[Accelerated aging as a risk of the education digitalization: possibilities for prevention.]

The work is devoted to the analysis of the education digitalization negative effects and the possibilities of their prevention consideration. The urgency of this problem in the modern conditions of combating the pandemic of the new coronavirus infection and moving a significant part of education and leisure to the virtual space is noted. Against the background of a deficit in physical activity and an increase in the information consumption duration, the participants in the experiment showed a significant increase in the frequency of mental and physical maladjustment symptoms occurrence, a decrease in performance indicators and a deterioration in the biological age parameters. The geroprotective effect of correcting the student lifestyle with an emphasis on information hygiene, optimizing sleep, rest, motor and nutritional regimen in terms of qualitative and quantitative indicators is shown.

Neurotrophins of the Fetal Brain and Placenta in Prenatal Hyperhomocysteinemia.

Prenatal hyperhomocysteinemia (PHHC) in pregnant rats was induced by chronic L-methionine loading, resulting in a significant increase in the L-homocysteine content both in the mothers' blood and blood and brain of fetuses. Significant decrease in the weight of the placenta, fetus, and fetal brain was detected by the morphometric studies on day 20 of pregnancy. PHHC also activated maternal immune system due to the increase in the content of proinflammatory interleukin-1ß in the rat blood and fetal part of the placenta. PHHC elevated the levels of the brain-derived neurotrophic factor (BDNF, 29 kDa) and nerve growth factor (NGF, 31 kDa) precursors in the placenta and the content of the BDNF isoform (29 kDa) in the fetal brain. The content of neuregulin 1 (NRG1) decreased in the placenta and increased in the fetal brain on day 20 of embryonic development. An increase in the caspase-3 activity was detected in the brains of fetuses subjected to PHHC. It was suggested that changes in the processing of neurotrophins induced by PPHC, oxidative stress, and inflammatory processes initiated by it, as well as apoptosis, play an important role in the development of brain disorders in the offspring.

Role of Caspases in the Cytotoxicity of NK-92 Cells in Various Models of Coculturing with Trophoblasts.

Studies of interactions between natural killer (NK) cells and trophoblasts and identification of conditions for the NK cells to perform their cytotoxic function are of fundamental and practical importance for understanding their role in the development of pathological processes and complications during pregnancy. In this study, we examined changes in the content of caspases and studied activation of these enzymes in Jeg-3 trophoblasts in various models of their coculturing with NK-92 cells and demonstrated the necessity of direct contact between these cell populations for the activation of caspase-8 and caspase-3 in the trophoblasts. Contact coculturing of the two cell lines resulted in the appearance of the cytotoxic protein granzyme B in Jeg-3 cells that was accompanied by a decrease in the content of this enzyme in NK-92 cells. Distant coculturing of NK-92 and Jeg-3 cells did not trigger initiator and effector caspases characteristic for the apoptosis development in Jeg-3 cells. The observed decrease in the content of procaspases in the trophoblasts may be associated with alternative non-apoptotic functions of these enzymes.

[Melatonin as a marker of the grade of cardiac disorders during cachexia development in oncological patients of different ages].

We have examined 103 patients at the age from 28 to 78 with the newly diagnosed oncological disease at stages II-IV before the beginning of anticancer treatment. The identification of the signs of the cachexia syndrome and its stage (pre-cachexia, cachexia) were carried out in the accordance with the CASCO criteria (2011) and taking into the account the age of the patients. The cardiovascular infringements were found to be comorbid to the oncological disease significantly more often in patients with signs of cachexia syndrome on the pre-cachexia stage and the total index of cardiovascular disorders in oncological patients increases with the severity of cachexia. In the course of the cachexia symptoms development the significant decline of melatonin excretion level (evaluated by the excretion of its main metabolite 6-sulfatoximelatonin level - aMT6s) in oncological patients was noted. The lowest changes in aMT6s levels were observed in patients older than 60 years, referred to the group of pre-cachexia, which may indicate the heterogeneity of the investigated groups as a result of the combination of manifestations of geriatric syndromes and cancer pathology. The possibility of false-positive diagnosis of pre-cachexia due to a combination of polygenic metabolic and age-related changes in elderly patients should be taken into account. Therefore, evaluation of melatonin excretion can be recommended as an additional marker in diagnosis and differential diagnosis of cachexia syndrome particularly in geriatric patients. A significant correlation between the occurrence and/or worsening of cardiac disease in cancer patients, cachexia symptoms and reduced level of aMT6s were revealed.

[Age-related changes in biogenic amine content and oxidative stress profile in the rat hypothalamus in hyperhomocysteinemia].

The article presents a detailed analysis of correlations between the content of a variety of biogenic amines in the hypothalamic structures responsible for the luteinizing hormone releasing hormone synthesis and secretion (the medial preoptic area and median eminence) and such independent factors as total L-homocysteine plasma level elevation induced by L-methionine loading and aging. Both a nature and a pattern of changes in oxidative stress profile were evaluated. It was shown that ageing, when compared to hyperhomocysteinemia, is a determining factor influencing biogenic amine content in the studied hypothalamic structures. Unlike antioxidant defense system profile, considerable changes in macromolecule oxidative modification were not found, which evidences a balanced activity of pro- and antioxidant systems in the hypothalamus.

[The influence of hyperhomocysteinemia on monoaminoergic systems of hypothalamus and hippocampus of female rats at aging].

The data presented have shown the different effect of hyperhomocysteinemia (induced by 0,12-0,15 mg of methionine loading per os during 30 days) on monoamines content in hypothalamus and hippocampus of young (6-7 month) and old (20-22 month) female rats. It has been established that the level of catecholamines (noradrenaline, dopamine), 5 oxitryptamine and 5 oxyindolacetic acid in hypothalamic areas responsible for synthesis and secretion of gonadoliberin (medial preoptic area and medial eminence with arcuate nuclei) is considerable less in old animals compared with young ones. These data are in agreement with the low content of gonadoliberin found by us in medial eminence with arcuate nuclei. It has been also shown the decreased level of monoamines level in hippocampus of old rats, which does not depend on methionine loading. However in hippocampus of young animals hyperhomocysteinemia induced a noticeable reduction of noradrenaline and 5 oxyindolacetic acid, which can lead to weakening of animal's cognitive function.

[Protective effect of melatonin and epithalon on hypothalamic regulation of reproduction in female rats in its premature aging model and on estrous cycles in senescent animals in various lighting regimes].

Potential neuroprotective effects of the pineal gland hormone melatonin and peptide preparation epitalon on estrous cycles and the central regulation of reproduction in female rats exposed to unfavourable environmental factors have been studied. Estrous cycles of young, mature and aging rats exposed to light pollution were described. The diurnal dynamics and daily mean content of biogenic amines in the hypothalamic areas responsible for gonadotropin-releasing hormone synthesis and secretion in animals of different age groups were investigated. An effect of a chemical factor on the noradrenergic system of the medial preoptic area and on the dopaminergic system of the median eminence with arcuate nuclei of the hypothalamus was studied in premature aging of reproduction model. Administration of the pineal gland peptide melatonin and peptide preparation epitalon was shown to be able to correct a number of impairments of the hypothalamic-pituitary-gonadal axis that can be observed, when the experimental animals were exposed to permanent artificial lighting and a neurotoxic xenobiotic 1,2-dimethylhydrazine. The data obtained testify to an important role of the pineal gland in the circadian signal formation needed for gonadotropin-releasing hormone in order to exert its preovulatory peak secretion and to the protective effect of melatonin and epitalon, which are able to reduce unfavourable environmental influences on reproduction of young and aging female rats.

Maternal Hyperhomocysteinemia Induces Neuroinflammation and Neuronal Death in the Rat Offspring Cortex.

Maternal hyperhomocysteinemia is one of the common complications of pregnancy that causes offspring cognitive deficits during postnatal development. In the present work, we evaluated the effect of prenatal hyperhomocysteinemia on structural and ultrastructural organization, neuronal and glial cell number, apoptosis (caspase-3 content and activity), inflammatory markers (tumor necrosis factor-α, interleukin-6, and interleukin-1ß), and p38 mitogen-activated protein kinase (p38 MAPK) phosphorylation in the offspring brain cortex in early ontogenesis. Wistar female rats received methionine (0.6 g/kg body weight) by oral administration during pregnancy. Histological and biochemical analyses of 5- and 20-day-old pups' cortical tissue were performed. Lysosome accumulation and other neurodegenerative changes in neurons of animals with impaired embryonic development were investigated by electron microscopy. Neuronal staining (anti-NeuN) revealed a reduction in neuronal number, accompanied by increasing of caspase-3 active form protein level and activity. Maternal hyperhomocysteinemia also elevated the number of astroglial and microglial cells and increased expression of interleukin-1ß and p38 MAPK phosphorylation, which indicates the development of neuroinflammatory processes.

Plasma lipid peroxidation and progression of disability in multiple sclerosis.

Oxidative stress has been implicated in the pathophysiology of multiple sclerosis (MS), but its relation to disease progression is uncertain. To evaluate the relationship of plasma lipid peroxidation with progression of disability in MS, we measured blood plasma fluorescent lipid peroxidation products (PFLPP) levels in 23 patients with RRMS with a benign course, 32 with secondary progressive MS, 24 with primary progressive MS and 30 healthy controls. None of the patients had a relapse within the previous 3 months. Progression of disability was evaluated during a follow-up period of 5 years by the Expanded Disability Status Scale (EDSS) and the Multiple Sclerosis Severity Score (MSSS). We found plasma PFLPP levels elevated in patients with MS compared with controls (P < 0.0001), but there was no difference between patients with a benign and progressive disease course. There was no correlation between PFLPP levels and worsening of disability on the EDSS and speed of progression on the MSSS. Our data suggest that there is no relation between the degree of oxidative stress in plasma and progression of disability in MS.

Antioxidant properties of geroprotective peptides of the pineal gland.

It was shown that peptide preparations from the pineal gland (epithalamin and epitalon) possess antioxidant properties exceeding in some cases the effects of the well-known scavenger of reactive oxygen species (ROS), the melatonin, which is also produced by the pineal gland. The methods used in our experiments in old rats included determination of total antioxidant and antiradical activities, as well as those of antioxidant enzymes (superoxide dismutase=SOD, glutathione peroxidase, glutathione-S-transferase, etc.) in blood serum, liver and brain. It has been revealed that epithalamin (polipeptide preparation from bovine brain) and its active fragment, epitalon (Ala-Glu-Asp-Gly) along with their ability to stimulate melatonin production, have an antioxidant mechanism that is quite different from the action of melatonin. Epithalamin can be more beneficial than melatonin because the former not only produces direct antioxidant effects, but also is able to stimulate the expression of SOD, ceruloplasmin and other antioxidant enzymes. The possibility of oxidation chains by their interaction with different ROS by means of binding of transition metals (Fe(2+)) cannot also be excluded. Thus, the results of our experiments testify that the pineal gland peptides enhance the antioxidant defense system, which can contribute to their geroprotective properties.

Cooling garment treatment in MS: clinical improvement and decrease in leukocyte NO production.

Ten heat-sensitive patients with MS were randomly allocated in a cross-over study to wear a cooling garment for 60 minutes at 7 degrees C (active cooling) and 26 degrees C (sham cooling). In contrast to sham cooling, active cooling improved fatigue and postural stability with eyes closed and muscle strength. There was no decrease in tympanic temperature, but active cooling was associated with a 41% decrease in mean leukocyte nitric oxide (NO) production (p = 0.004). This effect on NO could be relevant because it blocks conduction in demyelinated axons.

Melatonin increases both life span and tumor incidence in female CBA mice.

From the age of 6 months until their natural deaths, female CBA mice were given melatonin with their drinking water (20 mg/l) for 5 consecutive days every month. Intact mice served as controls. The results of this study show that the consumption of melatonin did not significantly influence food consumption, but it did increase the body weight of older mice; it did not influence physical strength or the presence of fatigue; it decreased locomotor activity and body temperature; it inhibited free radical processes in serum, brain, and liver; it slowed down the age-related switching-off of estrous function; and it increased life span. However, we also found that treatment with the used dose of melatonin increased spontaneous tumor incidence in mice. For this reason, we concluded that it would be premature to recommend melatonin as a geroprotector for long-term use.

Functional and biochemical criteria for investigation of brain development disorders.

Functional state and creatine kinase (CK) activity in the amniotic fluid and blood of anencephalic fetuses was studied in the second trimester of pregnancy with the following pathomorphological investigation of the state of their CNS to reveal possible markers of development disorders. The extent of neurological disorders in newborn infants was retrospectively compared with data from functional studies of components of a biophysical profile (motor-cardiac reflex, heart rhythm oscillations, respiratory movements) and with CK activity in the amniotic fluid and blood of fetuses with hemolytic disease and fetuses of diabetic mothers and normal mothers in the third trimester of pregnancy. The results revealed informative indices of fetal CNS developmental disorders in the prenatal period that are of importance for predicting a prognosis of the extent of neurological disorders in newborn infants. These results will allow the establishment of criteria for evaluation of fetuses to reveal possible disorders in the formation of the CNS.

Effects of pineal peptide preparation Epithalamin on free-radical processes in humans and animals.

OBJECTIVES: The review on our own data on the effect of the pineal peptide preparation Epithalamin on free radical processes in rodents and humans is presented in this paper. RESULTS: The activity of Cu, Zn-superoxide dismutase (SOD) was found decreased in the brain of aged rats (30 months old) by 46.8% as compared to young animals. Concentration of Schiff's bases in the brain also went down with age (by 13.6%), while the level of dien conjugates (DC) and protein peroxidation (PPO) remained unchanged. General antioxidation activity (AOA) in the brain also remained stable with age. The liver of aged rats showed significant increase of Schiff's bases (by 27.1%) and PPO products (by 109.2%) and considerable decrease of SOD activity. The level of DC and general AOA in the liver remained unchanged with age. Considerable elevation of protein and lipid peroxidation products contents was registered in the blood serum of aged rats. At the same time, general AOA and SOD activity remarkably decreased. The results obtained evidence from both significant age-related alterations in the activity of free radical processes in animal organism and organic peculiarities of their dynamics. Application of peptide drug epithalamin suppressed significantly the intensity of peroxide chemoluminescence in the blood serum (2.8-fold) and lipid peroxide oxidation (LPO) expressed in the considerably decreased DC contents (4,1-fold). The contents of Schiff's bases showed only a tendency towards decrease (by 14.4%, p > 0.05) and PPO level remained unchanged. Epithalamin administration was followed by considerable (by 36.6%, p < 0.01) increase of general AOA and increased SOD activity (by 19.7%) in males. Epithalamin decreased significantly the contents of conjugated hydroperoxides and ketodienes in tissues of D.melanogaster females, increased catalase activity in drosophila males and females, and increased SOD activity in males of D.melanogaster by 41%. Humans reveal significant age-related decrease of antioxidation defence indices. CONCLUSION: Epithalamin administration to patients with age-related pathology eliminates imbalance in prooxidation and antioxidation systems.

Disturbances of diurnal rhythms of biogenic amines contents in hypothalamic nuclei as an evidence of neurotropic effects of enterotropic carcinogen 1,2-dimethylhydrazine.

OBJECTIVES: Our data on the contents of norepinephrine (NE), dopamine (DA) and the metabolite of serotonin 5-hydroxyindoleacetic acid (5-HIAA) measured in the suprachiasmatic nuclei (SCN), preoptic area (PA) and median eminence (ME) of hypothalamus of rats after single subcutaneous injection of 1,2-dimethylhydrazine (DMH) as well as the effect of this carcinogen on formation of reactive oxygen species (ROS) in the PA are presented in this paper. RESULTS: Diurnal changes of DA in all studied brain structures and of NE in the PA have been observed in the control group. Their morning levels were higher than evening ones. Rhythms of 5-HIAA in the SCN and diurnal changes of ROS formation have been shown to have contrary changes in control. Both the morning (11 a.m.) and evening (11 p.m.) subcutaneous administration of DMH at the dose of 21 mg/kg of body weight resulted in changes of all rhythms observed in control. In some cases a phase shift was found, in others the rhythms of neurotransmitters and ROS formation disappeared entirely. CONCLUSION: The data obtained confirm the idea of dopaminergic and serotoninergic systems taking part in mechanisms of a response of the hypothalamic nuclei to non-photic stimuli. It is suggested that the effect of DMH on the content and diurnal rhythms of neurotransmitters in the hypothalamic structures under study is due to its affecting activities of the enzymes of biogenic amines synthesis, synaptic transmission, melatonin synthesis and secretion rhythms. The change in ROS formation that is caused by administration of DMH is likely to be due to a disturbance of diurnal rhythms of neurotransmitters that are one of the sources of formation of free radicals in the brain.

Plasma homocysteine levels in multiple sclerosis.

BACKGROUND: There is evidence that homocysteine contributes to various neurodegenerative disorders, and elevated plasma homocysteine levels have been observed in patients with multiple sclerosis (MS). OBJECTIVE: To investigate if and why plasma homocysteine levels are increased in MS, and whether they play a role in the disease course. METHODS: We compared plasma levels of homocysteine in 88 patients with MS and 57 healthy controls. In the MS group, 28 had a benign course, 37 were secondary progressive, and 23 primary progressive. To explore the underlying mechanisms, we measured serum levels of vitamins B6 and B12, folate, interleukin (IL)-12, tumour necrosis factor (TNF)-alpha, leukocyte nitric oxide production, and plasma diene conjugate levels (measure of oxidative stress). RESULTS: Mean (SD) plasma homocysteine concentration was higher in patients (13.8 (4.9) micromol/l) than in controls (10.1 (2.5) micromol/l; p<0.0001). However, there were no significant differences in homocysteine levels between the three clinical subgroups of MS. Serum concentrations of vitamin B6, vitamin B12, and folate were not different between patients with MS and controls. In the MS group, there were no correlations between plasma homocysteine levels and the serum concentrations of IL-12 or TNF-alpha, leukocyte nitric oxide production, or plasma diene conjugate levels. CONCLUSIONS: Elevated plasma homocysteine occurs in both benign and progressive disease courses of MS, and seems unrelated to immune activation, oxidative stress, or a deficiency in vitamin B6, vitamin B12, or folate.

Low leucocyte myeloperoxidase activity in patients with multiple sclerosis.

The gene for myeloperoxidase (MPO) has been implicated in multiple sclerosis (MS). By measuring H(2)O(2) dependent oxidation of 3,3'5,5'-tetramethylbenzidine with spectrophotometry the authors investigated MPO activity in peripheral blood leucocytes from 42 patients with MS (12 with secondary progressive MS, 17 with primary progressive MS, and 13 with relapsing remitting benign MS) and 32 healthy controls. Leucocyte MPO activity was significantly lower in patients with benign MS (mean (SEM) 0.086 (0.029) U/mg protein; p<0.01), secondary progressive MS (0.038 (0.009) U/mg protein; p<0.001), and primary progressive MS (0.057 (0.016) U/mg protein; p<0.001) compared with healthy controls (0.322 (0.053) U/mg protein). These data suggest that low MPO, which may be genetically determined, plays a part in MS pathogenesis.