Pavel Rohan

Humoral conditioning for necrosis

ZusammenfassungNach Vorbehandlung mit verschiedenen Mastzellentladern, Histamin, oder Serotonin, bilden sich bei der Ratte an Stellen, wo sonst gut vertragene Dosen hypertonischer Lösungen subcutan injiziert werden, ausgedehnte Hautnekrosen aus. Viele andere, in ihrer chemischen Struktur und pharmakologischen Aktivität sehr verschiedene Agenzien, sowie schwere Stressoren sind in dieser Beziehung inaktiv.SummaryOtherwise well tolerated amounts of subcutaneously injected hypertonic solutions produce extensive local skin necroses in rats pretreated with a variety of mast-cell dischargers, histamine or serotonin. Numerous other agents, differing widely in chemical structure and pharmacologic activity, as well as severe stressors proved to be devoid of this effect.

Prevention of the acute conditioned necrosis phenomenon

ZusammenfassungVersuche an Ratten bestätigen und erweitern die Beobachtung, daß Behandlung mit zahlreichen Mastzellentladern, Serotonin oder Histamin den Organismus für die Erzeugung akuter lokaler Nekrosen sensibilisiert, die dann an jenen Stellen auftreten, wo gleichzeitig bestimmte Gewebsreizstoffe (z. B. hypertonische NaCl-Lösung) in das Bindegewebe eingeführt werden. Diese akute, konditionierte Nekrose (ACN) kann durch Vorbehandlung mit Mastzellentladern oder Histamin verhindert werden, während Serotonin — zumindest unter unseren Versuchsbedingungen — keine solche Schutzwirkung erkennen ließ. Vorbehandlung mit Antihistamin- und Antiserotoninpräparaten (Cyproheptadin und Phenoxybenzamin) verhindert ebenfalls die Entwicklung der ACN, aber die Schutzwirkung aller testierten Prophylaktica ist von kurzer Dauer; sie unterscheidet sich dadurch von der anhaltenden Immunität, welche durch serologische Reaktionen herbeigeführt wird.SummaryExperiments on the rat confirm and extend the observation that conjoint treatment with numerous mast-cell dischargers, 5-HT or histamine sensitizes the organism for the production of acute necrosis at sites where certain tissue irritants, such as hypertonic NaCl, are introduced into the connective tissue. This acute conditioned necrosis (ACN) can be prevented by pretreatment with mast-cell dischargers or histamine while — at least under the conditions of these experiments — 5-HT exhibited no such protective effect. Pretreatment with antihistaminic and antiserotonin compounds (cyproheptadine and phenoxybenzamine) likewise prevents the development of the ACN but the protective action of all prophylactic agents tested is of short duration thereby differing from the long lasting immunity induced by specific serologic reactions.

CROSS‐RESISTANCE BETWEEN AGENTS WHICH CONDITION FOR ACUTE NECROSIS

It has been observed recently that after systemic sensitization with certain “conditioning factors” (e.g., mast-cell dischargers, mast-cell products, vasoconstrictors, microemboli) extensive skin necrosis is produced by the subcutaneous administration of normally well-tolerated doses of certain “challengers” (e.g., hypertonic solutions, proteolytic enzymes, acetic acid).’ -3 This phenomenon of “acute conditioned necrosis” (ACN) occurs a few hours after challenge; thus, it differs from the “delayed conditioned necrosis” (DCN) which develops much more slowly-for example, after conditioning with glucocorticoids-at sites of treatment with long-acting inflammatory irritants:” Preliminary experiments have shown that pretreatment with certain mast-cell dischargers given prior to challenge can protect the rat against the production of an ACN by a second injection of a mast-cell discharger, this time given simultaneously with a challenger. In similarly conducted experiments, histamine pretreatment protected against histamine but not against 5-HT, while 5-HT pretreatment failed to protect against either its own ACN-producing effect or that of histamine! From these experiments it was concluded that the tendency of tissues to undergo acute necrosis under the influence of local irritants can be decisively influenced by natural compounds, particularly the biologic amines of mast cells. In view of the great importance of necrosis in the pathogenesis of diverse morbid lesions, a systematic study of these phenomena appeared to be desirable. The object of this communication is to report upon a first series of experiments performed along these lines, mainly with the view of determining which among the conditioners can give cross-resistance against each other. It was hoped that such a study would also shed additional light upon the singular phenomenon of nonimmunological crossresistance and nonspecific resistance in general, phenomena whose importance in pathology has been reviewed in detail elsewhere?

Äthylalkohol als Sensibilisator für die akute Hautnekrose

SummaryWhen given intravenously, ethyl alcohol sensitizes rats for an acute type of skin necrosis by subcutaneous treatment with otherwise well-tolerated hypertonic solutions of Bromelain, glucose or NaCl. Acetic acid and ox-bile proved to be less active in this connection. Papain and urea were totally inefficient as challengers. The intravenous doses of ethyl alcohol required for conditioning to this necrosis phenomenon (ACN) are relatively high.Oral ethyl-alcohol administration caused only a slight ACN-phenomenon; better results could be obtained by using the “pneumoderma technique”.ZusammenfassungIntravenös verabreichter Äthylalkohol sensibilisiert Ratten für akute nekrotische Hautläsionen, bei unmittelbarer subcutaner Anwendung von normalerweise gut vertragenen hypertonischen Lösungen von Bromelain, Glucose oder NaCl. Essigsäure und Rindergalle erwiesen sich in dieser Beziehung als weniger aktiv. Papain und Harnstoff waren als Provokatoren vollkommen wirkungslos. Die i.v. Alkoholdosen für die Infuktion dieses akuten Nekrose-Phänomens (ACN) sind relativ sehr hoch.Perorale Verabreichung von Äthylalkohol hatte lediglich ein geringes ACN-Phänomen zur Folge; bessere Resultate konnten hier durch Anwendung der „Pneumoderma-Technik” erzielt werden.