What is known and objectiveUlipristal acetate, a progesterone receptor modulator, pharmacologically inhibits endometrial proliferation and thereby prevents pregnancy. It is primarily used as emergency contraception, but also for the treatment of fibroids in women of reproductive age. There have been no published cases of pregnancy, while on therapy with ulipristal acetate. Case descriptionIn this article, we present a case report of spontaneous pregnancy during ulipristal acetate therapy. What is new and conclusionTo our knowledge, this is the first patient with spontaneous conception, while on ulipristal acetate treatment. There were no drug-related complications, and the pregnancy resulted in the delivery of a healthy baby.

Plasma level of IgG autoantibodies to plasminogen was measured by ELISA in patients with benign prostatic hyperplasia ( n =25), prostatic cancer ( n =17), lung cancer ( n =15), and healthy volunteers ( n =44). High levels of IgG to plasminogen were found in 2 (12%) of 17 healthy women, in 1 (3.6%) of 27 specimens in a healthy man, in 17 (68%) of 25 specimens in prostatic cancer, in 10 (59%) of 17 specimens in lung cancer, and in 5 (30%) of 15 specimens in benign prostatic hyperplasia. Comparison of plasma levels of anti-plasminogen IgG by affinity chromatography showed 3-fold higher levels in patients with prostatic cancer vs. healthy men.

The comparative in vitro study of the kinetics of various reactions involved in the process of thrombolysis initiated by streptokinase (SK) and staphylokinase (STA) has been carried out. It has been shown that upon the interaction of plasminogen (Pg) with SK or STA in equimolar quantities, the formation rate and the specific esterase activity of the complex plasmin (Pm) with SK (Pm•SK) is higher than those of the complex Pm•STA. The catalytic efficiency (k cat/K m) of hydrolysis of the chromogenic plasmin substrates by Pm•SK complex is 2 times higher than by Pm•STA complex. In the absence of fibrin, the catalytic efficiency (k Pg/K Pg) of activation of Glu-plasminogen and Lys-plasminogen glycoform II by Pm•SK complex is higher than by Pm•STA complex, but the presence of fibrin increases k Pg/K Pg of activation of both plasminogens by Pm•STA complex much more than by Pm•SK complex due to a decrease in K Pg In contrast to STA (15.5 kDa), an SK molecule (47 kDa) creates remarkable steric hindrances for the interaction of plasmin in Pm•SK complex with protein inhibitors. In addition, SK causes higher fibrinogen degradation in plasma than STA. It has been shown that Pm•SK and Pm•STA complexes lyse fibrin clots in buffer with similar rates, while the rate of lysis of plasma clots, immersed in plasma, by Pm•STA complex is remarkably higher than in the case of Pm•SK complex. It has been revealed that the species specificity of STA and SK is determined mainly by the rate of formation and the efficiency of Pm•SK and Pm•STA complexes in the activation of autologous plasminogen. The lysis efficiency of plasma clots of mammals falls in the series: human > dog > rabbit for SK and dog > human > rabbit for STA. The results show that in the purified system SK is a more effective plasminogen activator than STA. In the system containing fibrin and α2-AP, the activator and fibrinolytic activities of STA are higher than those of SK, due to the increased stability in plasma and fibrin specificity of STA, the fast reaction of the complex Pm•STA with α2AP, and the ability of the STA to recycling in the presence of α2AP.

Ковалентные конъюгаты СК-ПЭГ2 и СК-ПЭГ5 с различными степенями модификации аминогрупп белка получены вариацией времени инкубации стрептокиназы (СК) с активированным полиэтиленгликолем (M 2 и 5 кДа, ПЭГ2 и ПЭГ5); изучены их свойства в сравнении со свойствами свободной СК in vitro. Показано, что максимально стабильные в плазме и сохраняющие 80% исходной фибринолитической активности конъюгаты СК-ПЭГ2 и СК-ПЭГ5 образуются при степенях модификации аминогрупп белка 54 и 52% соответственно. При взаимодействии данных конъюгатов с плазминогеном в эквимолярных концентрациях образуются активаторные комплексы плазмина (Пл) Пл.-ПЭГ2 и Пл.-ПЭГ5, максимальная амидазная активность которых равна активности комплекса Пл с нативной СК. Найдено, что каталитическая эффективность активации плазминогена (kПг/KПг) комплексом Пл.-ПЭГ2 немного выше (2.84 мин-1 мкM-1), а комплексом Пл.-ПЭГ5 ниже (1.17 мин-1 мкM-1), чем немодифицированным комплексом Пл. (2.1 мин-1 мкM-1). Исследование кинетики лизиса сгустков из плазмы крови человека и истощение уровней плазминогена и фибриногена в плазме под действием равных доз свободной СК и указанных конъюгированных образцов СК показало, что конъюгаты СК-ПЭГ2 и СК-ПЭГ5 обладают высокой тромболитической активностью (89 и 72% от активности свободной СК соответственно) и вызывают в 3.5–4 раза меньшие побочные эффекты, чем свободная СК. Полученные нами конъюгаты СК-ПЭГ2 и СК-ПЭГ5 с повышенной стабильностью в плазме и низким уровнем побочных эффектов могут быть использованы в терапии тромботических заболеваний.

Covalent SK-PEG2 and SK-PEG5 conjugates with various degrees of modification of the protein amino groups were obtained by variation of the duration of streptokinase (SK) incubation with activated polyethylene glycol ( M 2 and 5 kDa, PEG2 and PEG5); their properties were studied in comparison with the properties of unmodified SK in vitro. SK-PEG2 and SK-PEG5 conjugates with the highest stability in plasma retaining 80% of initial fibrinolytic activity were formed at modification degrees of 54 and 52%, respectively. Interaction of the conjugates with equimolar plasminogen resulted in the formation of plasmin (Pm) activator complexes Pm·SK-PEG2 and Pm·SK-PEG5 with the maximum amidase activity being the same as that of Pm complex with native SK. Catalytic efficiency of plasminogen activation ( k Pg / K Pg ) was found to be slightly higher (2.84 min −1 μM −1 ) in case of Pm·SK-PEG2 complex and slightly lower, in case of the Pm·SK-PEG5 complex (1.17 min −1 μM −1 ), if compared to that of the unmodified complex Pm·SK (2.1 min −1 μM −1 ). Investigation of lysis kinetics of human plasma clot and depletion of plasminogen and fibrinogen plasma levels under the effect of equal doses of SK in free and conjugated forms demonstrated that SK-PEG2 and SK-PEG5 conjugates possess high thrombolytic activity (89 and 72% to the activity of free SK, respectively) and cause 3.5–4-fold lower side effects than free SK. The SK-PEG2 and SK-PEG5 conjugates with increased stability in plasma and reduced side effects may be used in therapy of thrombotic disorders.

By variation of incubation time of streptokinase (SK) with activated polyethylene glycol (M 2 and 5 kDa, PEG2 and PEG5) it was obtained covalent SK-PEG2 and SK-PEG5 conjugates with different modification degrees of amino groups of protein and their properties were studied in vitro as compared with free SK. It was shown, that maximal stable and retaining 80% fibrinolytic activity SK-PEG2 and SK-PEG5 conjugates are formed when the modification degrees of amino groups of protein are 54 and 52%, respectively. At interaction of the given conjugates with equimolar plasminogen concentration it were formed the plasmin (Pm)·SK-PEG2 and Pm·SK-PEG5 activator complexes, the maximal amidase activity of which is equal to activity of unmodified Pm·SK complex. It was found, that the catalytic efficiency of plasminogen activation (kPg/KPg) by Pm·SK-PEG2 complex is some higher (2.84 min(-1) μM(-1)) and by Pm·SK-PEG5 complex is lower (1.17 min(-1) μM(-1)), than that by unmodified Pm·SK complex (2.1 min(-1) μM(-1)). Investigation of lysis kinetics of human plasma clots and depletion of plasminogen and fibrinogen in plasma under the action of free SK and SK-PEG2 and SK-PEG5 conjugates showed, that the latter's have high thrombolytic activity (89 and 72%, respectively) and cause 3.5-4 fold lower side effects, than free SK. Obtained by us SK-PEG2 and SK-PEG5 conjugates with increased stability and decreased side effects may be used in the therapy of thrombotic disorders.

Results 31 patients (24.8%) were treated with StTh prior to admission. Leading diagnoses for patients previously on StTh were STEMI (39%) and unstable angina (39%), while in the group of patients without StTh the leading diagnosis was STEMI (60%). In patients who were treated with StTh the proximal and middle segment of LAD were the most common locations of stenosis. The frequency of single-vessel, two-vessel and three-vessel CAD was equal amongst both groups, while single-vessel CAD was more frequent in patients without prior StTh. According to ACC/AHA classification, type C lesion was discovered in 41% of patients without StTh and in 26% of patients with StTh. Conclusion According to the results of studies, 10-20% of patients experiencing an ACS were being treated with statins prior to the event. In our study, 24.8% of patients had been on StTh. The number of vessels with lesions was seen with equal frequency amongst patients with and without StTh. This apparent lack of benefit can most likely be explained by the increased number of risk factors amongst patients on StTh. Another advantageous finding seen in patients previously treated with statins was a significantly lower proportion of total occlusions, especially STEMI.

Results Leading diagnosis at admission in ACS patients with DM and without DM was STEMI (53%, 55% respectfully). According to the ACC/AHA classification of coronary lesions patients with DM had 56% of type B lesion, 41% of type C lesion and 3% of type A lesion. In our study, the largest number of significant stenosis was observed in the proximal and middle segment of LAD: 74% of patients with DM and 60% in patients without DM. In patients with DM single-vessel CAD was observed in 26%, twovessel in 41% and three-vessel in 32%, whereas in patients without DM, 52% single-vessel CAD, 30% two-vessel and 18 % three-vessel CAD. Conclusion Most of the studies showed that patients with DM are more likely to have diffuse distribution of CAD. Results of studies about the association of DM with the location of the lesion in CAD is also contradictory, in some studies was observed a higher incidence of proximal, and in other distal lesions. In our study, mostly affected was LAD, usually its proximal and middle segment. Also, RCA and ACx were more affected in the proximal and middle segment. The study found a higher prevalence of type C lesions and a higher prevalence of three-vessel CAD in patients with DM which confirms previous findings that patients with DM usually have diffuse CAD.

The frequency of venous and arterial thromboses and plasminogen level have been investigated in 78 patients with the antiphospholipid syndrome (APS), including 35 patients with systemic lupus erythematosus (SLE + APS) and 43 patients with primary APS (PAPS). The levels and genotypes of plasminogen activator inhibitor type 1 (PAI-1) were determined in 45 patients with APS (21 patients with SLE + APS and 24 patients with PAPS). A control group included 10 individuals without autoimmune disease signs and thromboses during the observation period and in anamnesis. It has been shown for the first time that for one third of 67 patients with APS and thromboses, high-positive levels of antiphospholipid antibodies (aPL) are associated with low plasminogen levels. The levels of PAI-1 antigen measured by the ELISA method, which detects active, latent and bound to plasminogen activator PAI-1, were compared with frequency of thromboses in APS patients. In one third of 43 patients with APS and thromboses the high and increased levels of PAI-1 were associated with high-positive aPL levels. One of possible mechanisms of this interrelationship was considered. It was shown that arterial and, to a greater extent, venous thromboses are associated with the 4G/5G polymorphism of the PAI-1 gene and high plasma level of the inhibitor in 79% of APS patients. In the presence of the 4G allele SLE + APS patients had higher PAI-1 levels than PAPS patients. The data obtained show that measuring the levels of plasminogen and PAI-1 as well as the 4G/5G polymorphism of the PAI-1 gene associated with thromboses may have the practical importance for identification of high risk of thrombosis in APS patients.