[Delayed medical consequences of the Chernobyl accident in Armenia. Assessment of life quality and accelerated biological aging of accident liquidators].

In this paper, some final results of 25-year investigations carried out in Scientific Centre for Radiation Medicine and Burns MH RA (SCRMB) on the Armenian cohort of the Chernobyl accident consequences liquidators are shown. These results show that health conditions of the liquidators became worse during the whole observation period. A considerable development of both pathological states atypical of radiation damages and diseases, which may be considered as radiation-induced ones, was determined. Rise of the sickness rate of almost all organism systems, first of all, nervous, cardiovascular, respiratory and digestive ones, was observed. In 70% of liquidators the main disease was primarily detected after working on CNPP. In the intervening years, the average number of diagnoses per 1 liquidator increased from 1.5 in 1987 to 7-8 in the recent time. In addition to the detected diseases, particular functional shifts in neuropsychological and vegetative status of the liquidators were observed. The overwhelming majority of them have increased tonicity of the sympathetic vegetative nervous system, asthenic and depressive syndromes occurring in the form of weakness, somnolence, mood instability, mental capacity decrease, and memory defects. In the paper, the results of investigations aimed at clarification of changes in biological aging processes of the liquidators and assessment of their "life quality" features in terms of physical, psychical and social welfare are considered. Biological aged-related passportization in a definite part of liquidators elucidated an accelerated aging rate. The studies were performed with the help of SF-36 inquirer and indicated that health status aggravation of the liquidators also affected their life satisfaction. The "life quality" indices of the liquidators significantly concede the overall average standards by both physical health and psychical and social welfare scales.

[Dynamics of the functional status of autonomic nervous system in rats under combined radiation/thermal injury in case of an open burn wound and wound covered by the polymer film].

The peculiarities of the functional status of autonomic nervous system and physical efficiency were studied in white inbred rats under dynamics of combined radiation/thermal injury (CR/TI). The CR/TI model was obtained under total X-ray irradiation at dose level of 4.37 Gy and inflicting III degree burn injury making 12% of body surface in 24 rats. The studies were performed under conditions of both spontaneous CR/TI development and protecting the burn wound against infection. In 12 rats the wounds were covered by polymer films treated with iodine and succinic acid. On days 3, 7, 14, 21 and 28 of CR/TI, as well as prior to CR/TI (datum level), heart rate variability (HRV) indices, the level of physical efficiency (the retention time of own weight on the vertical pole), indices of body mass, survival, and average life-soan of animals were recorded. For registration of ECG in awake rats, corrections of motor artifacts and analysis of HRV the original software program was used. R-R intervalograms were analyzed in time and frequency domains. The sliding window technique was used (100 R-R intervals with the step of 10 seconds; epoch of analysis--7 minutes). The obtained data indicated that the survival level and the average life-span in rats with the film-covered burn wound were higher as compared to the "pure" CR/TI. At the same time body mass and physical efficiency in animals of both groups did not differ in practice. Data on the functional status of autonomic nervous system were more informative. In rats with film-covered burn wound the dynamics of HRV indices had a biphasic character with the tending to normalization beginning from day 7 of CR/TI, whereas in case of an open wound HRV indices were characterized by monotonous growth until the end of observations. In the overall picture of the CR/TI in both groups of animals the sympathotropic effects of burn stress prevailed. Methods of mathematical analysis of HRV under conditions of CR/TI were for the first time used in this study. The research outcomes signify to the expediency to apply these methods for obtaining data on functional state of the autonomic nervous system in CR/TI models in small laboratory animals.

[On the occasion of the 20th anniversary of the accident on the Chernobyl NPP: medical consequences in Armenia].

The aim of this work is the analysis of the indices of the health and of the structure of the sicknesses of the inhabitants of Armenia who took part in the liquidation of the consequences of the Chernobyl accident. Also it is the determination of possible dependence of the frequency of diseases for the most widespread classes of sicknesses on the received dose of the irradiation, according to the data of the clinical examination and dispensarysation; and also it is the revelation of the role of other factors influenced on the health indexes.

[Variability of short tandem repeats on the human Y chromosome]. / Izmenchivost' korotkikh tandemnykh povtorov Y-khromosomy cheloveka.

Nine rare (biallelic) mutations and six short tandem repeats (STR) mapping to the nonrecombining portion of the Y chromosome were genotyped in 734 males from different geographical regions inhabited by the contemporary Armenian population. The analysis of molecular variance (AMOVA) showed that 48.9% of total STR genetic variation was explained by the differences between the haplogroups isolated based on biallelic polymorphism, whereas only 1.3% of genetic variation could be attributed to the differences between the geographic groups.

Clastogenic factors in the plasma of Chernobyl accident recovery workers: anticlastogenic effect of Ginkgo biloba extract.

Clastogenic factors are found in the plasma of persons irradiated accidentally or therapeutically. They persisted in the plasma of A-bomb survivors over 30 years. Clastogenic factors were found in 33 of 47 Chernobyl accident recovery workers (often referred to as liquidators) in a previous study (I. Emerit et al., J. Cancer Res. Clin. Oncol. 120, 558-561, 1994). In the present study, we show that there is a positive correlation between clastogenic activity and dose and that these biomarkers of oxidative stress can be influenced successfully by appropriate antioxidant treatment. With the authorization of the Armenian Ministry of Health, 30 workers were treated with antioxidants from Ginkgo biloba leaves. The extract EGb 761 containing flavonoids and terpenoids was given at a daily dose of 3 x 40 mg (Tanakan, IPSEN, France) during 2 months. The clastogenic activity of the plasma was reduced to control levels on the first day after the end of the treatment. A 1-year follow-up showed that the benefit of the treatment persisted for at least 7 months. One-third of the workers again had clastogenic factors after 1 year, demonstrating that the process which produced clastogenic factors continued. However, the observation that antioxidants do not have to be given continuously is encouraging for intervention trials on a large-scale basis. These appear justified, since clastogenic factors are thought to be risk factors for the development of late effects of irradiation.

Radiation-induced clastogenic factors: anticlastogenic effect of Ginkgo biloba extract.

Clastogenic factors (CFs) were first described in the blood of persons irradiated accidentally or for therapeutic reasons. Work of our laboratory has shown that they occur also under other circumstances, which are characterized by oxidative stress, and that CF-induced chromosome damage is regularly prevented by superoxide dismutase (SOD). Recently we found CFs in a high percentage of salvage personnel of the Chernobyl reactor accident. These liquidators represent a high-risk population and might benefit from cancer chemoprevention by antioxidants. SOD would have to be injected and is not appropriate for long-term prophylactic treatment. In the present study, we therefore evaluated the anticlastogenic effect of the Ginkgo biloba extract EGb 761, which is known for its superoxide scavenging properties. EGb 761 was tested on CF-treated blood cultures of healthy donors. After establishing the optimal protective EGb concentration, using CFs produced by irradiation of whole blood from healthy volunteers, the extract was tested on cultures exposed to CFs from plasma of persons irradiated as liquidators. The anticlastogenic effect could be confirmed for a final concentration of 100 micrograms/ml. In 12 consecutive experiments, CFs induced an average of 18.00 +/- 4.41 aberrations/100 cells. This was reduced to 7.33 +/- 3.08 in the parallel cultures receiving 100 micrograms/ml EGb 761 (p < .001). SOD was anticlastogenic in the same system at concentrations of 30 cytochrome C units/ml (approximately 10 micrograms/ml). Preliminary results obtained in a small series of liquidators showed regression or complete disappearance of CFs in the plasma after 2 months of treatment with EGb 761 (3 x 40 mg/d).

[Results of a follow-up of participants in the liquidation of the effects of the Chernobyl AES accident]. / Rezul'taty nabliudeniia za uchastnikami likvidatsii posledstvii avarii na Chernobyl'skoi AES.

The paper is concerned with the results of analysis of a clinico-laboratory study of persons (residents of Armenia) who took part in the elimination of the effects of the Chernobyl accident. Investigation of general morbidity revealed no correlation with exposure to ionizing radiation. The symptom complex of pathological changes included CNS functional disorders, a transition from the hypokinetic type of a heart response to exercise to the normokinetic one, lowered immune status and tissue peripheral blood flow, unmarked hematological and biochemical shifts, suggesting suppression of the body antioxidant system.

[Hemodynamics of pulmonary circulation in hypertension based on data from radionuclide studies]. / Gemodinamika malogo kruga krovoobrashcheniia pri gipertonicheskoi bolezni po dannym radionuklidnykh metodov issledovaniia.

The authors presented the results of a combined radionuclide study of the state of pulmonary hemodynamics in patients with essential hypertension. Altogether 132 patients were investigated. Radiocardiography, perfusion scintigraphy and a study of the regional pulmonary blood flow using radioactive Xe were conducted. An analysis of the results has shown that in some patients pulmonary hypertension develops even at early stages of the disease and is particularly marked in stages IIB-III. The mechanism of development of pulmonary hypertension depended at each stage on the interrelationship and time course of indices that characterized pulmonary circulation, and was of different nature. Hemodynamic disorder was manifested in blood mass redistribution from the lower lung regions to the upper ones, slowing down of rate parameters and a raise of pulmonary vascular resistance.

[Possible reverse development of myocardial hypertrophy and ischemia in patients with hypertension after short-term antihypertensive therapy]. / Vozmozhnosti obratnogo razvitiia gipertrofii i ishemii miokarda u bol'nykh gipertonicheskoi bolezn'iu pod vliianiem kratkovremennoi antigipertenzivnoi terapii.

The effects of short-term antihypertensive therapy were assessed using echo- and electrocardiography, in patients with first- or second-stage essential hypertension, with respect to possible reverse development of left-ventricular hypertrophy and myocardial ischemia. A reduction of left-ventricular hypertrophy was found to be possible, with regard to the hemodynamic type, in patients with mild or moderate essential hypertension provided their blood pressure was controlled effectively. Reverse development of electrocardiographic signs of myocardial ischemia (ST segment and T wave reaching their normal values) is possible through a decrease of arterial BP and a reduction of adrenergic effects on the heart.

[Radionuclide evaluation of the cardiovascular system in arterial hypertension]. / Radionuklidnaia otsenka serdechno-sosudistoi sistemy pri arterial'noi gipertonii.

Proceeding from a study of the nature of changes in hemodynamics during development of hypertensive disease (HD) at its different stages it was shown that hemodynamic changes in 42.1% of the patients with Stage I-IIA HD were of hypertensive type, in the patients with Stage IIB-III HD normal and hypokinetic types of the blood circulation prevailed. After bicycle ergometry exercise the reactivity of the cardiovascular system was revealed more completely. The transition of one hemodynamic type into another and its detection acquired a great importance. The definition of the types of hemodynamics at rest and of effort was very important in terms of adequate antihypertensive therapy and the prediction of a subsequent course of disease. The most complete information on function of the cardiovascular system and myocardial contractility can be obtained with the help of radio-angiocardiography and radionuclide ventriculography. However in the absence of a gamma-chamber radiocardiography can provide necessary information on function of the cardiovascular system in case it is used in one and the same patient over time using bicycle ergometry testing.

[Formulation of the composition of a polymyxin ointment using a mathematical experimental design]. / Razrabotka sostava polimiksinovoi mazi s primeniem matematicheskogo planirovaniia éksperimenta.

Mathematical design of the experiment permitted detection of the action of independent factors of the component composition on antibacterial activity and rheological properties of polymyxin ointment. Optimal compositions of polymyxin ointment based on polyethylene oxide emulsion were scientifically grounded and recommended for further experimental investigation on animals.

[Changes in cerebral circulation in arterial hypertension]. / Izmeneniia mozgovogo krovotoka pri arterial'noi gipertenzii.

The state of the cerebral blood flow in essential hypertension has been studied in relation to various clinical and hemodynamic parameters. The authors emphasize that the regulation of the cerebral blood flow depends to a great degree on the level of the systolic and pulse pressure as well as on the type of hemodynamics.

[Study of the stability of hybrid plasmids replicating in Saccharomyces cerevisiae due to DNA fragments from polyoma virus]. / Izuchenie stabil'nosti gibridnykh plazmid, replitsiruiushchikhsia v Saccharomyces cerevisiae za schet fragmentov DNK virusa poliomy.

Hybrid plasmid pSP97 carrying the entire genome of polyoma virus (PY), inserted into bacterial vector psV3, transforms yeast cells with the frequency 1 x 10(-2). Plasmid pSP97 is capable of autonomous replication in S. cerevisiae, while its structure remains unaltered, the stability of hybrid plasmid in transformants is 44%--100%. Plasmid pSP155 consisting of Ori-containing DNA segment from polyoma, pBR322 and yeast gene arg4, transforms yeast cells with the frequency 5 x 10(-3), the stability of plasmid in transformants is 23%--29%. Two types of plasmids were isolated from transformants: one was identical to SP155, while the another differed structurally and phenotypically from SP155. Plasmids pSP113 and pSP114, in addition to pBR322 and yeast gene arg4, contain a viral DNA segment that encodes genes from small and middle T-antigens. These plasmids transform yeast cells with low frequency (2 x 10(-4), 3 x 10(-5)), the stability of plasmids in yeast transformants is 100%. However, hybrid plasmids identical to pSP113 were isolated from transformants. Structural rearrangements have been observed in pSP114, which carries the arg4 gene in reversed orientation compared to pSP113.

[Mechanisms of action of nonachlazine]. / O nekotorykh mekhanizmakh deistviia nonakhlazina.

In animals with a ligated anterior descending left coronary artery, a single administration of nonaclazine (5 mg/kg bw) leads to a marked increase in the coronary blood flow and to an improvement in cardiovascular system function. Administration of nonachlazin for 7 days helps normalize the electrophysiological and hemodynamic characteristics and produces a beneficial effect on the myocardial blood flow and contractility. Interaction of nonaclazine with adrenergic receptors does not appear to have any decisive significance in the drug action mode.