Pharmacological properties of some derivatives of 1,3-benzoxazine

Riassunto Sono stati studiati 22 derivati della 1,3-benzossazina, 8 dei quali sono risultati attivi sulla depressione da reserpina. Tra essi il più efficace è stato il 4H-3-carbossamidometil-1,3-benzossazin-2-one. Correlando la struttura chimica all'attività farmacologica si è visto che la distanza del gruppo amidico dall'anello benzossazinico, la linearità della catena, come pure la presenza di un gruppo amidico libero sono essenziali per l'esplicarsi dell'effetto. Anche sostituzioni in R₄ o nell'anello benzenico portano a perdita dell'attività. Il carbonile in 2 può essere sostituito da un gruppo CS senza sostanziali variazioni di attività.     

Pathogenesis of the uremic syndrome. Pharmacological studies on acetoin and 2,3-butylene glycol

Zusammenfassung Acetoin und 2,3-Butylenglykol entstehen bei Menschen und Tieren aus Brenztraubensäure. Beide Substanzen bewirken bei Mäusen Narkose. Bei Ratten tritt der Bezold-Jarisch-Reflex auf. Die Rolle von Acetoin und 2,3-Butylenglykol bei urämischen und hepatischen Bewusstseinsstörungen wird diskutiert.

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The study was aided by grants from Schweizerischer Nationalfonds' and from F. Hoffmann-La Roche & Co. AG, Basel.

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3rd Communication. 2nd Commun. see:F. Bigler, H. Thölen, andH. Staub, Helv. physiol. pharmacol. Acta19, C 11 (1961).     

P/E changes: some new results

The P/E ratio is often used as a metric to compare individual stocks and the market as a whole relative to historical valuations. We examine the factors that affect changes in the inverse of the P/E ratio (E/P) over time in the broad market (S&P 500 Index). Our model includes variables that measure investor beliefs and changes in tax rates and shows that these variables are important factors affecting the P/E ratio. We extend prior work by correcting for the presence of a long‐run relation between variables included in the model. As frequently conjectured, changes in the P/E ratio have predictive power. Our model explains a large portion of the variation in E/P and accurately predicts the future direction of E/P, particularly when predicted changes in E/P are large or provide a consistent signal over more than one quarter. Copyright © 2008 John Wiley & Sons, Ltd.     

A new small molecular tracer for permeability studies with the electron microscope

Résumé Le gluconate de fer a la propriété de suivre les molécules d'un poids moléculaire de } 500. Il traverse avec elles l'endothélium des vaisseaux sanguins et l'épithélium de la vessie en passant par les joints ou, pour une faible part, entre les vésicles.

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We are most grateful for the skilful assistance of Mr.B. R. Dixon and the partial support of the Australian Research Grants Committee.     

Cephalopod myocardial receptors: Pharmacological studies on the isolated heart ofSepia officinalis (L.)

Summary This paper presents a synopsis of the information available about the pharmacological action of various substances on the cephalopod heart, with special emphasis on the central heart ofSepia officinalis. Threshold concentrations, EC₅₀ values and maximum effective concentrations have been experimentally determined. Studies with various transmitter substances, analogous compounds and antagonists have led to the following picture: Acetylcholine is the natural inhibitory transmitter substance; it acts via receptors with nicotinic properties which can be blocked by d-tubocurarine and -bungarotoxin. The probable excitatory transmitter system is represented by a noradrenergic innervation. Noradrenaline has a positive inotropic and a positive chronotropic action on in vitro heart preparations. A positive inotropic response can also be evoked by serotonin (5-HT); this effect is not due to stimulation of the catecholamine receptor, as is shown by cross-over experiments with specific blocking agents. Furthermore, a peptidergic receptor system has been described which reacts with the molluscan cardioactive peptide FMRF amide most effectively. It is assumed that cardioactive peptides may reach the central heart in the circulating blood; the sites of synthesis and release are still unknown. Possibly the NSV-layer of the vena cava is involved in hormonal cardiovascular regulation processes.     

A new glandular organ in some toxic caterpillars.

The nodes formed by the mid-ventral tracheal anastomoses in abdominal segments 3-6 are modified into conspicuous glandular organs in larvae of certain Lepidoptera. They comprise clusters of extremely large cells penetrated by an extensive lacunar system opening onto the tracheal wall. These cells appear to sequester substances from the haemolymph which may be conjugated with a lipoid synthesized within them and the product excreted into the lacunar system, ultimately passing into the tracheal lumen.     

Pharmacological modification of hemoglobin F expression in sickle cell anemia: An update on hydroxyurea studies

The most studied pharmacological intervention in sickle cell anemia aiming at elevating HbF expression is the use of hydroxyurea. At the present time the experience has been that after 1 year of treatment with maximum tolerated doses (MTD) all patients showed increases of percent HbF, with a mean of 15% HbF, without apparent side effects besides the reversible ones observed during the process of attaining the MTD. The question of efficacy is presently being investigated by a multicenter placebo controlled double blind clinical trial that involves more than 20 sites. The goal of the study is to determine if hydroxyurea can decrease the incidence of painful crises by 50%. Results of this study are not expected before the end of 1993.     

Cardiotonic activities of some new type of bufadienolide- and cardenolide-conjugates

Summary Some new type of bufadienolide-and cardenolide-conjugates, including bufotoxins and 3-sulfates recently isolated from the toad skin, were tested for their cardiotonic activities by using isolated frog hearts and guinea-pig atria. The relative potencies were obtained and reported.This study was reported at the 49th General Meeting of theJapanese Pharmacological Society, 31 March 1976, Osaka. The authors are grateful to Prof. T. Nambara, Pharmaceutical Institute, Tohoku University, Sendai, for his kind supply of the compounds used in this study.     

Pharmacological studies on thiamine deficiency IV. Blood catecholamine content and blood pressure of thiamine deficient rats

Zusammenfassung Wegen der Senkung des Blut-Katecholamin-Spiegels in unter experimentell erzeugtem Thiaminmangel stehenden Ratten kommt es zu einer Hypotonie. Die Abschwächung der spontanen Freisetzung des Katecholamins aus dem katecholaminspeichernden Gewebe bei Thiaminmangelratten ist als ein Faktor bei der Aminakkumulation bei Thiaminmangel zu denken.     

Electron spin resonance studies of catalase and some of the catalase compounds

Zusammenfassung Rinderleberkatalase und einige Katalasekomplexe wurden bei einer Temperatur von 77°Kelvin mit der Methode der Elektronenspinresonanz untersucht. Aus den Elektronenspinresonanzspektren ist zu entnehmen, ob es sich bei der Katalaseverbindung um einen Gross-spin-Komplex, um einen Klein-spin-Komplex oder um eine Mischform beider Komplexarten handelt.     

Pharmacological actions of caerulein

Riassunto La caeruleina, nonapeptide attivo della pelle diHyla caerulea, possiede un insieme di potenti azioni farmacologiche sulla muscolatura liscia vasale ed extravasale e sulle secrezioni del tubo digerente. La caeruleina provoca una relativamente prolungata caduta della pressione del sangue nel cane e nel coniglio, contrae potentemente la muscolatura in situ dello stomaco, dell'intestino e soprattutto della cistifellea, stimola poderosamente la secrezione gastrica, la secrezione pancreatica e, in misura minore, la secrezione biliare. In queste sue multiformi azioni farmacologiche la caeruleina risulta più potente rispettivamente della bradichinina, della gastrina e della colecistochinina-pancreozimina.

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Supported by grants from the Consiglio Nazionale delle Ricerche, Roma.     

7-Chloro-3-(4-methyl-1-piperazinyl)-4H-1,2,4-benzothiadiazine-1,1-dioxide a new antihypertensive agent

Summary 7-Chloro-3-(4-methyl-1-piperazinyl)-4H-1,2,4-benzothiadiazine-1,1-dioxide (DU-717) is a new compound having sustained antihypertensive activity in a similar manner to that of hydrochlorothiazide. However, this compound shows neither diuretic nor hyperglycemic effect, being different from those of hydrochlorothiazide or diazoxide.