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Biomedical subjects

P Layer

Publications and source records attributed to P Layer.

At least 91 records · Page 5Linked to original sources
PubMed1994

[Ocular involvement in Whipple disease].

PATIENTS AND METHODS We present a 57-year-old white man with progressive deterioration of vision, who had a prolonged history of weakness, migratory arthralgias and loss of weight. Bilateral panuveitis, with iritis, inflammatory vitreous opacities associated with small, round, grayish retinal lesions. The duodenum showed a swollen mucosa, which was flecked over with pinpoint grayish grains. A small-bowel biopsy disclosed PAS-positive granules in the macrophages of the lamina propria mucosa, pathognomonic of Whipple's disease. RESULTS After antibiotic treatment with trimethoprim and sulfamethoxazole there was no relapse of the panuveitis during the follow-up period of 18 months.

Humans↗
PubMed1993

[The terminal ileum as a co-regulator of cyclic interdigestive pancreatic secretion in man].

Nutrients present in the ileum of humans can modulate endogenously stimulated pancreatic secretion. To determine whether cyclic interdigestive pancreatic secretion can also be influenced by nutrients in the ileum, six fasting volunteers were intubated with an oro-ileal multi-lumen tube for perfusing test and marker solutions, aspiration of duodenal contents and recording of motility. At the beginning of the interdigestive cycle, the ileum was perfused intermittently with solutions of carbohydrates, proteins or lipids in the physiological amounts observed in the ileum after a meal; saline solution was perfused as a control. After saline, protein and calcium perfusion, the expected periodic increase in chymotrypsin secretion was observed during phase II of the interdigestive cycle (p < 0.05 vs phase I). In contrast, carbohydrates and lipids inhibited the phase-II-associated increase in pancreatic secretion. These findings indicate that the ileum may be involved in the regulation of human interdigestive pancreatic secretion.

Adult↗
PubMed1993

[The synthetic somatostatin analog octreotide: effect on interdigestive pancreas secretion and gastrointestinal motility in man].

The aim of the present study was to determine the effects of a therapeutical dose of the long-acting cyclic somatostatin analogue octreotide (SMS 201-995) on cyclical interdigestive small intestinal motor function and exocrine pancreatic secretion in humans. Five fasting healthy subjects swallowed a gastroduodenal multi-lumen tube assembly and received continuous infusions of saline and octreotide (720 ng/kg/hr) for at least one interdigestive motor cycle or two hours. Upper gastrointestinal motility was recorded continuously by standard manometry. Duodenal chymotrypsin outputs were measured at 15 minutes intervals using polyethylene glycol as a dilution marker. Octreotide significantly decreased the length of the interdigestive motor cycle to one third of the control period (p < 0.01). Phase II proportion was reduced to less than 5% of the cycle length (controls: 66%; p < 0.01). The propagation velocity of octreotide-induced motor activity fronts was significantly slower compared with migrating motor complexes during the control period (controls: 6.8 +/- 0.4 cm/min, octreotide: 2.3 +/- 0.4 cm/min; p < 0.05). Overall duodenal chymotrypsin output was markedly inhibited by octreotide (5% of controls; p < 0.01). Moreover, during octreotide administration coupling between interdigestive motor activity and pancreatic exocrine enzyme secretion was disrupted. In conclusion short administration of a therapeutical dose of octreotide exerts similar effects on upper intestinal interdigestive human motor secretory parameters as naturally occurring molecular forms of somatostatin at pharmacological doses.

Adult↗
PubMed1993

[Effect of the prostaglandin E2 analog nocloprost on motility and acid clearance of the tubular esophagus in man].

UNLABELLED: The effects of the E2 prostaglandin nocloprost (9b-chloro-16,16-dimethyl-prostaglandin E2) on esophageal motility and acid clearance were evaluated in a double-blind placebo controlled study in six healthy volunteers. Motility of the tubular esophagus was measured by means of a low compliance perfusion system (four channels, recording ports 10 cm apart, the distal localized in the stomach). After eight hours fasting and a 60-minutes baseline measurement (with standardized swallowing of 5 cc water every three minutes) the volunteers swallowed on two separate days in randomized order either 200 micrograms nocloprost (solved in 50 cc water) or placebo. Then the motility of the tubular esophagus was assessed for another 60-minutes during standardized swallowing. Thereafter, the motility probe was removed and a pH-electrode placed 10 cm above the lower esophageal sphincter. In order to assess the esophageal clearance, four times 5 cc of 0.1 N HCl were infused into the esophagus 10 cm above the electrode and the time between the infusion of HCl and the increase of the pH above pH 4.0 measured. RESULTS: In five out of six volunteers the duration of esophageal contractions were decreased after administration of nocloprost as compared to placebo (6.23 +/- 1.2 vs. 5.80 +/- 1.1 seconds, p = 0.07). In contrast, neither propagation velocity, nor amplitude of contraction or acid clearance were significantly affected by nocloprost. CONCLUSIONS: These findings suggest that in healthy volunteers nocloprost changes the pattern of esophageal contractions (duration) without affecting amplitude, velocity of propagation or acid clearance.

Adult↗
PubMed1993

Cholinergic regulation of phase II interdigestive pancreatic secretion in humans.

Small fluctuations in cholinergic input may be involved in the regulation of human interdigestive pancreatic secretion. To determine the effects of small changes in cholinergic tone on phase II interdigestive trypsin secretion, we gave cholinergic agonists or antagonists to 17 healthy fasting subjects who underwent gastrointestinal intubation. Duodenal trypsin outputs, gastroduodenal motility, and plasma levels of pancreatic polypeptide (PP) as a marker of cholinergic tone were measured during intravenous infusion of bethanechol (0, 5, or 40 micrograms.kg-1.h-1) or atropine (0, 4, or 16 micrograms.kg-1.h-1) given during phase II alone or in combination based on a 3 x 3 factorial design. Data were evaluated by a response surface analysis of the average log values for the test period (using the average of log values of the control period as a covariate). Bethanechol increased trypsin output (p < 0.05) and plasma concentrations of PP (p < 0.05) within the ranges of spontaneous fluctuations of trypsin output and PP during phase II, but did not disrupt the periodicity of pancreatic secretion or the characteristic cyclical pattern of interdigestive motility and induction of phase III activity. Atropine markedly decreased trypsin output (p < 0.05) and plasma concentrations of PP (p < 0.05) and abolished the cycling of interdigestive pancreatic secretion and motor activity. These data suggest the hypothesis that cholinergic pathways participate in the control of interdigestive pancreatic secretion during phase II, while enzyme secretion during phase III may be regulated by other mechanisms.

Acetylcholine↗
PubMed1993

Modulation of human periodic interdigestive gastrointestinal motor and pancreatic function by the ileum.

Following ingestion of a meal, unabsorbed nutrients may reach the distal intestine partly after the termination of the prandial period, i.e., in the presence of interdigestive motor and secretory patterns. To determine if interdigestive motility and pancreatic enzyme secretion are modulated by the delivery of nutrient into the ileal lumen, six fasting volunteers were intubated with an oroileal multilumen tube system that permitted multiple small intestinal manometry, gastric and duodenal aspiration, and perfusions of marker and test solutions. Ileal perfusions of nutrient or saline solutions were started during phase I of the interdigestive motility cycle. Ileal perfusion with carbohydrate or lipids increased the duration of motor quiescence and decreased the length of the interdigestive cycle, mainly by decreasing the proportion of phase II activity compared with ileal saline (p < 0.01). Pancreatic outputs of amylase, trypsin, and chymotrypsin prior to ileal perfusions were low because, due to the protocol, perfusions were started during phase I. With ileal saline, enzyme outputs increased (p < 0.05) in association with the occurrence of phase II motility, as expected. By contrast, ileal carbohydrate and triglyceride perfusion prevented the phase II-associated increase in enzyme outputs (p < 0.05). The data suggest that the presence of nutrients within the ileal lumen may modulate interdigestive motor and pancreatic functions.

Adult↗
PubMed1993

Oroileal transit of slow release 5-aminosalicylic acid.

The predominant active anti-inflammatory moiety in chronic inflammatory bowel disease is 5-aminosalicylic acid (5-ASA). As unprotected 5-ASA is rapidly absorbed in the upper gastrointestinal tract several slow release preparations have been developed to permit passage of 5-ASA to the lower small bowel and to the colon. To investigate luminal kinetics and extent of the release of 5-ASA intraluminal concentrations and loads of this compound together with that of its main metabolite acetyl-5-aminosalicylic acid (ac-5-ASA) were studied, over 15 hours after giving the slow release preparation Salofalk at a dose of 500 mg orally together with a test meal. Plasma concentrations and urinary excretion were also measured. Six healthy volunteers swallowed an 11 lumen oroileal tube, which allowed marker perfusion, aspiration of luminal content from the duodenum, mid-jejunum, and ileum, and recording of intestinal motility. Emptying of 5-ASA into the duodenum started after emptying of the meal, together with the first phase III of interdigestive motility. Mean luminal concentrations of 5-ASA and ac-5-ASA increased continuously from duodenum (both: 15 to 30 micrograms/ml) to ileum (60 to 110 micrograms/ml and 80 to 150 micrograms/ml respectively) over three hours and decreased over the next three hours. During 10 hours after eating, 30% of the total dose passed the ileum in solution and another 10% were excreted in urine. Thus about 60% reached the colon unreleased from tablets and another 30% were in solution. The ratio of 5-ASA and ac-5-ASA in solution was about 1:1 in the duodenum and 1:1.5 to 1:2 in the more distal small intestine. The data suggest that the large quantities of intraluminal ac-5-ASA are generated in the intestinal mucosa and reach the lumen by back diffusion. The results show that most of the 5-ASA from this slow release preparation is delivered into the colon, which explains its effectiveness in ulcerative colitis. The considerable luminal concentrations already present in the distal ileum might justify therapeutic trials in Crohn's disease.

Administration, Oral↗
PubMed1993

Fate of pancreatic enzymes in the human intestinal lumen in health and pancreatic insufficiency.

The activities of pancreatic enzymes decrease during their passage from the duodenum to the terminal ileum, but degradation rates of individual enzymes are different. Whereas lipase activity is lost most rapidly, proteases and amylase are more stable. The mechanism by which lipase activity is destroyed is proteolysis, mainly by the action of chymotrypsin. This mechanism is also operative in patients with chronic exocrine pancreatic insufficiency. It explains why fat malabsorption develops earlier compared with protein or starch malabsorption. The substitution of lipase is also more difficult than that of other enzymes, because it is more rapidly destroyed by proteases. Conversely, inactivation of proteases improves intraluminal activity of lipase not only in healthy individuals but also in patients with chronic pancreatitis. Other factors that contribute to problems in lipase substitution therapy include acid-peptic destruction of unprotected enzyme preparations and unphysiological particle sizes of enteric-coated capsules or pellets. Recent data suggest that the adaptation of the diameter of enteric-coated pancreatin micropellets into the range that permits gastric emptying in synchronicity with the meal improves their digestive efficacy.

Amylases↗
PubMed1992

Novel generation of hormone receptor specificity by amino terminal processing of peptide YY.

The physiological significance of multiple Y receptors has not been determined since until recently only one form of endogenous agonists was known, namely PYY1-36 and NPY1-36. Recently, a new molecular form of PYY was characterized as des(Tyr-Pro)PYY (PYY3-36 or PYY-II). Its ability to interact at various Y receptors was not characterized. Analytical chromatography of fresh canine colon extracts shows two peaks of immunoreactivity eluting in the positions of PYY-II and PYY1-36 (PYY). PYY-II was about 40% of the total PYY immunoreactivity indicating that it is one of the major forms of PYY expressing its biological activity. It is shown that PYY-II will not displace label from the Y1 receptors found on a human neuroblastoma cell line. It is further shown that PYY-II is as potent as PYY for the inhibition of pancreatic secretion, which must occur through Y2 receptors. The enzymatic removal of Tyr-Pro from PYY to form PYY-II must therefore regulate the relative expression of a non-selective agonist (PYY) to a highly selective Y2 agonist (PYY-II). Amino terminal processing of PYY represents a novel type of regulation of peptide hormone specificity. It has important biological implications for PYY and potential relevance for other peptide hormone receptor systems.

Animals↗
PubMed1992

Somatostatin 28 and coupling of human interdigestive intestinal motility and pancreatic secretion.

To determine the effects of small increases in somatostatin 28 plasma concentrations on human interdigestive gastrointestinal motility and pancreatic secretion, six fasting volunteers were intubated with gastroduodenal multilumen tubes and motility and pancreatic enzyme secretion were measured. Subjects received intravenous NaCl and somatostatin 28 at 11 and 44 pmol.kg-1.h-1 for 120 minutes or at least one interdigestive cycle. The two doses increased plasma somatostatin 28 levels within the physiological or into the supraphysiological range, respectively. Somatostatin 28 at 11 and 44 pmol.kg-1.h-1 decreased the length of the interdigestive motility cycle by 50% and 67% compared with controls, respectively (both P less than 0.002). Propagation velocity of the migrating motor complex (P less than 0.01) and plasma motilin were decreased (P less than 0.01). The smaller and larger dose decreased pancreatic enzyme outputs by 50% and 65%, respectively (P less than 0.005), but with the smaller dose, phase III-associated enzyme outputs were greater than phase I outputs. These findings suggest that small changes in somatostatin 28 plasma concentrations modulate human interdigestive motility and pancreatic enzyme output while coupling of motor and secretory events is preserved.

Adult↗
PubMed1992

[Regulation of gastrointestinal functions by the ileocecal area].

The importance of the distal small intestine and the ileocecal region for the regulation of gastrointestinal functions in humans has not been investigated in depth until recently. A regulatory role is postulated because even in healthy subjects, undigested nutrients pass across the ileocecal junction after most meals (physiologic malabsorption). Nutrient exposure of the ileocecal region causes slowing of gastric emptying and small intestinal transit, and decrease in small intestinal motor activity; under certain experimental conditions, ileal nutrients induce conversion of intestinal motility from digestive to interdigestive patterns. In addition, the secretory activity of the proximal gastrointestinal tract is inhibited by the ileocecal region. Inhibition of gastric secretion and exocrine pancreatic secretion are well established responses to ileal nutrient exposure; inhibition of bile secretion likely occurs, but is not proven. The intermediary mechanisms of these effects have not been clarified; the most likely candidates include endorphins, peptide YY (PYY), and glucagon-like-peptide-1 (GLP-1). Overall, the available data support the concept that the ileocecal region participates in the physiologic control of gastrointestinal motor and secretory functions. Whether disturbances of these regulatory mechanisms participate in the pathophysiology of gastrointestinal disease has not been investigated.

Animals↗