The association of thyroid autoimmunity with ovarian reserve in women with type 1 diabetes with and without polycystic ovary syndrome.

The aim of the study was to investigate the relation between thyroid autoimmunity (TAI), reflected as the presence of thyroid peroxidase antibodies (TPOAb), and parameters of ovarian reserve in women with type 1 diabetes (T1DM) and polycystic ovary syndrome (PCOS). We studied 83 euthyroid women with T1DM (age - 26 ± 5 years, BMI - 24 ± 3 kg/m2) - 12 with PCOS and positive TPOAb (PCOS + TPOAb), 29 with PCOS with negative TPOAb (PCOS + noTPOAb), 18 without PCOS with positive TPOAb (noPCOS + TPOAb), 24 without PCOS with negative TPOAb (noPCOS + noTPOAb). Serum concentrations of anti-Müllerian hormone (AMH), sex hormones, TSH, thyroid hormones and TPOAb were assessed. The prevalence of TAI was comparable between PCOS and noPCOS. We did not observe differences in hormonal profile or AMH concentration between two PCOS groups-PCOS + TPOAb and PCOS + noTPOAb (p > 0.05). Women with PCOS + TPOAb had lower FSH concentration and higher LH/FSH index than noPCOS + noTPOAb (p = 0.027; p = 0.019, respectively). Moreover, PCOS + TPOAb had lower oestradiol level than noPCOS + TPOAb (p = 0.041). AMH concentration was higher in both groups with PCOS, independent of TPOAb presence, than in noPCOS + noTPOAb (both p < 0.001). The presence of positive TPOAb titre was not related to the studied parameters of ovarian reserve - AMH and ovarian follicle number. In multiple linear regression analysis, the only significant predictor of AMH in the whole studied group with T1DM was total daily insulin dose U/kg (ß = - 0.264; p = 0.022). The presence of TAI did not affect the hormonal profile or ovarian reserve in women with T1DM with and without PCOS.

The Influence of Prepubertal Onset of Type 1 Diabetes and Age of Menarche on Polycystic Ovary Syndrome Diagnosis.

CONTEXT: Higher prevalence of polycystic ovary syndrome (PCOS) in women with type 1 diabetes (T1DM) is linked to exogenous insulin, especially when diabetes is diagnosed before puberty. OBJECTIVE: The study evaluates the impact of prepubertal onset of T1DM and insulin therapy on PCOS diagnosis and phenotypic characteristics in women with T1DM. DESIGN, SETTING, AND PATIENTS: We studied 83 women with T1DM (age 26 ± 5 years, BMI 24 ± 3 kg/m2) 36 with premenarchal (PM) onset of T1DM [17 with PCOS diagnosed (PCOS+PM) and 19 without PCOS (noPCOS+PM)] and 47 women with postmenarchal onset of T1DM [24 with PCOS (PCOS-noPM) and 23 without PCOS (noPCOS-noPM)]. OUTCOME MEASUREMENTS: Clinical examination, assessment of serum sex hormones, glycated hemoglobin (HbA1c) and ultrasonographic evaluation of the ovaries were performed in all women. RESULTS: Applying Rotterdam criteria, 49% of women with T1DM were diagnosed with PCOS. There were no differences in hormonal profile and ovarian parameters between PCOS+PM and PCOS-noPM. Women with T1DM+PM had higher insulin dose/24 h and U/kg bw/24 h than T1DM-noPM (P-values = 0.014 and 0.001, respectively). Both PCOS+PM and noPCOS+PM groups had higher insulin dose U/kg bw/24 h in comparison to PCOS-noPM (P-values = 0.004 and = 0.006, respectively). In multivariable logistic regression analysis, age of menarche [odds ratio (OR): 0.672; 95% confidence interval (CI): 0.465-0.971] and HbA1c (OR: 0.569; 95% CI: 0.383-0.846) were associated with the diagnosis of PCOS. CONCLUSIONS: There were no differences in the prevalence of PCOS between T1DM+PM and T1DM-noPM; however, earlier menarche might have an influence on PCOS diagnosis in women with T1DM.

Metabolic syndrome and the risk of cardiovascular complications in young patients with different phenotypes of polycystic ovary syndrome.

PURPOSE: Insulin resistance is an important factor in the pathogenesis of polycystic ovary syndrome (PCOS), which is associated with higher risk of metabolic syndrome (MetS) and cardiovascular complications. Early atherosclerotic lesions may be diagnosed by ultrasonographic parameters: brachial artery flow-mediated dilation after reactive hyperaemia (FMD) and intima-media thickness of common carotid artery (IMT). The aim of the study was to assess the relation of IMT and FMD with clinical and laboratory parameters reflecting metabolic status in young women with different PCOS phenotypes. METHODS: The study included 154 PCOS patients diagnosed with the Rotterdam criteria, divided into four phenotypes, and 113 healthy women. Laboratory analyses, transvaginal ultrasound, and IMT and FMD measurements were conducted. MetS was diagnosed with International Diabetes Federation/American Heart Association (IDF/AHA) consensus criteria. RESULTS: MetS was more prevalent in PCOS patients than healthy women (14.29 vs. 5.31%; p = 0.019), with highest prevalence in phenotypes I and II (p = 0.039). IMT and FMD did not differ between PCOS patients and the controls, nor between the PCOS phenotypes. PCOS patients with MetS presented lower FMD than other PCOS patients (p = 0.018). In women with PCOS, FMD correlated with glucose and insulin concentrations in the fasting state (R = -0.33, p = 0.002; R = -0.23, p = 0.026) and at 2 h of OGTT (R = -0.29, p = 0.006; R = -0.26, p = 0.014). In patients with phenotype I, correlations were found between IMT and BMI (R = 0.45, p = 0.006) and between FMD and fasting glucose concentrations (R = -0.46, p = 0.011). CONCLUSIONS: Metabolic disturbances and the diagnosis of MetS in patients with PCOS, especially in hyperandrogenic phenotypes, might be associated with alterations in IMT and FMD.

Ovarian Reserve and Serum Concentration of Thyroid Peroxidase Antibodies in Euthyroid Women With Different Polycystic Ovary Syndrome Phenotypes.

Objective: It has been shown that women with polycystic ovary syndrome (PCOS), as well as Hashimoto's thyroiditis (HT), are characterized by increased incidence of infertility. Serum anti-Müllerian hormone (AMH), which reflects ovarian reserve, is elevated in PCOS women and is decreased in women with HT. The Rotterdam criteria recognize four clinical PCOS phenotypes, i.e., phenotypes A, B, C, and D. The aim of the present study was to investigate the relation between serum concentrations of thyroid peroxidase antibodies (TPOAbs) and ovarian reserve in different PCOS phenotypes. Patients and methods: We examined 141 women with PCOS [phenotype A was diagnosed in 67 (47.5%) women, phenotype B in 30 (21.3%), phenotype C in 28 (19.9%), and phenotype D in 16 (11.3%)] and 88 control subjects of similar age; all women were euthyroid. Serum concentrations of AMH, thyroid-stimulating hormone (TSH), thyroid hormones, and TPOAbs were assessed. Results: We observed positive serum TPOAbs in 21.9% women with PCOS and in 23.9% controls (p = 0.07). We did not find differences in the frequency of detection of positive serum TPOAbs between phenotypes A, B, and C and the control group (p > 0.05). We did not observe a difference in AMH levels between TPOAbs-positive and TPOAbs-negative women, both in the control group and the PCOS women (all p > 0.05). However, serum AMH concentration was markedly higher in the whole PCOS group (p < 0.01) and in phenotype A (p < 0.01) vs. controls when the serum concentration of TPOAbs was negative. In the groups with positive serum levels of TPOAbs, serum concentration of AMH did not differ between PCOS phenotypes and controls (p = 0.23). Additionally, we observed that serum AMH concentration was related to the level of TPOAbs in the PCOS group (r = -0.4, p = 0.02). Conclusions: The frequency of serum detection of positive TPOAbs did not differ between PCOS phenotypes with clinical/biochemical hyperandrogenism and the control group. The observation of the difference in serum AMH between the PCOS and control groups only in TPOAbs negative women together with the inverse relation of TPOAbs with serum AMH only in the PCOS group might suggest that ovarian reserve is influenced by TPOAbs in PCOS.

Increased serum fetuin-B concentration is associated with HOMA-ß and indices of liver steatosis in women with polycystic ovary syndrome: a pilot study.

OBJECTIVE: PCOS women are characterized by insulin resistance and have higher tendency to the development of hepatic steatosis. Fetuin-B has been introduced as a hepatokine/adipokine, which is increased in hepatic steatosis and may be connected with glucose metabolism disturbances. The aim of the study was to evaluate the relationships between serum fetuin-B concentration and indices of insulin resistance, insulin secretion and markers of liver steatosis in PCOS women in comparison to the control group. PATIENTS AND METHODS: The study group included 108 women - 57 women with PCOS and 51 women matched for age and BMI as a control group. Serum concentration of fetuin-B was estimated. Homeostasis model assessment of insulin resistance (HOMA-IR) and homeostasis model assessment ß cell function (HOMA-ß) were calculated. Fatty liver index (FLI), lipid accumulation product (LAP) and visceral adiposity index (VAI) were used as markers of liver steatosis. RESULTS: We found higher serum concentration of fetuin-B and FLI in PCOS women in comparison to the control group (all P < 0.05). We observed a positive relationship between serum fetuin-B concentration and HOMA-ß (r = 0.43, P = 0.01), HOMA-IR (r = 0.31, P = 0.01), FLI (r = 0.29, P = 0.02), VAI (r = 0.29, P = 0.02) and LAP (r = 0.32, P = 0.01) in PCOS women. We also noticed a relationship between HOMA-IR and FLI (r = 0.42, P = 0.01), VAI (r = 0.38, P = 0.004) and LAP (r = 0.41, P = 0.001) in this group. Multiple regression analysis revealed that HOMA-ß (ß = 0.39, P = 0.002) and LAP (ß = 0.27, P = 0.02) were independently connected with serum fetuin-B levels in women with PCOS. CONCLUSIONS: Serum fetuin-B levels are higher in women with PCOS and are independently connected with HOMA-ß and hepatic steatosis.

Decreased deiodinase activity after glucose load could lead to atherosclerosis in euthyroid women with polycystic ovary syndrome.

OBJECTIVE: Glucose and lipid disturbances, as well as higher tendency to atherosclerosis, are observed in women with polycystic ovary syndrome (PCOS). Thyroid hormones action has long been recognized as an important determinant of glucose and lipid homeostasis. Some studies suggest that even in euthyroid subjects, thyroid function may affect atherosclerosis risk factors. The aim of this study was to evaluate the relationships between thyroid hormonal status and glucose and lipid profile before and after oral glucose tolerance test (OGTT) in PCOS women in comparison to the control group. PATIENTS AND METHODS: The study group included 98 women-60 women with PCOS and 38 women matched for age and BMI as a control group. OGTT with estimation of plasma glucose and lipids, as well as serum insulin and thyroid hormones (TH) concentrations was performed. Activity of peripheral deiodinases at baseline (SPINA-GD1) and at the 120 min of OGTT (SPINA-GD2) was calculated according to the formula by Dietrich et al. as a measure of T4-T3 conversion efficiency. Delta GD was estimated as SPINA-GD1-SPINA-GD2, and delta fT3 was calculated as a difference between fT3 before and after OGTT. RESULTS: We did not find differences in TH, SPINA-GDs, and plasma lipid concentrations between PCOS and control group before and after OGTT. Glucose load resulted in a decrease of level TSH, TC, TG, HDL-C, and LDL-C concentrations in women with PCOS, as well as in the control group (all p < 0.05). We found that GD (p = 0.01) and serum fT3 concentration (p = 0.0008) decreased during glucose load only in the PCOS group. We observed a positive relationship between delta fT3 and plasma TG concentration (r = 0.36, p = 0.004), delta GD and plasma TG concentration after glucose load (r = 0.34, p = 0.007), only in the PCOS group. We also found negative relationship between SPINA-GD2 and plasma TC concentration (r = -0.29, p = 0.02) after glucose load and positive relationship between delta GD and insulin at the 60 min of OGTT (r = 0.29, p = 0.02), only in the PCOS women. CONCLUSIONS: These data showed insufficient conversion of fT4 to fT3, as well as a relationship of SPINA-GDs with insulin, TC and TG in PCOS women after glucose load. It may suggest that disturbances in deiodinase activity after glucose load might promote atherosclerosis in PCOS women.

Association between polycystic ovary syndrome and the risk of subclinical vascular disease in normal­weight women with type 1 diabetes.

INTRODUCTION    The prevalence of polycystic ovary syndrome (PCOS) among women with type 1 diabetes (T1DM) is higher than in the general population. Both diseases are associated with higher risk of premature atherosclerosis. OBJECTIVES    The aim of our study was to evaluate whether the cardiovascular risks conferred by T1DM and PCOS are additive. PATIENTS AND METHODS   The study group included 78 women divided into 4 groups: 19 women with PCOS and T1DM (T1DM+PCOS), 16 women with T1DM only (T1DM/no­PCOS), 27 women with PCOS only(PCOS), and 16 healthy women (control group). We evaluated the serum concentrations of cardiovascular disease biomarkers: soluble intercellular adhesion molecule 1 (sICAM­1) and soluble endothelial­leukocyte adhesion molecule 1 (sE­selectin). We also assessed brachial artery flow­mediated dilation (FMD) and estimated the intima-media thickness of the common carotid artery (CIMT) by ultrasonography. RESULTS    The serum concentrations of sICAM­1and sE­selectin were higher in the T1DM+PCOS group compared with women with PCOS only (P = 0.041 and P = 0.002, respectively) and were comparable to those in the T1DM/no­PCOS group. FMD and CIMT did not differ between the groups. In women with T1DM, sICAM­1 positively correlated with body mass index (r = 0.34, P = 0.047), CIMT with daily insulin dose (r = 0.37, P = 0.039), and FMD negatively correlated with diabetes duration (r = -0.42, P = 0.02). In a multivariable logistic regression model, the presence of T1DM, with adjustment for sICAM­1, was the only predictor of sE­selectin concentrations in the whole study group (odds ratio, 8.03; 95% confidence interval, 2.56-13.49; P = 0.005). CONCLUSIONS    The presence of PCOS does not increase the risk of subclinical vascular disease in young lean women with T1DM.

Forced Degradation and Photodegradation Studies of Pyrrolo[3,4-c]pyridine-1,3-dione Derivatives as Analgesic Active Compounds Using HPLC, UV and IR Spectrometry, and HPLC/MS Methods.

The stress and accelerated tests as well as photostability analysis in solutions and the solid phase of three selected derivatives of pyrrolo[3,4-c]pyridine-1,3-dione were carried out according the International Conference on Harmonization guidelines. For observation of the degradation of tested compounds, the RP-HPLC method was used. The study included the effect of temperature, relative humidity, water, H+ and OH- ions, hydrogen peroxide, and light (6.0×10(6), 1.2×10(6) lux·h) on the stability of pyrrolo[3,4-c]pyridine-1,3-dione derivatives. Studies have shown that these derivatives are photolabile, extremely unstable in an alkaline medium, labile in an acidic medium, and stable in a neutral medium. Their sensitivity to oxidizing agents depends on the chemical structure. The shortening of the aliphatic chain leads to an increase in the sensitivity to hydrolytic and oxidizing factors. The presence of the 1,3,4-tetraisoquinoline group promotes an increase in the susceptibility to photodegradation. The introduction of a carbonyl group to the aliphatic chain and the tetrafluoromethyl group to the phenyl ring stabilizes the molecule in the case of hydrolysis and oxidation and also increases sensitivity to light. The analysis of observed photodegradation products using the HPLC-diode array detector, HPLC/MS, and UV and IR spectrometry techniques showed degradation targeted at the breaking of the pyrrolo[3,4-c]pyridine-1,3-dione, piperazine, and/or tetrahydroisoquinoline rings.

HPLC and HPLC/MS/MS Studies on Stress, Accelerated and Intermediate Degradation Tests of Antivirally Active Tricyclic Analog of Acyclovir.

The degradation behavior of a tricyclic analog of acyclovir [6-(4-MeOPh)-TACV] was determined in accordance with International Conference on Harmonization guidelines for good clinical practice under different stress conditions (neutral hydrolysis, strong acid/base degradation, oxidative decomposition, photodegradation, and thermal degradation). Accelerated [40±2°C/75%±5% relative humidity (RH)] and intermediate (30±2°C/65%±5% RH) stability tests were also performed. For observation of the degradation of the tested compound the RP-HPLC was used, whereas for the analysis of its degradation products HPLC/MS/MS was used. Degradation of the tested substance allowed its classification as unstable in neutral environment, acidic/alkaline medium, and in the presence of oxidizing agent. The tested compound was also light sensitive and was classified as photolabile both in solution and in the solid phase. However, the observed photodegradation in the solid phase was at a much lower level than in the case of photodegradation in solution. The study showed that both air temperature and RH had no significant effect on the stability of the tested substance during storage for 1 month at 100°C (dry heat) as well as during accelerated and intermediate tests. Based on the HPLC/MS/MS analysis, it can be concluded that acyclovir was formed as a degradation product of 6-(4-MeOPh)-TACV.

Calculation procedures and HPLC method for analysis of the lipophilicity of acyclovir esters.

Acyclovir (ACV) belongs to a class of drugs with low bioavailability. Selected ACV esters including acetyl (Ac-), isobutyryl (iBut-), pivaloyl (Piv-), ethoxycarbonyl (Etc-) and nicotinoyl (Nic-) were synthesized, and their lipophilicity was determined by the high-performance liquid chromatography (HPLC) RP method. Statistical analyses of the comparative values of log P and clog P were carried out using computational methods. It was proved that the AC log P algorithm can be useful for the analysis of these compounds and has a statistically justified application in the assessment of the quantitative structure-activity relationship. Moreover, the lipophilicity determined by the HPLC method appears as follows: ACV < Ac- < Nic- < Etc- < iBut- < Piv-.

Ester groups as carriers of antivirally active tricyclic analogue of acyclovir in prodrugs designing: synthesis, lipophilicity--comparative statistical study of the chromatographic and theoretical methods, validation of the HPLC method.

Knowledge of the lipophilicity of candidate compounds for prodrugs may predict their predetermined course/effect in the body. Acyclovir (ACV) belongs to a class of drugs with low bioavailability. Its tricyclic analogues, the derivatives of 3,9-dihydro-3-[(2-hydroxyethoxy)methyl]-9-oxo-5H-imidazo[1,2-a]purine (TACV) exhibit similar antiviral activities and are more lipophilic as compared with acyclovir itself. In the search for new antiviral prodrugs 6-(4- methoxyphenyl) tricyclic compound (6-(4-MeOPh)-TACV) was modified by esterification of a hydroxyl group in the aliphatic chain. Selected esters (acetyl, isobutyryl, pivaloyl, ethoxycarbonyl and nicotinoyl) were synthesized and their lipophilicity was determined by the HPLC-RP method. The study compared the log kw calculated from the linear and quadratic equations and proved the correctness of the application of the linear relationship log k as a function of the concentration of ACN in the mobile phase (30-60%). Statistical analyses of the comparative values of log kw and clogP were carried out using computational methods. It was proved that the AC logP algorithm can be useful for the analysis of these compounds, which can have a statistically justified application in the assessment of the quantitative structure- activity relationship (QSAR). The lipophilicity determined by the HPLC method appears as follows: 6-(4-MeOPh)-TACV < Ac- < Nic- < Etc- < iBut- < Piv- (log kw = 0.65-2.26). Finally, the HPLC-RP method was developed and validated for simultaneous determination of synthesized esters.

Oocyte zona pellucida and meiotic spindle birefringence as a biomarker of pregnancy rate outcome in IVF-ICSI treatment.

OBJECTIVES: IVF-ICSI procedures are accompanied by a continuous search for predictors of ART outcome. The properties of zona pellucida (ZP) have been believed to reflect the history of oocyte cytoplasmic maturation. The meiotic spindle (MS) is crucial for chromosomal alignment and proper separation of the maternal chromosomes. There is data suggesting that birefringent ZP and MS can clinically predict the oocyte quality and developmental potential of an embryo. The aim of the study was to examine the possible effect of ZP birefringent properties and MS visualization and localization as valuable predictors of IVF-ICSI effectiveness. MATERIAL AND METHODS: The prospective study was performed during a 16-month period. A total of 51 patients undergoing in vitro fertilization--embryo transfer (IVF-ET) treatment procedure with intracytoplasmic sperm injection (ICSI) were included. Controlled ovarian hyperstimulation (COH) was done using either a long n = 32 (62.75%) or an antagonist protocol n = 19. In the group of the 48 examined patients (aged 25-40), 46 ET were performed, resulting in 24 positive pregnancy tests and 19 (39.59%) clinical pregnancies. Oocytes were examined as follows: ZP birefringence autoscoring (OCTAX PolarAIDE), numeral autoscoring, thickness and clinical evaluation; MS visualization, if MS was visualized, localization of MS in relation to the polar body (PB). RESULTS: On day 3, 64.3% of the embryos were of good and 40.3% were of top quality. Visible differences, not statistically significant, were observed in the numeral score of ZP between oocytes selected and non-selected for ET. In cases when embryos were not of good or top quality, ZP score was higher (p = 0.005 p = 0.001). ZP manual evaluation indicated significantly stronger birefringence when pregnancy was not achieved (p = 0.022). The rate of MS positive oocytes was the highest in the group with pregnancy but it did not reach statistical significance (p = 0.471). The MS localization in relation to the PB was in most oocytes very close (< 45 degrees) in 70.9% and not different in the studied groups. CONCLUSIONS: Unexpected polarization microscopy imaging and rating of ZP and MS cannot be a direct predictor of the IVF outcome.

[Analysis of the demographic profile of patients treated for infertility using assisted reproductive techniques in 2005-2010]. / Analiza profilu demograficznego pacjentów leczonych z powodu nieplodnosci metodami rozrodu wspomaganego w latach 2005-2010.

OBJECTIVES: Analysis of the demographic profile of patients, causes for infertility and effectiveness of infertility treatment methods in the years 2005-2010. MATERIAL AND METHODS: Retrospective research was conducted to analyze data of 1705 randomly selected couples who underwent in vitro fertilization procedure at the Department of Reproduction and Gynecological Endocrinology Medical University of Bialystok, between 2005 and 2010. The analyzed data included mainly causes for infertility age of the female and male subjects, place of residence and final treatment results. RESULTS: The percentage of pregnancy rate increased significantly to approximately 40% in 2007. The contribution of male and female infertility factors remained at a similar level, but the idiopathic factor continued to steadily increase (to 20% in the last years of the study). We observed a greater prevalence of the male factor among couples living in cities compared to inhabitants of rural areas (42.3% vs. 34.3%, p = 0.004), whereas the tubal factor dominated among couples living in the countryside when compared to city dwellers (29.7% vs. 21.6%, p = 0.001). The average age of women entering treatment was significantly higher in cities than the countryside (p < 0.001), thus, consequently treatment efficacy was also lower (33.9% vs. 38.9%, p = 0.04). Comparison of treatment efficacy and cause of infertility revealed statistically significant differences only with regard to the idiopathic factor (p = 0.03). In the group of patients with idiopathic infertility the treatment efficacy was higher than in the rest of patients (40.2% vs. 33.8%). Apart from the idiopathic infertility only the presence of the male factor was associated with a higher (but statistically insignificant) pregnancy rate (36.2% vs. 33.9%). For the other factors, their presence was associated with a lower percentage of pregnancy and the greatest differences (but still statistically insignificant) were observed for the polycystic ovary syndrome (31.5% vs. 35.1%) and for other ovulation disorders (31.3% vs. 35%). CONCLUSIONS: Advances in assisted reproductive techniques led to an increase in the efficacy of infertility treatment. Environmental factors, availability of treatment and level of awareness about womens health proved to have the strongest effect on the distribution of infertility causes between urban and rural areas. Significant efforts should be made, especially in cities, to decrease the average age of women's reproductive decisions and also to shorten the time to the first contact with the specialist after unsuccessful attempts at conception. It is also crucial to initiate the reimbursement of infertility treatment using ART (Assisted Reproductive Technology).

Stability of epidoxorubicin in solid state.

The influence of temperature and relative air humidity on the stability of epidoxorubicin hydrochloride (EP) was investigated. The degradation of the substance studied was determined: (a) in dry air at 393K, (b) at relative air humidity ~76% at 333K, 343K, 353K, 363K and 373K, (c) in the relative air humidity range 50-90% at 363K. The degradation of EP in the atmosphere of increased relative air humidity was a first-order reaction relative to substance concentration and in dry, hot air (RH 0%; 393K) is a reversible first-order reaction relative to substance concentration. The dependences lnk=f(1/T) and lnk=f(RH%) were described by the equation: lnk=(35.1±10.9)-(16,250±3823)(1/T) and lnk=(3.79±3.34) × 10(-2) (RH%)-(12.9±2.4), respectively. The kinetic and thermodynamic parameters of EP degradation were calculated. The parameters of separation were following: LiChrospher RP-18 column, 5 µm, 250 mm × 4 mm; mobile phase: the mixture of equal volume of acetonitrile and the solution containing 2.88 gl(-1) of sodium laurisulfate and 2.25 ml l(-1) of phosphoric acid (V) 85%; flow rate: 1.0 ml min (-1); UV detection - 254 nm.

Estrogen receptor beta participate in the regulation of metabolizm of extracellular matrix in estrogen alpha negative breast cancer.

The biology of breast cancer is closely releted to sex steroid hormones. Estrogen receptor beta is overexpressed in around 70% breast cancer cases, referrd to as "ER positive". Estrogens bind to estrogen receptor and stimulate the transcription of genes involved in control of cell proliferation. Moreover, estrogens may induce growth factors and components of extracellular matrix and interact with them in a complex manner. Extracellular matrix and integrins play an important role in cell functions and their aberrant expressions are implicated in breast cancer development, invasion and metastasis. ER beta is certainly associated with more differentiated tumors, while evidence of role of ER beta is controversial. The highly invasive breast cancer ER beta negative cell line MDA-MB 231 can be the model of exam the role of ER beta in breast cancer. The aim of this study was to examine the role of activation of ER beta on the metabolism of the extracellular matrix and the expression of beta-1 integrin in the breast cancer cell line MDA-MB 231. The cells were exposed on the estradiol, tamoxifen, raloxifen and genisteina in dose dependent concentrations. To determine the relative rate of collagen syntesis we measured the time-dependent reduction of collagen-bound radioactivity after pulse-chase labeling with [3 H] prolina by Peterkofsky methods. The expression of beta-1 integrin was determine by Western blot analysis. The activity of MMP2 and 9 were measured using gelatin zymography with an image analysis system. Our data suggest on the role of estrogen receptor beta on the metabolism of extracellular matrix in the breast cancer line MDA - MB 231. Estradiol and SERMs regulate the expression of ECM proteins: collagen, integrins and enhance activity of metaloproteinases 2 and 9.

[Health of children born after the infertility treatment with Assisted Reproduction Technology]. / Zdrowie dzieci z ciaz po leczeniu technikami rozrodu wspomaganego medycznie.

Since the birth of Louise Brown in July 1978 and the birth of the first intracytoplasmic sperm injection (ICSI) child in January 1992 many couples with female-factor or male-factor infertility can be helped to overcome their infertility resulting in a delivery and birth of a child. Over a million children have been born from assisted conception worldwide. Newer techniques being introduced appear less and less 'natural', such as intracytoplasmic sperm injection (ICSI), but there is little information on these children beyond the neonatal period. This risk varied according to the patient's age, the type of ART procedure performed, the number of embryos transferred, and embryo availability. ART is associated with low increase risk of congenital malformations, major birth defects and genetic and imprinting disorders.