[THE STUDY OF THE EFFECTS OF ANXYOLYTIC, ANTIOXIDANT, IMMUNOCORRECTOR AND HYPERBARIC OXYGENATION ON THE DYNAMICS OF MAIN BLOOD GAS AND ELECTROLYTE INDICES AND BEHAVIORAL RESPONSE IN EXPERIMENTAL STRESS MODEL].

Experiments on the model of immobilization stress in albino mice showed that a combination of mexidol, thymogen, and hyperbaric oxygenation reduced adverse effects of diazepam on behavioral response of animals in the black-and-white chamber and elevated cross maze tests and led to optimization of the blood gas composition as manifested by increased oxygen tension, normalization of the partial pressure of carbon dioxide, and restoration of the acid-base balance and blood bicarbonate level. The proposed combined treatment can be recommended for the treatment of patients with stress-induced pathology.

[Specifics of hormonal and energy balance in patients with hyperplasia and endometrial neoplasia with metabolic syndrome in the background].

We conducted a comparative investigation of the hormonal status (LH, FSH, estradiol, progesterone, testosterone, prolactin, SHBG), energy status (leptin, ghrelin, insulin), and carbohydrate and lipid metabolism in patients with endometrial hyperplasia and neoplasia (168 patients) with or without metabolic syndrome in the background. Patients with metabolic syndrome had a high frequency of elevated estrogen (72%), testosterone (65%), insulin (81%), leptin (68%). There was a marked increase in the basal level of luteinizing hormone, prolactin, index, LH/FSH, but decrease in FSH and progesterone. There were significant changes in carbohydrate and lipid metabolism. The possible mechanisms for the contribution of the investigated factors to the development of the pathological processes in the endometrium are presented.

[Regulation of insulin-like growth factors and NF-kappaB by proteasome system in endometrial cancer].

Insulin-like growth factors and the nuclear factor kappaB (NF-kappaB) are known to play an important role in pathogenesis of endometrial cancer. However, there is still uncertainty about their proteolytic regulation. We studied the correlation between chymotrypsin-like activity ofproteasomes and IGF-I, IGF-II and NF-kappaB levels in endometrial cancer tissues. The total activity of proteasomes and the 20S and 26S proteasome activities were shown to be significantly higher in malignant tumors than in unaltered endometrium. Negative correlations between the 26S proteasome activity and NF-kappaBp50 level as well as between the 26S and 20S proteasome activities and IGF-I level were found. The data obtained indicate a possible proteasome regulation of growth and transcription factors. As it is considered that the major pool of IGF-I is located in the extracellular space, it is likely that extracellular proteasomes also take part in the regulation of IGF-I content. The positive correlation between IGF-I level and PAPP-A metalloproteinase gives evidence that this proteolytic enzyme is another important regulator of growth factor level, which provides proteolysis of IGF-I binding proteins and increasing IGF-I concentration in tissues. The present data show possibility of proteolytic regulation of growth and nuclear factors that can play an important role in cancer pathogenesis.

[Evaluation of risk of progression of endometrial hyperplasia in patients with metabolic syndrome].

A mathematical model based on principles of multifactor analysis was developed to predict clinical outcome of endometrial hyperplasia (EH) in patients with metabolic syndrome (80). Seventy-seven factors--anthropometric, clinical, anamnestic, hormono-metabolic, immunohistochemical, etc.--were included. Evaluation of the most informative indices integrated with the discriminative model showed that anthropometric (waist and hip circumference, sagittal diameter, etc.) and clinico-anamnestic (age, age of secondary sexual characters appearance, body weight at birth, suckling pattern, etc.) ones are of similar significance. A profile of hormono-metabolic parameters (cholesterol-low density lipoprotein, leptin, testosterone, progesterone and fasting glucose levels) helped identify a wide range of EH-related disorders in patients with metabolic syndrome. Consistently with the literature data, level of PTEN expression pointed to the presence of this tumor's suppressor in most EH cases which was matched by absence of its expression in endometrial carcinoma. Our model provided high sensitivity (89%) and specificity (82%) in predicting risk of progression in patients with endometrial hyperplasia and metabolic syndrome.

[Sex hormones in the systemic and local circulation in endometrial hyperplasia and neoplasia: correlation with the activity of estrogen-metabolizing enzymes].

Sex hormone profile was investigated in uterine systemic and local blood flow in endometrial hyperplasia and carcinoma. The results were compared with levels of aromatase and steroid sulfatase - estrogen metabolism enzymes. Local hyperestradiolemia and hyperestronemia were detected in cancer patients. Estradiol and estrone in endometrial hyperplasia were lower than in cancer which conforms to estrogen theory of hormonal carcinogenesis. There was no evidence for the role of hyperestrogenemia in endometrial hyperplasia development. Aromatase was a factor of intensified estrogen synthesis in altered and hyperplastic endometrium. There was an inverse correlation between intratumoral steroid sulfatase levels and those of estrone in uterine local blood flow.

[Prognostic significance of assay of sex hormones, their receptors and enzymes involved in estrogen synthesis and metabolism in endometrial carcinoma].

Prognostic significance of sex hormones, sex hormone-binding globulin, estrogen and progesterone receptors as well as the activity of enzymes involved in estrogen synthesis (aromatase, steroid sulfatase, estrogen hydroxylase, catechol-O-methyl transferase, glutathione-S-transferase) were investigated in 74 endometrial carcinoma patients. Stage and duration of uterine myoma history appeared to be significant factors of overall survival. Such factors as stage, depth of myometrial invasion, body mass, blood-serum estradiol level as well as aromatase and catechol-O-methyl transferase concentration in tumor tissue were significant for free-relapse free survival period.

Enzymes of estrogen metabolism in endometrial cancer.

Activities of estrogen metabolism enzymes (aromatase, 2- and 4-estrogen hydroxylases, catechol-O-methyltransferase, and glutathione transferase) were studied by modern biochemical methods in tumors of patients with endometrial cancer. Relationships between enzyme activities and body weight index, age of menarche, stage of the disease, tumor histotype, differentiation degree, and depth of invasion into the myometrium were detected. The detected relationships between enzyme activities and serum concentrations of estradiol and progesterone and level of estrogen receptors in tumor tissue attest to hormone dependence of aromatase, estrogen hydroxylases, and glutathione transferase.

Synthesis of highly tritium labeled steroids for evaluation of aromatase and steroidsulfatase activities in endometrial tumors.

Data on activities of estrogen-synthesis enzymes (aromatase and steroidsulfatase) in endometrial tumors were obtained by sensitive and highly precise radioisotope methods. The results clear out some pathogenetic aspects in the development and progress of malignant tumors in the endometrium.

[The diagnostic significance of the antioxidant status in dysplastic changes of the gastric mucosa and in stomach cancer]. / Diagnosticheskoe znachenie antioksidantnogo statusa pri displasticheskikh izmeneniiakh slizistoi obolochki i rake zheludka.

Total antiradical activity (ARA) of the blood serum, saliva, and gastric juice, level of nonenzymatic antioxidants, and activities of antioxidant enzymes were measured in patients with moderate and severe gastric dysplasia and cancer. Informative laboratory tests are suggested for singling out the high-risk group. Evaluation of the serum ARA, tocopherol, retinol, and superoxide dismutase/glutathion peroxidase coefficient helps detect patients with gastric cancer at a high risk of postoperative complications.