[Cardioprotective effect of the new derivative of glutamic acid - glufimet in acute immobilization-painful stress in animals of different ages].

The effect of the 24-hour immobilization-painful stress on myocardial contractility of young (6-month), middle-aged (12-month) and old (24-month) female rats was studied. It was identified a reduction of the functional reserve of the heart, which showed a smaller growth rates of contraction and relaxation of the myocardium (+ dP/dt max and -dP/dt max), left ventricular pressure (LVP) and the maximum intensity of the functioning of the structures (MIFS) under increased pre- afterload and adrenergic stimulation of the heart, especially pronounced in the group of 24-month old rats. The animals of all ages treated before and after stressing glufimet in a dose 29 mg/kg, have higher rates of growth + dP/dt max, -dP/dt max, LVP and MIFS during load tests, most significant rates of growth are noticed in older rats compared with the young and middle-aged. Phenibut improves studied parameters equally at 6, 12 and 24-month old females, subjected to stress.

[COMPARATIVE STUDY OF THE HEART FUNCTIONAL RESERVE UNDER STRESS-INDUCED BLOCKADE OF NO-ERGIC SYSTEM AND GABA-A RECEPTORS IN RATS.]

Cardiac contractility in rats was decreased after 24-h immobilization-painful stressing, as indicated by lower growth rate of myocardium contraction and relaxation, LVP, heart rate, and maximum functioning intensity (MIF) in comparison to intact group during functional tests on adrenoreactivity and maximum isometric workload. Stressed animals pretreated with the GABA-A receptors blocker bicuculline (2 mg/kg, i.p.) exhibited more pronounced reduction in inotropic my- ocardial function in comparison to that in rats of the control group, as evidenced by a smaller increase in +dP/dtmax, -dP/dtmax, LVP, and MIF during functional tests. Under conditions of NO-synthase inhibition (L-NAME 10 mg/kg, i.p.), the resistance to stress and inotropic cardiac functio reserves in stressed animals decrease to a much greater degree (on average, by 50%; p < 0.05) than under conditions of GABA-A receptors blockade, which can be seen from weak growth rates of myocardium contraction and relaxation, LVP, and MIFS, as well as from high percentage of animal deaths during stressing, anesthesia, necropsy thorax, and after functional tests. Thus, NO deficiency leads to more pronounced myocardial contractility disorders in stressed animals than under conditions of inhibition of GABA-A receptors.

Effects of a New Glutamic Acid Derivative on Myocardial Contractility of Stressed Animals under Conditions of Nitric Oxide Synthesis Blockade.

Glufimet (glutamic acid derivative) in a dose of 28.7 mg/kg limited the reduction of the cardiac functional reserve in animals subjected to 24-h stress under conditions of nonselective NO synthase blockade with L-NAME (10 mg/kg). Adrenoreactivity and increased afterload tests showed that the increment of myocardial contraction/relaxation rates, left-ventricular pressure, and HR were significantly higher in glufimet-treated stressed animals with NO synthesis blockade than in animals which received no glufimet. The efficiency of glufimet was higher than that of phenibut (the reference drug).

[NO-DEPENDENT MECHANISM OF THE CARDIOPROTECTIVE ACTION OF PHENIBUT ON STRESS-INDUCED VIOLATION OF CONTRACTILE FUNCTION OF THE HEART].

A stressor action for 24 h reduces both ino- and chronotropic reserves of animal heart as evidenced by a decrease in rate growth increments of contraction and relaxation of the myocardium, left ventricular pressure (LVP), heart rate, and the maximum intensity of functioning (MIF) as compared to intact animals during testing for adrenoreactivity and maximum isometric load caused by clamping of the ascending part of the aortic arch. Blockade of NO-synthase leads to a high percentage of animal death during the stressor action, anesthesia, opening of the chest, and functional tests and causes marked reduction in the growth rates of contraction (+dP/dt max) and relaxation (-dP/dt max) speed, LVP, heart rate, and MIF--on the average about 2 times (p < 0.05) under load testing conditions as compared to a control group of stressed animals. Phenibut limits stress-induced violations of the myocardium contractility, as indicated by a higher growth of performance in stress tests--on the average about 1.8 times (p < 0.05) in comparison to the control group of animals. The cardioprotective effect of phenibut is less pronounced when it is introduced on the background of the blockade of NO-ergic system. Under these conditions, there are cases of animal death, predominantly during the stressor action. The results obtained suggest that, for ensuring cardioprotective action of phenibut under conditions of stress-induced myocardial damage, it is necessary to provide for participation of nitric oxide system.

[Cardioprotective properties of new glutamic acid derivative under stress conditions].

The effect of new glutamic acid derivative on the cardiac ino- and chronotropic functions has been studied in experiments on rats exposed to 24-hour immobilization-and-pain stress. It is established that glutamic acid derivative RGPU-238 (glufimet) at a dose of 28.7 mg/kg increases the increment of myocardial contractility and relaxation rates and left ventricular pressure in stress-tested animals by 13 1,1, 72.4, and 118.6%, respectively, as compared to the control group during the test for adrenoreactivity. Compound RGPU-238 increases the increment of the maximum intensity of myocardium functioning by 196.5 % at 30 sec of isometric workload as compared to the control group. The cardioprotective effect of compound RGPU-238 is 1.5 - 2 times higher than that of the reference drug phenibut.

[Change of cardiac ino- and chronotropic functions in stressed animals with blockade of different NO-synthases].

AIM: To investigate the effect of long-term immobilization-painful stress on ino- and chronotropic functions of the heart with inhibition of various NO-synthases. MATERIALS AND METHODS: 30 female albino rats were taken. Blockers of NO-system were: aminoguanidine (50 mg/kg), (50 mg/kg) and NG-nitro-L-arginine methyl ester (10 mg/kg). Stress was modeled by suspending the animals for cervical dorsal skin fold for 24 hours. The functional reserves of the heart were studied using adrenoreactivity and isometric load tests. RESULTS: experiments showed that painful stress leads to a decrease of cardiac ino- and chronotropic functions which is observed in the reduction of increment dp/dt+, dp/dt-, LVP and HR during load tests in comparison to control group of intact animals. Selective blockade of nNOS with 7-Nitroindazole causes even greater decrease an increment indices of myocardial contractility and LVP in stressed animals during load tests. The most pronounced inhibition of inotropic function of the stressed animal's heart observed in the non-selective inhibition of NO-synthases by L-NAME. Administration of aminoguanidine to animals (inducible NOS blocker) before and after stress causes an increase of inotropic reserve of the heart, resulting in increased increment of myocardial contractility and relaxation findings, left ventricular pressure and heart rate during load tests, CONCLUSIONS: NO-ergic system plays a significant role in limiting of the negative stress effects on the contractile function of the heart.

[Evaluation of the efficiency of external assessment of the quality of determining antibodies to hepatitis C virus in the network of screening laboratories].

A regional external quality assessment (EQA) system for determining anti-hepatitis C virus (HCV) was developed and introduced. For this, a control panel comprising 14 samples with anti-HCV and 6 samples without anti-HCV was tested in the reference laboratory of Moscow Infectious Hospital One. A total of 6 sessions were conducted with the participation of 8 laboratories. The regional EQA system covering a limited number of laboratories was shown to significantly improve the quality of detection of hepatitis C virus antibodies. The optimal multiplicity of sessions for the developed EQA system was ascertained to be once fortnight. It is possible to define the current rating of screening laboratories in the sensitivity criterion and to elaborate address organizational-and-methodic measures according to the results of control tests.

[The spread of hepatitis B and C viruses and the structure of HBsAg subtypes in Kabardino-Balkaria].

A seroepidemiological study of the spread of hepatitis B and C viruses (HBV and HCV) was conducted among some population groups in Kabardino-Balkaria. The structure of HBsAg subtypes was also studied in the residents of the republic. The presence of viral hepatitis B markers among the test groups of the healthy population corresponds to the parameters of moderate activity of an epidemic process. The analysis of the immunological structure of the population leads the author to assign Kabardino-Balkaria to highly HBC endemic areas. The occupational factor is demonstrated to be actively involved in the spread of HBC and it is practically of no significance for HCV. An examination could reveal the HBsAg subtype adrq+ that is uncharacteristic of this area.

[Prevalence of HBV and HCV markers in patients of specialized medical institutions].

240 medical histories of patients admitted to Moscow clinical narcological hospital No. 17 with "opium addiction" diagnosis in 2000 and 2003 (120 histories for each year) were analyzed. From 1997 to 2003 4220 patients registered in narcological dispensary of Cherepovets city (Vologda region) were tested for HBsAg and anti-HCV. It has been shown that in new injection opiate drug users young patients (15 - 19 y.o.) predominated (41.7%). Tendency to development of drug addiction in younger age was revealed - in 2003 compared to 2001 percent of new injection drug users aged 11 - 14 years admitted to hospital raised in 1.5 times. In 2000 and 2003 in Moscow markers of HIV and/or HBV/HCV infection were detected in 84.2 and 91.7% of injection drug users respectively. Maximal rates of HBV and HCV infection in injection drug users in Cherepovets city were detected in 2001 - 11.7 and 83.1% respectively. Leading role of injection drug users in maintenance of HBVand HCV epidemic process activity in Russia was established.

[Morbidity in acute virus hepatitis B on the territory of Kabardin-Balkaria].

Morbidity in acute virus hepatitis B (AVHB) in Kabardin-Balkaria during the period of 1992 to 2003 was analyzed. The dynamics of changes in the age groups of AVHB patients, as well as in the structure of the transmission routes of the disease, was analyzed. The level of AVHB morbidity in the Kabardin-Balkar Republic was lower in recent years than the average level of such morbidity in the whole of Russia. The sharply defined irregularity in the territorial distribution of AVHB cases was established. The highest morbidity rates in AVHB were registered in Nalchik, as well as in Chegem and Prokhladnensk regions. The leading role in the formation of the morbidity in acute virus hepatitis B on the territory of Kabardin-Balkaria belongs to Nalchik, where 56.8% of AVHB cases were registered. In the structure of the transmission routes of AVHB the prevalence of artificial paths was noted; among them, the highest proportion belonged to parenteral medical manipulations in outpatient clinics (32.9%). The proportion of AVHB cases associated with the intravenous use of drugs was 6.9%. In the age structure of AVHB patients adults prevailed, and among them the highest number of cases was registered in the age groups of 20 - 29 years and 30 - 39 years. In 2002 the total proportion of AVHB cases among the patients of these age groups reached 68.3%.

[A comparative evaluation of detection of antibodies to hepatitis C virus in different immunoassay test system and verification tests]. / Sravnitel'naia otsenka rezul'tatov opredeleniia antitel k virusu gepatita C pri ispol'zovanii razlichnykh immunofermentnykh test-sistem i podtverzhdaiushchikh testov.

Control tests and subsequent comparative analysis of their results related with the detection of anti-hepatitis C virus (anti-HCV) by different ELISA systems were made at a laboratory of the "Vector-Best" Company, Novosibirsk (A), a clinical diagnostic laboratory of Infection Clinical Hospital No. 1, No. 1 (B), and at a laboratory of chronic viral infections of Andjaparidze Institute of Viral Drugs of the Russian Academy of Medical Sciences (C). Two thousand three hundred and fifty blood sera of donors and 236 blood sera of patients with acute and chronic renal pathology were examined. The comparative research made at the above facilities by different ELISA systems produced diversified results. An analysis of 2350 blood samples from donors made in 3 ELISA systems at laboratory A showed divergence in 19 (0.8%) cases. At laboratories B and C, 5 ELISA systems (a set of 236 samples) denoted differences in 28 (11.9%) cases. Significant variances were registered in confirmation of disputable results of ELISA with immunoblot, which is apparently related with differing criteria applicable to confirming the positive results from using the confirmative tests. A possibility is discussed of using different ELISA systems in screening examination.

[Viral hepatitis in different population groups of Republic of Sakha (Iakutia)]. / Shirota rasprostraneniia virusnykh gepatitov sredi razlichnykh grupp naseleniia na territorii respubliki Sakha (Iakutia).

A survey for the presence of markers of viral hepatitis B, delta, C and E among different groups of the population of the arctic and agricultural zones of the Republic of Sakha (Yakutia), as well as in Yakutsk, was carried out. The survey revealed that viral hepatitides with the parenteral mechanism of the transmission of infective agents were widely spread among the population. In the arctic zone HBsAg was detected in persons aged 20 years and older in 10.8-17.1% of cases. On the average, in the arctic zone antibodies to virus delta were detected in 2.4% of cases. In different regions of the agricultural zone the detection rate of HBsAg was also high (10.4-23.8%). In the Namsk and Vilyui regions delta infection was registered among adolescents (15-19 years of age) in 8.7 and 22.4% of cases respectively. In the Mountainous region anti-delta antibodies were detected among persons aged 20 years and older in 31% of cases. The survey showed the presence of considerable differences in the detection rate of the markers of hepatitis B, depending on the ethnic origin of the examined patients. Similar tendencies were found to exist with respect to delta infection.

[Evaluation of morbidity and etiological structure of acute and chronic viral hepatitis in the Sakha Republic (Yakutiia)]. / Otsenka zabolevaemosti i étiologicheskoi struktury ostrykh i khronicheskikh virusnykh gepatitov na territorii Respubliki Sakha (Iakutiia).

The morbidity of viral hepatitis was epidemiologically analyzed and the etiological structure of severe and chronic viral hepatitis was studied in the Republic of Sakha (Yakutia). Acute viral hepatitis B, whose portion is 43.5%, was found to be of the key significance within the structure of acute viral hepatitis (AVH). Acute viral hepatitis C (with 4.7% in the AVH structure) is by far more rare. The latter is close to the value registered in other Russia's regions. Apart from the prevalence of viral hepatitis B (32.4%) an exceptionally high share of chronic hepatitis delta (24.5%) was established for the etiological structure of chronic viral hepatitis, which is a specificity of the discussed region. The epidemic situation in the Republic of Sakha (Yakutia) was stated to be linked with the mentioned extra dangerous diseases, which requires appropriate emergency measures with the prevention vaccination program against hepatitis B being a priority.

[Evaluation of the system for controlling the quality of the HBsAg detection in the system of screening laboratories]. / Otsenka sistemy kontrolia kachestva detektsii HBsAg v seti skriningovykh laboratorii.

The two-stage control system, ensuring the high quality of serological investigations in the network of screening laboratories in Moscow was developed and introduced into practice. At the first stage the entry control of the quality of the test system for the detection of HbsAg, coming to the screening laboratories, is made in the reference laboratory with the use of specially developed "representative" panels, as well as the test systems for comparison ("reference" test systems). Then "minipanels" are formed from specimens included into the "representative" panels, which are used for the evaluation of the quality of laboratory investigations made in the screening laboratories. The high quality of such system for controlling the quality of the detection of HBsAg in the screening laboratories of Moscow is shown.