Effects of Melatonin on Morphological and Functional Parameters of the Pineal Gland and Organs of Immune System in Rats During Natural Light Cycle and Constant Illumination.

We studied the response of the pineal gland and organs of the immune system to melatonin treatment in Wistar rats kept under conditions of abnormal illumination regimen. The animals were kept under natural light regimen or continuous illumination for 14 days and then received daily injections of melatonin (once a day in the evening) for 7 days. Administration of melatonin to rats kept at natural light cycle was followed by a decrease in percent ratio of CD4+8+ splenocytes and CD4-8+ thymocytes. In 24-h light with the following melatonin injections were accompanied by an increase in percent rate and absolute amount of CD4+8+ cells in the spleen, and a decrease in percent rate of CD11b/c and CD4-8+ splenocytes. In the thymus amount of CD4-8+ cells increased, and absolute number of CD4+25+ cells reduced. Melatonin significantly decreased lipofuscin concentration in the pineal gland during continuous light. Direction and intensity of effects of melatonin on parameters of cell immunity and state of the pineal gland were different under normal and continuous light conditions. It should be taken into account during using of this hormone for correction of immune and endocrine impairments developing during change in light/dark rhythm.

[BEHAVIOR, MEMORY AND IMMUNOLOGICAL STATUS IN MICE MODEL OF DESYNCHRONOSIS].

Interstrain differences in behavior and parameters of the immune system of CBA and C57BL/6 mice with round the clock coverage (KO) were investigated. Open field, light/dark, acoustic startle response, forced swimming, elevated plus-maze, passive avoidance were used for measuring emotional behavior and memory. The number of lymphocyte subpopulations CD3+, CD4+8-, CD4-8+, CD4+8+, CD19+, CD3+hi spleen and thymus, the ratio of cells in different phases of the cell cycle was determined by flow cytometry. C57BL/6J mice strictly increased anxiety in response to the KO compared to CBA mice. Moreover, KO-treated C57BL/6J mice impaired the passive avoidance learning. We found that KO evoked significant changes in the cellular composition of the thymus and decrease of thymocytes proliferation in C57BL/6J mice. In opposite KO-treated CBA mice showed change of splenic cellular structure with increased % CD19+ cells and the proliferation of splenocytes. Our study demonstrated genotype-dependent reactions of the nervous and immune systems in response chronic constant light.

[INTERSTRAIN AND SEASONAL DIFFERENCES IN THE RESPONSE OF BLOOD AND ORGANS OF THE IMMUNE SYSTEM TO ROUND-THE-CLOCK ILLUMINATION OF CBA AND C57/BL6 MICE].

The study of the immune system of mice of CBA (n=7) and C57BL/6 (n=7) strains was performed during a 12-hour photoperiod (12:12) and round-the-clock illumination (RI) in December and March. The numbers of CD3+, CD4+8-, CD4-8-, CD4+8+, CD19+, CD3+hi lymphocyte subpopulations in the thymus and spleen, as well as the proliferative activity of thymocytes and splenocytes were measured by flow cytometry. It was found that the most pronounced. interstrain differences in the cellular composition of the thymus were observed in March, while those in the cellular composition of the spleen were detected in December. Overall, in C57BL/6 mice as compared with CBA mice, the number and proliferative activity of the cells of lymphoid organs was increased. In December, the influence of RI on the cellular composition of the thymus was more pronounced in C57BL/6 mice, while the effect on cellular composition of the spleen was greater in CBA nice. In March, after exposure to RI, a number of CD3+, CD19+ and CD4+8-splenocytes was increased in CBA mice, while it was decreased in C57BL/6 mice. In C57BL/6 mice, after exposure to RI, the proliferative activity of thymocytes decreased in winter and increased in spring . Interstrain and seasonal differences in the cellular composition of lymphoid organs in CBA and C57BL/6 mice, with a photoperiod of 12:12 and RI should be taken into account in experimental work with aninials of different genotypes in different seasons of the year.

Chrono- and Immunocorrection of Inflammatory Disorders of Internal Reproductive Organs in Women of Reproductive Age.

We compared the effectiveness of immunomodulators used in the treatment of patients with chronic salpingitis and oophoritis with or without changes in succinate dehydrogenase (SDH) activity in blood lymphocytes at incubation with the drug. Diurnal variations in individual reaction of SDH in blood lymphocytes to thymalin or ridostin were revealed. In the groups of women receiving ridostin or thymalin during the reaction of lymphocyte SDH to it, improvement of clinical laboratory and immunological parameters was observed in the majority of the patients and no effect was found in a lesser group of patients than in the groups treated with drugs during the absence of lymphocyte SDH reaction thereto. The timing of the presence of SDH reaction to drugs in the immunocompetent cells makes it possible to set the optimal daily regime of their application and to select a drug that would be most effective in each particular case.

[THE CHANGES OF THE INTERRELATIONS OF THE PINEAL GLAND AND THE ORGANS OF THE IMMUNE SYSTEM IN RATS IN RESPONSE TO MELATONIN ADMINISTRATION IN LIGHT REGIME DISTURBANCES].

In this work the correlation analysis was applied to detect the integrated response of the pineal gland (PG) and immunocompetent organs of male Wistar rats in response to administration of melatonin (MT) in light regime disturbances. Animals were kept for 14 days under natural or continuous light (CL). Then for 7 days they received the injections of either 0.9% solution of sodium chloride or MT, after which the rats were decapitated and the mass of their body, PG, thymus and spleen was determined. The lymphocyte subpopulations of the thymus and spleen were studied by flow cytometry. The amount of lipofuscin in PG was assessed by the intensity of autofluorescence in organ frozen sections in 560-600 nm wavelength range. It was found that under the influence of MT, the number of intraorgan correlations in the immune system increased, regardless of the light regime. In animals on CL treated with MT, the number of interorgan connections was reduced, while negative correlations appeared between PG lipofuscin content and cellular composition of the spleen. The synchronizing and adaptogenic effects of MT were most pronounced under conditions of CL.

[Interrelations of pineal gland morpho-functional indices and immune system organs in rats exposed to natural illumination regime and continuous illumination].

The objective of this investigation was to determine the complex response of the pineal gland (PG) and of the organs of the immune system in Wistar rats in response to a violation of the illumination regime in the experiment. Animals were kept under natural light regime and continuous illumination for 14 days. After that rats were sacrificed and the mass of the body, PG, gonads, thymus and spleen was measured. Thymus and spleen cell subpopulations were determined by flow cytometry. The lipofuscin content in PG was determined by measuring an autofluorescence intensity in frozen tissue sections in the wavelength range of 505-545 nm using a confocal laser scanning microscope LSM 510 META (Carl Zeiss). The correlation analysis showed an increase in the amount and the change of sign and direction of relations between the indices of the state of PG and the immune system. This indicates the up-regulation of the intensity of inter-system relationships and the change of migration and differentiation vector of immunocompetent cells.

The influence of experimental desynchronosis on the morphofunctional characteristics of mouse immune system.

The aim of this study is to investigate the influence of experimental desynchronosis on the immune system and estimate benzo[a]pyrene (BP) influence on the immune reactivity of mice under the condition of desyncronosis (DS) in comparison with intact organisms. Mice (CBA X C57BL)F1 were kept under constant light during two weeks and natural alternation of darkness and light (control group). Animals of the two groups received benzo[a]pyrene solution in olive oil. The existence of diurnal variation of cell populations of lymphoid organs and blood, humoral immune response to SRBC were revealed. Changes of diurnal dynamics of these parameters and decrease of humoral immune response to SRBC have been observed in animals kept under constant light in comparison with animals kept under standard light conditions. It is likely to indicate the development of internal DS. BP influenced the cellular composition and immune response of intact and DS animals in a different way. So, the changes of light regime lead to development of the internal DS of immune system that influenced its functional capacity and sensitivity to damaging effect of chemical ecological factor.

Circadian variations in immune values and serum melatonin in asthmatics.

Circadian variations in the immune status and serum melatonin were studied in asthmatics during exacerbation stage before and after treatment. Deviations from the normal (donor) immunogram values at 9.00 and 21.00 and decreased correlations between immune values and blood melatonin level were detected. The correlations of immune values between each other and with melatonin over the circadian cycle increased after treatment.

Circadian dynamics of cell composition of the thymus and lymph nodes in mice normally, under conditions of permanent illumination, and after melatonin injection.

The effect of melatonin on disturbed circadian variations in the lymphocyte subpopulation composition of the thymus and inguinal lymph nodes was studied in CBA mice exposed to constant illumination for 14 days. The desynchronizing effect of permanent illumination on the thymus consisted in disappearance of circadian variations in the total number of thymocytes, absolute count of thymocytes, absolute counts of CD8(+) and CD4(+) cells, and in inversion of changes in the absolute counts of CD4(+)8(+) cells from 15.00 to 20.00. In lymph nodes circadian variations in the percentage of CD4(+)+ lymphocytes disappeared, while absolute counts of CD4(+)8(+) and CD8(+) cells changed from 15.00 to 20.00. Melatonin restored circadian dynamics of some parameters mainly in the thymus.

Circadian variations of melatonin concentration in saliva and blood content of immunocompetent cells in healthy individuals.

Salivary content of melatonin and parameters of the immune status were studied in young healthy individuals. Morning and evening levels of melatonin showed different correlations with some immunity parameters. It was assumed that the degree and type of correlation between the immune system and melatonin depend on the phase of circadian cycle, which should be considered during evaluation of immunoendocrine status.

Effects of amitriptyline on diurnal variations of oxidation-reduction enzyme activities in rat lymphocytes during experimental desynchronosis.

We studied the effects of amitriptyline on diurnal variations of oxidative-reduction enzyme activities (succinate dehydrogenase, lactate dehydrogenase, and NADPH diaphorase) in rat peripheral blood lymphocytes during experimental desynchronosis. Desynchronosis was induced by constant light exposure for 14 days and manifested in a morning shift of maximum lactate dehydrogenase activity and elevated morning NADPH diaphorase activity. Amitriptyline normalized morning lactate dehydrogenase activity and diurnal variations in NADPH diaphorase activity.

Effect of amitriptyline on daily variations in cell composition of immune organs in rats with experimental desynchronosis.

We studied the effects of amitriptyline (preparation stimulating melatonin synthesis in the pineal gland) on daily variations of cell composition in immune organs of Wistar rats with experimental desynchronosis. Amitriptyline administered in the evening restored the daily dynamics of the number of thymus cells.

[Chronobiology of immune system]. / Khronobiologiia immunoi sistemy.

The biological rhythmological programme of the immune system is a constituent of the body's common biological rhythmological programme. Its pattern seems to be genetically determined and reflects the functional status of the system. The chronobiological mechanisms responsible for the regulation of immune functions lie in the presence of certain phasic interrelations between the biological rhythms of the synthesis and production of regulatory agents on the one hand, and those of the receptor system and metabolic potential of immunocompetent cells on the other. The facts given in the paper may be a basis for a chronobiological approach to better understanding the mechanisms of the physiology and pathology of the immune system. The medical significance of study of the structural and temporal pattern of the immune system consists in the development of new techniques for diagnosis, prognosis, therapy, and assessment of risk factors in immunopathological conditions.

[Analysis of postoperative mortality in acute cholecystitis]. / Analiz posleoperatsionnoi letal'nosti pri ostrom kholetsistite.

The analysis of lethal outcomes in 108 (3.66%) of the 2974 patients operated on for acute cholecystitis was carried out. In 40.4% of the patients, mainly the elderly and senile, a death was caused by acute hepatorenal failure.