Endocrine Disruptors and Estrogens in Human Prostatic Tissue.

Endocrine disruptors (EDs) are ubiquitous substances both in the environment and everyday products that interfere with the hormonal system. Growing evidence demonstrates their adverse effects on the organism, including the reproductive system and the prostate, owing to their (anti)estrogenic or antiandrogenic effects. Since EDs can interact with steroid hormone actions on-site, understanding the levels of intraprostatic EDs in conjunction with steroids may hold particular significance. The aim of this study was to develop and validate a method for determining estrogens, various groups of EDs (bisphenols, parabens, oxybenzone and nonylphenol) and phytoestrogens in their unconjugated and conjugated forms in prostate tissue by liquid chromatography-tandem mass spectrometry, and subsequently analyze 20 human prostate tissue samples. The method enabled 20 compounds to be analyzed: estrogens (estrone, estradiol, estriol), bisphenols (bisphenol A- BPA, BPS, BPF, BPAF, BPAP, BPZ, BPP), parabens (methyl-, ethyl-, propyl-, butyl-, benzyl- paraben), oxybenzone, nonylphenol and phytoestrogens (daidzein, genistein, equol) with LLOQs between 0.017-2.86 pg/mg of tissue. The most frequently detected EDs in prostate tissues were propylparaben (conjugated and unconjugated forms in 100 % of tissues), methylparaben (unconjugated in 45 % and conjugated in 100 %), ethylparaben (unconjugated in 25 % and conjugated in 100 % BPA (unconjugated in 35 % and conjugated in 60 % and oxybenzone (both forms in 45 % To the best of our knowledge, this is the first study detecting EDs, phytoestrogens and estriol conjugate (E3C) in the prostate. E3C was the most abundant estrogen in prostatic tissue. This highlights the need for further explorations into estrogen metabolism within the prostate.

[Various approaches of endometrial preparation for frozen-thawed embryo transfer]. / Moznosti prípravy endometria ke kryoembryotransferu.

OBJECTIVE: Various approaches of endometrial preparation for frozen-thawed embryo transfer. DESIGN: Retrospective analysis. SETTING: Department of Obstetric and Gyneacology, Faculty of Medicine, Palacky University, University Hospital Olomouc. METHODS: Effectivity of frozen-thawed embryo transfers was carried out between January and August 2017 in the IVF unit at the University Hospital Olomouc. Results were compared among groups A, B, C with various approaches of endometrial preparation. Group A - natural ovulating cycle, group B - artificial cycle with oral estrogen, vaginal gestagen and group C - artificial cycle with transdermal estrogen and vaginal gestagen. One blastocyst (two blastocyst in five cycles) was transferred on day 6 post ovulation (group A) or after 6 days of using gestagens (group B, C). RESULTS: The highest pregnancy rate was observed in group C (56%), similar pregnancy rate was found in group B (52%) and the lowest was seen in group A (22%). All pregnancies in group A continued over 12 weeks, in group B continued 57 percent and in group C continued 56 percent of pregnancies. CONCLUSION: Frozen-thawed embryotransfers in natural cycles are highly time-consuming. Our study has demonstrated the lowest effectivity of frozen-embryotransfer in natural cycles. Artificial cycles managed by oral or transdermal form of estrogen have shown better results.

[Comparison of vaginal use of micronized progesterone for the luteal support. Randomized study comparison of Utrogestan and Crinone 8]. / Srovnání vaginálního uzití mikronizovaného progesteronu k luteální podpore. Randomizovaná studie porovnávající Utrogestan a Crinone 8.

OBJECTIVE: The study was focused on comparison of efficiency, safety and tolerance of vaginal use of micronized progesterone in preparations Utrogestan and Crinone 8%. DESIGN: Prospective randomized study. SETTING: Department of Gynecology and Obstetric, University Hospital, Olomouc, Faculty of Medicine and Dentistry, Palacky University, Olomouc. MATERIAL AND METHODOLOGY: Into a prospective randomized study was, after calculation of 80% of the power of the study, α = 0,05, included 111 women in age between 18-40 with a basal value FSH < 10 IU/l and a normal finding in uteral cavity. After evaluation of efficiency of both preparations there was selected a fertilization rate, an implantation rate, a pregnancy rate and a take-home baby rate. Comparison of tolerance was made from evaluation of 21 parameters which were obtained through a questionnaire. RESULTS: There were not been proven any significant differences in efficiency between both preparations. Crinone 8% was in patients better tolerated. CONCLUSION: Luteal support within the IVF/ICSI-ET remains an integral part of the treatment. According to the outcomes of the study it seems to be more suitable to use a vaginal gel for the luteal support with micronized progesterone.

[Luteal support in the IVF/ET programme]. / Luteální podpora v programu IVF/ET.

OBJECTIVE: The objective of this article is to review the recent information about luteal support in the IVF/ET programme. DESIGN: Review article. CONCLUSIONS: The luteal phase support is a necessary part of treatment in stimulated cycles for IVF/ET.

[Complications of laparoscopic and laparotomic treatment of endometrial cancer]. / Komplikace laparotomické a laparoskopické lécby karcinomu endometria.

OBJECTIVE: The aim of the study is to compare advantages, disadvantages and complications of the laparoscopic and clasical laparotomic operations in the patients treated for endometrial carcinoma at our Department and to find out the optimal strategy. DESIGN: Retrospective study. SETTINGS: Department of Gynaecology and Obstetrics, Medical Faculty, Palacky University and University Hospital, Olomouc. MATERIAL AND METHODS: A total of 165 endometrial cancer patients were operated on since 2004 till 2008 at our department. The clasical laparotomic approach was used in 141 patients and 24 were operated laparoscopically. Both groups were comparable in clinical staging and other parameters. The clinical parameters compared were the frequency of inflammatory complications, urinary passage injury, blood loss, transfusions, operating time and hospital stay. RESULTS: The average operating time for laparotomic operations was 137 minutes and for the laparoscopic ones 175 minutes. The mean hospital stay after clasical operation was 7.8 days, and 6.7 days after laparoscopy. The estimated blood after clasical operation was 410 ml and 8.5% of patients received blood transfusion. Blood loss after laparoscopy was only 214 ml but 12.5% of patients necessitated blood transfusion. Complications due to infection were more often in patients with laparotomy (5.7%) while they occurred only in 4.1% after laparoscopies. The injury of the urinary tract was recorded only in 1 patient (0.7%) in the laparotomy group while it was more frequent in the laparoscopic group (2 patients i.e. 8.3%). CONCLUSIONS: The main advantage of laparoscopy at the operations of the endometrial cancer is the shorter hospital stay resulting in lower costs, less postoperative discomfort and a minimum of inflammatory complications. On the other hand there were more frequent urinary tract injuries and the operating time was usually longer at laparoscopies compared to laparotomies. Nevertheless, it seems that the use of the laparoscopic operations for endometrial cancer will probably be increasing.

[Does the detection of disease in asymptomatic period improve the prognosis of patients with endometrial carcinoma?]. / Zlepsuje záchyt onemocnení v asymptomatickém období prognózu pacientek s karcinomem endometria?

OBJECTIVE: To analyse factors which led to the diagnosis of endometrial carcinoma in patients still in asymptomatic stage and to find out if such early diagnosis has an impact on further prognosis of this carcinoma. DESIGN: Retrospective study. SETTING: Department of Obstetrics and Gynecology, Medical Faculty of the Palacký University and University Hospital, Olomouc. METHODS: The analysis of reasons which made the patients with endometrial carcinoma to see a gynecologist and estimate the proportion of preventive measures in the diagnosis malignant diseases of uterine corpus. RESULTS: The study included 110 patients with diagnosis of endometrial carcinoma. The Common symptoms of endometrial carcinoma, e.g. most often irregular bleeding, brought 87 (79%) patients to gynecologists while in remaining 23 (21%) of patients the disease was found in asymptomatic stage at the preventive oncogynecologic examination or incidentally at the examination for other illnesses. Both groups differed in staging and grading. CONCLUSIONS: The asymptomatic patients where the disease was diagnosed incidentally or during preventive oncogynecologic examination had, in the beginning of treatment, markedly lower staging and more favorable grading than symptomatic patients, what generates preconditions for a better prognosis of these patients.

[Preoperative assessment of myometrial invasion in endometrial cancer patients by ultrasonography and magnetic resonance imaging (MRI)]. / Predoperacní zhodnocení myometriální invaze u pacientek s karcinomem endometria pomocí ultrazvuku a magnetické rezonance.

OBJECTIVE: To compare the accuracy of transvaginal sonography and magnetic rezonance imaging (MRI) in determining the depth of myometrial invasion in proven cases of endometrial cancer. DESIGN: A prospective study. SETTING: Department of Obstetrics and Gynecology, Department of Medical Genetics and Fetal Medicine, Department of Radiology, University Hospital, Olomouc. METHODS: Fifty five patients diagnosed as having FIGO stage I endometrial carcinoma were evaluated preoperatively by transvaginal ultrasound; 44 cases of the same group were also evaluated by magnetic resonance imaging (MRI). The degree of invasion evaluated by transvaginal sonography and by MRI was compared to the pathological specimens. RESULTS: Transvaginal sonography was successful in evaluating myometrial invasion in 44 of 55 cases (accuracy 80%, sensitivity 80%, specificity 88%, positive predictive value 77%, negative predictive value 87%). Evaluation with MRI was accurate in 37 of 44 cases (accuracy 84%, sensitivity 84%, specificity 91%, positive predictive value 81%, negative predictive value 91%). CONCLUSION: Although MRI is superior to transvaginal sonography in evaluating myometrial invasion, it is expensive and time consuming, and would not be suitable as a screening test for depth of invasion. On the other hand, transvaginal sonography is relatively low-cost technique, which can be easily performed and repeated. However, it requires more operator experience than MRI in order to achieve high accuracy.

In vivo metabolism of 2,6,9-trisubstituted purine-derived cyclin-dependent kinase inhibitor bohemine in mice: glucosidation as the principal metabolic route.

Synthetic cyclin-dependent kinase inhibitors have recently been referred to as effective antiproliferative agents. This study was conducted to characterize clearance of a 3H-labeled, trisubstituted purine-type inhibitor, 8-[3H]bohemine [6-benzylamino-2-(3-hydroxypropylamino)-9-isopropylpurine], in mice. Radioactivity profiles were analyzed by liquid scintillation counting and by thin layer chromatography followed by autoradiography. Metabolite structures were elucidated by mass spectrometry, NMR, and enzymatic analyses. Bohemine was rapidly and completely metabolized in vivo and disappeared from circulation during the first 60 min following intravenous administration. The metabolites were partly eliminated by the hepatobiliary tract and partly by renal excretion. The terminal hydroxyl group located at the C2 side chain of bohemine made the compound susceptible to main metabolic attacks, i.e., distinct types of conjugation reactions with glycosyl donors as well as an oxidative reaction. Other pathways were of relatively minor significance. Bohemine O-beta-D-glucoside was the most abundant metabolite to be excreted. The enzymatic mechanism responsible for bohemine glucosidation in vitro required the presence of a UDP-glucoside donor. Additional glycosidation products were observed after inclusion of UDP-glucuronide, UDP-xylose, UDP-galactose, or UDP-N-acetylglucosamine into microsomal incubates. Glycosidations occurred faster in the kidney incubates than in hepatic ones. The second principal bohemine metabolite was a carboxylic acid, 6-benzylamino-2-(2-carboxyethylamino)-9-isopropylpurine. A cytosolic, 4-methylpyrazole-sensitive alcohol dehydrogenase class I was shown to mediate oxidation of the terminal hydroxyl group of bohemine into this acid, which was the only metabolite found in the blood in significant amounts. However, it displayed only weak cyclin-dependent kinase-1-inhibitory activity (IC(50) > 100 microM) when compared with that of bohemine (IC(50) approximately 1 microM).