[Changes in hemostasis-related parameters of blood and lacrimal fluid in patients with retinal vein occlusion]. / Sostoianie sistemy gemostaza krovi i sleznoi zhidkosti pri okkliuzii retinal'nykh ven.

High prevalence of retinal vein occlusion in young people as well as treatment complexity and inadequate control of hemostatic parameters of blood and lacrimal fluid determine the significance of relevant research in patients with retinal vascular pathology. The data thus obtained may be useful for disease prognosis, severity evaluation and therapy control. This review is aimed to study hemostasis-related parameters of blood and lacrimal fluid in such patients.

[Kallikrein-Kinin System. Long History and Present. (To 90th Anniversary of Discovery of the System)].

The kallikrein-kinin system (KKS) is the key proteolytic system participating in control of a wide spectrum of physiological functions and the development of many pathological conditions. This explains great interest in structures, functions and molecular biology of separate components of the system, molecular mechanisms of their interaction and relationship with other regulatory systems. The information in this field for the last two decades clarifies the role of KKS in morphogenesis of cells, regulation of smooth muscular contractility of some organs, decrease of blood pressure, increase of vascular permeability, the development of inflammation, transformation of cells and the other functions of both physiological and pathological processes. Essential progress in understanding of functions KKS was made by the discovery and study of bradykinin receptors, cloning of kininogen and kallikrein encoding genes, revealing of domain structure of kininogen, prekallikrein and some kininases and decoding of mechanisms of contact phase of proteolytic system activation in blood plasma.

[Kallikrein-kinin system as a target for diabetic retinopathy treatment].

Multifactor etiology of diabetic retinopathy (DR) determines difficulty of understanding of pathogenesis and need of search of effective approaches to study key mechanisms of development of this microvascular complication of diabetes mellitus (DM). Significant achievements of the last years show the contribution of two proteolytic systems into pathogenesis of DR, that control vascular tone and permeability - kallikrein-kinin (KKS) and renin-angiotensin systems (RAS). Among new approaches to DR treatment one of the most appropriate is an influence on KKS by means of inhibiting kallikrein, that leads to reduction of retinal vascular permeability and allows to prevent the development of macula oedema and other consequences of vascular wall damage in DR.

[Inflammatory response mediators in newborns and infants with congenital heart diseases during surgical treatment under extracorporeal circulation].

Surgical treatment of complex congenital heart disease under extracorporeal circulation is accompanied by a systemic inflammatory reaction occurring in neonatal infants and babies. There were drastic increases in the concentration of tumor necrosis factor, interleukin-8, neutrophilic elastase and a predominance of a proinflammatory response over an inflammatory one at the warming stages and after administration of protamine sulfate. The rate of an inflammatory response depended on the duration of extracorporeal circulation. Modified ultrafiltration could remove cytokines; however, their concentration in the body remains high. A relationship was found between the course of a postoperative period and the rate of a developing reaction to extracorporeal circulation in the surgical treatment of congenital heart diseases.

[Change in activity of angiotensin-converting enzyme in pneumonia and chronic obstructive lung diseases]. / Izmenenie aktivnosti angiotenzinprevrashchaiushchego fermenta pri pnevmonii i khronicheskikh obstruktivnykh bolezniakh legkikh.

AIM: To study the activity of angiotensin-converting enzyme (ACE) in patients with pneumonia and chronic obstructive lung diseases (COLD). MATERIAL AND METHODS: Sixty nine patients with pneumonia and 77 with COLD were examined. The activity of ACE in the serum and bronchoalveolar lavage (BAL) and the effects of leukocytic elastase and concentrations of zinc, endogenous inhibitors, and activators were studied. RESULTS: The patients with pneumonia in the acute phase of the disease have been found to have low ACE activity in both blood and BAL. As the inflammatory process comes to an end, ACE activity normalizes. In the patients with COLD, the activity of ACE is primarily decreased at remission. When COLD aggravates, the activity of ACE in blood and BAL increases. In pneumonia and COLD, the changes in ACE activity are more profound in BAL than in blood. CONCLUSION: The only cause of the altered activity of ACE in patients with COLD and pneumonia is a change in the concentration of the enzyme.

[Changes in angiotensin-converting enzyme activity in pneumonia and chronic obstructive lung diseases]. / Izmenenie aktivnosti angiotenzinprevrashchaiushchego fermenta pri pnevmonii i khronicheskikh obstruktivnykh bolezniakh legkikh.

The activity of angiotensin converting enzyme (ACE) was analysed in blood serum and bronchial fluid of 69 patients with acute pneumonia and 77 patients with chronic obstructive pulmonary diseases (COPD). In patients with pneumonia in acute phase ACE activity was lower in both serum and bronchial fluid. During recovery of patients with acute pneumonia ACE activity was normalizated. In patients with COPD ACE activity was lower in remission stage and higher (both serum and bronchial fluid) during COPD exacerbation. The changes of ACE activity were more pronounced in bronchial fluid than serum in both COPD and pneumonia.

[The change in the activity of angiotensin converting enzyme in patients with pneumonia and chronic obstructive pulmonary diseases]. / Izmenenie aktivnosti angiotenzinprevrashchaiushchego fermenta u bol'nykh pnevmoniiami i khronicheskimi obstruktivnymi zabolevaniiami legkikh.

The activity of angiotensin-converting enzyme (ACE) was measured in the serum and bronchial contents of 69 patients with pneumonia and 77 with chronic obstructive pulmonary diseases (COPD). ACE activity was decreased both in the blood and bronchial contents during the acute phase of pneumonia. With resolution of the inflammatory process, ACE activity normalized. In patients with COPD, the activity of ACE is decreased during remission in comparison with the mean values in the population. During COPD exacerbation the activity of ACE increases both in the blood and bronchial contents. Changes in ACE activity in pneumonia and COPD are more pronounced in the bronchial contents than in the blood. Presumably alteration of the enzyme concentration is the only cause of alteration of its activity in patients with COPD and pneumonia.

Contact system. New concepts on activation mechanisms and bioregulatory functions.

This review considers the data of recent years concerning the contact system initiating the activation of blood plasma proteolytic systems, such as hemocoagulation, fibrinolysis, kininogenesis, and also complement and angiotensinogenesis. The main proteins of the contact system are the factors XII and XI, prekallikrein, and high-molecular-weight kininogen. The data on the structure, functions, and biosynthesis of these proteins and on their genes are presented. Studies in detail on the protein-protein interactions during formation of the ensemble of the contact system components on the anionic surface resulted in the postulation of the mechanism of activation of this system associated with generation of the XIIa factor and of kallikrein. This mechanism is traditionally considered a trigger of processes for the internal pathway of the hemocoagulating cascade. However, the absence of direct confirmation of such activation in vivo and the absence of hemorrhagia in the deficiency of these components stimulated the studies designed to find another mechanism of their activation and physiological role outside of the hemostasis system. As a result, a new concept on the contact system activation on the endothelial cell membrane was proposed. This concept is based on the isolation of a complex of proteins, which in addition to the above-mentioned proteins includes cytokeratin 1 and the receptors of the urokinase-like plasminogen activator and of the complement q-component. The ideas on the role of this system in the biology of vessels are developed. Some of our findings on the effect of leukocytic elastase on the key components of the contact system are also presented.

[Isolation, purification, and properties of factor XII and its active fragment (beta-XIIa)]. / Poluchenie, ochistka, svoistva faktora XII i ego aktivnogo fragmenta (beta-XIIa).

A procedure of isolation of human blood plasma prekallikrein, coagulation factor XII and active fragment beta-XIIa has been developed. This procedure includes the traditional chromatography steps and FPLC. Disc-electrophoresis revealed that the preparations of factor XII and beta-XIIa were homogeneous. Their specific activity was 70.6 U and 2.5 U, respectively. The procedure described is less time consuming and it allows to isolate these factors in the preparative quantities.

[The effect of leukocyte elastase on high molecular weight kininogen from human plasma in the presence of alpha-1 protease inhibitor. Analysis of proteolytic degradation]. / Deistvie leikotsitarnoi élastazy na vysokomolekuliarnyi kininogen plazmy krovi cheloveka v prisutstvii al'fa-1-proteinaznogo ingibitora. Analiz proteoliticheskoi degradatsii.

Degranulation of polymorphonuclear leukocytes (neutrophils) and releasing of leukocyte elastase during inflammation occur not only in injured tissue but in plasma in the presence of considerable excess of alpha-1 proteinase inhibitor (alpha-1PI). However, in spite of the absence of free elastase in patients' plasma, even in such severe inflammation as peritonitis and septicaemia, degradation of the connective tissue structures and plasma proteins may be determined. However the reasons of such destructive action are not yet determined. In this paper the action of leukocyte elastase on human plasma high molecular weight kininogen (HMWK) was studied in the absence or in the presence of different concentrations of alpha-1PI. The results showed that degradation of the intact molecules of HMWK occurred under the action of elastase during 1-2 hours of combined incubation even if the concentration of alpha-1PI in the mixture in 3-5 fold exceeds the molar elastase concentration. The rate of elastase inhibition by alpha-1PI in the presence of HMWK did not depend on an order of enzyme and inhibitor addition to the incubation medium. HMWK degradation by elastase in the presence of alpha-1PI was accompanied by impairments in its adhesion function although high tolerance of HMWK inhibitory activity with respect to SH-proteinases preserved. Thus, total inhibition of leukocyte elastase by alpha-1PI, in the presence of high molecular weight kininogen develops during relatively long time interval. The pronounced destruction of intact HMWK molecules takes place during this period of gradual elastase inhibition. This fact seems to be very important in pathogenesis of thrombo-haemorrhage syndrome as a complication of severe inflammation.

[Leukocyte elastase in blood plasma from tuberculosis patients and its role in disturbances of blood coagulation regulatory processes]. / Elastaza leikotsitov v plazme krovi bol'nykh tuberkulezom i ee rol' v narushenii reguliatsii protsessov svertyvaniia krovi.

UNLABELLED: 53 patients with lung tuberculosis were divided in 3 groups in accordance with severity of disease. Leukocyte elastase, cationic proteins in neutrophils, activities of alpha 1-proteinase and alpha 2-macroglobulin were determined in patients' plasma. Thromboelastographic, coagulating, fibrinolytic indices, and antithrombin III activity were also determined in 28 patients of all 3 groups. Results demonstrated the high level of leukocyte elastase (6-fold more than normal) in plasma of patients with acute tuberculosis process. This group of patients demonstrated activation of intravascular coagulation proceeded on the background of significant decrease (up to 60%) of AT III activity. CONCLUSION: Acuity and severity of tuberculosis process in lung may be characterized by high activity of leukocyte elastase. Degranulating activity of neutrophils and releasing of elastase are the reason of AT III deficiency and increasing of intravascular coagulating activity in tuberculosis patients.

The possible role of plasma kallikrein-kinin system and leukocyte elastase in pathogenesis of schizophrenia.

The main purpose of this paper is to study the possible causes of blood-brain barrier (BBB) damage during the acute condition of schizophrenia (Sch), which makes brain antigens accessible to the immunocompetent cells. The development of autoimmune reactions in this disease has to be preceded by the damage of BBB. We have studied the level of activity of plasma kallikrein-kinin (KKS) and complement systems, C-reactive protein (CRP) concentration, proteinase inhibitory potential as well as the oxidized and degranulating activity of neutrophils as the main factors affected the permeability of tissue-blood barrier. Our results suggested that the acute stage of Sch was accompanied by the activation of KKS on the background of enhance in the functional activity of the alpha-1-proteinase inhibitor. The increased level of CRP, the high haemolytic activity of complement and significant degranulating activity of polymorphonuclear leukocytes testified to inflammatory character of Sch. The treatment with psychotropic drugs have led to decrease of polymorphonuclear elastase (PMN-E) activity in patient's plasma. Our in vitro study indicates that Haloperidol causes the lowering of PMN-E activity in the dose-dependent fashion.

[Overall trypsin-like, elastase-like and antitryptic activity in patients with eye contusion]. / Obshchaia tripsinopodobnaia élastazopodobnaia i antitripticheskaia aktivnost' u patsientov s kontuziei glaza.

The investigations of tear fluid of eye after contusion injury revealed on increase of trypsin-like activity in 1-3 day and 10-19 day after trauma, the progressively elevation of elastase-like activity and lowering of inhibitory potential along 2-3 week. It was detected indirect correlation between the elastase-like activity and severity of the contusion injury of the eye, the grade of corneal edema, corneal erosion and conjunctival wound, hyphema. This results was shown the participation and the role of proteolytic and inflammatory processes in pathogenesis of eye blunt trauma. It was establish that the during of local inflammation is 2 week end more and is necessary antiinflammatory therapy with use the proteases inhibitors.

[The role of angiotensin-converting enzyme in pathogenesis of post-contusion disorders of ophthalmotonus and hemodynamics]. / Uchastie angiotenzinprevrashchaiushchego fermenta v patogeneze postkontuzionnykh narushenii oftal'motonusa i gemodinamiki.

Angiotensin converting enzyme (ACE) activity was studied in tear fluid of the contusion injured eye. We found substantial decrease of ACE activity during 1 month after trauma. Reduced ACE activity can potentiate kinin action and may contribute to the maintenance of reduced vascular tone, high capillary permeability inducing ciliochoroidal effusion which leads to ocular hypotony. We have found decrease of ACE activity in another healthy eye.

[Role of kallikrein-kinin system in pathogenesis of eye contusions]. / Rol' kallikrein-kininovoi sistemy v patogeneze kontuzii glaza.

Studies of the plasma components of the kallikrein-kinin system (KKS) in the lacrimal fluid (LF) of damaged eyeball of 32 patients hospitalized for contusion for the eyeball showed an appreciable increase of KKS activity during the first three days and its less expressed increase on days 10-19 after the injury. The content of prekallikrein in the damaged eye LF depends on the severity of eye contusion and plasma KKS status, and the levels of LF prekallikrein in the damaged and intact eye correlate. Serum kallikrein activity depends on the severity of injury.

[Activation of kallikrein-kinin system, degranulating activity of neutrophils and blood-brain barrier in schizophrenia]. / Aktivatsiia kallikrein-kininovoi sistemy, degranuliatsionnaia aktivnost' neitrofilov i gematoéntsefalicheskii bar'er pri shizofrenii.

To evaluate permeability of blood-brain barrier (BBB) some immunological and biochemical indices were used. The levels of the activity of serum kallikrein-kinin system (KKS), compliment system, C-reactive protein (CRP) concentration, blood inhibitory potential, metabolic and degranulating activities of neutrophils, as well as functional activity of leukocytic elastase were investigated in 30 patients. Acute schizophrenic attack was accompanied by both activation of KKS and by the increase of functional activity of alfa-1-proteinase inhibitor. The increase of CRP levels, high hemolytic activity of complement as well as considerable degranulating activity of polymorphonuclear leukocytes may be the causes of the damage of BBB permeability during acute schizophrenic attack.

[Possible participation of angiotensin-converting enzyme and leukocyte elastase in the pathogenesis of insulin-independent diabetes mellitus]. / O vozmozhnom uchastii angiotenzin-prevrashchaiushchego fermenta i leikotsitarnoi élastazy v patogeneze insulin-nezavisimogo sakharnogo diabeta.

It is commonly accepted that the tolerance to insulin and hyperglycemia of the patients with non-insulin dependent diabetes mellitus (NIDDM) is due to some defect of insulin receptors or disturbances in the signaling pathway of the cell. This disease is often accompanied by hypertension. In this paper the high activity of plasma kallikrein-kinin system (KKS) (kallikrein activity was 6-8 times higher than normal), of angiotensin-converting enzyme (ACE) (4 times greater than normal), and of leukocyte elastase (2.7 times higher than normal) were demonstrated in plasma of patients with NIDDM. Increasing of KKS activity was coincident with rising of ACE activity, which may be the cause of the fast bradykinin inactivation and arising of hypertension. The treatment with ACE inhibitor during 3 months (4 mg of Perindopril per day) decreased ACE activity in patients' plasma which was accompanied with decreasing of the arterial pressure and some restoration of the carbohydrate metabolism indicators. The hyperinsulinemic euglycaemic clamping of 7 patients with NIDDM and essential hypertension showed that ACE-inhibitor (Perindopril, 4 mg) prevented bradykinin from destruction and increased the glucose consumption by tissues. The high activity of polymorphonuclear leukocytes and secretion of the elastase in NIDDM patients' plasma and/or instability of plasmatic and granular membranes of leukocyte in conditions of hyperglycaemic plasma are probably the cause of endothelial irritation and high ACE secretion. Secondly, the leukocyte may be the cause of injuring and decreasing of susceptibility of the cell receptors for insulin and bradykinin.

Activity of leukocyte elastase in patients' plasma is a significant indicator of atopic diseases.

It is commonly known that activation of plasma kallikrein-kinin system is of great importance in the pathogenesis of atopic diseases. Plasma kallikrein most likely activates other arginine-esterases in human plasma. Diagnostic and prognostic values of the total arginine-esterase activity and the activity of leukocyte elastase (LE) in plasma of patients with allergic rhinitis (AR), atopic bronchial asthma (ABA) and atopic dermatitis (AD) were examined in this study. Our results demonstrate that the level of arginine-esterase activity was slightly elevated only in plasma of patients with ABA (424 +/- 24; N-360 +/- 20 mU/ml), but not with AR and AD. Elastase-like activity in human plasma proved to be a far more informative indicator of the atopic states than arginine-esterase activity. In plasma of patients with AR, ABA and AD the activity of LE exceeded the normal level in 1.7, 1.8, and 2.4 times, respectively. Treatment of these atopic states with Ditec (Boehringer Ingelheim) led to some improvements of the patient' states. The main component of this drug (disodium chromoglycate) inhibited the activity of leukocyte elastase in experiments in vitro.

Molecular and functional aspects of alterations in the kallikrein-kinin system activity in human blood plasma at different stages of peritonitis and chronic renal failure.

We are concerned with the investigation of dynamics of the plasma kallikrein-kinin system, elastase-like activity and some serpins, alpha 1-protease inhibitor, alpha 2-macroglobulin and antithrombin III, in patients suffering from general peritonitis and chronic renal failure. The results indicate that activation of the kallikrein-kinin system, as well as elastase-like activity are elevated and while decreased inhibitory potential becomes more intensive with disease progression. However, sharply decreased levels of kallikrein, prekallikrein and serpins were seen in patients a few days before death. We suggest that exhaustion of these components during the end-stage of general peritonitis and chronic renal failure (in the cases with lethal outcome) may be produced by leukocyte elastase release. Evidence is presented for the destructive action of leukocyte elastase on components of the kallikrein-kinin system.

Hageman factor and kallikrein in pathogenesis of senile cataracts and the pseudoexfoliation syndrome.

It is thought that dystrophic changes in the human aging anterior eye are due to lipid peroxidation in both the cortical and nuclear structures of the lens under the conditions of ischemia. These changes are often accompanied by only lens opacification (senile cataract-SC) or by formation of amorphous or fibrillar deposits in anterior eye, disturbances of eye hydrodynamics and lens opacification (pseudoexfoliation syndrome-PES). Our results suggest that the main reason of dystrophic changes in the tissues of the aging anterior eye is the disturbance of the haemato-ophthalmic barrier and that the plasma kallikrein-kinin system takes part in this disturbance. Penetration of plasma proteins, such as C-reactive protein, complement components, immunoglobulins and coagulation factors, from plasma into the aqueous humor is responsible for damaging epithelial structures of anterior eye and formation of pseudoexfoliative material. Using ELISA, the C-reactive protein, IgG and IgM antigens have been shown to localize on the surface of the opaque lenses. Presence of these complement binding proteins in the superficial lens structures as well as the high C3a concentration in the aqueous humor substantiates the pathogenic role of complement activation in the lenticular epithelium upon cataract and PES formation.