Morphological features of haemostatic plugs formed in vitro under high shear forces were investigated. Electron microscopy confirmed the relevance of such haemostatic plug to a platelet-rich arterial thrombus, which is formed in vivo . In rat blood samples, the effects of anticoagulants and various antiplatelet agents on platelet reactivity (rate of haemostatic plug formation) and subsequent coagulation of the flowing blood were investigated. Haemostasis did not occur in citrated blood, and heparin greatly inhibited the shear-induced platelet reaction. Aspirin (1 mM), a thromboxane A(2) receptor antagonist (5 microM), a stable prostacyclin (0.55 nM), a stable prostaglandin E(1) (141 nM) and a phosphodiesterase inhibitor (100 microM) were tested. All these agents exerted significant inhibitory effect on shear-induced platelet reaction, including the inhibition of the very first phase of platelet plug formation, due to aggregation of shear-activated platelets. Except for the phosphodiesterase inhibitor, which prolonged clotting time, none of the above agents affected dynamic coagulation. These results suggest that the employed in vitro shear-induced thrombosis/haemostasis test can reveal in vivo the antithrombotic effect of various agents independently of their mechanism of action.
SummaryThe combined effects of ethanol and components in fresh garlic on ethanol metabolism were investigated in the livers of mice. Male, 11-wk-old C3H/HeNCrj mice were intragastrically administered 2g ethanol/kg body weight after being administered fresh garlic juice for 8d (garlic group), and changes in the concentrations of ethanol, acetaldehyde and acetate in the serum, and changes in the activity of hepatic enzymes related to ethanol metabolism in mice were examined. The increases in the concentrations of acetaldehyde and acetate in the serum after ethanol administration tended to be diminished following garlic administration. The microsomal ethanol-oxidizing system (MEOS) in the livers of the garlic groups was significantly lower than that of the control microsomes at 2h after ethanol administration. It therefore seems that the decrease of MEOS in hepatic microsomes caused a smaller increase in the acet aldehyde concentration in the serum of the garlic groups because cyto solic alcohol dehydrogenase showed no significant difference between the control and garlic groups. After ethanol administration, the content of cytochrome P-450 in the hepatic microsomes of the control groups increased, while that of the garlic groups did not change although cytochrome P-450 (CYP) 2E1 and 1A2 in the hepatic microsomes of the garlic groups increased. These results indicate that the induction of isozymes of cytochrome P-450 other than CYP 2E1 and 1A2 was inhibited following garlic administration. Cytosolic high Km and total aldehyde
Five-week-old male mice, C3H/HeNCrj (C3H/He), were given a 5% (v/v) ethanol solution, commercial alcoholic beverages (Jap anese sake (sake) or red wine) or a Japanese seasoning (mirin [con taining ethanol and a large amount of glucose]) ad libitum for 45d, and were then examined for changes in the hepatic enzymes related to eth anol metabolism 2h after oral administration of 5g of ethanol/kg body weight. The specific activity of aniline hydroxylase (ANH) in the hepatic microsome increased significantly in all groups chronically administered ethanol solution, sake, red wine or mirin, and the greatest increase was in the hepatic microsome of mirin-administered mice. The cytochrome P-450 (CYP) 2El increased in the hepatic microsome of the mice administered ethanol solution, red wine or mirin where accompanied by high ANH activity. The immunoreactive band for CYP1A1 showed high specificity in the microsome of mice given sake, red wine or mirin. It was assumed that CYP1A1 was induced by unknown component(s) other than ethanol in these solutions. In the cytosolic fraction, following the chronic administration of sake and mirin, the total aldehyde dehy drogenase (AlDH) activity with high-Km decreased significantly. In the mitochondrial fraction, the activity of high-Km AlDH increased sig nificantly in the mirin-administered mice which drank a large amount of ethanol, whereas that in the red wine-administered group tended to decrease. These results indicate that the enzyme activities related to the * To whom correspondence should be addressed .
Abbreviations: CYP, cytochrome P-450; ADH, alcohol dehydroxylase; AlDH, aldehyde dehydroxylase; MEOS, microsomal ethanol-oxidizing system; ANH, aniline hydroxylase; MAb, monoclonal antibody. R KISHIMOTO et aloxidation of both ethanol and acetaldehyde in the cytosolic , mitochondrial and microsomal fractions of the liver were affected by either the action of ethanol or its interaction with other constituents of sake , red wine and mirin.
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