[Physiological effects induced by dermorphin synthetic analogue--opilong].

The effects of repeated opilong injections in a dose of 50 microg/kg/day on subsequent learning of Wistar rats have been studied. The substance caused significant anxiolytic and analgesic effects, as the majority of animals could be learned (90% against 40% in control group) despite of painful stimulus preceding to education. Opilong in a small dose displaced a relation of excitatory-inhibit processes to significant prevalence of excitation although the substance was already absent in an organism for a long time. Raised peripheral sensitivity in all rats, provoked by opilong, correlated with CNS hyper excitability, expressed in stressful, neurotic psychoemotional reactions and in the form of active avoidance. The biochemical blood analysis in opilong-induced rats demonstrated the attributes of prethrombosis in the form of fibrinolysis depression and hypercoagulation. A view is expressed, that the neuromediator brain systems can be the basic point of opilong action, that are responsible for the excitatory-inhibit conditions of CNS functioning referred on maintenance of conditioned field stability.

[Significance of the markers of endothelial dysfunction and hemorheological disorders for assessing the activity and prognosis of chronic glomerulonephritis].

AIM: to define the clinical value of changes in blood rheological properties and renal endothelial function in patients with hematuric and nephritic forms of chronic glomerulonephritis (CGN) and to ascertain whether the indices under study can be applied to assess the activity (progression) of nephritis and used as a prognostic criteria. SUBJECTS AND METHODS: Sixty-one patients, including 30 with hematuric nephritis (Group 1) and 31 with nephrotic nephritis (Group 2), were examined. A control group consisted of 12 healthy individuals. The rheological properties of blood, such as its viscosity; kinetics of spontaneous aggregation and disaggregation of red blood cells in shear flow; their deformability; urinary excretion of functionally active von Willebrandt factor (WF), a plasminogen activator inhibitor type 1 (PAl-1); urine total fibrinolytic activity (UTFA), activity of urinary urokinase-type plasminogen activator (UPA) were studied. RESULTS: The patients with CGN were found to have signs of impaired blood rheological properties (increased viscosity, an accelerated rapid phase of erythrocyte aggregation, increased strength of erythrocyte aggregates) and vascular endothelial dysfunction in the microcirculatory bed, among other factors, increased urinary excretion of functionally active WF, PA-1, which correlated with the activity of CGN. Data were obtained on the negative impact of the level of urinary PAl-1 excretion, red blood cell aggregation on the prognosis of CGN regardless of its form, the markers of endothelial damage/activation. Low urokinase activity and decreased red blood cell deformability in parallel with higher diurnal proteinuria are of poor prognostic value for hematuric nephritis. CONCLUSION: The findings illustrate two ways of the involvement of the endothelium in the mechanisms contributing to the development of tubular interstitial fibrosis, namely: endothelial dysfunction and as a substrate that links the processes of immune inflammation, hemorheology, and fibrinolysis/proteolysis in the kidney. The regularities revealed by clinical and laboratory comparison suggest that the indices under study may be used to determine the prognosis of the disease and may serve as a basis for the application of treatments aimed at correcting the detected disorders.

[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.

[Urine fibrinolytic activity as an indicator of kidney damage in uric acid metabolic imbalance]. / Fibrinoliticheskaia aktivnost' mochi kak pokazatel' porazheniia pochek pri narushenii obmena mochevoi kisloty.

AIM: To determine functional fibrinolytic activity of the urine in patients with different forms of purine metabolism disorder. MATERIAL AND METHODS: Uricemia, 24-h uricosuria, serum creatinine, GFR, maximal urinary specific gravity, urokinase activity in the urine, total fibrinolytic activity of the urine (TFAU), activity of plasminogen activator inhibitor (PAI) in blood were studied in 33 patients with genetically determined purine metabolism disorders. RESULTS: Patients with purine metabolism disorders vs controls had decreased TFAU and urokinase activity. There was no significant difference between the study and control groups in the levels of PAI in blood. No statistically significant difference was found between the patients with hyperuricemia and patients with hyperuricosuria in the levels of TFAU and urokinase activity, while the group with hyperuricemia was characterized by a decreased maximal specific urinary gravity. CONCLUSION: A decrease in TFAU and urokinase activity in patients with purine metabolism disorder was observed in the isolated hyperuricosuric stage of urite renal damage.

[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.

[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.

[The effect of piyavit on hemostatic processes and fibrinolysis in patients with ischemic heart disease]. / Vliianie piiavita na protsessy gemostaza, fibrinoliza u bol'nykh ishemicheskoi bolezn'iu serdtsa.

The oral use of the drug Piavit (derived from freeze-dried medicinal leeches) in 50 patients with coronary heart disease for 7 days in a daily dose of 600 mg (20 patients) and 1200 mg (30 patients) caused a moderate dose-independent increase in enzymatic, fibrinolysis, non-enzymatic fibrinolysis and antithrombin III activity. In half the patients who had low fibrinolytic levels, the agent stimulated mainly the release of plasminogen activator on administration days of 2 and 7. In other 15 patients the activity of plasminogen activator remained unchanged, but non-enzymatic fibrinolysis enhanced. Piavit prolonged the hypocoagulative effect of heparin and aspirin in the group of patients pretreated with these drugs. There were no clinical manifestations of the disease during 7 days.

[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.

[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.

[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.

[Thrombolytic effect of urokinase upon various methods of administration into the body]. / Tromboliticheskoe deistvie urokinazy pri raznykh sposobakh ee vvedeniia v organizm.

A preparation of urokinase, obtained from human kidney cell culture, was administered into rats at a single dose of 5,000-10,000 U/200 g of body mass in a variety of ways using intravenous, intraperitoneal and subcutaneous inoculations. After intraperitoneal and subcutaneous administrations an increase of fibrinolytic activity in blood was more long-term although less distinct; the phase of reactive hypercoagulation was only slightly detected within 24 hrs after these procedures. Thrombin-produced provocation of thrombosis led to a lesser ratio of death in these animals as compared with the animals group administered intravenously. However, thrombolytic effect of similar doses of urokinase was the highest in intravenous administration. The fibrinolytic activity correlated well with content of the antigen (enzyme) in blood but not with the antiplasmin content in all the procedures used.

[The fibrinolysis system in recurrent myocardial infarction]. / Sistema fibrinoliza pri povtornykh infarktakh miokarda.

Studies of blood fibrinolytic activity in 112 patients with repeated acute myocardial infarction or injury to the myocardium have revealed reduced fibrinolytic activity on non-heated fibrin plates, decreased plasmin activity and euglobulin+ fraction lysis, lowered levels of plasminogen activator, total nonenzymic fibrinolysis, antithrombin III, ++FFDP, and elevated soluble complexes of fibrin-monomer level. Complications of myocardial infarction presenting as thromboembolism; ciliary arrhythmia, chronic aneurysm with thrombosis are associated with still more marked disorders of the fibrinolysis system.

[Changes in the hemostasis and fibrinolysis system in rats with experimental renal hypertension]. / Izmenenie sistemy gemostaza i fibrinoliza u krys pri éksperimental'noi pochechnoi gipertenzii.

The arterial renal hypertension (170-180 mm Hg compared to the norm 100-120 mm Hg) developed in 2 months after one side nephrectomy and partial occlusion of the other renal artery. The level of high molecular weight plasma proteins was raised which led to the increase in the peripheral vessel resistance and hypertension degree. Fibrinolysis was depressed in the blood and in the cortical zone of the kidney. In early stages of hypertension fibrinolysis was sharply elevated, and high molecular weight compounds content was decreased. The antithrombin III and nonenzymatic fibrinolysis level were increased during the whole period (10-150 days).

[The effect of thymoptin on enzymatic fibrinolysis]. / Vliianie timoptina na protsess fermentativnogo fibrinoliza.

Stimulation of fibrinolysis, decrease in content of fibrinogen and inhibitors were observed after intravenous, intramuscular or subcutaneous administrations of thymoptine preparation (complex of peptides, isolated from mammalian thymus) at doses of 0.1 microgram, 1.0 microgram/200 g of rat body mass. A more long-term effect was found after a course of treatment involving 5 subcutaneous or intramuscular injections (1.0 microgram). Single intravenous administration of thymoptine (0.1 microgram/200 g) caused a moderate thrombolytic action. Development of thrombosis, provoked by subtotal dose of thrombin, was inhibited after subcutaneous injection of the preparation.

[Effects of tissue-type plasminogen activator from a culture of calf kidney cells on hemostasis and fibrinolysis in experimental nephritis]. / Vliianie aktivatora plazminogena tkanevo tipa iz kul'tury kletok pochki telenka na gemostaz i fibrinoliz pri éksperimental'nom nefrite.

The plasminogen activator 960 IU/mg protein activity isolated from cultured fluid of the calf kidney cells was introduced to albino rats (180-200 g) with experimental Heynmann nephritis every day during 4 days. Nephritis caused activation of haemostasis and inhibition of fibrinolysis in the blood. There was increased excretion of the fibrin, fibrinogen degradation products in urine as a results of the local fibrin deposition in diseased kidneys. The fibrinolytic activity of the cortical zone of kidney was markedly decreased. The plasminogen activator, infused to experimental animals, resulted in normalization of the altered indexes.

[The role of fibrinolytic system in pneumonias complicated by exudative pleurisy in children]. / O znachenii fibrinoliticheskoi sistemy pri pnevmoniiakh, oslozhnennykh ékssudativnymi plevritami u detei.

Phasic alterations in fibrinolytic activity were found in blood plasma of children with pneumonia complicated by exudative pleurisy. Hypercoagulation and inhibition of fibrinolytic activity were observed at the beginning of the disease. Hypercoagulation and an increase in the fibrinolytic activity occurred during restoration. In the children with lung destruction the fibrinolytic activity was increased in blood and in exudates before the appearance of roentgenologic indications of the destructive alterations. The fibrinolytic activity was inhibited in children with metapneumonic pleurisy formed during pneumonia and characterized by long-term and severe course. Role of fibrinolysis as possible pathogenetic factor responsible for development of complications is discussed.