Polymorphism of the Oxytocin Receptor (OXTR) Gene Affects the Circulating Oxytocin Receptor Levels in Late-Term Pregnancy in a Turkish Population.

INTRODUCTION: Postterm and late-term pregnancies still remain a serious health problem, and underlying exact mechanisms are not fully elucidated. These mechanisms are influenced by many factors. OBJECTIVE: The aim of this study was to investigate the relationship between plasma oxytocin and oxytocin receptor levels and oxytocin receptor polymorphisms in term and late-term pregnant women. METHODS: Sixty-eight singleton pregnant women with late-term pregnancy and 83 singleton pregnant women with term parturition were included in this study. A comparison was performed between pregnancies and neonates born at term (37 0/7 and 41 6/7 weeks' gestation). Plasma oxytocin, oxytocin receptor, estradiol, and progesterone levels were measured by using enzyme-linked immunosorbent assay kits. TaqMan® SNP Genotyping Assays and qPCR ProbesMaster were used to investigate the polymorphisms of rs237911, rs2228485, rs53576, and rs2254298. RESULTS: There was not any difference in gene distributions of 4 common single-nucleotide polymorphisms of oxytocin receptor of rs237911, rs2228485, rs53576, and rs2254298 between subjects in late-term and term pregnancy groups. With rs53576 of the GG genotype, serum oxytocin levels were 21.50 ± 10.69 (ng/L) in the late-term group and 62.71 ± 18.01 (ng/L) in the term group (p = 0.049). Oxytocin receptor levels in the late-term and term pregnancy groups of the GG genotype were 17.92 ± 8.15 (pg/mL) and 45.77 ± 11.66 (pg/mL), respectively (p = 0.046). CONCLUSION: Our findings suggest that the rs53576 oxytocin receptor single-nucleotide polymorphism is associated with late-term pregnancy through acting by direct modulation of oxytocin and oxytocin receptor levels.

Paraoxonase 1 (PON1) Q192R and L55M polymorphisms, lipid profile, lipid peroxidation and lipoprotein-a levels in Turkish patients with pregnancy-related disorders.

The aim of this study was to investigate the role of PON1Q192R and L55M single nucleotide polymorphisms(SNPs) and its association with the maternal levels of lipid parameters in gestational diabetes mellitus(GDM) and preeclampsia(PE). Ninety-nine pregnant with GDM, 97 pregnant with PE and 98 healthy pregnant were included in the study. No statistically significant difference was observed in the alleles or in the genotypes frequencies of SNPs between groups. In GDM patients, total cholesterol was higher in MM genotype of L55M gene (p < .05); Lp(a) were lower in LM genotype of the gene compared to their respective control (p < .05). In PE, HDL-C levels were higher in LM genotype (p < .05); LDL-C levels were lower in MM genotype of the gene compared to their respective control (p < .05). In PE patients, malondialdehyde(MDA) were higher in QQ genotype compared to their respective control (p < .05). Triglyceride levels were higher in PE patients with QR genotype compared with GDM patients with QR genotype (p < .05). Our results indicated that lipid profiles, Lp(a) and MDA levels showed significant differences in GDM and PE pregnants. These findings support the importance of the lipid profile, oxidized lipid and Lp(a) in different genotypes of L55M and Q192R in Turkish pregnant women with PE/GDM suggesting their roles in etiopathogenesis in these pregnancy-related disorders.

Midkine in vitamin D deficiency and its association with anti-Saccharomyces cerevisiae antibodies.

OBJECTIVES AND DESIGN: The growth factor midkine (MK) is a protein that is involved in cancer, inflammation, immunity. Vitamin D is a potent immunomodulator. Anti-Saccharomyces cerevisiae antibody (ASCA) is reported in autoimmune disorders, some of which are among the causes of vitamin D deficiency. The objective of this study was to investigate a possible association of MK and ASCA with vitamin D deficiency. MATERIALS AND METHODS: 208 adults presented to internal medicine outpatient clinic for history and physical examination has been studied. Serum biochemistry, vitamin D, MK, ASCA-IgG and -IgA, IL-1ß, IL-6, IL-8, TNF-α, PDGF, VEGF were obtained. RESULTS: Vitamin D deficiency was 74.2%. Serum MK level was significantly higher in vitamin D-deficient compared to vitamin D-sufficient individuals (1138.1 ± 262.8 vs 958.6 ± 189 pg/mL, respectively; P < 0.009). Serum MK levels were also significantly higher in both ASCA-IgG and -IgA positives compared to negatives (1318.5 ± 160.3 vs 1065.5 ± 256.1, P = 0.008 and 1347.7 ± 229.7 vs 1070.1 ± 250.9 pg/mL, P = 0.011, respectively). Vitamin D was significantly lower in ASCA positives (P = 0.044).Vitamin D showed positive correlation with IL-1ß (r 0.338, P < 0.009) and negative correlation with VEGF (r -0.366, P < 0.004). CONCLUSIONS: MK was significantly elevated in vitamin D deficiency and associated with ASCA positivity which was significantly increased in vitamin D deficiency. These findings suggested that molecular mechanism of vitamin D deficiency may be related with some inflammatory processes.

LOX-1 gene variants and maternal levels of plasma oxidized LDL and malondialdehyde in patients with gestational diabetes mellitus.

PURPOSE: The aim of this study was to investigate the relationships between the maternal levels of oxidized LDL (ox-LDL), lipid peroxidation marker malondialdehyde (MDA) and LOX-1 3'UTR188C/T and K167N single nucleotide polymorphisms in pregnant Turkish women with gestational diabetes mellitus (GDM). METHODS: 116 pregnant women with GDM and 120 healthy pregnant women from the same geographic region were included in the study. Polymerase chain reaction-based restriction analysis was used to identify 3'UTR188C/T and K167N polymorphisms of the LOX-1 gene. Plasma ox-LDL and MDA levels were determined by enzyme-linked immunosorbent assay and spectrophotometric method in all study subjects, respectively. RESULTS: Our results indicated that the distribution of the LOX-1 3'UTR188C/T and K167N genotypes and alleles did not differ significantly among subjects with or without GDM (p > 0.05). TT and NN genotype carriers are associated with some glucose metabolism parameters (p < 0.05). There were no significant differences among plasma ox-LDL and MDA levels with regard to LOX-1 3'UTR188C/T and K167N polymorphisms in GDM group and control subjects (p > 0.05). According to the combined genotype analysis of LOX-1 3'UTR 188 TT and K167N NN polymorphisms, plasma MDA and ox-LDL levels were significantly different between women with GDM and healthy subjects either with or without combined TT/NN genotype carriers (p < 0.001). CONCLUSIONS: According to our results, ox-LDL and MDA levels were increased in GDM pregnant women and healthy pregnant women either with or without combined TT/NN genotype carriers, for our Turkish sample, these genotype carriers appear to be related with increased oxidative stress in patients with GDM.

The association of lectin-like oxidized LDL receptor 1 (LOX-1) K167N and 3'UTR188CT polymorphisms with maternal plasma soluble LOX-1 levels and preeclampsia risk in Turkish population.

PURPOSE: To investigate the main effect of polymorphisms in genes involved in endothelial pathophysiological mechanisms, LOX-1 K167N and 3'UTR188CT single nucleotide polymorphisms (SNPs) in relation to preeclampsia (PE) risk and possible interactions between the gene polymorphisms and plasma oxLDL and soluble LOX-1 (sLOX-1) levels on PE in Turkish population. METHODS: LOX-1 K167N and 3'UTR188CT polymorphisms were studied in 113 pregnant women with preeclampsia and 96 healthy pregnant women by the PCR-RFLP techniques. sLOX-1 and oxLDL levels were determined by enzyme-linked immunosorbent assay (ELISA) in all study subjects. RESULTS: Patients having LOX-1 3'UTR188CT (OR 3.55, 95% CI 1.89-6.67, P = 0.001) or 3'UTR188CC (OR 3.04, 95% CI 1.25-7.38, P = 0.012) genotype had a significantly higher risk of PE than those with 3'UTR188TT genotype. Also, patients having K167N KK (OR 2.73, 95% CI 1.33-5.61, P = 0.005) genotype had a significantly higher risk of PE than those with K167N NN genotype. LOX-1 3'UTR188TT and LOX-1 K167N NN genotype carriers were associated with significantly increased serum sLOX-1 level (P = 0.001). We further investigated the potential combined effect of these polymorphic variants on risk of PE development. According to the combined genotype analysis of LOX-1 3'UTR188TT and K167N NN polymorphisms, sLOX-1 and oxLDL levels also showed significant differences between PE patients and controls with or without combined TT/NN genotype carriers. CONCLUSIONS: Our findings indicate that higher plasma sLOX-1 and oxLDL concentrations, and the LOX-1 3'UTR188C>T and LOX-1 K167N gene polymorphisms were significantly associated with risk of developing preeclampsia. Plasma sLOX-1 may be a potential therapeutic target in the treatment of preeclampsia.

The relationship between copper, homocysteine and early vascular disease in lean women with polycystic ovary syndrome.

This study investigates copper (Cu) levels and vascular dysfunction in lean women with polycystic ovary syndrome (PCOS). 44 subjects with PCOS, diagnosed according to Rotterdam criteria, and 42 healthy subjects matched for body mass index and age. Comparison of serum Cu, homocysteine, carotid intima-media thickness (CIMT), brachial artery flow mediated dilation (FMD) was carried out between PCOS patients and the control group. Clinical study was done in Namik Kemal University School of Medicine. The CIMT and concentration of Cu in PCOS patients was significantly higher than the healthy controls. FMD levels in PCOS patients were significantly lower than those in controls. In PCOS patients, CIMT was correlated with estrogen and Cu levels. However, FMD was correlated with age and Cu levels. Among these contributing factors, Cu levels were correlated with a change in CIMT and FMD. CIMT and FMD in PCOS patients were related to Cu levels as well as several cardiovascular risk factors. Thus, increased Cu levels may be responsible for the increased risk of early vascular disease in women with PCOS.

Visfatin, Leptin, and TNF-α: Interrelated Adipokines in Insulin-Resistant Clinical and Subclinical Hypothyroidism.

PURPOSE: This study is designed to evaluate the interrelationships among adipokines-visfatin, leptin, and tumor necrosis factor-α (TNF-α)- and insulin resistance (IR) in overt (n = 40) and subclinic hypothyroid (n = 25) patients and compare our findings with sex and body mass index-matched healthy controls (n = 25). METHODS: Serum visfatin, leptin, and TNF-α levels were measured by enzyme-linked immunosorbent assay and C-reactive protein by immunoturbidimetry. Thyroid status (TSH, FT3, FT4) and lipid status (triglyceride, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, total cholesterol) parameters were measured. IR was determined by homeostatic model assessment (HOMA-IR) and McAuley (McA) indices. RESULTS: HOMA-IR (p < 0.05) and McA indices (p < 0.01) revealed the presence of IR in overt hypothyroid patients. C-reactive protein, TNF-α, leptin, and visfatin levels were significantly higher (p < 0.01, p < 0.01, p < 0.001, and p < 0.001) in overt hypothyroid patients than euthyroid control group. Subclinic hypothyroid patients were observed to have significantly higher leptin and visfatin levels (p < 0.05) than euthyroid control group. In overt hypothyroid patients, we found plasma visfatin to be significantly positively correlated with HOMA-IR index (r = 0.336, p < 0.05) and body mass index (r = 0.445, p < 0.01) and negatively correlated with McA index (r = -0.574, p < 0.01). CONCLUSION: This study demonstrates the presence of IR in overt hypothyroid patients by HOMA and McA indices. Increased levels of visfatin, leptin, and TNF-α in overt and subclinic hypothyroid patients and the correlations among these adipokines highlighten their crucial role in the IR-associated disorders.

Apelin, Omentin-1, and Vaspin in patients with essential hypertension: association of adipokines with trace elements, inflammatory cytokines, and oxidative damage markers.

BACKGROUND: Hypertension (HT) is a disease associated with endothelial dysfunction which is related to some adipokines and pro- and anti-inflammatory cytokines. AIMS: Our aim was to investigate roles of apelin, omentin-1, and vaspin in essential HT and to evaluate their relationships with other pro- and anti-inflammatory cytokines, trace elements, and oxidative stress. We also investigated these parameters to determine asymptomatic target organ damage period and grading essential hypertension. METHODS: One hundred fifty-three patients diagnosed with essential hypertension and 45 healthy controls were included in the study. Hypertension was defined as a systolic blood pressure > 140 mmHg and/or a diastolic blood pressure > 90 mm Hg or current use of an antihypertensive medication. The patients who had secondary HT, other chronic metabolic, cardiovascular, cerebrovascular diseases were excluded. History and physical exam including detailed cardiovascular examination were performed in all participants. Adipokines, cytokines, trace elements, lipid peroxidation, and ischemia-modified albumin levels were measured in blood samples by biochemical methods. RESULTS: Vaspin, IL-4, IL-8, IL-10, selenium, and zinc levels were significantly lower in the HT group compared to healthy controls while omentin-1, TNF-α, copper, iron, MDA, SOD, and IMA-C levels were significantly higher in HT patients compared to controls. Multiple ordinal regression revealed that TNF-α, IL-10, and body mass index of patients were statistically significant independent predictors (P = 0.024, P = 0.019, and P = 0.032, respectively) for grading of HT. IL-4 and IL-10 were significantly higher in patients with asymptomatic target organ damage, compared to patients without asymptomatic target organ damage (P = 0.032 and P = 0.015, respectively). Our findings suggest that adipokines apelin, omentin, and vaspin may be involved in hypertension by a complex interaction with the anti- and pro-inflammatory cytokines, trace elements, and oxidative stress pathways.

The role of oxidative stress and antioxidant defenses in Buerger disease and atherosclerotic peripheral arterial occlusive disease.

The aim of this study was to determine the status and the role of oxidative stress and antioxidant defenses in patients with Buerger disease and atherosclerotic peripheral arterial occlusive disease (PAOD). Seventy-three subjects resembling each other in general characteristics were involved in the study: 21 with lower extremity PAOD (mean age 53.05 +/- 10.8 years, 17 men and four women), 22 with Buerger disease (mean age 38.59 +/- 6.4 years, 19 men and three women), and 30 healthy volunteers (mean age 38.59 +/- 6.4 years, 22 men and eight women). We measured the levels of plasma malondialdehyde (MDA), paraoxonase (PON1), protein carbonyls, arylesterase, nitric oxide (NO), serum oxidized low-density lipoprotein (ox-LDL) and MDA, glutathione (GSH), glutathione reductase (GSH-red), glutathione peroxidase (GSH-px), superoxide dismutase (SOD), and catalase (CAT) in erythrocytes. Plasma protein carbonyls, serum ox-LDL, and plasma and erythrocyte MDA were significantly high in the Buerger disease group compared to the PAOD and control groups (p < 0.001). Plasma PON1 levels and GSH and GSH-px levels in erythrocytes in the Buerger disease group were significantly low compared to the PAOD and control groups (p < 0.001). GSH-red, SOD, and CAT levels in erythrocytes in the Buerger disease group were significantly lowcompared to the PAOD group (p < 0.01, p < 0.001, and p < 0.001, respectively). NO levels were significantly lower in the PAOD group compared to the control group (p < 0.05). The balance between oxidative stress and antioxidant capacity is more seriously impaired in Buerger disease than PAOD.

Salt stress induces endoplasmic reticulum stress-responsive genes in a grapevine rootstock.

Grapevines, although adapted to occasional drought or salt stress, are relatively sensitive to growth- and yield-limiting salinity stress. To understand the molecular mechanisms of salt tolerance and endoplasmic reticulum (ER) stress and identify genes commonly regulated by both stresses in grapevine, we investigated transcript profiles in leaves of the salt-tolerant grapevine rootstock 1616C under salt- and ER-stress. Among 1643 differentially expressed transcripts at 6 h post-treatment in leaves, 29 were unique to ER stress, 378 were unique to salt stress, and 16 were common to both stresses. At 24 h post-treatment, 243 transcripts were unique to ER stress, 1150 were unique to salt stress, and 168 were common to both stresses. GO term analysis identified genes in categories including 'oxidative stress', 'protein folding', 'transmembrane transport', 'protein phosphorylation', 'lipid transport', 'proteolysis', 'photosynthesis', and 'regulation of transcription'. The expression of genes encoding transporters, transcription factors, and proteins involved in hormone biosynthesis increased in response to both ER and salt stresses. KEGG pathway analysis of differentially expressed genes for both ER and salt stress were divided into four main categories including; carbohydrate metabolism, amino acid metabolism, signal transduction and lipid metabolism. Differential expression of several genes was confirmed by qRT-PCR analysis, which validated our microarray results. We identified transcripts for genes that might be involved in salt tolerance and also many genes differentially expressed under both ER and salt stresses. Our results could provide new insights into the mechanisms of salt tolerance and ER stress in plants and should be useful for genetic improvement of salt tolerance in grapevine.

The influence of oxidative damage on viscosity of seminal fluid in infertile men.

Increased oxidative damage has been suggested to play an important role in the viscosity changes of blood. However, changes in levels of oxidative damage products in semen and their relationship to seminal fluid viscosity are unknown. The aim of our study was to investigate whether oxidative damage was associated with seminal plasma viscosity in infertile subjects. The levels of malondialdehyde, and protein carbonyls were measured in sperm and seminal plasma from 102 individuals, including 60 infertile patients. Seminal fluid viscosity and semen viscosity were studied by use of capillary viscometer and glass pipettes, respectively. Significantly higher levels of oxidative stress and damage markers were found in subfertile subjects compared with the control subjects. The seminal fluid viscosities of patients were found to be significantly higher, although all of the control and patient subjects had normal viscoelasticity when semen samples were assessed according to World Health Organization guidelines. From Pearson correlation analysis, there were significant positive correlations between seminal fluid viscosity and seminal malondialdehyde and carbonyl levels in infertile males (r = .676, P < .01; r = .276, P < .05, respectively). Our results suggest that increased oxidative damage might be a factor for hyperviscosity of seminal plasma in infertile males.

Toxic-dose warfarin-induced apoptosis and its enhancement by gamma ionizing radiation in leukemia K562 and HL-60 cells is not mediated by induction of oxidative stress.

The purpose of this study was to test the hypothesis that warfarin may enhance free radical production and oxidative damage on cancer cells. We examined the possible concentration-dependent effect of warfarin on cytotoxicity with respect to oxidative stress on leukemia cell lines (K562 and HL-60) and normal human peripheral blood mononuclear cells (PBMC). Gamma radiation was used as a positive control agent for oxidative stress. At all concentrations of warfarin (5-200 muM), 5-amino-2,3-dihydro-1,4-phthalazinedione (luminol)- and bis-N-methylacridinium nitrate (lucigenin)-amplified chemiluminescence responses and lipid peroxidation and protein oxidation were stable after 72 h incubation at 37 degrees C. However, The 2',7'-dichlorofluorescein diacetate (DCFH-DA) oxidation was increased when cells were incubated with high concentrations (50-200 muM) of warfarin. In these concentration ranges, warfarin reduced cell growth in a dose-dependent manner, producing apoptosis. Our results also revealed that at concentrations above 5 muM, warfarin had a potentiating effect on radiation-mediated growth inhibition and apoptosis. Furthermore, marked effects were observed on leukemic cells compared with PBMC. We report here that the increase of DCFH oxidation might be due to the increase in the release of cytochrome C caused by warfarin, as cytosolic cytochrome C content was significantly elevated in the warfarin-treated cells compared with control cells, and because cotreatment with antioxidants N- acetylcysteine or 4,5-dihydroxy-1,3-benzene-disulfonic acid (Tiron) was unable to prevent cytochrome C release and DCFH oxidation induced by the drug. Taken together, these results suggest that high warfarin concentrations may be toxic to leukemic cells in vitro through apoptosis, although at the pharmacological concentrations (<50 muM), warfarin has no prooxidant or cytotoxic effect on PBMC, K562, and HL-60 cells. In addition, when the treatment of leukemic cells with warfarin at concentrations above 5 muM is combined with radiation, we observed an increase in radiation-induced cytotoxicity. The mechanism by which warfarin potentiates this cytotoxicity is unclear, but it may not be directly due to toxic damage induced by warfarin-generated free radicals.

Postmitotic tissue selenium and manganese levels in alpha-lipoic acid-supplemented aged rats.

Redistribution of selenium and manganese in postmitotic tissues of alpha-lipoic acid-supplemented aged rats has been proposed to contribute to metal-catalyzed protein oxidation. DL-Alpha-lipoic acid (LA) (100 mg/[kg body wt.day]) was administered intraperitoneally to the Sprague-Dawley rats for 14 days. Serum selenium levels were lowered in the aged rats with LA supplementation compared with those of the rats without LA supplementation. Similarly, the selenium levels of the heart, brain and muscle were found to be significantly lower in LA-supplemented rats when compared to control rats. On the other hand, serum manganese levels were not changed in the aged rats with LA supplementation compared with those of the rats without LA supplementation. The heart manganese levels detected in LA-supplemented rats were significantly lower than controls. Manganese levels of the brain and muscle tissues were increased in the aged rats with LA supplementation compared with those of the rats without LA supplementation. Based on the findings of our study, we conclude that LA may exhibit pro-oxidant effect depending on the altered selenium and manganese homeostasis. Thus, our results stress the importance of monitoring the dose of LA supplementation and serum selenium levels, duration of treatment and its potential harmful pro-oxidant effects in the postmitotic tissues of aged rats.

Relationships among iron, protein oxidation and lipid peroxidation levels in rats with alcohol-induced acute pancreatitis.

It has been previously shown that alcohol induces the damage of pancreatic parenchyma tissue, but the mechanism of this damage is still poorly understood. Assuming that oxygen radical damage may be the involved, we measured markers of oxidative damage in pancreatic tissue, blood serum, plasma, and whole blood of rats with early-stage alcohol-induced acute pancreatitis. Thirty-eight male Wistar rats were divided into three groups: the control group (group 1), the acute pancreatitis group 1 day (group 2), and 3 days (group 3) after the injection of ethyl alcohol into the common biliary duct, respectively. The levels of Fe in tissue and serum, whole blood viscosity, plasma viscosity, fibrinogen and homocysteine (Hcy) levels, erythrocyte and plasma malondialdehyde (MDA), and tissue and plasma protein carbonyl levels were found to be significantly higher in groups 2 and 3 than in group 1. However, the levels of reduced glutathione (GSH) in tissue and erythrocytes were significantly lower in groups 2 and 3 than in group 1. These results suggest that elevated Fe levels in serum and pancreatic tissue in rats with early-stage alcohol-induced acute pancreatitis is associated with various hemorheological changes and with oxidative damage of the pancreas.

Monitoring of platelet function parameters and microRNA expression levels in patients with prostate cancer treated with volumetric modulated arc radiotherapy.

Radiotherapy (RT) may result in platelet activation and thrombosis development. To the best of our knowledge, the potential effect of volumetric-modulated arc therapy (VMAT), a novel radiotherapy technique, on platelet function and microRNA (miRNA/miR) expression has not been previously investigated. The present study aimed to determine the effect of VMAT on the alterations in platelet function parameters and miRNA expression levels. A total of 25 patients with prostate cancer and 25 healthy subjects were included in the present study. Blood samples were collected from the patient group on the day prior to RT (pre-RT), the day RT was completed (post-RT day 0), and 40 days following the end of therapy (post-RT day 40). Platelet count, mean platelet volume (MPV) value, platelet aggregation, plasma P-selectin, thrombospondin-1, platelet factor 4, plasma miR-223 and miR-126 expression levels were measured. A significant decrease in platelet count in the post-RT day 0 group was measured in comparison with the pre-RT and the post-RT day 40 groups. Pre-RT MPV values were higher than those of the post-RT day 0 and the post-RT day 40 groups. No significant differences were observed in the levels of platelet activation markers or miR-223 and miR-126 expression levels between the RT groups. Although RT may result in a reduction in platelet and MPV counts, the results of the present study indicate that platelet activation markers are not affected by VMAT. Therefore, it is possible that no platelet activation occurs during VMAT, owing to the conformal dose distributions, improved target volume coverage and the sparing of normal tissues from undesired radiation.

Increased oxidative damage of sperm and seminal plasma in men with idiopathic infertility is higher in patients with glutathione S-transferase Mu-1 null genotype.

AIM: To examine whether a relationship exists between glutathione S-transferase Mu-1 (GSTM1) gene polymorphism and the susceptibility of sperm and seminal plasma from patients with idiopathic infertility to oxidative stress. METHODS: Fifty-two men with idiopathic infertility and 60 healthy fertile men were recruited to this study. GSTM1 gene polymorphism was determined by polymerase chain reaction (PCR) and both the infertile and control individuals were divided into GSTM1 null and GSTM1 positive groups according to their GSTM1 gene structure. We compared reactive oxygen species (ROS) generation, malondialdehyde (MDA), protein carbonyls and glutathione (GSH) concentrations, and glutathione S-transferase (GST) activity in seminal plasma and spermatozoa from infertile patients and controls with respect to GSTM1 genotype. RESULTS: Significantly higher levels of oxidative stress and damage markers were found in idiopathic infertile men with the GSTM1 null genotype compared with those with the GSTM1 positive genotype. There was no significant difference in genotype distribution for the GSTM1 variant between the idiopathic infertile subjects and fertile subjects. Patients with the GSTM1 null genotype also had lower sperm concentrations than those with GSTM1 positive genotype. CONCLUSION: Our results suggest that the susceptibility of sperm and seminal plasma to oxidative stress is significantly greater in idiopathic infertile men with the GSTM1 null genotype compared with those possessing the gene. Therefore, in patients with idiopathic infertility, GSTM1 polymorphism might be an important source of variation in susceptibility of spermatozoa to oxidative damage.

Mercury levels in cord blood and meconium of healthy newborns and venous blood of their mothers: clinical, prospective cohort study.

OBJECTIVES: The purpose of this study is to investigate the chronic mercury intoxication in pregnant women and newborns living in Istanbul, Turkey. METHODS: The research was carried out as a prospective with 143 pregnant women and their newborns. Venous blood from the mother, cord blood from the neonate, and meconium were collected for mercury analysis. Frequency of fish and vegetable-eating and the number of teeth filled were investigated. Analyses were made in cold vapor Atomic Absorption Spectrophotometer (AAS, microg/L). RESULTS: Mercury levels were 0.38+/-0.5 microg/L (0-2.34) in venous blood of pregnant women, 0.50+/-0.64 microg/L (0-2.36) in umbilical cord blood and 9.45+/-13.8 microg/g (0-66.5) in meconium. Maternal blood mercury level was lower than the known toxic limit for humans (EPA, 5 microg/L). Mercury levels of the maternal venous blood were significantly correlated with umbilical cord blood. The primary risk factors affecting mercury levels were eating fishmeals more than twice a week and having filled teeth more than five. The fact that the mother had a regular vegetable diet everyday reduced the mercury levels. Increased levels of mercury in the mother and umbilical cord blood could lead to retarded newborns' weight and height. CONCLUSION: Pregnant women living in Istanbul may be not under the risk of chronic mercury intoxication. Fish consumption more than twice per week and tooth-filling of mother more than five may increase mercury level. On the contrary, regular diet rich in vegetable decreases the mercury level.

High levels of cadmium and lead in seminal fluid and blood of smoking men are associated with high oxidative stress and damage in infertile subjects.

We measured the levels of malondialdehyde (MDA), protein carbonyls, glutathione S-transferase (GST) and reducte glutathione (GSH) in seminal plasma and spermatozoa from 95 subjects including 50 infertile patients to evaluate the association between oxidative stress and damage and the components of the anti-oxidant defenses in seminal plasma and spermatozoa of infertile subjects and concentrations of cadmium (Cd) and lead (Pb) in the blood and seminal plasma because of tobacco smoke exposure. The reactive oxygen species (ROS) in spermatozoa were also evaluated by luminol (5-amino-2,3-dihydro-1,4-phthalazinedione)-enhanced chemiluminescence assay. The sperm count, motility, and morphology in the smokers infertile group were found to be lower than those in the fertile male group and nonsmokers infertile group (p < 0.001). Concentrations of Cd, Pb, MDA, protein carbonyls, and ROS levels in the smokers infertile group were significantly higher than those in the fertile male and nonsmokers infertile male groups (p < 0.001). However, GSH levels and GST activities were decreased in the smokers infertile male group than those in the fertile male and nonsmokers infertile male groups (p < 0.001). The results indicate that smoking could affect semen quality and oxidative lipid and protein damage in human spermatozoa. From Pearson correlation analysis, positive correlations were demonstrated between the seminal plasma Cd and seminal plasma protein carbonyls and between seminal plasma Pb and spermatozoa ROS levels in smokers of the subfertile group, while there was a significant positive correlation between blood Cd and ROS levels in smokers of the fertile group. There was also a significant negative correlation of the Cd level of the blood and GSH levels of the sperm and seminal plasma. These findings suggest that cigarette smoking enhances the levels of Cd and Pb in seminal plasma and blood and the extent of oxidative damage associated with a decrease in components of the anti-oxidant defenses in the sperm of infertile males.

Effect of alpha-lipoic acid supplementation on trace element levels in serum and in postmitotic tissue in aged rats.

Redistribution of redox-active divalent metal ions (e.g. copper, zinc, and iron) in postmitotic tissues of lipoic acid supplemented aging rats has been proposed to contribute to metal-catalyzed protein oxidation. DL-alpha lipoic acid (LA) (100 mg/kg body wt/day) was administered intraperitoneally to the Sprague-Dawley rats for 14 days. Serum copper levels lowered in the aged rats with LA supplementation compared to the rats without LA supplementation. On the other hand, serum zinc and iron levels increased in the aged rats with LA supplementation compared to the rats without LA supplementation. Copper levels of the postmitotic tissues were not changed in the aged rats with LA supplementation compared to the controls. The heart zinc levels detected in LA supplemented rats were significantly lower than controls. Similarly, the iron levels of the heart were found to be significantly lower in LA supplemented rats when compared to control rats. LA supplementation did not affect brain and muscle iron levels. The brain and muscle zinc levels remained the same in both group of rats. Based on the findings of our study, we have concluded that LA may exhibit prooxidant effect depending on the altered trace element homeostasis. Therefore, our results emphasize the importance of monitoring the dose of LA supplementation, duration of treatment and its potential harmful effects in the postmitotic tissues of aged rats.

Association of NFKB1A and microRNAs variations and the susceptibility to atherosclerosis.

Atherosclerosis (AT) is a chronic immuno-inflammatory disease characterized by inflammatory mediators and immune activation in arterial wall. Although NF-κB and microRNAs are involved in the atherosclerotic lesions, the pathogenesis of atherosclerosis is still unknown. The aim of this study was to investigate the association of atherosclerosis with NFKB1-rs28362491, NFKBIA-rs696, pre-miRNA-146a-rs2910164 and pre-miRNA-499-rs3746444 polymorphisms as well as the analysis of their single and combined effects on its susceptibility in a Turkish population. We analysed the distribution of NFKB1-94 ins/del ATTG (rs28362491), NFKBIA (rs696), pre-miR-146a (rs2910164) and pre-miR-499 (rs3746444) genetic polymorphisms using PCR-RFLP assay in 150 atherosclerotic patients and 145 healthy controls in a Turkish population. The data revealed no significant differences in the distribution of the genotype and alleles of rs28362491 ,whereas AA genotype of rs696 lead to a higher risk for atherosclerotic patients. TT genotype and T allele of pre-miR-499 rs3746444 were found to be associated with atherosclerosis risk. In addition, significant differences were found between atherosclerotic patients and control subjects, concerning pre-miR-146a rs2910164 polymorphism. The subjects carrying the GG genotype and G allele of rs2910164 were found to have an increased risk against AT. The results of combined genotype analysis, showed no notable differences between the multiple comparisons of rs28362491- rs696 whereas rs28362491-rs2910164 ins/ins/GG is associated with increased AT risk. The combined genotypes of rs28362491/rs3746444 ins/ins/TT, revealed a significant protective effect on AT. These findings indicate that genetic polymorphisms of NFKB1A rs696, pre-miR-146a rs2910164 and pre-miR-499 rs3746444 may represent novel markers of AT susceptibility.