Mammatumorhemmende Antiöstrogene vom Typ des 3,3′-Dihydroxy-α,β-dialkylstilbens

Mammary Tumor Inhibiting Antiestrogens of the 3,3′-Dihydroxy-α,β-dialkylstilbene Type. The trans-3,3′-dihydroxy-α,β-dialkylstilbenes 1, 3–5 are antiestrogens with a marked effect on the DMBA-induced hormone dependent mammary carcinoma of the SD-rat (especially 3 and 4 ). They are synthesized by reaction of (3-methoxyphenyl)diazoalkanes c with SO₂ to give 1,1-dioxo-2,5-dialkyl-2,5-bis-(3-methoxyphenyl)-Δ³-1,3,4-thiadiazolines d . Thermal decomposition yields the 3,3′-dimethoxy-α,β-dialkylstilbenes e which are then subjected to ether cleavage.     

Close correlation between behavioural response and binding in vivo for inhibitors of the rolipram-sensitive phosphodiesterase

The antidepressant rolipram interacts in vitro with a binding site in brain tissue labeled by³H-rolipram. A³H-rolipram binding assay was employed in vivo to compare the affinity of rolipram-related compounds and reference phosphodiesterase (PDE) inhibitors with their potency in behavioural measures for potential antidepressant property. In two species, mice and rats, the potency of a number of compounds to antagonise reserpine-induced hypothermia (mice) and to induce head twitches (rats) was determined, as well as their potency to displace³H-rolipram from forebrain binding sites in vivo. The treatment schedules for the two series of experiments were identical. Significant correlations between pharmacological effects and displacement of³H-rolipram binding in vivo were observed in both species. Since the reference PDE inhibitors closely fit into the binding-pharmacological activity relationship, the PDE inhibitory properties of the substances involved are discussed.     

Kinetic and morphological changes induced in human blood leucocytes by cytochalasin D and E

Summary The effect of increasing concentrations of cytochalasin D and E, up to toxicity, on the velocity of blood leucocytes from normal subjects was measured in vitro using a high-resolution objective and phase-contrast time-lapse photography. The dose-response effect for the two different cytochalasins differed in accordance with the different cell specificity of their membrane binding. The average velocity of granulocytes was reduced at cytochalasin D concentrations above 5×10^–7M and cytochalasin E concentrations above 5×10^–5M. The effect on monocytes and eosinophils was similar. In contrast the velocity of lymphocytes was not affected until cytotoxic concentrations were reached.The concentration ranges which inhibited locomotion corresponded well with the concentration ranges of the cytochalasins which have an in vitro effect on microfilaments. The concentrations which induced additional morphological changes in lymphocytes also correlate well with the concentrations found to inhibit cross-linking in vitro, as well as those known to induce morphological changes in, for example, fibroblasts in vivo. Cytotoxic effects were first observed with ten-fold higher concentrations of cytochalasin E than of cytochalasin D.     

Measurement of septal release of vasopressin and oxytocin by the push-pull technique following electrical stimulation of the paraventricular nucleus of rats

The release of vasopressin (AVP) and oxytocin (OXT) within the septum was studied with the push-pull perfusion technique in 6 conscious, freely behaving male rats. Push-pull perfusion was performed viaa chronically implanted cannula and samples collected for 3 consecutive 30-min periods. Stimulating electrodes were implanted in both the left and right paraventricular nuclei 4 days before the experiment. Bilateral electrical stimulation (10-s trains every 4 min) of the paraventricular nuclei during the second 30-min period resulted in a significant increase in the release of both AVP and OXT (128% and 159% of control values respectively); release returned to the pre-stimulation value during the final 30-min collection.     

Activity of cis-bis(glycylglycine ethyl ester)platinum(II) chloride-effects on nucleic acid metabolism

Studies on the Activity of cis-Bis(glycylglycine ethyl ester)platinum(II) Chloride — Action on the Nucleic Acid Metabolism cis-Pt(GlyGlyOEt)₂Cl₂ (2) interfers with the nucleic acid metabolism by inhibiting the DNA template activity, the DNA and RNA polymerase and the ribonucleotide reductase system.     

Bildung und Ausscheidung der proteolytischen Magenfermente beim Fetus und Neugeborenen

Zusammenfassung Fermentuntersuchungen an der Magenmucosa aus dem Fundus- und Antrumbereich bei 118 6-40 Wochen alten Feten und 52 1-28 Tage alten Neugeborenen ließen den Beginn der Fermentproduktion ab 3. Schwangerschaftsmonat, eine langsame Erhöhung bis zum Ende der Schwangerschaft in der Fundusmucosa und nur geringe Fermentmengen im Antrum erkennen. Durch die Nahrungsaufnahme erwirbt der Neugeborenenmagen rasch seine volle Funktionsreife; die Fermentmengen im Fundus sind schon am 2. Lebenstag vervierfacht.Mit graduierten Ultracellafiltern und Cellophanfiltern von bekannter Porenweite in einem Hochdruckgerät (30 atü) wurde das Molekulargewicht des Pepsinogen, dessen Fermentaktivität nach der Methode von West, Ellis u. Scott ²⁰ bestimmt wurde, bei 40000 ermittelt und damit die Nierenfähigkeit (renale Ausscheidung) dieses Fermentes bestätigt. Beim Erwachsenen wird die Fermentmenge im Harn u. a. vom Hypophysen-Nebennierenrinden-System gesteuert.Im Fruchtwasser wird Pepsinogen erstmals im 7.-8. Schwangerschaftsmonat in Spuren nachweisbar, dessen Menge und Konzentration bis zum Ende der Schwangerschaft, besonders im 10. Monat, deutlich ansteigt. Da die fetale Nebennierenrinde im 8. Lunarmonat einen vorläufigen Reifezustand erreicht, wird das zeitliche Zusammentreffen verständlich. Die niedersten Werte wurden bei Eklampsie, die höchsten bei Erythroblastose beobachtet.Während der Neugeborenenharn gegenüber dem Fetalharn bereits am 1. und 2. Lebenstag eine 7-8mal höhere Fermentkonzentration zeigt, werden die absoluten Fermentmengen nur langsam, aber kontinuierlich größer und sind erst am 10. Lebenstag verzehnfacht.