Masashi Murakami

Effects of FUT-175, a New Synthetic Protease Inhibitor on Endotoxin-Induced Disseminated Intravascular Coagulation in Rats

The effects of FUT-175 (6-amidino-2-naphthyl-4-guanidino benzoate-dimethanesulfonate), a new synthetic protease inhibitor, on endotoxin-induced experimental disseminated intravascular coagulation (DIC) were studied in rats. Experimental DIC was induced by a 4-hour sustained infusion of endotoxin at a dose of 100 mg/kg. The rats were infused continuously with FUT-175 at 0.001, 0.01, 0.1, 1.0 or 10.0 mg/kg into a femoral vein for 4 h. Simultaneously with the agent infusion, endotoxin (100 mg/kg/4 h) was administered into the contralateral femoral vein. A protective effect against DIC was noted in the rats treated with 0.01 or 0.1 mg/kg of FUT-175 in the following parameters: fibrinogen and fibrin degradation products, fibrinogen level, prothrombin time, partial thromboplastin time, platelet count and the number of renal glomeruli with fibrin thrombi. These results demonstrated that FUT-175 reduces the extent of changes of the coagulation parameters caused by DIC.

Experimental Model of Disseminated Intravascular Coagulation Induced by Sustained Infusion of Endotoxin

SummaryExperimental disseminated intravascular coagulation (DIC) was induced by sustained infusion of endotoxin into the femoral vein in rats. The severity of DIC was determined with reference to various parameters, such as fibrinogen and fibrin degradation products (FDP), prothrombin time (PT), partial thromboplastin time (PTT), platelet count, and number of renal glomeruli having fibrin thrombi.Experimental DIC could be induced by a 4-h sustained infusion of endotoxin in a dose of 100 mg/kg. The DIC induced in rats showed a close resemblance to human DIC as judged from such changes as an elevation in FDP, prolongation of PT and PTT, depression in fibrinogen and platelet count, and increase in glomeruli having fibrin thrombi.This experimental model has an advantage in that the severity of DIC can be determined by measuring various parameters. It will be of use in the studies aimed at the establishment of a therapy for DIC as well as in the studies on DIC in rats.

Effects of Vitamin E on D-Galactosamine-Induced or Carbon Tetrachloride-Induced Hepatotoxicity

Experimental liver disorders were induced by the use of carbon tetrachloride or D-galactosamine hydrochloride in rats maintained on a vitamin E deficient diet and in rats fed a diet supplemented with vitamin E, and the protective effect of vitamin E on the liver was determined. After exposure to carbon tetrachloride or D-galactosamine hydrochloride the serum levels of transaminases, lysosomal enzyme beta-glucuronidase, and acid phosphatase were elevated, and thiobarbituric acid reactive substances in serum and liver homogenate were also increased. The changes were conspicuous in the vitamin E deficient rats, but were only slight in rats fed a diet supplemented with vitamin E. The results of this study suggest that vitamin E has a protective effect on liver disorders by inhibiting lysosomal enzyme liberation and lipid peroxidation.

Endotoxin-induced disseminated intravascular coagulation in vitamin E deficient rats

The effect of vitamin E on endotoxin-induced experimental disseminated intravascular coagulation (DIC) was studied in rats deficient in and supplemented with vitamin E. Experimental DIC was induced by a 4-hr sustained infusion of endotoxin at a dose of 13.3 mg/kg. After the infusion, fibrinogen and fibrin degradation products were increased, platelet count and fibrinogen level were decreased, and prothrombin time and partial thromboplastin time were prolonged. In addition, the number of renal glomeruli with fibrin thrombi was increased. These changes were significantly greater in vitamin E deficient rats when compared to those changes found in rats supplemented with vitamin E. These results indicate that vitamin E plays a protective role in endotoxin-induced DIC.

Protective Effect of Gabexate Mesilate against Experimental Disseminated Intravascular Coagulation in Rats

Experimental disseminated intravascular coagulation (DIC) can be induced by 4 h sustained infusion of endotoxin at a dose of 100 mg/kg in rats. The experimental model of DIC in rats was used to study the preventive effect of gabexate mesilate (GM) against DIC. Before the infusion of endotoxin, 10(-6), 10(-3), 1, 10, 50 or 100 mg/kg of GM was injected intraperitoneally. The preventive effects against DIC were noted in all the parameters, such as fibrinogen and fibrin degradation products, fibrinogen level, prothrombin time, partial thromboplastin time, platelet count, and the number of renal glomeruli with fibrin thrombi, in rats treated with 1, 10 or 50 mg/kg of GM. From these results it was shown that GM inhibited the aggravation of endotoxin-induced experimental DIC in rats.

Effect of dipyridamole on experimental disseminated intravascular coagulation in rats.

Experimental disseminated intravascular coagulation (DIC) can be induced by 4-h sustained infusion of endotoxin in a dose of 100 mg/kg in rats. The experimental model of DIC in rats was used to study the preventive effect of dipyridamole against DIC. Before the infusion of endotoxin, 0.5, 5.0 or 50.0 mg/kg of dipyridamole was injected intraperitoneally. The preventive effect against DIC was noted in all the parameters, such as fibrinogen and fibrin degradation products, fibrinogen level, prothrombin time, partial thromboplastin time, platelet count, and the number of renal glomeruli with fibrin thrombi, in rats treated with 5.0 or 50.0 mg/kg of dipyridamole. From these results, it was shown that dipyridamole inhibited the aggravation of endotoxin-induced experimental DIC in rats.

Prevention by Methylprednisolone of Disseminated Intravascular Coagulation Induced by Sustained Infusion of Endotoxin in Rats

An experimental model of disseminated intravascular coagulation (DIC) could be induced by a sustained infusion of 100 mg/kg of endotoxin for 4 h. Using this experimental model of DIC, the preventive effect of methylprednisolone against DIC was examined. Rats were injected with methylprednisolone at 0.1, 1.0, 10.0 or 30.0 mg/kg i.p., and thereafter infused continuously with 100 mg/kg/4 h of endotoxin. When compared with rats given no methylprednisolone, the significant prevention was noted in parameters, such as fibrinogen and fibrin degradation products, fibrinogen level, prothrombin time, partial thromboplastin time, platelet count, and the formation of fibrin thrombi in the glomeruli, in rats pretreated with 1.0, 10.0 or 30.0 mg/kg of methylprednisolone.

Role of Free Radical Lipid Peroxidation in Burn and Endotoxin Shock

Enhanced free radical generation leading to lipid peroxidation has been claimed to be associated with various disorders (Bulkey, 1983). There is considerable indirect evidence supporting a role for oxygen radicals in circulatory shock. Crowell et al. (1969) and Cunningham and Keaveny (1978) reported that allopurinol, a competitive inhibitor of xanthine oxidase, substantially increased the survival rate of dogs subjected to hemorrhagic shock. Severe burns result in both local and systemic hemodynamic changes (Gilmore and Handford, 1956; Wolfe and Miller, 1976; Adams et al., 1981), as well as in endocrine (Turinsky et al., 1977), neuroendocrine (Cova and Glaviano, 1968; Goodall and Moncrief, 1965), and metabolic (Robinson and Miller, 1981; Wolfe et al., 1977) alterations. Acute endotoxin shock is rapidly produced with Escherichia coli endotoxin (Balis et al., 1978).

The effects of defibrinogenation with batroxobin on endotoxin-induced disseminated intravascular coagulation in rats

Experimental disseminated intravascular coagulation (DIC) can be induced by a 4-hr sustained infusion of endotoxin at a dose of 100 mg/kg in rats. This experimental model of DIC in rats was used to study the effects of defibrinogenation with batroxobin against DIC. One hour before the infusion of endotoxin, 200 batroxobin unit (BU)/kg of batroxobin was injected intraperitoneally. Immediately after the injection, fibrinogen level markedly decreased and fibrinogen and fibrin degradation products increased. Prothrombin time and partial thromboplastin time were also prolonged. Blood counts, platelet counts and hematocrit level only showed a slight decrease after the injection. The preventive effect against DIC was noted by the partial inhibition of the fall in the platelet counts and lessened number of renal glomeruli with fibrin thrombi, in the rats treated with 200 BU/kg of batroxobin 1 hr before the infusion of endotoxin (100 mg/kg/4 hr). From these results, it was shown that fibrinogen metabolism plays an important role in the DIC state.

Influence of Human Serum on Bactericidal Activity of Ceftizoxime Sodium

The influence of normal human serum on bactericidal activity of ceftizoxime sodium (CZX) was studied in vitro against Escherichia coli and Staphylococcus aureus. Subminimal inhibitory concentrations of CZX inhibited the growth of bacteria. Normal human serum as a source of complement and low doses of CZX, such as 1/20 or 1/10 the minimal inhibitory concentration, had a strong synergic action on the gram-negative bacteria E. coli, but not on the gram-positive bacteria S. aureus. However, the combination of CZX and fresh human serum had a stronger inhibitory effect on the growth of S. aureus than CZX alone. It is concluded that subminimal inhibitory concentrations of CZX inhibited the growth of bacteria in vitro in the presence of human serum, indicating that smaller dosages of CZX may act to eliminate the invading bacteria in vivo together with serum complement.