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Objectives: Intrahepatic cholestasis in pregnancy (ICP) is a pregnancy-specific liver disorder. Its etiology is not fully understood. Increasing evidence indicates the important role of vitamin D and the vitamin D receptor (VDR) in this disorder. The presence of polymorphic variants in the VDR gene could influence its activity and susceptibility to ICP development. The goal of the study was to investigate the role of four genetic polymorphisms of the VDR gene — Fok (rs731236), Bsm (rs1544410), Apa (rs7975232), and Taq (rs731236) — in the etiology of ICP in Polish women. Material and methods: Ninety-eight women with confirmed ICP and 215 healthy pregnant women as a control group were recruited to the study. We examined four SNPs of the VDR gene: BsmI (rs7975232), TaqI (rs1544410), ApaI (rs228570), FokI (rs731236). Genotyping was performed using the PCR/RFLP method. Results: We observed higher frequency (borderline significant) of the Ff-ff genotypes containing at least one mutated allele of the VDR FokI polymorphism in the control group compared to the ICP group (p = 0.045, OR = 1.71, 95% CI 1.01–2.88). The frequency of the mutated f allele was slightly higher in controls (49.1%) than in the ICP group (43.4%) (OR = 1.26, 95% CI 0.90–1.77), but the difference was not statistically significant (p = 0.196). Conclusions: Our results showed that the maternal VDR FokI polymorphism could play a protective role in ICP development and probably modulate the risk of ICP occurrence in pregnant women in the Polish population. In the future, to confirm these observations, research in larger, ethnically stratified and clinically analyzed groups is necessary.

Vitamin D3 (VD3) and its steroidal nuclear receptor are necessary for proper development of a pregnancy. They play a key role in implantation, modulate the mother's immune response to the developing fetus, influence the final development of a placenta, and regulate blood pressure and glucose tolerance. VD3 deficiency can lead to the occurrence of obstetric complications such as recurrent miscarriages, preeclampsia, intrauterine growth restriction, gestational diabetes and preterm labor. VD3 deficiency is a common phenomenon across the globe; because of the higher demand placed on their bodies, pregnant women are more likely to develop VD3 deficiency. During pregnancy, VD3 supplementation is a safe method of treatment without risk of side effects or intoxication. To obtain the greatest efficacy, VD3 supplementation should start at the pregnancy planning stage, under control of the VD3 serum concentration, which should exceed 30 ng/mL (75 nmol/L); this is to start the positive effect of the optimal VD3 concentration from the beginning of a pregnancy.

AIM Physiological homocysteine (Hcy) concentrations depend on several factors, both dietary (including folate and choline intake) and biological (such as polymorphism of the genes involved in Hcy metabolism). This study aimed to thus test the associations between genes functionally linked with Hcy metabolism (MTHFR, BHMT and PEMT), folate and choline intakes, and total Hcy (tHcy) concentrations of healthy pregnant women. METHODS One hundred and three healthy Polish women aged 18-44 years, in the third trimester of pregnancy, were enrolled. RESULTS Mean blood tHcy and glutathione (GSH) concentrations were 8.08 ± 3.25 μM and 4.84 ± 1.21 μM, respectively. Concentrations of tHcy were found to be lower in the women who were taking folic acid supplements than in those who did not take these supplements (7.42 ± 1.78 μM vs 9.28 ± 4.42 μM, P

Summary Flavonoids and their conjugates are the most important group of natural chemical compounds in drug discovery and development. The search for pharmacological activity and new mechanisms of activity of these chemical compounds, which may inhibit mediators of inflammation and influence the structure and function of endothelial cells, can be an interesting pharmacological strategy for the prevention and adjunctive treatments of hypertension, especially induced by pregnancy. Because cardiovascular diseases have multi-factorial pathogenesis these natural chemical compounds with wide spectrum of biological activities are the most interesting source of new drugs. Extracts from one of the most popular plant used in Traditional Chinese Medicine, Scutellaria baicalensis Georgi could be a very interesting source of flavonoids because of its exact content in quercetin, apigenin, chrysin and scutellarin as well as in baicalin. These flavonoids exert vasoprotective properties and many activities such as: anti-oxidative via several pathways, anti-in-flammatory, anti-ischaemic, cardioprotective and anti-hypertensive. However, there is lack of summaries of results of studies in context of potential and future application of flavonoids with determined composition and activity. Our review aims to provide a literature survey of in vitro, in vivo and ex vivo pharmacological studies of selected flavonoids (apigenin, chrysin and scutellarin, baicalin) in various models of hypertension carried out in 2008–2018.

Objectives: To evaluate the role of MTHFR genetic variants in the etiology of intrauterine fetal death in the second part of pregnancy at women from Polish population. Material and methods: A case-control study was performed on a 76 women with a positive history of at least one in- trauterine fetal death after 22 gestational week and 400 healthy controls. The MTHFR genotyping for polymorphic sites 667C > T, 1298A > C, 1793G > A was determined by polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP) method. Results: For 1298A > C polymorphism, no statistically significant higher frequency of AA vs. AC+CC genotype was observed in the IUFD group 67.1 % vs. 55.2% in the control group (OR = 0.61, p = 0.05, pcorr = 0.15). We observed overrepresentation of three-locus haplotype CCG (p = 0.20; pcorr = 0.56) and two-locus haplotype CC (p = 0.17; pcorr = 0.48) in the IUFD group compared to controls. Conclusions: There was no observed relationships in genotype frequency of MTHFR 677C > T and 1793G > A variants, however 1298A > C showed a slightly higher but statistically insignificant prevalence in IUFD compared to the controls in Polish population. Further studies on a larger population are needed.

Intrauterine fetal death (IUFD) is a multifactorial disorder and one of the most severe obstetrical complications. Our primary aim was to study the possible associations between polymorphic variants of the PEMT gene and IUFD in the Polish population.The case-control study involved 76 mothers with IUFD occurrence and 215 mothers of healthy children. Genetic analysis of the four single nucleotide polymorphisms in the PEMT gene (rs4646406, rs4244593, rs897453 and rs12325817) was performed with the PCR/RFLP method.Three oef the analyzed PEMT polymorphisms (rs4646406, rs4244593, and rs8974) were significantly associated with IUFD in the Polish population. Among them, PEMT variant rs4244593 was associated with increased risk of IUFD in three genetic inheritance models. Results were statistically significant even after applying Bonferroni correction for multiple comparisons (p 0.0125). The distribution of all haplotypes except TAGC was not different between cases and controls, however, after applying permutation test, none of the haplotypes showed a relation with IUFD.The present findings indicate that PEMT polymorphisms may be associated with the susceptibility to IUFD in the Polish population.

The aim of the study was to investigate combined effects of flavonoids (apigenin, baicalein, chrysin, quercetin, and scutellarin) and methyldopa on the expression of selected proinflammatory and vascular factors in vitro for prediction of their action in pregnancy-induced hypertension. The research was conducted on a trophoblast-derived human choriocarcinoma cell line and a primary human umbilical vein endothelial cell line. Cytotoxicity of compounds in selected concentrations (20, 40, and 100 µmol) was measured using the MTT test and the concentration of 40 µmol was selected for further analysis. Subsequently, their effects with methyldopa on the expression of selected markers responsible for inflammation (TNF-α, IL-1β, IL-6) and vascular effects (hypoxia-inducible factor 1α—HIF-1α, placental growth factor—PIGF, transforming growth factor β—TGF-β, vascular endothelial growth factor—VEGF) at the mRNA and protein levels were assessed. It was found that every combined administration of a flavonoid and methyldopa in these cells induced a down-regulating effect on all tested factors, except PIGF, especially at the mRNA expression level. As hypertension generally raises TNF-α, IL-1β, IL-6, HIF-1α, TGF-β, and VEGF mRNA expression and/or protein levels, the results obtained in the studied model may provide a positive prognostic factor for such activity in vivo.

The Polish Society of Colposcopy and Cervical Pathophysiology (PTKiPSM) together with the Polish Society of Gynecologists and Obstetricians (PTGiP) issued a final summary of interim guidelines for secondary cervical cancer prevention during the SARS-CoV-2 pandemic based on the analysis of the latest directional publications and the authors' own experiences. The aim of the summary is to facilitate the implementation of the most effective possible screening of cervical precancerous lesions and cervical cancer due to temporary significant limitation of screening as a consequence of the ongoing epidemiological threat. These final guidelines are taking into account the 2020 call of the World Health Organization (WHO) for global epidemiological elimination of cervical cancer. The guidelines supplement the interim guidelines of PTKiPSM and PTGiP announced in March 2020 on the possible deferral of diagnostic and therapeutic procedures in patients with abnormal screening tests results in secondary prevention of cervical cancer in current pandemic.

The global outbreak of a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) highlighted a requirement for two pronged clinical interventions such as development of effective vaccines and acute therapeutic options for medium-to-severe stages of "coronavirus disease 2019" (COVID-19). Effective vaccines, if successfully developed, have been emphasized to become the most effective strategy in the global fight against the COVID-19 pandemic. Basic research advances in biotechnology and genetic engineering have already provided excellent progress and groundbreaking new discoveries in the field of the coronavirus biology and its epidemiology. In particular, for the vaccine development the advances in characterization of a capsid structure and identification of its antigens that can become targets for new vaccines. The development of the experimental vaccines requires a plethora of molecular techniques as well as strict compliance with safety procedures. The research and clinical data integrity, cross-validation of the results, and appropriated studies from the perspective of efficacy and potently side effects have recently become a hotly discussed topic. In this review, we present an update on latest advances and progress in an ongoing race to develop 52 different vaccines against SARS-CoV-2. Our analysis is focused on registered clinical trials (current as of November 04, 2020) that fulfill the international safety and efficacy criteria in the vaccine development. The requirements as well as benefits and risks of diverse types of SARS-CoV-2 vaccines are discussed including those containing whole-virus and live-attenuated vaccines, subunit vaccines, mRNA vaccines, DNA vaccines, live vector vaccines, and also plant-based vaccine formulation containing coronavirus-like particle (VLP). The challenges associated with the vaccine development as well as its distribution, safety and long-term effectiveness have also been highlighted and discussed.

Objectives: Osteoporosis is a multifactorial disease that causes a loss of bone density. However, genetic factors play an increasingly important role in its development. To thoroughly understand the molecular mechanisms, polymorphic variants of genes candidate for osteoporosis are still being sought. The aim of our study was to investigate the influence of NFκB1 gene rs4648068 (A>G) and RUNX2 gene rs7771980 (-1025T>C) polymorphisms on the risk of osteoporosis. Material and methods: A group of 675 postmenopausal Caucasian women (109 women with osteopenia, 333 with osteoporosis and 233 with normal T-score) were examined. The bone mineral density (BMD) at the lumbar spine (L1-L4) was measured by dual energy x-ray absorptiometry (DXA). The analysis of NFκB1 and RUNX2 polymorphisms was performed using real-time PCR method. Results: Analysis of NFκB1 gene rs4648068 polymorphism showed that the GG genotype was slightly more frequent in the study groups compared to the control group. In the osteoporosis group, patients with the G allele in the genotype have lower bone mineral density values. For the RUNX2 rs7771980 polymorphism, in women with osteopenia we observed an increased incidence of TC heterozygotes compared to the control group (29.40% vs 24.90%, p > 0.05), and in women with osteoporosis, the TT genotype was more common (78.70% vs 73.80%, p > 0.05). No correlation was observed between the genotypes and the clinical parameters. Conclusions: The analysis showed no significant relationship between the genotypic distribution and the individual clinical parameters. However, it is suggested an association between the rs4648068 polymorphism of the NFκB1 gene and an increased risk of developing osteoporosis.

Objectives: Collagen type I plays an important role in the bone matrix and is encoded by COL1A2 (collagen type I alpha 2) gene that may be a potential candidate for osteoporotic fracture. The aim of this study is to determine whether EcoR I, Del 38 and Pvu II polymorphisms of COL1A2 are associated with the development of osteoporosis and osteopenia in post­menopausal Polish women. Moreover, analysis of relationship between frequency of COL1A2 gene polymorphic variants and clinical parameters of bone turnover and degree of osteoporosis was performed. Material and methods: The study group comprised of women with osteoporosis (n = 90), osteopenia (n = 56) and healthy individuals (n = 56). The EcoR I, Del 38 and Pvu II polymorphisms in COL1A2 gene were detected by PCR-RFLP method. Results: In women with osteoporosis the TT genotype of EcoR I polymorphism had the lowest Z-score value compared to other genotypes (p = 0.034). In case of Del 28 polymorphism, there was a statistically significant correlation between lower BMI values and the DD genotype in women with osteopenia (p = 0.041). There was no statistically significant correlation between polymorphic variants of Del 28 polymorphism and clinical parameters of women with osteoporosis. The analysis of Pvu II polymorphism showed that in women with osteopenia the CC genotype had the lowest body weight compared to other genotypes (p = 0.039). Pvu II polymorphism and clinical parameters in the group of women with osteoporosis had no statistically significant correlations. Conclusions: The analyzed COL1A2 polymorphisms seem to be related to osteoporosis development and their particular clinical parameters. Hence, the COL1A2 polymorphism may be a genetic risk factor related to the development of osteoporosis.

Introduction: The aim of the study was to evaluate the contribution of genetic variants determining inherited thrombophilia to recurrent miscarriage (RM) in the Polish population. The following polymorphisms were analyzed: 1691G>A , 1328T>C of coagulation factor V, 20210G>A of coagulation factor II, R353Q (11496G>A) of coagulation factor VII, 667C>T , 1298A>C , 1793G>A of MTHFR . Material and methods: A total of 359 women with ≥ 2 subsequent recurrent miscarriages (303 < 13 weeks of gestation (w.g.) and 56 between 13–22 w.g.) and 400 healthy controls were included in the study. Frequency of the genetic polymor­phisms was determined with the PCR/RFLP method. Results: Higher frequency of the 20210GA genotype was found in the RM < 13 w.g. (2.97 vs. 1.50% in controls, OR = 2.01, ns) and the RM 13–22 w.g. (5.36 vs. 1.50% in controls, OR = 3.72, p = 0.09) subgroups. Statistically significantly higher frequency of the 11496GA genotype was noted in controls as compared to the RM 13–22 w.g. subgroup (10.71 vs. 23.00% in controls, OR = 0.40, p = 0.02). Statistically significantly higher frequency of the 1793GA genotype was observed in the RM < 13 w.g. subgroup as compared to controls (12.21 vs. 7.75% in controls, OR = 1.66, p = 0.03). No significant correlations were found as far as the rest of the analyzed polymorphisms are concerned. Conclusions: The obtained results suggest that the 1793G>A MTHFR, R353Q (11496G>A) factor VII gene and the 20210G>A factor II gene polymorphisms play a role in the etiology of RM in the Polish population.

Objectives: Choline and folate metabolism disturbances may be involved in the occurrence of intrauterine fetal death (IUFD). The proper activity of this metabolism could be determined by genetic variants involved in choline pathway e.g. CHKA (gene encoding choline kinase α), PCYT1A (gene encoding CCTα) and CHDH (gene encoding choline dehydrogenase). Our study aimed at determining the genotype and allele frequencies of CHKA rs7928739, PCYT1A rs712012, PCYT1A rs7639752, CHDH rs893363 and CHDH rs2289205 polymorphisms in mothers with IUFD occurrence. Material and methods: The study involved 76 mothers with IUFD occurrence and 215 mothers of healthy children. Genetic analysis was performed with the use of PCR/RFLP method. Results: The frequency of genotypes and alleles of studied polymorphisms was similar in both groups. The study revealed no association of PCYT1A, CHKA and CHDH polymorphisms in analysed groups of women. While evaluating the co-existence of analysed polymorphisms statistically significant correlation was revealed. Co-existence of CHKA rs7928739 AC/CHDH rs2289205 AA genotypes was observed statistically more frequently in the study group than in the control group (p = 0,031). Conclusions: There is no correlation between single CHKA rs7928739, PCYT1A rs712012, PCYT1A rs7639752, CHDH rs893363 and CHDH rs2289205 polymorphisms and the incidence of intrauterine fetal death. However, revealed statistically significant difference between co-existence of CHKA rs7928739 AC/CHDH rs2289205 AA genotypes between study groups suggest the need of further analysis.

Objectives: SGA is associated with higher incidence of postnatal complications, including suboptimal neurodevelopment and increased cardiovascular risk. Screening for SGA, carried out at 11–13 (+ 6d) gestational weeks enables to reduce or completely eliminate the above mentioned complications. The aim of this study was to assess the correlation between chorionic thickness, concentration of PIGF protein and foetal birth weight in a single low-risk pregnancy. Material and methods: The study included 76 patients at 11–13 (+ 6d) gestational weeks, monitored throughout preg­nancy. Ultrasound examinations identified the location and thickness of the chorion by measuring it in its central part at its widest point in a sagittal section. Additionally, at each visit venous blood was collected to determine the level of PlGF, PAPP-A, and BhCG. Results: A significant positive correlation (r = 0.37) was found between the foetal weight and chorionic thickness. This correlation was affected by the location of the chorion and a significant negative correlation was observed between the level of PLGF, FHR, weight and length of the newborn. Maternal early-pregnancy BMI did not affect neonatal weight and body length, FHR, chorionic thickness, and the levels of PlGF, PAPP-A, and BhCG. Conclusions: The preliminary analysis indicates an association between chorionic thickness assessed during ultrasound at 11–13 (+ 6d) gestational weeks, PIGF levels assayed at the same time and birth weight. Increasing chorion thickness was accompanied by increasing foetal birth weight. PlGF level showed an inversely proportional effect on the foetal weight. This correlation was significant for the posterior location of the chorion.

The aim of the study was to determine the MTR (methionine synthase) and MTRR (mehionine synthase reductase) polymorphisms in pregnant women with preeclampsia (PE).The group of 98 women with PE and the group of 120 healthy pregnant women were analyzed. Determination of MTR 2756A G and MTRR 66A G polymorphisms was performed using polymerase chain reaction (PCR)/restriction fragment length polymorphism (RFLP) method.The study did not show any statistically significant differences in frequency of genotypes and alleles of MTR 2756A G polymorphism between PE group and controls. Higher frequency of 66GG genotype and 66G allele of MTRR 66A G polymorphism was observed in the women with PE compared to control group. Moreover, the 66GG genotype correlated with higher doses of methyldopa, lower birth weight and higher placenta weight in women with PE.The obtained results for 66A G polymorphism of MTRR gene suggest the predisposition to PE in carriers of mutated 66GG genotype and - 66G allele.

The current health requirements set the direction in pharmacological research, especially as regards diseases that require improvement of existing therapeutic regimens. Such diseases include preeclampsia, which is a hypertensive disorder of pregnancy during which there occurs progressive increasing activation of the immune system through elevation of pro-inflammatory cytokines and antiangiogenic factors, which is dangerous for the mother and fetus. A promising field of research for new drugs to treat this disease is the study of natural phenolic compounds of plant origin and herbal extracts, which are complex matrices of chemical compounds with broad biological activities. Many plant substances with anti‑inflammatory and anti‑hypertensive properties are known, but studies in animal models of preeclampsia and clinical trials concerning this disease constitute a new and developing research trend of significant medical importance. The aim of our research review was to identify and analyze the results of already available studies on baicalin, curcumin, epigallocatechin gallate, punicalagin, quercetin, resveratrol, salvianolic acid A (danshensu), silibinin, and vitexin, as well as plant extracts from Brassica oleracea L., Euterpe oleracea Mart., Moringa oleifera Lam., Punica granatum L., Silybum marianum (L.) Gaertner, Thymus schimperi Ronniger, Uncaria rhynchophylla (Miq.) Miq. ex Havil., and Vitis vinifera L., which are potential and promising candidates for further research and for potential new therapies.

Osteoporosis is a metabolic bone disease, manifested by decreased bone mineral density microarchitectural disturbances of bone tissue, and increased risk of bone fractures. Owing to large-scale morbidity particularly among postmenopausal women, nowadays osteoporosis constitutes a significant global health problem. In recent years, much attention has been paid to the role of signaling Wnt/β-catenin pathway and LRP protein in the pathomechanism of osteoporosis, indicating a possible contribution of polymorphic variants of the candidate LRP5 gene to disease development. The goal of our study is to present contemporary research on signaling Wnt/β-catenin pathway and mechanism of LRP protein action in the process of bone tissue metabolism and etiology of osteoporosis.

Osteoporosis is a multifactorial skeletal disorder characterized by low bone mass and microarchitectural deterioration of bone tissue, resulting in increased risk of fracture. Peak bone mass is an important predictor of later risk of osteoporosis. Epidemiological studies revealed that the risk of osteoporosis might be modified by exposure to environmental factors during intrauterine life and early postnatal period. This review summarizes the influence of fetal programming on the development of osteoporosis based on the epidemiological studies and potential mechanisms of epigenetic regulation of gene expression.

Changes in body posture, musculoskeletal disorders and somatic dysfunctions are frequently observed during pregnancy especially ligament, joint and myofascial impairment. The aim of the paper is to present the use of osteopathic manipulative treatment (OMT) for back and pelvic pain in pregnancy on the basis of a review of the available literature. MEDLINE and Cochrane Library were searched in January 2014 for relevant reports, randomized controlled trials, clinical and case studies of OMT use in pregnant women. Each eligible source was verified and analyzed by two independent reviewers. OMT procedures appear to be effective and safe for pelvic and spinal pain management in the lumbosacral area in pregnant women.

Objectives: Osteoporosis is a chronic, generalized bone disease conditioned by many factors among which the genetic background plays the significant role. Bone morphogenetic protein (BMP2), a growth factor belong to superfamily of TNF- proteins, is actively involved in bone tissue metabolism. BMP2 protein shows the osteoinduction potential and regulates growth of cartilage plate, and the same directly influences the process of osteogenesis. The aim: The aim of study was to examine the frequency of genotypes and alleles of 570A>T and 5375G>A of BMP2 gene polymorphisms in population of Polish postmenopausal women, as well as to analyze the relationship between investigated polymorphic variants and bone turnover parameters. Material and methods: Into the study 117 postmenopausal women, Caucasian race (average age 55,1 years) living in Wielkopolska region were classified. The analysis of 570A>T and 5375G>A BMP2 polymorphisms was performed by polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP) while bone mineral density (BMD) was measured by DEXA method. In the research the chosen clinical and bone turnover parameters were analysed. Results: In both 570A>T and 5375G>A BMP2 polymorphisms the similar frequency of genotypes and alleles in investigated groups of postmenopausal women with osteoporosis, osteopenia and in the group with correct T-score were noted. The analysis do not show the relationship of clinical and bone turnover parameters with particular genotypes of BMP2 polymorphisms in women with osteoporosis, osteopenia and in the group with correct T-score. Conclusions: The research did not confirm directly relationship of 570A>T and 5375G>A BMP2 polymorphisms with osteoporosis development in population of Polish postmenopausal women. The investigation also shows lack of correlation of 570A>T and 5375G>A BMP2 polymorphisms polymorphisms with analysed clinical and bone turnover parameters.

Introduction: The consequences of uncomplicated PPROM are serious, and the presence of overt intraamniotic infection (IAI) is associated with a significant increase in both, the maternal and fetal morbidity and mortality rate. TNF-alpha is a cytokine involved in systemic inflammation and plays an important role in modulating the acute phase reaction. Aim: the aim of this study was to evaluate the predictive value of tnf-alpha levels in maternal serum within 6 hours after pprom and in the period of up to 12 hours after delivery, in the prediction of neonatal and maternal infection. Material and methods: The investigation was conducted on a group of 56 women diagnosed with PPROM between 30+0 and 36+6 weeks gestational age. In the period of up to 6hrs from pprom first sample of 10ml of maternal venous blood for laboratory testing was taken and the level of tnf-alpha was measured. A second sample of venous blood was taken within 12hrs from delivery to reassess the tnf-alpha levels. All the participants were divided retrospectively into four groups depending on the occurrence of adverse neonatal and maternal outcome. Measuring the concentration of tnf-alpha in maternal serum was performed using the elisa method (enzymelinked immunosorbent assay). Results: A statistically significant difference in the second assay (up to 12 hours after delivery) between the patients with and without signs of maternal infection was observed concerning the tnf-alpha serum level. The concentration of this cytokine in maternal serum after delivery was 1.79 and 1.36 pg/ml (p

Objectives Introduction: Survivin is a member of the inhibitor of apoptosis protein (IAP) family, which are selectively overexpressed in human neoplasms, and its expression has been shown to be connected with cell proliferation. We analyzed survivin expression in ovarian epithelial neoplasms to evaluate its role in the development of ovarian tumors. Material and methods: Immunohistochemistry assays were conducted in 137 cases (48 ovarian carcinoma, 43 borderline ovarian carcinoma, 46 benign ovarian tumor, and 20 samples of normal ovarian tissue of ovarian epithelial neoplasms. Histological types included serous (n=68) and mucinous (n=69) tumors. All tumors were reviewed histopathologically and classified according to the WHO criteria. Results: Survivin expression in the group of serous neoplasms was detected in 24.0% (6 of 25) of benign cases, in 60.0% (12 of 20) of borderline tumors, and 91.0% (24 of 47) of ovarian carcinomas. In the group of mucinous tumors, survivin expression was found in 33.5% (7 of 21) of benign cases, 43.5% (10 of 23) of borderline tumors, and 80.0% (20 of 25) of malignant tumors. Conclusions: Our results demonstrate that survivin overexpression may play a crucial role in the development of epithelial ovarian neoplasms and be an important prognostic factor for the influence of survivin expression on epithelial ovarian cancers.

The first hormonal pill was approved in the 60s of the twentieth century Since that time, oral contraception has been used worldwide by dozens of women due to its high availability as well as relative ease and safety of taking. The main side effects of oral contraception include elevated risk for venous thromboembolism (VTE). Estrogens increase the probability of VTE development, depending on the dose in medication, and third-generation progestins increase the risk of VTE development more than older-generation progestins. Also, the coexistence of hereditary thrombophilia increases the risk of VTE development in women using oral contraceptives. Other side effects include changes in the carbohydrate and lipid economy Progestins in oral contraceptives decrease HDL cholesterol levels but increase LDL cholesterol and total cholesterol levels. Additionally estrogens are a recognized mitogenic factor for the epithelium of the mammary gland, acting proliferative on the glandular tissue and in the same way influence on the increased risk of breast cancer development. Patients sometimes complain about some subjective side symptoms such as headache, mood changes, nausea, back pain, breast pain and swelling, as well as decreased libido. Some patients discontinue oral contraception due to fear of side effects or temporary ailments before con- sulting their doctor what may result in unintended pregnancy The aim of the following paper was to present most frequent side effects of oral contraception, ways of their moni- toring and diagnosis.

Background: Polymorphisms which are presented below may be the cause of inherited thrombophilia and may result in pregnancy loss. The hypothesis is based on a number of cardiology studies which have confirmed the involvement of these polymorphisms in thrombotic incidents. Objectives: To evaluate the role of polymorphisms of factor VII gene ( Arg353Gln, -122T > C ) and PAI-1 gene ( -675 4G/5G ) in the etiology of recurrent miscarriage. Material and methods: The study group included 152 women with a positive history of ≥ 2 consecutive pregnancy losses (114 and 38 women with 2 and ≥ 3 miscarriages, respectively), while 180 healthy women were recruited as controls. Genetic analysis was performed with the use of PCR/RFLP. Results: Lower frequency of Arg353/Gln353 was observed in women with 2 and ≥ 3 miscarriages as compared to controls (21.1% vs. 23.9% and 13.2% vs. 23.9%, respectively). The frequency of Gln353 was lower in women with ≥ 3 miscarriages as compared to controls (6.6% vs. 11.9%, p = ns). The frequency of -122TT was higher in women with ≥ 3 miscarriages as compared to controls (86.84% vs. 76.67%, p = ns), whereas -122TC was more frequent in controls (13.16% vs. 22.78% in controls, p = ns). The frequency of -122T was higher in patients with ≥ 3 abortions as compared to controls (93.42% vs. 88.06%, p = ns), and -122C was observed more frequently in controls (6.58% vs. 11.94% in controls, p = ns). There were no significant differences as far as the -675 4G/5G polymorphism was concerned . Conclusions: The obtained results suggest a possible protective role of Gln353 and -122C alleles in recurrent miscarriage.

Objectives: Recurrent miscarriage (RM) is one of the most common obstetric complications. Numerous studies have suggested that genetic variants leading to an impaired balance between coagulation and fibrinolysis may contribute to elevated risk of pregnancy loss. The aim of the study was to investigate a possible association between angiotensin-converting enzyme (ACE, rs1799752) I/D and plasminogen activator inhibitor type 1 (PAI-1, rs1799768) 4G/5G polymorphisms with RM among Polish women. Material and methods: DNA was extracted from peripheral blood samples of 152 women with a history of ≥ 2 consecutive pregnancy losses before 22 weeks of gestation, and 180 healthy controls with at least 1 live birth at term and no history of pregnancy loss. Polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) were used to identify the polymorphisms. Results: No statistically significant differences were found in genotype and allele frequencies of the studied polymorphisms. The most relevant difference between the study group and controls was found for the ID genotype distribution of the ACE gene (52.6 vs. 46.7%, OR = 1.27, p = 0.28). The analysis of genotype coexistence revealed a higher incidence of the combination of the ACE II and the PAI-1 4G/4G genotypes in the control group (10.0 vs. 5.9% in control group; p = 0.17). Conclusions: The obtained results suggest no apparent association between the ACE I/D, PAI-1 4G/5G polymorphisms and increased RM susceptibility in the analyzed Polish population.

Pregnancy in the uterine scare after previous caesarean section is the rarest type of ectopic pregnancy Due to the possibility of life-threatening complications, cesarean scar pregnancy (CSP) needs rapid and proper diagnosis and management. Hereby we present 3 cases of women with CSP, diagnosed and treated at the Department of Gynecology and Obstetrics of Jagiellonian University Medical College, in Krakow, in 2013, as well as literature review.

Objectives: The aim of the study was to evaluate the frequency of the 677C>T and 1298A>C polymorphisms of the methylenetetrahydrofolate reductase (MTHFR) gene, as well as the coexistence of both these genetic variants in women from the Polish population. Material and methods: A total of 662 women from the Polish population were enrolled in the study group. The frequency of the investigated genotypes of the 677C>T and 1298A>C polymorphisms of the MTHFR gene was analyzed with the use of PCR/RFLP methods. Results: The frequency of the 677CC, 677CT and 677TT genotypes in the studied population of women was 50.60%, 39.88% and 9.52%, respectively. As to the 1298AA, 1298AC and 1298CC genotypes, the obtained results were as follows: 42.75%, 47.88% and 9.37%, respectively (Tables II and III). Simultaneous analysis revealed the most frequent coexistence of 677CC/1298AC (28.85%), 677CT/1298AA (20.85%) and 677CT/1298AC (19.03%) genotypes. The coexistence of 677CC/1298AA (12.39%), 677CC/1298CC (9.37%) and 677TT/1298AA (9.51%) genotypes was observed less frequently. In the studied population of Polish women, the coexistence of 677CT/1298CC, 677TT/1298AC and 677TT/1298CC genotypes has been not observed. Conclusions: The frequency and coexistence of genotypes of the 677C>T and 1298A>C MTHFR gene polymorphisms in the studied population of Polish women is similar to other North-European populations. Women carriers of the mutated variants of both, 677C>T and 1298A>C polymorphisms of the MTHFR gene should receive special perinatal care in order to prevent fetal defects and thrombosis-related complications during pregnancy. It is vital to emphasize the significance of proper education of folate supplementation, especially in pregnant patients and women of reproductive age.

The aim of our study was to evaluate the frequency of genotypes and alleles of the -11391GA and +45TG polymorphisms of the ADIPOQ gene in Polish women with excessive weight gain during pregnancy. A possible correlation between these polymorphisms and selected clinical and anthropometric parameters has been analyzed.A total of 153 pregnant Caucasian women of Polish origin with normal pre-pregnancy body mass were analyzed: 78 women with excessive weight gain (study group) and 75 women with normal weight gain during pregnancy (control group). The analysis of the polymorphisms was performed by PCR/RFLP.The influence of the -11391GA polymorphism on body mass and BMI values at the end of pregnancy (p0.05) was observed. We also detected a correlation of the +45TG polymorphism with body mass at the end of pregnancy and pre-pregnancy WHR values (p0.05).The observed effect of the -11391GA polymorphism on the parameters assessed at the end of pregnancy (BMI and body mass), suggests a protective role of the -11391A genetic variant in excessive weight gain. It is claimed that the mutated +45G allele of the +45TG ADIPOQ polymorphism shows a possible connection with higher pre-pregnancy WHR values and body mass at the end of pregnancy Our findings suggest a possible contribution of the -11391GA and +45TG polymorphisms of the ADIPOQ gene to the pathomechanism of excessive weight gain in pregnant women from the Polish population. This observation should be confirmed in a larger sample size study

Introduction: Recently, an increasing number of reports indicate the participation of genetic factors in the pathogenesis of preeclampsia (PE). The genes involved in the synthesis of nitric oxide that participates in the vasolidation, may play an important role in the development of this disorder. Hydrogen sulfide (H2S) which is produced by cystathionine gamma-lyase exhibits a similar effect to nitric oxide. It is suggested that certain polymorphisms of the CTH gene may participate in the development of chronic hypertension and preeclampsia. Aim of the study: To evaluate the frequency of genotypes and alleles of rs1021737 and rs482843 polymorphisms of CTH gene in women with preeclampsia from Wielkopolska region. Material and methods: The study group consisted of 60 patients with diagnosed preeclampsia, into the control group 120 healthy pregnant women were enrolled. The examined rs1021737 and rs482843 polymorphisms of CTH gene were determined using PCR-RFLP method. Results: Analysis of rs482843 polymorphism in the CTH gene showed a statistically significant difference in the prevalence of mutated GG genotype (p

Women have three very important physiological functions that are not observed in men--menstruation, pregnancy and lactation. Each of these mechanisms influences pharmacokinetics and pharmacodynamics of many drugs. Individualization of pharmacotherapy is a major challenge of modern medicine. The differences in response to drug are responsible for the effectiveness of pharmacological treatment and the occurrence and severity of toxic effects and side effects. Therapeutic decision should be based not only on account of the dose-effect, but the consideration of gender, genetic and environmental differences affecting the final therapeutic effect. Many important differences between men and women like sex-based differences in normal physiology, or in the predisposition to a specific disease, can be due to genetic differences, the actions of the sex steroid hormones or an interaction between these factors. Women generally have a lower body mass, a reduced hepatic clearance, differences in activity of cytochrome P450 (CYP) enzymes (increase in CYP3A4, decrease in CYP2D6, CYP2C19 and CYP1A2) and different from men's rate of drug metabolism. Other important factors contributing to gender differences in the pharmacokinetics of drugs are conjugation, absorption, protein binding and urinary excretion. It still remains unexplained how gender differences affect the increased risk of side effects. This review is an attempt to assess the biological, physiological and hormonal basis of women differences in the pharmacokinetics and pharmacodynamics of many drugs.

Osteoporosis is a disease with low bone mass and disorganization of the internal microarchitecture of bone tissue. Determination of biochemical markers allows for early diagnosis of changes in bone tissue metabolism. The search for a marker whose biological function could be directly connected with bone metabolism, clearly indicating a connection between its concentration and risk fracture as well as response to treatment, continues. Currently measurement of collagen-derived markers of bone resorption is used in the majority of cases. They are, first of all, telopeptides of collagen type 1 localized on the amino end-N-terminal telopeptide of type 1 collagen (NTX), as well as on the carboxy end-C-telopeptide of type 1 collagen (CTX) of collagen molecule. Among markers of bone synthesis, special attention is paid to the procollagen type 1 carboxy-terminal propeptide (POCP) and procollagen type 1 amino-terminal propeptide (P1NP). Simultaneous application of bone synthesis and resorption markers allows for a full imaging of the bone remodeling process and application of biochemical markers in the diagnosis and therapy of osteoporosis.

Objective Preeclampsia (PE) is a major cause of maternal and perinatal mortality and morbidity. The studies suggest that both polymorphisms and changes of expression in genes encoding enzymes involved in the methionine and homocysteine metabolism (MHM), such as methylenetetrahydrofolate, reductase (MTHFR), methionine synthase (MTR), methionine synthase reductase (MTRR) and cystathionine gamma-lyase (CSE), could play a role in the development of hypertension during pregnancy. The aim of the study was to determine the expression level of MTHFR, MTR, MTRR and CSE genes in the development of PE in Caucasian women. Study design The control group consisted of 74 healthy pregnant women and 90 patients with diagnosed pre-eclampsia. Total RNA was isolated from placenta and the mRNA level of examined genes was to determine using real-time PCR. Results The expression level of MTHFR gene showed no statistically significant difference in the study group as compared to the control group. An increase of mRNA levels for MTR and CTH was observed by 124.7% (p 0.05), respectively. However, a decrease of placental expression was noted for MTRR by 50% in preeclamptic women as compared to control group (p Conclusions Our findings suggest that the elevated RNA expression of MTR in placenta of preeclamptic patients is probably results of a potential compensation mechanism of the MHM while elevated CSE expression indicates that homocysteine may be eliminated through the alternate transsulfuration pathway.

OBJECTIVES The goal of this study was to evaluate the frequency of Sp1 +1245G>T (rs 1800012) and -199 7G>T (rs 1107946) COL1A1 gene polymorphisms in postmenopausal women with osteoporosis and osteopenia as well as assessing their relations with the clinical parameters and parameters of bone turnover. STUDY DESIGN The study included 538 (236 postmenopausal and 302 healthy reproductive) Polish women. The postmenopausal group included women with osteoporosis (n = 90), osteopenia (n = 90), as well as healthy individuals (n = 56). All women of reproductive age were healthy BMD was marked in the L2-L4 lumbar region of the spine using dual energy X-ray absorptiometry (DXA). Genomic DNA was isolated from peripheral blood, the genotype frequency of investigated polymorphisms was determined by PCR-RFLP technique. RESULTS The frequency of Sp1 +1245G>T and -1997G>T polymorphisms of COL1A1 gene showed no statistically significant differences between group with osteoporosis, osteopenia and correct T-score and women of reproductive age. In postmenopausal women it was found that osteopenia and osteoporosis were correlated with age, birth weight, age of last menses occurrence, height, body weight and BMI value. Clinical parameters in all groups of women did not show any statistically significant correlation with frequency of Sp1 +1245G>T and -1997G>T COL1A1 polymorphisms. CONCLUSIONS An evaluation of Sp1 +1245G>T (rs1800012) and -1997G>T(rs 1107946) COL1A1 polymorphisms showed any influence of these genetic variants on osteoporosis development in Polish postmenopausal women. The presented correlation between osteoporosis and age, birth weight, age of last menses occurrence, height, body weight and BMI value confirms the important role of environmental factors in disease etiology.

Background and Aims Recognition of different genetic variants underlying development of osteoporosis would make it possible to administer individual symptomatic treatment as well as early prophylactics of osteoporosis. The aim of the study was to evaluate frequency of polymorphism 326A/T of gene ITLN-1 and assessment of its relations with the clinical parameters of osseous turnover and degree of postmenopausal osteoporosis. Methods The study included 800 women at the postmenopausal (505) and reproductive (295) age throughout Wielkopolska region in Poland. The postmenopausal group included women with osteoporosis and osteopenia and the healthy ones. Women at the reproductive age were healthy. Frequency of the tested gene polymorphism was evaluated in the group where BMD was marked and in the control group. Results The analysis of the polymorphism A326T of gene ITLN-1 showed that in healthy postmenopausal female with genotype AA birth weight, BMD L2–L4 YA (%) and BMD L2–L4 AM (%) were significantly higher (BMD– bone mineral density ; L2–L4 – lumbar vertebrae no 2, 4 ; YA– peak adult bone mass ; AM– age-matched bone mass ). In women with osteopenia BMD L2–L4 YA (%) and BMD L2–L4 AM (%) were significantly higher in women with genotype AA, but BMD L2–L4 was significantly higher in women with genotype TT. In women with osteoporosis with genotype AA T-score was significantly higher, but BMD L2–L4 and BMD L2–L4 YA (%) were significantly lower in this group. BMD L2–L4 AM (%) was significantly higher in women with AA genotype. Conclusion In women with osteoporosis and osteopenia homozygous AA genotype may predispose to lower BMD in the lumbar spine.

Introduction: Toll-like receptors (TLR) may play a key role in initiating cellular signaling pathways by increasing the levels of inflammatory cytokines which, cooperating with osteoclasts, influence bone turnover. Numerous research articles focused on the genetic background of this condition, among others on polymorphic variants in TLR genes. The aim of the study was to examine the role of 20877G>A (Arg753Gln) in TLR2 gene and 8993C>T (Thr399Ile) in TLR4 gene in the etiopathogenesis of postmenopausal osteoporosis in Polish women. Material and methods: This study included 180 postmenopausal women (t-score ≤ -2.5), 153 postmenopausal women with osteopenia (t-score between -2.5 and -1), and 91 postmenopausal healthy women with correct t-score (t-score >-1). The 20877G>A TLR2 and 8993C>T TLR4 polymorphisms were determined by PCR/RFLP analysis. Results: The analysis did not reveal statistically significant differences in the distribution of genetic variants of 20877G>A TLR2 polymorphism between the investigated groups of women. The most interesting results were connected with 8993C>T TLR4 polymorphism. Comparison of the group with osteoporosis and controls revealed overrepresentation of heterozygous 8993CT genotype (13.3 vs. 5.5%, OR=2.65, p=0.03). Also, mutated 8993T allele was overrepresented in the group with osteoporosis (6.7 vs. 2.7%, OR=2.52, p=0.04). Higher frequency of heterozygous 8993CT genotype (13.3 vs. 4.6%, OR=3.21, p=0.004) and mutated 8993T allele (6.7 vs. 2.3%, OR=3.05, p=0.005) was noted in osteoporotic women as compared to the group with osteopenia. Higher frequency of heterozygous 8993CT genotype (13.3% vs. 5.3%, OR=2.73, p=0.003) and mutated 8993T allele (6.7 vs. 2.7%, OR=2.61, p=0.004) was observed in the group with osteoporosis as compared to women with osteopenia and with correct t-score. Conclusions: Results of our study suggest an important role of mutated 8993T allele of 8993C>T TLR4 polymorphisms in the etiology of postmenopausal osteoporosis. Nevertheless, this observation requires further investigation with larger sample size comprised of Polish women.

Introduction: Nowadays the strong genetic background of preterm delivery (PTD) in connection with immune answer has been indicated. The purpose of the study was the assessment of frequency of TNF-α -238G>A, -308G>A, -376G>A gene polymorphisms in the etiology of preterm delivery. Material and methods: The study group consisted of 150 women with PTD (22+0 - 36+6 gw.), the controls of 150 women who delivered at term (>37 gw.). PTD group was divided into subgroups: a/ delivery between 22-28 gw., b/ 28-32 gw., and c/ 32-36+6 gw. Genetic analysis was performed by PCR/RLFP method. Results: Overrepresentation of -238GA genotype (12.7 vs. 4.7%, p=0.011) and -238A allele (7.7 vs. 2.3%, p=0,002) in PTD group has been observed. In PTD 28-32 gw. subgroup, higher frequency of -238GA genotype (31.6 vs. 4,7%, p=0.00095), and mutated -238A allele (21.1 vs. 2.3%, p=0.00004) was noted. Moreover in PTD 28-32 gw. subgroup we have noted higher presence of heterozygous -376GA genotype (10.5 vs. 1,3%, p=0,063) and mutated -376A allele (5.3 vs. 0,7%, p=0.064). Analysis of TNF-α polymorphisms co-occurrence showed statistically significant overrepresentation of genotypes containing mutated -238A allele in PTD group (-238GA/-308GG/-376GG: 8.0 vs. 2,7%, p=0.035). Haplotype analysis revealed statistically significant difference between PTD and controls in the incidence of -376G/-308G/-238A haplotype containing mutated -238A allele (0.063067 vs. 0.016634, p=0.030).Conclusion: The study indicated the strong association of mutated -238A allele of TNF-α gene with increased risk of PTD. Analysis of genotypes and alleles prevalence in PTD women divided according to gestational age suggests the possible role of mutated variants of -238G>A and -376G>A TNF-α polymorphisms in Polish women delivering between 28 and 32 gw.

Objectives: Changes of kinase activity of non-genomic cellular signaling pathway may influence the effectiveness of pharmacotherapy in case of hormone-dependent tumors. Our study investigated a possible interaction at the molecular level between an aqueous herbal extract of Epilobium angustifolium as well as a lipid-sterolic fruit extract of Serenoa repens and synthetic drugs used in the treatment of hormone-dependent cancers. Material and methods: E. angustifolium and Serenoa repens extracts were orally administered to testosteroneinduced rats for 21 days. Changes of RafA/Mapk3/Mapk1 mRNA levels were analyzed by real-time quantitative PCR using target specific primers. Results: The level of RafA mRNA slightly increased in rats receiving Epilobium angustifolium (p=0.076) and Serenoa repens (p=0.016) extracts. Administration of these extracts resulted in significantly elevated Mapk1 and Mapk3 transcripts in the investigated animals (p

Objectives: Genetically determined disturbances in the activity of coagulation factor VII may lead to obstetric complications. The aim of the study was to evaluate the correlation between -323P0/P10 factor VII gene polymorphism and the risk of recurrent miscarriage. Material and methods: The study group consisted of 152 women with a history of ≥2 miscarriages. The control group comprised 180 women with no history of miscarriage and ≥1 pregnancy who gave birth to a healthy newborn at term. The study group was further subdivided twice into two subgroups: 114 patients with a history of 2 miscarriages and 38 subjects with a history of ≥3 miscarriages, and 123 patients with miscarriages

In multiple pregnancy, the following may be considered to delay the delivery: bed rest, antibiotics, tocolytics, steroids, and, possibly, cervical cerclage. Analysis of uterine contraction intensity, reevaluation of the chorion and the amnion, as well as monitoring of the mother and the fetus are also very important. Clinical and laboratory parameters ought to be carefully monitored to prevent intra-amniotic infection. We present a case of a delayed delivery in a trichorionic, triamniotic, triplet pregnancy after IVF. The first and the second fetuses were delivered spontaneously at 23 and 26 weeks of gestation, respectively. The third fetus was delivered by a cesarean section at 26 weeks of gestation. The delay between the first and the second/third fetuses was 18 days. Only the second child survived. At present, the psychomotor development of the infant is considered as normal.