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Biomedical subjects

A Danielsson

Publications and source records attributed to A Danielsson.

At least 163 records · Page 9Linked to original sources

Effect of fifteen months of double-blind treatment with cimetidine and placebo on peptic ulcer recurrence.

Forty-Five consecutive patients with chronic peptic ulcer disease completed a double-blind controlled trial in which they were given cimetidine 0.8 g daily or placebo in order to evaluate the preventative effect of the drug on ulcer recurrence. On entering the trial all patients had endoscopically healed ulcers. Endoscopy was performed again at 6 and 15 months, or if there were severe epigastric pains. The period of medication was 15 months, and the patients still in remission at that time were observed for a further 9 months. During the course of the study 11 out of 23 patients (47.8%) in the placebo group developed re-ulceration, whereas 4 out of 22 (18.2%) patients relapsed while on cimetidine (p less than 0.05). There were significantly fewer weeks of dyspepsia and better general well-being in the cimetidine group as compared to the placebo group. No early ulcer recurrence or increased rebound acid secretion was noted after cessation of the cimetidine treatment. Vitamin B12 absorption was not affected by the 15-month cimetidine treatment. Two men developed gynaecomastia, one died of myocardial infarction and one had transient sinus bradycardia during cimetidine medication. Cimetidine improves the symptomatic state and postpones ulcer recurrence as long as treatment is maintained.

Adult↗

Characterization of the rat parotid beta-adrenoceptor.

1 The effects of various beta-adrenoceptor agonists on amylase secretion from the rat parotid gland were studied by means of two different in vitro techniques. 2 The dose-response relation for each agonist was established, as also were the ED50 values. 3 All drugs appeared to act directly on the acinar cells, as reserpine-treatment did not abolish their secretagogic effects. 4 Two groups of agonists could be distinguished: one group consisting of adrenaline, noradrenaline and the B1-selective agonist prenalterol (H133/22) with a high enzyme discharge potency and a second group consisting of the beta 2-agonists, terbutaline and salbutamol, with a markedly lower effect. 5 The present data further support the theory that rat parotid acinar cells are supplied mainly with beta-adrenoceptors of the beta 1-subtype, similar to those present in heart and adipose tissue.

Adrenergic beta-Agonists↗

The relationship between active peptic ulcer, endoscopic duodenitis and symptomatic state after treatment with cimetidine.

Fifty patients with active peptic ulcers on endoscopy were randomly allocated for treatment with placebo or cimetidine (1.0 g daily) over a period of four weeks. All patients had free access to antacids to relieve epigastric pain. In the cimetidine group a significantly higher proportion of the ulcers had healed (82.6% of the patients) compared with the placebo group (48.0%). There was poor correlation between the healing of the ulcer and dyspeptic symptoms in the placebo group. The results suggest that the presence of endoscopic duodenitis is to a great extent responsible for the dyspepsia. Cimetidine treatment, besides healing the ulcers, also improved the endoscopic duodenitis and the symptomatic state more than placebo treatment. No significant clinical side effects were observed. Chemical abnormalities were only noted with respect to serum creatinine. In the cimetidine group there was a statistically significant rise in serum creatinine, which was most apparent after two weeks of treatment. However, the increase was slight and not significant among the males, whereas in the case of the females there was a large and highly significant rise. The reason for this sex difference is at present unknown.

Adolescent↗

Dynamics of beta adrenoceptor induced amylase release and cyclic AMP accumulation in the guinea pig submandibular gland.

The dynamics of amylase release from the guinea pig submandibular gland were studied in vitro by applying a multi-channel microperfusion set. This technique makes it possible to measure time related enzyme release more accurately and to take samples of perifused tissue at short intervals. Stimulation of the beta-adrenoceptor with norepinephrine gives rise to a rapid initial enzyme discharge, detectable within 15 s. Administration of propranolol inhibits enzyme release, which is not restored after removal of the agent. Simultaneous measurements of tissue cyclic AMP during norepinephrine stimulation at various time intervals display a significant increase of cAMP as early as 15 s after stimulation of secretion. This increase of cAMP thus coincides with the discharge of amylase. In addition, cAMP continuously accumulates during 30 min of norepinephrine perifusion of the slices. The present study describes a valuable tool with high sensitivity for visualizing the relations between enzyme secretion from the salivary gland and the intracellular biochemical processes. The data obtained further indicate a close correlation between amylase and cAMP during the initial phase of enzyme discharge.

Amylases↗

Effect of long term treatment with hydrophilic colloid on serum lipids.

Thirteen patients with essential hyperlipoproteinaemia were treated over periods of 2--29 months with hydrophilic colloid made from Psyllium. Reduction of the increased serum cholesterol levels averaged 16.9 per cent, and the corresponding figure for the increased triglyceride levels was 52.0 per cent. The reduction of cholesterol and triglyceride was statistically significant (p less than 0.0025 and p less than 0.0005 respectively). No significant change in normal blood lipid levels was observed on administration of the Psyllium colloid.

Adult↗

Quantitative structural analysis and the secretory behaviour of the rat parotid gland after long and short term isoprenaline treatment.

Isoprenaline (IPR) was administered as daily subcutaneous injections into newborn rats for a period of 9 weeks (long-term treatment) and into 8 week-old rats for 10 days (short-term treatment). Both the parotid and the submandibular glands increased five- to six-fold in weight in the two groups due to hypoertrophy as well as to hyperplasia. The parotid glands were subjected to electron microscopic stereological analyses and to in vitro secretory studies. The results were compared with non-treated controls. Whereas mean total cell volume in the latter was 807 microns 3 it amounted to 5804 microns 3 in glands from long-term IPR-treated rats. A striking increase in size and number of cytoplasmic granules was noted after IPR treatment; there was also a marked decrease in granule electron density as compared with control cells. Granule volume density was 31.2 +/- 1.8% in controls and 58.0 +/- 1.5% in long-term IPR-treated rats. The increase in volume density, however, was accompanied by a relative decrease in amylase and cyclic AMP contents. On a percentage basis, the basal secretion of amylase from incubated IPR-treated parotid glands was markedly higher (roughly twice) than that of control glands; the absolute release of amylase into the medium, however, was only slightly increased. Basal secretion was not energy requiring, which would suggest a passive diffusion. Stimulation by beta-adrenoceptor agonists, including beta 1 and beta 2 selective agents, had no or only a small stimulatory effect in vitro on IPR-treated glands. Dibutyryl cyclic AMP was effective in controls but not in treated glands. Cholinergic stimulation caused a considerable amylase release from glands of IPR-treated rats; this release was comparable to that obtained in controls. The results suggest that superstimulation of the beta-adrenoceptor leads to a decreased sensitivity for adrenergic agonists. This may be due to membrane changes (e.g. modified receptor sites) and/or to an altered intracellular metabolism (e.g. a modified turnover of cyclic nucleotides).

Adrenergic beta-Agonists↗

Effects of cholecystokinin-pancreozymin on amylase synthesis and secretion in the mouse pancreas.

Perfusion of mouse pancreatic slices revealed that continuous exposition with cholecystokinin-pancreazymin (CCK-PZ) provokes an initially high peak of amylase secretion, which is followed by a slow decline in enzyme discharge. A return to the basal secretory level is noticed after about 45 min. Repeated pulse stimulations with CCK-PZ result in a more efficient stimulation of pancreatic amylase release, compared to a continuous stimulation. In the presence of CCK-PZ for 45 min, as well as during a post-stimulatory period of 45 min, a significant depression of L-(U-14C) leucine incorporation into amylase as well as total protein is recorded. In conclusion, in vitro incubated mouse pancreatic slices thus seem to be unable to increase their rate of protein synthesis during and after stimulation of secretion.

Amylases↗

Secretory behavior and ultrastructural changes in mouse gallbladder principal cells after stimulation with cholinergic and adrenergic drugs. A morphometric study.

Principal cells of mouse gallbladder epithelium were subjected to a quantitative electron microscope study after in vivo and in vitro exposure to pilocarpine, noradrenaline, atropine, and phenoxybenzamine. Stereologic measurements were performed on randomly selected principal cells, and special interest was paid to changes in the size of the secretory granule population of the cells. Thirty minutes after in vivo and in vitro stimulation with pilocarpine, there was a significant decrease of the volume density of the glycoprotein-containing granules in the principal cells. Thirty minutes after in vivo administration of the cholinergic antagonist atropine, a significant increase of this parameter was observed. In vitro incubation for 30 min with a combination of pilocarpine and atropine extinguished the pilocarpine-induced effect on the secretory granules. Noradrenaline and phenoxybenzamine (an alpha-adrenergic blocking agent) in vivo and in vitro (30 min) had no effect on the volume density of the secretory granules. The authors' findings suggest that principal cells of the mouse gallbladder epithelium exhibit an increased rate of secretion of glycoprotein granules after stimulation in vivo and in vitro with cholinergic agents, whereas adrenergic agents are without effect.

Animals↗

The binding of low-affinity and high-affinity heparin to antithrombin. Fluorescence studies.

The interaction between antithrombin and two forms of heparin, differing in their affinity for the matrix-linked protein, has been studied by fluorescence. The binding of the high-affinity heparin fraction to antithrombin leads to activation of the inhibitor, allowing it to react more rapidly with a number of serine proteases of the coagulation cascade. The interaction with the low-affinity heparin fraction, however, has considerably less influence on this inhibition rate. The binding of either fraction to antithrombin was found to result in an increase of the tryptophan fluorescence of the protein. This increase was much larger for high-affinity heparin than for low-affinity heparin, suggesting a different mode of binding of the two fractions to the protein. The fluorescence enhancement caused by high-affinity heparin is consistent with a conformational change of antithrombin related to its activation. Only the fluorescence enhancement observed on the binding of high-affinity heparin was of a sufficient magnitude to allow quantitative studies. These showed high-affinity heparin to bind to antithrombin with a stoichiometry of about one and with a binding constant at physiological ionic strength of about 8 X 10(7) M-1. At higher ionic strengths, however, the affinity decreased markedly.

Animals↗

Effects of a new selective beta1-adrenoceptor agonist on amylase secretion from the rat parotid gland.

The effects of a new selective beta1-adrenoceptor agonist, (--)-1-(4-hydroxyphenoxy)-3-isopropyl-amino-propanol-2-hydrochloride (H 133/22), on amylase secretion from the rat parotid gland were investigated in an in vitro system. The results were compared to the secretory responses obtained with noradrenaline, adrenaline, methoxyamine and terbutaline. H 133/22 was found to be a potent enzyme secretagogue and appeared even more effective than noradrenaline and adrenaline, particularly at low concentrations. The beta1-adrenoceptor agonist, terbutaline, also stimulated amylase discharge from the parotid gland but was much less potent than H 133/22. Methoxyamine had no effect on enzyme secretion. We suggest that the adrenergic stimulation of amylase secretion from the rat parotid gland is mainly mediated by beta1-receptors.

Adrenergic beta-Agonists↗

Ultrastructural cytochemistry of the secretory granules of the hamster submandibular gland.

The ultrastructure and cytochemistry of the secretory granules of the male hamster submandibular salivary gland were studied; After fixation in glutaraldehyde followed by osmium tetroxide the granules exhibit a characteristic bipartite substructure, with an electron lucid crescenteric rim and a more dense central core. A differentiation into two regions of the granules could also be visualized in specimens primarily fixed in Millonig's osmium tetroxide or in potassium permanganate. The electron lucid peripheral portion of the membrane bounded secretory granules further displays a strong positive reaction after staining of ultrathin sections with the periodic acid-chromic acid-(PA-CrA)-silver technique. The strong periodate reactivity of the rim relative to the core, suggests a difference in mucin composition of the two granule regions. With the PA-CrA-silver straining technique a positive reaction was also observed within the Golgi apparatus of the acinar cells.

Animals↗

Effect of cholecystokinin-pancreozymin (CCK-PZ) on glycoprotein secretion from mouse gallbladder epithelium: an ultrastructural and cytochemical study.

Structural changes in the gallbladder epithelial cells of the mouse were studied following in vivo and in vitro stimulation of the gallbladder with the gastrointestinal hormone cholecystokinin-pancreozymin (CCK-PZ). Signs of increased secretory activity were observed within the first 2-3 min after hormone administration. At the ultrastructural level, best visualized with the PA-CrA-silver technique, granule discharge was observed, as was an overall increase in size of the granules. After prolonged in vitro incubation or repeated in vivo stimulation, there was an almost total depletion of secretory granules. This phenomenon is accompanied by an enhanced uptake of extracellular thorium dioxide by endocytotic vesicles at the apical cell surface. An exocytosis-endocytosis coupling mechanism may be important for membrane conservation in the gallbladder epithelial cells. The findings establish that the hormone CCK-PZ stimulates the secretion of glycoproteins from the mouse gallbladder epithelium.

Animals↗

Uptake, localization and secretagogic action of some biogenic amines in the submandibular and pancreatic glands of the guinea pig.

The effects of noradrenaline, 5-hydroxytryptamine (5-HT) 5-hydroxyptophan (5-HTP), dopamine, L-DOPA and carbamylcholine on the secretion of amylase from guinea pig submandibular gland and pancreas were studied. Carbamylcholine stimulated both pancreatic and salivary gland amylase release, whereas the biogenic amines elicted amylase secretion only from the submandibular gland. L-DOPA and 5-HTP, the precursor amino acids of dopamine and 5-HT, were without effects. In both glands 5-HT and dopamine were accumlated to a greater extent than their precursor amino acids. The uptake of biogenic amines into acinar cells and their effects on amylase secretion are compared and dicussed in terms of receptor specificity.

5-Hydroxytryptophan↗