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Biomedical subjects

L Demling

Publications and source records attributed to L Demling.

At least 199 records · Page 11Linked to original sources

[Gastrointestinal hormones].

Gastrointestinal hormones are considered to be those that are formed in the gastrointestinal tract and there, in physiological concentrations, develop their effects on motility, secretion, trophism, bloodflow and absorption. Structural analysis, synthesis or a high degree of purity after extraction, and its exact demonstration by means of a useful radioimmunoassay, form the basis for the establishment of a polypeptide as a gastrointestinal hormone. To this category belong, at the present time, gastrin, cholecystokinin-pancreozymin (CCK-PZ) and secretin. GIP, VIP, motilin, glucagon and somatostatin are considered likely candidates. The substances gastrin and CCK-PZ, which are structurally related and have a predominantly stimulating effect, and the structurally dissimilar motilin, contrast with the partially or totally inhibiting hormones of the glucagon family, namely, secretin, VIP, glucagon-enteroglucagon, GIP and somatostatin. By the combined action of these hormones with one another and with the autonomic nervous system, the digestive processes are regulated. Disturbances in the formation of these hormones, in particular an overproduction, give rise to disease syndromes that can now be diagnosed and, in part, treated by surgery. The therapeutic application of gastrointestinal hormones has now also become a possibility.

Cholecystokinin↗

[Redioimmunoassay for secretin (author's transl)].

The synthesis of a secretin with an elongated N-terminus, namely Nalpha-(deaminotyrosyl-beta-alanyl)- secretin (DATA-secretin), using a conventional strategy, is described. After purification of the product by means of ion exchange chromatography on SP-Sephadex C-25 and by continuous carrier-free electrophoresis, immunological studies on the synthetic DATA-secretin were carried out using secretin antibodies. In comparison to 125iodine-labelled secretin and [Tyr6]secretin, 125iodine-DATA-secretin proved to be by far the best "tracer". Elaboration of a radioimmunoassay for secretin is therefore possible.

Animals↗

Effects of in vivo administration of pentagastrin, secretin, and 13-Nle-Motilin on the in vitro incorporation of 14C-leucine into protein of human gastric mucosa.

Under endoscopic control, biopsy specimens were taken from the oxyntic gland area of the stomach before and after administration of pentagastrin, synthetic secretin, and 13-norleucine motilin (13-nle-motilin), respectively. In 29 volunteers, the basal rate of 14C-leucine incorporation into mucosal protein averaged 41.2 +/- 7.7 X 103 cpm/mg protein (mean +/- S.D.). One and 4 hours after s.c. administration of pentagastrin (6 mug/kg body weight), values were significantly increased (p less than 0.05) by 18.9 and 21.8%, respectively, with respect to the basal level. One hour after an intravenous shot of 2 CU per kg body weight of secretin, gastric mucosal protein synthetis was not substantially inhibited, whereas a 1-hour continuous i.v. infusion of 13-nle-motilin (0.4 mug/kg body weight, hr) significantly decreased 14C-leucine incorporation rates by 17.5% (p less than 0.05). In contrast to rats, 1 hour after s.c. pentagastrin, protein synthesis in human duodenal mucosa was not altered. From these results it may be concluded that pentagastrin has a trophic influence on gastric mucosa in man. Moreover, the data presented are compatible with the hypothesis that gastrin and motilin may be involved in the regulation of human gastric mucosal protein synthesis.

Adult↗

[Pancreatic response to graded doses of synthetic secretion: comparison between intravenous and pernasal administration in man].

The response of the human pancreas to varying doses of pure synthetic secretin administered intravenously and, for comparison, 8 days later in the form of snuff was examined, intraindividually, in 10 healthy test subjects. After intubation of the stomach and duodenum and continuous instillation of radioactive vitamin B12, the recovery rate of the marker substance was measured in duodenal aspirates and employed to compute the pancreatic bicarbonate and enzyme outputs. The dose-response relationship between pancreatic bicarbonate production and varying doses of synthetic secretin administered intravenously and in the form of snuff, was good. The pancreatic response to a dose of secretin snuff was only about 1/25 of the response obtained with the same dose of secretin injected intravenously. The level of the pancreatic enzyme output remained relatively uninfluenced by varying doses of synthetic secretin.

Administration, Intranasal↗

[Patients' attitudes towards the physician's duty to inform. Results of an inquiry].

More than 200 patients filled in questionnaires on their attitude towards doctors' duty to inform them on all possible diagnostic and therapeutic hazards. 8% wanted none of this information, 49% wanted to be informed of the important risks, and 43% wished to know all possible hazards. If fully informed about possible risks, 88% felt they would undergo medical treatment with less anxiety, while 12% believed anxiety would be enhanced. 3% wanted no information about any incurable disease, 35% wanted to know part and 62% all of the truth.

Attitude to Health↗

[Mode of action of bisacodyl (dulcolax) on isolated muscles of human colon (author's transl)].

The effects of bisacodyl (4,4-diacetyl-bis-hydroxyphenyl-pyridyl-(2)-methan, Dulcolax) on the tone of isolated muscle strips of human colon were examined. Maximal contractions achieved by 10 mug/ml of bisacodyl were quite comparable to those due to 1 mug/ml of acetylcholine, 1 mug/ml of histamine and 0.5 mug/ml of nicotine, respectively. However, peak contractions were attained with a greater latency and could not be prevented by the anticholinergic agent atropine, the H1-antihistaminic diphenhydramin or tetrodotoxin blocking axonal conduction. On the other hand, pretreatment with verapamil -- antagonizing calcium influx into the muscle cell -- abolished bisacodyl effects. These results provide evidence for a direct action of bisacodyl on smooth muscle cells of human colon.

Acetylcholine↗

[The effect of caerulein on gastric mucosal blood-flow and gastric secretion (author's transl)].

The effect of Caerulein, a decapeptide produced from the skin of the Australian frog Hyla caerulea, on the mucosal blood-flow and the gastric acid secretion as well as the pepsin secretion has been investigated in 15 patients. Caerulein administered at a dose rate of 0.1 mug/kg-h significantly inhibited the gastric mucosal blood-flow (p greater than 0.005) and the acid secretion (0.05 greater than p greater than 0.01), which had been stimulated by pentagastrin at a dose rate of 1.5 mug/kg-h. The pepsin secretion stimulated with pentagastrin also decreased, but not significantly. Caerulein at the above mentioned dose rate however caused a slight but not significant increase of the acid secretion stimulated by 40 mug histamine/kg-h. At the same time, gastric mucosal blood-flow and pepsin output decreased slightly but not significantly. Caerulein given alone stimulates acid secretion, yet it causes a significant reduction of the acid output when administered together with pentagastrin. This response has to be explained by the fact, that the similar chemical structure of pentagastrin and caerulein leads to a competitive inhibition. The mucosal blood-flow of the stomach measured with the heat-clearance technique also decreases with the administration of caerulein after pentagastrin stimulation. The fact that the mucosal blood-flow remains unchanged after the administration of histamine, suggests that the reduction in mucosal blood-flow observed with pentagastrin is a consequence and not the cause of the acid inhibition occurring at the same stage.

Adult↗

Exocrine pancreatic function in juvenile diabetics.

In 11 juvenile diabetics and 13 control subjects, the secretin-pancreozymin test was performed. Duodenal-volume losses were corrected by use of radioactive vitamin B12 as marker substance. As compared to normal subjects, juvenile diabetics had significantly decreased pancreatic outputs of amylase, trypsin, chymotrypsin, and to a lesser degree, of bicarbonate. Clinical evidence of disease of the exocrine pancreas was missing. There was no discernible relationship between the abnormality of external pancreatic function and the duration of diabetes mellitus or the dose of insulin required. Possible factors that may be responsible for the exocrine deficiency of the pancreas in juvenile diabetics are discussed.

Adult↗

Cyclic-AMP and pancreatic bicarbonate secretion in response to secretin in dogs.

In anesthetized dogs given secretin intravenously in doses doubling every 60 min and ranging from 0.5 to 8 units per kg body weight per hr, cyclic-AMP levels in pancreatic tissue rose continuously, whereas DNA concentrations were slightly decreased. Bicarbonate concentrations and bicarbonate outputs, cyclic-AMP tissue concentrations and bicarbonate outputs, as well as cyclic-AMP tissue concentrations and juice outputs, were significantly correlated. In conscious pancreatic fistula dogs, there was also a significant correlation between cyclic-AMP and bicarbonate concentrations and outputs in the pancreatic juice after stimulation by exogenous secretin. Accordingly, enhanced release of endogenous secretin achieved by intraduodenal acidification led to a dose-dependent increase in bicarbonate and cyclic-AMP outputs in both conscious and anesthetized dogs. Phosphodiesterase inhibitors (aminophylline, caffeine, and papaverine) given alone to the conscious dogs did not initiate pancreatic bicarbonate secretion, but they potentiated bicarbonate responses to exogenous secretin. These data suggest that cyclic-AMP plays a part in secretin-stimulated pancreatic secretion.

Aminophylline↗

Effects of 13-nle-motilin in man--inhibition of gastric evacuation and stimulation of pepsin secretion.

In 3 healthy male volunteers, graded doses of 13-norleucine-motilin (13-nle-motilin)--synthetic analogue of motilin and biologically equivalent to the natural polypeptide--were given intravenously on separate days. Gastric emptying, as determined by means of a radioisotope method, was slowed down dose-dependently by increasing doses of 13-nle-motilin. This was indicated by increasing "half-lives" and "starting indices" of the gastric emptying process, and by decreasing pyloric loss rates, respectively. The gastric pepsin output rose markedly from the basal level during intravenous infusion of 13-nle-motilin.

Adult↗

Analysis of the motor effects of 13-norleucine motilin on the rabbit, guinea pig, rat, and human alimentary tract in vitro.

Motor effects of 13-norleucine motilin (13-Nle-M), a synthetic analog of motilin and biologically equivalent to the natural polypeptide, on the rabbit, guinea pig, rat, and human alimentary tract were investigated in vitro. Whereas guinea pig and rat preparations proved refractory to 13-Nle-M action, muscle strips of the stomach and upper small intestine from rabbits and man were highly sensitive to 13-Nle-M, contractile responses being elicited with concentrations of less than 2 times 10-minus 9 M. Although circular muscle from rabbit colon responded to 13-Nle-M, Taenia coli preparations were unaffected by the polypeptide; in man, the reverse was observed. Gallbladder, uterine, and vascular smooth muscle were unresponsive to 13-Nle-M. Pharmacological analysis revealed that the effects of 13-Nle-M on the gastrointestinal muscle are not mediated via nervous pathways: ganglion blockade by hexamethonium, blockade of axonal conduction by tetrodotoxin, or anticholinergic action by atropine failed to affect 13-Nle-M actions. It was therefore concluded that 13-Nle-M caused contractions by stimulating receptors on or in the muscle cell. By use of the antihistaminic pheniramine, histamine receptors could be differentiated from the site of 13-Nle-M action. As the contractile response to 13-Nle-M was abolished by the Ca++ antagonistic compound verapamil, a role for 13-Nle-M in the transport of Ca++ to the cytosol of intestinal smooth muscle might be considered.

Acetylcholine↗