Hormone Preparations Research Articles

The emergence of levothyroxine as a treatment for hypothyroidism.

To describe the historical refinements, understanding of physiology and clinical outcomes observed with thyroid hormone replacement strategies. A Medline search was initiated using the search terms, levothyroxine, thyroid hormone history, levothyroxine mono therapy, thyroid hormone replacement, combination LT4 therapy, levothyroxine Bioequivalence. Pertinent articles of interest were identified by title and where available abstract for further review. Additional references were identified in the course of review of the literature identified. Physicians have intervened in cases of thyroid dysfunction for more than two millennia. Ingestion of animal thyroid derived preparations has been long described but only scientifically documented for the last 130 years. Refinements in hormone preparation, pharmaceutical production and regulation continue to this day. The literature provides documentation of physiologic, pathologic and clinical outcomes which have been reported and continuously updated. Recommendations for effective and safe use of these hormones for reversal of patho-physiology associated with hypothyroidism and the relief of symptoms of hypothyroidism has documented a progressive refinement in our understanding of thyroid hormone use. Studies of thyroid hormone metabolism, action and pharmacokinetics have allowed evermore focused recommendations for use in clinical practice. Levothyroxine mono-therapy has emerged as the therapy of choice of all recent major guidelines. The evolution of thyroid hormone therapies has been significant over an extended period of time. Thyroid hormone replacement is very useful in the treatment of those with hypothyroidism. All of the most recent guidelines of major endocrine societies recommend levothyroxine mono-therapy for first line use in hypothyroidism.

Growth Hormone Research Society perspective on the development of long-acting growth hormone preparations.

ObjectiveThe Growth Hormone (GH) Research Society (GRS) convened a workshop to address important issues regarding trial design, efficacy, and safety of long-acting growth hormone preparations (LAGH).ParticipantsA closed meeting of 55 international scientists with expertise in GH, including pediatric and adult endocrinologists, basic scientists, regulatory scientists, and participants from the pharmaceutical industry.EvidenceCurrent literature was reviewed for gaps in knowledge. Expert opinion was used to suggest studies required to address potential safety and efficacy issues.Consensus processFollowing plenary presentations summarizing the literature, breakout groups discussed questions framed by the planning committee. Attendees reconvened after each breakout session to share group reports. A writing team compiled the breakout session reports into a draft document that was discussed and revised in an open forum on the concluding day. This was edited further and then circulated to attendees from academic institutions for review after the meeting. Participants from pharmaceutical companies did not participate in the planning, writing, or in the discussions and text revision on the final day of the workshop. Scientists from industry and regulatory agencies reviewed the manuscript to identify any factual errors.ConclusionsLAGH compounds may represent an advance over daily GH injections because of increased convenience and differing phamacodynamic properties, providing the potential for improved adherence and outcomes. Better methods to assess adherence must be developed and validated. Long-term surveillance registries that include assessment of efficacy, cost-benefit, disease burden, quality of life, and safety are essential for understanding the impact of sustained exposure to LAGH preparations.

A Word About Bioidenticals

A Word About Bioidenticals

Analysis of 17β-estradiol (E2) role in the regulation of corpus luteum function in pregnant rats: Involvement of IGFBP5 in the E2-mediated actions.

BackgroundIn several species, considerably higher levels of estradiol-17 (E2) are synthesized in the CL. E2 has been suggested to participate in the regulation of luteal steroidogenesis and luteal cell morphology. In pregnant rats, several experiments have been carried out to examine the effects of inhibition of luteal E2 synthesis on CL structure and function.MethodsDuring days 12–15 of pregnancy in rats, luteal E2 was inhibited by way of daily oral administration of anastrozole (AI), a selective non-steroidal aromatase inhibitor, and experiments were also performed with E2 replacement i.e. AI+ E2 treatments. Luteal tissues from different treatment groups were subjected to microarray analysis and the differentially expressed genes in E2 treated group were further examined for expression of specific E2 responsive genes. Additional experiments were carried out employing recombinant growth hormone preparation and flutamide, an androgen receptor antagonist, to further address the specificity of E2 effects on the luteal tissue.ResultsMicroarray analysis of CL collected on day 16 of pregnancy post AI and AI+E2 treatments showed significantly lowered cyp19a1 expression, E2 levels and differential expression of a number of genes, and several of them were reversed in E2 replacement studies. From the differentially expressed genes, a number of E2 responsive genes were identified. In CL of AI pregnant rats, non-significant increase in expression of igf1, significant increase in igbp5, igf1r and decrease in expression of Erα were observed. In liver of AI treated rats, igf1 expression did not increase, but GH treatment significantly increased expression that was further increased with AI treatment. In CL of GH and AI+GH treated rats, expression of igfbp5 was higher. Administration of flutamide during days 12–15 of pregnancy resulted in non-significant increase in igfbp5 expression, however, combination of flutamide+AI treatments caused increased protein expression. Expression of few of the molecules in PI3K/Akt kinase pathway in different treatments was determined.ConclusionsThe results suggest a role for E2 in the regulation of luteal steroidogenesis, morphology and proliferation. igfbp5 was identified as one the E2 responsive genes with important role in the mediation of E2 actions such as E2-induced phosphorylation of PI3K/Akt kinase pathway.Electronic supplementary materialThe online version of this article (doi:10.1186/s12958-016-0153-1) contains supplementary material, which is available to authorized users.

Dynamics of the content of H2O, Na, K, Ca and Mg in the eggs of bream, Abramis brama L. in natural conditions and under stress

Objective: To study the dynamics of H2O, Na, K, Ca and Mg content in the oocytes of bream, Abramis brama observed in prespawning period on breeding ground and in reply to catching, transportation and subsequent remaining of spawners in a cage. Methods: For research on the dynamics of H2O and cations content in the oocytes of bream females, Abramis brama in the course of eggs transition from maturity Stage IV to Stage V, fishes were caught from breeding ground in the coastal zone of the Volga Reach of the Rybinsk reservoir at the Vereteya Station. For studying the influence of stress, the bream (76 individuals) were caught from breeding ground by hauling the seine during 15 min. Capture, sorting and transportation for 3 h to the ponds were the stress factors. Samples of oocytes from 6-8 fishes were taken immediately after capturing, then two more were taken during transportation. Later fishes were removed from the cage in certain time intervals. Concentration of Na and K in the dissolved samples of oocytes was measured by the spectrometer (Flapho-4, Carl Zeiss, Iena, Germany) and content of Ca and Mg was measured by atomic-absorption spectrometer-1 (the same producer). Results: In natural conditions before spawning in the course of maturation of oocytes from maturity Stage IV to V, H2O content in the ovicells of bream has increased by 3.3% and concentration of Na, K, Ca and Mg has decreased by 24.9%, 38.1%, 56.2% and 65.7%, accordingly. Stress caused by capturing, transportation and the subsequent remaining of bream spawners in a cage did not change parameters of water-salt exchange of the oocytes. Conclusions: In natural conditions before spawning, the maturation of oocytes of bream from maturity Stage IV to V take place. Stress caused by capturing, transportation and the subsequent remaining of bream spawners in a cage prevents the transition of eggs from maturity Stage IV to V. It is suggested that in order to develop optimal technique stimulating oocytes maturation and the process of ovulation in industrial conditions, study of these reactions of spawners of one or another species in natural environment is preferentially conducted. Conditions of incubation and combination of hormonal preparations selected on the basis of these

State of bone tissue in patients with thyrotoxicosis syndrome

Оbjective. To determine the influence of thyroid functional state on bone mineral density indexes from data of ultrasound densitometry and laboratory methods of research.Materials and methods. 80 patients of reproductive age with thyrotoxicosis syndrome were recruited. The thyroid functional state was estimated by means of determination of thyroid-stimulating hormone (TSH) basal concentrations and free thyroxine in the blood serum. Subjects were invited to attend quantitative ultrasound densitometry (Sahara), and a fasting blood sample from which osteocalcin, serum N-terminal propeptide of type 1 procollagen and crosslinks were also measured.Results. Frequency of bone mineral density disorders in patients with thyrotoxicosis syndrome was 52,7%, including osteopenia in 40% and osteoporosis in 12.7%. A basic factor that results in the decline of bone mineral density in patients with thyrotoxicosis syndrome is excessive products of thyroid hormones, and also TSH-suppressive doses of levothyroxine. Ultrasound densitometry showed significant decrease of bone mineral density indexes and increase of frequency of osteopenia and osteoporosis as compared to healthy persons.Conclusions. Complex approach is the first brought to the estimation of bone metabolism state in patients with thyrotoxicosis syndrome. It contains an ultrasound densitometry and laboratory methods of research. Set factors (excessive products of thyroid hormones, reception of preparations of thyroid hormones in TSH-suppressive doses) and mechanisms of negative influence (stimulation of osteoclastic activity, decline of osteoblastic activity) on the state of bone metabolism in patients with thyrotoxicosis syndrome.

Thyroid Hormone Replacement in Patients Following Thyroidectomy for Thyroid Cancer.

Thyroid hormone replacement therapy in patients following thyroidectomy for thyroid cancer, although a potentially straightforward clinical problem, can present the clinician and patient with a variety of challenges. Most often the problems are related to the dose and preparation of thyroid hormone (TH) to use. Some patients feel less well following thyroidectomy and/or radioiodine ablation than they did before their diagnosis. We present evidence that levothyroxine (L-T4) is the preparation of choice, and keeping the thyroid-stimulating hormone (TSH) between detectable and 0.1 mU/L should be the standard of care in most cases. In unusual circumstances, when the patient remains clinically hypothyroid despite a suppressed TSH, we acknowledge there may be as yet unidentified factors influencing the body’s response to TH, and individualized therapy may be necessary in such patients.

CYP24A1 variant modifies the association between use of oestrogen plus progestogen therapy and colorectal cancer risk.

Background:Menopausal hormone therapy (MHT) use has been consistently associated with a decreased risk of colorectal cancer (CRC) in women. Our aim was to use a genome-wide gene–environment interaction analysis to identify genetic modifiers of CRC risk associated with use of MHT.Methods:We included 10 835 postmenopausal women (5419 cases and 5416 controls) from 10 studies. We evaluated use of any MHT, oestrogen-only (E-only) and combined oestrogen–progestogen (E+P) hormone preparations. To test for multiplicative interactions, we applied the empirical Bayes (EB) test as well as the Wald test in conventional case–control logistic regression as primary tests. The Cocktail test was used as secondary test.Results:The EB test identified a significant interaction between rs964293 at 20q13.2/CYP24A1 and E+P (interaction OR (95% CIs)=0.61 (0.52–0.72), P=4.8 × 10−9). The secondary analysis also identified this interaction (Cocktail test OR=0.64 (0.52–0.78), P=1.2 × 10−5 (alpha threshold=3.1 × 10−4). The ORs for association between E+P and CRC risk by rs964293 genotype were as follows: C/C, 0.96 (0.61–1.50); A/C, 0.61 (0.39–0.95) and A/A, 0.40 (0.22–0.73), respectively.Conclusions:Our results indicate that rs964293 modifies the association between E+P and CRC risk. The variant is located near CYP24A1, which encodes an enzyme involved in vitamin D metabolism. This novel finding offers additional insight into downstream pathways of CRC etiopathogenesis.

Growth Hormone Research Society perspective on the development of long-acting growth hormone preparations: Table 1

Growth Hormone Research Society perspective on the development of long-acting growth hormone preparations: Table 1

A Randomised Controlled Trial Comparing the Efficacy and Side-Effects of Intravaginal Ring (Nuvaring(®)) With Combined Oral Hormonal Preparation in Dysfunctional Uterine Bleeding.

Combined Oral Contraceptive (COC) pills are being used in patients of abnormal uterine bleeding, especially adolescents and reproductive age women considering their need for contraception. It decreases the blood loss due to haemostatic effect of estrogen and also regularizes the cycle. Intravaginal route has been found to be effective and acceptable; Gastrointestinal absorption and hepatic first-pass metabolism is avoided and steady, uniform blood concentration is achieved. Bioavailability of estrogen and progestogen through oral and vaginal route are same. The convenience of once-a-month administration is another major advantage. Sixty women fulfilling inclusion criteria were randomised into 2 groups in 1:1 ratio. In one group (n=30), monthly insertion of Nuvaring(®)) was done for three consecutive months. Nuvaring(®) releases 15μg ethinyl estradiol and 120 μg etonogesterol daily. The other group (n=30) received COC pill containing 30μg EE and 150 μg levonorgestrel for three consecutive months. Primary outcome measures were change in menstrual cycle pattern and pictorial Blood Loss Assessment chart (PBAC) score. Other Parameters included side effects, change in haemoglobin and weight. Data was analyzed by statistical software SPSS 20. Both Nuvaring(®) and COC were found to significantly decrease blood loss in each cycle. Decrease in PBAC score was more in Nuvaring(®) group compared to COC, however difference was not significant. Ideal bleed (IB) was frequently higher for Nuvaring(®) group than COC in all 3 cycles, although no statistically significant difference was observed between groups (p-value=0.286). Late withdrawl, intermenstural spotting was higher in COC group. Compliance was better and women were more satisfied in Nuvaring(®) group compared to COC group. Minor side effects like headache, mastalgia, nausea and mood changes were seen in both groups, which were not significant. Continuation rate was significantly higher in Nuvaring® group. 30% women discontinued treatment in OCP group after 3 month compare to 10% in Nuvaring(®) group. Present study shows Nuvaring(®) to be as effective as COC in controlling heavy menstural bleed, better cycle control, with minor acceptable systemic side effects.

The calcium-regulating system and recurrent peptic ulcer

To elucidate the functional state and value of the calcium-regulating system, calcium and phosphorus metabolism in the pathogenesis and sanogenesis of peptic ulcer (PU); to define the possible ways to correct shifts found in the treatment of disease relapse, by affecting the different levels of their disorders. A total of 220 patients with recurrent PU were examined by determining the blood levels of parathyrin, calcitonin, calcium and phosphorus, as well as gastric secretory and motor functions. Recurrent PU was accompanied by a considerable increase in the blood concentration of parathyroid hormone and calcium, a slight rise in that of calcitonin, and a significant reduction in that of phosphorus. These changes were attended by a substantial increase in gastric acid- and pepsinogen-forming functions, a decrease in the production of gastric mucoproteins, and hypermotor dyskinesia. The use of calcitrin, nifedipine, and etidronic acid, which eliminate dysfunction of the calcium-regulating system at different levels of its impairments, leads to a significant reduction in the time of alleviation of the clinical and endoscopic manifestations of a recurrence. Recurrent PU runs in the presence of calcium-regulating system dysfunction. Incorporation of the thyroid C-cell hormone preparation calcitrin, the slow calcium-channel blocker nifedipine, and etidronic acid bisphosphonate into a complex of treatment for a disease recurrence is pathogenetically sound and clinically effective.

Letrozole versus artificial hormonal endometrial preparation for vitrified–warmed embryos transfer cycles

Abstract Objective: To evaluate the efficacy of letrozole in the endometrial preparation of vitrified–warmed embryo transfer cycles and to compare it to the hormonal preparation with estradiol valerate and progesterone study. Design: Retrospective observational study. Methods: We analyzed 197 cycles of endometrial preparation for vitrified–warmed embryo transfer from January 2013 to August 2014. A final 94 cycles of letrozole were compared to 96 cycles of hormonal preparation. Results: Pregnancy rate was non significantly higher in the letrozole group (53.2%) than in the hormonaly prepared group (40.6%) while the ongoing pregnancy rate was significantly higher in the letrozole group 47.9% v 32.3% (P value 0.02). The abortion rate was non significantly lower in the letrozole group 5.3% v 8.3%. The mean endometrial thickness in the hormonaly prepared group was significantly higher than the letrozole 9.9 mm ± 1.7 and 9.1 mm ± 1.6 respectively. Conclusion: Endometrial preparation for vitrified-warmed embryo transfer using the aromatase inhibitor letrozole has a significantly higher ongoing pregnancy rate than that of the hormonal preparation.

The role of hormone replacement therapy in the intensive care management of deceased organ donors: a primer for nurses.

Donation after brain death remains the primary contributor to the supply of organs available for transplantation in the United States. After brain death, both a surge of catecholamines and a dysregulation of the neurohormonal axis may result in hypotension, decreased organ perfusion, and reduced viability of organs to be transplanted. Hormone replacement therapy is widely used to maintain organ perfusion and has been shown to increase the number of organs procured. This article reviews the literature and mechanisms supporting the use of hormone replacement therapy in brain-dead organ donors and provides clinicians with information regarding the administration, monitoring, and preparation of thyroid hormone, arginine vasopressin, and corticosteroids.

WITHDRAWN: Gonadotrophin therapy for ovulation induction in subfertility associated with polycystic ovary syndrome.

Background Approximately 15% of women with PCOS remain anovulatory despite treatment with oral anti-oestrogen medications such as citrate. In addition, about half of women with PCOS ovulating on anti-oestrogen treatment fail to conceive. Gonadotrophin stimulation is the next step in treatment for women who are clomiphene resistant, however, results of gonadotrophin stimulation in women with PCOS are less successful. In PCOS associated with hypersecretion of LH, purified urinary follicle-stimulating hormone (u-FSH) preparations have theoretical advantages over the use of human menopausal gonadotrophin (hMG) preparations (containing both FSH and LH) , but whether this claimed advantage extends into clinical practice remains uncertain. In addition, the use of gonadotrophin-releasing hormone analogues (GnRH-a) to produce pituitary desensitisation prior to ovulation induction in PCOS has been claimed to increase the success rates of treatment as well as reduce complications such as OHSS and multiple pregnancy. Gonadotrophin preparations have also been administered via different routes (intramuscular or subcutaneous), or using different stimulation regimens and protocols (step-up or standard) in an attempt to improve efficacy. Objectives To determine the effectiveness of urinary-derived gonadotrophins as ovulation induction agents in patients with PCOS trying to conceive. In particular, to assess the effectiveness of (1) different gonadotrophin preparations, (2) the addition of a gonadotrophin-releasing hormone agonist (GnRH-a) to gonadotrophin stimulation and (3) different modalities of gonadotrophin administration. Search methods The search strategy to identify RCTs consisted of (1) the Group's Specialised Register of Controlled Trials using the search strategy developed for the Menstrual Disorders and Subfertility Group as a whole (see the Review Group details for more information), (2) additional specific electronic MEDLINE searches and (3) bibliographies of identified studies and narrative reviews. Selection criteria RCTs in which urinary-derived gonadotrophins were used for ovulation induction in patients with primary or secondary subfertility attributable to PCOS. Data collection and analysis Twenty three RCTs were identified, nine of which were excluded from analysis. The data were extracted independently by two authors. The following criteria were assessed: (1) the methodological characteristics of the trials (2) the baseline characteristics of the studied groups and (3) the outcomes of interest: pregnancy rate (per cycle), ovulation rate (per cycle), miscarriage rate (per pregnancy), multiple pregnancy rate (per pregnancy), overstimulation rate (per cycle) and ovarian hyperstimulation syndrome (OHSS) rate (per cycle). Where suitable, meta-analysis was performed using Peto's OR with 95% CI with the fixed effect Mantel-Haentszel equation. Main results (1) A reduction in the incidence of OHSS with FSH compared to hMG in stimulation cycles without the concomitant use of a GnRH-a (OR 0.20; 95% CI 0.08-0.46) and (2) a higher overstimulation rate when a GnRH-a is added to gonadotrophins (OR 3.15; 95% CI 1.48-6.70). Authors' conclusions Although 14 RCTs were included in this review, few dealt with the same comparisons, all were small to moderate size and their methodological quality was generally poor. Any conclusions, therefore, remain tentative as they are based on a limited amount of data and will require further RCTs to substantiate them. In none of the comparisons was there a significant improvement in pregnancy rate but this may be due to the lack of power (i.e. insufficient patients randomised to demonstrate a significant difference between treatments). There was a trend towards better pregnancy rates with the addition of a GnRH-a to gonadotrophin stimulation and these interventions warrant further study. Despite theoretical advantages, urinary-derived FSH preparations did not improve pregnancy rates when compared to traditional and cheaper hMG preparations; their only demonstrable benefit was a reduced risk of OHSS in cycles when administered without the concomitant use of a GnRH-a. No conclusions can be drawn on miscarriage and multiple pregnancy rates due to insufficient reporting of these outcomes in the trials.

Thyroid Hormone Profile in Patients With Acute Coronary Syndrome.

Background:Thyroid hormone has the a major role in the cardiovascular system function and cardiac a As well as to maintain the cardiovascular homeostasis A slightly change ind thyroid status actually affects cardiovascular mortality hemodynamic. The background of this study was to define the prevalence of thyroid dysfunction in acute coronary syndrome (ACS).Objectives:The primary objective was to define the prevalence of thyroid dysfunction in acute coronary syndrome, including Non-ST Segment Elevation Myocardial Infarction (NSTEMI), ST-segment Elevation Myocardial Infarction (STEMI), and unstable angina groups. The secondary objective was to determine any associations of thyroids function tests with cardiac catheterization and mortality.Patients and Methods:In a prospective, observational, and cross section study, we enrolled 400 patients admitted at the coronary care unit of King Abdulaziz University Hospital in Jeddah, Saudi Arabia. Venous blood samples were collected from patients for the evaluation of thyroid function (thyroids stimulating hormones, free triiodothyronine, and free thyroxin).Results:Excluding those taking thyroid hormone preparations, 76.7% of patients admitted with acute coronary heart disease (ST-segment elevation myocardial infarction and Non-ST segment elevation myocardial infarction), and unstable angina had euthyroidism. Thyroid dysfunction was reported in 23.3% of patients with coronary heart disease. Overall hypothyroidism prevalence was 7.8%, while subclinical hyperthyroidism in our study was 2.7%. Overt hyperthyroidism and subclinical hyperthyroidism was reported 2.0% and 0.5%, respectively. Euthyroid sick syndrome was noticed in 41 (10.2%) of critically ill patients. The mortality rate was 9.8%; all death patients had low triiodothyronine (T3) syndrome and were associated with statistically significant low free triiodothyronine (FT3) (P > 0.001).Conclusions:No significant variance was observed among patients underwent for cardiac catheterization, STEMI, NSTEMI, unstable angina, and atrial fibrillation with respect to FT4, FT3, and TSH levels during coronary care unit hospitalization based on their profile data.

Functional hypothalamic amenorrhoea — diagnostic challenges, monitoring, and treatment.

Functional hypothalamic amenorrhoea (FHA) is associated with functional inhibition of the hypothalamic-pituitary-ovarian axis. Causes of FHA can be classified into the three groups: 1) stress-related factors, 2) consequences of weight loss and/or underweight, and 3) consequences of physical exercise or practicing sports. Diagnosis of FHA should be based on a history of menstrual disorders. During physical examination, patients with FHA present with secondary and tertiary sex characteristics specific for the pubertal stage preceding development of the condition and with the signs of hypoestrogenism. Laboratory results determine further management of patients with amenorrhea, and thus their correct interpretation is vital for making appropriate therapeutic decisions. Treatment of chronic anovulation, menstrual disorders, and secondary amenorrhea resulting from hypothalamic disorders should be aimed at the elimination of the primary cause, i.e. a decrease in psycho-emotional strain, avoidance of chronic stressors, reduction of physical exercise level, or optimisation of BMI in patients who lose weight. If menses do not resume after a period of six months or primary causative treatment is not possible, neutralisation of hypoestrogenism consequences, especially unfavourable effects on bone metabolism, become the main issue. Previous studies have shown that oestroprogestagen therapy is useful in both the treatment of menstrual disorders and normalisation of bone mineral density. Hormonal preparations should be introduced into therapeutic protocol on an individualised basis.

Namų ūkio vaistų krepšelio sandaros tyrimas

The main objective of the study was to explore home medicines cabinet contents and to estimate the effect of different household characteristics on the structure of the cabinet. The study was conducted in Vilnius, the capital of Lithuania, where a total of 148 households allowed for making inventory of their medicines cabinets. The results revealed that the average value of a home medicines cabinet was 70.1 EUR with the average price of 4.3 EUR for one drug package. The medicines cabinet of each household consisted of 16.2 drug packages on the average. There was no household that had no medicines; however, 10.8% of the households kept only non-prescription medicines. The ratio between prescription and non-prescription medicines was 1:2.4. The most popular medicines in the home medicines cabinets were for the treatment of respiratory system (24.6%), alimentary tract and metabolism (14.6%), nervous system (13.9%), and musculo-skeletal system (13.8%). At least one package of the medicines mentioned above was found in at least 8 households out of 10. The price of the whole medicines cabinet, also the value of prescription medicines of the households with at least one retired person or a person with chronic disease was significantly higher as compared to other families. Also households with at least one retired person were more likely to keep drugs for the treatment of blood and blood forming organs (OR = 9.2, 95% CI 3.9-21.6, P < 0.001), or cardiovascular system (OR = 6.0, 95% CI 1.3-28.4, P < 0.05) in their medicines cabinet. Households with at least one person with chronic disease had increased risk to top up their medicines cabinet with drugs for the treatment of cardiovascular system (OR = 5.6, 95% CI 2.2-14.4, P < 0.001), sensory organs (OR = 3.2, 95% CI 1.5-6.6, P < 0.01), or systemic hormonal preparations (OR = 6.6, 95% CI 1.4-32.4, P < 0.05). Effective prevention of chronic diseases with higher involvement of community pharmacists in prevention programs, therefore, is seen not only as a means to reduce total costs of health care, but also to reduce household expenditures for medicines.

PREPARATION OF THE ENDOMETRIUM FOR IMPLANTATION IN WOMEN OF THE REPRODUCTIVE AGE

Despite the success achieved by the use of assisted reproductive technologies, infertility remains one of the main problems of the present day medicine.The experts in this field consider that the tubal-peritoneal form of female infertility is the most leading form of infertility (60-70%). The second most important form is the endocrine form of infertility (20-25%). In 5-7% cases the cause of infertility remains unknown and it is considered to be idiopathic infertility. Idiopathic infertility is connected with inability to detect any dysfunctions of the reproductive system using the current diagnostics methods. Today there is no general consensus concerning the question how to prepare the endometrium for implantation. The majority of researchers suggest that the use of estrogens and progesterones in the cyclic regime as the main therapy-rehabilitation influences upon all the functions of the endometrium including proliferation and immune response modulation. In some cases, however, the endometrium abnormally responds to hormonal stimulation and can even show resistance, which explains spontaneous abortions and unsuccessful cycles of the extracorporal fertilization (ECF), the absence of pregnancy after laparascopic treatment of ovarian polycystic syndrome (OPCS).The objective of the study was to develop the optimal method to prepare the endometrium for implantation in women of the reproductive age.Materials and methods. The study involved 60 women of the reproductive age who were consulted concerning the problem of infertility. All the women examined with "inadequate" endometrium, were divided into two groups I and II, depending on the method of preparation of the endometrium for implantation. Group I (basic) included 30 women who underwent vacuum aspiration of the uterus. Group II (comparison) consisted of 30 women who underwent hormone (estradiol valerate) preparation of the endometrium.To determine the inclusion and exclusion criteria of "inadequate" endometrium the following examinations and tests were performed: somatic and gynecological examination of women, ultrasound investigation, aspiration paypel-biopsy followed by histological examination of the material, determination of blood hormone: follicle-stimulating hormone, luteinizing hormone, estradiol, progesterone, prolactin, testosterone, cortisol.Results of the study. Menstrual cycle disorders were observed in 56.6% of women in the I gr. and 63.3% in gr. II; miscarriage in 26.7% and 33.3%, repeated unsuccessful attempts of ECF in 16.7% and 23.3%, endoscopic surgery on the internal genital organs (salpingolysis, salpingostomy, salpingoplastiс, fimbrioplastic, resection of the ovaries, fenestration of the ovarian capsule, myomectomy) - 33.3% and 26.7%, respectively.In the blood of patients with "inadequate" endometrium a statistically significant increase of estradiol (p &lt;0.01) was found. No significant differences in the content of other hormones were identified (r˃0,05).The results of histological studies have shown that in the I gr. 15 (50%) and in gr. II in 17 (56.6%) women the endometrium corresponded to the phase of the menstrual cycle; in 12 (40%) in I gr. and in 10 (33.3%) in gr. II glandular hyperplasia of the endometrium was found and in 3 (10%) in I gr. and 3 (10%) in gr. II - endometrial polyp diagnosed. Thus, 53.3% of women have not had any histological changes in the endometrium.Out of 30 women of gr. I, who underwent vacuum aspiration - pregnancy occurred within 6 months in 25 (83.3%) women and in 23 (92%) cases the outcome of pregnancy was the birth of term infants with Apgar scores of 7-9 points with body weight 3150,0 ± 240,0 g; 2 (8%) women - had premature labour, which was significantly different from group II (women who underwent hormonal preparation of the endometrium ). Pregnancy occurred within 6 months in 10 (33.3% ) women, in 8 (80%) cases the outcome of pregnancy was the birth at 37 weeks of gestation and in 2 cases the pregnancy resulted in miscarriage (p &lt;0.01).Conclusion. The study performed has found that significantly more frequently pregnancy occurred in patients with «inadequate» endometrium who underwent endometrial preparation for implantation by using vacuum aspiration, than women with hormonal preparation of the endometrium.

Biochemical factors of common carpCyprinus carpioL. 1758, seminal plasma and its relationship with sperm motility parameters

Summary Compared were the volume and quality of carp Cyprinus carpio L. obtained from semen of males not subjected to hormonal stimulation (N = 10) but injected with 0.9% NaCl in the amount of 1 ml kg−1 b.w., as well as those stimulated using Ovopel (N = 10) in the amount of 1 granule kg−1 b.w. Semen was collected from the males 24 h after injection of hormonal preparation, to determine the pH, total volume (TVS) and volume recalculated per kg of body mass, concentration and total sperm production (TSP). Differences in sperm motility parameters between fish groups were determined by a computer-assisted sperm analysis (CASA) system. Sperm motility was activated using 10 mm Tris buffer, containing 100 mm NaCl (pH 9.0, osmolality 200 mOsm kg−1). The pH, osmolality, total protein concentration and activity of acidic phosphatase (AcP), lactate dehydrogenase (LDH), s-N-acetylglucosaminidase and arylsulfatase (AS) were determined in the seminal plasma of both test groups. The stimulation of male carp using Ovopel did not significantly affect CASA parameters, but did lead to an over ten-fold increase in the values of TVS and VOS and nearly six times higher values of TSP as compared to the Control group. A significant increase in pH following stimulation with Ovopel indicates that cyclic AMP increased, thanks to which sperm acquire a capacity to move during their passage through the sperm ducts. An increase in the values of CASA parameters is a likely reflection of these changes.

Expression of Bioactive Callithrix jacchus Follicle-Stimulating Hormone in Pichia pastoris

Callithrix jacchus (common marmoset) is a New World primate monkey, used as an animal model in biomedical research. Marmoset-specific follicle-stimulating hormone (FSH) preparation is required to improve superovulation protocols and to develop homologous FSH monitoring assays in these monkeys. In this study, we document the large-scale expression of recombinant marmoset FSH in methylotropic yeast, Pichia pastoris. The recombinant preparation was found to be immunologically active in Western blotting and radioimmunoassay. The preparation displayed receptor binding ability in radioreceptor assay. Based on the receptor binding ability, the yield of fermentation was estimated to be 7.2 mg/L. FSH-induced cAMP assay and estradiol assay revealed that the recombinant hormone is able to induce signal transduction. Both immunological and in vitro biological activity of marmoset FSH was found to be comparable to purified human pituitary FSH, which served as reference hormone for these assays. Thus, the study suggests that a Pichia expression system can be used for large-scale expression of bioactive recombinant marmoset FSH.