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Biomedical subjects

S Domschke

Publications and source records attributed to S Domschke.

At least 91 records · Page 5Linked to original sources
PubMed1977

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↗
PubMed1977

Acid releases motilin from human duodenum in vitro.

The effect of hydrochloric acid and sodium hydroxide on motilin release from human duodenal mucosa was studied in vitro. Tissue was incubated in 2 ml chambers continuously perfused with medium and was exposed repeatedly to the stimuli. Motilin released into the medium was determined by a specific radioimmunoassay. Whereas alkalinisation abolished basal motilin release, acidification resulted in a 14-fold increase of peptide secretion. The results indicate that motilin secretion can be stimulated in vitro and that the perfusion system described may be a useful tool in studying the mechanism of gastrointestinal hormone release.

Duodenum↗
PubMed1977

Gastric mucosal histamine in duodenal-ulcer patients: release by secretin.

In 5 duodenal-ulcer patients with anaphylactic skin reaction to intradermal secretin and in 4 healthy controls, biopsy samples from the fundic region of the stomach were superfused with phosphate buffer alone and with phosphate buffer containing 20 C.U./ml synthetic secretin. In response to secretin, the mucosa from duodenal-ulcer patients released significantly increasing amounts of histamine (P is less than 0.05) whereas control tissue did not respond. Additionally, in duodenal-ulcer patients the histamine content of untreated gastric mucosa was about twice as high as in controls (P is less than 0.02). It is suggested that the elevated mucosal histamine could account for the basal and stimulated gastric hypersecretion of duodenal-ulcer patients. In addition, the results are compatible with the concept that in a certain type of duodenal ulceration, secretin does drive rather than inhibit gastric secretion.

Adult↗
PubMed1977

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↗
PubMed1977

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↗
PubMed1977

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↗
PubMed1977

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↗
PubMed1976

[Effective treatment of duodenal ulcer with cimetidine (author's transl)].

Twelve male duodenal ulcer in-patients received in a double-blind trial either the histamine H2-receptor antagonist cimetidine (4 X 200 mg/d p.o.) or placebo capsules. Ulcer sizes were assessed endoscopically before therapy followed by repeat endoscopy at weekly intervals. Duodenal ulcer healing was significantly more rapid in cimetidine-treated patients than in those receiving the placebo (chi2 test; P less than 0.0005). Plotting of log ulcer sizes (mm2) against time (days) resulted in regression lines the slopes of which indicated the respective half-time of ulcer healing: about 6 days on cimetidine therapy and about 20 days on placebo treatment. Gastric secretion of acid, protein, pepsin, and N-acetylneuraminic acid-containing glycoproteins was not altered by a 4-week course of daily cimetidine or placebo, nor pancreatic secretion of bicarbonate and enzymes. No statistically significant changes in laboratory findings (haemoglobin, white blood-cells, neutrophils, platelets, alkaline phosphatase, blood-urea, serum-creatinine, GOT, GPT) were associated with treatment.

Adolescent↗
PubMed1976

[Histamine-H2-receptor antagonists. Physiological and clinical aspects].

Histamine-H2-receptor antagonists (Burimamide, Metiamide, Cimetidine) may inhibit histamine-stimulated gastric secretion in various species including man; in constrast, conventional antihistaminics (H1-antagonists) do not do so. Gastric secretion as stimulated by pentagastrin, insulin, 2-deoxy-glucose or an intragastrically instilled meal is also decreased by H2-antagonists, and a final common mediator role for histamine in the gastric secretory is discussed. H2-antagonists do also inhibit pancreatic enzyme secretion, but do not affect at all bicarbonate secretion. Recent clinical trials have shown Metiamide to be superior to placebo in therapy of duodenal ulcer.

Gastric Juice↗
PubMed1976

Release of motilin after duodenal acidification.

The physiological stimulus leading to motilin release in man has not yet been determined. Six healthy volunteers had 3-minute intraduodenal infusions of acid, alkali, or saline solutions. After infusing acid, plasma-motilin rose by 90% at 4 min and was still significantly raised at 45 min, whereas there was an insignificant fall in plasma-motilin after alkali and no change after saline solution. Release of motilin after duodenal acidification may be an important factor in inhibiting gastric emptying.

Adolescent↗
PubMed1976

Effects of 13-nle-motilin on salivary, gastric, and pancreatic secretions in man.

Salivary, gastric, and pancreatic secretory responses to intravenous 13-norleucine-motilin (13-nle-motilin), a synthetic analog of motilin and biologically equivalent to the natural polypeptide, were studied in healthy volunteers. 13-nle-Motilin in doses of 100 ng/kg body wt/hr significantly stimulated gastric pepsin output, while H + secretion and serum gastrin levels remained unchanged. Enhanced pepsin secretion was not accompanied by an increase in gastric secretion of cyclic 3', 5'-adenosine monophosphate, nor did gastric mucosal levels of the cyclic nucleotide rise. A dose of 13-nle-motilin, which stimulated gastric pepsin output, did not exert any significant effect on salivary and pancreatic secretions.

Adult↗
PubMed1976

Superior immunoreactivity of 125I (Des-Tyr-betaAla)-secretin with rabbit anti-secretin sera compared to 125I-secretin and 125 I-6-Tyrosyl secretin.

A secretin analogue in which the normal amino acid sequence had been elongated by a (Des-Tyr-betaAla)-residue was studied as tracer for secretin radioimmunoassay. 125I-(DATA)-secretin exhibited superior immunoreactivity with several rabbit anti-secretin sera compared to 125I-6-Tyr-secretin and also to secretin iodinated at its N-terminal histidyl residue. This may be due, at least in part, to higher conformational integrity of the secretin moiety in the 125I-(DATA)-secretin molecule. Thus, at present, 125I-(DATA)-secretin appears to be most suitable as tracer for sensitive secretin radioimmunoassay.

Amino Acid Sequence↗
PubMed1976

Potentiation between 13-Nle-motilin and acetylcholine on rabbit pyloric muscle in vitro.

The interaction of 13-nle-motilin-a synthetic analogue of the natural polypeptide-with acetylcholine was studied on rabbit isolated pyloric sphincter in vitro. Adding subthreshold doses of 13-nle-motilin reduced the calculated acetylcholine dose for half maximal contraction from 3.68 to 1.33 X 10(-6) g/ml and increased the calculated maximal response by 15.3%. Thus 13-nle-motilin caused potentiation of the acetylcholine response. Since 13-nle-motilin induced increase of endogenous acetylcholine levels could be excluded, a direct action of motilin on or in the smooth muscle cell is suggested. The results are compatible with the view that in vivo subthreshold doses of motilin may affect cholinergic driven pyloric motor activity.

Acetylcholine↗
PubMed1976

Release of motilin in man.

The effects on motilin release of various stimuli including an ordinary hospital lunch and ingestion of equicaloric amounts of protein (steamed cod), fat (double cream), or carbohydrate (glucose solution), and intraduodenal instillation of acid (0.1M HCl) and alkali (0.3M tris buffer, pH 10.2) have been investigated in healthy volunteers. Duodenal acidification resulted in a 90% rise of plasma motilin while after intraduodenal instillation of alkali motilin fell. No significant change was seen after a normal hospital lunch and the protein meal, and a small fall was observed after glucose. By contrast, after ingestion of 60 g fat motilin showed a peak increase of 65% at 30 minutes and was still significantly elevated at 60 minutes. Exogenous motilin has been reported to delay gastric emptying and this is also seen after duodenal acidification and fat ingestion. We conclude that motilin may be released physiologically by these stimuli and mediate their effects on gastric emptying in man.

Adult↗
PubMed1976

Intravenous 13-Nle-motilin increases the human lower esophageal sphincter pressure.

UNLABELLED: To elucidate whether, in principle, motilin could serve a role in LESP regulation, the effects of 13-norleucine-motilin (13-nle-m)-synthetic analogue of motilin and biologically just as active as the natural polypeptide-on LESP were investigated in normal subjects. LESP was monitored with the continual withdrawal method. Sets of tests: (1) i.v. pulse doses of 13-nle-m (0.05, 0.1, 0.2, and 0.4 mug/kg) were given to 6 subjects in random order on different days, (2) i.v. bolus injections of 0.6 mug/kg pentagastrin were given to elicit maximal LES contractions, (3) i.v. infusions of 13-nle-m (0.1, 0.2, and 0.4 mug/kg-h; doses doubling every 30 min) were used in 7 individuals, and (4) the effect of atropine infusion of 13-nle-m-stimulated LESP was studied in 6 subjects. RESULTS: (1) Graded i.v. pulse doses of 13-nle-m caused LESP to increase dose-dependently with maximum pressures exceeding basal levels by about 160% (p less than 0.01). After each bolus injection, peak values were achieved within 1-2 min followed by a steady decrease in LESP. (2) Maximum response to 0.4 mug/kg 13-nle-m was about 65% of that to 0.6 mug/kg pentagastrin. (3) i.v. infusions of varying doses of 13-nle-m caused a significant and dose-dependent increase in average LESP. (4) The stimulating effect of an i.v. pulse dose of 0.1 mug/kg 13-nle-m on LESP could be suppressed by concomitant atropine. CONCLUSION: the human LES is responsive, indeed, to exogenous motilin.

Adult↗
PubMed1976

Effect of 13-Nle-motilin on small intestinal transit time in healthy subjects.

In 6 female subjects without gastrointestinal diseases, 13-norleucine motilin (13-Nle-M) synthetic and biological analogue of the duodenal polypeptide, motilin, caused acceleration of intestinal transit time. Intravenous infusion of 0.4 mug/kg-h of 13-Nle-M reduced mean transit time by 50 percent. No side effects occurred during infusion of the polypeptide. Radiographic appearance of small intestinal peristalsis and mucosal relief was not influenced by 13-Nle-M.

Female↗