[Hemostasis system disturbances and their correction in patients with pyonecrotic forms of diabetic foot].

Severe hypercoagulation syndrome was diagnosed in patients with various forms of diabetic foot. Pathology at coagulogram parameters reflects systemic metabolic and inflammatory disturbances. Anticoagulant therapy should be combined with correction of glycemia, treatment of infection and critical ischemia. Only this complex therapy can normalize coagulation parameters and reduce the risk of thrombotic complications.

[Metabolic effects of mexidole during cardiosurgical operations using extracorporeal circulation].

The effect of mexidole on the levels of glutathione, the activity of its metabolic enzymes, glutathione reductase (GR) and glutathione peroxidase (GP), and antioxidative enzymes, superoxide dismutase (SOD) and catalase (CAT) in the red blood cells under hypothermic perfusion was studied. A total of 96 patients were examined. The study was performed before perfusion, at the cooling and warming stages, an hour after perfusion, and in the morning of a following day. Mexidole was administered to 26 patients in the evening, before surgery, and at the cooling and warming stages (Group 1). The agent was not given to 70 patients (Group 2). In Group 2, there was an association of the level of glutathione and the activity of the enzymes under study with temperature. There were the least changes observed at 30-34 and 26-29 degrees C and a substantial decrease (by more than 30%) at the cooling stage as compared with pre-perfusion values. In the mexidole group, the content of glutathione increased under all temperature conditions at the study stages (by 30 to 58%) and the activity of all the test enzymes: GR and GP up to 33%, SOD up to 20-60%, CAT by 20-30%. The elevated level of all the parameters was also preserved on the following postoperative day. It may be suggested that mexidole activates the biosynthesis of glutathione and antioxidative enzymes, thus enhancing the antioxidative defense of cell membranes.

Study of total lipid peroxidation and antioxidant activity in pulmonary and mediastinal malignant and benign tumor tissue.

Total lipid peroxidation and antioxidant activity were studied in pulmonary and mediastinal malignant and benign neoplasms. In malignant tumors total lipid peroxidation increased and antioxidant activity decreased; the intensity of these shifts depended on histological characteristics and degree of malignancy: the most pronounced changes were observed in thymoma and adenocarcinoma tissues and minimum changes were found in bronchoalveolar carcinoma tissue.

[The study of the antioxidant enzymes in erythrocytes in lung diseases]. / Issledovanie anioksidantnykh fermentov v éritrotsitakh pri zabolevanii legkikh.

The activity of antioxidative enzymes Cu, Zn-superoxidedismutase (SOD) and catalase as well as content of glutathione and activity of its metabolism enzymes--glutathione reductase (GR) and glutathione peroxidase (GP) were studied in red blood cells of 82 patients: with chronic obstructive pulmonary diseases (COPD, n = 26), chest osteomyelitis (n = 12), malignant (n = 21) and benign (n = 23) pulmonary lesions. Red blood cells from 26 donors served as a control. Enzymes of glutathione and catalase metabolism in the red cells inhibited their activity in all the above pulmonary diseases vs those of the controls: GR activity in COPD and chest osteomyelitis decreased by 40% and more, lung tumors--by 32-36%. GP activity--by 24-27%, 14-19%, respectively. Catalase activity in pulmonary diseases was suppressed by 38-45%. SOD activity in chest osteomyelitis and pulmonary tumors is lower by 37-40% while in COPD is higher by 36%. Activation of SOD in red cells in COPD may be regarded as a compensatory-adaptive response to excessive accumulation of free oxygen radicals in alveoli in COPD.

[Pathogenesis and combined surgical treatment of the pyonecrotic diabetic foot]. / Voprosy patogeneza i taktiki kompleksnogo khirurgicheskogo lecheniia gnoino-nekroticheskikh form sindroma diabeticheskoi stopy.

Three hundred and fifteen patients with necrotic forms of diabetic foot were examined and treated. Neuropathic infected form of diabetic foot was diagnosed in 45.7% patients, neuro-ischemic form--in 54.3%. Mixed aerobic-anaerobic infection in foot's necrotic focus was detected in 87.6% diabetic patients, only aerobic--in 12.4%. High level of intoxication was seen in these patients. Algorithm of complex surgical treatment of different forms of diabetic foot is presented.

Activity of glutathione-metabolizing and antioxidant enzymes in malignant and benign tumors of human lungs.

We measured the content of glutathione and activity of glutathione-metabolizing and antioxidant enzymes superoxide dismutase and catalase in samples obtained from 52 patients with malignant lung tumors and 20 patients with benign lung tumors. The content of glutathione and activity of glutathione-metabolizing enzymes underwent similar changes, but these changes were most pronounced in malignant tumors. Antioxidant enzyme activity changed insignificantly in benign tumors, but significantly decreased in malignant tumors (squamous cell carcinoma and adenocarcinoma). The severity of changes in malignant tumors depended on the degree of malignancy. Most pronounced changes were observed in adenocarcinoma, which often metastasizes and is resistant to chemotherapy. These changes were least pronounced in bronchoalveolar carcinoma sensitive to chemotherapy.

[Hypothermal perfusion: protection or damage?]. / Gipotermicheskaia perfuziia -- zashchita ili povrezhdenie?

Ninety six patients were examined during operations on the open heart and great vessels: 25 perfusions were performed at a temperature of 30-32 degrees C; 41 perfusions at 26-29 degrees C; 10 at 23-26 degrees C; 20 at 12-14 degrees C. It was found that with superficial hypothermia and moderate PaO2, blood myoglobin (MG) release was minimal and the count and activity of platelets were optimal. The degree of myoglobinemia increased as PaO2 rose. As the body's temperature lowered, the blood concentrations of MG, its differences smoothed in the subgroups with different PaO2 values. Critical myoglobinemia (over 30 times higher than the baseline values) was noted in a group with superdeep cooling to a temperature of 14 degrees C. By taking into account the fact that the myocardium contains large quantities of MG, loss of this heme-containing protein involves myocardial blood supply disorders and hence decreased myocardial contractility. A considerable platelet loss entails higher postoperative hemorrhagic diathesis and requires efforts in correcting coagulopathies.

Platelet monoamine oxidase activity during surgical intervention under condition of hypothermic perfusion.

Platelet and plasma monoamine oxidase activity was determined at early stages of hypothermic perfusion and circulatory arrest. Monoamine oxidase activity decreased more drastically and restored more slowly against the background of deep (14 degrees C) compared to moderate hypothermia (26-29 degrees C). The decrease in platelet monoamine oxidase activity was accompanied by its increase in the plasma, which attests to mechanical (in tubes) and toxic damage to platelets. The latter is associated with increased partial O(2) pressure in the plasma during hypothermia, which promotes the formation of reactive oxygen species.

In vitro effects of folic acid on gamma-glutamyltransferase and glutathione reductase activities in malignant lung and thymus tumors.

In vitro effects of folic acid (10(-5), 10(-4), and 10(-3)M) on activities of gamma-glutamyltransferase and glutathione reductase, the enzymes involved in glutathione metabolism, were studied in tissue samples obtained after surgical treatment of the lungs and thymus. Folic acid did not change gamma-glutamyltransferase activity in lung cancer tissue, but in thymoma tissue this substance in a concentration of 10(-3)M inhibited it by 16%. Folic acid had no effects on glutathione reductase activity in benign tumors and normal lung and thymus tissues, but increased this activity in thymoma and lung cancer tissues. Activation of glutathione reductase was probably related to binding of folic acid in the allosteric center of the enzyme, which probably induced conformational changes in the catalytic center, acceleration of electron transport from NADPH(2) to oxidized glutathione via flavin adenine nucleotide, and intense production of reduced glutathione.

[Causes of myoglobinemia in surgery with artificial circulation]. / Prichiny mioglobinemii pri operatsiiakh s iskusstvennym krovoobrashcheniem.

Release of myoglobin (Mg) into the plasma and increase of its concentration during perfusion are a result of muscle cell injury during artificial circulation. High values of oxygen tension and hypothermia during cardiosurgery are sources of active oxygen forms damaging the biomembranes. We investigated release of Mg into the blood and relationship of this parameter with oxygen tension and depth of cooling. 95 patients were tested during open-heart surgery and operations on the main vessels: 25 perfusions at 30-32 degrees C, 41 at 26-29 degrees C, and 20 at 12-14 degrees C. The patients were divided into subgroups depending on arterial blood oxygen pressure. Myoglobin release into the blood was minimum under mild hypothermia and moderate PaO2. The degree of myoglobinemia increased with elevation in PaO2. As body temperature decreased, the concentration of Mg increased and differences between the groups with different PaO2 leveled. Critical myoglobinemia (30-fold vs. the initial value) was observed in the group with the deepest hypothermia (14 degrees C). Since the myocardium contains high amounts of Mg, it is clear that loss of this heme-containing protein impairs the feeding of the myocardium and, hence, decreases its contractility.

[Substantiation and varieties of complex surgical treatment tactics for pyo-necrotic forms of diabetic foot]. / Obosnovanie i varianty taktiki kompleksnogo khirurgicheskogo lecheniia gnoino-nekroticheskikh form "diabeticheskoi stopy".

For the period from 1996 to 1998 in the Division of wounds and wound infection of A.V. Vishnevsky Institute of Surgery 92 patients with pyonecrotic forms of "diabetic foot" underwent thorough examination and treatment. The patients were divided into groups by the form of "diabetic foot": with pyonecrotic forms of "diabetic foot" without critical ischemia (group 1) and with it (group 2). In 18 patients of both groups the data of electron autoradiography were used to reveal peculiarities of the wound process. Group 1 patients had at admittance a large number of neutrophiles in various stages of destruction in biopsies of the wound. In patients of group 2 a great majority of the vessels in biopsies of the wound were in different stages of destruction with lost connections between their separate cells or some of their part absent. Separate cells (endotheliocytes and pericytes) which make up the walls of destroying vessels, were synthesizing RNA and were functionally active. In both groups, the studied parts of the wound before plastic repair of its defect usually represented as well developed granulation tissues with a number of microvessels and cells. Intensive synthesis of PNA in the cells of microvascular wall evidenced of their high functional activity, and the synthesis of DNA in them showed their ability for proliferation, i.g.--for growth. Thus, microangiopathy was reversible, and the solution of the problem of critical ischemia should be considered in the light of macroangiopathy. Thus, in patients of group 1 the cause of pyonecrotic damage consists in infection process, while in patients of group 2--in combination of infection with ischemia of the extremity. In both groups pyonecrotic disease of the extremity ruses at the background of severe disturbances of cellular immunity.

[The effect of the perfusion parameters on the functional characteristics of the thrombocytes]. / Vliianie nekotorykh parametrov perfuzii na funktsional'nye kharakteristiki trombotsitov.

Platelet and plasma monoamine oxidase (MAO) activity was evaluated in two groups of patients at different stages of surgery (before perfusion, at the depth of cooling, height of warming, and 1 h and 24 h after perfusion). Group 1 consisted of 26 patients with acquired heart diseases operated on under artificial circulation and hypothermia (26-29 degrees C), group 2 consisted of 13 patients subjected to reconstructive operations on the aorta under artificial circulation with deep hypothermia (14 degrees C) and circulatory arrest for 50 min. The activity of platelet MAO was decreased in group 1 (by more than 50% during cooling and by 68% during warming and 1 h after perfusion); 24 h after surgery MAO activity increased, but did not reach the initial value. In group 2 the decrease in MAO activity was more expressed, starting from the second switching of the artificial bypass device after circulatory arrest (by almost 50% during cooling, by almost 90% after second switching of artificial circulation, by 94% during warming, and by at least 70% 1 h after perfusion); 24 h after the intervention the platelet MAO activity increased negligibly. MAO activity in the plasma notably increased in both groups during surgery, more so in group 2, which indicates washing out of the enzyme from platelets during artificial circulation because of these cells' damage. These data suggest that platelet injury is a result of their mechanical injury in the bypass circulation and of excessive partial oxygen pressure (400 mm Hg and higher) during perfusion, due to increased oxygen solubility in the plasma at low temperature. This leads to production of excessive active oxygen forms which damage cell membranes and inhibit MAO activity.

[Effect of various perfusion temperature regimens in heart surgery with extracorporeal circulation on glutathione levels and activity of enzymes of glutathione metabolism in erythrocytes]. / Vliianie razlichnykh temperaturnykh rezhimov perfuzii pri kardiokhirurgicheskikh operatsiiakh s iskusstvennym operatsiiakh s iskusstvennym krovoobrashcheniem na soderzhanie glutationa i aktivnost' fermentov ego obmena v éritrotsitakh.

The level of glutathione and the activity of its exchange enzymes (glutathione reductase, glutathione-S-transferase, glutathione peroxidase), the content of malonic dialdehyde were studied in the red blood levels of 70 patients operated on under hypothermal perfusion for correction of acquired cardiac diseases. The plasma concentrations of myoglobin were also measured. There was a relationship of the time course of changes in the parameters in question to the depth of the body's cooling during surgical interventions. Shallow hypothermia (30-34 degrees C) caused a compensatory increase in the activity of glutathione peroxidase (by more than 30%) and in the concentration of glutathione (by more than 60%) at the cooling stage. Moderate hypothermia (26-29 degrees C) produced no impact on the level of glutathione and the activity of its exchange enzymes while deeper hypothermia (25 degrees C or below) induced decreases in the levels of glutathione (by more than 30 degrees C) and suppressed the activity of all the tested enzymes of its exchange. At the same time there are elevated concentrations of malonic dialdehyde at the warming-up stage and during early postperfusion. Myoglobin washing into plasma occurs under all temperature conditions of perfusion at the warming-up stages and in the early postperfusion period, but it is most profound in deeper hypothermia, which is caused by the toxic effect of oxygen whose plasma solubility increases with lowered temperatures.

[Mechanism of diagnostic significance of histidase release into the blood in lymphedema]. / Mekhanizm i diagnosticheskaia zhachimost' vykhoda gistidazy v krov' pri limfedeme.

The organ-specific enzyme histidase was measured as an indicator of skin involvement in the blood of 52 patients with primary and secondary lymphedema of the upper and lower limbs. A stable type of the disease (degree I) was characterized by washing histidase off the derma into the blood. Mild and moderate histidase washing associated with skin dystrophy occurred with progression of the disease (stage II and III, respectively). In advanced lymphedema (degree 4) histidase does not enter blood from the skin. This fact is explained by total impairment of skin cell elements and their replacement for fibrous tissue. Both in primary and secondary lymphedema complicated by erysipelas histidase is washed off the dermocytes. The findings justify use of blood histidase indices for assessment of lymphedema patients' condition, formulation of indications for operation and concluding on the latter efficacy.

[Activity of various enzymes of formed elements in the blood plasma during extracorporeal circulation]. / Aktivnost' nekotorykh fermentov formennykh élementov v plazme krovi pri iskusstvennom krovoobrashchenii.

The activity of the enzymes whose high activity is observed in blood cells, such as the glutathione metabolic enzymes glutathione reductase, glutathione-S-transferase, glutathione peroxidase in erythrocytes and monoaminooxidase in the platelets, was examined at different perfusion stages in the plasma of 30 patients undergone open heart surgery. The findings suggest that the enzymes release from the blood cells damaged during extracorporeal circulation into the plasma, which may be useful as a test for defining the degree of perfusion-induced damage of blood cells.

[Molecular mechanisms of antioxidant action of dalargin on the liver in experimental cholestasis]. / K voprosu o nekotorykh molekuliarnykh mekhanizmakh antioksidantnogo deistviia dalargina na pechen' v usloviiakh kholestaza v éksperimente.

Changes of antioxidant activity of dalargin in the liver after naloxone (100 micrograms/kg) administration were examined in experiment on 144 rats with cholestasis. It was found that dalargin inhibited the activity of xanthine oxidase by 32-37% in different time periods after the injection. Dalargin and naloxone, when used in combination, had no effect on the enzyme activity. Glutathione-S-transferase activity rose by 38.0% and 21.8% on hour 1 and 3 after the injection, respectively, while simultaneous injection of dalargin and naloxone induced no changes in the enzyme activity after 1 hour, though decreased it by 36.8% and 26.4% on hour 3 and 5, respectively. Dalargin inhibited lipid peroxidation by 29-35%, simultaneous injection of dalargin and naloxone raised lipid peroxidation by 109.2%, 80.7% and 25.7% after 1, 3 and 5 hours, respectively. Dalargin injection elucidated a marked tendency to lowering of blood release of the liver-specific enzymes histidase and urokaninase in line with enhancement of their activity in the liver. A combined injection of dalargin and naloxone promoted high release of histidase and urokaninase in blood and did not change histidase activity in the liver in all cases. Urokanidase activity elevated in 5 hours. It was noticed that dalargin raised leu-enkephalin levels in the liver 3.5-fold 1 h after the injection. The reduced dalargin antioxidant effect coupled with naloxone pretreatment demonstrated indirect action of the neuropeptide on the liver via neuron receptors of the liver.