Impact of Vanadium Complexes Treatment on the Oxidative Stress Factors in Wistar Rats Plasma

The aim of this study was to investigate the clinical efficacy of vanadium complexes on triglycerides (TG), total cholesterol (Chol), uric acid (UA), urea (U), and antioxidant parameters: nonenzymatic (FRAP—ferric reducing ability of plasma, and reduced glutathione—GSH) and enzymatic (glutathione peroxidase—GPx, catalase—CAT, and GPx/CAT ratio) activity in the plasma of healthy male Wistar rats. Three vanadium complexes: [VO(bpy)2]SO4·2H2O, [VO(4,4′Me2bpy)2]SO4·2H2O, and Na[VO(O2)2(bpy)]·8H2O are administered by gavage during 5 weeks in two different diets such as control (C) and high fatty (F) diets. Changes of biochemical and antioxidants parameters are measured in plasma. All three vanadium complexes statistically decrease the body mass growth in comparison to the control and fatty diet. In plasma GSH was statistically increased in all vanadium complexes-treated rats from control and fatty group in comparison to only control group. Calculated GPX/CAT ratio was the highest in the control group in comparison to others

The -323P0/P10 factor VII gene polymorphism and the risk of recurrent miscarriage

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

Znaczenie polimorfizmu CYP1A1 i regulacji jego transkrypcji w podatności na raka jajnika i endometrium

Abstract Human cytochrome P450 1A1 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-β-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 CYP1A1 activity could be responsible for different interindividual susceptibility to genital cancers in women.Streszczenie Ludzki cytochrom CYP4501A1 jest jednym z najważniejszych enzymów uczestniczących w procesie kancerogenezy, ponieważ metabolizuje wiele pro-kancerogenów do ich aktywnych kancerogennych metabolitów. Dodatkowo, enzymy z rodziny CYP450 odgrywają ważną rolę w katabolizmie estrogenów (17-β-estradiol i estron) do produktów pośrednich (2-, 4-hydroksyestradiol oraz 2-, 4-hydroksyestron) uwzględniając CYP1A1, który katalizuje hydroksylację do 2-hydroksyestrogenu w endometrium. Pochodne tych związków (4-hydroksyestrogeny) są kancerogenne i mogą indukować uszkodzenia DNA prowadząc do transformacji nowotworowej komórki. Obecność enzymu CYP1A1 w tkankach narządów płciowych może indukować chemiczną kancerogenezę inicjując rozwój nowotworu. Najnowsze badania potwierdziły rolę CYP1A1 w rozwoju raka jajnika i endometrium. Obecność zmutowanych wariantów polimorficznych genu CYP1A1 wpływających na aktywność CYP1A1 może być związana ze zróżnicowaniem osobniczym w podatności na nowotwory narządów płciowych u kobiet

Inherited thrombophilia as the reason of recurrent miscarriges in the first trimester of pregnancy

Summary Introduction: 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 (1691G>A) and factor II (20210G>A) of coagulation cascade in a group of women with two or more miscarriages in the first trimester of pregnancy. Material and methods: 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). Results: Investigation of 20210G>A 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 G>A 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 20210G>A 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). Conclusions: The analysis of obtained results suggests the possible influence of both considered polymorphisms 1691G>A of factor V gene and 20210G>A prothrombin gene on mechanism of recurrent miscarriages in the first trimester of pregnancy and participation of 1691G>A polymorphism in the etiology of recurrent miscarriages during the late period of the first trimester of pregnancy (10-13 week of gestation)

Frequency of G2677T/A and C3435T polymorphisms of MDR1 gene in preeclamptic women

Objective: Preeclampsia (PE) belongs to main causes of mortality rates of mothers, fetuses and new born children. Polymorphism of MDR1 gene is connected with reduction of P-glycoprotein expression in placenta and increased fetal exposure to xenobiotics. The aim of the study was to determine the frequency of C3435T and G2677T/A polymorphisms of MDR1 gene in pregnant women with preeclampsia. Materials and methods: The study consisted of 180 Polish women including 60 women with PE and 120 healthy pregnant women. Determination of C3435T and G2677T/A polymorphisms of MDR1 gene was performed using PCR-RFLP method. Results: No significant association between genotypes of the examined polymorphisms and the clinical parameters of pregnant women with PE was observed. However the interesting tendency to higher prevalence of mutated 2677A allele of G2677T/A MDR1 polymorphism in PE group has been shown (2,50 vs. 0,83% in controls, OR=3,05, ns). Conclusions: The results of this study suggest no significant effect of examined C3435T and G2677T/A MDR1 polymorphisms in PE pathogenesis. However given the noteworthy results related to mutated 2677A allele of G2677T/A MDR1 polymorphism in preeclamptic women further studies seem to be needed. Nevertheless, the frequency of investigated polymorphisms was consistent with the distribution in other Caucasian populations

Genetic conditioned changes in activity of 5,10-methylenetetrahydrofolate reductase (MTHFR) and recurrent miscarriages

Summary 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

Polimorfizm genu kodującego osteoprotegerynę a występowanie osteoporozy u kobiet po menopauzie

Summary Introduction: Osteoprotegerin (OPG) plays a crucial role in the control of bone resorption through competitive inhibition of receptor activator of nuclear factor κB ligand (RANKL). This process leads to inhibition of osteoclasts differentiation and activity. The aim of the following study was to evaluate the distribution of genotypes of -163A>G and 1181G>C polymorphisms in OPG gene, and analyze their relationship with bone mineral density (BMD) and other parameters of bone turnover in population of Polish postmenopausal women. Material and method: The study included 310 postmenopausal Caucasian women (54,48}8,53 years); 139 women with osteoporosis, 107 with osteopenia and 64 healthy women. Genetic analysis was performed by PCR/RFLP reaction. BMD value was measured by dual energy X-ray absorptiometry (DXA). Results: For -163A>G polymorphism the higher frequency of heterozygotes AG (26.6 vs. 18.7%, ns) and slight overrepresentation of mutated G allel (14,1 vs. 10,9%, ns) in the osteoporosis group was observed. The frequency of recessive CC homozygotes and C alleles of 1181G>C polymorphism did not differ among the investigated groups. The distribution of particular haplotypes of -163A>G and 1181G>C polymorphisms in all subgroups was similar. Correlation between values of investigated parameters of bone turnover and frequency of genotypes of investigated polymorphisms has not been observed. Conclusions: The overrepresentation of heterozygous AG genotype and mutated G allele of -163A>G polymorphism of OPG gene in the group of women with osteoporosis might suggest the significance of this variant in the development of osteoporosis. A more extensive analysis of genetic variants of RANKL/RANK/OPG signal pathways, joint with an investigation of modulated influence of estrogens, TNF-α or several interleukin influencing the development of osteoporosis is necessary.Streszczenie Wstęp: Białko osteoprotegeryna (OPG) pełni kluczowa rolę w kontroli resorpcji kości blokując kompetencyjnie ligan jądrowego czynnika aktywującego receptor κB (RANKL). Proces ten prowadzi do hamowania różnicowania i aktywności osteoklastów. Celem badania była ocena rozkładu genotypów polimorfizmów -163A>G oraz 1181G>C genu OPG, a także analiza związku genotypów z gęstością mineralną kości (BMD) oraz innych parametrów obrotu kostnego w populacji kobiet polskich po menopauzie. Materiał i metoda: Badaniem objęto 310 niespokrewnionych kobiet rasy kaukaskiej (54,48+/-8,53 lata) po menopauzie (139 kobiet z osteoporoza, 107 kobiet z osteopenią, 64 zdrowych kobiet). Analizę genetyczna przeprowadzono przy pomocy reakcji PCR/RFLP. Pomiar BMD wykonano przy zastosowaniu metody podwójnej absorpcjometrii rentgenowskiej (DXA). Wyniki: W przypadku polimorfizmu -163A>G zauważono częstsze występowanie heterozygot AG (26,6 vs 18,7%, ns) oraz nieznacznie wyższą częstość występowania zmutowanego allela G (14,1 vs 10,9%, ns) w grupie kobiet z osteoporoza. Częstość występowania homozygot recesywnych CC oraz alleli C polimorfizmu 1181G>C nie wykazywała różnic pomiędzy badanymi podgrupami. Rozkład występowania poszczególnych haplotypów polimorfizmów -163A>G oraz 1181G>C we wszystkich podgrupach był podobny. Nie zaobserwowano korelacji pomiędzy wartościami badanych parametrów obrotu kostnego a częstością pojawiania się poszczególnych genotypów badanych polimorfizmów w analizowanych podgrupach. Wnioski: Częstsze występowanie heterozygot AG oraz zmutowanego allela G polimorfizmu -163A>G genu OPG w grupie kobiet z osteoporoza może sugerować znaczenie tego wariantu w rozwoju osteoporozy. Wskazana jest szersza analiza wariantów genetycznych szlaku sygnałowego RANKL/RANK/OPG łącznie z badaniem modulacyjnego wpływu estrogenów, TNF-α oraz niektórych interleukin na rozwój osteoporozy

Polymorphism in the genes of Toll-like receptors type 2 and type 4 (TLR-2 and TLR-4) and the risk of premature rupture of the membranes – preliminary study

Introduction: 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. Aim: The aim of the following study was to evaluate the frequency of two genetic polymorphisms: Arg753Gln (G20877A) in TLR-2 and Thr399Ile (C8993T) in TLR-4 genes in a group of pregnant women with preterm rupture of membranes and preterm labour. Material and methods: 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 Thr399Ile polymorphism of TLR-4 gene, polymerase chain reaction and restriction fragments length polymorphism (PCR/RFLP) were used. Results: 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. Conclusion: 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

The (-2548G/A) polymorphism of leptin gene in women with gestational hypertension and preeclampsia

Abstract Introduction: 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. Materials and methods: 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). Results: 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. Conclusions: 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 influence of interleukin-6 and tumor necrosis factor α gene polymorphisms on bone mineral density in postmenopausal women

Summary Proinflammatory cytokines, interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α), 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-α genes could influence the transcription process of the genes and the cytokines level. Aim: Assessment of the influence of IL-6 and TNF-α gene polymorphisms on bone mineral density (BMD) and evaluation of their connection with osteoporosis prevalence in women from Wielkopolska region. Material and methods: 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. Results: 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-α genotypes frequencies has not been proven. Conclusions: The -174G/C polymorphism in the IL-6 and -308G/A polymorphism in TNF-α genes have no influence on bone mineral density value (BMD) in the investigated population of women from Wielkopolska region