Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acute pancreatitis was induced in 19 anesthetized dogs by retrograde injection of bile mixed with trypsin into the pancreatic duct. Two groups, of six animals each, were treated with intravenous infusion of synthetic antiproteases: gabexate mesilate and nafamostat mesilate in doses of 1 mg/kg per hr. One group of seven animals remained untreated. Two untreated dogs died during the experiment. All the treated dogs survived. Hemodynamic data were monitored hourly during a 6-hr observation period. In the untreated animals, cardiac output, mean arterial pressure, and left ventricular stroke volume decreased rapidly; an increase of pulmonary vascular resistance and systemic vascular resistance was observed. Synthetic antiproteases, given as a therapy, improved the hemodynamic parameters significantly and prevented the animals from developing shock. Gabexate mesilate and nafamostat mesilate seem to be of value in the treatment of experimentally produced acute pancreatitis in dogs.
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PMID:Synthetic antiproteases in acute pancreatitis: an experimental study. 173 37

Acute pancreatitis was induced in ten anesthetized dogs by retrograde injection for bile mixed with trypsin into the pancreatic duct. Five animals were treated with i.v. infusion of gabexate mesilate in a dose of 1 mg/kg per hour. Hemodynamic data were regulary monitored during a 10-h observation period. Cardiac output (CO), mean arterial pressure (MAP), and left ventricular stroke volume (LVSV) decreased rapidly in untreated animals. An increase of systemic vascular resistance (SVR) and pulmonary vascular resistance (PVR) was observed in dogs without treatment. Gabexate mesilate given as a therapy significantly improved the hemodynamic parameters. The study demonstrates an advantageous influence of synthetic antiprotease gabexate mesilate on the course of acute experimental pancreatitis.
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PMID:Effect on hemodynamics of therapeutic infusion of gabexate mesilate (FOY) in experimental acute pancreatitis. 249 22

The developments and trends of hemostatic and antithrombotic drugs in Japan were investigated chronologically for the last 50 years after the 2nd World War. 1. Hemostatic drugs are classified into three groups ; capillary stabilizers, blood coagulants and antifibrinolytics. l) As to capillary stabilizers, flavonoid (rutin, 1949), adrenochrome derivative (carbazochrome, 1954) and conjugated estrogen (Premarin, 1964) were introduced therapeutically. Especially, the soluble types of adrenochrome compounds (Adona 1956, S-Adchnon, 1962) were devised and used widely in Japan. 2) Drugs concerning blood coagulation, thrombin, introduced in 1953, and hemocoagulase, a snake venom introduced in 1966, were used clinically. V.K. groups producing various coagulation factors were introduced as V.K1 (Phytonadione, 1962) and V.K2 (rnenatetrenone,1972), and they were admitted in "The Japanese Pharmacopoeia"editions 8 and 14, respectively). 3) Regarding antifibrinolytic drugs, Japanese researchers have made remarkable contributions. e-Aminocapronic acid (Ipsilon, 1962) and tranexamic acid (Transamin, 1965) were developed and used for various abnormal bleedings or hemorrhage associated with plasmin over-activation. tranexamic acid also proved to suppress inflammations of the throat such as tonsillitis, pharyngitis or laryngitis. 2. Antithrombotic drugs are also divided into three groups; anticoagulants, antiplatelet drugs and fibrinolytics.1) The anticoagulants used therapeutically by injection are heparins (Na-salt, 1951; Ca-salt, 1962) and low-molecular-weight heparins such as dalteparin (1992), parnaparin (1994) and reviparin (1999). The low molecule compounds are superior to the original heparins in reducing the risk of bleeding. As oral anticoagulants, coumarin derivatives, dicumarol (1950), ethylbiscoumacetate (1954), phenylindandione (1956) and warfarin (1962) are known. Warfarin potassium is the main drug for oral therapy of thromboembolism lately. Gabexate mesilate (1989) and nafamostat mesilate (1989) were developed in Japan and used for DIC and acute pancreatitis to inhibit protease enzymes. Argatroban is a unique antithrombin product developed by Japanese researchers in 1990, and is used for vascular or cerebral thrombosis. After noticing in 1968 that aspirin inhibits platelet aggregation and prevents myocardial infraction, projects for developing antiplatelet drugs were initiated worldwide. Ticlopidine, originally developed in France, was introduced in 1981 and prevailed widely in Japan for reducing the risk of thrombotic stroke. Aspirin itself was recognized by the FDA (USA) as an antithrombotic drug in 1988, and was also approved by Japanese authorities in 2000. PGE1 clathrate compounds have also been developed as antiplatelet drugs; alprostadil alfadex for injection (1979), and limaprost alfadex for oral use (1988). The PGI2 product, beraprost sodium, for oral use followed them in 1992. Other antiplatelet drugs with unique mechanisms explored in Japan: Ozagrel (1988), which inhibits TXA2 synthetase, cilostazol (1988), which inhibits cAMP phosphodiesterase, and sarpogrelate (1993), which blocks 5HT in platelets, are the notable drugs in this field. Ethyl icosapentate, from fish oil, is available for antiplatelet therapy. Concerning the fibrinolytic system, plasminogen activators are useful for thromboembolism. The streptokinase from bacterial origin developed in the USA and Europe was not introduced, and urokinase (1965) was the first plasminogen activator developed in Japan. Then tissue plasminogen activators (t-PA) tisokinase (cell culture, 1991), alteplase (genetical recombination, 1991), nateplase (genetical recombination, 1996), monteplase (1998) and pamiteplase (1998) were developed and approved for acute myocardial infarction. Nasaruplase (prourokinase, cell culture,1991) was also approved for the same indication. While the development of the hemostatic drugs ceased in the 1960s, avid project studies for antithrombotic drugs including fibrinolytics began in the 1980s and are progressing now towards new molecular targets. This may be due to the increasing tendency of cardiovascular thromboembolic diathesis in Japan. (The figures in parentheses are the years approved by the Japanese Ministry of Health, Labor and Welfare.)
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PMID:[A 50-year history of new drugs in Japan-the development and trends of hemostatics and antithrombotic drugs]. 1457 69