Photooxidation of alpha-glucan phosphorylases from rabbit muscle and potato tubers.

Photooxidation of alpha-glucan phosphorylases from rabbit muscle and potato tubers in the presence of rose bengal leads to a rapid loss of enzymatic activity which follows first-order kinetics. The process is pH dependent, being more rapid at higher pH. The inactivation is closely related to the destruction of histidine residues in the enzyme. It is suggested that histidine residues are largely responsible for the loss of enzymatic activity in the photooxidation. The inactivation of potato phosphorylase is retarded by substrates, whereas that of the muscle enzyme is not. The rate of photoinactivation of muscle phosphorylase b is increased with AMP, and decreased with ATP, ADP, IMP and glucose-6-P. This finding is considered to be closely related to the allosteric transition of phosphorylase.

Purification of leukocytosis-promoting substance from bovine parotid gland extract.

A leukocytosis-promoting substance was purified from a crude bovine parotid gland extract. The purified substance was proved to be a single component by polyacrylamide gel disc electrophoresis. It stimulates an increase of peripheral leukocyte numbers in rabbits. The molecular weight of the physiologically active component was estimated to be 4.5 . 10(4), and the component was found by sodium dodecyl sulfate polyacrylamide gel electrophoresis to be dissociated into two subcomponents.

[Choleretic effects of methanol extracts obtained from various Chinese traditional medicine].

Choleretic effects of 60 kinds of Chinese traditional medicine frequently used in clinical practice were investigated. Consequently, significant effects of choleretics were found in the methanol extracts of Ko-so-san, Intinko-to, Saiko-seikan-to, Hange-koboku-to, Antyu-san, Syo-kankyo-to, Keisi-syakuyaku-timo-to, Senkan-meimoku-to, Bohu-tusyo-san, Juzen-taiho-to, Jumi-haidoku-to Kami-syoyo-san and Hange-syasin-to. Water extracts of these Chinese traditional medicine had no such effect. Alteration of excretion of various biliary components after administration of the methanol extracts with the choleretic effect was examined, and with all medicines, bile acid excretion decreased and sodium and potassium excretions increased. Therefore, a medicine inducing choleresis involves some selective increases in the bile acid-independent fraction of bile flow. And after administration of methanol extracts of Keisi-syakuyaku-timo-to and Bohu-tusyo-san, lithogenic index, an index of saturation level of cholesterol, decreased significantly. Therefore, with these medicines, a dissolving effect on cholesterol gallstone is expected.

[Effects of various methanol extracts of crude drugs on experimental subacute and chronic hepatic injury].

The effects of 5 crude drugs (Myricae Cortex, Polygoni Avicularis Herba, Hyperici Erecti Herba, Forsythiae Fructus, Desmodii Herba) on subacute and chronic hepatic injuries induced by carbon tetrachloride (CCl4) or alpha-naphthylisothiocyanate (ANIT) were investigated in rats. All of these crude drugs suppressed significantly the increase of several biochemical parameters with CCl4-injection twice per week for 4 weeks. Polygoni Avicularis Herba and Desmodii Herba among 5 crude drugs also protected the subacute hepatic injury induced by ANIT-injection for 4 weeks. In addition, the therapeutic effect of Desmodii Herba on the chronic hepatic injury induced by CCl4-injection for 9 weeks was recognized. Desmodii Herba has protective effects on the acute and subacute hepatic injuries induced by CCl4 or ANIT and an improving effect on the chronic injury induced by CCl4. Though the increase of hydroxylproline content in the liver began 4 weeks after the CCl4 or ANIT treatment, every crude drug had no significant effect against the liver fibrosis in these study.

[Protective effects of antioxidants on experimental liver injuries].

Protective effects of 14 kinds of antioxidant on liver injury induced by carbon tetrachloride (CCl4) were investigated in terms of serum enzyme activities and bilirubin concentration. Consequently, the significant protective effects were found in sesamol, ellagic acid, cysteamine and cysteine. These antioxidants clearly decreased the lipid peroxide in the liver tissue. The protective effects on CCl4-induced liver injury in vivo were independent of the inhibitory activities on lipid peroxidation in hepatic mitochondria fraction in vitro.

[Protective effects of various methanol extracts of crude drugs on experimental hepatic injury induced by alpha-naphthylisothiocyanate in rats].

Sixty seven methanol extracts of crude drugs were examined for their effects to protect hepatic injury induced by alpha-naphthylisothiocyanate (ANIT) in rats. In terms of the release of intrahepatic enzymes and bilirubin into the serum, 19 extracts were found to suppress the increase in the concentration of serum bilirubin by ANIT. Out of the 19 extracts those of Berchemia Racemosa Caulis, Aurantii Nobilis Pericarpium, Polygoni Avicularis Herba and Gentianae Scabrae Radix, also inhibited the release of several intrahepatic enzymes used as parenchymal injury parameter.

[Protective effects of sesamol and its related compounds on carbon tetrachloride induced liver injury in rats].

Sesamol is a kind of antioxidant and exists in sesame oil. This paper describes the protective effect of sesamol against carbon tetrachloride (CCl4)-induced liver injury in rats. Sesamol had a significant effect in case of intraperitoneal, subcutaneous and oral administration. In order to examine the relationship between the chemical constitution of sesamol and its protective effect, the protective effects of 20 kinds of sesamol related compounds against liver injury induced by CCl4 were investigated in rats. Consequently, significant protective effects were found in methylenedioxybenzene, isosafrole, safrole, methylenedioxyaniline and methylenedioxyacetophenone. These five compounds had a methylenedioxy group had protective effects, it was considered that the protective effects of the methylenedioxy group were influenced by substituent groups on 4 position of methylenedioxy phenyl compounds. In addition, sesamol, methylenedioxybenzene and isosafrole showed significant protective effects against cholestasis induced by CCl4.

[Protective effects of various methanol extracts of crude drugs on experimental hepatic injury induced by carbon tetrachloride in rats].

The protective effects of 67 methanol extracts of crude drugs on rat hepatic injury by carbon tetrachloride (CC14) were examined. In terms of the release of intrahepatic enzymes and bilirubin into the blood, 11 methanol extracts decreased these factors significantly. Among them methanol extracts of Caryophylli Flos, Angelicae Dahuricae Radix, Polygoni Avicularis Herba, Myricae Cortex and Forsythiae Fructus were newly found to have protective effects against acute hepatic injury induced by CCl4. And then these 11 extracts which protected hepatic injury by CCl4 were investigated for their membrane stabilizing and inhibitory effects of lipid peroxidation. The extract of Bupleuri Radix only decreased the hemolysis induced by hypotonic pressure. Nine kinds of extracts without those of Desmodii Herba and Bupleuri Radix suppressed the lipid peroxidation induced by CCl4 in rat hepatic microsomes. In addition, Scutellariae Radix, Caryophylli Flos and Myricae Cortex were shown to have inhibitory effects of non-enzymatic lipid peroxidation in rat hepatic mitochondria. This study reports that the methanol extracts of Caryophylli Flos, Angelicae Dahuricae Radix, Polygoni Avicularis Herba, Myricae Cortex and Forsythiae Fructus protect the hepatic injury by CC14 and these protective effects are connected with the inhibitory effects of the lipid peroxidation in hepatic microsomes.

[Protective effects of the bark of Myrica rubra Sieb. et Zucc. on experimental liver injuries].

The methanol extract from the bark of Myrica rubra SIEB. et ZUCC. showed protective effects on liver injuries induced by carbon tetrachloride (CCl4) and alpha-naphthylisothiocyanate (ANIT) in rats. In this study, the fractions and some compounds from the bark of M. rubra were investigated for the protection against CCl4 inducing liver injuries in rats. The active principles for the protection were recognized in two fractions (M-3 and M-5 Fr. 1) obtained from the methanol extract, and one of the active principles in the fraction (M-3) was found to be myricanol 5-O-beta-D-(6'-O-galloyl)-glucopyranoside. In addition, these fractions protecting liver injuries induced by CCl4 showed significant protective effects against cholestasis induced by ANIT.

[Protective effects of the stem of Berchemia racemosa Sieb. et Zucc. on experimental liver injuries].

The methanol extract and water extract from the stem of Berchemia racemosa (Rhamnaceae) showed protective effects on liver injuries induced by carbon tetrachloride (CCl4) and alpha-naphthylisothiocyanate (ANIT) in rats. The acetone extract of B. racemosa protected the liver injury induced by CCl4. One of the protective substances was identified as carpusin. Some fractions showed significant protective effects against the liver injury and cholestasis induced by ANIT.

[Influence of aging and circadian fluctuation of fibrinolytic factors to the responses of these factors during venous occlusion test in healthy subjects].

This study was aimed to clarify the influence of aging and circadian fluctuation of fibrinolytic factors to changes of tissue plasminogen (t-PA) and its inhibitor (PAI-I) during venous occlusion test. Venous occlusion was achieved by application of a sphygmomanometer cuff to the upper arm of elderly healthy subjects (n = 12) and young healthy subjects (n = 12) at 10:00 am and 4:00 pm. Plasma concentration of t-PA, free PAI-1 and total PAI-1 were measured by ELISA. The activity of t-PA was measured by bioimmunoassay using monoclonal antibody for t-PA. Circadian variation was observed in the change of t-PA activity and total PAI-1. These were highly increased in the evening. However, this phenomenon was different between age groups and increase of t-PA activity occurred in elderly subjects, whereas PAI-1 was observed in young subjects. In conclusion, circadian variation and the influence of age should be considered to evaluate results of venous occlusion test.

[Qualitative analysis of tissue plasminogen activator in plasma obtained from various liver diseases by gel filtration and affinity chromatography].

Tissue plasminogen activator (t-PA) in plasma obtained from patients with acute hepatitis, chronic hepatitis, liver cirrhosis, hepatocellular carcinoma, drug-induced intrahepatic cholestasis, obstructive jaundice, fulminant hepatitis or disseminated intravascular coagulation (DIC), was analysed chromatographically. Liver disease cases showed a new peak (peak C) on HPLC fractionation. The protein of peak C had a lower molecular weight than ovalbumin. Lysine- and zinc- chelating affinity chromatography revealed that the peak C consist with the light chain (L-chain) of t-PA. The L-chain was also found in patients with DIC, but disappeared after improvement of DIC. Therefore, it was suggested that appearance of the L-chain would be related to acceleration of secondary fibrinolysis in plasma. The L-chain was especially high in plasma obtained from patients with decompensated liver cirrhosis. These results indicated that high increase of the L-chain in cases of severe liver disease may be due to either impaired clearance of t-PA in the liver or secondary hyperfibrinolysis accompanied by DIC. We concluded that determination of the L-chain of t-PA may contribute to clarify the mechanism of hyperfibrinolysis in liver diseases.

[Changes in plasma tissue plasminogen activator (t-PA) and plasminogen activator inhibitor 1 (PAI-1) by the interferon treatment for chronic hepatitis C].

To determine the effects of interferon (IFN) treatment for chronic hepatitis C on vascular endothelium, we measured the concentrations of tissue plasminogen activator (t-PA) and its inhibitor (PAI-1) in the plasma from patients before and after IFN treatment for 14 consecutive days. The plasma t-PA and PAI-1 levels were measured before and after treatment. The plasma t-PA level was significantly increased after IFN treatment (p < 0.01) but no significant difference in plasma PAI-1 level was observed before and after treatment. The ratio of t-PA/PAI-1 was significantly increased after IFN treatment (p < 0.05). These changes may be caused by the effect of IFN on endothelium, leading to an activation of the endothelium derived fibrinolysis factors. Increase in plasma t-PA concentration may induce hyperfibrinolysis which may be one of the causes of suborbital hemorrhage. Further study on the fibrinolysis pathway in the blood is necessary to elucidate the mechanisms of the many side effects observed during IFN treatment.

[Effects on blood coagulation-fibrinolytic system after transcatheter hepatic arterial therapy in cases of hepatocellular carcinoma analyzed by plasma levels of plasmin-alpha 2-PI complex, D dimer and thrombin-ATIII complex].

To clarify the effects on blood coagulation-fibrinolytic system after transcatheter hepatic arterial therapy for cases of hepatocellular carcinoma (HCC), plasma levels of Plasmin-alpha 2PI complex (PIC), Ddimer and Thrombin-ATIII (TAT) before and after therapy were measured by EIA, in addition to other conventional coagulofibrinolytic parameters. In the group (9 cases) treated with intra-arterial injection of adriamycin, there were no significant changes of coagulofibrinolytic parameters except for Ddimer (P less than 0.05) which was elevated 1-2 days after therapy. However, only two cases in whom plasma PIC, Ddimer and TAT levels were clearly elevated before therapy, showed further marked elevation of those parameters after therapy. In the group (29 cases) treated with intra-arterial injection of adriamycin-lipiodol suspension, whether or not embolized with gelfoam, plasma PIC, Ddimer and TAT levels were significantly elevated (P less than 0.01) after therapy, as well as other conventional coagulofibrinolytic parameters. These results indicate that hypercoagulable and hyperfibrinolytic states were induced by treatment. Moreover, the secondary hyperfibrinolytic state tended to persist longer than the hypercoagulable state. The 14 cases embolized with gelfoam seemed to have more apparent effects on blood coagulation-fibrinolytic system than cases not treated with gelfoam. Therefore, we conclude that caution and prophylaxis for the occurrence of disseminated intravascular coagulation are necessary for transcatheter arterial therapy for cases of HCC.

[The clinical significance of plasma tissue plasminogen activator (t-PA) levels in severe acute or fulminant hepatitis].

We studied the tissue plasminogen activator (t-PA) levels in the plasma of patients with acute hepatitis (AH), severe acute hepatitis (AHs) and fulminant hepatitis (FH). Plasma t-PA levels were measured consecutively on the first, third and seventh days of hospitalization. Plasma t-PA levels were markedly higher in AHs and FH than in AH (p < 0.05, p < 0.01, respectively) on the first day, but did not differ significantly between AHs and FH on this day. The t-PA levels decreased markedly on the third and seventh days in AHs (both p < 0.05), but did not change from the first day to the third and seventh days in FH. The t-PA levels on the third and seventh days were higher in FH than in AHs (both p < 0.05). There was a significant increase in the plasma t-PA level before an episode of encephalopathy in FH compared with levels in AHs. These observations suggest that t-PA level may be useful as a prognostic parameter in patients with acute hepatic injury.

[Drug delivery system in cardiovascular drugs].

Various drug delivery systems are available when cardiovascular drugs are used. Various kinds of receptor inhibitors such as beta blockade or angiotensin II receptor inhibitor are frequently used in the daily cardiovascular clinic. Several different routes of drug administration exist. Conventional tablet or its liquid spray by sublingual or lingual administration is rapidly absorbed and specified oral tablet or transdermal patch for maintaining longtime is slowly absorbed from the digestive tract or skin. Some drugs have different type of tablets for obtaining different pharmacodynamics. Nifedipine has 3 kinds of tablets showing short, long and very long-time effect. Recent advance in drug delivery system makes possible to administer the drug to the small local area through stent or balloon catheter at the coronary interventional therapy.