Search

Proper metabolism of folates has a crucial role for body homeostasis. Folate metabolism regulates changing of amino acids (homocysteine and methionine), purine and pyrimidine synthesis and DNA methylation. These whole biochemical processes have significant influence on hematopoietic, cardiovascular and nervous system functions. The disturbances of folate cycle could result in chronic hypertension, coronary artery disease, higher risk of heart infarction, could promote cancers development, and psychic and neurodegenerative diseases. No less important is the connection with complications appearing in pregnant woman (recurrent miscarriages, preeclampsia, fetus hypotrophy intrauterine death, preterm placenta ablation, preterm delivery) and fetus defects (Down syndrome, spina bifida, encephalomeningocele, myelomeningocele). The complex process of folate metabolism requires adequate activity of many enzymes and presence of co-enzymes. A key enzyme in folate metabolism is methylenetetrahydrofolate reductase (MTHFR - methylenetetrahydrofolate reductase), and 677C>T polymorphism of MTHFR gene is connected with lower enzymatic activity In several researches it was indicated that 677C>T MTHFR polymorphism is an independent factor influencing homocysteine concentration in serum, and also folate concentration in serum and red blood cells. Nevertheless, it was also observed the correlation of 677C>T MTHFR polymorphism with Down syndrome, and neural tube defects appearance in fetus. In European populations frequency of mutated 677TT genotype ranges from a few to several percent. Women carriers of 677TT or 677CT MTHFR genotypes are exposed on folate metabolism disturbances and on the consequences of incorrect folate process during pregnancy Nowadays in this group of women folic acid supplementation is widely recommended. In the light of modern knowledge the attention was also focused on the importance of metafolin administration that omitted pathways of folic acid transformation after administration, and in pregnant women certainly is valuable complement of supplementation in this respect.

The primary pathologic reason for thrombotic thrombocytopenic purpura (TTP) lies in the systemic formation of platelet aggregations in association with endothelial cells damage. Endothelial damage is a result of an abnormal synthesis and metabolism of unusually large von Willebrand Factor (ULvWF) multimers. In normal conditions vWF cleaving metalloprotease, known as ADAMTS-13 (A Disintegrin And Metalloproteinase with Thrombospondin type-1 motif, member 13) prevents the ULvWF entrance in the circulation. It already has been proven that thrombotic thrombocytopenic purpura is strongly correlated with severe congenital or acquired deficiency of ADAMTS-13. Congenital ADAMTS-13 deficiency is known as Upshaw-Schulman Syndrome and it accounts for only 2-4% of all TTP cases. It is conditioned by genetic variants of the ADAMTS-13 gene causing reduced ADAMTS-13 synthesis and shows an autosomal recessive type of inheritance.We present an interesting case of a 20 year old patient, primigravida, nulliparous, in 28th gestational week of twin pregnancy with undiagnosed Upshaw-Schulman Syndrome. The patient was transferred from the district hospital to the Tertiary Perinatal Care Center because of thrombocytopenia and suspicion of hemolytic-uremic syndrome. Genetic analysis performed 5 years after patient's death (before 2008 that kind of genetic analysis had not been available in Poland) showed a homozygotic mutation in the ADMTS13 gene (4143insA) which confirmed the diagnosis of Upshaw-Schulman Syndrome.1. TTP, especially hereditary Upshaw-Schulman Syndrome, is extremely rare and complicates the course of pregnancy. It is usually very sudden and dramatic; 2. Differential diagnosis of this disease is difficult and treatment strategy very burdensome for the patient. For this reason, diagnosis of micro-angiopathic disorders need to be simultaneously based on both clinical symptoms and laboratory findings; 3. Genetic diagnosis that confirms exact recognition of Upshaw-Schulman Syndrome is not commonly available; 4. The described case was a huge diagnostic challenge, and actually the final diagnosis was published until five years after the patient's death. Before 2008, that type of genetic analysis had not been available in Poland; 5. Despite the enormous progress in medical knowledge and experience, the exact diagnosis of TTP, including Upshaw-Schulman Syndrome, of this condition remains very difficult.

Decreased nitric oxide (NO) plasma concentration may be involved in the development of preeclampsia. It has been suggested that genetic variants of endothelial nitric oxide synthase (eNOS) gene may reduce NO plasma levels.To evaluate the correlation of 894GT (Glu298Asp) and -786TC polymorphisms of NOS3 gene with the development of preeclampsia (PE) and gestational hypertension (GH).110 hypertensive pregnant women (mean age 29.46 +/- 4.54 years, mean gestational age 36.88 +/- 3.50 gw., mean systolic blood pressure 16782 +/- 16.87 mmHg, mean diastolic blood pressure 104.32 +/- 11.62 mmHg) were enrolled into the study group. The whole study group was further subdivided into two subgroups: women with gestational hypertension (GH, n = 69) and with preeclampsia (PE, n = 41). Gestational hypertension and preeclampsia were diagnosed according to the ACOG standards. All patients with multiple pregnancy diabetes, vascular changes and thrombotic complications were excluded from the study. The control group consisted of 150 healthy pregnant women (mean age 28.29 +/- 4.40 years, mean gestational age 39.06 +/- 1.28 gw., mean systolic blood pressure 12.07 +/- 10.75 mmHg, mean diastolic blood pressure 70.62 +/- 9.13 mm Hg). The frequency of investigated genotypes of NOS3 gene polymorphisms was examined by polymerase chain reaction and restriction fragment length polymorphism (PCR/RFLP) method.As far as the 894GT polymorphism was concerned, a higher frequency of 894TT genotype in the control group in comparison to the whole study group was observed (8.7 vs. 5.4%; WR = 0.61, p = ns). A similar observation was made about the 894T allele (25.4 vs. 30.0%, WR = 0.79, p = ns). The frequency of the 894T allele was also higher in controls in comparison to the PE group (30% vs. 26.8%, p = ns) and GH group (30% vs. 24.6%, p = ns). Analyzing the -786TC polymorphism no statistically significant differences between the whole study and the control groups was found. The frequency of the mutated -786CC genotype was similar in the entire study group and controls (13.6 vs. 15.3%, p = ns). The frequency of the mutated -786C allele was also similar in both analyzed groups (37.3 vs. 38.0%, p = ns). A statistically significant difference in the frequency of coexistence of mutated homozygotic genotypes 894TT/-786CC between the investigated groups (0.9% in the whole study group vs. 6.7% in the control group, p = 0.019) was observed. Coexistence of 894GT/-786TC genotypes was noted more frequently in the control group (19.1% in the whole study group vs. 24.7% in the control group, p = ns). The frequency of other combinations of investigated genotypes coexistence did not significantly differ between the control group, the entire study group, and the PE and GH groups. In the PE group, a higher systolic blood pressure was noted in patients with -786CC genotype (205.0 +/- 21.2 mmHg) in comparison to patients with -786TT (177.0 +/- 17.8 mmHg) or -786TC (173.4 +/- 13.5 mmHg) genotypes (p = ns).The presence of the 894TT genotype of the 894GT (Glu298Asp) polymorphism may play a protective role in the development of preeclampsia. The presence of the -786CC genotype of the -786TC polymorphism may correlate with the increase of the systolic blood pressure in pregnant women with preeclampsia.

Proper folate supplementation is required in order to ensure proper folate concentration in the organism, and consequently to prevent the development of numerous complications in general population and pregnant women. Metafolin (stable calcium salt of L-5-methyltetrahydrofolate acid, L-5-MTHF) is the most active form of reduced folate circulating in plasma, which directly enters the metabolic process of folate. After administration metafolin shows optimum absorption, comparable or higher bioavailability as well as physiological activity when compared to folic acid. Metafolin supplementation is effective in decreasing plasma homocysteine, as well as increasing folate in plasma and erythrocytes, in pregnant and breastfeeding women or those who wish to conceive. In addition, metafolin administration omits the multistage process of reduction before entering the folate cell cycle, as well as a possible deficiency of activity of enzymes participating in the reduction of folate process in the intestine epithelium (DHFR and MTHFR enzymes). So far no potential adverse and toxic effects of metafolin management have been reported. The published findings require confirmation in larger groups of patients and an additional analysis of the presence of particular genotypes of 677C > T polymorphism of the MTHFR gene. Analysis of the recent literature reposts suggests that metafolin could be an effective and safe alternative to folic acid supplementation and could effectively prevent complications in pregnancy and series birth defects in fetuses and newborns.

Objectives: The aim of the study was to evaluate the frequency of 20210G>A and 19911A>G prothrombin gene polymorphisms in a group of women with 2 or more miscarriages in the first trimester of pregnancy. Material and methods: The study involved 150 women with two or more miscarriages in the first trimester of pregnancy (mean age 31.5±4.1 years). The control group consisted of 180 healthy women (mean age 28.7±4.0 years). The frequency of genotypes and alleles of the investigated polymorphisms was evaluated by polymerase chain reaction/restriction fragments length polymorphism method (PCR/RFLP). Results: As to the 20210G>A prothrombin gene polymorphism, overrepresentations of 20210GA genotype have been observed in the group of women with miscarriages (2.7% vs. 1.1% in the control group, WR=2.44, ns), as well as overrepresentation of 20210A allele (1.3% vs. 0.6% in the control group, WR=2.42, ns). Considering the 19911A>G polymorphism, a similar frequency of mutated homozygous 19911GG genotype has been noted (22.6 vs. 21.1% in controls, OR=1.10, ns). Also, frequency of mutated 19911G allele was similar in both investigated groups with miscarriages and controls (48.6% vs. 45.7%, OR=0.89, ns). Conclusions: Our findings suggest lack of correlation of 20210G>A and 19911A>G prothrombin gene polymorphisms with the risk of recurrent miscarriages in the first trimester of pregnancy. Further studies, concerning other genetic variants conditioning inherited thrombophilia and environmental factors influencing the risk of recurrent abortions, are needed. Therefore, further research with more numerous group of women with recurrent miscarriages and taking into account other polymorphisms of thrombophilia and influence of environmental factors is required.

Adrenomedullin (ADM), a peptide with vasodilatory natriuretic and diuretic properties, is secreted in many tissues and shows multidirectional activity ADM activity may play an important role in the pathophysiology of gestational hypertension (GH) and preeclampsia (PE) by involvement in compensation of failed utero-placental unit circulation.The aim of the study was to evaluate the association of -1984AG ADM gene polymorphism with the development of GH and PE in maternal-fetal dyads.The study group consisted of 46 hypertensive pregnant subjects (further divided into two subgroups: 20 pregnant women with GH and 26 women with PE). 43 healthy pregnant women constituted the control group. The study and the control groups as well as the newborns were genotyped for -1984AG ADM gene polymorphism using PCR/RLFP procedures.Minor--1984G allele was found to be higher in both, the GH (15.00%, OR = 3.62, p = 0.05), and the PE groups (9.62, OR = 2.18, p=ns) when compared with controls (4.65%). A tendency for higher frequency of minor -1984G allele (12.50 vs. 6.98% in controls, OR = 1.91, p=ns) was observed in the newborns from the GH group. It was also noteworthy that coexistence of both heterozygous genotypes of maternal-fetal dyads (-1984AG mother/1984AG fetus) was overrepresented in the GH group (15.00 vs. 6.98%, OR = 2.35, p=ns) and in the PE group (11.54 vs. 6.98%, OR = 1.74, p=ns) when compared to controls.The observed tendency for overrepresentation of minor -1984G ADM allele in the GH and PE women and their newborns, despite lack of statistical significance, suggests participation of this genetic variant in the pathogenesis of the mentioned conditions. Additionally the obtained results could indicate that maternal-fetal gene-gene interaction may be a potential source of adverse perinatal outcomes.

The aim of the antibacterial therapy during pregnancy is to select a proper antibiotic and determine its effective dose, at the same time excluding the risk of potential teratogenic effect. Pregnancy is characterized by many physiological, disease-predisposing changes, particularly of bacterial etiology that have an influence on different pharmacokinetic of drugs. When determining an effective dose of an antibiotic, one should take into account changes in the pharmacokinetics (PK) of drugs in pregnant women, involving mainly the phase of distribution (increased volume of body fluids, cardiac output, reduced concentration of albumins), metabolism (induction of hepatic enzymes: CYP3A4, CYP2D6, CYP2C9, UGT1A4, UGT2B7, inhibition of CYP1A2, CYP2C19), and excretion (increased glomerular filtration rate). Results of few pharmacokinetic studies on pregnant patients point to the need of increasing the dose or reducing dosage intervals for some antibiotics (e.g. penicillin V ampicillin, piperacillin, imipenem, clindamycin). The aim of this study was to summarize current knowledge regarding the PK of antibiotics during pregnancy.

Human cytochrome P450 1A 1 is one of the most important enzymes participating in human carcinogenesis because it metabolites several procarcinogens to active carcinogenic metabolites. Additionally enzymes of CYP450 family play an important role in estrogenes catabolization (17-beta-estradiol and estron) to intermediate products (2-, 4-hydroxyestradiol and 2-, 4-hydroxyestrone) including CYP1A1 that catalyses hydroxylation to 2-hydroxyestrogens in the endometrium. Derivates of these compounds (4-hydroxyestrogens) are carcinogenic and could induce DNA damage leading to tumour transformation. The presence of CYP1A1 enzyme in genital tract tissues could induce chemical carcinogenesis initiating cancer development. Recent studies also confirmed the role of CYP1A1 in the development of ovarian and endometrial cancer in humans. The presence of mutated CYP1A1 polymorphic variants influencing the CYP1A 1 activity could be responsible for different interindividual susceptibility to genital cancers in women.

Adrenomedullin (ADM) is indicated to be a biologically active polypeptide released by endothelium with strong hypotensive, long-acting vasodilatator properties. It is suggested that development of preeclampsia is partly related to decreased ADM influence on blood vessels.The purpose of this study was to evaluate the adrenomedullin mRNA expression in placenta of preeclamptic women and additionally to assess the correlation between ADM mRNA expression and -1984AG ADM gene polymorphism.26 preeclamptic (PE), 20 with gestational hypertension (GH) and 43 normotensive healthy pregnant women have been involved into the study. The placenta samples were collected instantly after delivery from the central part of maternal side. The ADM gene expression was measured with the real-time polymerase chain reaction (rt-PCR). The results were standardized according to the reference glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene. The -1984AG ADM gene polymorphism was determined by PCR/RFLP assayLower expression of ADM mRNA in PE group (0.881 +/- 0.254 vs. 1.039 +/- 0.391 in controls, ns) has been investigated. In PE group the placental ADM mRNA expression was slightly higher at women carrying AA genotype (0.890 +/- 0.263 vs. 0.842 +/- 0.231, ns). In the control group higher placental ADM mRNA expression in women with AG + GG genotype of -1984AG ADM gene polymorphism (1.249 +/- 0.431) in comparison to women carrying AA genotype (1.036 +/- 0.356, ns) was observed. The study also revealed negative correlation between placental ADM mRNA expression and systolic blood pressure in hypertensive pregnant women (p = 0.020).Reduced mRNA expression for ADM in the placenta connected with reverse correlation of systolic blood pressure in preeclamptic women suggests the significant role of disturbances in placental secretion of ADM in etiology of preeclampsia.

For years much attention has been paid to the possible role of cytokines in the etiology of preterm delivery (PTD) in relation to anticipation of delivery in women with premature rupture of membranes (PROM). There are no clear indications introducing this observation to clinical practice. The goal of this study was to evaluate interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha), G-colony stimulating factor (G-CSF) concentration in serum of women with PROM in connection with the occurrence of the delivery35 patients with PROM (average age 29.6 +/- 3.8 years, average time of gestation 35.2 +/- 1.5 weeks) were analyzed. The pregnant women were divided into 2 groups: 15 women delivered24 h and 20 women delivered24 h since the appearance of PROM. In both analyzed subgroups, the levels of IL-6, TNF-alpha, G-CSF CRP and leucocytosis have been compared. The concentration of IL-6, TNF-alpha and G-CSF in serum was measured by immunoenzymatic ELISA method, CRP concentration by immunoturbimetric method.In the whole group of women with PROM, the differences in average serum concentration of IL-6 before and after delivery (6.01 +/- 3.71 pg/mL and 7.98 +/- 3.44 pg/mL p0.05) and G-CSF (130.92 +/- 110.32 pg/mL and 79.59 +/- 52, 13 pg/mL, p0,05) have been observed. Moreover, average TNF-alpha concentration before and after the delivery was 1.43 +/- 0.63 pg/mL and 1.72 +/- 1.06 pg/mL (p0.05), respectively. It is particularly interesting that the authors have observed higher concentration of G-CSF in women who delivered within 24 h since PROM (147.05 +/- 103.88 pg/mL), if compared to the women who delivered after 24 h since PROM (118.81 +/- 115.71 pg/mL, without statistically significant difference p0.05). The same remark was connected with difference of IL-6 concentration in analogical groups of women (6.42 +/- 4.14 pg/mL vs 5.71 +/- 3.42 pg/mL, p0.05). Equally interesting observation were statistically significant differences in G-CSF concentration before and after delivery (147.06 +/- 103,88 vs 74.67 +/- 46.84, p0.05) in the event of the delivery24 h since PROM, such as in IL-6 concentration (5.71 +/- 3.42 vs 8.11 +/- 3.41, p0.05) in case of the delivery24 h since PROM.Statistically significant differences in IL-6, G-CSF, and CRP concentration before and after the delivery suggest the participation of these factors in the etiology of preterm delivery in women with PROM. The higher IL-6 and G-CSF concentration in women delivering within 24 h since the appearance of PROM suggest that these cytokines could be involved in the processes leading to delivery Statistically significant differences in IL-6 and G-CSF concentration before and after the delivery in a group of women delivering24 h or24 could indicate an important contribution of changes in proportions of these cytokines in PTD the etiology in PROM.

Recently much attention has been focused on endothelin-1 (ET-1) and endothelin-1 converting enzyme (ECE-1) gene polymorphisms and connected changes in ET-1 concentration. Additionally these processes have been shown to be possibly involved in preeclampsia susceptibility. The aim of this study was to evaluate the correlation between ET-1 (Lys198Asn) and ECE-1 (Thr341lle) gene polymorphisms and the risk of gestational hypertension and preeclampsia.The study group consisted of 110 hypertensive (69 with gestational hypertension and 41 preeclamptic) pregnant women. The control group included 150 healthy pregnant women. The frequency of investigated polymorphisms was examined by polymerase chain reaction and restriction fragment length polymorphism (PCR/RFLP) assayThere were no statistically significant differences in genotype frequencies of ET-1 Lys198Asn and ECE-1 Thr341lle gene polymorphic variants between hypertensive pregnant women and the control group. There were also no remarkable differences between GH and PE groups when compared to the controls. However parallel presence of both Thr341lle ECE-1 and Lys198Asn ET-1 variant localisation showed a higher occurrence rate of ECE-1 CT/ET-1 GT heterozygotic genotypes in the control group (5,3%) than in the whole study or GH and PE groups (0.9%, 1.4% and 0.0% respectively p = ns). In preeclamptic women, the higher systolic blood pressure value was observed in GG Lys198Asn ET-1 genotype carriers (180.7 mmHg) than in patients with at least one mutated T allele (GT and TT) (167.3 mmHg, p = ns). The lowest blood pressure level was connected with the mutated TT Lys198Asn ET- 1 genotype presence.Results of this study suggest lack of direct correlation of Lys198Asn ET-1 and Thr341lle ECE-1 gene polymorphisms with risk of gestational hypertension and preeclampsia in the studied population of Polish women. High prevalence of ECE-1 CT/ET-1 GT heterozygote genotypes of both Thr341lle ECE-1 and Lys198Asn ET-1 polymorphisms in healthy pregnant subjects compared to GH and PE groups suggests the protective role of mutated alleles in the development of PE. The carrier of mutated TT genotype of Lys198Asn ET-1 polymorphism is probably connected with lower systolic blood pressure level in preeclamptic women. Future studies are needed to establish the role of analysed polymorphisms in the etiology of gestational hypertension and preeclampsia.

The antiphospholipid syndrome (APS) is a systemic non-inflammatory and autoimmune connective tissue disease. ASP is characterized by formation of autoantibodies against cell membrane phospholipids which act as procaogulation factors. Association with recurrent pregnancy loss, intrauterine growth retardation, preeclampsia and placenta ablation makes ASP a serious perinatologic problem. The primary form can evaluate into lupus-like disease or full-symptomatic lupus erythematosus, both usually preceded by acute form of APS. In pregnant women this situation may present considerable diagnostic problems. The aim of this work was to present a patient with acute primary antiphospholipid syndrome during pregnancy and puerperium, which subsequently was diagnosed as systemic lupus erythematosus flare. Such progression is rare and, despite several previous reports, requires extensive explanations and research.

Nowadays the possible role of vasoactive peptide adrenomedullin (ADM) is considered in the etiology of preeclampsia (PE), where ADM is indicated to be a protective factor decreasing blood pressure. The aim of this study was to evaluate the role of -1984AG ADM gene polymorphism and its connection with ADM plasma level in women with gestational hypertension (GH) and preeclampsia.63 hypertensive (30 with GH and 33 with PE) and 94 healthy pregnant women were included into the study The frequency of genotypes and alleles of -1984AG ADM gene polymorphism was examined by PCR/RFLP method. ADM concentration was measured by ELISA method.In GH subgroup higher frequency of heterozygous AG genotype (16.67% vs. 8.50%, O.R. = 2.68, p = ns) and G allele (11.67 vs. 4.30%, O.R. = 2.97, p = 0.043) was observed. In PE subgroup overrepresentation of heterozygous AG genotype (15.15% vs. 8.5%) and slightly higher frequency of G allele (p = ns) were noted. In AA genotype subgroup of hypertensive women in comparison to the AG+GG genotype group higher proteinuria value (212.1 vs. 90.9 mg/dl, p0.0001), lower systolic (171.1 vs. 177.3 mmHg), as well as lower diastolic blood pressure level (107.1 vs. 111.4 mmHg) were noted. The highest ADM plasma level was observed in the group of women with PE (1.817 vs. 1.692 ng/ml, p = ns). Moreover, higher ADM plasma concentration in patients with AA genotypes in comparison to the carriers of AG and GG genotypes (1.844 vs. 1.402 ng/ml, p = ns) was noted.Higher ADM plasma concentration in women with PE suggests possible correlation between ADM level and pathological changes in cardiovascular system during pregnancy Overrepresentation of genotypes containing at least one mutated G allele of the -1984AG ADM gene polymorphism in women with GH and PE suggests participation of this allele in pathogenesis of these conditions. Higher ADM concentration in carriers of homozygous AA genotype found in GH and PE groups indicates the possible important role of A allele in prevention of GH/PE appearance.

Side effects and contraindications connected with hormonal replacement therapy in climacterium resulted in search for new methods of softening menopausal symptoms. The aim of the following study was to evaluate, based on literature analysis, the effectiveness of phytohormonal therapy as an alternative method of relieving the symptoms of menopausal period and preventing the diseases connected with deficiency of estrogens after menopause. Phytoestrogens therapy reduces the number and strength of the vasomotor symptoms and improves serum lipid profile. Moreover phytoestrogens show beneficial effects on bone tissue metabolism, skin and mucous membranes condition and are applicable in chemoprevention. This therapy is an effective method, allowing to avoid further changes in blood and urogenital systems, which result from estrogen stimulation deficiency. Phytoestrogens administration is an efficient method of relieving postmenopausal symptoms, facilitating the difficult menopausal period and keeping good health condition.

Pain of lumbosacral segment of the vertebral column and the pelvis concerns about 45% of all pregnant women. The change of the body posture during pregnancy is the result of gravity centre relocation, which affects the musculosceletal system. Development of the joint, ligament and myofascial dysfunctions, as well as the pain in the lumbosacral segment and the pelvis, are the most common reasons of spine pain. The aim of this review is to present the current state of knowledge about lumbar spine pain in pregnant women with special focus on the pain connected with muscular, joint and ligament disorders. Pregnancy is a serious burden for the female osteo-skeletal system. Lumbar pain with different location and intensification is the negative consequence of the position changes during pregnancy. Pharmacotherapy could be useful only in cases of intensive low back pain, with possible application of small spectrum of drugs that are safe during pregnancy. Physical therapy including manual therapy exercises, massage and techniques of local anesthesia are alternative methods in case of low back pain in pregnant women.

Leptin, as many other hormones and metabolic factors, may play a role in fetal development in pregnancy complicated by type 1 diabetes. Different genetic variants in leptin gene and leptin gene receptor may have influence on leptin synthesis in the course of pregnancy and metabolic state of the mother.To assess the possible influence of metabolic factors on fetal weight in type 1 diabetic subjects with homozygotic variants in leptin gene (-2548 G/A) and leptin gene receptor (668 G/A).30 diabetic and homozygotic subjects (out of 100 diabetic subjects) were qualified to the study Genotyping was performed by PCR-RFLR The following factors were assessed: glycemia, leptin concentration, glycated hemoglobin, lipid profile (total cholesterol, LDL, HDL, triglycerides), maternal body weight. Multiple regression models were developed and ROC curves were used in the analysis.Mean fetal weight in the analyzed group was 3600 g. The following parameters were found to have influence on fetal weight: I trimester leptin (R2-0.80741288, p0.05), I trimester glycemia (R2-0.80741288, p0.05), III trimester glycemia (R2-0.80741288, p0.05), I trimester HbA1C (R2-0.80741288, p0.05), III trimester LDL (R2 = 0.63192254, p0.05). Moreover the influence of LDL and maternal BMI (R2-0.81869348, p0.05) was found. ROC curve analysis revealed the influence of I trimester leptin--AUC 0.62; sensitivity 0.75; specificity 0.5; cut-off 28.127 ng/ml, III trimester HbA1C AUC 0.66; sensitivity 0.23; specificity 0.91; cut-off 7.9%, III trimester mothers weight AUC 0.63; sensitivity 0.25; specificity 0.93; cut-off 98 kg.Apart from well-known metabolic factors influencing fetal weight, I trimester leptin concentration was found to have an impact on fetal growth.

Increasing evidence indicates that genetic factors are involved in the process of carcinogenesis. BRCA 1 mutation has been proven to be responsible for increased risk of ovarian cancer However the importance of other genetic disorders, such as MTHFR polymorphism for increased risk of carcinogenesis, is still to be determined. Abnormal methylation seems to play a significant role in ovarian cancer pathogenesis. MTHFR catalyses the conversion of 5,10-methylenetetrahydrofolate into 5-methyltetrahydrofolate which is a co-substrate in homocysteine remethylation into methionine. Thermolabile MTHFR protein variants with lower enzymatic activity are the effects of the mutation.The evaluation of 677CT MTHFR polymorphism frequency in the group of ovarian cancer women with BRCA 1 mutation. The assessment of the MTHFR 677CT polymorphism influence on ovarian cancer risk.A group of 153 patients with ovarian cancer (Caucasian, Polish population in Wielkopolska region) were included into the study 3 mutations: 5382insC, C61G and 4153delA in BRCA1 gene, and genotype frequency within 677CT MTHFR polymorphism, were identified. The analysis of genotype frequency was performed by means of PCR/RFLP method.127 women without BRCA1 mutation and 26 with one of the mutations: 5382insC, C61G or 4153delA were qualified for the investigation. In the group with BRCA 1 mutation, 3 out of 26 patients were with TT genotype mutation of 677CT polymorphism (12%). Heterozygotic genotype CT appeared in 13 cases out of 26 (50%), homozygotic CC in 10 out of 26 (38%). In the group of 127 ovarian cancer patients without BRCA1 mutation, TT genotype in 677CT polymorphism was present in 5 women (4%). Heterozygotic genotype CT appeared in 61 cases (48%), similarly to homozygotic genotype CC-61 (48%). The highest value (OR = 3.18) was obtained when comparing the homozygotic TT genotype groups. None of the obtained values was statistically significant.Contrary to numerous suggestions in various publications, we did not confirm the correlation between MTHFR 677CT polymorphism and the influence on the risk of ovarian cancer in BRCA1 mutation carriers in the investigated group of Polish women.

Soybean isoflavones are phytoestrogens that reduce menopausal symptoms and decrease the risk of certain chronic diseases, such as cancer and cardiovascular diseases. Despite the widespread use of soybean isoflavones as functional food and dietary supplements, data regarding the safety as well as herb-drug interactions, remain scarce. The aim of the study was to investigate the influence of soybean extract on the expression levels of cytochrome P450 (CYP) genes using real-time PCR (RT-PCR).Male Wistar rats were fed a standardized soybean extract containing 37% isoflavones (100 mg/kg) for 3 and 10 days. cDNA was synthesized from total RNA isolated from the liver using reverse transcription. The level of CYP genes expression was analyzed using RT-PCR method.Soybean extract administration resulted in a significant increase of CYP1A1 expression level compared with the control group (1.5-fold; p0.05). An inductory effect was also observed for CYP2D1 by 32% (p0.01) after 10 days of treatment. No statistically significant differences were noted for CYPIA2, CYP2C6 and CYP3A2. In case of CYP3A1, the mRNA level of this gene was reduced by almost 35% (p0.05) both, after 3 and 10 days. CYP2D2 expression was also inhibited by the extract, but to a lesser degree when compared to CYP3A1. Moreover insignificant decrease of CYP2E1 expression level by 25% (p0.01) was observed after 3 days of treatment.These findings suggest that soybean extract may change the expression of CYP enzymes involved in biotransformation of xenobiotics (drugs, procarcinogens).

The diagnosis of intraamniotic infection (IAI) is usually based on clinical signs and symptoms which are not always distinct and specific and may be probematic. Thus, a search for more sensitive markers, such as procalcitonin (PCT), and several cytokines in serum of pregnant women to predict IAI development, seems necessary. The goal of the study was to evaluate the usefulness of PCT IL-6 (interleukin 6) and CRP (C-reactive protein) concentrations in prediction of IAI development and newborn status.In serum of pregnant women (46 women with clinically diagnosed premature rupture of membranes) the concentrations of PCT was measured by immunolumimetric assay of IL-6 by ELISA kit, and of CRP by turbidimetric methods. To investigate the usefulness of the markers in predicting newborn infections and pregnancy prolongation, we have calculated sensitivity specificity negative, positive prognostic value and the area under the ROC curve (AROC--Area under Receive Operating Characteristic).PCT has the highest predictive value in predicting clinical symptoms of IAI in newborns (AROC 0.647, cut point--PCT concentration 0.5 mg/dL). The highest predictive value for IL-6 was obtained in predicting the time of pregnancy prolongation since the moment of the test to the delivery (AROC 0.690 for 7 days of pregnancy prolongation, cut point--IL-6 concentration 7 pg/ml). During analysis of CRP, the highest predictive value was obtained in predicting the newborn status, evaluated by the Apgar score in the first minute of life (AROC 0.706, cut point--CRP concentration 20 mg/dL).Analysis of PCT and IL-6 concentrations in serum allows to identify women that are more likely to deliver newborns with symptoms of severe infection. In cases of severe infection, the usefulness of PCT measurement surpasses any currently used methods, such as CRP concentration measurement, for example. This investigation confirmed the usefulness of IL-6 and CRP measurement in predicting the duration of time from the examination to delivery.

Recurrent miscarriages (RM) are significant social and clinical problem. One of suggested reason of RM is hyperhomocysteinemia. Polymorphic genes involved in homocysteine and folate metabolism, including 5,10-methylenetetrahydrofolate reductase (MTHFR) gene, are considered as an important risk factors for homocysteine accumulation and modulator of RM susceptibility. Therefore the aim of this study was to evaluate the frequency of MTHFR polymorphisms (677CT, 1298AC, and 1793GA) in women with recurrent miscarriages.We have analyzed 104 Polish women with a history of 3 or more unexplained recurrent miscarriages in the first pregnancy trimester (6-13 gestation week). The control group consisted of 169 women without obstetrical complication, any history of miscarriage and with at least one live birth in anamnesis. The investigated polymorphisms were determined by PCR/RFLP methods.For MTHFR 1793GA polymorphism we have observed significant overrepresentation of heterozygotic GA genotypes in RM group (15.38% vs. 4.14% in the controls, OR=4.21, p=0.003). For 677CT and 1298AC we have shown lack of significant association with RM. Nevertheless, such significant association was observed if more than one mutated MTHFR variant was present in one patient.Our research indicate the possible role of MTHFR 1793GA polymorphism in pathogenesis of RM. The noticed tendency to more frequent occurrence of haplotypes of MTHFR gene including two or three mutated alleles showed the possibility of summarized amplification of these variants effect influencing RM susceptibility.

During pregnancy the concentrations of many coagulation factors are increased what leads to a "physiological" hypercoagulability status and constitutes a natural protection against delivery hemorrhage. These changes may be conducive to venous thrombembolism. Antithrombin is one of the endogenous clotting inhibitors. As a serine protease, it inactivates thrombin and the efficiency of this reaction is intensified by heparin. Acquired antithrombin deficiency is caused by disseminated intravascular coagulation syndrome, deep vein thrombosis, neoplasms, nephritic syndrome, renal failure, liver diseases, long-term estrogen treatment, dialysis or extracorporeal circulation. There are also cases of inherited antithrombin deficiency which leads to thrombophilia. The following study presents a course of pregnancy and postpartum of a woman with deep vein thrombosis and acquired antithrombin deficiency as well as the applied treatment. The legitimacy of routine assay of antithrombin activity and antithrombin supplementation in pregnant women with thrombosis was considered. This procedure may be helpful when dealing with obese pregnant patients as it is difficulty to identify and establish a therapeutic dose of heparin in their cases. Therapy guidelines for pregnant patients with thrombosis and acquired antithrombin deficiency have not been established yet.

Thyroid disorders are quite a common health problem in pregnant women, thus adequate treatment in this period is very important in order to decrease maternal and fetal morbidity. The prevalence of hyperthyroidism is estimated to be present in approximately 0.2-0.4% of all pregnancies and the most common is Graves disease. Untreated hyperthyroidism is connected with disturbed fertilisation, recurrent miscarriages, preeclampsia development, hypotrophy of the fetus, and haemorrhage in the postpartum period. Hypothyroidism is found in pregnant women in 0.3-0.7% of all cases. Uncontrolled hypothyroidism in pregnancy can lead to preterm birth, low birth weight and mental retardation. The goal of the treatment of both hypo- and hyperthyroidism is to reach a stable euthyroid state by applying thyroid hormones or antithyroid drugs, respectively. It seems that well-controlled management of thyroid diseases does not pose any problem for pregnancy. However, the most important is to avoid any neurological abnormalities in the fetus in hyperthyroid women resulting from antithyroid drugs exposure. Moreover, it is also crucial to abstain from subclinical hypothyroidism and hypothyroxinaemia in the mother and its effect on the fetus's development which merits exact screening and intense monitoring. In this paper we described the complex pharmacology of the drugs that are used in pregnant women suffering from thyroid disorders, considering the clinical application, practical recommendation, and side effects in pregnancy and lactation. This systematic analysis could contribute some pharmacological knowledge which will be helpful in the clinical management of thyroid disorders during pregnancy.

Toll-like receptors (TLR) -2 and -4 are a part of basic defence mechanism protecting against bacterial infections. They recognize microbial products and increase immune response of the host organism. The relationship between the expression of TLR receptors and the occurrence of intraamniotic infection (IAI) as well as preterm labour was demonstrated. Therefore, a relationship between TLR-2 and -4 genes polymorphism, premature rupture of membranes (PROM), intraamniotic infection and preterm labour is claimed to exist.The aim of the following study was to evaluate the frequency of two genetic polymorphisms: Arg753Gln (G20877A) in TLR-2 and Thr399lle (C8993T) in TLR-4 genes in a group of pregnant women with preterm rupture of membranes and preterm labour.33 pregnant women with the diagnosis of preterm--between 30 and 36 weeks of gestation--rupture of membranes (study group), and 60 healthy pregnant women (controls) were enrolled into the study. To analyse Arg753Gln polymorphism of TLR-2 gene and Thr399lle polymorphism of TLR-4 gene, polymerase chain reaction and restriction fragments length polymorphism (PCR/RFLP) were used.For G20877A polymorphism in TLR-2 gene, the frequency of heterozygous GA genotype in the study group was 9.1% and was comparable with the control group (8.3%, p = ns). Moreover frequency mutated G allele was comparable in both examined groups (4.6% in the study group and 4.2% in the control group, p = ns). For C8993T polymorphism in TLR-4 gene, heterozygous CT genotype was less frequent in the study group in comparison with the control group (9.1 vs. 16.7%). The homozygous CC genotype was more frequent in the study group (90.0 vs 83.3%, p = ns), with relatively high value of the odds ratio (OR = 2,0). Similar observations were conducted by analysing the frequencies of the alleles in both examined groups.Overrepresentation of heterozygous CT genotype and mutated T allele of C8993T polymorphism in TLR-4 gene in the control group may indicate that, possibly, it plays a protective role against PROM. However this hypothesis requires further investigation on a larger group of patients with premature rupture of membranes.

Sacrococcygeal teratoma develops from all three germinal layers (endoderm, mesoderm and ectoderm). Sacrococcygeal teratomas (SCT) are the most common neoplasms in the fetus and newborns, with an estimated prevalence of 1 in 20,000 to 1 in 40,000. Female to male ratio is 3:1. Perinatal mortality rate among fetuses with prenatally diagnosed SCT is high, mainly due to cardiac failure. According to Polish Gynecology Society Recommendation, the main aim of intrauterine intervention or pharmacological treatment in case of prenatally diagnosed SCT is to prevent development of severe fetal cardiac failure. Fetal cardiac failure is one of the most important prognostic factors in surveillance of fetus and newborns with SCT. The following article describes a case report of a 34-year-old pregnant woman, 23 weeks of gestation, with a diagnosis of fetal sacrococcygeal teratoma. Each pregnant woman with suspicion of neoplasm in fetus should be referred to tertiary center of perinatal care to gain access to specific diagnostic methods and medical care of many specialists, such as obstetricians, neonatologists, general practitioners and infant surgeons. The role of psychological care during hospitalization is also invaluable and helps the patient to minimize the mental trauma, due to diagnosed fetal abnormalities.

It is claimed that application of botanical supplements or herbal medicinal products with synthetic drugs that are cytochrome P450 enzymes substrates may induce significant herb-drug interactions and may alter pharmacotherapy. Echinacea preparations are one of the best selling products in the Europe and their medicinal use is still increasing but data about interactions of Echinacea extract with CYP enzymes are limited. In this study, we have investigated potential influence of standardized Echinacea purpurea extract containing 3.7% polyphenolic compounds on the mRNA expression level of major CYP450 enzymes using animal model. Total RNA was isolated from the rat liver tissue according to the manufacturer's protocol. Complementary DNA was synthesized from a mature mRNA template using reverse transcription. The level of mRNA expression in liver was analyzed by real-time quantitative PCR using specific target primers for CYP450 genes. In this study, it was demonstrated a significant increase of rat CYP2D1 and CYP1A1 expression level by 40% (p = 0.007) and 80% (p = 0.01), respectively. A weak inductory effect of the extract was observed for CYP1A2 by 16% (p > 0.05) compared with the control group. The levels of rat CYP3A1 and CYP3A2 mRNA were reduced by 41% (p < 0.05) and 25% (p = 0.001), respectively. A weak inhibitory effect was observed for CYP2D2 by 15% (p = 0.008) and CYP2C6 by 18% (p = 0.004) after long application of the Echinacea ethanolic extract. CYP2D2 and CYP2C6 activities were also inhibited by extract but in a lesser degree than CYP3A1 activity. Moreover, very little or no inhibition was noted for CYP2E1 both after 3 and 10 days of treatment. Our in vivo data indicate that the Echinacea ethanolic extract can potently inhibit the expression of CYP3A1/2 and can also induce of CYP1A1, CYP2D1. These findings suggest that Echinacea extract may influence the P450-mediated metabolism of different drugs and may initiate chemical carcinogenesis by activation of some compounds to their carcinogenic metabolites.

5,10-methylenetetrahydrofolate reductase (MTHFR) is the key enzyme in folate, methionine and homocysteine metabolism. The disturbances in MTHFR activity could be the cause of increased serum level of homocysteine. Hyperhomocysteinemia is a risk factor of changes in coagulation cascade through direct cytotoxic influence on endothelium, atherogenesis, activation of coagulation factor V and VII, increased level of thrombin and platelets aggregation. Genetic disturbances in MTHFR enzyme activity in the presence of polymorphic variants of its gene are responsible for homocysteine augmentation and could be the reason of several gestational complications such as recurrent miscarriages.

It is currently believed that disturbances of maternal clothing system leading to occurrence of thrombotic abnormalities, conditioned by the presence of acquired or inherited thrombophilias, may be an important reason for recurrent abortions. The aim of this study was to investigate frequency and significance of polymorphisms in genes coding for factor V (1691GA) and factor II (20210GA) of coagulation cascade in a group of women with two or more miscarriages in the first trimester of pregnancy.The investigations were conducted in a group of 104 women with anamese history of two or more miscarriages in the first trimester of pregnancy and in a group of 169 women with correct obstetrical anamnesis and confirmed presence of at least one pregnancy that resulted in a birth of a healthy child. The analysis was performed by polymerase chain reaction and restriction fragment length polymorphism (PCR/RFLP).Investigation of 20210GA polymorphism of prothrombin gene revealed high overrepresentation of genotype GA (8.33% and 1.18% in the control group, p = 0.07) and allele A (4.17% and 0.59% in the control group, p = 0.07) in the subgroup of women with three or more miscarriages. Investigation of 1691 GA polymorphism showed preponderance of genotype GA (12.50% vs 6.51%, p = 0.31) and allele A (6.25% vs 3.25%, p = 0.31) in a group of women with miscarriages between 10 and 13 week of gestation in comparison to the control group. Investigation of 20210GA polymorphism showed majority of genotype GA (8.70%) in women with miscarriages in the early as well as in the late period of the first trimester in comparison to the control group (1.18%, p = 0.07). The frequency of occurrance of mutated allele A was 4.35% and 0.59% in the control group (1.18%, p = 0.07).The analysis of obtained results suggests the possible influence of both considered polymorphisms 1691GA of factor V gene and 20210GA prothrombin gene on mechanism of recurrent miscarriages in the first trimester of pregnancy and participation of 1691GA polymorphism in the etiology of recurrent miscarriages during the late period of the first trimester of pregnancy (10-13 week of gestation).

Hereditary or acquired thrombophilia may induce many complications in pregnant women, the relationship between thrombophilia and recurrent miscarriages as well as intrauterine death in the second half of the pregnancy being identified as a particularly frequent one. The introduction of detailed diagnostic methods in women with pregnancy loss in anamnesis allow for more frequent recognition of multifactorial thrombophilia. However, uniform recommendations connected with pregnancy course in these cases, application of anticoagulation prophylaxis and optimal dosage are lacking. In this manuscript we have described the course of a pregnancy, delivery and puerperium of a pregnant woman with recurrent miscarriages in anamnesis, antiphospholipid syndrome, being simultaneously a carrier of both--Leiden (1691GA) and 20210GA prothrombin mutations--(multifactorial thrombophilia), in which anticoagulant prophylaxis has been successfully applied.

In recent years much attention has been paid to the possibly significant role of the activity differences of factor VII (FVII) in the etiology of recurrent miscarriages.The aim of study was to evaluate the frequency of Arg353Gln genetic polymorphism of coagulation factor VII and the role of presence of Gln353 allele in the group of women with two or more spontaneous abortions in the first trimester of pregnancy.104 women (average age 30.15 +/- 4.07 years), with two or more spontaneous abortions in the first trimester (between 6 and 13 weeks of gestation) of pregnancy, and 163 healthy women (average age 29,40 +/- 3,56 years), with at least one pregnancy which had ended with the delivery of a healthy newborn, have been analyzed. The frequency of genotypes has been determined by means of polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP) methods.In the group of recurrent miscarriages, higher frequency of homozygotic Arg353/Arg353 genotype (82.69 vs 74.85%) and lower frequency of heterozygotic Arg353/Gln353 (17.31 vs 25.15%) genotype have been noted, comparing to the control group. Frequency of mutated Gln353 allele was lower in the group of spontaneous abortions (8.65 vs. 12.58%, ns). Observed frequency of mutated Gln353 allele in the control group (12.58%) was compatible with th frequency for Caucasian observed by other authors. In the subgroup of women with two (80 women), three or more abortions (24 women), the frequency of heterozygous genotype Arg353/Gln353 was lower if compared to the controls (16.25% and 20.83%, respectively) (controls 25.15%, ns). Lower frequency of heterozygous genotype Arg353/Gln353 in the subgroup of women with abortions in the early (6-9 week of gestation) period of the first trimester (13.85 vs 25.15%, p=0.04) has been observed.Research and investigation which have been carried out suggest a weak connection of Arg353Gln polymorphism of coagulation factor VII with the frequency of recurrent miscarriages. However, higher frequency of Gln353 allele in the control group of healthy women suggests its protective role in coagulation changes and recurrent miscarriages. A visibly lower frequency of heterozygous genotype Arg353/Gln353 in the miscarriages in the early period of the first trimester, which might suggest potentially great protective significance of Gln353 allele presence in this period of pregnancy, remains an interesting fact.

Single nucleotide polymorphisms of the genes coding for coagulation factors are the cause of congenital thrombophilia which might lead to recurrent miscarriages and fetal loss in advanced pregnancy. The most frequent reasons of thrombophilia are the following: factor V Leiden (1691GA), mutation 20210GA of prothrombin gene, and 677CT of 5, 10-methylenetetrahydrofoliate reductase gene. The following article briefly summarizes the administration of antithrombotic prophylaxis (low-molecular weight heparin, acetylsalicylic acid) which seems to be an effective course of action to prevent complications in next pregnancies. What is more, adverse events after long-term usage of low-molecular weight heparin and acetylsalicylic acid in prophylactic doses have not been observed. Due to lack of complete randomized investigation about the inclusion of antithrombotic prophylaxis in this group of pregnant women, common scheme of administration and optimal dosage is yet to be established.

Leptin, as well as many other hormones, may play an important role in the pathogenesis of obesity. Several genetic variants of both leptin and its receptor genes may influence human body weightTo investigate the role of leptin gene polymorphism promotion region (-2548G/A) and leptin gene receptor polymorphism (668 A/G) in regulation of body weight in the group of women with type 1 diabetes (PGDM-1).78 PGDM-1 first trimester pregnant women were qualified for the study group (SG). They were divided into normal and overweight subgroups, based on pre-pregnancy BMI. Control group (CG) consisted of first trimester healthy pregnant women with normal pre-pregnancy body weight Genetic variants of leptin gene and its receptor were analyzed with the help of PCR-RFLP assays. In the SG, the following metabolic parameters were estimated: MBG, HbA1c, insulin dose, LDL, HDL, T-CHOL, triglycerids, creatinine, creatinine clearance and blood pressure.A tendency for the majority of homozygous A and G variants in LEP -2548 G/A and LEPR 668 A/G was found in overweight and obese patients, in comparison to normal-weight subjects. No specific differences in selected first trimester metabolic parameters were found in relation to patients' genotypes in the diabetic group.

Recently the significance of genetic traits, influencing hormonal and environmental factors, in susceptibility to osteopenia and osteoporosis development has been indicated. Much attention to the polymorphic variants of vitamin D receptor (VDR) gene was paid. The restriction polymorphisms in VDR gene could be involved in the modulation of vitamin D action and modulate the level of bone mineral density (BMD) and the risk to develop osteopenia and osteoporosis.Total 321 postmenopausal women (mean age 63.26 +/- 8.90 years), including women with osteoporosis (163 patients) and osteopenia (95) have been compared to 63 women with normal t-score value. For detection of VDR polymorphisms PCR/RFLP (polymerase chain reaction/restriction fragment length polymorphism) assay have been used.The frequency of BsmI, ApaI, and TaqI polymorphic variants of VDR gene detected in investigated groups was not statistically different. The slight, not significant tendency to prevalence of a allele (ApaI polymorphism) in the controls comparing to women with osteoporosis and osteopenia have been noted. Higher prevalence of homozygous TT genotype (TaqI polymorphism) the in the both groups with lower BMD value (47.9 : 49.5 vs. 34.9% in the controls) and higher prevalence of T allele in these both groups (65.9 : 68.4 vs. 57.9) was been also observed.The presence of T allele of TaqI polymorphism could predict the higher risk to develop osteoporosis in postmenopausal woman; consequently t allele could have protective effect. The presence of A allele (ApaI polymprphism) seems to be weakly connected with osteoporosis susceptibility.

Proinflammatory cytokines, interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha), involved into osteoclastogenesis and responsible for bone resorption process, participate in the pathogenesis of the osteoporosis. In vitro studies have shown that single nucleotide polymorphisms of IL-6 and TNF-alpha genes could influence the transcription process of the genes and the cytokines level.Assessment of the influence of IL-6 and TNF-alpha gene polymorphisms on bone mineral density (BMD) and evaluation of their connection with osteoporosis prevalence in women from Wielkopolska region.In the group of 267 postmenopausal women (average age 58.5+/-5.9 years, average age of last period 49.8+/-3.9 years) bone mineral density in lumbar spine (L2-L4) was performed using dual energy X-ray absorptiometry (DXA). Genotypes frequencies were determined by polymerase chain reaction with restriction fragment length polymorphism (PCR/RFLP) using restriction enzymes Lwe I and Faq I, respectively. The connection between the polymorphisms of investigated genes and body mass index, age of menarche and menopause and length of reproductive age had been analyzed as well.No statistically significant association was found between examined genetic factors and the value of bone mineral density in the investigated group of postmenopausal women. The frequencies of investigated genotypes were in compliance with Hardy-Weinberg equilibrium. The correspondence between evaluated clinical parameters and IL-6 i TNF-alpha genotypes frequencies has not been proven.The -174G/C polymorphism in the IL-6 and -308G/A polymorphism in TNF-alpha genes have no influence on bone mineral density value (BMD) in the investigated population of women from Wielkopolska region.

Leptin is a polypeptide hormone (167 amino acids, molecular weight of about 16kDa), synthesized mainly in white adipose tissue. The hormone plays an important role in regulation of hunger and satiety processes, in metabolism of carbohydrates and fats, development of cardio-vascular diseases and obesity. The occurrence of the increased level of leptin in pregnant women with hypertension, especially in women with preeclampsia, has also been brought to our attention. In recent years it has been suggested that the presence of different variants of leptin and leptin receptor genes may modify the leptin level in serum, and, in this way, influence an increased risk of obstetric complications, such as preeclampsia or eclampsia.We have analyzed a group of 103 hypertensive pregnant women--61 women with gestational hypertension (GH) and 42 women with preeclampsia (PE). The control group consisted of 113 healthy pregnant women who have been investigated. Gestational hypertension and preeclampsia were recognized with the help of and assessed according to the ACOG criteria. The (-2548G/A) polymorphism was determined using polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP).In our study, a higher frequency of mutated AA genotype in GH group and PE groups (21.31% and 21.43% respectively vs. 16.81% in the controls) and the overrepresentation of mutated A allele in both analyzed groups (47.54% and 45.24% respectively vs. 41.59% in the controls) have been observed, without statistically significant differences.The overrepresentation of AA genotypes and higher frequency of mutated A allele of (-2548G/A) polymorphism of leptin gene in GH and PE groups might indicate its possible contribution in gestational hypertension and preeclampsia.

The intrauterine growth restriction (IUGR) frequently is a cause of fetal morbidity and mortality, and influences perinatal outcome. Several genes have been identified to explain aetiology of IUGR, beside others the gene coding for tumour necrosis factor alpha (TNF-alpha).To investigate frequency of AlwI polymorphism of TNF-alpha gene and its correlation with TNF-alpha level in maternal serum, Doppler velocimetry and perinatal outcome in pregnancies suspected for IUGR.42 pregnancies with IUGR and 50 matched healthy pregnant women were included in the study. Maternal venous blood samples were investigated in relationship to blood flow Doppler velocimetry in umbilical (UA) and middle cerebral (MCA) arteries. AlwI polymorphism was analysed using PCR/RFLP assays. TNF-alpha level was evaluated by immunoelectophoretic method.A higher frequency of mutated -238A alleles (13.1% vs. 7.0%) and genotypes containing at least one mutated -238A allele (23.8% vs. 14.0%) were found in the IUGR group. The tendency to the higher TNF-alpha level in IUGR subgroups with the presence of at least one mutated A allele (258.9+/-231.3 vs. 174.1+/-145.6 pg/ml) was detected. No statistical differences were detected for PI values in UA and MCA arteries considering particular genotypes (GG vs. GA + AA) separately in IUGR group.Increased UA vascular impedance and signs of brain sparing in MCA are related to IUGR and increased TNF-alpha level in maternal serum. AlwI polymorphism might play a role in IUGR aetiology and influence TNF-alpha expression in maternal serum, but was not related to Doppler velocimetry or with perinatal outcome.

The current knowledge allows for the definition of the genetic factors contributing to pathological body mass gain and obesity development. One of the possible candidates is the gene of beta3-adrenergic receptor (ADRB3). Due to the fact that the basic function of this receptor is the induction of thermogenesis process and an increase of energy expenditure, the significance of Trp64Arg polymorphism of ADRB3 gene in disturbances of metabolic processes, which may induce disturbances of adipocytes function and lead to excessive body mass gain, obesity and early beginning of diseases connected with obesity (dyslipidemia, obesity, chronic hypertension, diabetes mellitus type II), has been suggested. The investigations performed in pregnant women concern, in the majority of cases, women with obesity, diabetes mellitus and gestational hypertension. These studies indicate the possible correlation of higher value of body mass index (BMI) with the presence of mutated 64Arg allele. In healthy pregnant women the relationship between Trp64Arg polymorphism of ADRB3 receptor and body gain has been suggested. Additionally, in female carries of the mutated 64Arg allele, a higher placenta mass and birth mass of newborns have been noted. This publication is merely single voice in the discussion because only one cause of excessive body gain and obesity presented here - Trp64Arg polymorphism of ADRB3 receptor. The problem seems to be more complicated and requires an investigation of the influence of other genetic and environmental factors, and the future populate investigations in Trp64Arg polymorphism of ADRB3 receptor.

Thrombophilia is a congenital or acquired disorder of haemostatic imbalance leading to clot formation. Congenital thrombophilia is a result of different genetic polymorphisms in the genes coding for particular elements in coagulation and fibrinolysis processes and is connected with excessive readiness to thrombosis in the carriers the mutated alleles. A higher coagulation activity has been observed in case of pregnant women who are carriers of congenital thrombophilia, when compared to the pre-pregnancy activity. These changes concern first of all utero-placental circulation, and may lead to many complications during pregnancy such as: recurrent miscarriages, intrauterine fetal death in second and third trimester, preeclampsia/eclampsia, intrauterine growth restriction and placental abruption. Numerous research indicates that anticoagulation prophylaxis in pregnant women with the abovementioned complications in medical history might prevent a similar condition in the following pregnancies. What is more, it underlines that administration of low molecular weight heparin and acetylsalicylic acid may improve perinatal outcome in thrombophilic women. However, the notion whether anticoagulant prophylaxis should be applied in women with preeclampsia, fetal hypotrophy or fetal loss remains disputable. Furthermore, the question of when the prophylaxis should start and of its duration remains unanswered. The following summary focuses on congenital thrombophilia in pregnant women with burdened anamnesis and suggested pattern of anticoagulation prophylaxis.

Population studies have been suggesting genetic predisposition to the appearance of preeclampsia (PE) for a considerable period of time now. In familial occurrence of the disease higher frequency of preeclampsia has been observed in mothers, daughters and sisters of women burned of this poor medical history and higher risk to severe PE development. Although a single gene may contribute to the development of the patomechanizm of PE, most authors focus on the analysis of the common influence of candidate genes which are involved in a series of pathophysiological processes of PE. Thus, PE is often believed to be the final phenotype (increase of blood pressure and multiorgan complications development), being the result of intermediate phenotypes acting at the same time and being modulated by environmental factors. PE belongs to the complex human disease. The results of the findings connected with the contribution of maternal, paternal and fetal genotypes in PE development remain unclear, though a stronger influence of maternal genes, with a weaker influence of those transferred from the father, may be observed. Despite the existing divergences (the findings on the genetic background of PE are in conflict, no doubt due to the population differences and small number of investigated groups), the results obtained so far stress the necessity to discover the genetic risk factors as it may do both: facilitate the identification of groups of women predisposed to preeclampsia and allow for an early prophylactic administration.

The article presents information about leptin as the major metabolic hormone. The structure, localization of the hormone and its receptor have been described focusing on maturation and fertility processes. Several polymorphisms of leptin gene and its receptor have been described as potential developmental factors of pregnancy complications such as diabetes mellitus or pregnancy induced hypertension.

The body mass gain is conditioned by lifestyle, as well as many environmental and genetic factors. Recent studies suggest that renin-angiotensin system (RAS) plays a fundamental role in process of growth and differentiation of adipocytes through the acting of angiotensin II and seems to be a significant factor in excessive weight gain development. The purpose of this study was to determine the frequency and significance of insertion/deletion polymorphism (I/D) of the ACE gene in pregnant women with excessive weight gain.The examined group consisted of 212 pregnant women, including 107 women with normal (DeltaBMIor =5) and 105 women with excessive weight gain (DeltaBMI5). Genomic DNA was extracted from venous blood. The I/D polymorphism of ACE gene was determined by polymerase chain reaction (PCR).During the course of the study we did not observe the statistically significant higher frequency of ACE genotypes in any of the two investigated groups of women with normal and excessive weight gain. Nevertheless, an overrepresentation of II genotype frequency in group with excessive weight gain has been observed (33.3 vs 21.5%, p=ns). The same findings were visible as far as the frequency of I allele in group with excessive weight gain was concerned (55.2 vs 45.8%, p=ns). The frequency of observed genotypes was in agreement with Hardy-Weinberg equilibrium.Although overrepresentation of II genotype and I allele in the group of pregnant women with excessive weight gain (DeltaBMI5) has been observed, a close correlation between II genotype and higher risk of overweight could be not indicated (due to the lack of significant difference). The results should be confirmed in a more numerous group of pregnant women. At this stage the results of the study did not suggested the presence of association of I/D polymorphism of ACE gene with weight gain in investigated group of pregnant women.

In recent years, considerable attention has been paid to isoflavones and their proprieties to alleviate the climacteric symptoms. The goal of this study was to evaluate the efficacy of standardized isoflavones extract (Soyfem) in moderate and medium-severe climacteric syndrome.555 postmenopausal women were recruited for the study. Out of this group, 169 women completed the study (12-month observation period). The patients were classified according to the intensity of climacteric symptoms (or =34 points in Kupperman index). 1 or 2 tablets of Soyfem were administered twice a day,.A regular decrease of Kupperman index value and improvement of life quality were observed in the group of 169 postmenopausal women. We have noted a decrease in the intensity and number of hot flushes, diaphoresis (p0.05), diminished sleep disturbances (p0.05), decreased headache, dizziness, and arthrosis pain. The diminished intensity of tiredness, palpitation and breathlessness have been also observed (p0.05). 80% of all investigated women noted the regression of paresthesis, 20% indicated the decreased number of paresthesis (p0.05). Influence of Soyfem on the variability and moderation of depressive mood (p0.05) have been also positive evaluated by patients.Administration of Soyfem in the dosage 52 to 104 mg/24 hours (2 times daily 1 or 2 tablets) is a safe and effective therapy in the postmenopausal women with moderate and medium-severe climacteric syndrome evaluated according to the Kupperman index. Administration of Soyfem is connected with a good compliance and correlated with well-being in the investigated women allowing a long-term administration.

Obesity, one of the most common civilization diseases, is currently one of the major health problems in the society. It is estimated that in industrialized countries excessive weight appears in more than 30% of adult population, with adult women comprising 50% of the group. Considerable amount of attention is paid to the course, delivery and puerperium in women with excessive weight and obesity during pregnancy. A close correlation to fetal macrosomia, increased ratio of caesarean sections and perinatal death of fetuses has been indicated in this group. Spontaneous birth increases the risk of shoulder dystocia and brachial plexus injury in newborns. Much attention is also paid to higher risk of anesthesiological complications (difficulties in intubation, necessity of high dosages of anesthetic medication administration, problems with subarachnoideal and epidural anesthesia). An increased risk of endometritis in puerperium, thrombosis, vulvitis and infections of urinary tract have been observed in obese women. Maternal obesity is correlated with decreased percentage of breast-feeding women. Particular medical care and long-term observation should be applied in case of children of obese women, as the former are at a high risk of obesity in puberty and in adult life. Nowadays, it is suggested that maternal excessive body mass should be regulated before conception and the course of pregnancy in obese women should be closely monitored. Above-mentioned arguments seem to be reason enough for future investigations of etiology and treatment of obesity in pregnancy.

In recent years, considerable attention has been paid to isoflavones and their proprieties to alleviate the climacteric symptoms. The goal of this study was to evaluate the efficacy of standardized isoflavones extract (Soyfem) in moderate and medium-severe climacteric syndrome.555 postmenopausal women were recruited for the study. Out of this group, 169 women completed the study (12-month observation period). The patients were classified according to the intensity of climacteric symptoms (or = 34 points in Kupperman index). 1 or 2 tablets of Soyfem were administered twice a day.A regular decrease of Kupperman index value and improvement of life quality were observed in the group of 169 postmenopausal women. We have noted a decrease in the intensity and number of hot flushes, diaphoresis (p0.05), diminished sleep disturbances (p0.05), decreased headache, dizziness, and arthrosis pain. The diminished intensity of tiredness, palpitation and breathlessness have been also observed (p0.05). 80% of all investigated women noted the regression of paresthesis, 20% indicated the decreased number of paresthesis (p0.05). Influence of Soyfem on the variability and moderation of depressive mood (p0.05) have been also positive evaluated by patients.Administration of Soyfem in the dosage 52 to 104 mg/24 hours (2 times daily 1 or 2 tablets) is a safe and effective therapy in the postmenopausal women with moderate and medium-severe climacteric syndrome evaluated according to the Kupperman index. Administration of Soyfem is connected with a good compliance and correlated with well-being in the investigated women allowing a long-term administration.

The high prevalence of preterm delivery (PTD) (7.2 to 8.4% in Poland) may suggest that much more attention should be paid to the early detection, as well as prevention, of this condition. Spontaneous preterm birth is a multifactoral disease, with possible genetic and environmental determining factors. Genes of cytokines modulating the immunological answer, genes of metalloproteinases and genes of coagulation cascade and fibrinolysis may have a significant involvement in the development of PTD. Population studies conducted so far comprise exact, individual evaluation of risk factors in women with tendency to PTD and have indicated a genetic susceptibility to PTD occurrence. Another direction of research is the investigation of candidate genes which are directly or indirectly involved in the biochemical pathways related to the disease. Current studies allow to define several candidate genes predisposing to PTD. The next step is the family molecular analysis of candidate gene polymorphisms both: in women with burdened anamnesis and first and second degree relatives (mothers, grandmothers, sisters). Numerous studies, besides the individual genetic predisposition, focus on the possible gene-environmental interactions and their role in the development of PTD. In this manuscript we have summarized the current researches of genetic basis of preterm delivery.

The aim of this study was to examine the ability of extracts from root of Rhodiola rosea (RR) and Rhodiola kirilowii (RK) to inhibit the development of acute ethanol tolerance. The ethanol-water (1:1) extracts were standardized on phenylpropanoids (rosavin, rosin, rosarin) and phenylethanoids (salidroside, p-tyrosol) contents. The experiments were performed …

Introduction: Recent reports have suggested an association between genetic polymorphisms of dopamine receptors and the development of an increased risk of chronic hypertension, as well as preeclampsia (PE). Objectives: The aim of the study was to evaluate the impact of the -48A>G DRD1 and -521C>T DRD4 polymorphisms in the etiology of PE among Polish women. Material and methods: Ninety-eight preeclamptic women and 120 healthy pregnant controls were enrolled in the study. The investigated polymorphisms of the DRD1 and DRD4 genes were identified using PCR/RFLP methods. Results: As far as the -48A>G DRD1 polymorphism is concerned, the mutated -48GG genotype was more often found in controls (14.2% ) than in the PE group (10.2%, ns), and the subgroup with severe PE (8.2%). Also, the frequency of the mutated -48G allele was higher in controls (39.6%) than in the PE group (33.2%, ns), and in the subgroup with severe PE (31.6%, ns). As for the -521C>T DRD4 polymorphism, a similar occurrence of the mutated -521TT genotype and the -521T allele in all of the investigate groups was observed. Lower serum concentrations of total protein (5.59 g/L and 5.57 g/L vs. 6.17 g/L in carriers of the -521CC genotype, p=0.02) were noted in patients with the mutated homozygous -521TT genotype and heterozygous -521CT genotype of DRD4. Conclusions: The obtained results suggest a possible protective role of the mutated -48G DRD1 allele in the etiology of preeclampsia, especially its severe form. The presence of the mutated -521T DRD4 allele could influence the decrease of total blood protein in preeclamptic patients. The observed frequency of dopamine DRD1 and DRD4 polymorphisms is similar to the distribution of these variants in other Caucasian populations.

Considering the prolonged population lifetime, there is an increasing number of elderly people suffering from osteoporosis. At present the prevention of osteoporosis is one of the most important problems in medicine. The development of genetic investigations and molecular biology gives new possibilities for discovering risk factors and early prevention of this condition. This is a brief summary referring the polymorphisms of estrogen receptors and their significance in the pathogenesis and prevention of osteoporosis.