[Analysis of risk factors for the development of infertility in men from infertile couples, depending on age.]

According to the Russian Society of Urologists, the frequency of infertility in marriage in the Russian Federation is 8-17,2%; half of the cases are associated with the male factor. Among the risk factors for the development of male infertility, there are mainly medical reasons, lifestyle factors and negative environmental factors. Despite the fact that the problem of infertility is addressed by men of different ages, from youth to the elderly, the correction of risk factors is usually carried out without taking into account the age of the patient, which makes it difficult to develop a personalized strategy for the treatment or prevention of infertility. The aim of the study was to study the structure of the leading risk factors for the development of infertility in men from infertile couples, to identify and characterize their age-associated features. The analysis of the medical histories of 1 198 men from infertile couples and the collection of information on all available risk factors for infertility were carried out. The analysis of age features was performed by dividing the sample into 5 age groups: 1st (n=271) - men ≤29,9 years; 2nd (n=415) - 30-34,9 years; 3rd (n=291) - 35-39,9 years; 4th (n=141) - 40-44,9 years; 5th (n=80) - ≥45 years. It was shown that in the general sample of medical causes, factors associated with chronic inflammation predominate: sexually transmitted infections (STIs) - 54%; prostatitis - 32%; obesity - 27%; from non-medical: alcohol - 73%; stress - 47%; smoking - 41%. With increasing age, the frequency of obesity, STIs, prostatitis, hepatitis B/C, mumps increases statistically significantly, while the most unfavorable group of men is 40-45 years old for factors such as STIs, hepatitis B/C and mumps, and the group of men over 45 years old for factors such as obesity and prostatitis.

EXPRESSION AND ACTIVITY OF AMINOTRANSFERASES IN THE LIVER OF STREPTOZOTOCIN-DIABETIC RATS: THE EFFECT OF MIFEPRISTONE.

Context: Interventions that suppress hepatic gluconeogenesis from amino acids may be useful for improving glycemic control in diabetic patients. Objectives: It was shown that administration of glucocorticoid receptor antagonist Mifepristone (MIF) leads to variously pronounced changes in the alanine-, aspartate-, tyrosine- aminotransferases (ALT, AST, TAT) activity in the liver of experimental animals. It has been suggested that this selective effect of MIF may be related to differences in the expression of the corresponding genes. The aim of the study was to investigate the gene expression and activity of ALT, AST and TAT in the liver of rats with streptozotocin-related diabetes (StD) under the long-term oral MIF administration. Methods: Male Wistar rats (n=48) with StD under the 10-days oral MIF administration were used. It was measured the activity of ALT, AST, TAT enzymes and relative expression of this genes in the liver of experimental animals. Results: In rats with StD the gene expression of all three studied aminotransferases in the liver was statistically significantly increased and their activity was increased as well. MIF administration did not change the studied genes expression and enzymes activity to healthy rats and caused a decrease in expression of ALT and AST genes and activity of these enzymes to rats with StD. However, the expression of the TAT gene and the activity of this enzyme in the liver of rats with StD increased upon MIF administration in comparison with animals with StD. Conclusions: The introduction of MIF against the background of StD reduces the expression of genes and the activity of ALT and AST in the liver, what determine the transamination of amino acids to include them in gluconeogenesis, but increases the expression of genes and the activity of TAT, what determine the inclusion of tyrosine in the biogenic amines synthesis. The mechanisms of such selectivity require further study.

[Dynamics of sperm indicators in men with chronic prostatitis associated with secondary infertility based on the use of ANDROEXPERT SV1 suppositories].

INTRODUCTION: Chronic prostatitis (CP) is the most common cause of a disorder of not only sexual, but also reproductive functions in men, which is caused by a decrease in the quality of the ejaculate and is confirmed by a deterioration in spermogram parameters, up to oligoasthenoteratozoospermia and azoospermia. In such a situation, the onset of pregnancy in the natural cycle is impossible - even with a completely preserved reproductive function in a woman. As an active substance in the recovery of men with chronic prostatitis associated with secondary infertility, we proposed oxidised dextran in the form of a pharmaceutical composition, which was developed at Federal Research Centre for Fundamental and Translational Medicine, Novosibirsk, Russia; and produced by ANDROEXPERT Research and Manufacturing Company LTD, Novosibirsk, Russia. The purpose of the study was to evaluate the dynamics of spermogram parameters as a result of the use of suppositories with oxidised dextran "ANDROEXPERT SV1" in men with chronic prostatitis associated with secondary infertility. MATERIAL AND METHODS: The study included 52 patients with chronic prostatitis associated with secondary infertility. The mean age of the patients was 32+/-2.2 years. The examination of patients was carried out in accordance with the algorithm recommended by the Russian Society of Urology, the European Urological Association and the standard of primary health care for chronic prostatitis (Appendix to the order of the Ministry of Health of Russia No. 775n of 09.11.2012). The patients were divided into two groups: the 1st group of patients received oxidised dextran rectally once per day for 10 days, then 20 days every other day; The 2nd (comparison group) received a placebo in the form of rectal suppositories consisting of cocoa butter in a similar way. RESULTS: The volume of ejaculate among patients of the 1st group increased from 2.54+/-0.15 to 3.13+/-0.18 (ml), which amounted to 23.23%; p<0.05. The sperm concentration indicator increased from 26.40+/-4.18 to 41.12+/-5.37 (million/ml) - by 55.75%; p<0.05, which led to an increase in the total number of spermatozoa in the ejaculate by 88.5%, from 65.47+/-8.41 to 123.41+/-12.33 (million pieces); p<0.05. The number of leukocytes in the same group decreased by 2.8 times: from 1.25+/-0.17 to 0.44+/-0.10 (million/ml) - by 64.80%; p<0.05. The indicator of the severity of sperm agglutination decreased by 3 times: from 0.52+/-0.07 to 0.17+/-0.03 - by 0.35 arb. units, which was 67.31%; p<0.05. The indicators of the spermogram in patients with chronic prostatitis of the second group did not change in the course of treatment. CONCLUSION: Assessing the dynamics of spermogram parameters as a result of the use of "ANDROEXPERT SV1" in men with chronic prostatitis associated with secondary infertility, there is a decrease in the number of leukocytes and a significant improvement in the parameters of the ejaculate, both its general properties and the main characteristics of spermatozoa. Thus, ANDROEXPERT SV1 suppositories show high clinical efficacy and safety in monotherapy and may be promising when choosing the management tactics for this group of patients.

[Experimental study on the efficiency of rectal suppositories with oxidized dextran in patients with benign prostatic hyperplasia].

AIM: to evaluate therapeutic activity of oxidized dextran after rectal administration in a modified sulpiride model of benign prostatic hyperplasia in mice. MATERIALS AND METHODS: The therapeutic activity of oxidized dextran was studied in an experimental model of benign prostatic hyperplasia in mice (sulpiride model). All in vivo studies were carried out on 30 male BALB/c mice with an average body weight of 30-35 g. RESULTS: It was found that rectal administration of a solution of oxidized dextran effectively neutralizes pathomorphological changes in experimental model of benign prostatic hyperplasia. In the group of animals, which received 2% solution of oxidized dextran as treatment, the most prominent therapeutic effect in an experimental model was seen and it was confirmed by a decrease in the bladder detrusor thickness and the normalization of its lumen.

[Hypercorticism during streptozotocin diabetes and mifepristone administration: the role of cyclic adenosine monophosphate]. / Giperkortitsizm pri streptozototsinovom diabete i vvedenii mifepristona: rol' tsiklicheskogo adenozinmonofosfata.

It was studed basal and ACTH-stimulated production of cyclic adenosine monophosphate (cAMP) and corticosteroid hormones (progesterone and corticosterone) in rat adrenals in vitro under streptozotocin diabetes, in conditions of mifepristone administration and their combination. It was shown that in streptozotocin diabetes animals, both the basal and adrenocorticotropic hormone (ACTH) stimulated cAMP production significantly increased; this was accompanied by the increase in basal and ACTH-stimulated progesterone and corticosterone production in rat adrenals in vitro. Repeated administration of mifepristone to control and diabetic rats caused an increase mainly in ACTH-stimulated production of the main glucocorticoid hormone, corticosterone, without additional changes in the cAMP level. The results obtained suggest activation of two mechanisms of steroidogenesis enhancement in experimental animals. In rats with streptozotocin diabetes, both basal and ACTH-stimulated activity of all stages of steroidogenesis increase, which is mediated by the increased formation of cAMP as second messenger mediating the ACTH action on adrenocortical cells. Prolonged administration of mifepristone to control and diabetic rats resulted in increased activity of only late stages of steroidogenesis with predominant elevation of synthesis of physiologically active hormone corticosterone without additional changes in cAMP production level.

HORMONAL REGULATION OF CARBOHYDRATE AND FAT METABOLISM IN WOMEN WITH DIFFERENT OBESITY TYPES IN THE FOOD DEPRIVATION TEST.

CONTEXT: The dominant type of adipose tissue accumulation in the body is associated with the peculiarities of using key substrates in energy metabolism and their hormonal regulation. Hormonal and metabolic parameters were investigated in women with android and gynoid obesity before and after the short-term food deprivation test. RESULTS: At baseline, at gynoid obesity as compared to android obesity, the women's blood contained lower glucose and insulin levels and higher FFA levels. The reaction to food deprivation manifested by a decrease in glucose level and an increase in FFA level in the blood is less pronounced in women with gynoid obesity than in those with android obesity. At the same time, a similar (though varying in expression) decrease in insulin level and elevated levels of glucagon, growth hormone and thyroxine were revealed in women's blood in both groups. Blood cortisol level increased in women with gynoid obesity and remained unchanged in those with android obesity. CONCLUSIONS: More pronounced activation of hormonal mechanisms for maintaining blood glucose levels at gynoid obesity as compared to android one suggests that glucose is the preferable substrate for energy metabolism at gynoid obesity in women.

[Hormonal feature of the androgen status in different-aged males.]

The examined males (n=374) aged from 20 to 69 years were divided into five age groups: the 1st - 20-29 years; the 2nd - 30-39 years; the 3rd - 40-49 years; the 4th - 50-59 years; the 5th - 60-69 years. There was 16,1±7 nmol/l total testosterone level in serum of all aged group. Hormonal signs of androgen deficiency, increased elderly aged groups, were revealed in males of the 2nd group as compared with males of the 1st group. The frequency of androgen deficiency (total testosterone level less than 12,1 nmol/l) in the 1st group was 26,9%; in groups 2, 3 and 4 this index was similar, composed 30,6-33,9%. However, the frequency of androgen deficiency increased and amounted to 44% in the 5th group. The frequency of hypogonadism hormonal signs (total testosterone level less than 8 nmol/l) did not significantly differ in groups 1-4 (6,2-9,3%), and only in group 5 it increased and amounted to 28%. The age-related androgenic deficiency in males was associated with decrease in androgenic function both the gonads, and the adrenal glands, increased level of sex steroid-binding globulin, increased metabolism of testosterone in estradiol and was accompanied by compensatory increase of luteinizing hormone synthesis in the pituitary gland.

Effects Mifepristone on Aminotransferase Activities in the Liver in Rats with Streptozotocin-Induced Diabetes Mellitus.

The glucocorticoid status and activities of ALT, AST, and tyrosine aminotransferase in the liver are studied in rats with streptozotocin-induced diabetes mellitus in response to repeated intraperitoneal injections of mifepristone. Diabetic rats develop an increase of the blood corticosterone and liver aminotransferase levels in response to mifepristone. These results indicate that in diabetic animals the glucocorticoid hormones with high blood concentrations, increasing still more in response to mifepristone, overcome the receptor blockade, and realize their regulatory functions in hepatocytes. The effects of mifepristone on ALT activity are the most manifest. In normal rats, only ALT activity is increasing in response to mifepristone, while in rats with streptozotocin-induced diabetes mellitus, ALT activity increases more intensely than activities of tyrosine aminotransferase and AST.

Stress Response to Physical Exercise in Rats with Alimentary Obesity.

Stress response to physical exercise was studied in rats with alimentary obesity with and without caloric diet restriction. Daily excretion of corticosterone, progesterone, and testosterone, weights of internal organs, and serum levels of glucose, free fatty acids, triglycerides, corticosterone, and testosterone were estimated. Stress response to moderate exercise in rats with alimentary obesity was associated with predominance of anabolic influence of testosterone over the catabolic effects of corticosterone, which promoted the increase in the weight of reproductive organs. Exposure to physical loads against the background of restricted ration potentiated the response of the adrenocortical system and reduced the concentration and anabolic effects of testosterone.

Effect of Mifepristone on Corticosteroid Production in Vitro by Adrenal Glands of Rats with Streptozotocin Diabetes.

Changes in pregnenolone and corticosterone production by the adrenal glands of normoglycemic rats receiving the course of intraperitoneal mifepristone or NaCl administration were co-directed, but differed in magnitude. In rats with hyperglycemia, corticosteroid production increased after NaCl administration over 5 days and returned to the initial values after 15-day administration. On the contrary, pregnenolone and corticosterone production was suppressed after 5-day course of mifepristone, but significantly increased after mifepristone administration for 15 days. Intraperitoneal mifepristone administration almost completely abolished the response of rat adrenal glands with normo- and hyperglycemia to ACTH in vitro; this effect did not depend on the duration of administration.

Effects of Intraperitoneal Administration of Mifepristone on Glucocorticoid Status of Experimental Animals.

We studied the content of corticosterone and its precursors in the adrenal glands, corticosterone in blood serum and daily urine of rats, and activity of first and second isoforms of 11ß-hydroxysteroid dehydrogenase in the liver and kidneys of rats after 15 daily intraperitoneal injections of 0.9% NaCl or glucocorticoid receptor blocker mifepristone in 0.9% NaCl. Daily injections of NaCl reduced the levels of pregnenolone, progesterone, and corticosterone in the adrenal glands, increased corticosterone excretion with urine, enhanced activity of the first isoform of 11ß-hydroxysteroid dehydrogenase in the liver and reduction in activity of the second isoform of this enzyme in the kidneys. These changes are typical manifestations of chronic stress. Mifepristone restored pregnenolone content in the adrenal glands and increase in corticosterone concentration in the blood. Under these conditions, activity of the first isoform of 11ß-hydroxysteroid dehydrogenase in the liver did not change, and a decrease in activity of the second isoform of the enzyme in the kidneys was less pronounced. The results suggest that mifepristone abolished the stress-mediated increase in activity of the first isoform of 11ß-hydroxysteroid dehydrogenase in the liver and reduced local production of glucocorticoid hormones and their metabolic effects in hepatocytes.

[ASSOCIATION OF AGE OBESITY AND METABOLIC SYNDROME IN MEN].

The study included 253 men aged 22 to 74 years. Was shown that at the end of the first period of middle age the accumulation of adipose tissue was enhanced that was associated with the change of dominance from the gynoid to the android type of obesity. The most pronounced increase in the frequency of occurrence of individual components and the overall metabolic syndrome was diagnosed in men in the second period of middle age with a following decrease in the frequency such components as hypertriglyceridemia, low HDL cholesterol and hyperglycemia in elderly age. In the all three age groups the value of the index of visceral obesity was significantly higher in men with android type of obesity compared with gynoid. Thus, the men with gynoid compared with android type of obesity have a lower risk of development metabolic syndrome in all age groups.

[Adipokines and a risk for metabolic disturbances in different types of female obesity]. / Adipokiny i risk razvitiya metabolicheskikh narushenii pri raznykh tipakh ozhireniya u zhenshchin.

AIM: To investigate the effects of adiponectin and leptin on the development of metabolic disturbances in women with android and gynoid fat distribution. MATERIAL AND METHODS: A total of 101 women aged 40 to 65 years were examined. Anthropometric measurements were made; overweight and obese women with a waist/hip (W/H) ratio of less than 0.83 were referred to as a gynoid fat distribution (GFD) group; and those with a W/H ratio of 0.83 or more were to an android fat distribution (AFD) group. The serum concentrations of triglycerides, high-density lipoprotein cholesterol, and glucose were measured; the levels of insulin, leptin, and adiponectin were determined by enzyme immunoassay. Insulin resistance (IR), HOMA IR, and visceral obesity index (VOI) were calculated. RESULTS: With the same excess adipose tissue accumulation, the women with GFD had a less magnitude of hormonal and metabolic disturbances than those with AFD, whose HOMA-IR also pointed to the presence of IR. VOI was insignificantly higher in the women with GFD and 2.4-fold greater than that in normal weight (NW) women. In the women with GFD and AFD, the concentration of leptin was higher than that in the NW women, which was characteristic of obesity, but the concentration of adiponectin proved to be significantly lower in the patients with AFD and to be unchanged in those with GFD as compared with that in the NW women. CONCLUSION: The women with AFD are typified by a high VOI, hypoadiponectinemia, IR, and metabolic disturbances, which determine a high risk for cardiovascular events and type 2 diabetes mellitus. In the women with GFD, obesity is associated with normal adiponectinemia and a low VOI and, in terms of hormonal and metabolic characteristics, may be characterized as metabolically healthy obesity.

Activity of 11ß-hydroxysteroid dehydrogenase in the adrenal glands, liver, and kidneys of rats with experimental diabetes.

We studied activity of the key enzyme of the pre-receptor metabolism of glucocorticoid hormones, 11ß-hydroxysteroid dehydrogenase, in rat adrenal glands, renal cortex and liver in the course of development of alloxan diabetes (9, 20, and 28 day). The enzyme activity was increased 3-4 fold in the adrenal glands throughout the experiment. At the same time, according to the adrenal gland level of corticosterone, its precursor 11-deoxycorticosterone and reversible metabolite 11-dehydrocorticosterone, activity of the second isoform of the enzyme dominated at the early stages of diabetes, and that of the first isoform, at later stages. In long-term diabetes (28 days), along with reduced synthesis of corticosterone and production of 11-dehydrocorticosterone in the adrenal glands, the extra-adrenal formation of corticosterone was activated as indicated by enhanced activity of the first isoform in the liver and that of the second isoform in the kidneys. These changes in activity of the enzyme isoforms promote local formation of corticosterone from its reversible metabolite in the liver and persisting hyperglycemia in diabetes.

Production of corticosteroid hormones in vitro by adrenals in rats with streptozotocin-induced diabetes.

We studied baseline and ACTH-stimulated in vitro production of corticosteroids by rat adrenals. Production of the basic corticosteroids pregnenolone (early precursor in corticosteroid synthesis), progesterone (intermediate precursor in synthesis of gluco- and mineralocorticoid hormones), and corticosterone (major glucocorticoid hormone in rodents) in animals with streptozotocin-induced diabetes was enhanced by 1.8-2.0 times in comparison with the control animals. Addition of ACTH to the incubation medium stimulated pregnenolone production by the adrenals equally in the control and experimental (diabetic) groups, while the increase in corticosterone production was less pronounced in the experimental group. Stimulation of corticosterone production in response to ACTH after saturation of the incubation medium with pregnenolone was also less pronounced in diabetic rats.

Rats of hypertensive ISIAH strain are resistant to the development of metabolic syndrome induced by high-fat diet.

We studied the influence of high-fat diet on the development of metabolic syndrome in rats of hypertensive ISIAH strain and normotensive WAG strain. In contrast to ISIAH rats, high-fat diet in WAG rats led visceral obesity, glucose tolerance, and dyslipidemia. DNA-binding activity of the peroxisome proliferator-activated receptor α (PPARα) decreased in the liver of WAG rats and increased in ISIAH rats. Blood levels of TNF-α, IL-6, and corticosterone increased more significantly in WAG rats. Corticosterone content in the adrenal glands was more markedly reduced in WAG rats. High-fat diet had no effect on BP in ISIAH and WAG rats. It was concluded that ISIAH rats can be used as a genetic model in studies of the mechanism of resistance to the metabolic syndrome.

Effect of mifepristone on glucocorticoid receptor gene expression in the liver of rats with streptozotocin-induced diabetes.

The effects of mifepristone on activity of the adrenocortical system, expression of glucocorticoid receptor gene, and tyrosine aminotransferase activity in the liver were studied in rats with streptozotocin-induced diabetes. Administration of glucocorticoid receptor blocker mifepristone to rats without diabetes was followed by a 1.9-fold increase in serum corticosterone concentration and a 1.2-fold increase in tyrosine aminotransferase activity in the liver in comparison with the baseline values. In rats with streptozotocin-induced diabetes, mifepristone produced a less pronounced increase in the corticosterone concentration (by 1.5 times) and more drastic increase in enzyme activity (by 1.7 times). Mifepristone administration did not change the content of glucocorticoid receptor mRNA in the liver of rats without diabetes, but increase this parameter by 1.4 times in rats with streptozotocin-induced diabetes. The enhanced expression of glucocorticoid receptor gene in the liver of rats with streptozotocin-induced diabetes correlated with increased activity of tyrosine aminotransferase after mifepristone treatment.

[Corticosteroid hormones and angiotensin-converting enzyme in the dynamics of chronic granulomatous inflammation].

It was studied the contents of corticosteroid hormones in the adrenal gland, plasma and 11beta-hydroxysteroid dehydrogenase activity (11betaHSD) in the liver and kidneys, as well as the activity of angiotensin-converting enzyme (ACE) in blood plasma, lung, renal cortex and liver of male rats in the dynamics of SiO2-induced inflammation. The study showed that chronic granulomatous inflammation in rats was accompanied by an initial short-term reaction to the activation of synthesis of the main glucocorticoid hormone, followed by specific inhibition of synthesis of this hormone as well as 11betaHSD activity in the adrenal gland. Inflammation caused less pronounced changes in the functional state of the renin-angiotensin system, however, inhibition of ACE activity observed in plasma, liver and kidneys during the initial period of inflammation. Factor analysis revealed a violation of intersystem relations of hypothalamic-pituitary-adrenocortical and renin-angiotensin systems in inflammation due, probably, to the modulating influence of cytokines.

Adrenocortical system response to induction of inflammation with silicon dioxide in rats with alloxan-induced diabetes mellitus.

Alloxan-induced diabetes mellitus in rats was characterized by persistent increase in blood levels of corticosterone, while chronic granulomatous inflammation induced by silicon dioxide and its combination with alloxan-induced diabetes mellitus were associated with transient increase in blood corticosterone level followed by gradual development of hypoadrenocorticism. The content of corticosterone in the adrenal glands of rats with alloxan-induced diabetes mellitus remained unchanged in the dynamics of the disease, but the level of progesterone decreased at the early terms of diabetes and then returned to the initial values. After administration of silicon dioxide to intact rats and to rats with diabetes mellitus, changes in hormone content in the adrenal glands were observed only at the initial stages of inflammation and consisted in elevation of corticosterone concentration against the background of reduced progesterone content.

[Iodine availability, thyroid structure and function in residents of the city of Mirny, Republic of Sakha (Yakutia)].

Iodine availability for residents of the city of Mirny, Republic of Sakha (Yakutia), was estimated from urinary iodine and creatinine levels and their calculated ratio. Median of iodine/creatinine ratio in the groups of children and adults included in the study was 167.2 and 110.5 mcg/g respectively. Goiter was diagnosed by ultrasound in 0.4% of men and 4.9% of women. Diffuse and focal changes of the thyroid echographic pattern were revealed in the overwhelming majority of the examined subjects (91.7% of the adults and 66.1% of the children). The frequency of thyroid nodules was 5.0% and 20.3% in men and women respectively. Serum TSH level exceeded the respective reference values in 10.9% of the men and 18.2% of the women.