p-Hydroxyphenylpyruvate, an intermediate of the Phe/Tyr catabolism, improves mitochondrial oxidative metabolism under stressing conditions and prolongs survival in rats subjected to profound hemorrhagic shock.

The aim of this study was to test the effect of a small volume administration of p-hydroxyphenylpyruvate (pHPP) in a rat model of profound hemorrhagic shock and to assess a possible metabolic mechanism of action of the compound. The results obtained show that hemorrhaged rats treated with 2-4% of the estimated blood volume of pHPP survived significantly longer (p<0.001) than rats treated with vehicle. In vitro analysis on cultured EA.hy 926 cells demonstrated that pHPP improved cell growth rate and promoted cell survival under stressing conditions. Moreover, pHPP stimulated mitochondria-related respiration under ATP-synthesizing conditions and exhibited antioxidant activity toward mitochondria-generated reactive oxygen species. The compound effects reported in the in vitro and in vivo analyses were obtained in the same millimolar concentration range. These data disclose pHPP as an efficient energetic substrates-supplier to the mitochondrial respiratory chain as well as an antioxidant supporting the view that the compound warrants further evaluation as a therapeutic agent.

[Substitution of antithrombin III by synthetic thrombin inhibitors]. / Substitution von Antithrombin III durch synthetische Thrombininhibitoren.

Synthetic, low-molecular weight thrombin inhibitors may substitute for antithrombin III in inactivating thrombin in vitro and in vivo. They are superior to heparin as antithrombotic agents in antithrombin deficiency or consumption. Studies in experimental animals show the effectiveness of synthetic thrombin inhibitors in immunologic antithrombin depletion, thrombin-induced consumption and CCl4-induced liver failure.

[Diaplacental influence on the disseminated intravascular coagulation (DIC) in an asphyxia model. II. Influence on the vessel's content (author's transl)]. / Diaplazentare Einwirkung auf die disseminierte intravasale Gerinnung (DIC) im Asphyxiemodell II. Beeinflussung des Gefässinhaltes.

There is reported on the possibilities of diaplacental influencing on the DIC arising from the hypoxia we provoked with the help of an asphyxia model in rabbit fetuses. We could demonstrate the impossibility of influencing on the fetal vasal content by means of low molecular dextran, heparin or streptokinase. On the contrary, the possibility exists to influence on the fetal hemostasis by low molecular synthetic substances. The antifibrinolytic drug PAMBA causes in case of advanced acidosis diaplacental a definite growth of the intravascular coagulation, as well. But an inhibition of the fibrin sedimentation in the terminal vessels at the asphyctic shock can be achieved by applying the ethyl ester of the 4-amidinophenylpyruvic acid (APPA).

[Effect of 4-amidinophenylpyruvic acid on the generalized Sanarelli-Shwartzman phenomenon]. / Vliianie 4-amidinofenilpirovinogradnoi kisloty na generalizovannyi fenomen Sanarelli-Shvarttsmana.

The influence of 4-amidinophenylpyruvic acid (APPA)--a synthetic thrombin inhibitor--on the incidence of disseminated intravascular coagulation was tested with the aid of a model of the generalized Sanarelli-Schwarzman phenomenon. After application of APPA the thrombogenesis in different organs subsided quite significantly.