Genetic risk score for gestational weight gain.

Gestational weight gain (GWG) involves health consequences for both mother and offspring. Genetic factors seem to play a role in the GWG trait. For small effect sizes of a single genetic polymorphism (SNP), a genetic risk score (GRS) summarizing risk-associated variation from multiple SNPs can serve as an effective approach to genetic association analysis. The aim of the study was to analyze the association between genetic risk score (GRS) and gestational weight gain (GWG). GWG was calculated for a total of 342 healthy Polish women of Caucasian origin, aged 19 to 45 years. The SNPs rs9939609 (FTO), rs6548238 (TMEM18), rs17782313 (MC4R), rs10938397 (GNPDA2), rs10913469 (SEC16B), rs1137101 (LEPR), rs7799039 (LEP), and rs5443 (GNB3) were genotyped using commercial TaqMan SNP assays. A simple genetic risk score was calculated into two ways: GRS1 based on the sum of risk alleles from each of the SNPs, while GRS2 based on the sum of risk alleles of FTO, LEPR, LEP, and GNB3. Positive association between GRS2 and GWG (ß = 0.12, p = 0.029) was observed. Genetic risk variants of TMEM18 (p = 0.006, OR = 2.6) and GNB3 (p < 0.001, OR = 3.3) are more frequent in women with increased GWG, but a risk variant of GNPDA2 (p < 0.001, OR = 2.7) is more frequent in women with adequate GWG, and a risk variant of LEPR (p = 0.011, OR = 3.1) in women with decreased GWG. GRS2 and genetic variants of TMEM18, GNB3, GNPDA2, and LEPR are associated with weight gain during pregnancy.

Common Variants in One-Carbon Metabolism Genes (MTHFR, MTR, MTHFD1) and Depression in Gynecologic Cancers.

We investigated the association between methylenetetrahydrofolate reductase (gene MTHFR 677C>T, rs1801133), 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR 2756A>G, rs1805087), and methylenetetrahydrofolate dehydrogenase, cyclohydrolase and formyltetrahydrofolate synthetase 1 (gene MTHFD1 1958G>A, rs2236225)-well-studied functional variants involved in one-carbon metabolism-and gynecologic cancer risk, and the interaction between these polymorphisms and depression. A total of 200 gynecologic cancer cases and 240 healthy controls were recruited to participate in this study. Three single-nucleotide variants (SNVs) (rs1801133, rs1805087, rs2236225) were genotyped using the PCR-restriction fragment length polymorphism method. Depression was assessed in all patients using the Hamilton Depression Scale. Depression was statistically significantly more frequent in women with gynecologic cancers (69.5% vs. 34.2% in controls, p < 0.001). MTHFD1 rs2236225 was associated with an increased risk of gynecologic cancers (in dominant OR = 1.53, p = 0.033, and in log-additive models OR = 1.37, p = 0.024). Moreover, an association was found between depression risk and MTHFR rs1801133 genotypes in the controls but not in women with gynecologic cancers (in codominant model CC vs. TT: OR = 3.39, 95%: 1.49-7.74, p = 0.011). Cancers of the female reproductive system are associated with the occurrence of depression, and ovarian cancer may be associated with the rs2236225 variant of the MTHFD1 gene. In addition, in healthy aging women in the Polish population, the rs1801133 variant of the MTHFR gene is associated with depression.

Guidelines of the Polish Society of Gynecologists and Obstetricians, the Polish Society for Vaccinology, and the Polish Society for Family Medicine on vaccinating women with reproductive plans and pregnant or breastfeeding women.

The following Guidelines present the most up-to-date treatment and management recommendations, which may be modified and altered after detailed analysis of a specific clinical situation, which in turn might lead to future modifications and updates.

The Influence of Various Hydration Strategies (Isotonic, Water, and No Hydration) on Hematological Indices, Plasma Volume, and Lactate Concentration in Young Men during Prolonged Cycling in Elevated Ambient Temperatures.

BACKGROUND: Increased internal body temperature during dehydration can be accompanied by water-electrolyte imbalances, higher levels of lactate during and after physical exertion, and changes in blood volume. Adequate hydration with carbohydrate-electrolyte fluids during physical activity can prevent dehydration and delay the onset of fatigue, allowing for proper biochemical and hematological reactions during exertion. A suitable drinking plan should consider the pre-exercise hydration level as well as the requirements for fluids, electrolytes, and substrates before, during, and after exercise. The objective of this study was to assess the impact of different hydration strategies (isotonic, water, and no hydration) on hematological indicators (hemoglobin concentration, hematocrit number, erythrocyte count, leukocyte count, and mean corpuscular volume) and lactate concentration during prolonged physical exertion in a high-temperature environment in young men. METHODS: The research method was quasi-experimental. The study involved 12 healthy men aged 20.6 ± 0.9 years, who were characterized by a body height (BH) of 177.2 ± 4.8 cm, a body mass (BM) of 74.4 ± 7.6 kg, a lean body mass (LBM) of 61.1 ± 6.1 kg, and a body mass index (BMI) of 23.60 ± 0.48. Measurements were taken of body composition and hematological and biochemical indicators. The main tests consisted of three series of tests separated by a one-week break. During the tests, the men performed a 120 min exercise with an intensity of 110 W on a cycle ergometer in a thermo-climatic chamber at an ambient temperature of 31 ± 2 °C. During exertion, the participants consumed isotonic fluids or water in an amount of 120-150% of the lost water every 15 min. The participants who exercised without hydration did not consume any fluids. RESULTS: Significant differences in serum volume were observed between the use of isotonic beverage and no hydration (p = 0.002) and between the use of isotonic beverage and water (p = 0.046). Immediately after the experimental exercise, hemoglobin values were significantly higher with no hydration than with water (p = 0.002). An even stronger significance of differences in hemoglobin was observed between no hydration and isotonic beverage consumption (p < 0.001). There was a statistically significant difference in the number of leukocytes between the consumption of isotonic beverage and no hydration (p = 0.006). CONCLUSIONS: Each active hydration strategy allows for a better maintenance of water-electrolyte homeostasis during physical exertion in a high-temperature environment, and isotonic beverage consumption had a greater impact on hydrating extracellular spaces with the smallest changes in hematological indicators.

Anti-Candida and Antibiofilm Activity of Selected Lamiaceae Essential Oils.

BACKGROUND: Candidiasis is a common oral and vaginal infection. Some papers have presented that the essential oils of Lamiaceae plants can have antifungal activity. This study aimed to investigate the activity of 7 essential oils of the Lamiaceae family with known phytochemical compositions against Candida fungi. METHODS: Forty-four strains belonging to six species were tested: C. albicans, C. glabrata, C. guilliermondii, C. krusei, C. parapsilosis, and C. tropicalis. During this investigation, the following methods were used: determination of the minimal inhibitory concentrations (MICs), biofilm inhibition studies, and in silicotoxicity tests. RESULTS: Essential oils of lemon balm (Melissa officinalis) and oregano (Origanum vulgare) showed the best anti-Candida activity, with MIC values below 3.125 mg/mL. Lavender (Lavandula stoechas), mint (Mentha × piperita), rosemary (Rosmarinus officinalis), and thyme (Thymus vulgaris) essential oils were also very active (0.39 to 6.25 or 12.5 mg/mL). Sage (Salvia officinalis) essential oil presented the lowest activity, with MIC values ranging from 3.125 to 100 mg/mL. In an antibiofilm study using MIC values, oregano and thyme essential oils showed the greatest effect, followed by lavender, mint, and rosemary oils. The weakest antibiofilm activity was observed with the lemon balm and sage oils. In silico toxicity research suggests that most of main compounds of Lamiaceae essential oils probably do not exhibit carcinogenicity, mutagenicity, or cytotoxicity. CONCLUSIONS: The obtained results showed that Lamiaceae essential oils have anti-Candida and antibiofilm activity. Further research is required to confirm the safety and efficacy of essential oils in the topical treatment of candidiasis.

Expression of ABCA1 Transporter and LXRA/LXRB Receptors in Placenta of Women with Late Onset Preeclampsia.

BACKGROUND: Appropriate levels of cholesterol are necessary for the mother and developing fetus, but theirexcess may cause preeclampsia. The ABCA1 transporter mediates the secretion of cholesterol and is highly regulated at the transcriptional level via the nuclear liver X receptors (LXRs). METHODS: Sixteen preeclamptic and 39 normotensives healthy women with uncomplicated pregnancies were involved in the case-control study. The placental levels of ABCA1, LXRA and LXRB mRNA were quantified by real-time quantitative PCR. The concentrations of ABCA1, LXRA and LXRB proteins from the placenta were determined using an enzyme-linked immunosorbent assay Results: We found in the logistic regression model significantly lower placental expression of LXRB mRNA (crude OR = 0.26, 95% CI: 0.07-0.94, p = 0.040) and LXRA protein level (crude OR = 0.19, 95% CI: 0.05-0.69, p = 0.012) in late-onset preeclamptic women compared to healthy pregnant women. The values remained statistically significant after adjustment for possible confounders. CONCLUSIONS: Our results suggest that high placenta LXRA mRNA and LXRA protein expression levels decrease the risk of late-onset preeclampsia. These nuclear receptors could play a role in the development of preeclampsia through disturbances of lipid metabolism.

Plant Preparations and Compounds with Activities against Biofilms Formed by Candida spp.

Fungi from the genus Candida are very important human and animal pathogens. Many strains can produce biofilms, which inhibit the activity of antifungal drugs and increase the tolerance or resistance to them as well. Clinically, this process leads to persistent infections and increased mortality. Today, many Candida species are resistant to drugs, including C. auris, which is a multiresistant pathogen. Natural compounds may potentially be used to combat multiresistant and biofilm-forming strains. The aim of this review was to present plant-derived preparations and compounds that inhibit Candida biofilm formation by at least 50%. A total of 29 essential oils and 16 plant extracts demonstrate activity against Candida biofilms, with the following families predominating: Lamiaceae, Myrtaceae, Asteraceae, Fabaceae, and Apiacae. Lavandula dentata (0.045-0.07 mg/L), Satureja macrosiphon (0.06-8 mg/L), and Ziziphora tenuior (2.5 mg/L) have the best antifungal activity. High efficacy has also been observed with Artemisia judaica, Lawsonia inermis, and Thymus vulgaris. Moreover, 69 plant compounds demonstrate activity against Candida biofilms. Activity in concentrations below 16 mg/L was observed with phenolic compounds (thymol, pterostilbene, and eugenol), sesquiterpene derivatives (warburganal, polygodial, and ivalin), chalconoid (lichochalcone A), steroidal saponin (dioscin), flavonoid (baicalein), alkaloids (waltheriones), macrocyclic bisbibenzyl (riccardin D), and cannabinoid (cannabidiol). The above compounds act on biofilm formation and/or mature biofilms. In summary, plant preparations and compounds exhibit anti-biofilm activity against Candida. Given this, they may be a promising alternative to antifungal drugs.

Plant Phenolics and Extracts in Animal Models of Preeclampsia and Clinical Trials-Review of Perspectives for Novel Therapies.

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 anti­inflammatory and anti­hypertensive 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.

The importance of NFκB1 rs4648068 and RUNX2 rs7771980 polymorphisms in bone metabolism of postmenopausal Polish women.

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.

Vitamin D3 and its receptor in selected obstetrical complications.

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.

Cervical cancer screening in Poland in current SARS-CoV-2 pandemic: Interim guidelines of the Polish Society of Gynecologists and Obstetricians and the Polish Society of Colposcopy and Cervical Pathophysiology - a summary January 2021.

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.

Combined Effects of Methyldopa and Flavonoids on the Expression of Selected Factors Related to Inflammatory Processes and Vascular Diseases in Human Placenta Cells-An In Vitro Study.

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-1ß; IL-6) and vascular effects (hypoxia-inducible factor 1α-HIF-1α; placental growth factor-PIGF; transforming growth factor ß-TGF-ß; 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-1ß, IL-6, HIF-1α, TGF-ß, 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.

Vitamin D receptor gene polymorphisms and haplotypes in the etiology of recurrent miscarriages.

A few years ago it was shown that disturbed metabolism of the vitamin D/receptor (VD/VDR) complex may be important in the etiology of spontaneous abortion, as well as in the etiology of recurrent miscarriages (RM). The goal of this study was to investigate the association between four maternal VDR polymorphisms as well as haplotypes settings and RM occurrence in a Polish population of women in reproductive age. A total of 230 women were recruited to this study (110 with RM, 120 consecutively recruited age-matched healthy women with at least two full-term pregnancies and with no history of miscarriages). DNA samples were genotyped for VDR polymorphisms: FokI (rs2228570), BsmI (rs1544410), ApaI (rs7975232) and TaqI (rs731236). Significant differences in genotype distributions and allele frequencies between case and control groups were observed in VDR BsmI polymorphism (GG vs. GA and AA, OR = 0.56, p = 0.036 and OR = 1.49, p = 0.035, respectively). The best evidence of an association with RM prevention was observed for the TTGT haplotype, which was more frequent among controls than cases even after permutation test (0.09 vs. 0.017, p = 0.0024). Other haplotypes were also significantly more frequent in the control group: TGT (rs7975232, rs1544410, rs2228570), TG (rs7975232, rs1544410), TTG (rs731236, rs7975232, rs1544410), TT (rs731236, rs7975232). Our research indicated the possible role of VDR BsmI genetic polymorphism in RM etiology, suggesting at the same time the active role of maternal VD metabolism and its influence on pregnancy outcome. The significant influence of several maternal haplotypes was shown to prevent RM occurrence.

The 2020 race towards SARS-CoV-2 specific vaccines.

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.

Single nucleotide vitamin D receptor polymorphisms (FokI, BsmI, ApaI, and TaqI) in the pathogenesis of prematurity complications.

The vitamin D receptor (VDR), coded by the VDR gene, plays a pivotal role in executing cellular functions when bound by the active form of vitamin D. Gene polymorphisms in this receptor have been increasingly associated with a heightened state of vulnerability to certain diseases. However, limited data is available concerning the role of VDR gene polymorphisms in preterm infant complications. In 114 premature infants (< 32 weeks gestation) we analyze four single nucleotide VDR polymorphisms (rs2228570 (FokI), rs1544410 (BsmI), rs797532 (ApaI), rs731236 (TaqI)) for their association with respiratory distress syndrome (RDS), intraventricular hemorrhage (IVH), bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC) and retinopathy of prematurity (ROP). The results show that BPD was almost four times more likely in infants with the genotype CC of ApaI (rs7975232) (OR 3.845; p = 0.038). While both BPD and NEC were 2.1 times more likely to occur in preterm infants with the allele C of ApaI (rs7975232) (respectively: OR 2.111 and OR 2.129, p < 0.05). The ApaI VDR polymorphism appears to influence incidence of BPD and NEC in preterm infants. Considering VDR polymorphisms in future genetic investigations, in preterm complications, may prove clinically relevant.

FokI vitamin D receptor polymorphism as a protective factor in intrahepatic cholestasis of pregnancy.

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.

Associations between folate and choline intake, homocysteine metabolism, and genetic polymorphism of MTHFR, BHMT and PEMT in healthy pregnant Polish women.

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 < 0.05). There were no associations found between the examined parameters and BHMT (rs7356530), MTHFR (rs1801133) and PEMT (rs12325817) alone. However, blood tHcy concentrations differed in the PEMT genotype subgroups when choline and folate intakes were considered: respectively, 25% and 20% lower levels were observed in the C allele carriers who met their needs of choline or folate than in those who did not take enough these nutrients (P < 0.05 for both associations). CONCLUSIONS: This study suggests that choline and folate intakes might interact with MTHFR, BHMT and PEMT polymorphisms to determine tHcy and GSH blood concentrations in healthy pregnant women.

MTHFR genetic polymorphism and the risk of intrauterine fetal death in Polish women.

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.

Importance of polymorphic variants of phosphatidylethanolamine N-methyltransferase (PEMT) gene in the etiology of intrauterine fetal death in the Polish population.

OBJECTIVES: 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. STUDY DESIGN: 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. RESULTS: 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. CONCLUSIONS: The present findings indicate that PEMT polymorphisms may be associated with the susceptibility to IUFD in the Polish population.

Pharmacological Effect of Quercetin in Hypertension and Its Potential Application in Pregnancy-Induced Hypertension: Review of In Vitro, In Vivo, and Clinical Studies.

Since improving maternal and child health is a public health priority worldwide, the main aim of treatment of hypertension in pregnant women is to prevent complications during pregnancy, labor, and postpartum. In consequence, much attention is paid to the use of antihypertensive drugs that can be used safely during pregnancy. Several side effects of methyldopa, which is currently the most commonly used antihypertensive drug in pregnant women, mean that the search for an effective and safe alternative still continues. Flavonoid compounds present in medicinal plants, vegetables, and fruits may be a promising source of new drugs. In this aspect, quercetin, a well-known flavonoid due to its antihypertensive action, may be considered a prototype for safe antihypertensive drugs. This review focuses on the selective activity of quercetin. Based on recent studies, a few problems were discussed, including (1) pathology of pregnancy-induced hypertension; (2) search for new pharmacological treatments of pregnancy-induced hypertension; (3) issues with the use of herbal extracts during pregnancy; (4) flavonoids as natural active chemical compounds; (5) quercetin: its action during pregnancy, in vitro and in vivo pharmacological activities, clinical trials, and meta-analysis; (6) quercetin intake during pregnancy; (7) other natural compounds tested during pregnancy; (8) potential problems with the use of quercetin; (9) safety profile of quercetin. Various studies have shown a beneficial effect of quercetin on vascular endothelial function and its antioxidative and anti-inflammatory activity on cellular and tissue level. It is known that in animal models quercetin affects positively the development of embryo, fetus, and placenta. Because this flavonoid did not have teratogenic and abortive effect, it is generally recognized as safe. For this reason it should be appreciated and studied in the aspect of its potential use in the prevention and treatment of pregnancy-induced hypertension among women in this risk group.