Screening for producers of proteinases with fibrinolytic (plasmin like and plasminogen activa ting) and collagenolytic activities was carried out among 83 strains of microscopic fungi belonging to various ecological groups. Entomopathogenic micromycetes secreted proteinases with higher fibrinolytic and col lagenolytic activity than saprotrophic, potentially phytopathogenic, and epiphytic strains. Micromycete strains possessing proteolytic enzymes with collagenase activity were revealed, as were the strains producing proteinases with plasmin like activity. None of the strains studied secreted proteinases possessing only plas minogen activating activity. Tolypocladium inflatum k1 was found to be a producer of extracellular proteinases with high plasminogen activating, plasmin like, and collagenolytic activities. The specific plasminogen activating activity of T. inflatum k1 was shown to be 20% higher than its plasmin like activity.Specific values of plasminogen activating (1) and plasmin like (2) fibrinolytic activity of T. inflatum k1.
A model of venous thrombosis on the rabbit marginal ear vein was developed. It is based on occlusion of a segment of the left or right ear vein followed by injection of thrombin into this segment. Thrombolytic activity of longolytin applied externally onto the thrombotic venous segment was evaluated. The drug 2-fold shortened the time of clot lysis and 4-4.5-fold increased the rate of thrombolysis. The effect of longolytin was potentiated by heparin. The rate of lysis was higher in large thrombi and in the left vein (effect of asymmetry).
Цель исследования: изучение взаимодействия комплекса протеолитических ферментов препарата лонголитин из анаморфного гриба Arthrobotrys longa с антикоагулянтным и антитромботическим препаратом пиявитом.
Материалы и методы. Препарат пиявит смешивали в разных разведениях с различными концентрациями лонголитина и определяли фибринолитическую активность (ФА) смеси. В другой серии опытов пиявит добавляли в погруженную культуру гриба-продуцента. По окончании эксперимента в пробах культуральной жидкости (КЖ) определяли ФА. Антикоагулянтные свойства КЖ измеряли методом рекальцификации и записи тромбоэластограммы при добавлении КЖ к плазме крови здоровых интактных крыс.
Результаты. В опытах in vitro пиявит дозозависимо угнетал ФА лонголитина до полного ее подавления при концентрации 16 мг/мл. Добавление пиявита к культуре гриба-продуцента вызывало усиление биосинтеза препарата с увеличением ФА. КЖ при этом обладала высокой антикоагулянтной активностью. Время рекальцификации и показатель R тромбоэластограммы в КЖ были статистически достоверно удлинены, увеличивалась и антиполимеризационная активность КЖ.
Заключение. Совместное применение двух антитромботических средства (лонголитина и пиявита) в исследовании in vitro привело к уменьшению фибринолитических, а значит, и тромболитических свойств лонголитина. Таким образом, одновременное использование этих препаратов требует осторожности.
Aim: to study the interaction of Longolitin (complex of proteolytic enzymes from anamorphic fungus Arthrobotrys longa) with anticoagulative and antithrombotic drug Piyavit.
Materials and methods. We mixed diff erent dilutions of Piyavit with various concentrations of Longolitin and determined fibrinolytic activity (FA) of the mixture. In other experimental series we added Piyavit to submerged culture of the fungus-producer. At the end of the experiment we determined FA in culture liquid samples (CL). Anticoagulative properties of CL were measured by recalcification method and thromboelastograms recording with CL addition to blood plasma of healthy intact rats.
Results. In in vitro experiments Piyavit dose-dependently inhibited FA of Longolitin until it’s completely suppression at concentration of 16 mg/ml. Piyavit addition to the culture of fungus-producer caused the enhancement of drug biosynthesis with FA increasing. At the same time CL had a high anticoagulative activity. Recalcifi cation time and parameter R of thromboelastogram in CL were statistically signifi cant elongated, also CL anti-polymerization activity increased.
Conclusion. Combined application of two antithrombotic agents (Longolitin and Piyavit) in in vitro study led to decreasing of fibrinolytic, and so thrombolytic properties of Longolitine. Thus, the simultaneous use of these drugs requires caution. Adding piyavit to the culture of the producer fungus led to an increase in the biosynthesis of the preparation. Thus, caution is needed at simultaneous using of these drugs.
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