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Biomedical subjects

M Bickel

Publications and source records attributed to M Bickel.

At least 91 records · Page 5Linked to original sources
PubMed1986

New analogues of secretin.

For the evaluation of structure/activity relationships, some porcine secretin analogues, modified in the N-terminus, have been synthesized by segment condensation in solution. The secretin activity of the analogues was defined as the volume of pancreatic juice secreted in rats and dogs. The exchange of the N-terminal pentapeptide for the N-terminal pentapeptide of human somatotropin releasing factor (h-SRF) resulted in a peptide ([1-Tyr,2,4-Di-Ala,5-Ile]secretin) with practically no SRF-activity (less than 1% SRF-activity up to 100 micrograms/kg in the rat), but surprisingly high secretin activity (almost 100% in the rat, but only 1150 CU/mg (27%) in the dog). [3-L-Cysteic acid]secretin showed 1750 CU/mg (39%) in the dog, but a less activity (23%) in the rat. [6-D-Phe]secretin and [5-D-allo-Thr]secretin are again strongly species specific. They exhibited an activity of less than 1% in the dog, but about 10-15% in the rat. The smallest secretin activity was observed with [1-Cys,6-Cys]secretin in the oxidized form. The activity in the rat with this analogue was only about 0.2%.

Amino Acid Sequence↗
PubMed1986

Antisecretory effects of two new histamine H2-receptor antagonists.

N-(3-[3-(1-Piperidinylmethyl)phenoxy]propyl)acetoxyaceta mide hydrochloride (Hoe 760) and N-(3-[3-(1-piperidinylmethyl)phenoxy]propyl)glycolamine hydrochloride (Hoe 062) are highly specific H2-receptor antagonists. The compounds are equipotent after intragastrical or intravenous administration. The antagonists inhibited gastric acid secretion in the rat induced by all stimuli tested, carbachol, desglugastrin and histamine. In the Heidenhain pouch dog whose gastric acid secretion was stimulated by food or histamine the two receptor blockers proved to be 4-6 times more potent inhibitors than cimetidine.

Adenylyl Cyclases↗
PubMed1985

2-((2-Pyridylmethyl)sulfinyl)benzimidazoles: acid sensitive suicide inhibitors of the proton transport system in the parietal cell.

2-((2-Pyridylmethyl)sulfinyl)benzimidazoles, selective inhibitors of the H+/K+-ATPase in the parietal cells of the stomach, have been investigated concerning their chemical behaviour in acidic medium. Protonation of the sulfoxide and subsequent elimination of water forms a sulfenium ion or a chemical equivalent thereof. If no external nucleophiles are present, a rearrangement process takes place. In the presence of mercaptans, the sulfenium ion is trapped giving rise to a variety of products. On the basis of these results, a mechanistic scheme is proposed for the inactivation of the H+/K+-ATPase by these compounds.

Adenosine Triphosphatases↗
PubMed1985

Flow and albumin content of early (pre-inflammatory) gingival crevicular fluid from human subjects.

Gingival fluid was collected with glass capillaries tubing from the upper premolar area in a group of 7 volunteers, after allowing dental plaque to accumulate for 12-36 h, and in a group of patients with gingivitis. Whereas no fluid could be collected in the absence of plaque, increasing amounts were recovered during plaque accumulation, in the absence of clinical signs of gingival inflammation. The ratios of albumin concentrations in gingival fluid and plasma also increased significantly with increasing time of plaque accumulation. These fluid:plasma ratios of albumin concentrations were significantly lower than the ratios found for the inflamed sites in the second group of patients. These results support the hypothesis that, in an early inflammatory response, the fluid is not a typical inflammatory exudate and is probably modulated by an osmotic gradient.

Adult↗
PubMed1985

Acid-base properties of human gingival crevicular fluid.

The pH of human gingival crevicular fluid (GCF) has been reported by many authors to be very alkaline (pH 7.5 - 8.7). This alkalinity could be explained, at least partially, by the fact that all measurements were performed either at low PCO2 or in the absence of CO2. Therefore, we set up a procedure which allows for measurement of the pH of GCF samples from single inflamed sites at controlled PCO2. At a PCO2 of 4.7 kPa (= 35 mmHg) and at 37 degrees C, the pH was 7.96 +/- 0.10 (SEM, n = 9), a value which differs significantly from the value of 8.38 +/- 0.09 measured in the absence of CO2 in the same samples. The non-bicarbonate buffer value of the sample determined by CO2 titration was 6.0 slykes. It is because this value is low that pH varies so greatly with PCO2. At physiological PCO2, the total buffering power becomes very high above pH 8.0, because of the high bicarbonate concentration.

Adult↗
PubMed1985

Pharmacology of a gut motility stimulating enkephalin analogue.

The enkephalin analogue pentapeptide Hoe 825 (Tyr-D-Lys-Gly-Phe-L-homocysteine-thiolactone) is a mixed mu/delta opiate agonist. The peptide stimulated interdigestive gut motility at all parts of the intestine in conscious and anaesthetized animals. In dogs digestive motility, measuring mechanical activity, was stimulated with respect to segmental and propulsive properties. The canine uterus was sensitive to the enkephalin. Hoe 825 acts by i.v. or s.c. application, whereas the latter increases the duration of action significantly. The compound's effect can be blocked by naloxone indicating a receptor mediated action, which is localised peripherally. The compound is devoid of a dependence risk, because it does not penetrate into the CNS. At therapeutic doses (in the dog 0.5-2 micrograms/kg i.v.) the compound does not affect cardiovascular, renal or endocrine functions and was without effect on serum blood glucose levels in rats and rabbits.

Action Potentials↗
PubMed1983

Stimulation of colonic motility in dogs and rats by an enkephalin analogue pentapeptide.

Hoe 825 causes contractions of the large bowel in conscious dogs, this effect was poorly dose-dependent. The stimulatory effect could be blocked by naloxone. In the pentobarbital-anaesthetized rat, Hoe 825 led to a dose-dependent increase in contractions of the large bowel with a threshold dose of 0.3-1/microgram/kg i.v. and again the effect could be blocked by naloxone. The "in vitro" preparation of the rat colon strip could be brought to contractions in a dose-dependent manner with an IC50 of 2 X 10(-10) mol/ml. This sensitive in vitro test system might be a useful and simple bioassay for enkephalins, when their gut stimulating properties are under investigation. The enkephalin peptide Hoe 825 acts via peripheral opiate receptors and does not need central nervous innervation, at least in rats. The powerful effects of Hoe 825 on the large bowel in conscious and anaesthetized animals might be of therapeutic value in humans under conditions were gut motility is missing especially in paralytic ileus.

Animals↗
PubMed1983

Central and peripheral action of enkephalin analogues.

Chemical modifications of enkephalins led to analogues with strongly increased biological potency. Compounds such as H-Tyr-DLys(CHO)-Gly-Phe-L-homocysteinethiolactone (Hoe 825) additionally show a remarkable split between central and peripheral action, favouring the stimulation of gastrointestinal contractions. Hoe 825 could, therefore, be useful in the treatment of conditions where gut motility is lacking in humans, especially in adynamic ileus.

Animals↗
PubMed1981

Effect of 16,16-dimethyl prostaglandin E2 on gastric mucus gel thickness.

Direct measurements of the thickness of the layer of insoluble mucus gel lying on the gastric mucosa were made by using a slit lamp and an image-splitting system. Under resting conditions, the thickness (mean +/- SE) of the mucus gel on the gastric mucosa was 166 +/- 10 micrometers in the rat, 234 +/- 9 micrometers in the guinea pig, 429 +/- 17 micrometers in the dog and 576 +/- 81 micrometers in the human. Using a pylorus ligated rat model, topical application of 16,16-dimethyl prostaglandin E2 to the mucosa in concentrations of 1 microgram/ml and 10 micrograms/ml caused a dose dependent increase of the thickness of the mucus gel layer of 81% and 140% respectively. This drug-induced increase in mucus gel thickness may contribute to the cytoprotective effects of this prostaglandin analog.

Animals↗
PubMed1981

Gastric gel mucus thickness: effect of distention, 16,16-dimethyl prostaglandin e2, and carbenoxolone.

We made direct measurements of the thickness of the layer of insoluble gel mucus lying on the gastric mucosa by using a slit lamp and an image-splitting system known as a pachymeter. Under nonstimulated conditions, the thickness (mean +/- SE) of the gastric gel mucus on fundic mucosa was 166 +/- 10 micrometers in the rat, 234 +/- 9 micrometers in the guinea pig, 429 +/- 17 micrometers in the dog, and 576 +/- 81 micrometers in human stomach. Using a pylorus-ligation rat model, the effects of distention and of topical application of acid, 16,16-dimethyl prostaglandin E2 and carbenoxolone, on mucus gel thickness were studied. Distention of the stomach produced an increase in gel mucus thickness that was correlated with the degree of distention. This distention effect was not affected by pretreatment with methscopolamine or indomethacin. Topical application of 0.1 M HCl had no demonstrable effect on gel mucus thickness when compared with phosphate buffer, pH 7.4. 16,16-Dimethyl prostaglandin E2 applied to the mucosa in concentrations of 1 microgram . ml-1 and 10 microgram . ml-1 caused an increase in gel mucus thickness of 81% and 140%, respectively, and carbenoxolone, 2.5 mg . ml-1, an increase of 78%. These studies suggest that thickness of gel mucus overlying the gastric mucosa is dynamic, being subject to increase or decrease under certain physiologic and drug-treatment conditions.

16,16-Dimethylprostaglandin E2↗
PubMed1981

[Motility of the small intestine in dogs before and after total colectomy, proctomucosectomy and endorectal ileal pull-through].

In healthy dogs the parameters (amplitude and frequency) of small intestinal motility of segmental and propulsive contractions demonstrate a pressure-gradient directed from oral to aboral. The frequency of segmental contractions in the colo-rectal region shows a vector in the opposite direction. One rarely finds propulsive activity in this area. Following on colectomy, proctomucosectomy and ileum pull-through a distinct increase in segmental small intestinal activity is noticed, while the frequency of propulsive movements simultaneously decrease. Thus it comes to a slowing of the passage of intestinal contents, and to increased water resorption. From these findings we conclude that the small intestine plays an essential part in the regaining of fecal continence in these animals.

Animals↗
PubMed1980

Antiulcer effects of nomifensine, a new antidepressant, on stress-induced ulcers in the rat.

The effectiveness of the antidepressant agents 8-amino-1,2,3,4-tetrahydro-2-methyl-4-phenyl-isoquinoline (nomifensine, Alival) and amitriptyline on various ulcer models was tested by using at least 300 rats. Oral application of 3 mg/kg nomifensine resulted in a 50% decrease of stress ulcers produced by water immersion. Using an immobilisation ulcer model the ID50 of nomifensine was calculated to be 1.89 mg/kg p.o. Amitriptyline proved to be less active in both models. Neither er of the two compounds had any beneficial effects on ulcers produced by pyloric ligation. Gastric acid secretion stimulated with either histamine or pentagastrin, was not affected by nomifensine. Thus peripheral gastric effects of nomifensine could be ruled out, its antiulcer properties may be of central nervous origin. Affecting noradrenergic mechanisms in the hypothalamus could possibly play an important role.

Amitriptyline↗