[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.

[Nitric oxide and blood coagulation system in clinical practice].

The article presents data concerning the effect of endothelium NO on vascular wall antithrombogenic properties, and the mechanism of NO antithrobogenic activity. The authors summarize the results of their own investigations and literature data on the role of thrombocyte NO in intravascular antithrombogenesis and the regulation of coagulation factors. Thrombocytes produce 16 times more NO then other blood cells do. A correlation between thrombocyte NO and several coagulation factors has been proved; thus complex study of NO effect on internal and external coagulation mechanisms, factors of fibrinolysis and their inhibitors, acute-phase inflammatory proteins, playing an important role in hemostasis, may bring new interesting findings. It is evident, that this knowledge will help to find ways of pathogenetic hemostasis regulation in various extremal conditions.

[Interrelationship between platelet nitric oxide production and plasma fibrinogen level in emergencies].

Platelet nitric oxide production has been investigated in patients with thoracic and abdominal wounds, thermal trauma, varicose disease, methanol and leponex poisoning. There is correlation between absolute platelets nitric oxide production and fibrinogen plasma level in these patients. The maximal absolute platelets nitric oxide production has been revealed at surgical diseases, and minimal has been observed at methanol poisoning. Irrespectively to etiology and danger of disease, reliable correlation between absolute platelets nitric oxide production and fibrinogen plasma level of these patients is established. Consequently platelets nitric oxide production may be important for haemostatic processes.

[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.

[Pathogenetic implication of some laboratory parameters in the development of toxicohypoxic encephalopathy in acute poisoning by psychopharmacological agents].

In 62 patients with acute poisoning, blood gases, immunograms, hemorheology, oxidative stress, and the blood levels of biogenic amines were studied at the toxicogenic and somatogenic stages of poisoning. It was found that the development of toxicohypoxic encephalopathy was affected by the magnitude of changes in laboratory homeostatic parameters among which hemorheological and immunological were prominent.

[Laboratory changes in exo- and endotoxemia in toxicohypoxic encephalopathy occurring with acute poisoning by psychopharmacological agents].

Examinations of patients with acute oral poisoning by psychotropic agents have indicated that toxicohypoxic encephalopathy develops, when the high concentrations of toxicants and their active metabolites specifically affect brain structures, resulting in oxidative stress and impaired natural detoxification mechanisms.

[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.

[The nature of a relationship of nitric oxide with angiotensin-converting enzyme and malonic dialdehyde in patients with atherogenic stenosis of the internal carotid artery]. / Kharakter vzaimosviazi oksida azota s antiotenzinprevrashchaiushchim fermentom i malonovym dial'degidom u bol'nykh s aterogennym stenozom vnutrennei sonnoi arterii.

In patients with stenosis of the internal carotid artery (ICA), a relationship was studied between the level of nitric oxide (NO) and the activity of angiotensin-conversing enzyme (ACE) and malonic dialdehyde (MDA) in the blood serum taken from: 1) the cubital vein an hour before carotid endarterectomy; 2) ICA before surgery; 3) the internal jugular vein before surgery; 4) ICA 5 min after surgery; 5) the internal jugular vein 5 min after surgery; 6) the cubital vein an hour following surgery. There was a direct correlation between the level of NO and the activity of ACE and an inverse correlation between the content of NO and MDA in the sera taken from the cubital, internal jugular vein, and ICA before and after endarterectomy. There were significant increases in the level of NO, in the activity of ACE, and in the content of MDA and total cholesterol in the serum taken from the cubital vein before carotid endarterectomy, which is indicative of significant oxidative stress and the necessity of its pathogenetic correction.

[Analysis of nitrites/nitrates (NOx) in serum]. / Metod opredeleniia nitrita/nitrata (NOx) v syvorotke krovi.

Nitrite (NO2-) and nitrate (NO3-) concentrations are usually measured as a marker of NO metabolism. The aim of this study was to validate and standardize the method for the quantification of these two metabolites (nitrite and nitrate) in serum. The samples (serum) were deproteinized with NaOH, zinc sulfate and reduced with cadmium granules. Analytical recovery of NO3- added to serum samples after reduction with cadmium granules was 96-105% (Griess reaction). Calibration curves for nitrate and nitrite were linear over the concentration range of 2.1 to 200 micromol/L in plasma. The detection limit of the assay was 0.9 micromol/L and the quantitation limit was 2.1 micromol/l. Usual values were determined from healthy subjects: the mean concentration of NO2-/NO3- (NOx) was 26.2 +/- 1.1 micromol/l (mean +/- SEM) (n = 39). Within-run precision was 6.8% and between-day precision was 2.1%.

[The condition of the antioxidant system and lipid peroxidation in victims with a severe compound trauma]. / Sostoianie protsessov perekisnogo okisleniia lipidov i antioksidantnoi sistemy u postradavshikh s tiazheloi sochetannoi travmoi.

The study was made of lipid peroxidation (LPO) and antioxidant system (AOS) in 50 victims with a severe compound trauma regarding the patients' condition assessed by APACHE II scale at admission to a critical care unit. It is shown that disorders in the system LPO-AOS depend on severity of the trauma and manifest most obviously in most severe trauma, therefore the degree of LPO-AOS imbalance is a significantly informative criterion of pathobiochemical disturbances. The coefficient K, the indicator of imbalance in the system LPO-AOS, is proposed as a pathogenetically sound criterion of the assessment of the patient's condition severity in the victims with a severe compound trauma.

[Analysis of nitrites and nitrates (Unox) in urine]. / Opredelenie nitrita/nitrata (Unox) v moche.

Nitrite (NO2) and nitrate (NO3) concentrations are usually measured as a marker of NO metabolism. The aim of this study was to validate and standardize a method for the quantification of these two metabolites (nitrite and nitrate) in urine. The sample (urine) were deproteinized with NaOH, zinc sulfate and reduced with cadmium granules. Analytical recovery of NO3 added to urine samples after reduction with cadmium granules was 96-105% (Griess reaction). Calibration curves for nitrite and nitrate were linear over the concentration range of 2.1 to 200 micromole/L in urine. The detection limit of the assay was 0.9 micromole/L and the quantification limit was 2.1 micromole/L. Usual values were determined for healthy subjects: the mean concentration of NO2/NO3 (Unox) was 51.1 +/- 5.3 micromole/mmol creatinine (mean +/- SEM) (n = 15). Within-run precision was 6.6% and between-day precision was 2.2%.

[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.

[Formation of nitric oxide by peripheral blood leukocytes in the norm and in pathology]. / Generatsiia oksida azota leikotsitami perifericheskoi krovi v norme i pri patologii.

The study was made of nitric oxide (NO) generation by leukocytes of peripheral blood from healthy subjects and patients with a compound trauma. How to isolate leukocytes from the whole blood is shown. Leukocyte isolation rate reached 98%. Generation of NO by leukocytes was made in the medium containing medium RPMI 1640 (free of phenol red), calf embryonic serum (5%), L-glutamine (2 mM), gentamycin (80 mcg/ml), penicillin (100 U/ml), streptomycin (100 mcg/ml). Incubation lasted for 15 h at 37 degrees in tissue culture plates with 24 cells 16 mm in diameter (Costor, USA). NO generation was defined in supernatants of cultivated leukocytes (5 x 10(6)) with Griss reagent in reaction with stable metabolite nitrite. NO content among the leukocytes from healthy subjects was 0.63 +/- 0.08 nmol, in trauma 1.10 +/- 0.08 nmol, relative production of NO by healthy subjects was 1.27 +/- 0.17 mumol/l, in trauma 2/21 +/- 0.18 mumol/l, absolute production was 0.99 +/- 0.15 mumol/l and 1.98 +/- 0.19 mumol/l, respectively. The findings point to an important role of nitric oxide generation by leukocytes in reaction with superoxide radical in production of peroxynitrite responsible for severity of endotoxicity.

[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.

[Leukocytic and thrombocytic generation of nitric oxide in patients with bronchial asthma]. / Generatsiia oksida azota leikotsitami i trombotsitami krovi u bol'nykh bronkhial'noi astmoi.

Leukocytic and thrombocytic nitric oxide generation was studied in 23 healthy individuals and 17 patients with bronchial asthma. Differential centrifugation was used to isolate leukocytes and platelets from blood. The suspensions of leukocytes (5.10(6)) and platelets (0.5.10(8)) were incubated in 0.5 ml of the medium RPMI 1640 at 37 degrees C for 15 hours. The concentration of the stable metabolite of NO nitrite was estimated by the Griss test. The relative leukocytic NO production was 0.75 +/- 0.06 and 1.32 +/- 0.06 mumole/l in healthy individuals and patients, respectively (p < 0.001). The relative thrombocytic NO production was 2.15 +/- 0.14 and 2.26 +/- 0.07 mumole/l in healthy individuals and patients, respectively. The absolute leukocytic NO production was 0.47 +/- 0.05 and 0.65 +/- 0.05 mumol/l in healthy individuals and patients, respectively (p < 0.01). The absolute thrombocytic NO production was 7.70 +/- 0.55 and 5.32 +/- 0.27 mumole/l in healthy individuals and patients, respectively (p < 0.001). Therefore, the absolute production of NO by platelets is 16 times higher than that by leukocytes. In the patients, the relative and absolute leukocytic NO productions increased and the absolute thrombocytic NO production significantly decreased.

[Effect of nifedipine and verapamil on cytosolic glucocorticoid receptors in hemorrhagic shock]. / Vliianie nifedipina i verapamila na svoistva tsitozol'nykh gliukokortikoidnykh retseptorov pri gemorragicheskom shoke.

Function of rat liver cytosolic glucocorticoid receptors in the haemorrhagic shock and the effects of verapamil and nifedipine were investigated. Nifedipine administration normalised hepatic receptor functioning affected by the shock. Verapamil administration to animals subjected to shock treatment caused further suppression of the receptor functioning. Both drugs reduced blood corticosterone level in hemorrhagic animals up to control level. Verapramil potentiated hypotension and this deteriorated the course of posthamorrhagic period. This effect may be at least partially attributed to verapramil-induced inhibition of glucocorticoid receptor type II. Nifedipine maintained BP in the subnormal level and reduced the number of animals with the decompensated shock course, which is probably associated with its positive influence on glucocorticoid receptor properties and permits to recommend an introduction of this drug into the complex therapy of the shock.

[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.