Teratogenicity screening in standardized chick embryo culture: effects of dexamethasone and diphenylhydantoin

Teratogenic and toxic effects of DXM and DPH were tested using a standardized chick embryo culture. Survival, growth and malformations were scored with respect to the drug concentrations used. DXM (greater than 10(-8) mol/l) inhibited the differentiation of the extraembryonic blood circulation and induced craniofacial anomalies. DPH (greater than 1.5 10(-5) mol/l) induced cardiomegaly, craniofacial and somitic anomalies. Both drugs were lethal at 10(-3) mol/l. Comparison of results obtained with 8 drugs shows that the method has a good discriminative power and specificity and that it can be used as a simple, reliable and economical primary screening test, making it possible to reduce the use of animals in toxicological studies.     

Potentiating action of hexoprenaline on14C-aminopyrine uptake by isolated rat parietal cells

Summary Hexoprenaline potentiated the¹⁴C-aminopyrine uptake (a reliable index of H⁺ generation) of isolated rat gastric cells stimulated by 10^–6–10^–4 mol/l carbachol, and inhibited that in response to 10^–4 mol/l histamine without and in the presence of propranolol. It is concluded that hexoprenaline acts as a partial agonist on parietal cell H₂-receptors and that -adrenoceptor activation may functionally modualte gastric acid secretion.Acknowledgments. S. Maliski, Institute of Rheumatology, Warszawa, held a fellowship of the Alexander v. Humboldt-Foundation. The study was supported by the Deutsche Forschungsgemeinschaft. The skilful technical assistance of Mrs R. Maier and Mr R. Beer is gratefully acknowledged.     

Dexamethasone-induced neutrophilia. Negative correlation with increased plasma adrenaline concentrations

Summary Maximal increments in adrenaline and dexamethasone (DXM) plasma concentrations were observed c15 (T₅₀ 40 min) and 30 (T₅₀ 210–240 min) minutes after an i.v. DXM dose (6 mg/m² BSA) in man. There appears, however, to be no direct interaction between these agents in the development of induced neutrophilia, which occurs c240 min postinjection.Acknowledgments. The authors wish to thank Mrs C. Ditzler, Merck Sharp & Dohme Research Laboratories, USA, for determining the plasma dexamethasone concentrations J. M. M. is currently on sabbatical leave from McGaw Laboratories, USA. C. R. B. is a Rhodes scholar.     

Über «therapeutische» und «toxische» Digitoxigeninwirkungen auf elektrophysiologische Messgrössen des Meerschweinchenvorhofs

Summary Therapeutic concentrations of digitoxigenin (10^–7–3× 10^–7 g/ml), producing positive inotropic effects, did not alter resting and action potentials of electrically driven guinea-pig auricles. However, toxic concentrations of digitoxigenin (5 × 10^–7–10^–8 g/ml), producing arrhythmias and contracture of the myocardium, had a marked influence upon resting and action potentials and conduction velocity.     

Influence of atrazine (2-chloro-4-ethylamino-6-isopropylamino-s-triazine) on auxin metabolism of plants

Zusammenfassung Die Enzymaktivität der IES-peroxidase in Hafer-Koleoptilen wurde durch Atrazin in Konzentrationen von 10^–10–10^–21 M gehemmt, im Konzentrationsbereich von 10^–6–10^–8 M gesteigert. Atrazin förderte ferner das Wachstum von Sojabohnen-Kallusgewebe in Gegenwart von 5 mg/l Kinetin und 10^–10 bis 10^–18 M Atrazin im Nähragar. Diese Einwirkung von Atrazin auf den Wuchsstoffmetabolismus der Pflanzen gibt erste Anhaltspunkte, die zahlreich beobachteten Förderungen bzw. Hemmungen des Pflanzenwachstums unter dem Einfluss von Atrazin zu erklären. Die Resultate bilden weiterhin eine neue Grundlage für eine mögliche Interpretation des «Proteineffekts» der Triazine.     

Influence of cyclic nucleotides on protein synthesis in vascular smooth muscle

Summary The incorporation of leucice-¹⁴C into protein in bovine mesenteric arteries was augmented by cyclic GMP (10^–3 M) and decreased by cyclic AMP (10^–3 M). There was no effect of 5 AMP (10^–3 M). The phosphodiesterase inhibiting drugs theophylline (10^–3 M) and papaverine (5×10^–5 g/ml) both decreased the leucine-¹⁴C incorporation.We are indebted to Mrs.Lena Burlin for hear assistance. Finacial support has been provided by the Swedish State Medical Research Council (No. 04X-101X-4498).     

Catecholamines in bovine semen

Summary In seminal plasma 5×10^–6 M noradrenaline was found to induced head-to-head association in bull spermatozoa. The sum of noradrenaline and adrenaline in freshly collected semen was 10 ng/ml (5.2×10^–8M), i.e., about 100 times lower than previously reported.     

Nitric oxide-related pancreatic endocrine responses to hyperglycaemia in the conscious calf

Mean plasma insulin concentration was reduced and mean plasma glucose concentration increased following the administration of N-nitro-L-arginine methyl ester (L-NAME; 100 mol kg^–1 i.a.) in conscious calves given continuous infusions of exogenous glucose (30–60 mol min^–1 kg^–1 i.v.). It is concluded that the rise in plasma insulin concentration which occurs in these animals in response to glucose is mediated, at least in part, by a nitric oxide-related factor (NOx).     

Role of calcium in the histamine release induced by D-galactosamine from rat mast cells

Summary Rat peritoneal mast cells were isolated and purified by differential centrifugation in Ficoll. Cells pooled from three to four rats were suspended at approximately 10⁶ cells/ml in a buffered salt solution and incubated for 1 h at 37°C in 300 l volumes in the absence or presence (9×10^–4 M) of calcium chloride. Addition of D-galactosamine hydrochloride (DGM; 2.8×10^–4 M) caused (in addition to basal release) a mean ±SEM percent histamine release of 15.7±5.2 in the presence of Ca⁺⁺ and 19±4.9 in the absence of Ca⁺⁺ (p>0.05). It is suggested that D-galactosamine does not require extracellular Ca⁺⁺ for the release of histamine from the rat mast cell.A preliminary analysis of these results was presented at the International Symposium on calcium entry blockers and tissue protection, Rome, 15–16 March 1984.     

Activité antifibrillante chez l'animal d'un nouveau dérivé de la phényl-éthylamine

Summary A new synthetic phenyl-ethyl-amine derivative, the 2-[N- (3, 4-methylen-dioxyphenylethyl)-methylaminomethyl]-tetrahydrofuran, No. 11 081, exhibits a strong protective effect against cardiac fibrillation and arrhythmias produced by various experimental methods: against fibrillation due to aconitine 3 × 10^–8 on the isolated cat's heart, it is active in a concentration of 10^–6–2 × 10^–6. Against cardiac arrhythmias produced in the cat by adrenaline + CHCl₃ or cyclopropane, it shows a protective effect by 5–10 mg/kg i.v. and even perorally by 50 mg/kg. In these tests, the antifibrillatory activity of the new compound seems to be roughly the same as that of -fagarine, and higher than that of procaine.

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9^e communication sur les dérivés des alcoylène-imines; 8^e communication, cf. Exper.10, 261 (1954).     

The action of iodoacetate on the antigenic power of insulin

Résumé Nous avons observé que le iodoacétate en concentrations de 1·10^–4, 5 · 10^–5 et 1 · 10^–5 M et préalablement incubé à 37 °C, a une influence de l'ordre de 61, 50 et 44% respectivement sur la totalité du pouvoir antigénique de l'insuline de buf. L'effet inhibitif est proportionnel à la durée d'incubation et l'on ne constate pas de différences lorsque les concentrations de l'hormone se trouvent entre 100 et 300U/ml.     

The activation of membrane ATPase by ouabain in several tissues of the golden hamster (Mesocricetus auratus) in the absence of potassium

Summary The activity of the membrane ATPase of 5 organs of the golden hamster was increased by 10^–7–10^–3 moles/l ouabain in K⁺-free medium. In similar experiments on rats no increase was observed.     

Influence of serotonin on the radiation sensitivity of lactate dehydrogenase

Zusammenfassung Die Veränderungen in der Strahlenempfindlichkeit von Milchsäuredehydrogenase durch Serotonin, gebraucht als Serotonin-Kreatinin-Sulfat, wurden spektralphotometrisch untersucht. Die Bestrahlungsdosen variierten zwischen 0–9 · 10⁵ R. Die Serotonin-Konzentrationen variierten zwischen 0–1,23 mM. Die D³⁷-Dosis für eine Serotonin-Konzentration von 246M ist ca. 34mal grösser als für die Kontrollen. Der Schutzeffekt kann durch eine Komplexbildung zwischen Serotonin und den Metallionen, die im Enzym-Molekül vorhanden sind, erklärt werden.     

Effect of strychnine on the electroretinogram of the isolated rabbit retina

Zusammenfassung Strychnin in einer Konzentration von 3×10^–6 bis 3,5×10^–5 M/l verursacht eine vorübergehende Vergrösserung derb-Welle des ERG der isolierten Kaninchennetzhaut, in einer Konzentration von 7×10^–5 bis 7×10^–4 M/l verkleinert es dieb-Welle. Aus den Ergebnissen wird geschlossen, dass die Substanz zumindest teilweise schon auf die Schicht des zweiten Neurons wirkt.     

Cartsian diver studies on respiration of rat bone marrow cells in the presence of erythropoietin and anti-erythropoientin

Résumé L'étude de la respiration des cellules de la moelle des os du rat fut faite avec un plongeur Cartésien. Ces cellules, avec ou sans glucose, repirent à raison de 0,73±0,15 et 0,97±0,17×10^–6 l O₂/cellule/h. Comparée aux mesures de contrôle, la respiration des cellules médullaires de rats pléthoriques est plus fabile en présence de ESF (0,45 contre 0,99×10^–6 l, O₂/cellule/h). Cette inhibition fut supprimée par la présence d'anti-ESF (0,98 contre 0,99×10^–6 l O₂/cellule/h).

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This research was supported by funds from a Damon Runyon Cancer Research Training Grant and the US Public Helath Seervice. The senior author was a Damon Runyon Post-Doctoral Traince.     

A specific binding protein for the moulting hormone ecdysterone in locust haemolymph

Summary Specific binding of³H-ecdysterone to a high mol. wt. protein from Locusta migratoria haemolymph was shown by gel filtration. The hormone-protein complex shos a dissociation constant K_d3.10^–7 M, and the concentration of binding sites varies during the last larval instar.     

Inhibition and sex specific induction of spawning by serotonergic ligands in the zebra musselDreissena polymorpha (Pallas)

Serotonin (5-hydroxytryptamine, 5-HT) stimulates spawning in the zebra mussel (Dressena polymorpha), a macrofouling European bivalve that has recently invaded North America. To develop methods of controlling zebra mussel spawning, two vertebrate serotonin antagonists, methiothepin and metergoline, known to bind with high affinity to snail 5-HT receptors, were tested for their ability to block 5-HT-induced spawning in zebra mussels. Methiothepin inhibited 5-HT-induced spawning at concentrations as low as 10^–6 M. Metergoline (10^–4 M) inhibited 5-HT-induced spawning; however, at lower concentrations (10^–8 to 10^–5 M), metergoline by itself significantly induced spawning in male, but not female zebra mussels. Metergoline (10^–5 M)-induced male spawning was inhibited by 10^–5 M methiothepin. Thus, methiothepin is the most effective inhibitor and metergoline the most powerful inducer of spawning yet tested in zebra mussels.     

Über das Problem der Welkekrankheiten bei Pflanzen

Summary Lycomarasmin is a plasma poison produced byFusarium lycopersici Sacc., the pathogen of tomato wilt. In a dilution of 10^–2 and 10^–3 mol it causes a pathological wilting of tomato plants and usually disturbs their water balance; in a dilution of 10^–4 mol it only disturbs the latter.In the present paper, we develop the theory that in sufficient concentration lycomariasmin damages or destroys thesemipermeability of the plasma boundary layer.In a dilution of 10^–2 and 10^–3 mol of lycomarasmin the semipermeability of the plasma membranes iscompletely destroyed. Thus on the one hand the conditions for osmotic pressure disappear and irreversible pathological wilting appears, and on the other hand cellular fluid passes into the transpiration current of the cell-membrane and leads to a momentary excess humidity, particularly in the leaf-tissues, and thus also to a momentaryexcess transpiration.The water-deficit regularly observed in wilt-literature is therefore not the cause of pathological wilting but, just as the wilting itself, a consequence of the distruction of the semipermeability of the plasma boundary layer.In a dilution of 10^–4 mol lycomarasmin apparently only affects the permeability of the exterior plasma boundary layer forwater, but not for sugars etc. Therefore it only produces an excess of fluid in the leaf tissues and thus an excess transpiration, but no definite inactivation of the plasma membrane and therefore also no pathological wilt.     

Studies on hydrogen,halides and thiocyanate ions in dioxane-water mixtures at various temperatures

Summary The free enrgies of transfer (G _t ⁰ ) of H⁺, Cl^–, Br^–, I^– and SCN^– ions from water to 10, 20, 30 and 40% dioxanewater mixtures have been studied from potentiometric measurements. For anions the G _t ⁰ values are in the order Cl^–>Br^–>SCN^–>I^–.     

Dissociation-constants of metal-ion-complexes with alkaline phosphatase from pig kidney

Summary Using metal-ion buffers it was possible to remove Zn²⁺, Mg²⁺ and Mn²⁺ ions of pig kidney alkaline phosphatase reversibly. The dissociation constants obtained are K_EMg:4·10^–7 M, K_EMn:4·10^–8 M and K_EZn:8·10^–13 M (22°C, pH:9.6, :0.07).Acknowledgement: The authors thank Dr.H. U. Wolf for helpful suggestions and valuable discussion and MissH. Köth for technical assistance.