[Determining alpha-2-macroglobulin in human blood serum and its clinical value].
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Biomedical subjects
Publications and source records attributed to K N Veremeenko.
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Data on study of action plasma inhibitors on activity of pancreatic proteolytic enzymes (trypsin, chymotrypsin) and plant proteinases (papain, bromelain), included in composition of enzyme mixes, used for orally application are submitted. It is established, that serine proteases are more sensitive to inactivation of plasma inhibitors, than cysteine enzymes. Main inhibitor of the papain and bromelain is alpha-2-macroglobulin in complex with which they preserve significant part of initial activity. A high-sensitivity method of determination of activity enzyme combinations, enabling to detect nanograms of them in presence of plasma inhibitors is offered. It can be used for study pharmacokinetic and optimization of enzyme mixes application in clinical practice.
Data on biochemistry, physiological significance and clinical investigations of two main inhibitors of proteinases in human blood serum (alpha 1-antitrypsin and alpha 2-macroglobulin) are reviewed. Physico-chemical properties of the inhibitors, mechanisms of their interaction with proteinases and methods for determination are discussed. Modification of the specificity of some proteinases by alpha 2-macroglobulin, which probably plays a significant role in the regulation of enzymatic systems of proteolysis in blood, is considered. The use of the inhibitors of proteolysis for diagnostics of pathological processes is discussed. Data on the alpha 1-antitrypsin deficiency and its relation to the development of degenerative diseases in lungs are reviewed.
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Information about basic mechanisms of programmed cell death (apoptosis) development with participation of proteolytic enzymes is given in the review. The basic mechanisms of apoptosis launching are conditionally subdivided into three groups, depending on the "points of application" of apoptosis development initiating factor: membrane (receptor-dependent), mitochondrial and nuclear. Attention is accentuated on ubiquitin-dependent proteasomal proteolysis as the key system regulating apoptosis. The possible disturbances of apoptotic program realization are specified under various pathological processes and diseases.
Data on the study of activity of cysteine proteinases and their inhibitors in larynx neoplastic tissues and control mucosa surrounding them are submitted. It is established that cysteine activity was significantly increased and the content of cysteine inhibitors was decreased in the larynx cancer tissue compared to papilloma tissue and control mucosa. The ratios between cysteine activity and level inhibitors is the informative index of the trual potential proteolytic activity in cancer cells and their invasive capacity.
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Using clinical and biochemical data, the efficacy of the topical application of kontrikal, a polyfunctional inhibitor of proteinases, for the therapy of chronic purulent sinusitis is discussed. The drug was found to reduce the activity of proteolytic enzymes in the purulent exudate from the maxillary sinus. As compared with the controls (27 patients), the treated group (38 patients) showed a rapid disappearance of clinical manifestations, shortening of the therapeutic period, increase of proteinase inhibitors and decrease of protein in the exudate.
Simple procedure was developed for production of fibrinogen concentrate from small amounts of human autogenous blood using precipitation with polyethylene glycol and ammonium sulfate. Maximal yield of fibrinogen was obtained using polyethylene glycol 2,000 and 6,000 daltons at concentrations 7% and 4.5%, respectively. The fibrinogen preparations included fibronectin, inhibitors of proteinases, factor XIII of blood coagulation, plasminogen. Sigma-Aminocapronic acid and contrical should be added during bloodletting as well as into blood plasma before isolation of fibrinogen to avoid possible fibrinogen proteolysis.
The nature of protamine splitting proteinase, which was formed after treatment of human blood plasma by kaolin or silicone (aerosile), was studied. The activated enzyme did not exhibite the properties of thrombin and plasmin in reactions with specific substrates. Kyninogenic, TAME (N-tosyl-d-,l-arginine methyl ester)-esterase and protamine splitting activities were inherent in the proteinase; these properties enabled to group the enzyme with blood kallikreins. The purified preparations of human blood plasma kallikrein hydrolyzed protamine sulphate even at 10 mcg/ml concentration. alpha2-macroglobulin inhibited the protamine splitting activity of the plasma kallikrein.
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This paper describes the use of fibrin compositions derived from autogenous blood, contrykal, a fibrinolysis inhibitor, and thrombin combined with calcium chloride for fortifying sutures applied in the laryngoesophageal defect area at the final stage of laryngectomy.