[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.

[Serum neutrophil elastase and activity of its inhibitors in patients with pulmonary tuberculosis]. / Elastaza neitrofilov v syvorotke krovi i aktivnost' ee ingibitorov u bol'nykh tuberkulezom legkikh.

The paper presents the results of determination of some parameters that characterize the proteolytic and phosphohydrolase activities of neutrophils, as well as the levels of plasma inhibitors of neutrophilic elastase in 76 patients with pulmonary tuberculosis. Evidence is provided that the pretreatment activity of serum neutrophilic elastase and the levels of neutrophilic cationic proteins and alkaline phosphatase are increased in the patients. There is a trend for these parameters to become normal during effective treatment. It has been ascertained that the activity of the major elastase inhibitor, alpha 1-proteinase inhibitor, is much enhanced in patients with acute and subacute pulmonary tuberculosis, but is the same as the normal vales in patients with torpid tuberculosis.

[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.

[Participation of neutrophils in the pathogenesis of allergic inflammation: inhibitory-protease index in assessing and predicting atopic illnesses]. / Uchastie neitrofilov v patogeneze allergicheskogo vospaleniia: ingibitorno-proteaznyi indeks v otsenke i prognozirovanii atopicheskikh zabolevanii.

Total trypsin-like (BAEE esterase), elastase-like (BOC esterase) and antitryptic activities were studied in blood serum of patients with atopic diseases. The elastase-like activity was increased in blood serum of all the patients examined during the acute period of the disease; the enzyme activation depended on the pathology severity and clinical picture manifestations. The increase in blood plasma total proteolytic activity correlated with reverse alteration in blood antitryptic potential. The data obtained suggest that activation of neutrophils occurred in atopic diseases, thus the rate of elastase-like activity in blood might be used as an objective pattern in examination of patients and in checking of treatment course. The developed inhibitory-protease index may serve also as a criterion in evaluation of the pathological state severity.

[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)

[Detection of human leukocyte elastase from a plasma alpha-1-proteinase inhibitor complex by its enzymatic activity with a synthetic substrate]. / Vyiavlenie leikotsitarnoi élastazy cheloveka iz kompleksa s plazmennym alph1-proteinaznym ingibitorom po ee énzimaticheskoi aktivnosti s sinteticheskim substratom.

A spectrophotometric procedure was developed for estimation of elastase activity in human leukocytes in the form of complex with blood serum alpha 1 proteinase inhibitor after loosening of the complex and detection of the enzymatic activity with N-tert-butyl-hydroxy-carbonyl-Ala-p-nitrophenyl ester as a substrate in presence of acetone or acetonitrile. The optimal conditions were described, which were required for estimation of the enzyme 100% activity followed by addition of the leukocyte elastase standard preparation into blood serum as well as for measurement of the enzyme activity in the complex with alpha 1 proteinase inhibitor. The procedure took 6-10 min to evaluate the elastase activity in the complex with the inhibitor using simple buffer containing organic solvents at 30 degrees and the available two-beam spectrophotometer.

[Comparative study of the effectiveness of equivalent doses of the preparation ditek, disodium cromoglycate and fenoterol in atopic bronchial asthma]. / Sravnitel'naia éffektivnost' ékvivalentnykh doz preparata "Ditek", dinatrievogo khromoglikata i fenoterola pri atopicheskoi bronkhial'noi astme.

18-45-year-old patients with atopic bronchial asthma free of associated inflammatory diseases received ditek, lomudal and berotek (28, 10 and 10 patients, respectively). Biochemical assessment of allergic inflammation activity demonstrated that ditek is most effective of the above three drugs both in relation to induction of clinical remission and to inhibition of allergic inflammation.

[Disruption of regulatory possibilities of the plasma kallikrein-kinin system in chronic kidney failure and during hemodialysis]. / Narushenie reguliatornykh vozmozhnostei kallikrein-kininovoi sistemy plazmy krovi pri khonicheskoi pochechnoi nedostatochnosti i vo vremia gemodializa.

Activation of the kallikrein-kinin system was detected in chronic renal failure treated by routine therapy. In blood plasma of the patients with chronic renal failure, kallikrein was activated from 34.2 to 63.2 mU/ml, while activity of prekallikrein was decreased from 382.0 to 117.8 mU/ml; BAEE-esterase and elastase-like activities simultaneously increased from 340 +/- 20 to 464 +/- 43 mU/ml and from 150 +/- 20 to 340 +/- 18 mU/ml, respectively. In the patients on hemodialysis during the interdialysis period, there were reductions of BAEE-esterase and kallikrein activities to 265.8 +/- 18.5 and 25.9 mI/ml, respectively; and the content of prekallikrein remained decreased. During hemodialysis the elastase-like activity was markedly increased up to 501 mU/ml due to leukocyte activation. The findings suggest that during hemodialysis, due to leukocytic elastase, there is a possible occurrence of thromboses as a result of a potential depletion of the kallikrein-kinin system and decreased blood antiproteolytic potential, including antithrombin III.

[An effective single-stage method of obtaining elastase and cathepsin G from human leukocytes]. / Effektivnyi odnoétapnyi metod polucheniia élastazy i katepsina G izleikotsitov cheloveka.

A procedure for one-step rapid isolation of highly purified elastase and cathepsin G from human leucocytes including biospecific chromatography on Gordox-Sepharose is described. Electrophoresis in gradient (10-15%) polyacrylamide gel in the presence of sodium dodecyl sulfate revealed three elastase isoforms with molecular masses of 26.3, 27.8 and 28.9 kDa. Cathepsin G produced one protein band with a 27 kDa mobility. The pH optimum for elastase and cathepsin G are 7.0-7.5 and 7.5-8.0, respectively. The specific activities of elastase and cathepsin G preparations as measured by the p-nitrophenyl ester-tert butoxycarbonyl-L-alanine and the ethyl ester-benzoyl tyrosine, hydrolysis are equal to 3-8 and 20-40 mumol/min/mg protein, respectively.

[Status of the kallikrein-kinin system, proteinase inhibitors and nonspecific resistance factors in patients with chronic kidney failure on hemodialysis as well as in kidney transplant recipients]. / Sostoianie kallikrein-kininovoi sistemy, ingibitorov proteinaz i faktorov nespetsificheskoi rezistentnosti u bol'nykh s khronicheskoi pochechnoi nedostatochnostiu, nakhodiashchikhsiia na gemodialize, i uretsipientov pochechnogo transplantata.

A state of the kallikrein-kinin system, activity of proteolysis inhibitors were studied simultaneously with the functional activity of neutrophils and content of lysozyme in blood serum of 21 patients with chronic kidney insufficiency. Two types of alterations in the kallikrein-kinin system were found in 13 patients maintained on hemodialysis: in four patients content of kallikrein was increased 8-fold as compared with normal level with a decrease in content of prekallikrein, while in nine patients activity of kallikrein was similar to control values but content of prekallikrein was still further decreased. Content of alpha 1-proteinase inhibitor (PI) was distinctly decreased (2-2.5-fold) in these patients, however, the decrease of the inhibitor was not observed in four patients; activity of alpha 2-macroglobulin tended to decrease. The ratio of active neutrophils and content of lysozyme were increased in blood serum of the majority of the patients. Hemodialysis, activation of the kallikrein-kinin system and stimulation of neutrophils appear to be responsible for a decrease in PI activity. The decrease in the PI activity and stimulation of the kallikrein-kinin system suggest that impairments in regulation of proteolysis could be corrected by means of exogenous proteinase inhibitors. In crisis of allogenic kidney rejection activities of PI and prekallikrein were decreased. Drastic, uneven alterations of the patterns studied were detected in pyo-inflammatory complications not related to the rejection crisis.

[Proteolytic enzymes of the lacrimal fluid as pathogenesis factors of chronic corneal ulcer]. / Proteoliticheskie fermenty sleznoi zhidkosti kak faktory patogeneza khronicheskikh iazv rogovoi obolochki glaza.

Proteolytic enzymes, particularly collagenase, are involved in development of eye cornea chronic ulcers. Analysis of lacrimal fluid obtained from the patients enabled to find not only the collagenase activity but and serine enzymes exhibiting BAEE esterase activity. Plasmin, blood plasma and tissue kallikreins regulated permeability of capillaries in conjunctiva and lacrimal gland as well as they activated latent collagenase. Studies of BAEE esterase activity in lacrimal fluid of the patients are required for prescription of adequate pathogenetic treatment.

[Comparative analysis of methods of determination of kallikrein and prekallikrein in the human plasma (review of the literature)]. / Sravnitel'nyi analiz metodov opredeleniia kallikreina i prekallikreina v plazme krovi cheloveka (obzor).

Main procedures developed for estimation of kallikrein activity and of content of its precursor are reviewed; critical comparative analysis of their principles is presented. Specificity, advantages and limitations of these procedures are discussed. General rules of enzymatic kinetics are considered in connection with development and application of these procedures. Some cautions are discussed considering wrong conclusions and recommendations, based on the data obtained by means of the inadequate methods.

[The use of a tripeptide chromogenic substrate for simultaneous determination of 4 indices of kallikrein-kinin system]. / Ispol'zovanie tripeptidnogo khromogennogo substrata dlia odnovremennoi otsenki chetyrekh pokazatelei aktivnosti kallikrein-kininovoi sistemy.

Evaluation of the kallikrein-kinine system activity in blood plasma is of importance due to participation of the components of this system in regulation of blood plasma proteolysis. Using D-Pro-Phe-Arg-pNA as a substrate, a procedure for simultaneous estimation of four patterns of the kallikrein-kinine system activity was developed: I. maintenance of contact phase, 2. content of prekallikrein (1.49 un/ml in normal state), 3. activity of kallikrein (0.104 un/ml), 4. antikallikrein potential (0.700 IU/ml).