[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.

[The effect of carnosine on inflammatory processes during contusion of the eyeball].

The effect of dipeptide carnosine on proteolytic processes accompanying inflammation was investigated in lacrimal fluid of patients with eyeball contusion. Eye drops containing 5% carnosine in combination with traditional treatment reduced elastase-like activity in lacrimal fluid and increased effectiveness of therapy.

[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.

[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.

[Immune and enzyme disorders in patients with acute pancreatitis]. / Immunnye i fermentnye narusheniia u bol'nykh ostrym pankreatitom.

Analysis of immune and enzyme disorders in 85 patients with acute pancreatitis shows that persistent imbalance of immunoregulatory T-lymphocytes with suppression predominance; reduction of all immunoglobulines number, imbalance in phagocytic immunity with height of absorbing activity of neutropils and stimultaneous decrease of their digestive capacity are prognostically unfavourable for high risk of pyonecrotic complications and lethal outcome. It is necessary to include immunocorrectors in combined therapy. Direct assessment of leukocytic elastase activity and alpha-IP level in blood plasma permits to evaluate spreading of inflammatory process and it severity, efficacy and prognosis of treatment.

[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.

[Kallikrein-kinin system: novel facts and concepts (literature review)]. / Kallikrein-kininovaia sistema: novye fakty i konteptsii (obzor).

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 kininase and decoding of mechanisms of contact phase of proteolytic system activation in blood plasma.

[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.

[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.

[The prognostic significance of the level of the blood antiproteinase potential in peritonitis]. / Prognosticheskoe znachenie urovnia antiproteinaznogo potentsiala krovi pri peritonite.

It was shown that the level of proteinase alpha 1-inhibitor (alpha 1-i.p.) in the toxic phase of peritonitis was reduced. In transition of the toxic phase to the terminal one the level of alpha 1-i.p. increases which suggests the preserved function of the liver. The terminal phase proper is accompanied by a considerably decreased level of the inhibitor. For this phase proteinase inhibitors should be administered. The level of activity of alpha 1-i.p. can serve as a prognostic criterion of the peritonitis course.

[Status of the kallikrein-kinin systems and level of antiproteinase potential during postoperative treatment of various forms of peritonitis]. / Sostoianie kallikrein-kininovoi sistemy i uroven' antiproteinaznogo potentsiala pri posleoperatsionnom lechenii razlichnykh form peritonita.

Some parameters of the kallikrein-kinin system and the antiproteinase potential were studied in patients with diffuse peritonitis during the routine treatment course, after additional intramuscular administration of mexidol (inhibitor of free radical oxidation with antiproteinase activity) as well as after treatment of the patients with physiological solution containing ozone (4-7 mg/l used as a donor of free radicals), which was applied for washing of abdominal cavity in one group of patients during surgical operation and for intravenous administration in the other group. The kallikreinkinin system parameters were distinctly altered in the patients with peritonitis and the rate of the system activation correlated with the disease severity. Content of the alpha 1-inhibitor of proteinases (alpha 1-PI) was increased by the middle period of the treatment course and decreased as the inflammation lowered. alpha 2-Macroglobulin (alpha 2-MG) was altered less distinctly as compared with alpha 1-PI. Patterns of the antiproteinase potential in blood plasma (alpha 1-PI and alpha 2-MG) may be used for diagnostic and prognostic purposes in post-surgical treatment of patients with diffuse peritonitis; a decrease in the potential value proved to be a symptom of danger. Both mexidole and ozone exhibited positive clinical effect in treatment of the disease. Although these drugs had an opposing effect on the proteinases activity, their similar action on the antiproteinase potential appears to be responsible for the medicinal efficiency. Clinical effect of the drugs may be arranged as follows: mexidole, ozone administered intravenously and ozone used for intraabdominal washing.

[The kallikrein-kinin system and blood plasma proteolysis inhibitors in various childhood nephropathies]. / Kallikrein-kininovaia sistema i ingibitory proteoliza plazmy krovi pri razlichnykh nefropatiiakh u detei.

Activity of the kallikrein-kinin system and proteinase inhibitors were studied in blood plasma of children at various stages of tubulointerstitial nephritis, pyelonephritis and dysmetabolic nephropathy. Similar alterations in the activities of kallikrein-kinin system and in the rate of proteolysis inhibition were observed in tubulointerstitial nephritis and pyelonephritis. Supplementary demonstrations were obtained about development of inflammation in tubulointerstitial nephritis. Absence of the kallikrein-kinin system activation and a decrease in the alpha 2-macroglobulin content were detected in dysmetabolic nephropathy. Definite components of the kallikrein-kinin system and the proteolysis inhibitors may be used as indicators in differential diagnosis of tubulointerstitial nephritis and dysmetabolic nephropathy.

[Secretion of membrane-bound serine proteinases by polymorphonuclear leukocytes during adhesion to various types of receptor-dependent and receptor-independent sorbents]. / Sekretirovanie serinovoi sviazannoi s membranoi proteinazy polimornoiadernymi leikotsitami v usloviiakh adgezii na razlichnykh tipakh retseptorzavisimykh i retseptornezavisimykh sorbentov.

A high level of the membrane-bound proteinase (LMP) secretion by human polymorphonuclear leukocytes (up to 680 nmol/min/ml with N-benzoyl-L-arg-EE as a substrate) was shown during the cell adhesion to receptor-dependent (immobilized aggregates of IgG and C3b) and receptor-independent (DEAE-Sephadex and polymethyl methacrylate) absorbents. Incubation medium contained 6.10(6) cells/ml. The rate of secretion reached the maximal level during 15 min although its level was already high to the 5 min of C3b- and hydrophobic surface-induced activation (491 +/- 55 and 382 nmol/min, respectively). The high level of LMP secretion coincided with the peak of luminol-dependent chemoluminescence during the receptor-dependent adhesion, but did not correlate with a low level of luminescence in the receptor-independent adhesion. Localization of LMP in latent form in neutrophil membrane was shown earlier; the enzyme activation may occur due to effect of polycationic molecules of bovine tissue proteinase inhibitor of Kunitz type, protamine sulfate, alkaline fraction of ampholines. The enzyme (with BAEE as a substrate) was identified as serine proteinase of the trypsin-like type which activated Hageman factor (the XII factor of clotting system) and demonstrated the kininogenase activity. Only slight elastase-like activity was detected after incubation of neutrophils with all the adsorbents studied (0-2 nmol/min/ml with MeOSucAlaAlaProValpNA as a substrate). Chymotrypsin-like activity achieved maximum only by 30 min of activation with all the types of adsorbents (up to 270 nmol/min/ml with N-benzoyl-Tyr-EE as a substrate); this suggests impairment of azurophilic granules and appearance of cathepsin G.(ABSTRACT TRUNCATED AT 250 WORDS)