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[Follow-up study on the hemostatic effect of the Vasolamin preparation in domestic animals].

In this paper the haemocoagulative effect of the Vasolamin preparation was examined after intravenous application in cattle, sheep, and horses by means of tests. After a laboratory confirmation of the coagulative effect of the tested preparation we used it for the purpose of haemostasis in the clinical practice. After an administration of the preparation faster coagulation of the blood was observed in all examined animals. The setting in of the effect could be observed already after 5 minutes, the maximum effect was recorded between the 15th and 30th minutes after application, and the effect lasted, although gradually weakened, for one to two hours. In the case of bleeding clinical patients the application of Vasolamin was always successful.

Animals↗

Hemorrhage induced by intrauterine devices: control by local proteinase inhibition.

The intrauterine application of proteinase inhibitors, tranexaminc acid and the pancreatic trypsin inhibitor (Trasylol), reduces or eliminates menorrhagia and intermenstrual bleeding (spotting) produced by an intrauterine device (IUD). A decrease in pain and vaginal (cervical) discharge is also frequently observed. A single application is usually sufficient, more than three never being required. The effect lasts for an average of three cycles. In addition to the clinical use of these agents for the treatment of uterine hemorrhage, the slow release of proteinase inhibitors from an IUD may well be useful in minimizing its side effects without interfering with its contraceptive activity.

Administration, Topical↗

Zymogen-activation kinetics. Modulatory effects of trans-4-(aminomethyl)cyclohexane-1-carboxylic acid and poly-D-lysine on plasminogen activation.

The kinetics of plasminogen activation catalysed by urokinase and tissue-type plasminogen activator were investigated. Kinetic measurements are performed by means of a specific chromogenic peptide substrate for plasmin, D-valyl-L-leucyl-L-lysine 4-nitroanilide. Two methods are proposed for the analysis of the resulting progress curve of nitroaniline formation in terms of zymogen-activation kinetics: a graphical transformation of the parabolic curve and transformation of the curve for nitroaniline production into a linear progress curve by the addition of a specific inhibitor of plasmin, bovine pancreatic trypsin inhibitor. The two methods give similar results, suggesting that the reaction between activator and plasminogen is a simple second-order reaction at least at plasminogen concentrations up to about 10 microM. The kinetics of both Glu1-plasminogen (residues 1-790) and Lys77-plasminogen (residues 77-790) activation were investigated. The results confirm previous observations showing that trans-4-(aminomethyl)cyclohexane-1-carboxylic acid at relatively low concentrations enhances the activation rate of Glu1-plasminogen but not that of Lys77-plasminogen. At higher concentrations both Glu1- and Lys77-plasminogen activation are inhibited. The concentration interval for the inhibition of urokinase-catalysed reactions is shown to be very different from that of the tissue-plasminogen activator system. Evidence is presented indicating that binding to the active site of urokinase (KD = 2.0 mM) is responsible for the inhibition of the urokinase system, binding to the active site of tissue-plasminogen activator is approx. 100-fold weaker, and inhibition of the tissue-plasminogen activator system, when monitored by plasmin activity, is mainly due to plasmin inhibition. Poly-D-lysine (Mr 160 000) causes a marked enhancement of plasminogen activation catalysed by tissue-plasminogen activator but not by urokinase. Bell-shaped curves of enhancement as a function of the logarithm of poly-D-lysine concentration are obtained for both Glu1- and Lys77-plasminogen activation, with a maximal effect at about 10 mg/litre. The enhancement of Glu1-plasminogen activation exerted by trans-4-(aminomethyl)cyclohexane-1-carboxylic acid is additive to that of poly-D-lysine, whereas poly-D-lysine-induced enhancement of Lys77-plasminogen activation is abolished by trans-4-(aminomethyl)cyclohexane-1-carboxylic acid. Analogies are drawn up between the effector functions of poly-D-lysine and fibrin on the catalytic activity of tissue-plasminogen activator.

Aprotinin↗

Echo-encephalographic study of ventricular dilatation after subarachnoid hemorrhage, with special reference to the effect of antifibrinolytic treatment.

Echo-encephalographic examinations were performed in 144 patients after subarachnoid hemorrhage. Ninety-three of the patients received antifibrinolytic treatment (AMCA). The width of the third ventricle could be measured in all the patients, and lateral ventricle measurements were obtained in 94 patients. Third ventricular dilatation developed in 78 patients (54 per cent), and lateral ventricle enlargement was seen in 55 patients (58 per cent of those examined). The incidence of third ventricle dilatation was higher in the AMCA-treated group (62.5 per cent) than in the non-treated group (39.2 per cent), and this difference was statistically significant (P less than 0.05). The hydrocephalus in most cases developed 2-3 weeks after the bleeding, and reached its peak within the first 2-3 months, with subsequent complete or partial normalization of the ventricular size. At later follow-up examinations 1-4 years after the bleeding, only nine patients had persisting dilatation of moderate or pronounced degree. There was no indication that the dilatation was more severe or pronounced degree. There was no indication that the dilatation was more severe or protracted in the AMCA-treated group than in the non-treated group. In 11 patients the hydrocephalus required a shunt-operation, but the frequency of shunt-operations was not significantly different in the two groups. It is concluded that although AMCA-treated patients in comparison with non-treated patients are exposed to a somewhat higher risk of complicating hydrocephalus after subarachnoid hemorrhage, this risk cannot at present be considered as any serious contraindiction to this sort of treatment.

Adolescent↗

Intestinal lymphangiectasia markedly improved with antiplasmin therapy.

A 35-yr-old woman with intestinal lymphangiectasia was treated with trans-4-aminomethyl cyclohexane carboxylic acid. After 6 wk of antiplasmin therapy, her serum total protein increased to normal levels and 131I-polyvinyl pyrrolidone excretion was also normalized. With a daily administration of trans-4-aminomethyl cyclohexane carboxylic acid, the patient has manifested no symptoms for 8 yr up to the present. Throughout the clinical course, the values for euglobulin lysis time showed a close relationship to changes in serum total protein. It was then suggested that increased plasma fibrinolysis may enhance lymphatic permeability to plasma proteins. During this treatment, a decreased percentage of T lymphocytes became normalized together with serum immunoglobulin values. In addition, the therapy has resulted in the disappearance of duodenal lesions observed endoscopically.

Adult↗