[Prevention of deteriorations of blood biochemical indices in experimental stress in rats].

Results of the research of the impact of extract from the byproducts of guelder-rose, containing a complexflavonoides (65% of dry weight), in the conditions of experimental a stress (vertical fixing of rats by a dorsal cervicalfold for 22 o'clock) are presented. The impact of a stress was shown to be followed by the gain in mass of adrenal glands by 42%. In blood serum there were noted marked hypertriglyceridemia, hypercholesterolemia, increased superoxide dismutase activity, decline in the number of reduced glutathione and anti-radical activity, the gain in lisofractions of phospholipids, decrease of phosphatidylcholine, phosphatidylethanolamine, cholesterol esters. Administration of the extract from the byproducts of guelder rose crushing promoted the normalization of indices of mass of adrenal glands and lipid metabolism in blood serum, was more effective, than a reference stress protector "Extract eleuterokokka®". The introduction of eleuterococcus was followed by the persistent both elevated level of cholesterol, free fatty acids, lisofraction of phospholipidsand low level offatty acids esters, cholesterol esters and a diphosphatidilglicerin. Byproducts of guelder-rose were shown to represent a perspective view of raw materials for the producing of stress protective preparations.

[Emotional stress as a clinical model to study the pathogenesis of the initial phase of the general adaptation syndrome].

INTRODUCTION: General adaptation syndrome (GAS), the basis of the development of which is stress phenomenon, is an essential component of the pathogenesis of many diseases and syndromes. However, the patho genesis of GAS hitherto is considered exclusively from the endocrinological viewpoint. This relates primarily to the initial phase of the GAS, a clinical model for the study of which may be psycho-emotional stress (PES), which we studied using three groups of volunteers. METHODS: The first one consists of 25 students who were waiting for unaccustomed physical activity (17 men) and play debut on the stage (8 women). The second group consists of 48 children (2-14 years) who expected for "planned" surgery. The third group of volunteers is made up of 80 students (41 women and 39 men) during the first exam. The concentration of cortisol, endotoxin (ET), the activity of antiendotoxin immunity (AEI) and the haemostatic system parameters were determined in the blood serum of volunteers in various combinations. RESULTS: We found laboratory evidence for PES at 92% of students of the first group, 58% of children of the second one and in 21% of students of the third group of volunteers (mostly women). The concentration of ET increased at 13 (52%) volunteers of the first group with a significant increase of average indicators in the whole group (from 0.84 ± 0.06 to 1.19 ± 0.04 EU/ml). At children of the second group, the average concentration of ET increased even more significantly (from 0.42 ± 0.02 to 1.63 ± 0.11 EU/ml), which was accompanied by the activation of the hemostasis system. A degree of the activation was directly dependent on the level of ET in the general circulation and on an activity of AEI. Examination stress in the third group of volunteers is accompanied by activation of plasma hemostasis (increased initial thrombosis rate and reduced the time it starts, lag-period) in 26% of female students and 15% of male students. CONCLUSION: We suggest that it is possible to use the PES as a clinical model for studying the initial phase of the GAS, examine the role of excess of intestinal ET in the general blood circulation (endotoxin aggression) in the induction of systemic inflammation, which is very likely participated in the initiation of the GAS.

[Influence of enzymatic hydrolyzate of mussel meat on growth and some indicators of general adaptation syndrome in rats].

The impact of the 15-day consumption of enzymatic hydrolyzate of the mussels meat as a part of semi-synthetic diet on some stress biomarkers and apoptosis activity in various organs of growing male Wistar rats have been studied. Enzymatic hydrolyzate of the mussels meat (EMM) was obtained in pilot conditions using the enzyme preparation "Protozim". The animals of control group 1 (n = 8 with initial body weight of 179.4 ± 5.9 g) and experimental group 2 (n = 8, 176.3 ± 4.5 g) received a semi synthetic diet; the animals of the experimental group 3 (n = 8, 177.6 ± 4.0 g) received the same semi synthetic diet in which 50% of the casein was replaced by the peptides of EMM. On the penult day of the experiment animals of groups 2 and 3 were subjected to stress exposure by electric current on their paws (current 0.4 mA for 8 seconds) and were placed in metabolic cages for the collection of daily urine. At the 15th day of the study, all control and test animals were killed by decapitation under ether anesthesia and necropsied. The content of prostaglandin E2 and ß-endorphin in blood plasma was determined by ELISA test. The concentration of urine corticosterone was measured by HPLC. DNA damage and percentage of apoptotic cells (apoptotic index) were calculated in thymus by single-cell gel electrophoresis assay (Comet assay). The relative body weight increase of animals treated with EMM was significantly (p < 0.05) higher (68.2 ± 3.0%) than those in animals of groups 1 and 2 (57.2 ± 4.0 and 59.7 ± 2.8%, respectively). The apoptotic index in thymus cells of tested groups of animals (2 and 3) was significantly (p < 0.05) higher (1.13 ± 0.09 and 1.09 ± 0.01%) compared to intact animals of control group (1.04 ± 0.01%). Determination of ß-endorphin and prostaglandin E2 levels did not shown any significant differences between the groups. Significantly (p < 0.05) lower concentrations of corticosterone was found in the daily urine of stressed animals from group 3 (452 ± 78 ng/ml), treated with EMM, compared to stressed animals of group 2 that received a casein diet (834 ± 167 ng/ml). It has been shown that consumption of EMM with a high content of short and medium peptides has an impact on effectiveness of body weight gain of growing laboratory animals, and restrict the increase of corticosterone level in rats blood, which is typical for general adaptation syndrome.

[Characteristics of oxidative stress in mental maladaptation].

Changes in the balance of pro and antioxidant systems were studied in persons in state of mental maladaptation, developed under the influence of emotional stress. Activation of lipid peroxidation has been revealed associated with increase of amount of malondialdehyde in erythrocytes and blood serum in persons surveyed. Activity of catalase and glutathione peroxidase in erythrocytes in persons in state of mental stress was increased and glutathione preductase, glutathione-S-transferase and glucose-6-phosphate dehydrogenase has been reliably reduced as compared with group of healthy people. Comparative chemiluminiscent analysis of common antioxidant properties of serum of blood of studied groups has also revealed decrease of antioxidant properties of blood under influence of mental stress.

[Stress-protective activity of the CH3CO-Lys-Lys-Arg-Arg-NH2 synthetic peptide (protektin)].

The CH3CO-Lys-Lys-Arg-Arg-NH2 peptide (the author has named it protectin) was synthesized, and its activity was studied during different stress actions. Protectin was found to normalize the content of corticosterone and adrenalin in adrenal glands and blood after its intranasal administration to rats one day before a cold or heat shock, or hypobaric hypoxia at doses of 1-10 microg/animal and after its intravenous administration just after acute hemorrhage at doses of 0.5-2 microg/animal. The intranasal administration of protectin at doses of 1-10 microg/rat one day before the heat or cold shock was also shown to prevent a change in the content of free histamine and the activity of diamine oxidase in myocardium, which was induced by the dramatic change in the activity of the enzyme after the temperature actions.

Endocrine stress response in jugular-vein cannulated rats upon multiple exposure to either diethyl-ether, halothane/O2/N2O or sham anaesthesia.

The main objective of this study was to assess the endocrine stress response to multiple anaesthesia followed by sham anaesthesia in order to detect any memory effects. For this purpose, jugular-vein cannulated rats were subjected to either sham, diethyl-ether or halothane/O2/N2O anaesthesia, and their plasma ACTH, corticosterone, glucose, adrenaline and noradrenaline levels measured. The study had three separate experiments, each consisting of a control and treatment group. In two experiments, the rats were exposed to high or low concentrations (40-15%) of diethyl ether, using either a jar containing cotton soaked in diethyl ether or a vaporizer. In the third experiment, rats were exposed to halothane/O2/N2O. Control animals underwent sham anaesthesia. Blood samples were taken 6 min before and at 5, 15 and 55 min after starting the exposure (t = 0 min). For each variable, the dt5 (level at t = 5 min minus that at t = -6 min) and the cumulative levels over the one-hour period as determined by the area under the curve (AUC) were calculated. Further, the peak levels (Cmax) were determined. The mean time needed to induce anaesthesia was 68, 121 and 55 s for exposure to high and low concentrations of diethyl ether and to halothane/O2/N2O, respectively. Increased noradrenaline and adrenaline dt5 levels were observed only after the first exposure to the high concentration of diethyl ether. Multiple anaesthesia sessions using either diethyl ether or halothane/O2/N2O did not clearly influence adrenaline and noradrenaline levels. Diethyl ether induced a sharp rise in plasma ACTH and glucose levels, irrespective of the concentration used. The response of the ACTH and glucose was similar for single and multiple exposure. An increased response of ACTH, corticosterone and glucose to sham anaesthesia following multiple induction of anaesthesia was observed for the high concentration of diethyl ether only. Halothane/O2/N2O raised plasma glucose without differences between single and multiple anaesthesia sessions. Upon sham anaesthesia following multiple exposures to halothane/O2/N2O, glucose levels were significantly increased. This study indicates that repeated anaesthesia in rats can elicit an increased stress response during subsequent handling and change of environment.

[The characteristics of the development of an adaptation syndrome in severe gestosis]. / Osobennosti formirovaniia adaptatsionnogo sindroma pri tiazhelom gestoze.

Basic metabolic pathways were studied of formation of the adaptive syndrome in the organism of patients with grave gestoses: glycolysis, gluconeogenesis, and pentosephosphate pathway of production of nicotinamide coenzymes. It has been found out that a stressful character of reconstruction of metabolic homeostasis tends to change the processes of glycolysis and gluconeogenesis that had come to be formed by evolution. This warrants further study, its purpose being a specific correction of intracellular metabolism and prevention of complications. Ozonohemo- and antioxidant therapy in a complex of intensive treatment measures for patients with severe gestoses make for stimulation of pentosephosphate pathway and glycolysis.

[Morphofunctional changes in the lysosomal apparatus of the peripheral blood neutrophilic leukocytes in aseptic inflammation]. / Morfo-funktsional'ni zminy lizosomal'noho aparatu neitrofil'nykh leikotsytiv peryferychnoï krovi pry aseptychnomu zapalenni.

The investigation was carried out on 47 adult rabbits. The reaction of lysosomal apparatus of neutrophilic leucocytes of peripheral blood was investigated under conditions of aseptic inflammation, caused by intramuscular injection of formaline. The conclusion is made that neutrophilic leucocytosis and a decrease of lysosomes in neutrophils under conditions of inflammation are nonspecific components of a general adaptation syndrome and result from the vivid granulocytopoesis and leucergy process.

[Neuropeptides in atopic dermatitis in children]. / Neiropeptidy pri atopicheskom dermatite u detei.

Radioimmunoassay was used to measure the blood plasma content of endogenous opioid peptides (beta-andorphine, methionin- and leucine-enkephalins), R substance, calcium-regulating hormones (parathyroid hormone and carcitonin), ionized calcium and cortisol in 152 children aged 6 months to 12 years with atopic dermatitis. The data obtained were compared to those obtained in healthy children. The stress-activating and stress-limiting systems were established to be activated in all the patients. It is concluded that the intensity of the adaptation compensatory process depends on the clinical form, disease standing, and spreading of skin impairment.

[The characteristics of a differential approach to therapy in the stress syndrome taking into account the stages of the process]. / Osobennosti differentsirovannogo podkhoda k terapii stress-sindroma s uchetom stadiinosti protsessa.

Hereby is stated the data of the necessity of the differential approach to the therapy of stress-syndrome taking into consideration the stages of the process. Pharmacological corrections of the oscillations of the antioxidation system of protection during stress is carried out in the stage of quick adaptation and its conversion into long acting, i.e. into the period, when oscillations of biochemical indexes of the antiradical system of protection are compensated. In this an important role is played by using psychotropic substances, which have a quality of the antiradical protection.

[The dependence of the formation of stress stomach ulcers on the function of the hypothalamo-hypophyseal-adrenal cortical system]. / Zavisimost' obrazovaniia stressornykh iazv zheludka ot sostoianiia gipotalamo-gipofizarno-adrenokortikal'noi sistemy.

The effect of supraphysiological doses of corticosteroids on mucosal ulceration of stomach was studied in rats. Cortisol (30 mg/100 g) blocked the PACS. During the PACS block, ulcerogenic properties of stressor increased. This effect was reduced by subsequent corticosterone replacement therapy. The new concept of supraphysiological doses of corticosteroids effect is discussed. The stomach ulceration seems to result from the corticosteroid insufficiency.

[Stress and the endogenous opioid system. III. Classification of the opioid system in the process of adaptation]. / Stress und endogenes Opioidsystem. III. Einordnung des Opioidsystems in die Prozesse der Adaptation.

In this article the effects of stress-induced release of opioid peptides are integrated into the local (LAS) and general adaptation (GAS) syndrome. Findings are explained which plead for a participation in the LAS and AAS in the sense of a reserve mechanism for the maintenance of the homoeostasis. Three areas in which these opioid peptides possibly interact are discussed, articularly the adrenal glands because of their possible importance in effectuation of stress processes. Interactions between opioid system and catecholamines as well as of opioid peptides with substance P entitle to classify the opioid system as an effective regulator of biochemical processes in stress.

[Changes in the lysosomal apparatus of the human formed blood elements in the adaptation syndrome based on electron microscopy data]. / Izneneniia lizosomal'nogo apparata nekotorykh formennykh élementov krovi cheloveka pri adaptatsionnom sindrome po dannym élektronnoi mikroskopii.

An electron-microscopic examination of human leucocytes and thrombocytes under an effect of noninfectious stress factor (delivery) on organism shows that lysosomes of neutrophilic leucocytes move to plasmalemma, merge with it and secrete completely or partially their content to the blood plasma. Exocytosis of lysosomes results in a decrease of their amount in neutrophils. No changes in lysosomes of other leucocytes and thrombocytes are revealed. The fact that lysosomal neutrophilic enzymes enter the blood plasma is probably due to their participation in humoral regulation of organism functions.

Platelet morphology and membrane bound calcium in porcine stress syndrome.

Platelets of normal and stress susceptible pigs were subjected to electron microscopic examination and energy dispersive x-ray microanalysis in an attempt to study whether the cell membrane defect implicated in porcine stress syndrome is detectable at the platelet level. Electron microscopic studies revealed that the platelets of stress susceptible pigs are morphologically distinguishable from those of normal pigs by virtue of their highly dilated surface connected open canalicular system rendering the "Swiss cheese" appearance and the absence of the circumferential band of microtubules. A comparison of the data from spot analysis of cell membrane and the membranes of the open canalicular system using the energy dispersive microanalysis system showed that the calcium content of the plasma membrane of stress susceptible pigs is significantly lower than that of normal pigs. It would appear that the morphologic feature and the reduced levels of calcium bound to platelet membrane are related to the generalized membrane defect postulated to be the primary lesion in porcine stress syndrome and that these parameters could be included among the criteria for the detection of stress susceptible pigs.