[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.

[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.

[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%.

[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%.

[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.

[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.

[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.

[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.

[Pathogenesis of arterial hypertension in the Itsenko-Cushing syndrome]. / K patogenezu arterial'noi gipertenzii pri sindrome Itsenko-Kushinga.

The search and measurements of the activity of angiotensin-converting enzyme (ACE) and glucocorticoid receptors of type II (GR II) were made in the adrenals of 19 patients with Icenko-Cushing syndrome (ICS). ACE and GR II were detected in the tissues of the adrenal cortex and cortisol-producing tumors. It is suggested that glucocorticoids may induce ACE activity and in this way potentiate synthesis of angiotensin II. The effect is mediated by GR II. Activation of such tissue components of the renin-angiotensin system contributes much to the mechanism underlying arterial hypertension.

[Adrenal ACE and type II glucocorticoid receptors in primary hyperaldosteronism]. / Nadpochechnikovyi angiotenzinprevrashchaiushchii ferment i gliukokortikoidnye retseptory II tipa pri pervichnom giperal'dosteronizme.

Adrenal tissue from 6 patients with primary hyperaldosteronism has been examined for the presence of angiotensin-converting enzyme (ACE). Its activity and amount of glucocorticoid receptors of type II (GR-II) were measured. ACE and GR-II were detected in adrenal tissue. GR-II induce ACE activity in interaction with plasma hydrocortisone. The glucocorticoid-receptor mechanism is an essential element in regulation of ACE activity determining a vasopressor effect. Disclosed is one of the aspects of tissue renin-angiotensin system function in primary hyperaldosteronism.

[Receptor mechanisms for realizing the effect of glucocorticoid hormones in traumatic and hemorrhagic shock]. / Retseptornye mekhanizmy realizatsii éffekta gliukokortikoidnykh gormonov pri travmaticheskom i gemorragicheskome shoke.

Blood corticosterone concentrations showed a 2-fold increase in traumatic and hemorrhagic shock. Following 4 hours of injury, the rat hepatic cytasol density of glucocorticoidal receptor II and III decreased to 76 and 67% of the level of intact animals, respectively. There were changes in the physicochemical properties of glucocorticoidal receptors: an increase in Ka and a decrease in Kd of the hormone-receptor complexes. A direct relation was found of the glucocorticoid-binding capacity of receptors II to blood pressure (BP) in shock. The most marked suppression of receptors II was noted in hemorrhagic shock, which seems to be due to more profound systemic hemodynamic changes and low BP in this type of shock. There was a concurrent reduction in the density of receptors I and II up to the certain decrease in the levels of receptors II, then was an increase in receptor III binding of [3H]-corticosterone. With the low density of receptors II and with the high concentration of corticosterone, this appears to be aimed at preserving the glucocorticoid-dependent activation of the cell genetic apparatus. Dysfunctions found in the glucocorticoidal receptors are a cause of the development of relative glucocorticoid deficiency in shock.

[Urapidil effects on oxidative stress in hypertensive crises]. / Vliianie urapidila na okislitel'nyi stress pri hypertonicheskikh krizakh.

Urapidil effects on oxidant stress were studied in 36 patients with hypertension stage I-III running with crises. Acute hypertensive crisis was managed by intravenous injections of urapidil (20-50 mg) for 5 min. After that for a week they received urapidil monotherapy followed by combined treatment for another week (quinapril--25 mg/day or ramipril--5-10 mg/day in combination with hypothiaside--25 mg/day; lokren--20 mg/day or atenolol--50-100 mg/day and diltiazem--180-360 mg/day) to stabilize arterial pressure finally. Oxidant stress was estimated by lipid peroxidation (LPO) and state of antioxidant system (AOS). Catabolism and anabolism were evaluated by blood levels of hydrocortisone and insulin. LPO, AOS, the blood hormones were measured before management of hypertensive crisis, immediately after it and 1, 3, 7 and 14 days after. Before the crisis treatment LPO was found high. Urapidil administration reduced levels of hydrocortisone, dienic conjugates, lipid peroxidation, oxidant stress rate (OSR). Later, LPO and OSR slowly increased. It is concluded on validity of the antioxidants use in hypertensive patients with crises.

[Nitric oxide and lipid peroxidation as factors in endogenous intoxication in emergency states]. / Oksid azota i perekisnoe okislenie lipidov kak faktory éndogennoi intoksikatsii pri neotlozhnykh sostoianiiakh.

K coefficient which is an integral indicator of the unbalance in the system lipid peroxidation--antioxidant system (LPO-AOS) and content of nitrite, nitric oxide end product, were followed up in 31 patients with concomitant brain injury, in 24 patients with burn injury and 72 patients in hypertensive crisis. Coefficient K was estimated by serum levels of dienic conjugates, malonic dialdehyde, lipid peroxidation degree, alpha-tocopherol, ceruloplasmin on the disease day 1, 3, 7 and 14. Nitrite serum levels rose by day 14 in all the patients and were the highest in hypertensive crisis patients. Coefficient K was significantly elevated in all the patients compared to controls being maximal in patients with concomitant brain injury. Thus, activation of LPO and biosynthesis of nitric oxide contribute much to endogenic intoxication in patients on critical care.

[The dynamic of biochemical stress reaction inductors in various tactics for surgical treatment of patients with a combined trauma of cranium and lower limbs ]. / Dinamika biokhimicheskikh induktorov stress-reaktsii pri razlichnoi taktike khirurgicheskogo lecheniia bol'nykh s sochetannoi travmoi cherapa i nizhnikh konechnostei.

In 31 patients after a craniocerebral trauma combined with a trauma of locomotor system (CCCT), and in 28 patients with only a limb fractures a time course (1, 3, 7, and 14 days) of biochemical stress reaction inductors (cortisol, serotonin, histamine, lipid peroxidation products) in various tactics of surgical treatment was studied. It was established that CCCT in a significantly stronger degree increases cortisol and lipid peroxidation products' levels than an isolated locomotor system trauma. An early postponed surgical intervention in lower extremities in CCCT results in the same increase in the biochemical stress reaction inductors as a late postpone surgical intervention in the lower extremities. In an early postponed osteosynthesis in CCCT patients, a mean term of hospital stay was 67 days, and in a late postponed one 117 days. The disability period was correspondingly 200 vs 315 days.