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Background: In recent years, the incidence of gynecomastia in adult men has increased significantly. It is of interest to study the specific features of the disease in these patients., Aim: To identify the main characteristics of acute gynecomastia in adult men., Materials and Methods: A continuous one-stage study including 160 adult males with acute onset gynecomastia, who were he was treated in Endocrinology Research Centre, Moscow. Total bilirubin, hepatic transaminases, creatinine, urea, luteinizing hormone, prolactin, sex hormone binding globulin, estradiol, total testosterone, alpha-fetoprotein, chorionic gonadotropin and mammary gland condition were evaluated in all patients. Baseline significance threshold level of p<0.05., Results: The incidence of gynecomastia increased from 5,4% in 2020 to 14,4% in 2024. Tumor forms of gynecomastia were rare, with 1,2% (95% CI 0,0; 3,0) of cases. In 30% (95% CI 22,9; 37,1) of men, gynecomastia was due to the intake of anabolic steroids for athletic stimulation. In 11,2% (95% CI 6,4; 16,1) of patients, gynecomastia was hepatogenic. In 7,5% (95% CI 3,4; 11,6), it was due to elevated sex hormone binding globulin. 47,5% (95% CI 39,8; 55,2) were endocrine non-tumorigenic form of gynecomastia due to excess body weight with formation of changes in sex hormone levels. The patients who took anabolic steroids were characterized by young age, as well as decreased luteinizing hormone levels and increased testosterone levels. The group of patients with elevated sex hormone binding globulin had no clinically significant features. Men from the group of hepatogenic gynecomastia were characterized by hyperestrogenism. Patients in the group with altered sex hormone levels were characterized by high body mass index and either increased estradiol or decreased testosterone or a combination of both., Conclusion: The number of adult male patients with acute gynecomastia is progressively increasing. In the examined sample of patients, the main causes of gynecomastia were patients taking anabolic steroids, liver dysfunction and weight gain with the formation of changes in sex hormone levels. Patients taking anabolic steroids were characterized by a drug--induced increase in testosterone and estradiol levels, which was accompanied by suppression of pituitary gonadotropic function. Estradiol elevation was also characteristic of patients with hepatogenic form of gynecomastia and men with excess body weight with formation of changes in sex hormone levels.

On March 28, 2024, the Council of Experts "High-dose vitamin D (Devilam) in the practice of obstetrician-gynecologist, gynecologist and endocrinologist" was held in Moscow with the participation of leading experts gynecologists, endocrinologists and obstetricians-gynecologists, during which new possibilities for the use of high-dose vitamin D in patients of various ages who need correction of existing vitamin D deficiency or insufficiency.

Background: 2025 is going to be the 100th anniversary of the first historical description of Turner syndrome - complex of  genomic abnormalities, congenital gonadal disruption and hypergonadotropic hypogonadism. Total estrogenic deficiency triggers development of age-related comorbidities. There is no doubt that personalized search for replicative markers of cellular aging among females with Turner syndrome is needed., Aim: To evaluate features of replicative (telomere length) and biochemical (lipid profile, calcium-phosphate album, thyroid hormones, markers cytolysis and cholestasis, carbohydrate metabolism, nitrogenic metabolism, electrolytes, FSH) markers among females with Turner syndrome., Materials and Methods: Research has been provided in collaboration between Endocrinology Research Centre of the Russian Ministry of Health and Lomonosov Moscow State University Medical Research and Educational Centre in the period since 10.01.2021 until 01.08.2022. Females with non-iatrogenic hypergonadotropic hypogonadism caused by Turner syndrome (45,X0; 45,X/46,XX; 45,X/46,X,r(X); 13-40 y.o.; n=26) and primary ovarian insufficiency (18-39 нyears=26); healthy females of reproductive age (15-49 y.o.; n=24). Patients have undergone laboratory genetic (leucocyte telomere length), biochemical (fasting glycaemia, urea, creatinine, common/conjugated bilirubin, ALT, AST, gamma-glutamyl transferase, triglycerides, HDL-P, LDL-P, common cholesterol, common/ionized calcium, phosphate, vitamin D, sodium/potassium/chlorides, FSH, HbA1c) analyses. Body measurements - body mass, body height. DNA extraction - provided with Qiagen DNA blood mini kit (Germany). Leukocyte telomere length - with real-time polymerase chain reaction PCR (Flow-fish). Soft program IBM SPSS Statistics (version 26,0 for Windows)., Results: 1. Females with Turner syndrome have significantly lower mean telomere length (8,22 kB [6,63-9,30]) than with primary ovarian insufficiency (10, 34 кБ [8,41-13,08], p<0,001) and healthy reproductive age females (10,77 kB [9,95-13,16], р>0,05).2. Telomere length correlates directly and significantly with longevity of menopausal hormonal therapy among females with primary ovarian insufficiency (ρ = 505; p<0,001).3. Patients with Turner syndrome are inclined to vitamin D deficiency (р<0,001), dyslipidemia (р=0,01); increase of levels of aminotransferases, cholestasis markers, phosphate and FSH (р<0,001)., Conclusion: Turner syndrome is serious genetic disease that leads not only to infertility but to significant decrease of quality/life longevity out of "healthy aging" conception.

The article presents data on the relationship of pathogenetic mechanisms for the development of menstrual disorders of functional and organic origin in connection with mental disturbances from the point of view of the psychosomatic concept. According to the latter, functional disorders of the menstrual cycle are considered as psychosomatic, in which gynecological pathology develops as a result of psychopathological illness. A striking example of such a disorder is functional hypothalamic amenorrhea. At the same time, endocrinopathies, such as polycystic ovary syndrome and premature ovarian insufficiency, can also be considered in the paradigm of psychosomatic illnesses of ovarian function due to the high prevalence of anxiety and depressive disorders in this cohort of patients. This review highlights the importance of interdisciplinary collaboration between a gynecologist and a psychiatrist for the most effective reproductive rehabilitation of patients with amenorrhea. Literature search was carried out in national (eLibrary, CyberLeninka.ru) and international (PubMed, Cochrane Library) databases in Russian and English. The priority was free access to the full text of articles. The choice of sources was prioritized for the period from 2018 to 2023.However, taking into account the insufficient knowledge of the chosen topic, the choice of sources dates back to 1985.

Polycystic ovary syndrome (PCOS) is one of the most pressing problems in endocrine gynecology. The main signs of the disease are hyperandrogenism, menstrual and/or ovulatory dysfunction, and polycystic ovarian structure according to ultrasound. Women with PCOS are at risk for developing metabolic syndrome, type 2 diabetes, cardiovascular disease, and endometrial cancer. In this connection, the pathogenetic mechanisms of the occurrence of this syndrome are continuously studied and new methods of treatment are being sought. PCOS is characterized by a wide range of various disorders of the neuroendocrine regulation of the reproductive system. The main focus of the review is aimed at summarizing information about the etiological role of neuropeptides and neurotransmitters, such as phoenixin, galanins, orexins, GABA, in the pathophysiology of PCOS and about the possibility of their use for diagnostic and therapeutic purposes. In recent decades, the interest of scientists has been focused on the study of KNDy neurons, because it is the kisspeptin synthesized by them that is one of the main regulators of the hypothalamic-pituitary-ovarian axis. This article discusses data on the significance of KNDy neurons in the pathogenesis of the syndrome. Information is provided on the effect of elevated levels of androgens and anti-Müllerian hormone on GnRH neurons. Also analyzed are studies on functional and structural disorders in the hypothalamus in PCOS. Literature search was carried out in national (eLibrary, CyberLeninka.ru) and international (PubMed, Cochrane Library) databases in Russian and English. The priority was free access to the full text of articles. The choice of sources was prioritized for the period from 2018 to 2023.However, taking into account the insufficient knowledge of the chosen topic, the choice of sources dates back to 1998.

Menopausal symptoms can disrupt the life course of women at the peak of their career and family life. Currently, the most effective treatment for these manifestations is menopausal hormone therapy (MHT). The presence of cardiovascular and metabolic diseases in itself does not exclude the possibility of prescribing MHT to relieve menopausal symptoms and improve quality of life. However, often an obstacle to the use of this type of hormonal therapy is the fear of doctors who are afraid of doing more harm to patients than good. Caution is especially important when it comes to women with underlying health conditions. Moreover, it should be recognized that there is a lack of high-quality research regarding the safety of MHT for major chronic non-infectious diseases and common comorbid conditions. The presented consensus document analyzed all currently available data obtained from clinical trials of various designs and created a set of criteria for the acceptability of prescribing MHT to women with concomitant cardiovascular and metabolic diseases. Based on the presented document, doctors of various specialties who advise women in menopause will receive an accessible algorithm that will allow them to avoid potentially dangerous situations and reasonably prescribe MHT in real practice.

Ageing (as known as eldering, senescence) is a genetically and epigenetically programmed pathophysiological process. Velocity of biological ageing is defined as balance between alteration and reparation of body structures. According to last World Health Organization (WHO) highlights ageing still stays an extremely actual scientific, social and demographic problem: in 2020 total number of people older than 60 years and older was 1 billion people; in 2030 future number may be 1,4 billion people, in 2050 - 2,1 billion people. Absence of single universal theory of aging nowadays is reason for scientifical and clinical collaboration between biologists and doctors, including endocrinologists. Designing of potentially effective newest anti-ageing strategies (such as natural/synthetic telomerase regulators, mesenchymal stem cells etc.) is of interest to scientific community. The aim of present article is a review of modern omics (genomic, proteomic, metabolomic) ageing mechanisms, potential ways of targeted prevention and treatment of age-related disease according to conception of personalized medicine. Present review is narrative, it does not lead to systematic review, meta-analysis and does not aim to commercial advertisement. Review has been provided via PubMed article that have been published since 1979 until 2022.

Menopausal symptoms can impair the life of women at the peak of their career and family life. At the present time, the most effective treatment for these manifestations is menopausal hormone therapy (MHT). The presence of cardiovascular and metabolic diseases in itself does not exclude the possibility of prescribing MHT to relieve menopausal symptoms and improve quality of life. However, often an obstacle to the use of this type of hormone therapy is the fear of physicians to do more harm to patients than good. Caution is especially important when it comes to women with concurrent diseases. Moreover, it should be recognized that there is a shortage of high-quality research on the safety of MHT for underlying chronic non-infectious diseases and common comorbidities. The presented consensus analyzed all currently available data from clinical trials of various designs and created a set of criteria for the appropriateness of prescribing MHT to women with concomitant cardiovascular and metabolic diseases. Based on the presented document, physicians of various specialties who advise menopausal women will receive an accessible algorithm that will allow them to avoid potentially dangerous situations and reasonably prescribe MHT in real-life practice.

Aim: To compare the efficiency of two surgical methods, holmium laser enucleation of prostate (HoLEP) and laparoscopic retropubic simple prostatectomy with clamping of internal iliac arteries and vesicourethral anastomosis [LPA+CIIA+VUA]) for treating of patients with benign prostatic hyperplasia (BPH) and type 2 diabetes mellitus (T2DM)., Materials and Methods: A total of 56 men with T2DM who underwent surgical treatment of BPH in the National Research Centre for Endocrinology of the Russian Ministry of Health (director - corresponding member of RAS Mokrysheva N.G..) in a period from 2021 until 2022 were included in the study. Patients with T2DM received two types of antidiabetic drugs: basal-bolus insulin therapy and metformin (1000 mg/day per os). Patients were divided into the group of LPA+CIIA+VUA (n=28) and HoLEP (n=28). Preoperative, intraoperative and postoperative examinations with an evaluation of intraoperative and early postoperative complications (I, II, III, IV grades according to the Clavien-Dindo scale) were performed. After 1 year of follow-up, International Prostatic Symptom Score (IPSS), "Quality of Life" score (QoL), International Index of Erectile Function-5 score (IIEF-5), maximal urine flow rate (Qmax), and postvoid residual volume (ml) were assessed. Efficiency of surgical procedures was estimated according to "trifecta": absence of postoperative complications, urine continence, maximal urine flow (Qmax) >15 ml/sec., Results: In the group of HoLEP, shorter postoperative bladder catheterization time but higher risk of urinary incontinence, bladder neck contracture and urethral strictures was found. LPA+CIIA+UVA leaded to a two-fold decrease in intraoperative hemoglobin loss with no necessity of repeat procedures., Conclusions: Our preliminary results demonstrated higher efficacy of LPA+CIIA+VUA for treatment of BPH in patients with T2DM than HoLEP. Patients who underwent LPA+CIIA+VUA were more often achieved the "trifecta". In order to implement LPA+CIIA+VUA into clinical practice, multi-center, large-scale, double-blind, placebo-controlled ("scar-surgery") randomized studies are required.

Background: Estrogenic deficiency is the basic condition of human ageing that leads to hypergonadotropic hypogonadism. The existence of correlation between hypergonadotropic hypogonadism, replicative (leukocyte telomere length) and biochemical data is widely supposed among females with physiological (menopausal) and pathological (primary ovarian insufficiency) estrogenic deficiency is not unreasonable., Aim: To evaluate features of replicative (telomere length) and biochemical (metabolic syndrome) ageing markers among females with physiological (menopausal) and pathological (primary ovarian insufficiency) estrogenic deficiency., Materials and Methods: Research has been provided in collaboration between Endocrinology Research Centre of the Russian Ministry of Health and Lomonosov Moscow State University Medical Research and Educational Centre in the period since 10.01.2021 until 01.08.2022.110 females (20-75y.o.) have participated in the present research.Group 1: 26 females receiving menopausal hormonal therapy (MHT) ≥ 5 years with 0,5; 1; 2 mg estrogenic component.Group 2: 27 females in physiological menopause without MHTGroup 3: 33 females with primary ovarian insufficiency and receiving sex-steroid replacement therapy.Group 4: 24 healthy reproductive age females without sex-steroid replacement therapy.Patients have undergone laboratory genetic (leucocyte telomere length), biochemical analyses.DNA extraction - with Qiagen DNA blood mini kit (Germany). Biological material was cito conserved with Ficoll solution. Leukocyte telomere length - with real-time polymerase chain reaction PCR (Flow-fish).Soft program IBM SPSS Statistics (version 26,0 for Windows) has been used for statical analysis., Results: 1.Menopausal females receiving MHT were inclined to highest HDL-P levels (p<0,006).2.Females with primary ovarian insufficiency were inclined to relatively highest serum creatinine level (p<0,001).3.Reproductive age females had relatively highest telomere length (p<0,001).4.FSH level correlates negatively and moderately (ρ= - 0,434) leukocyte telomere length (р<0,001) among females., Conclusion: Females with premature ovarian insufficiency are most sensible to ageing due to features of replicative and biochemical markers.

Background: One of the most dangerous reproductive pathologies is primary ovarian insufficiency (POI). Except manifestation in the age <40 years old it leads to demographical losses, decrease of chances for healthy aging. POI can be characterized as summary of secondary amenorrhea, total estrogenic deficiency and hypergonadotropic hypogonadism. Hence, POI has probably harmful effect on telomere length. Telomere length determining and sex steroid replacement therapy may be promising and effective to prevent decrease of life quality/ longevity among females with POI., Aim: To evaluate features of replicative (telomere length) and biochemical (metabolic syndrome) markers among females with primary ovarian insufficiency., Materials and Methods: Research has been provided in collaboration between Endocrinology Research Centre of the Russian Ministry of Health and Lomonosov Moscow State University Medical Research and Educational Centre in the period since 10.01.2021 until 01.08.2022. Females with non-iatrogenic hypergonadotropic hypogonadism caused by primary ovarian insufficiency (n=33); healthy females of reproductive age (18-49 y.o.; n=24). Patients have undergone laboratory genetic (leucocyte telomere length), biochemical analyses. DNA extraction - with Qiagen DNA blood mini kit (Germany).Leukocyte telomere length - with real-time polymerase chain reaction PCR (Flow-fish). Soft program IBM SPSS Statistics (version 26,0 for Windows)., Results: Females with POI due to estrogenic deficiency have slightly shorter mean telomere length (10,0 [7,9-10,7] kB, than healthy females of reproductive age (10,8 [10,0-13,1] кБ, р<0,001). Females with POI due to estrogenic deficiency have higher chances for development of carbohydrate metabolism disturbances (prediabetes) (р<0,043), increasement of FSH level (р<0,001). FSH level correlates moderately and negatively (ρ=0,434) with leukocyte telomere length (р<0,001)., Conclusions: Female with POI and receiving sex steroid replacement therapy have decrease of telomere length and increase of chances for carbohydrate metabolism disturbances in opposite to healthy reproductive females.

Aim: To reveal the peculiarities of steroidogenesis and arterial hypertension in «physiological» hyperandrogenism in men., Materials and Methods: One-stage simultaneous study. The groups of men with hyperandrogenism caused by increased total testosterone (n=34) and those with hyperandrogenism caused by increased dihydrotestosterone (DHT) (n=66) were compared. In determining the type of hyperandrogenism and allocating patients to groups, DHT and total testosterone levels were determined by enhanced chemiluminescence. Subgroups of men with and without arterial hypertension were compared in the group of patients with hyperandrogenism due to an increase in total testosterone. Body mass index, waist circumference, systolic and diastolic blood pressure, pulse, and LH, SBHG, estradiol, blood multisteroid levels by isotope dilution liquid chromatography/tandem mass spectrometry, glucose, blood lipid spectrum, uric acid, creatinine, renin, potassium, sodium, and blood chloride were assessed in all patients. Patients with arterial hypertension additionally underwent daily BP monitoring, albuminuria assessment, electrocardiography, ocular fundus examination. The baseline threshold level of significance was p<0.05. For multiple comparisons, the p significance level was calculated using the Bonferroni correction., Results: Statistically significant differences were found in the levels of 17-hydroxypregnenolone, 17-hydroxyprogesterone, and androstenedione, which were higher in men with elevated levels of total testosterone. No statistically significant differences in other laboratory parameters were found. No cases of increased blood pressure were detected in the group of men with elevated DHT. In the group of men with elevated total testosterone, 23,5% of men with arterial hypertension without targetorgan lesions were identified, while hyperandrogenism was associated with 17,6% of cases. Arterial hypertension associated with hyperandrogenism was characterized by a rise in blood pressure in the early morning hours. Estradiol levels, while remaining within normal limits, were statistically significantly lower in patients with arterial hypertension compared with men with elevated testosterone but without hypertension., Conclusion: No cases of arterial hypertension were observed in «physiological» hyperandrogenism due to elevated DHT levels, whereas its incidence in «physiological» hyperandrogenism due to elevated total testosterone was 23,5%. The features of steroidogenesis were increased production of 17-hydroxypregnenolone, 17-hydroxyprogesterone, and androstenedione in men with testosterone hyperandrogenism and decreased estradiol production in patients with arterial hypertension compared with patients without testosterone hyperandrogenism.

Studies of recent decades show a steady increase in the average life expectancy of a person, and women in particular. The World Health Organization predicts a four-fold increase in the number of women over 70 by 2030, and many of them over the age of 45 may face menopausal problems. Menopause is a physiological state in a woman's life, during which, against the background of age-related changes, there is a gradual decrease and shutdown of ovarian function and the cessation of estrogen production. Genitourinary syndrome occurs in every third woman in this period. Estriol is the main estrogen that specifically addresses problems associated with estrogen deficiency: dyspareunia, dryness and itching in the vagina and lower genitourinary tract, urinary incontinence, moderate urinary incontinence, and recurrent vulvovaginitis and cystitis. Vulvovaginal dystrophy in women of the older age group is a multidisciplinary problem at the intersection of gynecology, urology and dermatology, which can and should be solved to prevent more severe gynecological and urological pathologies.

Background: COVID-19 is a disease that has a negative systemic effect on the human body, including the male gonads. Therefore, the androgenic status in men with COVID-19 needs to be studied., Aim: To evaluate the levels of total testosterone, sex hormone binding globulin (SHBG) and free testosterone in men in the acute phase of COVID-19 and during convalescence., Materials and Methods: A continuous dynamic prospective study of 70 men with moderate to severe COVID-19 at the age of 50[44; 64] years. During the study, the levels of total testosterone, SHBG were determined with further calculation of the level of free testosterone by Vermeullen. The data were collected twice - at the patient's hospitalization and at his discharge. The differences between the groups were considered statistically significant at p <0.05., Results: At the time of hospitalization for COVID-19, hypogonadism syndrome was observed in 61 people - 87%. Patients with hypogonadism did not statistically significant differ in age and severity of COVID-19 disease compared to men without hypogonadism. Inpatient treatment lasting 12[10;14] days resulted in a statistically significant increase in the levels of total testosterone from 4,7[2,96;8,48] to 12,85[8,62;19,2] nmol/l, p<0,001; SHBG from 27,87[20,78;36,57] to 33,76[26,27;52,60] nmol/l, p<0,001 and free testosterone from 107[65;174] to 235[162;337] pmol/l, p<0,001. This led to the elimination of hypogonadism in 28 patients - 40%. Patients with persistent hypogonadism were statistically significantly older than men with normalized testosterone, there were no statistically significant differences in the initial levels of total testosterone, SHBG and free testosterone, and there were also no differences in the prevalence of severe COVID-19 (3,97[2,86;7,46] vs 4,26[2,93;5,96] nmol/l, p=0,100; 28,76[20,78;48,59] vs 24,63[18,85;31,70] nmol/l, р=0,994; 100[58;118] vs 96[64;143] pmol/l, p=0,522; 24 против 18%, p=0,754, respectively)., Conclusion: COVID-19 has a pronounced negative effect on the production of testosterone in men, leading to the development of laboratoric hypogonadism, which is potentially reversible. The reversibility of laboratoric hypogonadism is typical for younger patients.

Present worldwide healthcare researches prove that female patients are more sensitive to the population aging. Menopause or climacteria (climax) - is not as ageing itself, but a physiological unstoppable process. The main task for a physician is to improve life quality for female despite of ageing problems. Menopausal hormone therapy (MHT) due to the estrogen component has an anti-inflammatory, antioxidant effect and promotes the expression of telomerase, which together changes the homeostasis and integrity of telomeres. The use of MHT for five years or more can not only significantly change the quality of life, but also increase its duration. Literature search was carried out in national (eLibrary, CyberLeninka.ru) and international (PubMed, Cochrane Library) databases in Russian and English. The priority was free access to the full text of articles. The choice of sources was prioritized for the period from 2019 to 2021. However, taking into account the insufficient knowledge of the chosen topic, the choice of sources dates back to 1989.

According to present medical databases there many trials to provide in vivo researches in vivo to confirm/refute shortening process of telomeres among patients with Turner syndrome. Despite the successful clinical experience of providing such patients with Turner syndrome, a lot of omics (proteomic and metabolomic) aspects still stay unclear. Main disadvantages of most researches are small volume and minimized mathematical correlation with chronic disease (coronary heart disease, essential hypertension, cardiovascular malformations). Finally, organization of international prospective multi-centered researches in vivo including patients with mosaic cariotype and co-operation between physicians and biologists are optimal solutions for this present problem.

Polycystic ovary syndrome (PCOS) is a polygenic endocrine disorder caused by both genetic and epigenetic factors. Depending on the period of a woman's life, the clinical picture, diagnosis, and treatment tactics of the disease are different. PCOS has a complex of reproductive, metabolic and psychological characteristics. The target audience of these clinical recommendations are obstetrician-gynecologists, endocrinologists, general practitioners, general practitioners. In these clinical guidelines, all information is ranked according to the level of persuasiveness of recommendations and the reliability of evidence, depending on the number and quality of studies on this issue.

Background: Melatonin is the main hormone of the pineal gland. By regulating circadian rhythms and being an immune regulator and antioxidant, this hormone takes part in the work of the ovaries: its high concentrations block apoptosis and neutralize reactive oxygen species involved in folliculogenesis, ovulation, egg maturation and corpus luteum formation., Aim: To study melatonin status and its relationship with menstrual dysfunction and sleep disorders in obese women of reproductive age., Materials and Methods: In a one-stage comparative study, women 18-35 years old took part: 30 patients with obesity and menstrual disorders of an inorganic nature and 30 healthy women in the comparison group with normal weight and regular menstrual cycle. All participants underwent a questionnaire to identify somnological disorders, and the level of melatonin in saliva and 6-sulfatoxymelatonin in urine was also investigated., Results: In the group of patients with obesity (n=30), various sleep disorders were encountered in 47% of cases (p=0.003), including more often obstructive sleep apnea syndrome was recorded (30% of cases), and a correlation was found between the indicators of the questionnaire survey of subjective sleep characteristics and body mass index of patients (r=0.450, p=0.030) compared with a group of healthy women with normal weight (n=30). In the main group, the level of melatonin in saliva was statistically significantly lower than in the control: median 12.6 pg / ml and 25.5 pg / ml, respectively (p=0.008), the same pattern was recorded for 6-sulfatoxymelatonin: 14, 72 pg / ml and 31.12 pg / ml, respectively., Conclusion: Patients with obesity and menstrual dysfunction are more likely to suffer from various sleep disorders and have lower levels of melatonin in saliva and 6-sulfatoxymelatonin in urine.

Background: The cocaine-amphetamine regulated transcript has been discovered long time ago (circa over 25 years ago) but still stays not enough investigated. Just during last five years scientist's society started providing interest to the genomic, proteomic and metabolic essence of the cocaine-amphetamine regulated transcript., Aim: The evaluation of historical pathway and perspectives of the cocaine-amphetamine regulated transcript medical investigations., Materials and Methods: The literature search has been provided via Russian (eLibrary, CyberLeninka.ru) and international (PubMed, Cochrane Library) databases and among articles on Russian and English languages. The main criteria for article selection was free access and 2019-2021 years of publishing. Although the introduction is based on the articles published in 1989. The present article was created according to the federal project «Central and peripheral pathophysiological mechanisms of adipose tissue diseases and their clinical and hormonal manifestations патофизиологические механизмы развития болезней жировой ткани с учетом клинических и гормональных характеристик» (2020-2022)RESULTS AND CONCLUISON: It is necessary to keep on investigating genomic, proteomic and metabolomic markers because they contain important clues for successful resistance against human diseases. The 21st century is the era of transformation from simple clinical medicine to personalized science. For example, researches in the area of cocaine-amphetamine regulated transcript may result in invention of genetic medicine against dangerous metabolic diseases.

Teratomas are one of the most common tumors diagnosed in fetuses and newborns. In this age group, extragonadal teratomas predominate, among which the mediastinum ones accounts for up to 15% of teratomas of the perinatal period. They may be associated with the thymus or thyroid gland; in some cases a clear connection with adjacent organs cannot be identified. Teratomas of the heart, also localized in the mediastinum, are often considered separately from the mediastinal ones; most often the tumor affects the pericardium. The article describes two cases of mediastinal teratomas detected by ultrasound in the second trimester of pregnancy, with signs of rapid growth and compression symptoms typical for this localization of the tumor - hydropericardium and other manifestations of non-immune fetal hydrops. In both cases, immature teratomas (grade 2 and 3) were diagnosed with a predominance of immature neuroectodermal tissue, as well as with the presence of endoderm derivatives, including areas of the hepatoid structure, microglandular structures and cysts lined with mucus-forming epithelium. The mesodermal component was represented by hyaline cartilage. An immunohistochemical study revealed an extremely high proliferative activity in the immature neuroectodermal component - more than 90% of positive nuclei were detected in the neuroepithelium upon reaction with Ki67 antibodies. In all other tissue elements, proliferative activity was low.

Primary hyperparathyroidism (PHPT) is an endocrine disorder of parathyroid glands characterized by excessive secretion of parathyroid hormone (PTH) with an upper normal or elevated blood calcium level. Classical PHPT refers to a symptomatic, multi-system disorder, wich can lead to a significant decrease in the quality of life, disability of patients, and even an increased risk of premature death. Hypercalcemia and the catabolic effect of PTH on various cells are considered as the main pathogenetic mechanisms of the PHPT associated complications. In the last two decades, there has been an increase in the incidence of PHPT, mainly due to the mild forms of the disease, primarily due to the routine calcium screening in North America, Western Europe and, Asia. High prevalence of the disease, as well as the variety of clinical manifestations, cause the attention of different specialists - physicians, rheumatologists, urologists, nephrologists, cardiologists and other doctors. This review cover the main issues of Russian guidelines for the management of PHPT, approved in 2020, including laboratory and instrumental methods, differential diagnosis, surgical and conservative approach, short-term and long-term follow-up. This guidelines also include the recommendations for special groups of patients with hereditary forms of PHPT, parathyroid carcinoma, PHPT during pregnancy.

Hypoparathyroidism is a rare disorder characterized by the absent or inappropriately decreased serum parathyroid hormone in the parathyroid glands, which is accompanied by impaired calcium-phosphorus metabolism.The main etiology of hypoparathyroidism remains damage or removal of the parathyroid glands during neck surgery. In view of the incidence of thyroid cancer, primary hyperparathyroidism and other pathologies of the neck organs, which radical treatment can lead to the parathyroid gland impairment, an increased number of patients with hypoparathyroidism is expected. Autoimmune hypoparathyroidism is the second most common form of the disease, usually occurring as part of type 1 autoimmune polyglandular syndrome. Autoimmune hypoparathyroidism usually occurs in childhood and is characterized by a severe course of the disease, especially in the case of concomitant malabsorption syndrome.Chronic hypoparathyroidism of any etiology requires lifelong multicomponent therapy, as well as careful monitoring and an individual approach to choose the optimal treatment strategy. In the absence of adequate follow-up, the risks of long-term complications significantly increase, particularly in the renal, cardiovascular systems; in the soft tissues and in the brain, it could lead to visual disturbances; pathology of the musculoskeletal system with a decreased bone remodeling and a potential risk of fractures, as well as to the neurocognitive disorders and an impaired health-related quality of life.Timely diagnosis, rational medical therapy and management strategy may reduce the risks of short-term and long-term complications, frequency of hospitalizations and disability of patients, as well as improve the prognosis.This review covers the main issues of Russian guidelines for the management of chronic hypoparathyroidism, approved in 2021, including laboratory and instrumental evaluation, treatment approaches and follow-up. This guidelines also include the recommendations for special groups of patients: with acute hypocalcemia, hypoparathyroidism during pregnancy.

Background: The increasing prevalence of gestational diabetes mellitus (GDM), the high probability of unfavorable pregnancy outcomes for the mother and the fetus, as well as a number of long-term consequences in GDM are a serious medical and social problem and require the need for its prevention by correcting risk factors, timely diagnosis and effective treatment., Aim: Analysis of risk factors for the development of gestational diabetes mellitus (GDM), the relationship between GDM, the course and outcomes of pregnancy., Materials and Methods: Retrospective analysis of 79 case histories of patients with confirmed GDM in the period from 2015 to 2017., Results: In the structure of risk factors for mother and fetus, age over 30 years (73.1%), burdened heredity for type 2 diabetes mellitus (T2DM) (30.8%), mother's pre-pregnancy body mass index (BMI) (overweight / obesity (26.9%)) had the greatest impact. Among the complications of pregnancy, the most common was the caesarean section (47.4%). The incidence of other complications (macrosomia (9%), premature birth (7.7%), congenital malformations of the fetus (5.1%), preeclampsia (5.1%) was lower than the average frequency of these complications in GDM, described in the literature. Nevertheless, it is 1.5-2 times higher than the average population indicators. In the course of statistical analysis of the data it was revealed, that the higher the mother's pre-pregnancy BMI, the lower the Apgar score for the first minute in the newborn., Conclusion: Women with GDM require intensive monitoring of the course of pregnancy and timely hospitalization for planned delivery, and the provision of competent obstetric benefits.

One of the new directions in the study of reproductive disorders in obese women is the effect and receptor sensitivity of  melatonin on the gonadotropic function of the pituitary gland and ovariogenesis, taking into account the chronology of «light pollution». At the present stage, there is very little literature on the influence of the aspects of «light pollution» on the problem of obesity and reproductive disorders in the literature. This review is an attempt to combine the above problem in terms of the impact of «light pollution» and the level of receptor sensitivity of melatonin in women of reproductive age with obesity. The literature search was carried out in Russian (eLibrary, CyberLeninka.ru) and international (PubMed, Cochrane Library) databases in Russian and English. Free access to the full text of the articles was a priority. The selection of sources was prioritized for the period from 2015 to 2019. However, given the insufficient knowledge of the chosen topic, the choice of sources was dated from 1992. The work was carried out as part of the study «Central and peripheral pathophysiological mechanisms of development of adipose tissue diseases, taking into account clinical and hormonal characteristics» 2020-2022.

The paper describes a case of a perinatal lethal Gaucher disease in a 29-week-old fetus with non-immune hydrops, facial dysmorphia, hepatosplenomegaly, and hypoplasia of cerebellum and pons. Gaucher cells were found in the lymph nodes, spleen, lungs, thymus, cerebellum, and bone marrow. No storage cells have been detected in the placenta. There was a significant placental weight increase due to swelling. The diagnosis of Gaucher disease was confirmed by biochemical analysis (deficiency of glucocerebrosidase activity and sharply increased hexanoylsphingosine concentration) and molecular genetic techniques (the presence of two mutations of the GBA gene). Our observation shows that characteristic histologic signs of disease can be detected at early stages of development.

Background: It has been proven that vitamin D plays an important role in pregnancy. Deficiency of this element may be associated with the risk of developing gestational diabetes mellitus, preeclampsia, placentar insufficiency, low birth weight and premature birth., Aims: To conduct an epidemiological analysis of vitamin D supply in women at different stages of pregnancy, living in Russia., Materials and Methods: We included 1198 pregnant women living in 3 regions of Russia in the observational, multicenter, cross-sectional, continuous study. All pregnant women were tested for serum 25(OH)D levels. We collected biomaterial from August 2018 to December 2019. The end point of the study was the indicator of vitamin D supply in pregnant women and its level depending on the trimester of pregnancy and region of Russia. Statistical analysis included counting and grouping according to vitamin D levels, and calculating the median vitamin D concentration in each region., Results: We confirmed vitamin D deficiency in all regions. The optimum level of this element is present in less than 7% of women. Insufficiency of this element is present in 20,62% of all women. The largest percentage of them is in a deficit of this element - 46,66%. We found that the lowest rates are in Smolensk, where the median was 12,75 ng/ml. In addition, we found changes in vitamin D concentration: with an increase in gestational age revealed a decrease in its level., Conclusions: In our study, we confirmed the presence of a 25(OH)D deficiency in most of the examined pregnant women, which is consistent with international epidemiological data. We should remember about these both at the stage of pre-gravid preparation and at the stage of pregnancy itself in order to achieve the optimal level of vitamin D.

The WHO has declared a SARS-CoV-2 pandemic. During a pandemic, the researches aimed at finding the new treatments for SARS-CoV-2 become relevant. The review focuses on studies of androgens and antiandrogens in this disease. Since the beginning of the COVID-19 epidemic, it has been noted that men have more severe forms of infection and higher mortality. The main cause of both the severity of the disease and the high mortality of men from COVID-19 are associated with androgens. It was found that patients receiving androgen deprivation are less likely to become infected and easily tolerate COVID-19. The researchers explain the effect of the therapy by the effect on the TMPRSS2 protein. It was found that both TMPRSS2 expression and a more severe course of coronavirus infection are observed in men with hyperandrogenism - androgenic alopecia, acne, excessive facial hair growth and increased skin oiliness. In this regard, some researchers suggest to use androgen deprivation for men at high risk of developing COVID-19. Steroid and non-steroidal antiandrogens are used for androgen deprivation. At the same time, obtaned scientific data on the relationship of severe forms and mortality of COVID-19 with low testosterone levels leads to a hypothesis about the possibility of a positive effect not of androgen devrivation therapy but of androgen replacement therapy in case of hypogonadism have diagnosed. These studies have not been completed recently, and data on the effectiveness and safety of antiandrogens and androgens in the treatment of a new coronavirus infection require clarification.

This article reviews the literature on placental morphofunctional changes in placenta of patients with type 1 and type 2 diabetes mellitus and gestational diabetes mellitus. The detailed analysis of features of pathogenesis of various abnormalities of the fetoplacental complex depending on the type of diabetes, its influence on the formation of the placental vascular bed. The analysis of mechanisms of development of placenta formation disorders, pathologies of placental vascular bed, the role of hyperglycemia and hyperinsulinemia in villous maturation, placental weight gain, perinatal outcomes. The discussed anomalies have a significant impact on the fetoplacental complex, acting as epigenetic factors, forming the environment for the fetus, which may later affect the health of the unborn child. They lead to adverse perinatal outcomes, including high infant morbidity and mortality. Literature search was performed in Russian (eLibrary, CyberLeninka.ru) and international (PubMed, Cochrane Library) databases in Russian and English languages. The free access to the full text of the articles was in priority. The selection of sources was prioritized for the period from 2016 to 2020. However, due to the lack of knowledge of the chosen topic, the selection of sources was dated from 2001.

Aim: To compare ovarian reserve in healthy women of reproductive age - carriers of antithyroid antibodies (ATA) and in healthy women of reproductive age negative for ATA., Materials and Methods: 70 healthy women of young reproductive age in the state of euthyroidism (from 18 to 38 years old) were examined. Participants were divided into equal groups (n=35) depending on the status of the presence of antithyroid antibodies (AT-TPO, AT-TG). On the 2nd-4th days of the menstrual cycle, the following markers of the ovarian reserve were determined: serum levels of anti-Müllerian hormone (AMG), inhibin B, FSH, LH, estradiol, testosterone and progesterone, as well as ultrasound parameters - the number of antral follicles and the volume of the ovaries. In addition, to determine the predisposition to premature ovarian failure, an analysis was performed to the number of CGG repeats in the FMR1 gene., Results and Discussion: Statistically significantly differs such parameters as the level of estradiol and testosterone, while the differences were not clinically significant. All the parameters evaluated were within the normal range, the main predictors of the ovarian reserve (levels of AMG and inhibin B, the number of antral follicles) remained in the normal range. An increase in the number of repeats of CGG in the FMR1 gene was not detected in any of the participants in the study., Conclusion: In healthy young reproductive age women, the status of ATA does not have a direct effect on the ovarian reserve.

Aim: To evaluate the ovarian reserve function in female patients with obesity in comparison with women without obesity., Materials and Methods: This study evaluated 500 caucasian women, age 20-30 years, 250 with obesity (body mass index, BMI ≥30 kg/m2) and 250 without obesity (BMI &lt;30 kg/m2). Anthropometrics, serum concentrations of anti-Mullerian hormone (AMH), inhibin B, follicle stimulating hormone, luteinizing hormone, estradiol, progesterone, and testosterone were compared as ovarian volume (cm3) and antral follicle count (AFC), determined by ovarian transvaginal ultrasonography., Results: We reveal statistically significant difference in following parameters: AMH (2.7±0.47 ng/ml vs. 3.8±0.63 ng/ml; p&lt;0.05), testosterone (1.4±0.3 nmol/l vs. 0.7±0.2 nmol/l; p&lt;0.01), ovarian volume (7.2±1.9 cm3 vs 9.5±1.7 cm3; p&lt;0.05), and AFC (13.3±4.5 vs 20.7±7.2; p&lt;0.01) in obesity group vs. control group respectively., Conclusion: Ovarian reserve function is significantly lower in obese patients than in healthy control subjects of young reproductive age, but ovarian reserve parameters are in normal reference range even in obese patients.

Endocrine Medical Research center (EMRC) of the Ministry of health of Russia is unique clinical center, that have no analogs in the world. All forms of endocrine disorders may be diagnosed and treated here by implication of innovative methods. Institute of reproductive medicine of EMRC was open on 2017, director of this institute - MD, PhD E.N. Andreeva. Staff of this institute include highly experienced investigators and physicians. One of the most ambitious projects of the institute is development of prevention, diagnostic and treatment algorithm for patients with infertility of endocrine origin. For these purposes large prospective clinical trial (5000 patients) will be conducted with implementation of most modern genetic, laboratory and instrumental diagnostic methods. Results of this trial will allow diagnose, treat and prevent reproductive pathology in patients with endocrine diseases.

Aim: To investigate the impact of menopausal hormone therapy (MHT) on the expression of risk factors for cardiovascular events (CVEs) in patients with Shereshevsky-Turner syndrome (STS); to elaborate an algorithm for patient management using MHT., Subjects and Methods: From 2010 to 2012, a total of 41 patients aged 14 to 35 years with STS were examined in the framework of a prospective observational study. 100 STS case histories in 2000 to 2009 were retrospectively analyzed. The indicators of the so-called cardiometabolic risk, such as body mass index (BMI), lipidogram readings, venous plasma glucose levels, and blood pressure, were estimated in relation to the type of MHT. In the prospective part of the investigation, an angioscan was used to estimate vessel characteristics (stiffness, wall tone, endothelial function (EF)), by using the examination data., Results: 90% of the patients with STS were found to have risk factors for CVEs: atherogenic dyslipidemia (85%; 51% in the general female population of the same age), diastolic hypertension (36%; no more than 5% that is not typical for age-matched healthy general female population). In addition to increased arterial wall stiffness (AWS), obvious EF disorder is typical for STS patients. MHT was accompanied by a dose-dependent (estradiol, at least 2 mg) reduction in diastolic blood pressure by an average of 13% over 24 months, an increase in high density lipoprotein levels by more than 10% over 24 months and also contributedto a decrease in AWS and an improvement in EF., Conclusion: By favorably affecting the EF of vessels and reducing the severity of atherogenic dyslipidemia, MHT potentially enables a reduction in CV risk in patients with STS.

Polycystic ovary syndrome (PCOS) is the most common chronic endocrine disease in women. The prevailing complaints at a young age are menstrual irregularities, infertility, and hyperandrogenism-related problems. However, metabolic disorder-induced complications have been in the foreground over years. The review gives the current ideas on a change of clinical manifestations in the natural course of PCOS, as well as the pathogenetically grounded prevention of complications in patients.

Pregnancy in women with type 1 or 2 diabetes mellitus (DM) is associated with an increased risk for complications in both the mother and her fetus. The impact of these complications on modifiable risk factors may substantially improve pregnancy outcomes and reduce malformation rates in children. This is a goal of pregravid preparation (PGP) in this category of patients. The review gives the main points of PGP in patients with types 1 and DM and shows the results of main studies providing evidence for PGP in DM. In particular, by the moment of conception, DM patients should achieve a glycosylated hemoglobin (HbA1c) goal of <6% no later than 4 weeks before conception and during the first trimester of pregnancy, take folic acid in a high dose (at least 4000 µg, or 4 mg, daily), quit tobacco smoking and alcohol use, receive potentially teratogenic drugs, and, if need be, lose weight (the target body mass index of <27 kg/m2).

Significant progress in the developmental biology of Drosophila is largely due to the improvement of methods of genetic manipulation and, in particular, development of ways to create mosaic organisms. The main characteristic of the mosaic organisms is the presence of genetically different populations of cells. For example, some tissues express a transgenic reporter gene that is absent in other cells of the body. This principle is used in a variety of the methods with the common name lineage tracing. The essence of these approaches is to perform the targeted changes in the genetic apparatus of progenitor cells that give rise to cell lines or organs and tissues. Genetic modification in progenitor cells, such as the ability to express a fluorescent protein, will be inherited by the next cell generations, and, as a result, the entire cell line or tissue will have a tag, which distinguishes it from the rest of the body. The lineage tracing methods allow tracking the cell generations, studying the cell proliferation process, tracing their origin and investigating the function of genes of interest in the development of a single tissue or organ. We have designed an approach to selectively label germ line or somatic cells in the gonads of Drosophila.

The modern concept of intercalary heterochromatin as polytene chromosome regions exhibiting a number of specific characteristics is formulated. DNA constituting these regions is replicated late in the S period; therefore, some strands of polytene chromosomes are underrepresented; i.e., they are underreplicated. Late-replicating regions account for about 7% of the genome; genes are located there in clusters of as many as 40. In general, the gene density in the clusters is substantially lower than in the main part of the genome. Late-replicating regions have an inactivating capacity: genes incorporated into these regions as parts of transposons are inactivated with a higher probability. These regions contain a specific protein SUUR affecting the rate of replication completion.

The molecular biological features of the eutopic and ectopic endometrium were studied in 46 patients with adenomyosis, 44 with endometrioid cysts in the ovaries, and 34 with disseminated mixed forms of genital endometriosis. Reproductive-aged patients with the eutopic endometrium in a proliferation phase with hyperplastic or inflammatory changes were selected. Ten samples of the endometrium in a phase proliferation, which had been obtained at medicolegal autopsy of women without reproductive disorders, were studied as a control group. Both the glandular and stromal components of the ectopic and eutopic endometrium in different forms of endometriosis were shown to differ from the intact endometrium in their molecular biological features (the expression of Ki-67, Bcl-2, Bax, vascular endothelial growth factor, transforming growth factor-beta1, matrix metalloproteinases 2 and 10, matrix metalloproteinase-2 inhibitor, the enzyme cytochrome P450 aromatase.

Aim: To evaluate the effect of the vaginally inserted hormone-releasing system 'NuvaRing' on carbohydrate metabolism and acceptability (menstrual cycle control) of extended regimens of using as compared with the standard regimen (21/7) in women with type 1 diabetes mellitus (DM) in reproductive period during 24 months., Methods: The open randomised study included a total of 109 women with type 1 DM, using 'NuvaRing' in different regimens (21/7, 42/7, 84/7 and 357/7). Average daily insulin requirements, the levels of glycosylated haemoglobin were determined at baseline, after 6, 12, 18 and 24 months of contraception. The control group was composed of 22 age-matched women with type 1 DM using no methods of contraception., Results: Using the contraceptive system 'NuvaRing' in type 1 DM women in the reproductive period has proved to exert no clinically significant effect on carbohydrate metabolism in prolonged regimens, as well as in standard regimen. The overall number of bleeding days and spotting days was comparable in different groups. Longer regimens with fewer breaks were associated with fewer days of bleeding but a larger number of spotting days as compared with the shorter regimens, with a tendency towards a gradual decrease in spotting days during a year., Conclusion: The releasing system 'NuvaRing' proved to be a reliable and safe means of contraception for late reproductive age women with type 1 DM.

Type 1 diabetes mellitus (DM) has negative effect on the development and functioning of the reproductive system in young girls. The time of onset of type 1 DM (especially in the puberty period), duration of the disease, and poor compensation of disturbed carbohydrate metabolism are supposed to be the most probable causes of delayed pubertal development exerting negative effect on the age of menarche and increasing the frequency of menstrual problems (largely oligo- and amenorrhea). Despite a wealth of relevant investigations, the cause of reproductive dysfunction remains unknown even though negative effect of type 1 DM on different components of the hypothalamo-pituitary-ovarian axis has been fairly well documented. The pathogenetic mechanisms of reproductive disorders may consist of suppression of pulsed production of gonadotropin releasing hormone (GnRH) due to enhanced central dopaminergic and opiate activities, decreased concentration of insulin receptors on GnRH-synthesizing neurones, and changes of serum leptin level in the affected girls. In patients with type 1 DM, hypothalamic effects on the pituitary may be supplemented by the direct action of products of free radical oxidative activity leading to a decrease in the production of trophic hormones. Also considered, is primary ovarian origin of menstrual disturbances in girls with type 1 DM. Of great importance are studies concerning autoantibodies against different ovarian structures, variations in concentrations of insulin-like growth factor-1 (IGF-1) and hormone ghrelin.

The review gives updates on the pathogenesis of background, precancer, and cancer of the cervix uteri. Epidemiological and molecular biological studies have established that human papillomavirus infection is the most important factor of carcinogenesis of the cervix uteri. The impact of reproductive dysfunction on the development of cervical pathology has been assessed and a possible mechanism of involvement of sex steroids in carcinogenesis assumed.

Aim: To evaluate the effect of the vaginally inserted hormone-releasing system NuvaRing on carbohydrate and lipid metabolism and the hemostasis system, over 6 months of use, in late reproductive-age women with type 1 diabetes mellitus (DM)., Methods: The open randomized study included a total of 25 women with type 1 DM using NuvaRing. Average daily insulin requirements, levels of glycosylated hemoglobin (HbA1c), total cholesterol, triglycerides, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol, the state of coagulation hemostatis and fibrinolytic activity were determined at baseline and after 3 and 6 months of contraception. The control group was composed of 20 age-matched women with type 1 DM using no methods of contraception, as well as 20 apparently healthy women using the NuvaRing device., Results: Use of the NuvaRing contraceptive system in type 1 DM women in the late reproductive period was shown to exert no clinically significant effect on carbohydrate and lipid metabolism on the background of persistent and satisfactory compensation of carbohydrate metabolism (HbA1c < or = 7.5%), with a neutral impact on the hemostasis system., Conclusion: The NuvaRing hormone-releasing system proved to be a reliable and safe means of contraception for late reproductive-age women with type 1 DM.

The primary structure of the coat protein (CP) gene was examined for pathogenic strain MS-1 and vaccine strain VIROG-43M of the cucumber green mottle mosaic virus (CGMMV). In CP amino acid composition, strains MS-1 and VIROG-43M are typical representatives of CGMMV: their CPs have 98-100% homology to CPs of other tobamoviruses of the group. The CP gene has the same nucleotide composition in pathogenic MS-1 and vaccine VIROG-43M, indicating that strain attenuation is not determined by this gene. The CP amino acid sequences of the two Russian strains are fully identical to the CP sequences of two Greek strains, GR-3 and GR-5. However, the nucleotide sequences of their genes differ in 13 bp, testifying to the difference between the Russian and Greek strains.

The identity of Chironomus atrella Townes has been confusing because the name has been used for at least 2 quite different species. This situation is clarified karyosystematically by describing the banding patterns and chromosomal polymorphisms from a number of locations in Canada and the US. Most populations show only moderate levels of polymorphism (average heterozygosity, 0.36), although in some samples from shallow waters, the level of polymorphism is much higher (average heterozygosity, up to 0.92). The banding patterns of the polytene chromosomes are either identical or closely related to those found in Holarctic species with a northern distribution. These patterns and the distribution of inversions in the C. atrella populations are consistent with a progenitor that colonized North America across the Bering Strait and spread down the Rocky Mountain chain; at the same time, new gene combinations developed that allowed it to spread eastward over the majority of the continent.

A significant portion of a eukaryotic genome is silent (epigenetically repressed). In Drosophila melanogaster, this portion includes mainly regions of pericentric and intercalary heterochromatin and euchromatin regions subject to position-effect variegation. Detailed study of the organization of intercalary heterochromatin regions of Drosophila melanogaster polytene chromosomes started from the discovery of the SuUR gene (Suppressor of UnderReplication). The ability of the SuUR mutation to suppress underreplication in intercalary heterochromatin regions was used for molecular tagging of these regions. We showed that underreplicated intercalary heterochromatin regions contained silent unique genes and retained the features of late replication and transcriptionally inactive chromatin state in various cell types. Over 50% of these regions contain unique genes clustered on the base of coordinated expression. The origin of clusters and putative mechanisms of their gene expression are discussed. Data on the SuUR gene, its expression, and effect on polytene chromosome structure and replication are summarized.

Aim: To assess the effect of combined oral contraceptives (COCs) and intrauterine devices (IUDs) on carbohydrate and lipid metabolism and hemostasis in perimenopausal diabetic women., Methods: The open randomized study included a total of 113 diabetic women using COCs with different estrogen/progestogen profiles - ethinylestradiol (EE) 20 microg/desogestrel 150 microg, EE 30 microg/desogestrel 150 microg and EE 30 microg/gestodene 75 microg - and levonorgestrel-releasing or copper IUDs. Average daily insulin requirements, levels of glycosylated hemoglobin, total cholesterol, triglycerides, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol, the state of coagulation hemostatis and fibrinolytic activity were determined at baseline and after 3, 6, 9 and 12 months of contraception. The control group was composed of 40 age-matched diabetic women who did not use any methods of contraception., Results: Neither COCs nor IUDs influenced glycosylated hemoglobin and had little or no influence on the elevation in the requirements for insulin preparations. The majority of the preparations did not exert any unfavorable effect on the blood lipid profile. Taking COCs was accompanied by increased intravascular activation of blood platelets and to a lesser degree by alterations in parameters of hemostatic homeostasis. The use of IUDs had a neutral effect on blood coagulation and fibrinolysis systems., Conclusion: Comparing lipid levels and hemostatic variables as a function of glycosylated hemoglobin level, we conclude that diabetes control has greater influence on these parameters than the type and dose of steroids involved in the contraceptive devices.

Using gold labeled antibodies, we developed and tested an immunoelectron microscope (IEM) method for detection of protein localization in Drosophila melanogaster polytene chromosomes. This method is based on procedures widely used for indirect immunofluorescent (IF) staining of salivary gland polytene chromosome squashes. The application of IEM was evaluated by using specific antibodies against proteins earlier localized in both decondensed (interbands and puffs) and compact (bands) regions of polytene chromosomes. In all the experiments, IEM and IF images for homologous chromosome regions were compared. When applied to regions of loose structures, IEM enabled us to localize, with high precision, signals in fine bands, interbands and puffs. There was a good correspondence between immunogold EM and IF data. However, there was no correspondence for dense bands: gold particles were distributed at their boundaries, while the entire bands showed bright fluorescence. This discrepancy probably resulted from a poor penetration of antibodies conjugated to gold particles in the tightly packaged structures. From the results obtained it may by concluded that the IEM method is advantageous for studying the fine protein topography of loose decompacted regions of polytene chromosomes. And this must be taken into consideration when protein localization in polytene chromosomes is performed.

Using reversed-phase high-performance liquid chromatography, two components of the coat protein of isolate No. 3 of the cucumber green mottle mosaic virus (CGMMV, cucumber strain), Cp1 (minor) and Cp2 (major), were isolated and characterized by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS). In the Cp2 mass spectrum, two polypeptides with Mr of 16,727.0 and 16,813.5 were detected. By Edman degradation in combination with mass spectrometry, the primary structure of the tryptic peptides of Cp2 comprising in total 150 amino acid residues was determined. Two amino acid substitutions, Val-56-->Ala-56 and Asp-64-->Ser-64, were revealed in Cp2, as compared to the watermelon strain of the virus. Cp1 was shown to consist of three polypeptides with Mr of 10,014.2, 10,224.9, and 10,355.9 corresponding to the N-terminal regions of Cp2 (positions 1-92, 1-94, and 1-95). The observed heterogeneity of the coat protein of CGMMV, cucumber strain, may be due to proteolysis during protein isolation.

In a group of patients with endometriosis and in a control group of healthy women, the polymorphism of the following systems were studied: ABO and RH blood-group systems; serum proteins haptoglobin (HP), transferrin (TF), vitamin D-transporting protein (GC), protease inhibitor (PI), and the third component of the complement (C3); serum enzymes-amylase of the loci 1 and 2 (AMY1 and AMY2), pseudocholinesterase (E2), and alkaline phosphatase (PP); erythrocytic enzymes-acid phosphatase (ACP1), phosphoglucomutase (PGM1), superoxide dismutase (SOD-A), esterase D (ESD), and glyoxalase (GLO1). Statistically significant differences between the groups compared were established for five genetic systems: ABO, E2, C3, TF, and PGM1. Among patient with endometriosis, the rare alleles of the locus ESD-ESD5 and ESD7-were found, along with ESD 5-5 homozygotes. Several genetic loci can be involved in the pathogenesis of endometriosis; their products can be specifically realized due to peculiarities of biochemical reactions in the organisms of people predisposed to this pathology.