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The effects of pressure and pharmacologically active substances on gastric peristalsis in a transmurally stimulated rat soomach-duodenum preparation.

1. A rat stomach-duodenum preparation in which pressures in the body and the antrum and flow through the pylorus could be recorded simultaneously has been used to study the effects of pressure and pharmacologically active substances on the peristalsis induced by transmural stimulation.2. Vagal and transmural stimulation produced vigorous peristalsis and episodic flow. Simultaneous stimulation of the peri-arterial nerves abolished peristalsis and relaxed the pylorus.3. After repeated stimulation the preparation lost tone and peristalsis failed. Peristalsis and tone could then be improved by lowering intragastric pressure. Vigorous peristalsis could be restored in an inactive preparation by eserine and more transiently by 5-HT.4. Drugs which increased smooth muscle tone improved peristalsis and, under the conditions used, they reduced flow. Eserine was more active in this respect than acetylcholine or 5-HT.5. Adrenaline and hyoscine abolished peristalsis and caused the stomach and the pylorus to relax.6. The results suggest that the peristaltic activity of the antrum is more important than the tone of the pylorus itself in controlling gastric emptying.

Acetylcholine↗

Comparison of the actions of porcine secretin and extracts of chicken duodenum on pancreatic exocrine secretion in the cat and turkey.

1. Extracts were prepared of chicken duodenum and their actions on pancreatic secretion in urethane anasthetized turkeys and in conscious cats were compared with those of pure natural porcine secretin. 2. The chicken extracts and porcine secretin stimulated dose-dependent increases in the rate of flow, but not the rate of protein secretion, from the pancreas in cats and turkeys. 3. Porcine cholecystokinin stimulated both the rate of flow and the rate of protein secretion from the pancrease in turkeys. 4. The doses of chicken extract required to evoke half maximal rates of flow of pancreatic juice were similar in the turkey (0-55 mg/kg) and in the cat (0-72 mg/kg). The highest concentration of bicarbonate recorded in the turkey responses was 30 m-equiv/l. compared with 112 m-equiv/l. in the cat. 5. The dose of porcine secretin required for half maximal rate of flow in the bird (5-9 mug/kg) was 180 times higher than in the mammal (0-33 mug/kg). In the cat the duration of responses to porcine secretin was significantly greater than to the chicken extract. 6. It is concluded that in birds there is a factor with biological properties similar but not identical to those of porcine secretin, and that this factor may regulate pancreatic secretion by a mechanism resembling the secretin mechanism in mammals.

Animals↗

Comparative study of the smooth muscle layers of the rabbit duodenum.

1. Intracellular electrodes were used to compare the electrical activity of smooth muscle cells from the longitudinal and circular layers of the rabbit duodenum and their responses to stimulation of the intramural nerves. 2. The longitudinal muscle cells had an average membrane potential of 52 mV when measured between slow waves. Spontaneous action potentials were superimposed on every slow wave. 3. The circular muscle cells had a higher membrane potential of 64 mV although the amplitude of the slow waves was similar to that of the longitudinal muscle cells. Spontaneous action potentials were rarely observed in the circular muscle cells. 4. Lowering the temperature from 36 to 30 degrees C caused a reduction in the membrane potential of the longitudinal muscle cells but not in the circular muscle cells. However, the amplitude of the slow waves of the two layers was reduced to a similar extent. 5. Electrical stimulation produced advances of the slow wave cycles if the stimuli were applied between slow waves. The responses of the cells from the two layers were identical. 6. Under normal conditions, electrotonic coupling was observed only in cells of the muscle layer whose long axis was aligned along the direction of the applied current. 7. In the longitudinal muscle, cholinergic responses blocked by atropine were observed. Inhibitory potentials were the predominant response in the circular muscle. 8. Excitatory responses were recorded in 9% of the circular muscle cells. "Off' excitation following termination of a train of repetitive stimulation pulses was also observed. 9. The differences in membrane potentials, spontaneous spiking activities, neural responses, and the failure to demonstrate good electrotonic coupling between the muscle layers suggest that there was poor electrotonic interaction between the muscle layers. The amplitude of the slow waves of the two layers was nevertheless similar. Thus the validity of the hypothesis that slow waves were transmitted passively from the longitudinal layer into the circular layer through electrotonic coupling must be questioned.

Animals↗

Modulation of vagal efferent fibre discharge by mechanoreceptors in the stomach, duodenum and colon of the ferret.

1. A single-fibre-dissection technique was used to investigate the reflex modulation of vagal efferent fibre discharge by afferent fibres from various parts of the gastrointestinal tract of the urethane-anaesthetized ferret. 2. All but four of the 168 efferent fibres isolated in this study were spontaneously active. The majority of these had discharge frequencies of less than 6 spikes/sec. 3. All the efferent units received an afferent input from mechanoreceptors in the stomach. Two main types of response to gastric distension were seen: (i) an increase in efferent discharge and (ii) a decrease or complete suppression of efferent discharge. 4. The vagal efferent discharge was also modulated by duodenal and colonic distension, with the major effect being one of inhibition. 5. Bilateral vagotomy completely abolished the response to gastric distension in 68% of the units tested. The response to colonic and duodenal distension, however, was relatively unaffected by vagotomy. Thus the vagus provides the major afferent pathway from the stomach to these vagal efferent fibres, whilst the major input from the duodenum and colon is via a non-vagal pathway. Both vagal and splanchnic afferents therefore converge on to the vagal nucleus. 6. The destinations of these vagal efferent fibres and their possible functions are discussed.

Action Potentials↗

Activation of enteric nerve pathways in the guinea-pig duodenum by cholecystokinin octapeptide and pentagastrin.

The action and mechanism of action of cholecystokinin octapeptide (CCK-8) and pentagastrin on isolated segments of guinea-pig duodenum were examined using contractility studies and by intracellular recordings made from smooth muscle cells. Both CCK-8 and pentagastrin caused an excitatory contractile response. The threshold concentration ranged from 5 X 10(-11) to 10(-9) M for CCK-8 and 5 X 10(-10) to 10(-8) M for pentagastrin. The excitatory response was abolished by tetrodotoxin (3.1 X 10(-6) M) and atropine (1.5 X 10(-6) M) and inhibited by d-tubocurarine (up to 2.9 X 10(-5) M). In the presence of atropine a proportion of preparations relaxed in response to CCK-8 (nineteen of thirty-one) and pentagastrin (thirteen of seventeen). This response was only seen at high concentrations of the peptides (10(-8)-10(-7) M) and was abolished by tetrodotoxin (3 X 10(-6) M). Intracellular recordings from duodenal smooth muscle revealed multiple excitatory junction potentials (e.j.p.s) in response to CCK-8 and to pentagastrin. These e.j.p.s were identical to those evoked by transmural nerve stimulation and were abolished by atropine (1.5 X 10(-7) M) and by tetrodotoxin (3 X 10(-6) M). Inhibitory junction potentials (i.j.p.s) were not recorded in response to the peptides except on one occasion. It is suggested that CCK-8 and pentagastrin cause an increase in duodenal motility by the selective activation of excitatory pathways in the enteric nervous system.

Animals↗

Effect of opioid peptides on circular muscle of canine duodenum.

1. The effects of opioid peptides on inhibitory transmission in the circular muscle layer of canine duodenum were investigated in vitro using simultaneous mechanical and intracellular electrical recording techniques. 2. Exogenously added [Met5]enkephalin, [Leu5]enkephalin and dynorphin (1-13) decreased the amplitude of non-adrenergic, non-cholinergic inhibitory junction potentials (IJPs) evoked by transmural nerve stimulation. 3. A selective delta-receptor agonist, DPDPE ([D-Pen2, D-Pen5]enkephalin), and a selective mu-receptor agonist, PL017 (Try-Pro-NMePhe-D-Pro-NH2), decreased the amplitude of IJPs whereas a selective kappa-receptor agonist, U-50,488H ([trans-3,4-dichloro-N-methyl-N-(2-91-pyrolidinyl)-cyclohexyl]- benzeneacetamide methanesulphonate), in large doses (1 microM) produced only a small reduction. 4. A selective delta-receptor antagonist, ICI-174,864, blocked the effect of DPDPE but not that of PL017 suggesting the presence of distinct delta- and mu-opioid receptors on inhibitory motor nerves. 5. Exogenously added dynorphin (1-13) decreased the amplitude of IJPs. delta-Opioid receptors appeared to be involved because ICI-174,864, a selective delta-antagonist, blocked the inhibitory effect of exogenously added dynorphin (1-13). 6. The inhibitory effect of the opioid peptides was still observed in preparations of circular muscle devoid of myenteric and submucosal plexuses, indicating that the site of action was on inhibitory motor nerve fibres located within the circular muscle layer and not on neuronal cell bodies in the enteric plexuses. 7. It was concluded that in the canine small intestine, opioid peptides could modulate release of inhibitory transmitter(s) at or near nerve terminals of inhibitory motor nerves innervating circular muscle cells.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

Segmentation induced by intraluminal fatty acid in isolated guinea-pig duodenum and jejunum.

Small intestinal movements depend on the composition of the chyme with mixing predominating at high nutrient levels and propulsion being prevalent at low nutrient levels. The mechanisms coupling nutrients to motility are unknown. We used computer analysis of video recordings of isolated guinea-pig duodenum, jejunum and ileum to examine movements induced by a fatty acid, decanoic acid. Increasing intraluminal pressure past a threshold using control saline consistently evoked propulsive reflexes: lumen-occluding constrictions appeared at the oral end propagating at 20.4 +/- 2.4 mm s(-1) (mean +/-s.d., jejunum) to the anal end before being repeated until the intraluminal pressure was returned to control. Subthreshold pressure increases sometimes evoked a transient series of constrictions appearing at the oral end and propagating anally at 18.4 +/- 4.7 mm s(-1) (jejunum). At basal pressures, decanoic acid dose-dependently induced motor activity consisting of 40-60 s episodes of constrictions separated by 40-200 s periods of quiescence and lasting up to 2 h. Five contraction patterns were identified within episodes including localized stationary constrictions; constrictions that propagated slowly (5-8 mm s(-1)) for short distances orally or anally; and constrictions that propagated orally or anally for the length of the preparation at 14-20 mm s(-1). Decanoic acid induced motor activity was reversibly abolished by tetrodotoxin (3 microm), hyoscine (1 microm) and hexamethonium (100 microm), but was insensitive to blockade of P2 purinoceptors by PPADS (60 microm). Thus, decanoic acid induces motor activity equivalent to segmentation in guinea-pig small intestine in vitro and this depends on intrinsic neural pathways.

Animals↗

Circadian rhythm in uptake of tritiated thymidine by kidney, parotid, and duodenum of isoproterenol-treated mice.

The total uptake of [(3)H]thymidine by the mouse parotid gland, kidney, and duodenum exhibits a circadian rhythm. A single injection of isoproterenol changes the phasing and amplitude of these rhythms. Depending on the organ, there are certain points in the circadian time structure when isoproterenol stimulates or inhibits the uptake of thymidine; at other time points there is no difference between the responses to isoproterenol and to saline.

Animals↗

The endocrine polypeptide cells of the human stomach, duodenum, and jejunum.

Thirty specimens of stomach, duodenum, and jejunum, removed at operation, were examined by optical microscopical, cytochemical, and electron microscopical techniques. The overall distribution of four types of endocrine polypeptide cell in the stomach, and three in the intestine, was determined. The seven cell types are described by names and letters belonging to a scheme for nomenclature agreed upon at the 1969 Wiesbaden conference on gastrointestinal hormones. The gastrin-secreting G cell was the only cell for which firm identification with a known hormone was possible. Although there was wide variation in the distribution of the various cells, from one case to another, striking differences were nevertheless observable, with respect to the G cell, between antra from carcinoma and from ulcer cases.

Bile Duct Neoplasms↗

Cellular localization of gastric inhibitory polypeptide in the duodenum and jejunum.

Indirect immunofluorescence studies using an antiserum to purified porcine gastric inhibitory polypeptide indicate, in the gastrointestinal tract of dog and man, that this polypeptide is present in cells situated predominantly in the mid-zone of the glands in the duodenum and, to a lesser extent, in the jejunum. Absolute correlation of the gastric inhibitory polypeptide cell with one or other of the known endocrine-like cells identified by electron microscopy awaits confirmation by electron immunocytochemistry. It is here identified as an endocrine polypeptide cell of the APUD series and, provisionally, as the D(1) cell. While the hormonal status of a given polypeptide depends ultimately on physiological experiments the present results strengthen the view that gastric inhibitory polypeptide is indeed a hormone.

Animals↗

The electrical and motor actions of gastrointestinal hormones on the duodenum in man.

The electrical and motor activity was recorded from the duodenum in 16 conscious human subjects in resting conditions. The main electrical wave form variously known as the pace-setter potential or slow wave was constantly present and periodically accompanied by a second electrical trace consisting of rapid bursts of fast waves or action potentials which were related to motor waves. Secretin and the synthetic analogue of gastrin, pentagastrin, were given in separate tests and their complementary actions on myoelectrical activity are reported. In general, secretin (in six subjects) depressed and pentagastrin (in eight subjects) enhanced motor activity and bursts of action potentials.

Action Potentials↗

Histological appearances of oesophagus, antrum and duodenum and their correlation with symptoms in patients with a duodenal ulcer.

Clinical data and histology from the oesophagus, gastric antrum, and duodenum were collected from 36 patients undergoing surgery for duodenal ulcer. Gastritis was present in 94% of the patients (25% of atrophic type), oesophagitis in 72% and duodenitis in 39%. Abnormal biopsies were present from all three sites in 33% of the patients. Only one patient showed three normal biopsies. The low incidence of duodenitis does not support the theory that duodenitis is part of the same spectrum as duodenal ulcer. Heartburn was related to the presence of gastritis (100%) and oesophagitis (76%) but not to duodenitis (52%). No relationship was found between the length of history, severity of pain, and histological abnormalities.

Adult↗

Adenovirus 12 E1A gene detection by polymerase chain reaction in both the normal and coeliac duodenum.

A 12 amino acid sequence from the adenovirus 12 E1B protein is homologous at the protein level with a similar 12-mer derived from the wheat protein A-gliadin. It has been suggested that exposure to Ad 12 could sensitise individuals to gliadins with resultant gluten sensitive enteropathy. In this study, the polymerase chain reaction (PCR) was used to analyse duodenal biopsy tissue from patients with coeliac disease for the presence of Ad 12. The sensitivity of the assay system was at least 1 in 10(5) cells and specificity was confirmed both by probing with an internal oligonucleotide and by direct sequencing. Ad 12 sequences were detected in three of 17 patients with adult coeliac disease and in five of 16 adult controls with normal duodenal biopsies. Since exposure to the virus would be predicted to occur in infancy we also studied patients with childhood coeliac disease diagnosed at less than 1 year of age. Ad 12 was positive in three of 10 childhood coeliac patients and one of seven controls. In addition, we studied a cohort of patients who presented with a diarrhoeal illness and associated anti alpha gliadin antibodies in 1983. These patients had duodenal biopsies performed at this time. One of three patients with abnormal histology had detectable Ad 12 while two of 14 with normal findings were positive for Ad 12. Finally, the potential oncogenic nature of Ad 12 prompted examination of a group of patients with intestinal tumours. Ad 12 DNA was, however, in only two of 19 tumour samples tested. These data indicate that Ad 12 can be successfully detected using PCR on paraffin embedded tissue. Furthermore, Ad 12 was detected at a relatively high level in normal duodenum. The results do not, however, support the hypothesis that prior exposure to Ad 12 is implicated in the pathogenesis of coeliac disease.

Adenocarcinoma↗

Effect of Helicobacter pylori eradication on gastric metaplasia of the duodenum.

Helicobacter pylori associated duodenal ulcers occur in patches of gastric metaplasia. The pathogenesis of gastric metaplasia is unclear, but it has been produced in experimental animals by acute injury and has been shown to be present to a greater extent of H pylori positive subjects. This study aimed to discover if gastric metaplasia regressed with eradication of H pylori or healing of duodenal ulcers, or both. Thirty two duodenal ulcer patients with H pylori infection confirmed by biopsy urease test and by antral histological examination were studied. Patients were treated with triple therapy (deNol 240 mg twice daily, amoxycillin 500 mg three times daily, and metronidazole 400 mg three times daily) for two weeks after the first endoscopy and were subsequently re-endoscoped. Three duodenal bulb biopsy specimens were obtained per patient at each endoscopy. Biopsy sections were stained with haematoxylin and eosin to determine the severity of duodenitis, and with diastase periodic acid-Schiff/alcian blue to assess the extent of gastric metaplasia. Slides were assessed by two histopathologists unaware of treatment status. H pylori was eradicated in 63% of subjects and all ulcers were healed at follow up. The median extent of gastric metaplasia at the start of treatment and 6-18 months (median 10) after treatment was compared in the two groups. Gastric metaplasia declined in eradicators from 16% to 8% (p < 0.05) while in non-eradicators there was no significant change (25% initially and at follow up). A positive relation between extent of gastric metaplasia and duodenal inflammation score was present before treatment (r(s) = 0.74, p < 0.001) and was unchanged after treatment in the non-eradicator group (r(s) = 0.89, p < 0.001). In the eradicator group, however, the inflammation score had significantly declined (p < 0.02) and the close relation with gastric metaplasia was no longer present. These results suggest that H pylori itself is at least in part responsible for producing gastric metaplasia of the duodenum.

Adult↗

Immunochemical studies of the endocrine cells of the gastrointestinal tract. II An immunoperoxide technique for the localization of secretin containing cells in human duodenum.

Endocrine cells containing secretin have been identified in the epithelium lining human duodenum by direct and indirect immunoperoxidase techniques using immune sera raised against pur natural secretin. The techniques were applied to sections of carbodiimide-fixed tissue embedded in polyethylene glycol. Some sections, stained by a modified indirect technique, were processed for electron microscopy; secretin-containing granules were present by ultrastructural preservation was too poor to be of value. The potential advantages of a peroxidase technique over fluorescein-coniugated antisera are discussed.

Carbodiimides↗

A reliable method for the simultaneous identification of H pylori and gastric metaplasia in the duodenum.

While an association of Helicobacter pylori infection with duodenal mucosa gastric metaplasia has been described, the details and extent of the interaction are lacking. One of the limiting factors has been the lack of a staining technique that allows simultaneous visualisation of the bacteria and gastric metaplasia in the duodenum. This report describes a new stain that allows the simultaneous visualisation of duodenal gastric metaplasia and H pylori and compares the new stain with the component stains.

Duodenum↗

Carcinoma of the duodenum.

We report two patients with primary adenocarcinoma of the duodenum who underwent successful pancreatico-duodenectomy (modified Whipple operation). One patient died from an unrelated cause three years following surgery whilst the other remains well and clinically free of disease 3 years after resection. An aggressive surgical policy in patients with this rare tumour seems justified.

Adenocarcinoma↗

Trophic effects of chronic bethanechol on pancreas, stomach, and duodenum in rats.

Rats received a daily injection of 2, 6, or 12 mg kg-1 bethanechol for 7 or 14 days. Pancreatic weight and content of protein, amylase, and chymotrypsinogen were increased in a dose and time dependent fashion by bethanechol. After 14 days of treatment with the highest dose, pancreatic weight and total pancreatic DNA content increased to 1.18 times control (P less than 0.05) while protein increased to 1.25, amylase to 1.85, and chymotrypsinogen to 1.72 times control. There was a slight increase in oxyntic gland area weight in bethanechol-treated rats, but content of DNA, protein, and pepsinogen were not changed. Bethanechol had no effect on duodenal weight or content of DNA, protein, or maltase. Acute administration of 12 mg kg-1 bethanechol increased circulating gastrin levels for at least 4 h in unanesthetized rats. We conclude that long-term treatment with a cholinergic agonist produces pancreatic hyperplasia and increases protein and enzyme content. Under the conditions of this study, no effects were seen on oxyntic gland area of stomach or duodenum.

Animals↗