum. The luminal release of duodenal SLI was stimulated by a cholinergic agonist, carbachol, and the carbachol-induced release of SLI was completely blocked by atropine, but not by hexamethonium. These data suggest that the luminal release of SLI from rat duodenum is under the control of a cholinergic muscarinic stimulation. The ratio of somatostatin-14 to somatostatin-28 in picograms was about 1 during basal release but increased to approximately 2 during carbachol stimulation.

Animals↗

Differential feeding-related regulation of ubiquitin and calbindin9kDa in rat duodenum.

Analyses of the calcium-binding protein, calbindin9kDa, purified to apparent homogeneity (SDS-PAGE) from rat duodenum, revealed variable contamination by two other 9 kDa proteins (up to 0.2 mol equivalent each) which were identified as ubiquitin and its C-terminal variant, des-Gly-Gly-ubiquitin. We found that the co-purification of these proteins did not reflect a tight molecular interaction but instead their unexpectedly similar physical characteristics in nondenaturing conditions. Like calbindin9kDa, free ubiquitin was abundant (1% and 0.4% of soluble protein, respectively) in duodenum mucosa of 7-8-week-old rats and its concentration varied daily and with feeding status. In rats fed from midnight to 8.30 a.m., the ubiquitin concentration was specifically higher at 10 pm than at 10 a.m. (11.2 +/- 0.7 and 7.7 +/- 0.8 nmol per g wet weight, respectively, P < 0.02), whereas calbindin9kDa tended towards an opposite variation (18.0 +/- 1.9 and 21.8 +/- 1.7 nmol per g, respectively). Based on its unusually high abundance and novel feeding-related variations, ubiquitin must have an important functional role in the rat duodenum which is distinctly regulated from the calcium transport-associated role of calbindin9kDa.

Amino Acid Sequence↗

Comparative study on mucus glycoproteins in rat stomach and duodenum.

The density of mucus glycoprotein compared to that of the corpus, antrum and duodenum was; 1.52, 1.49 and 1.57 g/ml respectively. Carbohydrate composition of gastrointestinal mucus glycoprotein consisted of N-acetylgalactosamine, N-acetylglucosamine, galactose, fucose and sialic acid. Ratios of carbohydrate composition among corpus, antral and duodenal mucus glycoproteins differed. The average length of an oligosaccharide was found to be about 12-13, 14 and 10 sugars in the corpus, antrum and duodenum, respectively. In the corpus, the amino acid content was found to have the following quantitative order: Thr greater than Ser greater than Glx = Pro; in the antrum: Thr greater than Ser greater than Glx; and in the duodenum: Thr greater than Ser greater than Pro. Corpus, antral and duodenal mucus glycoproteins have the blood-group A antigen; antral mucus glycoprotein in particular exhibited strong blood-group A activity.

Animals↗

Effect of insulin on the decreased beta-adrenergic responses of duodenum and atrium isolated from streptozotocin diabetic rats.

1. Decreased beta-adrenergic responses have been reported in both gastro-intestinal tract and atrium of experimentally-induced diabetic rats. The present study was undertaken to investigate in vitro effects of insulin on decreased beta-adrenergic responses of the duodenum and atrium from streptozotocin-diabetic rats. 2. Insulin incubation (16.67 micrograms/ml) in bathing medium for 5 hr enhanced the decreased beta-adrenergic responses in the diabetic rat duodenum, but not those in the diabetic atrium. Incubation of bovine insulin with anti-bovine insulin antibody in the test-tube inhibited the improving effect of insulin on the decreased beta-adrenergic responses of diabetic rat duodenum. 3. In vitro treatment with the same dose of bovine insulin in bathing medium caused a decrease in the beta-adrenergic responses of the atria from both non-diabetic and diabetic rats. Anti-bovine insulin antibody also abolished the inhibitory effect of insulin on the rat atria. 4. These results strongly suggest that the experimental diabetes affects beta-adrenergic responsiveness of the rat gastro-intestinal tract through a different mechanism from that of the rat myocardium.

Albuterol↗

The prevalence and severity of late effects in normal rat duodenum following intraoperative irradiation.

In humans, a portion of the duodenum is often at risk for radiation-induced complications following intraoperative radiation therapy for pancreatic carcinoma. To determine experimentally the prevalence and severity of late effects in the normal mammalian duodenum, 190 rats received single doses of 0, 15, 20, 25, 30, or 40 Gy orthovoltage X rays to temporarily exteriorized 3 cm circumferential segments of duodenum. The animals were killed 2, 6, 8, or 10 months later. Actuarial survival, change in body weight, and a radiation injury score based on eight histopathologic alterations were used as endpoints. Epithelial atypia, intestinal wall fibrosis, serosal thickening, and vascular sclerosis were the dominant histopathologic alterations at all dose levels throughout the 10-month observation period. The prevalence and severity of histologic radiation injury showed sigmoidal dose-response relationships with the plateaus starting at 20 Gy. Doses of 20 Gy or greater also resulted in a substantial loss of body weight and a high level of early deaths (20-80 days). All endpoints indicate that intraoperative doses of 20 Gy or greater are associated with unacceptable risks of late and irreversible complications.

Animals↗

Altered expression of neuronal nitric oxide synthase in the duodenum longitudinal muscle-myenteric plexus of obesity induced diabetes mouse: implications on enteric neurodegeneration.

Type 2 diabetes caused by obesity shows autonomic neuropathy. Molecular mechanism involved in enteric neurodegeneration is not clear. Neuronal nitric oxide synthase (nNOS) is one of the important agents involved in gastrointestinal function. Therefore, expression of nNOS in the duodenum LM-MP of type 2 diabetes model mouse was studied. Real time RT-PCR analysis showed reduction in nNOS expression in male diabetic LM-MP compared to male control. In contrast, female diabetic LM-MP had high level of nNOS mRNA compared to female control. Western blot determination of LM-MP showed reduction in nNOS protein in male diabetic LM-MP and high level of nNOS in female diabetic LM-MP compared to their respective controls. Expression of nNOS observed by Western blot was further confirmed by nNOS immunostaining of the mouse duodenum. TUNEL staining of mouse duodenum showed apoptosis in male diabetic enteric neurons. These studies suggest that nNOS expression in LM-MP varies with gender during early stage of type 2 diabetes. In addition, reduced expression of nNOS is likely to contribute to apoptosis seen in the enteric neurons of male type 2 diabetic mice.

Animals↗

Marginal nutritional status of zinc, iron, and calcium increases cadmium retention in the duodenum and other organs of rats fed rice-based diets.

Dietary minerals Zn, Fe, and Ca are antagonistic to Cd absorption. We showed earlier that rats fed a rice-based diet with a marginal content of these nutrients absorbed more Cd than rats fed adequate Zn-Fe-Ca (Environ. Sci. Technol., 36 (2002) 2684-2692). The present experiment was designed to determine the effects of marginal dietary Zn, Fe, and Ca on the uptake and turnover of Cd in the gastrointestinal tract. Two groups of weanling female rats (six per treatment) were fed a diet containing 40% cooked, dried rice containing 0.6 mg Cd/kg. The diet of one group contained adequate Zn (35 mg/kg), Fe (30 mg/kg), and Ca (5000 mg/kg), while that of the other group contained marginal Zn (6 mg/kg), Fe (9 mg/kg), and Ca (2500 mg/kg). Rats were fed for 5 weeks and then orally dosed with 1g of diet containing rice extrinsically labeled with 109Cd. From 0.25 to 64 days after dosing, 109Cd and total Cd concentrations were determined in intestinal segments. Shortly after dosing, 109Cd, as a percentage of the dose, was about 4 times higher in the duodenum of marginally fed rats than in that of control rats (10% vs 40%, respectively). Sixty-four days after dosing, 109Cd was 10 times higher in marginally fed rats than in controls; however, of the amount at day 1, <0.1% remained at day 64. After 5 weeks, the concentration of elemental Cd in the duodenum of the marginally fed rats was 8 times higher than that of control rats (24 microg/g dry wt. vs 2.9 microg/g dry wt., respectively). Cd concentrations in liver and kidney were 5 times higher in the marginally fed rats than those in controls (liver, 0.81 microg/g dry wt. vs 0.14 microg/g dry wt.; kidney, 4.7 microg/g dry wt. vs 0.92 microg/g dry wt., respectively). These data suggest that marginal intakes of Zn, Fe, and Ca cause the accumulation of Cd in the duodenum, which results in a greater rate of Cd absorption and a greater accumulation in the internal organs. Results are discussed in relation to mineral nutrient status and risk assessment of Cd in natural food sources.

Animal Feed↗

Radiological features of vascular compression of the duodenum occurring as a complication of the treatment of scoliosis (the cast syndrome).

The application of a body cast or the surgical correction of scoliosis is occasionally associated with acute obstructive vascular compression of the duodenum. The clinical and radiological manifestations observed in 10 such patients are described. All cases manifested abdominal distension and vomiting, while epigastric pain was present in 50%. Plain radiographs of the abdomen demonstrated duodenal distension with little gas in the remainder of the bowel in three cases. Barium studies in nine patients demonstrated an intact mucosal pattern and a duodenum dilated proximal to the site where the superior mesenteric vessels crossed it. All cases recovered with non-operative treatment which included nasogastric suction, intravenous fluids, change in position, particularly nursing in the prone position, and, occasionally, cast removal. The obstruction may sometimes persist or recur and then duodenojejunal side-to-side anastomosis is the surgical procedure of choice. The term "cast syndrome" is a misnomer as vascular compression of the duodenum may also occur in patients who are undergoing treatment for scoliosis without the use of a body cast.

Adolescent↗

Radiological and endoscopic diagnosis of infrapapillary carcinoma of the duodenum.

Primary carcinoma of the duodenum is an uncommon cause of epigastric pain, weight loss, and vomiting. The diagnosis is frequently made at a late stage and the prognosis is poor. These tumours may easily be overlooked if the whole of the duodenum is not examined at barium meal or endoscopy. The clinical, radiological and endoscopic findings in three cases are described and the differential diagnosis is discussed. The possibility of an infrapapillary carcinoma of the duodenum should be considered in all patients with unexplained upper gastrointestinal symptoms or blood loss.

Adenocarcinoma↗

Pain and biomechanical responses to distention of the duodenum in patients with systemic sclerosis.

BACKGROUND & AIMS: Abnormalities of the small intestine have been indicated in systemic sclerosis. The aim was to use a new method to study the active-passive mechanical and sensory properties of the duodenum in these patients. METHODS: A volume-controlled ramp-distention protocol was used in the duodenum in 9 patients and 8 healthy controls. The nonpainful/painful sensations, pressure, cross-sectional area, wall tension, and strain were evaluated. Using butylscopolamine for muscle relaxation, the active (contractile muscular component) and passive (other mechanical tissue components) were computed. RESULTS: The contraction amplitude was smaller and the cross-sectional area higher in the patients (P < 0.05). Both the active and passive tension as function of strain was translated to the left in the patients, indicating a stiffer wall. The maximum active tension and the corresponding strain were 62% and 69% lower in the patients (P < 0.05). An association was found between the duration of the disease and the strain (P < 0.05). The perception score was higher as function of pressure, tension, and strain (P = 0.01, P = 0.03, and P < 0.01, respectively) in the patients than in the controls, with strain as the most sensitive variable to describe the sensory response. In 5 patients who complained of regular clinical symptoms, the referred pain area to distention was enlarged. CONCLUSIONS: Systemic sclerosis resulted in increased stiffness and impaired muscle function of the duodenum. The pain evoked by a controlled strain of the gut was increased and can explain many of the symptoms reported in the clinic.

Adult↗

Comparison of endoscopic forceps biopsies and capsule biopsies in determining disaccharidase activity in the duodenum.

Endoscopic biopsy is an accepted technique for obtaining samples of small bowel mucosa for histological examination. In this study a comparison between endoscopic forceps biopsies and capsule biopsies in estimating disaccharidase enzyme activity in the small bowel was evaluated. Disaccharidase levels on 168 consecutive small bowel biopsies obtained by either endoscopic biopsy or capsule biopsy were reviewed retrospectively. There was no significant difference in enzyme activity in samples collected by either method. Another 18 patients had simultaneous endoscopic and capsule biopsies from the second part of the duodenum. Again, there was no difference in enzyme activity between samples collected by either technique at the same level in the duodenum. The disaccharidase activity in forceps biopsies taken from the second part of the duodenum is equivalent to those obtained by capsule biopsy.

Adult↗

Diagnosis and management of gastrointestinal perforations in childhood dermatomyositis with particular reference to perforations of the duodenum.

Four children with dermatomyositis were recently seen with gastrointestinal perforations. The sites of perforation in the four cases were: (1) the duodenum, esophagus, and colon; (2) the duodenum; (3) the distal stomach; and (4) the traverse colon. The gastric and transverse colon perforations were intraperitoneal and easily diagnosed. The gastric perforation was treated successfully by partial gastrectomy. The patient with the colon perforation underwent exteriorization; death occurred from cerebral complications possibly related to vasculitis. Both duodenal perforations were posterior in the distal descending portion. Enzymatic dissection into the right lower quadrant produced confusing clinical and radiographic signs and extensive retroperitoneal necrosis. Successful treatment was obtained by partial gastrectomy, sump drainage of the perforation, and parenteral nutrition. Gastrointestinal perforation is a well-recognized complication of vasculitis in childhood dermatomyositis. In particular, perforations of the distal duodenum, as reported by others, are associated with delay in diagnosis and high mortality.

Child↗

Effects of selective cyclooxygenase-2 inhibitors on alkaline secretory and mucosal ulcerogenic responses in rat duodenum.

Effects of the selective cyclooxygenase-2 (COX-2) inhibitors such as NS-398 and nimesulide on duodenal HCO3- secretory and ulcerogenic responses to mucosal acidification were examined in rats, in comparison with indomethacin, a nonselective COX inhibitor. Duodenal HCO3- secretion in anesthetized rats was increased in response to mucosal acidification. The increased HCO3- response to acid was significantly suppressed by pretreatment with indomethacin (10 mg kg(-1), s.c.), while both NS-398 and nimesulide (10 mg kg(-1), s.c.) had no effect on this response. The luminal release of prostaglandin E2 (PGE2) was increased during and after mucosal acidification, and this response was significantly inhibited by indomethacin but not NS-398 or nimesulide. Indomethacin provoked hemorrhagic lesions in the duodenum when acid hypersecretion was concomitantly induced by histamine (8 mg kg(-1) hr(-1), i.v.), while either NS-398 or nimesulide did not cause damage in the duodenum. Either of these drugs had no effect on histamine-induced acid secretion. On the other hand, both NS-398 and nimesulide showed a significant suppression against carrageenan-induced rat paw edema, similar to indomethacin. The present study supports a mediator role for endogenous PGs in duodenal HCO3- secretion in response to mucosal acidification and suggests that COX-1 but not COX-2 is a key enzyme in regulating this process and maintaining the mucosal integrity against acid in the duodenum.

Animals↗

In vitro characterisation of intramural neural pathways between the duodenum and the sphincter of Oddi of the brush-tailed possum.

The aims of this study were to determine if neural pathways between the duodenum and sphincter of Oddi are intramural, activated by duodenal electrical field stimulation (EFS) in vitro, and contain capsaicin-sensitive primary afferents. The possible involvement of cholinergic (muscarinic and/or nicotinic) and adrenergic receptors in these pathways were also investigated. Duodenal EFS (5-60 Hz, 70 V, 0.5 ms duration, 10 s train) at sites 2 cm oral and 2 cm anal to the sphincter of Oddi-duodenal junction produced frequency-dependent excitatory responses in the sphincter of Oddi, measured by manometry (n = 3). Excitatory responses from duodenal circular muscle were also evident. Tetrodotoxin (1 microM; n = 7) pretreatment abolished both sphincter of Oddi and duodenal responses to duodenal EFS. Crushing the duodenum between the site of stimulation and the sphincter of Oddi-duodenal junction also abolished sphincter of Oddi response. The sphincter of Oddi responses to duodenal EFS at the oral and anal sites were reduced by pretreatment with (i) atropine (100 nM: n = 7) to 19 +/- 6% (P < 0.05) and 22 +/- 8% (P < 0.05) of control respectively. (ii) hexamethonium (100 microM: n = 9) to 10 +/- 2% (P < 0.01) and 6.0 + 2.5% (P < 0.01) of control respectively and (iii) guanethidine (1 microM; n = 6) to 75 +/- 6% (P < 0.05) and 78 +/- 10% (P < 0.05) of control, respectively. Combined pretreatment with phentolamine and propranolol (both 1 microM; n = 7) was without effect, as was capsaicin (1 microM; n = 12) pretreatment. Excitatory intramural pathways between the sphincter of Oddi and the duodenum are primarily cholinergic in nature and contain an adrenergic component. Capsaicin-sensitive primary afferents are not involved.

Adrenergic Agents↗

Correlation of electrophysiological and morphological characteristics of myenteric neurons of the duodenum in the guinea-pig.

Intracellular recording, dye filling and immunohistochemistry were used to investigate neurons of the proximal duodenum of the guinea-pig. Recordings were made from neurons of the myenteric plexus in the presence of nicardipine to quell muscle contractions, using microelectrodes that contained the marker substance Neurobiotin. Preparations were subsequently processed histochemically to reveal nerve cell shapes and immunoreactivity for calbindin, calretinin or nitric oxide synthase. Neurons were distinguished by their shapes and axonal projections as Dogiel type II, Dogiel type I, filamentous descending interneurons and small filamentous neurons. Dogiel type II cells had large cell bodies and multiple axon processes. They each had a broad action potential (mean half-width, 2.9 ms) and a prominent inflection (hump) on the falling phase of the action potential. The majority (70%) of Dogiel type II cells were AH neurons, defined by their having a prolonged hyperpolarizing potential that followed a soma action potential and lasted more than 2 s. Fast excitatory postsynaptic potentials were not recorded from Dogiel type II neurons. Two thirds of Dogiel type II neurons fired phasically in response to intracellularly injected 500 ms depolarizing current pulses and one-third fired tonically. Calbindin immunoreactivity occurred in 70% of Dogiel type II neurons. Dogiel type I neurons had lamellar dendrites and a single axon. They had brief action potentials (mean half-width, 1.7 ms) with no, or a slight hump. They responded to fibre tract stimulation with fast excitatory postsynaptic potentials. Only 2/21 exhibited a prolonged hyperpolarization following action potentials. The majority of Dogiel type I neurons thus belong to the S neuron category. Nine Dogiel type I neurons fired phasically in response to 500 ms depolarizing current pulses, while 12 fired tonically. Filamentous descending interneurons had long, branching filamentous dendrites and a single anally-projecting axon which gave rise to varicose branches in myenteric ganglia. Action potential characteristics of filamentous interneurons ranged between those of Dogiel type II and type I neurons. Small neurons. Small neurons with short filamentous, or few simple dendrites were also characterized. They had single axons, which could be traced either locally to the circular muscle, or to the longitudinal muscle. None of 12 filamentous interneurons or of 10 small filamentous neurons exhibited a prolonged post-spike hyperpolarization, whereas fast excitatory postsynaptic potentials were recorded from a majority. It is concluded that the morphological types of neuron that are encountered in the ileum also occur in the duodenum, but the electrophysiological characteristics of the neurons are more variable for each morphological class. Thus, it is not always possible to predict the morphology of myenteric neurons in the duodenum from their electrophysiological properties. Part of the electrophysiological variability appears to be due to duodenal neurons being more excitable than ileal neurons.

Action Potentials↗

Antispasmodic effect of Achillea nobilis L. subsp. sipylea (O. Schwarz) Bässler on the rat isolated duodenum.

The aim of the present study was to investigate the antispasmodic effect of the total extract of Achillea nobilis L. subsp. sipylea (Schwarz) Bässler (Asteraceae) on rat duodenum. In the first part of experiments, cumulative dose-response curves for acetylcholine (Ach) were obtained and then dose-response curves are repeated after addition of atropine, papaverine and different doses of the extract. In the second part, cumulative dose-response curves to CaCl(2) were obtained in the absence and presence of verapamil and different doses of the extract. In the third part, papaverine and extract were applied to the tissues after contraction with K(+). The extract has exhibited an inhibitory effect on the dose-response curves induced by Ach and CaCl(2) on rat duodenum and significantly reduced the maximal response in a concentration-dependent manner. A similar effect was observed with papaverine but not with atropine on the dose-response curves obtained by ACh. Verapamil also reduced the maximal response in curves induced by CaCl(2). The present results demonstrate that total extract of A. nobilis subsp. sipylea exerts antispasmodic activity on rat duodenum.

Acetylcholine↗

Plasma growth hormone (GH) responses after administration of the peptidergic GH secretagogue KP102 into the oral cavity, rumen, abomasum and duodenum in adult goats.

The study was performed to determine whether orally administered KP102 (also known as GHRP-2) stimulates GH release in adult goats, and how the orally administered KP102 passes through the digestive tract and stimulates GH release in ruminant animals. Five mg/kg body weight (BW) of KP102 dissolved in 9 ml of saline were administered into the oral cavity, rumen, omasum and duodenum of adult goats, and GH release after administration of KP102 was examined. The GH levels were significantly elevated at 20 min after administration of KP102 into the oral cavity, and plasma concentrations of GH remained significantly elevated until 60 min (P < 0.05). The GH levels after administration of KP102 into the abomasum were variable. However, the GH level tended to increase within 30 min after administration, and were significantly higher than those of controls after 120 to 150 min (P < 0.05). The GH levels after administration of KP102 into the duodenum were significantly elevated at 40 min after administration, and plasma concentrations of GH remained significantly elevated until 140 min (P < 0.05). The administration of KP102 into the rumen failed to stimulate GH release. The GH response curves (AUC) produced after administration of KP102 into the abomasum or duodenum were 2.2-fold greater than those for after administration into the oral cavity (P < 0.05). The oral administration of 5 mg/kg BW of KP102 in the powder state, not dissolved in 9 ml of saline, failed to stimulate GH release. These results suggested that orally administered KP102 dissolved in saline transiently stimulates GH release in adult goats, and this phenomenon might be due to small amounts of the peptides entering directly into the abomasum with liquid bypassing the rumen.

Abomasum↗

Villous tumors of the duodenum: reappraisal of local vs. extended resection.

Benign villous tumors of the duodenum are often managed by transduodenal local excision. Risk of local recurrence, coupled with improving safety of radical pancreaticoduodenectomy, has prompted reexamination of the roles of conservative and radical operations. The aim of this study was to determine long-term outcome after local and extended resection in order to identify factors to consider in planning operative strategy. Eighty-six patients (mean age 64 years) with villous tumors of the duodenum managed surgically from 1980 to 1997 were reviewed. Histologic findings, size, presence of polyposis syndromes, and extent of resection were correlated with outcome. Villous tumors were benign adenomas in 64 patients (74%), contained carcinoma in situ in three (4%), and invasive carcinoma in 19 (22%). The presence of cancer was not known preoperatively in 9 (47%) of the 19 with invasive carcinoma. Operative treatment included transduodenal local excision in 53 patients, pancreaticoduodenectomy in 20, pancreas-sparing duodenectomy in five, full-thickness excision in four, and other in six. Among the 50 patients with benign tumors managed by local excision, 17 had a recurrence with actuarial rates of 32% at 5 years and 43% at 10 years; four of the recurrences (24%) were adenocarcinomas. The recurrence rate was influenced by the presence of a polyposis syndrome but not by tumor size. Recurrence of benign villous tumors after local excision is common and may be malignant. Pancreaticoduodenectomy is appropriate for villous tumors containing cancer and may be considered an alternative for select patients with benign villous tumors of the duodenum. If local excision is performed, regular postoperative endoscopic surveillance is mandatory.

Adenocarcinoma↗