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Biomedical subjects

L Demling

Publications and source records attributed to L Demling.

At least 145 records · Page 8Linked to original sources

Gastric epithelial cell turnover, mucus production, and healing of gastric ulcers with carbenoxolone.

Nineteen healthy subjects were studied and 17 patients with gastric ulcer before and after ulcer healing with carbenoxolone. Gastric deoxytibonucleic acid (DNA) loss was measured as an index of epithelial cell turnover, and N-acetylneuraminic acid (NANA) content of gastric juice as an index of mucus secretion. In normal subjects there was a negative correlation (p less that 0-025) between gastric DNA loss and NANA secretion; the lower the cell turnover the higher the NANA production. In gastric ulcer patients DNA loss or turnover was significantly (p less than 0-01) higher than normal, and fell significantly (p less than 0-01) after four weeks' treatment with carbenoxolone when 16 of the 17 ulcers had healed. At the same time NANA output increased significantly (p less than 0-01). It is suggested that patients with gastric ulcer lose cells at a high rate, a state of affairs which is returned towards normal by carbenoxolone, thus allowing the epithelial cells to mature within the mucosa and produce more mucus.

Adult↗

Plasma secretin and pancreatic bicarbonate response to exogenous secretin in man.

The dose response of duodenal bicarbonate production during synthetic porcine secretin infusions was studied in six healthy volunteers and related to plasma secretin immunoreactivity. Secretin was infused in each individual at four different doses from 0-1 to 2-7 CU/kg/h, each infusion lasting for 60 minutes. Mean maximal bicarbonate secretion was 33 +/- 4 mEq/h. The secretin plasma level for half maximal bicarbonate response was estimated to be 22 pmol/l. As this level is reported to be achieved by intraduodenal acidification in man, it is concluded that secretin may well play a part in the control of duodenal pH.

Adult↗

Effect of secretin on plasma motilin in man.

Graded doses of 0-1, 0-3, 0-9, and 2-7 clinical units/kg/h of pure synthetic secretin were infused over 60 minute periods in six healthy volunteers. Duodenal bicarbonate output and pH were recorded and plasma secretin and motilin levels were measured by radioimmunoassay. During the infusions plasma motilin fell in a dose dependent manner to a nadir of 35%. This fall was linearly correlated with pancreatic bicarbonate output, whereas a non-linear correlation was observed between plasma motilin and both plasma secretin level and duodenal pH. It is suggested that plasma motilin levels are decreased by secretin-induced pancreatic bicarbonate juice flow. This may be important for the control of motilin secretion initiated by duodenal acidification and the concomitant delay in gastric emptying.

Adult↗

Comparison of pancreatic responses to portal and systemic secretin and VIP in cats.

This study was designed to compare pancreatic bicarbonate responses to secretin and vasoactive intestinal peptide (VIP) administered either by peripheral or portal route in 24 anesthetized cats. Continuous intravenous infusion of graded doses of secretin (rang from 0.04 to 0.68 nmol/kg per h), stimulated pancreatic volume flow and bicarbonate outputs dose dependently and not statistically differently when given into the peripheral or portal vein. VIP infused in graded doses (range from 0.60 to 9.62 nmol/kg per h) into the peripheral vein produced pancreatic volume flow and bicarbonate outputs not statistically different from those obtained with secretin. In contrast, the biological activity of VIP administered intraportally was reduced by 60% at lower VIP doses (0.60 and 1.20 nmol/kg per h) and by 40% at 2.40 nmol/kg per h, whereas at higher doses it was not significantly changed. This study provides evidence that VIP in the cat is a secretin-like full agonist of pancreatic bicarbonate secretion and that it is only partially inactivated by the liver.

Animals↗

Inhibition by somatostatin of gastrin release and gastric acid responses to meals and to pentagastrin in man.

The inhibitory actions of intravenous somatostatin on the gastric secretory responses to pentagastrin (1.5 microng/kg-h i.v.) and to a meal (10% peptone, pH 5.5) were studied in six healthy subjects. Meal-induced gastric acid output was estimated by means of a modified Fordtran and Walsh method of intragastric titration. Somatostatin (5 microng/kg-h; cyclic form) significantly inhibited the total 1-hour acid response to pentagastrin by about 70% (inhibition of pepsin secretion: about 70%) and that to a test meal by about 75%. During the last 30 min of somatostatin infusion the pentagastrin-stimulated secretion of acid was significantly reduced by about 90% (inhibition of pepsin output: about 85%) while the corresponding figure in the test with meal-induced secretion was about 95%. Serum gastric--elevated in response to the test meal--was found to be merely lowered by about 30% during somatostatin infusion. Consequently, it is tempting to assume that inhibition of human gastric acid secretion by exogenous somatostatin largely results from a direct antisecretory effect upon parietal cells and, only to a minor extent, from an indirect action via reduction of gastrin release.

Adult↗

Inhibition by somatostatin of secretin-stimulated pancreatic secretion in man: a study with pure pancreatic juice.

The action of somatostatin on compostition and flow rate of pure pancreatic juice obtained by endoscopic cannulation of the main pancreatic duct was evaluated in 5 healthy volunteers. Synthetic secretin (0.06 CU/kg-h) was intravenously infused throughout the 80-min study. Bicarbonate concentrations in pancreatic juice achieved constant levels (117 +/- 3 muEq/ml) after 10 min, whereas a steady state of juice flow (7.3 +/- 1.4 ml/5 min) was attained after 15 min of secretin infusion. In the third 20-min period, cyclic somatostatic (5 mug/kg-h i.v.) was given, leading to a decrease in pancreatic flow rate by 47% after 10 min, and by 67% after 15 min of somatostatin administration. Alrady 5 min after the infusion of somatostatin had been discontinued, pancreatic flow rate gradually recovered; presomatostatin levels, however, were not reached within 20 min. Cyclic AMP varied roughly in accordance with bicarbonate concentrations, whereas the chloride concentrations were reciprocally related. Bicarbonate, sodium, potassium, protein, and cyclic GMP concentrations did not change substantially due to somatostatin.

Adult↗

Glucocorticoid and mineralocorticoid actions on gastric secretion in man.

The effects of a 6-day course of treatment with a glucocorticoid (prednisolone, 1 g per day i.v.), a mineralocorticoid (9-alpha-fluorohydrocortisone, 0.3 mg per day orraly), or both the drugs on gastric secretion of acid, protein, pepsin, and N-acetylneuraminic acid (NANA) containing glycoproteins were investigated in 22 volunteers. None of the treatments produced any statistically significant changes in gastric secretion of aggressive factors, acid and pepsin. However, the output of protective NANA bound to glycoproteins was found to be decreased following prednisolone. The prednisolone effect was not prevented by 9-alpha-fluorhydrocortisone given concomitantly. Gastroduodenoscopy did not reveal any lesions attributable to drug adminstration.

Adult↗

Pharmacokinetics of motilin in man.

The study provides pharmacokinetic data for exogenous synthetic and endogenous natural motilin in man. Synthetic 13-norleucine-motilin was infused into 6 healthy volunteers at a dose of 0.6 and 2.4 (pmoles per kg) per min over 60 min and plasma motilin was measured by radioimmunoassay. During the infusions mean plasma levels of 124.8 +/- 14.8 and 360 +/- 19.6 pmoles per liter, respectively, were achieved. Disappearance half-time on stopping the infusion was 4.36 min. The apparent volume of distribution was calculated to be 49.4 +/- 3.3 ml per kg, and the metabolic clearance rate was 7.8 +/- 0.5 (ml per kg) per min. To measure the decay of endogenous motilin somatostatin was used in the same 6 subjects. A bolus of 100 mug and a subsequent 15-min infusion of 15 mug per min of somatostatin suppressed the fasting motilin level by 50%. The disappearance half-time was 4.56 min. It is concluded that both synthetic and endogenous motilin are eliminated by first order kinetics with very similar half-times. Our data also suggest that the previously reported motilin infusions at these dose levels gave plasma concentrations within the physiological range and that the effects noted may thus have reflected the physiological actions of motilin.

Adult↗

Effect of lysine-acetylsalicylate on serum gastrin levels.

The effect on serum gastrin levels of lysin-acetylsalicylate (LAS), water soluble derivative of acetylsalicylic acid, was investigated in mice. Intragastrically administered LAS did not at all alter serum gastrin values while--when given via the intravenous route--LAS not earlier than at the very high dose of 450 mug/g caused a short-lived significant increase in serum gastrin. These results are in keeping with the view that salicylates do not owe their potential ulcerogenic properties to stimulation the gastrin-gastric secrection mechanism.

Animals↗

Enkephalins inhibit intestinal motility: mode of action.

In the guinea pig isolated terminal ileum the opioid pentapeptides, methionine-enkephalin and leucine-enkephalin, dose-dependently inhibit contractile responses induced by electrical field stimulation releasing endogenous acetylcholine, and by specific noncholinergic compounds including histamine, barium chloride, and beta-acetyl-digoxin. Tissue levels of cAMP and cGMP remain unchanged. We conclude that enkephalins exert their effects by a direct action at or within the muscle cell and may play a physiological role in the local control of the gut smooth muscle motility.

Animals↗

Vasoactive intestinal peptide: a secretin-like partial agonist for pancreatic secretion in man.

The responses of pancreatic volume flow and bicarbonate output to intravenous vasoactive intestinal peptide (VIP, 0.8 to 3.2 microgram per kg per hr) and synthetic secretin (32.2 to 129 ng per kg per hr) were compared intraindividually in 5 healthy volunteers. Pure pancreatic juice was obtained by endoscopic cannulation of the main pancreatic duct. The mean +/- SEM observed maximal response of secretin-stimulated juice flow was 248 +/- 7 microliter per kg per 5 min, whereas the observed maximal response for VIP-evoked juice flow was 48 +/- 6 microliter per kg per 5 min. The observed maximal secretin-induced bicarbonate output was 30 +/- 2 muEq per kg per 5 min, and the maximal VIP-related response was 4.3 +/- 0.9 muEq per kg per 5 min. In addition to low efficacy, high dose requirements, and side effects (significant rise in pulse rate and cutaneous flushing at 3.2 micrograms per kg per hr) argue against a major physiological role of VIP as a hormonal stimulant of human pancreatic bicarbonate secretion.

Adult↗

The gastrointestinal myoelectric response to 13-Nle-motilin infusion during interdigestive and digestive states in the conscious dog.

Gastrointestinal myoelectric activity was studied in three conscious fasted dogs with electrodes surgically implanted in the stomach and small intestine, during separate and combined intravenous infusions of 13-norleucine motilin (13-nle-motilin) and pentagastrin (PG). Basal recordings confirmed the presence of regular interdigestive myoelectric complexes (MC's). 13-nle-motilin infusion below 50 ng/kg-h was without effect: higher doses up to 400 ng/kg-h resulted in the interpolation of one or more MC's in the spontaneous sequence. The rate of aboral transit of 13-nle-molitin-induced MC's did not differ significantly from that of spontaneous MC's. When MC's were abolished by feeding or PG infusion, simultaneous 13-nle-motilin administration was without effect on spike activity, but slightly attenuated the accelerating effect of gastrin on the gastric pacemaker frequency. The myoelectric events triggered by 13-nle-motilin suggest that in the conscious dog the polypeptide may not act directly on the smooth muscle cell, as it does in vitro, but through an extra-enteric neural control mechanism which is uncoupled by gastrin.

Aminocaproates↗

Endoscopic papillotomy.

Obstruction of the common bile duct can now be relieved by endoscopic electrosurgery. This report describes our experience with 267 patients. In 192 of 222 patients with choledocholithiasis all calculi were evacuated by endoscopic papillotomy (EP). The remaining patients had EP because of papillary stenosis. Complications of EP included nine instances of pancreatitis, seven of bleeding, and two perforations. In 2 of 32 patients having EP for papillary stenosis, restenosis has appeared on follow-up. The two fatalities were attributable to purulent cholangitis and acute bleeding. This required to manage these situations. The endoscopic method requires less hospitalization and recuperation. EP and stone extraction are the methods of choice for managing common duct obstruction in high risk patients before cholecystectomy, for retained or reformed stones after cholecystectomy, and for papillary stenosis.

Ampulla of Vater↗

Endogenous acid releases secretin in man.

In search of a physiological stimulus for secretin release, the effect of gastric acid secretion was investigated. In six healthy volunteers, pentagastrin (1.5 microgram/kg, hr i.v.) was administered without and with aspiration of gastric contents, and plasma secretin was estimated by radioimmunoassay. Administration of pentagastrin without aspiration of gastric juice resulted in steadily increasing plasma secretion which was significantly elevated at the end of 60 min of pentagastrin infusion and also in the post-infusion hour. These results are compatible with the concept that endogenous acid being delivered from the stomach to the duodenum does contribute to the release of secretin which in turn may serve as a physiological stimulus for pancreatic bicarbonate secretion.

Adult↗