The differential effects of chemical carcinogens on vitamin A status and on microsomal drug metabolism in normal and vitamin A-deficient rats.

Male Sprague-Dawley rats were maintained on a vitamin A-deficient diet for 5 weeks. Although serum and hepatic levels of vitamin A were significantly lower at this time, no outward signs of vitamin A deficiency were present. Hepatic microsomal levels of cytochrome P-450 in the vitamin A-deficient animals were 70% that of the control animals. Of the three microsomal enzymes studied, ethylmorphine N-demethylase, aniline hydroxylase, and aminopyrine N-demethylase, only the last one was adversely affected by vitamin A deficiency. 3-Methylcholanthrene, phenobarbital, and 2-acetylaminofluorene had a greater inductive effect and cytochrome P-450 in vitamin A-deficient rats. 4-Dimethylaminoazobenzene treatment decreased in the level of cytochrome P-450 in control rats more than in deficieny rats. The hepatic concentration of vitamin A was significantly reduced in control rats that were given injections of 3-methylcholanthrene, 2-acetylaminofluorene, or phenobarbital. Benzo(a)pyrene and 4-dimethylaminoazobenzene had less effect.

The interference of plasmic degradation products of human crosslinked fibrin with clot formation.

The role of plasmic degradation products of human crosslinked fibrin on polymerization of fibrin monomer and clot formation was studied. Both reactions were inhibited by Fragment DD, which formed a complex with fibrin monomer in a molar ratio 1 : 1. The rate of polymerization was slightly increased by Fragment E but it was not affected by (DD)E complex and Fragment A. Approximately the same amount of fibrin was formed in the presence and absence of Fragments A, E and the complex. It was concluded that of the degradation products of crosslinked fibrin, only Fragment DD is a potent anticoagulant at physiologic pH. The (DD)E complex is inert and Fragments A and E have only marginal effects.

Fibrinogenolytic afibrinogenemia after envenomation by western diamondback rattlesnake (Crotalus atrox).

The absence of fibrinogen and the presence of plasmic fragments X, Y, D, and E were demonstrated in a patient bitten by a western diamondback rattlesnake, Crotalus atrox. The factor VIII level and the platelet count were within normal limits. There were distinct changes of protease inhibitors in the patient's plasma. Alpha-1-protease inhibitor was elevated. Antithrombin-III was only slightly decreased after the envenomation, but alpha 2-antiplasmin and alpha 2-macroglobulin were initially significantly lowered, returning to normal values in 38 and 3 days, respectively. Plasmin-alpha 2-antiplasmin complex was present until day 10 after the envenomation. However, purified plasminogen was not activated in vitro by the venom. Cultured endothelial and smooth muscle cells from human blood vessels released an increased amount of plasminogen activator upon incubation with the venom. The release did not result from cell lysis. Platelets in normal human platelet-rich plasma were aggregated by 10 micrograms/ml of the venom, without serotonin secretion. The aggregation kinetics and serotonin secretion induced by adenosine diphosphate (ADP) or arachidonate were not significantly affected by the venom at 1-10 micrograms/ml. It is concluded that the predominant mechanism of afibrinogenemia in the patient after Crotalus atrox bite resulted from primary fibrinogenolysis and not from a consumptive coagulopathy. The lytic state seemed to be induced through an indirect activation of plasminogen by vascular plasminogen activator, which was probably released from endothelial cells and smooth muscle cells by the snake venom.