Women dealing with hot flushes: the role of ß-alanine.

Hot flushes (HFs) are a very frequent condition in menopausal women, associated with a marked decrease in quality of life, impaired ability to carry on daily activities and sleep disturbances. However, this condition is often only given poor attention in daily practice and in clinical research. Indeed, several treatments for HFs exist. The most effective is considered to be hormone replacement therapy, but this strategy has been associated with a poor risk-benefit ratio given its link with the development of cancer. Other treatments have been tested and are currently used, but they are usually only poorly effective or cannot be recommended in all patients due to potential side effects or interference with other molecules. Therefore, there is a major need for new treatment options for HFs. ß-alanine supplementation is widely used for the enhancement of energetic metabolism and is known to be devoid of any relevant adverse effect. BA has also been widely used for the treatment of HFs. This narrative review will discuss the current pharmacological management of HFs and will present the role of ß-alanine in this setting.

THE PREVALENCE OF HIRSUTISM AND ETHNICAL PECULIARITIES OF HAIR DISTRIBUTION IN GEORGIAN ADOLESCENT POPULATION IN TBILISI.

Objective - the purpose of the study is evaluation of the Hirsutism prevalence and ethnical peculiarities of the hair distribution in Georgian female adolescents of Tbilisi, Georgia. 2592 randomly selected female adolescents of Tbilisi were included in the study. They completed standard questionnaires consisted of questions about the existence of hirsutism and its locations. For clinical assessment 2 groups were selected from them: group 1 - 117 adolescents with hirsutism and 178 without it. For clinical evaluation of hirsutism modified Ferriman-Gallwey score was used. Based on the self-estimation the hirsutism prevalence was 26.62% (690 out of 2592), while clinically established prevalence of hirsutism was 20.61%. The most prevalent areas of hair distribution by self-estimation were the face and the abdomen. Clinical assessment of patients with hirsutism showed that mean value of Ferriman-Gallwey Score was 12.87±5.94. Hair distribution by clinical assessment was most significantly observed in the lower abdomen (78.33%), upper lip (76.67%) and chest (68.33%). This is the first study of hirsutism prevalence in ethnically Georgian adolescent female population. The study has shown that the value of prevalence by self-estimation exceeds analogous value established clinically, and the sites with hair excess are lower abdomen, upper lip and the chest.

IMPORTANCE OF ISOLATED GESTATIONAL HYPOTHYROXINEMIA IN THE DEVELOPMENT OF OBSTETRIC AND SOMATIC PATHOLOGIES.

The isolated hypothyroxinemia of pregnancy (IHP) has gained specific attention in the specialized literature during the recent years as the possible factor impeding the intellectual development of fetus and increasing the risk of complications related with pregnancy, delivery and perinatal period. Aim of the study was to define the importance of isolated hypothyroxinemia in the development of obstetric and somatic pathologies in outpatient population of pregnant females. The study of prospective design was performed at the base of "David Gagua Clinic" Ltd. Based on hospital referral we selected the pregnant patients who were diagnosed for isolated hypothyroxinemia in the 1st trimester of pregnancy by clinical-laboratory studies. 104 pregnant females with isolated hypothyroxinemia were included in the main group, and 58 pregrant females of reproductive age who were not identified to have thyroid pathology by screening studies were included in the control group,. The questionnaire used in the study process included the retrospective medical history data, demographic findings, information about premorbid background, genetic burden of somatic pathology, social-economical factors (including education level, living conditions, economic income, family environment etc.) and concomitant somatic pathology. In addition, it included the clinical and para-clinical study data and pregnancy follow-up findings. The test studies for thyroid status were performed every trimester and after one month postpartum. The software packages Microsoft Excel (2010) and SPSS/v.12 was used for statistical treatment of data. The digital data is presented by M±STD, where M is the arithmetic mean and STD is the standard deviation of arithmetic mean. To define the confidence interval for the indices and their relation, we calculated 2 and p, whose critical value was defined to be 0.05. Based on analysis of the acquired data, we found out that pregnant females with isolated hypothyroxinemia were more statistically demonstrating asthenia, dry skin, increased hair loss and fragile nails, and from somatic disorders - pregnancy-associated vomiting and anemia. From concomitant diseases, allergic disorders (18.2%), primary dysmenorrhea (27.8%), spontaneous abortions (25%) were taking the highest incidence rate and other obstetric complications (premature delivery, late delivery) were higher in the main group, though statistically significant difference was not demonstrated. It must be noted that isolated hypothyroxinemia in the studied cohort was mostly found in 1st trimester of pregnancy, whereas according to the literature data, the latter is demonstrated more frequently in the second or third trimester. The above mentioned makes us consider that the iodine deficit in the cohort of pregnant females studied by us was probably present before pregnancy as well and maybe with even higher extent. Thus, the isolated hypothyroxinemia developed in the very first trimester of pregnancy still has its negative impact on the pregnancy course and outcome, despite of applied treatment. According to performed studies and their results, for the prevention of obstetric and perinatal complications, its important to administer iodine preparations together with folic acid at pregravid stage in addition to complete elimination of diet abnormalities, plan the pregnancy in stable normothyroxinemia conditions and at positive energetic balance. In addition, its desirable to perform the repeated thyroid status evaluation in the first trimester of pregnancy and timely administration of adequate therapeutic measures in case of finding any pathology.

PROGNOSTIC RISK OF OBSTETRIC AND PERINATAL COMPLICATIONS IN PREGNANT WOMEN WITH THYROID DYSFUNCTION.

Maternal thyroid pathology takes important role in obstetric and peri-neonatal morbidity structure. Despite of the number of studies conducted in the field of thyroid disorders of pregnant females, the definition of influence of thyroid gland dysfunction on maternal and neonatal health still remains actual. The mentioned topics draw specific interest in the aspect of prognosticaiton of complications and unfavorable outcome. Aim of the study - to define the specificities of gestation period and determine the prognostic risk of obstetric and perinatal complications in pregnant females with thyroid pathology. The study was performed at the base of "David Gagua Clinic" Ltd. Prospective, open controlled study design was applied. Based upon the referral to the clinic, 292 pregnant females with thyroid pathology were involved in the main group. The control group involved 58 conditionally healthy pregnant females of reproductive age. Thyroid status had been monitored accoding to trimesters during the whole period of prgnancy and 1 month following the delivery. The health state of neonates was assessed by international protocols. To define the confidence interval for relative ratio between quantitative data of compared groups, c2 , P and RR indices were calculated, and its critical level was considered to be 0.05. The risks ratio with defining of the data was determined for obstetric and perinatal complications. 120 (41.4%) of pregnant subjects demonstrated hypothyroidism, 104 (35.6%) - isolated hypothyroxinmia, and 13 (4.5%) - hyperthyroidism. High levels of anti-thyroid peroxidase antibodies were observed in 54 (18.5%) of cases, nodular gout was found in 38 (13%) patients, 5 (12.3%) of which was associated with hypothyroidism and 9 (23%) - with isolated hypothyroxinemia. Correcting treatment was administered to all pregnant subjects during the pregnancy period. Based on the analysis of acquired data, the high probability of prengancy-related nausea/vomiting and iron-deficiency anemia was demonstrated in the population of pregnant females with thyroid pathology, especially in those with hypothyroidism and isolated hypothyroxinemia. The prognostic risk of early spontaneous abortion, premature delivery and obstetric surgical interventions was statistically significant in pregnant females with hypothyroidism. The relative ratio for low neonatal weight, maternal iron deficiency anemia in postpartum period, abnormal weight gain and chronic lower limb venous disorders were high in the aspect of perinatal outcomes. Thus, despite of timely diagnosis and adequate treatment, thyroid pathology revealed in the gestational period is related with particular risk for development of obstetric and perinatal complications, which indicates on absolute necessity of pregravid preparation and achievement of euthyroid state at preliminary stage of pregnancy planning.

RISK FACTORS OF THYROID PATHOLOGY FORMATION IN OUTPATIENT PREGNANT POPULATION.

Several medical - biological and social - hygienic factors have been found to account for the definite increase in the incidence of thyroid gland disorders in reproductive age and pregnant women. Aim of our study was to identify the risk factors for development of thyroid gland pathology in outpatient pregnant women. Observational study - "case - control" study has been conducted at the base of David Gagua Hospital Ltd. Main (study) group involved 292 pregnant patients with established thyroid pathology. Control group included 58 conditionally healthy pregnant participants without any demonstrated thyroid pathology. Study of risk factors was performed by initial interviewing and specialized questionnaire recording process (so-called two-stage model of interviewing). Characteristics of diet, sleep, physical activity, including harmful habits, socio-economic and hereditary factors were studied; quantitative indices of risk for each component were calculated: odds ratio (OR) and attributable risk (AR), taking into account 95% confidence interval (CI). The Pearson's criterion χ2 with respective P value and the calculator developed by International Society of Evidence-based Medicine were used to obtain the final results. Statistically significant risk factors for development of thyroid pathology were identified, which included: Thyroid gland diseases and hereditary history of diabetes mellitus; low economic income, unfavorable living conditions, unhealthy dietary habits. Despite of the difficulty of assessment of causative relationship between above mentioned components, their strong correlation should be taken into account when defining the strategy of preventive measures, moreover the most part of identified risk factors are manageable.

[An assessment of the level of knowledge on congenital malformations among pregnant residents of Tbilisi].

Congenital malformations (CM) are considered as 10 leading causes for global burdens of the disease. The study aimed to assess the knowledge on CM among pregnant residents of Tbilisi. Investigation was carried out on the base of "D. Gagua Clinic", LLC, Tbilisi. 470 women, visiting the clinic for antenatal monitoring, were involved in the study to provide an appropriate assessment of pregnant. Assessment of basic knowledge of the women was conducted according to the specially developed questionnaire and completed by the respondents at their visiting to the doctors. The level of knowledge on prevention of CM among the pregnant residents of Tbilisi is low while relationship to CM in the first place is associated with this group of population. The knowledge on CM is comparatively higher in women older than 30 and among the pregnant with higher education. Certain differences in the level of knowledge on CM was found among temporary unemployed women (housewives) and employed respondents. The differences in knowledge on CM among women with first and second delivery were not revealed. On the background of the obtained results it should be concluded that the level of knowledge on CM among reproductive age women residents of Tbilisi is not satisfactory. There is direct evidence of low preventive activity and bareness of measures regarding to family planning as well.

Primary dysmenorreah-leading problem of adolescent gynecology (review).

Adolescent gynecology is a rapidly developing area. Dysmenorrhea is one of the most common complaints among women of young reproductive age. About 25-95% of young women suffers with dysmenorrhoea and is associated with significant psychological, physical, behavioral and social distress. This review summarizes epidemiology, strategies of establishing the diagnosis, discussion of pathophysiology of the disease and risk factors. We performed a comprehensive search through MEDLINE, EMBASE, Scopus, MD consult and Web of Science. Inclusion criteria specified review and research articles reporting primary dysmenorreah in adolescents. The search resulted in 214 articles. We point out a variety of noninvasive nutritional and psychological therapeutic interventions that have been suggested to relieve dysmenorrheal. This review of Primary Dysmenorreah identifies gaps in the literature, some contradictions and highlights the need for further study.

[Study of anxiety level and passive avoidance response in rats that in neonatal period undergo the prolonged dexamethasone treatment].

The decrease in locomotor activity and the number of crossed sectors in open field, has been shown in the group of animals, which for four days in the neonatal period received dexamethasone treatment. Based on these data we decided in the same experimental conditions to study the animals' state of anxiety and the behavior in passive avoidance chamber. The newborn male pups were divided on four groups. The first group was left intact, the pups of the second group were injected by saline, the third group - by dexamethasone and the fourth group - with combination of dexamethasone and L-arginine. The received results show, that deficiency of nitric oxide in the early neonatal period caused by administration of dexamethasone led to statistically significant increase of anxiety level, but statisticaly significant changes in their behavior in a passive avoidance chamber was not observed.

[Possible mechanism of behavioral disorders in rats under long term treatment with dexamethasone in neonatal period].

Despite the fact that the side effects of prolonged treatment with dexamethasone are well known, information about its effects on the central nervous system is very limited. Experimental study of long-term effects of dexamethasone administration in the neonatal period on behavioral activity of rats in the open field was conducted. Four groups of newborn males were selected from the offspring of pregnant rats. The first group was left intact, the animals of second group were injected saline solution, the third group - with the dexamethasone and the fourth group - along with dexamethasone received L-arginine. Tests in an open field for all groups of animals were carried out on the 45th (first test) and 60th (second test) days after birth. The results showed that the decrease in motor activity of animals and in the number of sectors crossed in the open field with a high statistical significance was observed only in the group of animals, which for four days in the neonatal period underwent dexamethasone treatment. At the same time, another group of animals, which was also injected dexamethasone in the same doses, but additionally was injected L-arginine, the behavior in the open field did not differ from the intact animals or animals which were injected (as a control) saline solution. It was concluded that it is the lack of nitric oxide in the early neonatal period, which occurs as a result of dexamethasone treatment that causes observed changes in animals' behavior.

[Usage of unimag during dynamic hysterosalpingo-contrast sonography in the experimental study].

The purpose of this experimental study was to investigate the contrasting ability of magnetic fluid, Unimag, during dynamic hysterosalpingo-contrast sonography (HyCoSy) performed in sexually mature female rabbits. 5 ml of diluted and undiluted solution Unimag was slowly injected into the intact and amputated uterine tubes as experimental animals via a catheter. Dynamic observation was achieved with the aid of ultrasound machine - Siemens Sonoline Antares. Observation revealed a well - defined contrasting ability of this magnetic fluid regardless of its dilution. X-ray was additionally performed in above mentioned animals, also proved the contrasting ability of Unimag.

The echo-contrasting ability of the medical magnetic fluid unimag and its peculiarities during the elimination from the body in an experiment.

The aim of our study was to evaluate the unimag effect and its dynamic elimination from the unligated uterine horns. During the experiment, 5ml of undiluted unimag and its diluted solutions (1:10; 1:20) were injected via the catheter in adult female rabbits, (the whole number of animals - 18). For its next morphological evaluation the materials were taken on the first, on the 3rd and 5th day following the injection. The 10th times diluted unimag elimination time includes 5 days. Non-diluted unimag elimination process lasts more then 5 days. In a case of the unimag's 20th times dilution, the mononuclear- phagocytic system doesn't activate and the elimination procces is performed naturally, by the extracorporaly way.

[Development of audiogenic kindling during the gestation period].

Some peculiarities of audiogenic kindling were studied in rats with genetically determined epileptic seizures during gestation period. In the period of gestation the development of audiogenic kindling in response to repetitive acoustic stimulation is markedly reduced. This indicates the strengthening of inhibitory processes in the brain. It is supposed that in the period of gestation in rats with genetically determined audiogenic seizures excess of sexual hormones and enhancement of GABA-ergic transmission causes marked reduction of development of audiogenic kindling.

[Peculiarities of metabolic characteristics in females of reproductive age with hyperplastic processes of cervix and mammary glands].

The aim of our investigation was the evaluation of character of metabolic disorders in patients with hyperplastic processes of uterine corpus, cervix and mammary glands. 88 patients of reproductive age with several gynaecological complaints have been investigated. 72 patients with hyperplastic processes of endometrium and endocervix (hyperplasia, polyposis), myoma of uterus, fibroadenoms and adenomatosis of mammary glands were selected in main group. Control group consisted of 16 patients without any hyperplastic processes of genital organs. Metabolic syndrome in main group was revealed in 28% of cases, in control--18.8% (chi(2)=3.95, p=0.047); insulin resistance--30.5% and 18.7% (chi(2)=4.01, p=0.046), respectively. In main group in comparison with control group took place the tendency of the increase triglyceride plasma level and the decrease of levels of HDL-cholesterol. b-cell function was significantly increased in patients with hyperplastic processes of uterine corpus and cervix, in subgroup of uterine myoma revealed the tendency. Insulin resistance revealed in patients with hyperplasia of endocervix and pathologies of mammary glands. Our results suggest that metabolic syndrome and its components significantly influences on the formation of hyperplastic processes of uterine corpus, cervix and mammary glands.

[Peculiarities of development of rat's audiogenic convulsive responses in the period of gestation].

In rats, with genetically determined audiogenic epileptic seizure some peculiarities of convulsive responses before and during gestation as well as after the delivery were studied. Depending on responses to audio stimuli the rats of Krushinsky-Molodkina line might be divided on two groups. The responses of first group are: fear and facial muscles clonus; the responses of other group--fear, wild running and then development of clonic and tonic seizures. The rats of this (second) group were used in our experiments. In the period of gestation: (a) extended latency of development of convulsive activity; (b) significant prolongation of the intervals between wild running and (c) marked reduction of behavioral manifestation of clonic and tonic seizures have been observed. These indicate the strengthening of inhibitory processes in the brain. It is supposed that in the period of gestation in rats with genetically determined to development of audiogenic seizures excess of sexual hormones causes the gaining of anticonvulsive processes in the brain. Evidently, this should be connected with GABA-ergic inhibitory mechanisms of the brain.

[Endocrine-metabolic peculiarities in women of reproductive age with hyperplastic processes of cervix and mammary glands].

The aim of our investigation was the detection of endocrine-metabolic disorders in patients with hyperplastic processes of endomyometrium, uterine cervix and mammary glands. 88 patients of reproductive age with several gynaecological complaints have been investigated. 72 patients with hyperplastic processes in endomyometrium, uterine cervix (hyperplasia, polyposis, myoma) and mammary glands (fibroadenomatosis, adenomatosis) were selected in main group. Control group consisted of 16 patients without any hyperplastic processes of reproductive organs. Metabolic syndrome in main group was revealed in 28% of cases, in control - 18,8% (chi(2)=3,95, p=0,047); insulin resistance - 37,5% and 18,7% (chi(2)=4,59, p=0,033), respectively; obesity - 52,8% and 25,0% (chi(2)=4,05, p=0,045), respectively; dyslipidemia - 52,8% and 0,0%; hypertension - 26,4% and 12,5% (chi(2)=1,88, p=NS), respectively. Blood leptin level in main group was - 13,7+/-10,9 ng/ml, and in control - 5,0+/-2,9 ng/ml (p=0,005). Our results suggest that metabolic syndrome and its components significantly influences the formation of hyperplastic processes of endomyometrium, uterine cervix and mammary glands. Blood leptin level is significantly increased in patients with hyperplastic pathologies.

[Possibilities of colposcopy in the diagnostics of cervical Chlamydia-mycoplasmatic infections (population prospective study)].

Possibilities of colposcopy in the diagnostics of cervical chlamydia-mycoplastic infections are less investigated. The aim of given work was the study of this problem. Colposcopic examination was performed in 952 women (age - from 16 to 67) asked to clinics for examination and more precise definition of diagnosis because of different complaints. It was revealed specific colposcopic features of chlamydia-mycoplastic genital infections, which were compared with the results obtained from "gold standard" methods - direct immunofluorescence method and bacteriological analysis of cervical smears. High sensitivity (Se) - 0,96, specificity (Sp) - 0,79 and diagnostic effectiveness (De) - 0,93 of colposcopy were established. Authors conclude that the application of colposcopy for diagnostics of chlamydia-mycoplastic genital infection is particularly important: during urgent cases; during the case, when it is impossible to carry out the deep diagnostics of the sexually transmitted infections; for optimization of the diagnostics of the sexually transmitted infections.