Oncostatin M Is Related to Polycystic Ovary Syndrome-Case Control Study.

Background: Oncostatin M, a novel adipokine, plays a role in oogenesis, lipogenesis, and inflammation and may contribute to polycystic ovary syndrome pathogenesis and related metabolic problems. Adipokines are believed to contribute to developing polycystic ovary syndrome and its accompanying metabolic parameters, such as dyslipidemia, insulin resistance, and cardiovascular diseases. Methods: In this case-control study, the patients were grouped in a 1:1 ratio into either the polycystic ovary syndrome (n = 32) or the control group (n = 32). Serum levels of fasting glucose, insulin, C-reactive protein, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglyceride, white blood cell count, thyroid-stimulating hormone, luteinizing hormone, follicle-stimulating hormone, total testosterone, prolactin, estradiol, homeostasis model assessment of insulin resistance, and oncostatin M were analyzed. Results: Oncostatin M levels were significantly lower, but C-reactive protein levels were substantially higher in the polycystic ovary syndrome group than in the control group (p = 0.002, p = 0.001, respectively). Oncostatin M was inversely correlated with total cholesterol, non-high-density lipoprotein cholesterol, fasting glucose, and the luteinizing hormone/follicle-stimulating hormone ratio (ρ = -0.329, p =0.017; ρ = -0.386, p = 0.005; ρ = -0.440, p = 0.001; ρ = -0.316, p = 0.023, respectively). Conversely, there was no correlation between oncostatin M and total testosterone level (ρ = 0.220; p = 0.118). In the context of inflammation and metabolic parameters, oncostatin M was inversely correlated with C-reactive protein, homeostatic model assessment for insulin resistance score, and low-density lipoprotein cholesterol (ρ = -0.353, p = 0.019; ρ = -0.275, p = 0.048; ρ = -0.470, p < 0.001, respectively). Conclusions: Plasma oncostatin M levels were considerably lower in patients with polycystic ovary syndrome than in the control group, and this was inversely correlated with the hormonal and metabolic parameters of polycystic ovary syndrome. Thus, oncostatin M may be a novel therapeutic target for polycystic ovary syndrome and its metabolic parameters.

Is the clinical course of non-arteritic ischemic optic neuropathy associated with oxidative damage and the dynamics of the antioxidant response?

PURPOSE: Oxidative stress is known to be a decisive factor in the wide etiopathogenesis of optic neuropathy. This study aimed to comprehensively evaluate the interaction of optic neuropathy's clinical course with systemic oxidative damage and antioxidant response dynamics in a large series. METHODS: This case-controlled clinical study included 33 non-arteritic anterior ischemic optic neuropathy (NAION) patients and 32 healthy individuals. Extensive systemic oxidation profiles were statistically compared between the two groups, and correlations between the clinical and biochemical data in the study group were analyzed. RESULTS: Vitamin E and malondialdehyde (MDA) levels were significantly higher in the study group. Significant correlations were observed in the analyses between clinical findings and oxidative stress parameters. Correlations between vitamin E and intraocular pressure (IOP), between B12 and cup-to-disk ratio (c/d), between antioxidant glutathione and superoxide dismutase (SOD) enzyme systems, and between uric acid (UA) and age were found to be very significant. As significant correlations were found in either clinical and biochemical data or in oxidative stress parameters, correlations between vitamin E and cholesterol, MDA were found to be very significant. CONCLUSIONS: This study not only supplies significant information regarding oxidative damage and antioxidant response in NAION, but also points out the specific interactions of neuromodulators, like vitamin E, in intracellular signaling pathways and regulation mechanisms. A better reading of these connections may help improve diagnosis, follow-ups and treatment criteria and strategies.

Assessment of Plasma-Free Cortisol Concentrations by LC-MS/MS in Patients with Autonomous Cortisol Secretion.

Autonomous cortisol secretion (ACS) of an adrenal incidentaloma (AI) is associated with mild cortisol excess that could result in poor metabolic and cardiovascular outcomes. The biological activity of glucocorticoids depends on the unbound, free fraction. We aimed to evaluate plasma free cortisol (FC) concentrations in patients with ACS in this cross-sectional study. One hundred and ten AI patients in 3 groups; non-functioning (NFA, n=33), possible ACS (n=65), ACS (n=12) were enrolled. Following measurements were conducted: Clinical data and total serum cortisol (TC), plasma corticotrophin (ACTH), serum dehydroepiandrosterone sulfate (DHEA-S), cortisol after 1 mg dexamethasone by both immunoassay and LC-MS/MS (DexF), serum corticosteroid binding globulin (CBG), plasma dexamethasone concentration [DEX] and plasma FC by LC-MS/MS. Patients with ACS featured an unfavorable metabolic profile. Plasma [DEX] and serum CBG levels were similar between groups. Plasma FC was significantly higher in ACS when compared to NFA and possible ACS groups p<0.05 and p<0.01, respectively. In multiple regression analysis DexF (beta=0.402, p<0.001) and CBG (beta=-0.257, p=0.03) remained as the independent predictors of plasma FC while age, sex, BMI, smoking habit, and existing cardiovascular disease did not make a significant contribution to the regression model. In conclusion, the magnitude of cortisol excess in ACS could lead to increased plasma FC concentrations. Further studies in AI patients are needed to demonstrate whether any alterations of cortisol affinity for CBG exist and to establish whether plasma FC concentrations predict the unfavorable metabolic profile in ACS.

Association between early oxidative DNA damage and iron status in women with gestational diabetes mellitus.

This study aims to assess the relationship between oxidative DNA damage and iron status in women with gestational diabetes mellitus (GDM) compared to those with normal glucose tolerance in the first and the second trimesters of pregnancy. Maternal serum and urine samples were collected in the 11th-14th weeks and the 24th-28th weeks of gestation. In addition to oral glucose tolerance test in the second trimester, fasting blood glucose, HbA1c, ferritin and hemoglobin levels were measured in blood samples. Urinary levels of oxidative DNA damage products 8-hydroxy-2'-deoxyguanosine (8-OH-dG) and 8,5'-cyclo-2'-deoxyadenosines (S-cdA, R-cdA) were determined using liquid chromatography-tandem mass spectrometry with isotope-dilution. In the first trimester, urinary 8-OH-dG levels were found higher in the GDM group (n = 33) than in the control group (n = 84) (p = 0.006). R-cdA and S-cdA levels were not significantly different between the two groups (p = 0.794 and p = 0.792 respectively). When the cases were stratified according to their first trimester ferritin levels, women with ≥50th centile (≥130 ng/mL) demonstrated higher levels of 8-OH-dG and R-cdA than those under <50th centile (p = 0.034, p = 0.009). In the GDM group, there was a positive correlation between the second trimester 8-OH-dG and ferritin and 1st-hour glucose levels (p = 0.014, p = 0.020). This is the first study where oxidative DNA damage is evaluated in both early and late periods of pregnancy. Our findings reveal an association between GDM and iron status and oxidative DNA damage.

Functional vitamin B12 deficiency in phenylketonuria patients and healthy controls: An evaluation with combined indicator of vitamin B12 status as a biochemical index.

BACKGROUND: Vitamin B12 deficiency frequently appears in phenylketonuria patients having a diet poor in natural protein. The aims of this study were to evaluate vitamin B12 status in phenylketonuria patients by using combined indicator of vitamin B12 status (cB12) as well as methylmalonic acid and homocysteine, more specific and sensitive markers, in comparison with healthy controls. METHODS: Fifty-three children and adolescents with phenylketonuria under dietary treatment and 30 healthy controls were assessed cross-sectionally. Serum vitamin B12 and folate concentrations were analysed by chemiluminescence immunoassay. Plasma methylmalonic acid and total homocysteine concentrations were measured by liquid chromatography-tandem mass spectrometry and liquid chromatography, respectively. cB12 was calculated by using a formula involving blood parameters. RESULTS: Methylmalonic acid and folate concentrations in phenylketonuria group were higher compared with controls. Methylmalonic acid concentrations were high in 56.5% of the patients and 26.7% of the controls with normal vitamin B12 concentrations. Based on cB12, a significant difference within the normal values was detected between the groups. However, although 24.5% of phenylketonuria patients and 13.3% of controls had decreased vitamin B12 status according to cB12, there was no significant difference. CONCLUSION: Children and adolescents with phenylketonuria having a strict diet can be at risk of functional vitamin B12 deficiency. This deficiency can be accurately determined by measuring methylmalonic acid concentrations. Calculation of cB12 as a biochemical index did not provide additional information compared with the measurement of methylmalonic acid alone, but may be helpful for classification of some patients with increased methylmalonic acid as having adequate vitamin B12 status.

Alterations in levels of 8-Oxo-2'-deoxyguanosine and 8-Oxoguanine DNA glycosylase 1 during a current episode and after remission in unipolar and bipolar depression.

INTRODUCTION: Previous studies showed significant increases in DNA base damage markers and significant alterations in base excision repair enzymes in patients with unipolar and bipolar depression. We aimed to investigate changes in urine 8-Oxo-2'-deoxyguanosine (8-oxo-dG) and gene expression levels of 8-Oxoguanine DNA glycosylase 1 (OGG1) during a current depressive episode and after remission in bipolar and unipolar disorders. METHODS: Twenty-four acutely depressed bipolar (BD), 33 unipolar depression (UD) patients and 61 healthy controls were included in the study. Clinical evaluations, blood and urine sampling were completed at baseline and at remission after eight weeks. The urine 8-oxo-dG levels were assessed by liquid chromatography tandem mass spectrometry and adjusted for urine creatinine levels. The gene expression levels of OGG1 were determined from cDNA extracted from blood samples, using real time-polymerase chain reaction. RESULTS: At baseline, patients presented significantly higher levels of 8-oxo-dG (p = 0.008), and lower gene expression of OGG1 (p = 0.024) compared to controls. Levels of either 8-oxo-dG or OGG1 expression did not differ between BD and UD. In patients who remitted by the 8th week (n = 30), 8-oxo-dG decreased significantly (p = 0.001), and gene expression levels of OGG1 increased by 2.95 times compared to baseline levels (p = 0.001). All comparisons were adjusted for age, sex, smoking status and body mass index. CONCLUSION: Our results suggest that patients with bipolar and unipolar mood disorders present increased 8-oxo-dG and decreased gene expression levels of OGG1 in current depressive episodes, and that these changes might be reversed by the resolution of depressive symptoms. The causal relationship between DNA damage and repair requires further exploration.

A prospective study on first trimester prediction of ischemic placental diseases.

OBJECTIVE: The objective of the study is to assess the predictive power of mean uterine artery pulsatility index (UtA PI), maternal serum placental growth factor (PlGF) and placenta associated plasma protein A levels for the development of ischemic placental diseases (IPD) in a cohort of unselected singleton pregnancies during the first trimester combined test period. MATERIALS AND METHODS: A sample of 880 pregnancies was registered between September 2014 and January 2016. After routine examination for first trimester combined test, UtA PI was measured, and maternal serum was obtained and stored at -80 °C for PlGF assessment. RESULTS: Early-onset preeclampsia, late-onset preeclampsia and placental dysfunction-related fetal growth restriction were observed in 6 (0.7%), 17 (2.0%) and 27 (3.2%) cases, respectively. IPD requiring delivery before 34 weeks of gestation could be predicted with a sensitivity, specificity, positive predictive value and negative predictive value of 76.2%, 90.2%, 20.2% and 99.1%, respectively. CONCLUSION: A combination of UtA PI, placenta associated plasma protein A and PlGF was proven to be successful in the first trimester prediction of IPD, with the highest sensitivity in the subgroup who required delivery before 34 weeks of gestation. In reducing the number of pregnancies that should be followed-up, further studies for new biomarkers are needed. © 2017 John Wiley & Sons, Ltd.

Elevated urinary levels of 8-oxo-2'-deoxyguanosine, (5'R)- and (5'S)-8,5'-cyclo-2'-deoxyadenosines, and 8-iso-prostaglandin F2α as potential biomarkers of oxidative stress in patients with prediabetes.

Prediabetes is the preclinical stage of type 2 diabetes mellitus (T2DM) with intermediate state of hyperglycemia. Hyperglycemia results in a state of oxidative stress, which may contribute to the production of insulin resistance, ß-cell dysfunction and long-term complications of diabetes. Novel approaches are required for prevention and treatment of diabetes. New biomarkers that can be used in risk stratification and therapy control as supplementary to current parameters are needed. These biomarkers may facilitate a more individualized and sufficient treatment of diabetes. Therefore, the aim of this study was to investigate the levels of oxidatively induced DNA damage products, 8-oxo-2'-deoxyguanosine (8-oxo-dG) (also known as 8-OH-dG), (5'R)- and (5'S)-8,5'-cyclo-2'-deoxyadenosines (R-cdA and S-cdA), and the lipid peroxidation product 8-iso-prostaglandin F2α (8-iso-PGF2α) as reliable oxidative stress markers in patients with prediabetes or T2DM in comparison with healthy volunteers. Urine samples were collected from these subjects. Absolute quantification of 8-oxo-dG, R-cdA, S-cdA and 8-iso-PGF2α was achieved by liquid chromatography-isotope dilution tandem mass spectrometry. The levels of 8-oxo-dG, S-cdA and 8-iso-PGF2α were significantly greater in prediabetes patients than those in healthy volunteers. T2DM patients also had higher levels of 8-oxo-dG than healthy volunteers. No statistically significant difference was observed for R-cdA levels. 8-Oxo-dG levels positively correlated with R-cdA and S-cdA levels for prediabetes and newly diagnosed T2DM. S-cdA levels and HbA1c were found negatively correlated in prediabetes patients. Also 8-iso-PGF2α levels and HbA1c were found negatively correlated in prediabetes patients. These results indicate that oxidatively induced macromolecular damage appears before the establishment of T2DM. Thus, our data suggest that oxidatively induced DNA damage and lipid peroxidation products that were found to be elevated in prediabetic stage may be used as early disease markers in patients at risk for T2DM.