Reaching-related potentials in caudate nucleus and cerebellum of rats

Summary Electrical correlates of the lateralized reaching reaction were studied in rats with implanted electrodes. Averaged event-related potentials (ERPs) in the cerebellar dentate nucleus consisted of a negative wave coinciding with reach onset and followed 70 msec later by a positive deflection. The most prominent component of the more variable caudate ERPs was a negative wave culminating 60–120 msec after reach onset. The positive and negative ERP deflections corresponded to inhibitory and excitatory reactions respectively, at the single neuron level.     

Laktationshemmende Wirkung von N-[d-6-Methyl-8-isoergolin-I-yl]-N′, N′-diäthylharnstoff (VÚFB-6638)

Summary The inhibiting effect of orally administered N-[d-6-methyl-8-isoergolin-I-yl], N, N-diethylurea (VÚFB-6638) on the production of milk was found in rats. The inhibition of lactation was ascertained through the observation of the daily weightgains of the suckled puppies (ED₅₀=0.112 mg/kg/day) and through the observation of the presence of milk in the stomach of these puppies, as seen through their abdomen wall (0.084 mg/kg/day). This inhibition could be abolished with exogenous prolactin, which gives evidence that the drug studied acts via the endocrine system.

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Für die technische Assistenz danken wir FrauM. Kommersová und FrauV. Maitová.     

Nachweis der Bisulfit-Addukte (α-Oxysulfonsäuren) von Carbonylverbindungen in den mit SO2 behandelten Erbsenkeimlingen

Summary The intoxication of 15-day-old green pea seedlings with 1% gaseous SO₂ causes an important concentration fall of some free ketoacids (pyruvic, oxalacetic, -ketoglutaric) and of glyceraldehyde in the roots and shoots. This fall is a consequence of the reaction of these carbonyl compounds with SO₂ in the plant tissue under the formation of bisulphite adducts (-hydroxysulfonic acids), which have been chemically proved and quantitatively estimated.     

A contribution on the effect of noradrenaline on heat production in mice

Zusammenfassung Bei ausgewachsenen Mäusen wurde nach i.p. Noradrenalininjektion die Steigerung der O₂-Aufnahme über den Grundumsatz in der Thermoneutralzone verfolgt. Nach einer Dosis von 1,6 mg/kg wurde ein bedeutender Unterschied (p < 0,05) der O₂-Aufnahmesteigerung zwischen der Gruppe normaler (155%) und normaler, auf 17°C adaptierter Mäuse (165%) und der Gruppe haarloser Mäuse (195%) festgestellt.     

Some pharmacological properties of [4-Leucine]-arginine-vasotocin

Zusammenfassung Die pharmakologischen Eigenschaften von [Leu⁴]-Arginin-vasotocin sind in der Tabelle zusammengefasst. Am isolierten Rattenuterus in magnesiumfreiem Medium wirkt das Peptid als Oxytocinantagonist.     

Substituierte t-Hexylamine als neuer Typ hypotensiv wirksamer Verbindungen

Summary A series of primary, secondary, and tertiary 2,2,3-trimethylbutylamines-(3) and their salts substituted in position 3 with a methyl, ethyl,n-butyl, phenyl, and benzyl group has been prepared. One member of the series, N,N,2,2,3-pentamethylbutylamine-(3) (Penbutamine) as well as the corresponding amino and methylamino derivatives were compared with other compounds of a similar type as regards their ganglioplegic and hypotensive effect. The tested compound revealed a high degree of activity in both the above mentioned directions.

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11. Mitteilung « Ganglioplegica », 10. Mitteilung siehe Collection, im Druck.     

Relationship between the chemical structure of thiazolidine acetic acid derivatives and the antiherpetic activity in human embryonic cell cultures

Zusammenfassung Durch Abwandlung der Struktur der 4-Oxo-5-thiazolidinessigsäure ergeben sich starke inhibitorische Effekte auf die cytopathogenen Wirkungen, die vom VirusHerpes simplex in Kulturen menschlicher Embryonalzellen ausgeübt werden.     

Über pharmakodynamisch interessante Aminoalkylderivate von Acridan- und Phenthiazinhomologen

Summary The synthesis of aminoalkyl derivatives of 1-aza-2, 3; 5,6-dibenzocycloheptadiene (homoacridane) and 1-aza-4-thia-2, 3; 5,6-dibenzocycloheptadiene (homophenothiazine) is described. Salts of these bases possess high antihistamine and local anaesthetic activity.     

Aging alters resynchronization of the circadian system in rats after a shift of the light-dark cycle

Summary Four days following an 8-h advance of the light-dark cycle, the circadian rhythms in the pineal N-acetyltransferase activity and melatonin content reappeared in 7-week-old rats, but were still abolished in 24-month-old animals.     

An inhibitor of Bcl-2 family proteins induces regression of solid tumours

Proteins in the Bcl-2 family are central regulators of programmed cell death, and members that inhibit apoptosis, such as Bcl-X(L) and Bcl-2, are overexpressed in many cancers and contribute to tumour initiation, progression and resistance to therapy. Bcl-X(L) expression correlates with chemo-resistance of tumour cell lines, and reductions in Bcl-2 increase sensitivity to anticancer drugs and enhance in vivo survival. The development of inhibitors of these proteins as potential anti-cancer therapeutics has been previously explored, but obtaining potent small-molecule inhibitors has proved difficult owing to the necessity of targeting a protein-protein interaction. Here, using nuclear magnetic resonance (NMR)-based screening, parallel synthesis and structure-based design, we have discovered ABT-737, a small-molecule inhibitor of the anti-apoptotic proteins Bcl-2, Bcl-X(L) and Bcl-w, with an affinity two to three orders of magnitude more potent than previously reported compounds. Mechanistic studies reveal that ABT-737 does not directly initiate the apoptotic process, but enhances the effects of death signals, displaying synergistic cytotoxicity with chemotherapeutics and radiation. ABT-737 exhibits single-agent-mechanism-based killing of cells from lymphoma and small-cell lung carcinoma lines, as well as primary patient-derived cells, and in animal models, ABT-737 improves survival, causes regression of established tumours, and produces cures in a high percentage of the mice.