[First case of thrombolysis with non-immunogenic staphylokinase in a patient with ischemic stroke receiving dabigatran etexilate followed by thrombectomy]. / Pervyi sluchai tromboliticheskoi terapii pri pomoshchi neimmunnogennoi stafilokinazy u patsientki s ishemicheskim insul'tom, poluchayushchei dabigatrana eteksilat, s posleduyushchei trombektomiei.

Currently, five oral anticoagulants have been shown to be effective in preventing recurrent ischemic stroke and/or systemic embolism in patients with non-valvular atrial fibrillation. However, 1.1-2.2% of patients taking oral anticoagulants develop ischemic strokes. The use of oral anticoagulants limits the possibility of systemic thrombolytic therapy, as this is associated with an increased risk of symptomatic hemorrhagic transformation. The exception is cases when, with the help of a specific antagonist, it is possible to neutralize the effect of the anticoagulant in the shortest possible time and achieve normocoagulation. Currently, the Russian Federation allows two drugs for systemic thrombolytic therapy in patients with ischemic stroke in the «therapeutic window¼ up to 4.5 hours from the onset of the disease - recombinant tissue plasminogen activator and non-immunogenic staphylokinase, which showed no less efficacy and safety in the FRIDA study compared to recombinant tissue plasminogen activator. This article describes a clinical case of the first systemic thrombolytic therapy with a non-immunogenic staphylokinase after the use of idarucizumab in a patient taking dabigatran etexilate, followed by thrombectomy.

[CORRECTION OF HEMOSTASIS DISORDER IN HEMORRHAGIC SHOCK].

It is a clinical case of successful correction of hemostasis disorder in hemorrhagic shock. This case demonstrates the need to perform advanced tests that assess hemostatic system in patients with ongoing bleeding. Using of thromboelastography helped us to make a comprehensive assessment of hemostatic system that allowed to detect the point of application of drugs and substitution therapy. Coagulation disorder was treated by intravenous injection of Ca2+. In this case the cause of hypocalcemia was combination offactors such as electrolytes losing during massive bleeding and progressing metabolic acidosis. Therefore, monitoring the level of ionized calcium is especially important in patients undergoing massive blood loss and receiving large doses of donor blood components.

[Correlation between biochemical parameters of oxidative stress, endogenous intoxication and regulation of vascular tone in patients with burn injury].

Burn injury is accompanied by the formation of reactive oxygen species (ROS). Excessive production of ROS results in oxidative stress. Peroxidation damage of proteins causes their degradation and the formation of toxic fragments con- tributing to the development of endogenous intoxication. Furthermore, burns cause pronounced inflammatory reaction in the lesion site leading to poor circulation. The purpose of this study was an investigation of relationship between disturbances in the prooxidant/antioxidant system, severity of endogenous intoxication and disturbances of endogenous vascular regulation to assess the severity and prognosis of complications in patients with burn injury. 26 patients with- burn injury were investigated; they were divided into 2 groups according to the severity of injury on the basis of Frank index (FI): group 1--FI < 60 CU and group 2--FI ≥ 60 CU. The investigation of blood serum was performed on 1-3, 7, 14, 21 and 28 day after burn injury. Malondialdehyde (MDA), total antioxidant status (TAS), the level of middle weight molecules, stable metabolites of nitric oxide (NOx) and angiotensin-converting enzyme (ACE) activity were determined in the serum. Significant increase of MDA level, decrease of TAS and NOx level were found in two groups of patients throughout the observation period. We also found a disturbance in coupled interaction of NO and ACE. These data point to the development of oxidative stress and imbalance in endogenous regulation of vascular tone. There was a trend toward more pronounced oxidative stress in group 2. Significant correlations between parameters of oxidative stress, endogenous intoxication, endogenous factors of vascular regulation, depth of burn injury and FI were obtained in two groups. MDA, TAS can serve as one of the prognostic markers of condition severity of burned patients and therapy adequacy.

[Effect of normobaric hyperoxia on cerebral oxygenation, metabolism and oxidative stress in patients with subarachnoid hemorrhage caused by intracranial aneurysm rupture].

The development of cerebral vasospasm in subarachnoid hemorrhage (SAH) due to cerebral aneurysms rupture results in cerebral circulation disturbances. Application of normobaric hyperoxia can be an effective way for improving of oxygen delivery to injured brain tissues. The purpose of this study was to assess of normobaric hyperoxia influence on intracranial pressure (ICP), cerebral oxygenation and metabolism, oxidative stress and endogenous factors of vascular regulation in II critically ill patients with nontraumatic SAH due to cerebral aneurysms rupture. Increase of FiO2 from 0.3 to 0.5 and 1.0 was accompanied with brain oxygen tension (PbrO2) increase and cerebral extraction ratio for oxygen (O2ER) decrease. Application of normobaric hyperoxia had no effect on ICP, cerebral perfusion pressure, arterial blood pressure and cerebral metabolism. The results obtained from patients with nontraumatic SAH showed an evident increase of oxidative stress which had a significant effect on vascular endothelial function, causing an imbalance in the endogenous regulation of vascular tone. Application of normobaric hyperoxia was not accompanied by an increase of free-radical processes in critically ill patients with nontraumatic SAH due to cerebral aneurysms rupture.

[The endogenic intoxication during the early post-operational period in patients with combined intraabdominal injury and massive loss of blood].

The sample of 39 patients with combined intraabdominal injury and massive loss of blood are examined. The loss of blood consisted from 1.5 to 3.0. The assessment of endogenic intoxication was established according the indices of total and effective concentrations of albumin and mean molecular weight peptides. The endogenic intoxication coefficient (mean molecular weight peptides/effective concentration of albumin x 1000) was used. The application of endogenic intoxication coefficient permits to monitor more meaningfully the development of endogenic intoxication in victims against the background of treatment measures. The results are the pathogenic foundation of implementation of more intensive disintoxication activities in the complex therapy of this category of patients.

[The oxidation stress, lipid metabolism and their relationship in patients with severe course of hypertension disease in aggregate with carotid stenosis].

The experimental samplings consisted of 25 patients with severe course of hypertension disease in aggregate with atherogenic carotid stenosis before and after carotid endarterectomy and 21 donors. The study was organized to analyze in lipid profile blood serum the content of malonic dialdehyde, ceruloplasmin, alpha-tocopherol, nitric oxide and angiotensin converting enzyme. The study established that in patients took place a reliably increased level of malonic dialdehyde, ceruloplasmin, alpha-tocopherol, nitric oxide and angiotensin converting enzyme. The patients with this pathology have a reliable positive correlation between the concentration of malonic dialdehydeand lipoproteids of very low density (r = 0.51), malonic dialdehyde and triglycerides (r = 0.36), malonic dialdehyde and cholesterol (r = 0.3). This data confirms the important role of peroxidation of lipids in the development of atherosclerosis. Therefore, the enhancement of oxidation stress and expressed dislipoproteidemia are established in patients with hypertension disease with carotids atherosclerosis as a background. This result testifies the pathogenic significance of these phenomena in the mechanisms of homeostasis disorders.

[Criteria for assessment of endogenous intoxication in patients with pelvic peritonitis].

The time course of changes in the serum levels of average mass molecules and malondialdehyde in patients with pelvic peritonitis was studied within two weeks after surgery. The values of the above indices of endogenous intoxication (EI) were found to be 1.3-2.9 times higher than the normal values almost throughout the follow-up (p < 0.05). An integral EI coefficient (EIC) including relative (as compared with the normal values) EI indices was proposed to evaluate the magnitude of EI. In patients with pelvic peritonitis, EIC was established to be 2.9-4.8 times greater than the normal values (p < 0.05) in all follow-up periods. Thus, the application of EIC enhances the sensitivity of EI diagnosis in patients with pelvic peritonitis as compared with that in the determination of individual EI indices.

[Interrelations between endogenous factors of vascular regulation, oxidative stress, and polytrauma severity].

Patients with polytrauma were divided into two groups according to injury severity score (ISS). Group I (10 subjects) consisted of patients who scored less than 25; group II included patients who scored 25 to 49. The study demonstrated a significant increase in NO(x) and MDA levels, as well as ACE activity in groups I and II. NO(x) level displayed a positive correlation with ISS in both groups. The same was demonstrated for ACE activity. In the control group (21 donors) NO(x) level positively correlated with serum ACE activity. However, while NO(x) level positively correlated with ACE activity in group I, this correlation was not observed in group II, suggesting an impairment of conjugated vascular tone regulation caused by imbalance between NO(x) and ACE in patients with more severe injuries. The multifold increase in the level of MDA, the main oxidative stress parameter, in group I and II, indicates the necessity to include antioxidants in complex therapy of patients with polytrauma.

[Integral estimate of endogenous intoxication and its correction with sodium hypochlorite in inflammatory diseases of small pelvic organs].

The parameters of endogenous intoxication (EI) were studied in patients with inflammatory small pelvic organs diseases complicated by organs pelviperitonitis and generalized peritonitis. The integral index of EI--endogenous intoxication coefficient (EIC) was developed, which included relative values (as to the normal values) of the total and effective concentration of albumin, medium molecular peptides and leukocytic intoxication index. The values multiplied together are EIC. In patients with inflammatory small pelvic organs diseases, the level of EI was shown to considerably increase. The use of EIC was ascertained to significantly increase the accuracy of diagnosis of early-stage EI, to perform detoxifying therapy, and monitor its efficiency, as confirmed by the use of sodium hypochlorite in the combined treatment of patients with inflammatory small pelvic organs diseases.

[Effect of mexicor on oxidative stress in acute myocardial infarction].

Mexicor (5% solution and capsules) was used in 40 of 80 conventionally treated patients with acute myocardial infarction. The drug was given intravenously for 5 days, than intramuscularly (6-9 mg/kg) for 9 days and orally (0.1 mg t.i.d.) thereafter until discharge. Severity of oxidative stress was evaluated by K coefficient. Calculation of this coefficient required data on degree of oxidation of lipids in blood serum, serum levels of diene conjugates, malonic dialdehyde, alpha-tocopherol and ceruloplasmin. These parameters as well as activity of superoxide dismutase, glutathione peroxidase and catalase in erythrocytes were measured at admission, on days 2, 3, 7, 14 and at discharge. Mexicor treated compared with untreated (n=40) patients were characterized by diminished severity of oxidative stress at the account of lower levels of lipid peroxidation products and augmented compensatory potential of the endogenous antioxidant system.

[The relationship of the nitric oxide level with angiotensin-converting enzyme activity in the chest injury].

We have studied NO production, ACE activity and their correlation in pleural fluid of patients with and without lung wound, in the blood serum of the wounded and blood donors. Chest wound was associated with a significant elevation of NO levels in all study groups versus controls. The greatest increase of ACE activity was observed in pleural fluid of patients with a lung wound. There was a negative correlation between NO and ACE in pleural fluid of patients with a lung wound. In all the other groups, a positive correlation between NO and ACE was revealed. ACE overactivity in the pleural fluid may be one of the factors of impaired relationship between NO and ACE in lung wound. Determination of ACE activity in the pleural fluid may serve as a diagnostic criterion of the lung injury.

[Criteria for assessment of endogenous intoxication in burn trauma]. / Kriterii otsenki éndogennoi intoksikatsii pri ozhogovoi travme.

Registered in patients with burn trauma was the presence of endogenous intoxication (EI), which was determined by a higher value of coefficient CLP/AOS, a higher contents of medium-molecular peptides (MMP), a lower total and effective concentration of albumin (TAC and EAC) and by a reserve of the binding albumin ability. Intoxication coefficients, i.e. IC MMP/EAC and IC C/EAC showing the deposition and binding of toxic ligands, were acknowledged as the most informative EI parameters.

[Generation of nitric oxide by peripheral blood leukocytes and platelets in thoracic and abdominal wounds]. / Generatsiia oksida azota leikotsitami i trombotsitami perifericheskoi krovi pri raneniiakh grudi i zhivota.

Generation of nitric oxide (NO) by human blood leukocytes and platelets was studied in 23 healthy persons and in 22 patients with thoracic and abdominal wounds. The sum of points ranged, in victims, from 12 to 19 according to the APACHE II severity-degree condition. Leukocytes and blood platelets were isolated from blood by differential centrifuging. The leukocyte suspension was diluted by an absolute medium (RPMI 1640, embryonic calf serum, L-glutamine, antibiotics) up to 5 x 10(6) cells in 0.5 ml; while the blood platelet suspension was diluted to 05 x 10(8) in 0.5 ml, and they were cultivated for 15 at 37 degrees C. The concentration of NO nitrite metabolite was determined by Griss reaction. The NO content in leukocyte supernatant of healthy persons amounted to 0.38 +/- 0.03 nmol/0.5 x 10(6) leukocytes; while in patients this figure essentially increased--up to 1.06 +/- 0.08 nmol/5 x 10(6) leukocytes, (p < 0.001). The NO content in blood-platelet supernatant amounted, in the normal condition, to 1.07 +/- 0.07 nmol/0.5 x 10(8) blood platelets; in the victims it was 1.52 +/- 0.11 nmol/L blood platelets, (p < 0.01). The relative production of NO by leukocytes was found to be, in healthy persons, 0.75 +/- 0.06 mumol/L, (p < 0.001), in patients--3.05 +/- 0.22 mumol/L, (p < 0.01). The absolute NO concentration was determined with regard for an actual content of leukocytes and blood platelets in each healthy person and in each patient with thoracic and abdominal wounds. The absolute production of NO by leukocytes was, in healthy persons, 0.47 +/- 0.05 mumol/L, in patients--2.29 +/- 0.23 mumol/L, (p < 0.001). The absolute generation of NO by blood platelets was, in norm, 7.70 +/- 0.55 mumol/L, and in patients--11.45 +/- 0.84 mumol/L, (p < 0.0011). Consequently, the absolute production of NO by blood platelets is by 16 times higher than the absolute production of NO by leukocytes in healthy people. Thus, stress enhances the NO generation by both leukocytes and blood platelets.

[Effect of mexidol on oxidative stress in cerebral variant of hypertensive crisis]. / Vliianie meksidola na sostoianie okislitel'nogo stressa u bol'nykh gipertonicheskoi bolezn'iu, oslozhnennoi gipertonicheskim krizom po tserebral'nomu variantu.

Parameters of oxidative stress were studied in 44 patients with grade II-III essential hypertension and cerebral variant of hypertensive crisis. All patients received antihypertensive treatment. Mexidol was administered intravenously (300 mg o.d.) for 7 days starting with the second day of a hypertensive crisis. Control group consisted of 27 patients who were not treated with mexidol. The level of lipid peroxidation products and parameters of antioxidative system were used for assessment of the state of oxidative stress. Significant increases of the coefficient of oxidative stress were registered at all study points in patients who were not treated with mexidol. Treatment with antioxidant mexidol was associated with decreased coefficient of oxidative stress throughout the whole study period (up to 14-th day).

[Nitric oxide generation by human peripheral blood platelets in the norm and after thoracic and abdominal wounds]. / Generatsiia oksida azota trombotsitami perifericheskoi krovi cheloveka v norme i pri raneniiakh grudi i zhivota.

Nitric oxide production by the human peripheral blood platelets in normal condition and after thoracic and abdominal wounds was investigated. The platelets were obtained from blood by differential centrifuging. The nitric oxide production by platelets (0.5 x 10(8)) was studied in RPMI 1640 medium containing bovine fetal serum, glutamine, and antibiotics, during incubation at 37 degrees C for 15 hours. Nitric oxide level was determined by Griss reaction. A large-scale absolute production of nitric oxide by platelets was revealed both in normal condition (7.70 +/- 0.55 mumol/l), and after thoracic and abdominal wounds (11.45 +/- 0.84 mumol/l). Severe trauma course is associated with hyperproduction of nitric oxide possessing multiple damaging effects, including the anti-thrombogenic one, which should be taken into account in clinical practice.

[Impact of blood loss on lipid peroxidation and on the antioxidative system in victims with isolated injury to the chest and abdomen]. / Vliianie krovopoteri na sostoianie protsessov perekisnogo okisleniia lipidov i antioksidantnoi sistemy u postradavshikh s izolirovannoi travmoi grudi i zhivota.

The paper deals with the impact of the volume of blood loss on the time course of changes in the parameters of lipid peroxidation (LPO) and the antioxidative system (AOS) in the sera of 22 and 31 victims with isolated chest and abdominal injuries, respectively, on days 1, 3, 7, and 14 days after injury. All the victims were found to have enhanced LPO processes and altered AOS. The severity of disorders in the LPO-AOS system depends on the size of blood loss, the disorders manifest themselves to a greater extent with over 2-liter brisk bleeding and enhance on days 7 and 14 after injury. In mild blood loss equal to as low as 1.0 liters, there was a mobilization of AOS components, such as (-tocopherol and ceruloplasmin, to the blood bed in the victims with both isolated chest and abdominal injury. AOS failure remaining during all periods of the study was detected in victims with abdominal organs and over 2-liter blood loss. Disorders in the LPO-AOS system were pronounced in abdominal injury. Multimodality treatment in victims with isolated injury of the chest and abdomen does not normalize impaired LPO processes and AOS, which makes it necessary to include into antioxidative therapy for brisk bleeding.