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Biomedical subjects

D Andersen

Publications and source records attributed to D Andersen.

At least 37 records · Page 2Linked to original sources

Scientific dishonesty: a Danish proposal for evaluation and prevention.

The term scientific dishonesty covers the wide scope from consciously fraudulent actions to gross negligence and refers both to character trait and to actions. Scientific dishonesty may occur in any country, but reactions in Europe have been slow to emerge. On the basis of a thorough review, the Danish Medical Research Council therefore has made recommendations on how to handle and how to prevent scientific dishonesty. Suspected cases must be referred directly to a national committee chaired by a High Court judge. An ad hoc investigatory committee may be appointed in each case. If dishonesty is established, the institution then is asked to implement appropriate sanctions and to report on the actions taken to the national committee. Prevention of scientific dishonesty forms an essential part of good scientific practice and must have an impact on research training, requirements for data storage, guidelines for scientific publication, and criteria for evaluating grant proposals and promotions.

Denmark

Thermal chemistry of podophyllotoxin in ethanol and a comparison of the cytostatic activity of the thermolysis products.

Podophyllotoxin (1) in buffered ethanolic solution is degraded by two pathways. One leads to (a) picropodophyllin (2), which undergoes dehydration to give alpha-apopicropodophyllin (5), which rearranges to give beta-apopicropodophyllin (6), (b) the ethyl ether of picropodophyllotoxin, 8, and (c) the ethyl ether of epipicropodophyllotoxin, 7. The other pathway leads directly to epipodophyllotoxin (10) and the corresponding ethyl ether, 9, and possibly, via a transient 3,4-dehydropodophyllotoxin (5'), to beta-apopicropodophyllin (6). The 1H NMR spectra of these compounds are described, their in vitro cytostatic activity compared, and their syntheses, including that of podophyllotoxin ethyl ether, reported.

Antineoplastic Agents

Beta adrenoceptor density and adenylate cyclase response in right atrial and left ventricular myocardium of patients with mitral valve disease.

Beta adrenoceptor density, measured by radioligand binding techniques, is reportedly much higher in atrial than in ventricular myocardium of patients with mitral valve disease. In the present study adenylate cyclase activity, both basal and in response to beta adrenergic agonists and sodium fluoride, in biopsy preparations from these same patients was significantly lower in atrial than in ventricular tissue when stimulated with either isoproterenol, noradrenaline, isoproterenol combined with terbutaline, or sodium fluoride. Terbutaline stimulated and basal adenylate cyclase activity was not significantly different in the two cardiac regions. The ratios of receptor density to isoproterenol stimulated and to sodium fluoride stimulated adenylate cyclase activity were 4-5 times higher in atrial than in ventricular biopsy specimens. Thus ventricular beta receptors, although present in comparatively low concentrations, are coupled to considerably more catalytic moieties of the receptor-adenylate cyclase complex than their atrial counterparts. The reason for this is probably a relative lack of coupling proteins (N components) in atrial tissue. A weak positive correlation between receptor density and isoproterenol stimulated adenylate cyclase activity was found in atrial but not in ventricular tissue. This may indicate individual variation in receptor-adenylate cyclase coupling. Furthermore, no correlation was found between atrial and ventricular values for any variable. One reason for this may be the different haemodynamic stresses in the two cardiac chambers.

Adenylyl Cyclases

The use of indium-111-labelled platelets for scintigraphic localization of gastrointestinal bleeding, with special reference to occult bleeding.

Gamma-camera imaging of the abdomen after injection of autologous 111In-labelled platelets was applied for localization of gastrointestinal bleeding in a study of 22 patients. In 15 studies showing scintigraphic signs of bleeding, the clinical presentation included occult bleeding in 6, melaena in 4, and bloody stools in 5. Scintigraphy could be done repeatedly for up to 1 week after a single tracer injection. The time interval between the injection and scintigraphic visualization of bleeding ranged from 10 min to 68 h, being longest in cases of occult bleeding. In most cases the scintigraphic findings were supported by other diagnostic modalities, including surgical removal of presumed sources of bleeding. In seven studies without scintigraphic signs of bleeding a probable source of bleeding was identified by other means in one patient. The 111In-platelet method seems to be a promising method for localization of gastrointestinal bleeding which may prove particularly useful in cases of occult or recurrent bleeding.

Adolescent

Hypertrophic cardiomyopathy characterised by beta-adrenoceptor density, relative amount of beta-adrenoceptor subtypes and adenylate cyclase activity.

The total quantity of beta-adrenoceptors and the relative amount of beta 1 and beta 2 receptor subtypes were determined in heart biopsies of 10 patients with various heart diseases and 5 patients suffering from hypertrophic cardiomyopathy (HOCM). In membrane particle preparations from the same patients we also examined the activity of the adenylate cyclase (AC), and its response to isoprenaline, terbutaline, histamine and sodium fluoride (NaF). The high affinity ligand [125I] (1)-cyanopindolol (CYP) was used in the binding assays, and the highly beta 2-selective antagonist ICI 118 551 for the determination of beta-adrenoceptor subtypes. No differences were found in total beta-adrenoceptor density between patients with HOCM and "controls" (27.6 +/- 14.2 vs 26.5 +/- 10.7 fmol . mg-1 protein). The relative amounts of beta 1 and beta 2 receptor subtypes were similar, patients with HOCM had 82.1 +/- 4.9% of beta 1 and 14.4 +/- 3.9% of the beta 2 receptor subtype, compared with 76.3 +/- 11.5% of beta 1 and 20.7 +/- 11.0% of the beta 2 subtype in the "control" patients. Both absolute activity of AC (pmol . mg-1 protein . min) as well as the relative responses to the various stimulators were not significantly different between the two groups. Thus, this study does not support the hypothesis that HOCM is a disorder with altered beta-adrenoceptor number or adenylate cyclase response to adrenergic agonists. Furthermore, HOCM is not associated with altered response of the AC system to histamine or NaF.

Adenylyl Cyclases

Effect of serotonin on pentagastrin-stimulated gastric acid secretion and gastric antral motility in dogs with gastric fistula.

The effects of exogenous serotonin on pentagastrin-stimulated gastric acid secretion and antral motility were evaluated with regard to inhibition kinetics and receptor mediation. Conscious gastric fistula dogs were used. Serotonin inhibited the acid secretion dose-dependently, whereas the antral motility was initially stimulated and thereafter inhibited. The inhibition of secretion was counteracted by different beta-adrenergic blocking drugs and methysergide, whereas the inhibition of antral motility was blocked by methysergide and indomethacin. Dose-response analysis showed inhibition of non-competitive types. This study supports the concept of differences in the regulation of gastric acid secretion and motility, but further experiments with simultaneous registration are required.

Animals

Effect of serotonin on pentagastrin-stimulated gastric pepsin secretion in dogs with gastric fistula.

The effect of serotonin on pentagastrin-stimulated gastric pepsin secretion in dogs was evaluated with regard to dose-response kinetics and receptor mediation. The pepsin secretion showed a dual response to exogenous serotonin. The high and low doses of serotonin stimulated, whereas the doses in between inhibited. The inhibition was of a non-competitive type and could be significantly counteracted by beta-adrenergic blocking drugs. This study supports the concept that the serotonin effect on gastric functions is mediated via sympathetic nerves releasing noradrenaline.

Adrenergic beta-Antagonists

Exogenous serotonin and gastric mucosal blood flow in conscious dogs.

The effects of serotonin on pentagastrin- and bethanechol-stimulated gastric mucosal blood flow (GMBF) and acid secretion were evaluated. Conscious gastric fistula dogs were used, with neutral red clearance as the method to estimate the mucosal blood flow. Serotonin inhibited the acid secretion, with a counteracting effect of propranolol and methysergide. Serotonin inhibited the pentagastrin- and bethanechol-stimulated GMBF after 15 min of infusion. The ratio between GMBF and acid secretion was increased during serotonin infusion, which suggests primary and independent changes in both variables. Propranolol and methysergide counteracted the serotonin inhibition of the GMBF. It may be concluded from this study that the acid-inhibitory effect of serotonin is not mediated by changes in the GMBF. The actions of serotonin on acid secretion and GMBF are mediated by specific receptors.

Animals

Effect of somatostatin on bethanechol-stimulated gastric pepsin secretion in gastric fistula dogs.

The effect of somatostatin on pepsin secretion was determined in six dogs with gastric fistulas during stimulation with bethanechol. Somatostatin inhibited dose-dependently the stimulated pepsin secretion, with a dose of 0.3 micrograms/kg/h being 35% inhibitory during stimulation with bethanechol, 80 micrograms/kg/h. Continuous infusion of somatostatin for 3 h did not cause any signs of tachyphylaxis. Withdrawal of somatostatin produced a return to the control level. The dose-response kinetics with five doses of bethanechol with and without somatostatin showed inhibition of a noncompetitive type. The effects of somatostatin were not altered by using adrenergic, dopaminergic, or serotonergic blocking drugs.

Adrenergic beta-Antagonists

Effect of somatostatin on bethanechol-stimulated gastric acid secretion and gastric antral motility in dogs with gastric fistula.

The purpose of the present study was to evaluate the effect of somatostatin on gastric acid secretion and gastric antral motility in conscious dogs with gastric fistula. Infusion of bethanechol stimulated dose-dependently acid secretion, whereas the frequency and strength of antral motility was maintained at a high level. Somatostatin inhibited dose-dependently the stimulated acid secretion, whereas the effect on antral motility was more complex, acting especially on the amplitude of the contractions. The effects of somatostatin were not altered by using alpha-adrenergic, beta-adrenergic, dopaminergic, and serotonergic blocking drugs. The dose-response kinetics with four doses of bethanechol with and without somatostatin showed inhibition of a non-competitive type for gastric acid secretion and of a competitive type for antral motility with regard to amplitude.

Adrenergic alpha-Antagonists