Effect of thymoptin on hemostasis and fibrinolysis in rats with experimental nephritis.

Immune nephritis in rats was induced by administration of nephrotoxic rabbit antiserum. The development of severe renal inflammation (proteinuria, edema, lipemia, increased erythrocyte sedimentation rate, and 30% mortality) was accompanied by hypercoagulation and inhibition of fibrinolysis. Repeated subcutaneous injections of thymoptin in a low dose of 0.1 microg/200 g (5 injections every other day) increased the severity of inflammation and prethrombotic state of the blood. Lengthening the period between injections (5 injections at 5-day intervals) was followed by a tendency toward attenuation of nephritis and correction of hypercoagulation. In healthy rats, thymoptin produced an opposite effect on hemostasis, which was manifested in moderate stimulation of fibrinolysis and hypocoagulation.

[The fibrinolytic system in uric acid dysmetabolism].

The subjects of the study were 50 first-degree relatives of patients with uric acid (UA) dysmetabolism. The subjects were divided into three groups: 15 with hyperuricosuria and normal UA blood level (group 1), 17--with hyperuricosuria and hyperuricemia (group 2), and 18--with hyperuricemia and lowered UA clearance (group 3). All of them displayed inhibited urine fibrinolytic activity (UFA) and reduced urokinase activity. The degree of UFA inhibition correlated with urokinase activity (r = 0.60) and grew from group 1 to group 3; the subjects in the latter had maximal manifestations of tubulointerstitial nephritis, which suggests that disorder of the local fibrinolytic mechanisms plays an important role in the development and progress of urate tubulointerstitial renal lesion. No changes of blood fibrinolysis were observed.

[Effect of diet therapy on status of hemocoagulation and fibrinolysis in type 2 diabetes patients]. / Vliianie dietoterapii na sostoianie gemokoaguliatsii i fibrinoliz u bol'nykh sakharnym diabetom 2 tipa.

The changes in parameters of blood coagulation and the fibrinolytic system in 60 patients with type 2 diabetes mellitus was studied. We conclude what the non insulin depended diabetes mellitus is associated with disturbances in hemostatic and fibrinolytic systems that could contribute to the development of diabetic vascular disease. Besides favorable influence to a clinical picture of disease universal normalizing influence of traditional diet therapy on parameters of coagulation and the fibrinolytic system. Our results show that diet therapy improve metabolic control in type 2 diabetic patients could reflect a reduces thrombotic potential and decreased cardiovascular risk.

Coagulation and fibrinolysis in rats after surgery with monopolar electrical scalpel.

Blood coagulation, fibrinolysis in plasma and peritoneal fluid, and activity of tissue plasminogen activator in the peritoneum and uterine horns were studied in albino rats after surgery on the uterine horns with a monopolar electrical scalpel. This instrument induced severe inflammatory reaction and disturbances in the fibrinolysis and coagulation systems.

[Fibrinolytic activity of the urine during chronic glomerulonephritis and amyloidosis]. / Fibrinoliticheskaia aktivnost' mochi pri khronicheskom glomerulonefrite i amiloidoze.

Correlative interconnections between plasminogen activator (PA) activity (fibrin plate method) and level of urokinase antigen (Ag UAP) and tissue PA antigen (Ag TAP) in urine and blood (ELISA) were studied in 60 patients with chronic glomerulonephritis (CGN) and 38 patients with amyloidosis. The high degree of positive correlation between blood and urine initial PA activity and Ag UAP content was found. This suggests the possible leading role of UAP in formation of the basal fluctuations of fibrinolytic activity in blood and urine. High degree of correlation--r = +0.84 and p < 0.001--was found between blood Ag UAP and urine Ag TAP in amyloidosis only. The functional protein loading probe revealed great importance of high urine and blood AP activity in realizing of ultrafiltration renal process--in CGN and amyloidosis.

[Urokinase as a blood and urine plasminogen activator in chronic glomerulonephritis and amyloidosis]. / Urokinaza kak aktivator plazminogena krovi i mochi pri khronicheskom glomerulonefrite i amiloidoze.

To estimate the individual role of the plasminogen activators (PA) urokinase (u-PA) and tissue (t-PA) in the development of two renal diseases (the nephrotic forms of chronic glomerulonephritis (CGN) and amyloidosis, the baseline plasma and urine levels of u-PA and t-PA antigens, their functional activity (FPAA), and changes in these parameters were determined after protein loading test (0.7 g/kg). In healthy individuals and patients with amyloidosis, the baseline FPAA changes from 0 to the maximum were caused only by the alterations of u-PA levels, in those with CGN, they were induced by the changes in the content of u-PA and t-AP antigens. The functional loading test revealed PA reserves solely in patients having a high baseline FPAA for both nephropathies: u-PA in amyloidosis and t-PA in CGN. In all the patients, the urine levels of u-PA antigens were 20-40 times more than those of t-PA antigens and 5-6 times less than those plasma u-PA. The findings suggest that urokinase may be regarded as the major plasminogen activator involved in CGN and amyloidosis.

[Effect of the proteolytic substance morikrase on the status of scar tissue under in vitro conditions]. / Deistvie proteoliticheskogo preparata morikrazy na sostoianie rubtsovoi tkani v usloviiakh in vitro.

Proteolytical preparation moricrasa was isolated from hepatopancreas of Paralithodes camtshatic. Moricrasa and its fractions were used for lysis of cicatricial tissue under in vitro conditions. It was found that moricrasa in concentrations 0.5 mg/ml and 2 mg/ml lysed the cicatrix during 72 and 14-16 hours, respectively. The fraction consisted of collagenolytic proteinase PC and trypsin revealed maximal activity of fraction of moricrasa was absent.

[Role of local fibrinolytic activity of the uterine horns in rats in the pathogenesis of formation of postoperative adhesions]. / Rol' lokal'noi fibrinoliticheskoi aktivnosti matochnykh rogov u krys v patogeneze formirovaniia posleoperatsionnykh spaek.

Experimental models were used to examine the impact of corrections of the uterine horns on the activity of tissue plasminogen activator (tPA). The application of sutures was shown to suppress the activity of tPA in the uterine horns to a greater extent than other surgical techniques. With this, the use of catgut caused the highest suppression of tPA activity and increases in the frequency and density of formation of postoperative adhesions. Depleted tPA reserves and its higher inhibitor levels were found to lead to depressed fibrinolysis, which is a pathogenetic factor for developing an adhesive process.

[Activators and inhibitors of fibrinolysis in chronic glomerulonephritis and amyloidosis]. / Aktivatory i ingibitory fibrinoliza pri khonicheskom glomerulonefrite i amiloidoze.

Functional activities of plasminogen activators (FPAA) and their inhibitors and plasminogen activators's (PA), antigen level were determined in 31 patients with chronic glomerulonephritis, 23 patients with amyloidosis and 15 healthy persons. High FPAA correlated with favourable prognosis of diseases, elevated PA antigen level and diminished alpha 1-antitrypsin, alpha 2-macroglobulin and antiactivator activities. There were decreased PA antigen level and increased inhibitor's activities in group with zero FPAA. Protein loaded functional probe demonstrated the presence of PA reserves in high FPAA patients and "pathological proteolysis" in zero FPAA patients. The last phenomenon was likely connected to nonspecific proteases differed from PA.

[Effect of docanol on the status of hemostasis and fibrinolysis systems, as well as lipid spectrum in patients with ischemic heart disease depending on the initial level of fibrinolytic activity]. / Vliianie dokanola na sostoianie sistem gemostaza, fibrinoliza i lipidnyi spektr u bol'nykh ishemicheskoi bolezn'iu serdtsa v zavisimosti ot iskhodnogo urovnia fibrinoliticheskoi aktivnosti.

Forty patients with coronary heart disease (CHD) concurrent with hyperlipidemia were divided into 2 groups according to the baseline fibrinolytic activity. The group with the depressed fibrinolytic system displayed the highest atherogenicity index and levels of cholesterol, low and very low density lipoprotein cholesterol and half levels of high density lipoproteins. After 45-day ingestion of docanol, a new Russian food additive containing docosahexanoic and eicosapentaenoic acids there were positive changes in the lipid spectrum in the both groups. The fibrinolytic changes were heterodirectional: activator and plasma activities increased in the group of fibrinolytic depression while in the group of baseline normal fibrinolysis the activity of plasminogen activator fell.

[The venous occlusion test in assessing the fibrinolytic activity of the vascular endothelium in lupus nephritis patients]. / Test venoznoi okkliuzii v otsenke fibrinoliticheskoi aktivnosti sosudistogo éndoteliia u bol'nykh volchanochnym nefritom.

A venous occlusion test was used to evaluate the reserves of the kidneys and that of vascular endothelium fibrinolytic activity (VEFA) in patients with lupus nephritis (LN). Prior to and following venous occlusion functional activity of plasminogen activators in plasma and urine (PAPU), plasma activity of antiactivator (PAAA), urokinase urine activity (UUA) were measured by fibrin plate lysis test in 24 patients with active LN, 6 SLE patients with intact kidneys, 10 healthy subjects. Venous occlusion test revealed normal reserve of plasma activator activity in mild LN and depletion of this reserve in LN patients with nephrotic syndrome and rapidly progressive LN. In the latter patients PAPU and PAAA were suppressed. PAPU reserve existed in all the patients, but those with rapidly progressive LN. UUA in LN was close to normal and did not change significantly after venous occlusion. The data obtained suggest that patients with severe LN had reduced reserves of VEFA, while in those with progressive LN there were also diminished reserves of renal fibrinolytic activity reflecting the severity of endothelial lesion.

[Tissue-type plasminogen activator in patients with lupus nephritis]. / Aktivator plazminogena tkanevogo tipa u bol'nykh volchanochnym nefritom.

ELISA was used to measure tissue plasminogen activator antigen in blood plasma and urine of 42 patients with active lupus nephritis (16 with isolated urinary syndrome, 13 with nephrotic syndrome, 13 with rapidly progressive LN). Control groups consisted of 17 patients with inactive LN and 15 healthy subjects. Inhibition of fibrinolysis in vascular system correlating with the disease severity was found in patients with active LN. This may result from both defective synthesis of tissue plasminogen activator and neutralizing action of antiactivator. Urinary fibrinolytic activity was inhibited only in patients with rapidly progressive LN because of hyperactive synthesis of antiactivator. The above changes occur as endothelial cell dysfunction due to activating and damaging action of immune complexes, antibodies, cytokines on vascular endothelium. Zero activator activity of plasma and urine in patients with active LN reflects severe dysfunction of endothelial cell caused by its structural disorganization.

[Fibrinolytic and thrombolytic properties of the drug morikrase]. / Fibrinoliticheskie i tromboliticheskie svoistva preparata morikrazy.

Fibrinolytic and thrombolytic properties of morikrase, a complex of proteinases obtained from hepatopancreatic tissues of king crab (Paralithodes camtschatica), were studied in vivo and in vitro. High fibrinolytic activity and dose-dependent activating properties were detected on standard and heated fibrin plates. The preparation maintained its properties during long-term storage at 4 degrees and 22 degrees C. The thrombolytic activity of the drug, affecting the preformed thrombus, was observed both in vitro and in vivo, in rats with experimental thrombosis. Two-phase alteration of the fibrinolytic system and moderate hypocoagulation were found after intravenous administration of morikrase.

[The wound healing effect of ointment with morikrase]. / Ranozazhivliaiushchee deistvi mazi s morikrazoi.

An ointment containing, 1% morikrase (a complex of proteinases isolated from hepatopancreatic tissues of king crab Paralithodes camtschatica) exhibited the wound healing properties and did not irritate the skin tissues during long-term treatments of rats. Only slight hypocoagulation was observed in intact animals after external application of the ointment. At the same time, the drug caused an increase in fibrinolytic activity in blood of rats with purulent wounds due to activation of the plasminogen activator.

[The functional activity of plasminogen activators in the blood plasma and urine of patients with lupus nephritis]. / Funktsional'naia aktivnost' aktivatorov plazminogena v plazme krovi i v moche bol'nykh volchanochnym nefritom.

A fibrin plate technique was employed to study functional activity of plasminogen activators in plasma and urine (FAAP, FAAU), activity of antiactivator in plasma (AAAP), urokinase urine activity (UUA) in 35 lupus nephritis (LN) patients. The latter comprise 3 groups by the disease severity: 22 patients with active LN attended by urinary syndrome (group 1), 7 patients with LN associated with nephrotic syndrome (group 2), 6 patients with rapidly progressing LN (group 3). Control groups included 5 SLE patients with unaffected kidneys and 25 healthy subjects. FAAP proved heterogeneous both in SLE and healthy subjects. SLE patients with progressive LN had diminishing FAAP which was accompanied by growing AAAP. The latter reached maximal values in groups 2 and 3. UUA declined with LN aggravation. The relation of low FAAP in LN patients to affection of vascular endothelium and binding of plasminogen activators with the inhibitors to form inactive complexes is considered.

[Physico-chemical properties of the thrombolytic compound longolytin]. / Fiziko-khimicheskie svoistva tromboliticheskogo preparata longolitina.

A preparation exhibiting high fibrinolytic activity and ability to activate plasminogen was isolated from cultivation medium of Arthrobotrys longa. Homogeneous protein, obtained after gel filtration on Sephadex G-100, had molecular mass 28,600, pI-3.68-3.74, optimum activity at pH 6.0-9.0 and temperature optimum at 37 degrees. The enzyme proved to be serine proteinase as shown by analysis using inhibitors; it required thiol groups.

[The effect of a protein loading test on the fibrinolytic system in patients with chronic glomerulonephritis and amyloidosis]. / Vliianie belkovoi nagruzochnoi proby na fibrinoliticheskuiu sistemu u bol'nykh khronicheskim glomerulonefritom i amiloidozom.

Investigation of the reserves of the fibrinolytic system with the aid of protein stimulation was carried out in 10 patients with chronic glomerulonephritis and in 10 patients suffering from amyloidosis. All the patients manifested proteinuria exceeding 3.5 g/day and other symptoms of nephrotic syndrome of varying intensity. Renal function was preserved in all the patients. The reserves of the fibrinolytic system were measured by analyzing blood plasma and urine before and after beef protein stimulation. The data revealed reciprocal responses of activator activity in blood plasma and urine in patients suffering from chronic glomerulonephritis and amyloidosis. In patients with amyloidosis, the test revealed complete depletion of activator activity in urine while its considerable reserves were preserved in blood plasma of the systemic channel.