Assessment of the Relationship between Serum Vitamin D and Osteocalcin Levels with Metabolic Syndrome in Non-Osteoporotic Postmenopausal Women.

Introduction The aim of this study was to compare serum vitamin D and osteocalcin levels in non-osteoporotic postmenopausal women with and without metabolic syndrome and to analyze the relationship between serum vitamin D and osteocalcin levels and the relationships between these two factors and other clinical/biochemical parameters. Material and Method This cross-sectional study was carried out in 191 postmenopausal non-osteoporotic (T-score > - 2.5) women. Patients were divided into two groups according to the presence or absence of metabolic syndrome. Blood samples were obtained and evaluated for 25-hydroxyvitamin D, osteocalcin, insulin resistance (using a homeostatic model assessment of insulin resistance), glycosylated hemoglobin (HbA 1c ), calcium, phosphorus, deoxypyridinoline, thyroid-stimulating hormone, lipid profile, fasting insulin, fasting glucose and HbA 1c levels. Demographic and laboratory parameters were recorded for each woman. Results Vitamin D was found to be lower in women with metabolic syndrome compared to controls (16.1 ± 11.2 vs. 20.4 ± 13.1 mg/dL; p = 0.013). Similarly, osteocalcin was found to be significantly lower in the metabolic syndrome group compared to the control group (4.2 ± 2.1 vs. 5.5 ± 3.0; p < 0.001). A significant positive correlation was observed between vitamin D and osteocalcin levels (r = 0.198; p = 0.008). There was an inverse correlation between vitamin D and some of the lipid parameters. However, osteocalcin levels were negatively correlated with C-reactive protein, insulin resistance, and HbA 1c in both groups (p = 0.003, p = 0.001 and p = 0.048, respectively). Conclusion Vitamin D deficiency is common in postmenopausal women, even in women who are non-osteoporotic. Serum levels of vitamin D are significantly decreased in cases with metabolic syndrome. Vitamin D may directly improve serum lipid profiles and may indirectly decrease insulin resistance and subclinical systemic inflammation through the impact on the metabolic functions of osteocalcin.

The Possibly Reversible Isotretinoin Effect of Decreased Ovarian Reserve in Sprague-Dawley Albinos: Part I, Biochemical Analyses.

BACKGROUND: The study aims to determine the detrimental effects of 7.5 mg/kg/day isotretinoin treatment on the anti-Mullerian hormone (AMH) levels in an experimental study to see whether the effects on ovarian reserve are reversible. METHODS: Blood was sampled in 16 Sprague-Dawley albinos before any treatment to see baseline AMH levels. Then, the rats were randomly divided into 2 groups. Control group received only 1.0 ml soybean oil per oral for 30 days, whereas the study group received 7.5 mg/kg/day isotretinoin suspended in soybean oil. AMH levels were measured at the 30th day - immediately after the last medication - and on 60th day - 1 month after the last medication. RESULTS: The mean values of AMH levels were 8.16 ± 1.47, 6.95 ± 1.87, 6.27 ± 0.71 and 8.20 ± 1.48, 6.56 ± 1.45, 7.07 ± 0.96 ng/ml before, immediately after and 1 month after the last medication in the control and isotretinoin treatment group, respectively. The mean AMH levels significantly decreased (p = 0.02) immediately after isotretinoin administration. The mean AMH levels 1 month after the last dose of isotretinoin therapy were higher than the levels immediately after the medication; however, the difference was not statistically significant. CONCLUSION: This study indicates that exposure to isotretinoin is responsible for decreased AMH levels in experimental rat model and this effect seems to be reversible.

A randomized controlled experimental study of the efficacy of platelet-rich plasma and hyaluronic acid for the prevention of adhesion formation in a rat uterine horn model.

PURPOSE: Platelet-rich plasma (PRP) has been known to possess an efficacy in tissue regeneration. The aim of this study was to determine the role of PRP on post-operative adhesion formation in an experimental rat study. METHODS: Thirty Sprague-Dawley rats were randomly divided into control, hyaluronic acid, and PRP treatment groups and operated on for uterine horn adhesion modeling. Blood was collected to produce a PRP with platelet counts of 688 × 10(3)/µL, and 1 ml of either hyaluronic acid gel or PRP was administered over the standard lesions, while the control group received no medication. The evaluation of post-operative adhesions was done on the 30th post-operative day. The location, extent, type, and tenacity of adhesions as well as total adhesion scores, tissue inflammation, fibrosis and transforming growth factor-1beta (TGF-1ß) expressions were evaluated. RESULTS: The total adhesion score was significantly lower in the PRP group (3.2 ± 1.5) compared with the hyaluronic acid (5.0 ± 1.3) and control (8.1 ± 1.7) groups. The extent of the adhesions was significantly lower in the PRP group. There was no significant difference in the type and tenacity of adhesions between the hyaluronic acid and the PRP group. The level of inflammation was significantly higher in the control group than the others, while there was no difference between the PRP and hyaluronic acid groups. TGF-1ß expression was significantly lesser in the PRP group than the control and hyaluronic acid groups. CONCLUSIONS: PRP is more effective than hyaluronic acid treatment in preventing post-operative adhesion formation in an experimental rat uterine horn adhesion model.

Diagnostic value of CA 19-9 in pregnancies complicated by spinal neural tube defects: a preliminary study.

OBJECTIVES: Various physiological and pathological conditions can induce significant variations in plasma concentrations of tumor markers, such as CA 19-9, which is present in the serum and amniotic fluid of pregnant women. Herein, we aimed to determine the clinical importance of maternal serum CA 19-9 levels in the diagnosis of neural tube defects (NTDs). MATERIAL AND METHODS: A total of 100 women were included in this controlled cross-sectional study. Thirty-three patients whose pregnancies were complicated by isolated meningocele or meningomyelocele constituted the study group, whereas 33 normal, healthy pregnant women constituted the control group, and 34 age- and body mass index (BMI)-matched non-pregnant women were chosen for the validation group. RESULTS: The mean maternal serum CA 19-9 levels were 17.2 ± 17.0 IU/mL, 7.1 ± 5.9 IU/mL, and 4.7 ± 3.6 IU/mL in the study, control, and validation groups, respectively (p < 0.001). ROC analyses showed that elevated CA 19-9 values may predict NTDs (p < 0.001). The cut-off value for CA 19-9 was found to be 9.6 IU/mL at 70% (51%-84%, 95% CI) sensitivity and 84% (74%-92%, 95% CI) specificity. CONCLUSIONS: CA 19-9 may be a promising noninvasive marker for NTDs. Further studies are needed to reveal the clinical applicability and diagnostic potential of maternal serum CA 19-9 levels in the identification of NTDs.

First trimester interleukin-6 levels help to predict adverse pregnancy outcomes in both thyroid autoantibody positive and negative patients.

AIM: The aim of the present study is to compare pregnancy outcomes among patients with and without thyroid antibodies and/or subclinical hypothyroidism and investigate whether there is an association between first trimester maternal plasma interleukin-6 (IL-6) levels and adverse pregnancy outcomes. METHODS: A case-control study was carried out including 83 pregnant women (40 thyroid antibody positive and 43 healthy controls). The predictive value of first trimester maternal plasma IL-6 levels on adverse pregnancy outcomes were investigated. The optimal cut-off points of IL-6 for determining maternal and fetal outcomes were evaluated by receiver operating characteristic analyses. RESULTS: Compared with the control, median IL-6 levels were significantly higher in thyroid antibody positive pregnancies (median 1.58 vs 1.63 pg/mL; P = 0.047). IL-6 levels were found to be significantly higher in women who had suffered a miscarriage (P = 0.002), preterm delivery (P < 0.001), intrauterine growth restriction (P = 0.047), preterm premature rupture of membranes (P = 0.043) and overall prenatal complications (P < 0.001). A statistically significant negative correlation between gestational week at birth and IL-6 levels was also determined among all participants involved in the study (r = -0.385, P < 0.001). CONCLUSION: IL-6 levels are significantly increased in thyroid antibody positive patients and predictive for future adverse outcomes, irrespective of thyroid autoimmunity. Increased first trimester IL-6 levels independently predict adverse pregnancy outcomes, regardless of subclinical hypothyroidism.

Factor XII (Hageman) levels in women with recurrent pregnancy loss.

OBJECTIVE: To evaluate factor XII levels in women with recurrent pregnancy loss (RPL) in a tertiary referral hospital. METHODS: Women who were referred to our hospital for two consecutive abortions or three abortions in between 2007 and 2013 were included in this retrospective observational study. Women were further grouped according to factor XII levels, as <60% and ≥ 60%. RESULTS: Mean factor XII level was 109.1 ± 35.7% (range: 9-200). Ninety-three (7.4%) women had factor XII levels < 60%. Mean factor XII level was 44.8 ± 13.1, and levels ranged between 9 and 60 in this group. Only one woman had factor XII level < 10 %. Remaining 1164 (92.6%) women had factor XII levels ≥ 60%. Mean factor XII level was 114.3 ± 31.7, and levels ranged between 60.3 and 200 in this group, while 1015 (72.4%) women had factor XII levels within the normal range (60%-150% [100% = 30 µg/mL]). CONCLUSION: Decreased activity of F-XII was diagnosed in 7.4% of women with RPL. We concluded factor XII deficiency that might be a rare but significant factor for RPL, and should be evaluated in women who are investigated for recurrent pregnancy loss.

Mid-trimester maternal serum and amniotic fluid biomarkers for the prediction of preterm delivery and intrauterine growth retardation.

AIM: Our purpose was to evaluate the predictive value of maternal serum and amniotic fluid biomarkers that were obtained at the time of genetic amniocentesis for preterm delivery and intrauterine growth retardation (IUGR). METHODS: A prospective cohort analysis was conducted in 107 singleton pregnancies that underwent amniocentesis at 16-22 weeks according to standard genetic indications. Maternal blood and amniotic fluid obtained from genetic amniocentesis were tested for glucose, alkaline phosphatase (ALP), lactate dehydrogenase (LDH), ceruloplasmin, ferritin, high-sensitivity C-reactive protein and interleukin-6 (IL-6). Ninety-four pregnancies were followed until delivery. RESULTS: Of the 94 patients, 16 (18.1%) delivered before 37 weeks and seven (7.5%) delivered a baby below the 10th percentile for gestational age. Amniotic fluid glucose levels were significantly lower in patients with preterm delivery than term deliveries (P = 0.01). Median amniotic fluid ferritin and IL-6 levels and mean amniotic fluid ALP levels were higher in the preterm group but this difference did not reach statistical significance. Mean maternal ALP and LDH levels tended to be insignificantly higher. Only median maternal blood ferritin levels in the IUGR group were found to be higher than patients who were appropriate for gestational age (P = 0.03). CONCLUSION: Low amniotic fluid glucose levels are associated with risk of preterm delivery, whereas high maternal blood ferritin levels increase the risk for IUGR. Although this result is significant and notable, there is not enough clinical evidence to recommend their use as a screening test for preterm delivery and IUGR in routine practice.

Na+/I- symporter and type 3 iodothyronine deiodinase gene expression in amniotic membrane and placenta and its relationship to maternal thyroid hormones.

Placental type 3 iodothyronine deiodinase (D3) potentially protects the fetus from the elevated maternal thyroid hormones. Na(+)/I(-) symporter (NIS) is a plasma membrane glycoprotein, which mediates active iodide uptake. Our objectives were to establish the distribution of NIS and D3 gene expressions in the placenta and the amniotic membrane and to investigate the relationship between placental D3 and NIS gene expressions and maternal iodine, selenium, and thyroid hormone status. Thyroid hormones, urinary iodine concentration (UIC), and selenium levels were measured in 49 healthy term pregnant women. NIS and D3 gene expressions were studied with the total mRNA RT-PCR method in tissues from maternal placenta (n = 49), fetal placenta (n = 9), and amniotic membrane (n = 9). NIS and D3 gene expressions were shown in the fetal and maternal sides of the placenta and amniotic membrane. Mean blood selenium level was 66 ± 26.5 µg/l, and median UIC was 143 µg/l. We could not demonstrate any statistically significant relationship of spot UIC and blood selenium with NIS and D3 expression (p > 0.05). Positive correlations were found between NIS and thyroxine-binding globulin (TBG) (r = 0.3, p = 0.042) and between D3 and preoperative glucose levels (r = 0.4, p = 0.006). D3 and NIS genes are expressed in term placenta and amniotic membrane; thus, in addition to placenta, amniotic membrane contributes to regulation of maternofetal iodine and thyroid hormone transmission. Further studies are needed to clarify the relationship between maternal glucose levels and placental D3 expression and between TBG and placental NIS expression.

Ghrelin and motilin levels in hyperemesis gravidarum.

PURPOSE: Ghrelin, an endogenous ligand for the growth hormone secratogogue receptor, and its receptors are found in the reproductive organs and placenta. Motilin is produced from the endocrine cells of the duodeno jejunal mucosa and considered to be a regulator of interdigestive migrating contractions. Aim of this study is to investigate ghrelin and motilin levels in patients with hyperemesis gravidarum. METHODS: A total of 56 patients with singleton pregnancies in the first trimester were recruited in the study, 39 with hyperemezis gravidarum and 17 normal pregnant women. Patients with medical complications and body mass index <18 or >25 were excluded. Fasting plasma ghrelin and motilin concentrations were measured. Fasting blood glucose, liver enzymes, blood urea nitrogen, creatinin, estradiol, progesterone, human chorionic gonadotropin, and thyroid function tests were also investigated. RESULTS: Ghrelin levels were significantly higher in patients with hyperemesis group than the normal pregnant women (p = 0.025). Serum estradiol levels were also higher in the hyperemesis group (p = 0.001). No significant difference was observed in plasma motilin levels between the two groups. In correlation analyses, maternal ghrelin was positively correlated with estradiol (r = 0.29, p = 0.029) in the whole cohort. CONCLUSION: There are a few studies about the course of circulating ghrelin levels during human pregnancy. Ghrelin administration increases food intake through central mechanisms but its effects on appetite in relation to human pregnancy is unknown. The increased levels of ghrelin in hyperemesis gravidarum might be a compensatory mechanism to restore the energy metabolism of the pregnant women.

Role of oxidative stress in preeclampsia and intrauterine growth restriction.

AIM: The aim of the present study was to evaluate the role of oxidative stress and DNA damage in preeclampsia and intrauterine growth restriction (IUGR). MATERIAL AND METHODS: Twenty-four patients with preeclampsia, 20 patients with IUGR fetus and 37 healthy pregnant women were enrolled in the study. The total oxidant status (TOS) and antioxidant status (TAS) of plasma were measured using a novel automated colorimetric measurement method. Sister chromatid exchange (SCE) and micronuclei analysis were performed on peripheral blood lymphocytes of cases and controls. RESULTS: Women whose pregnancies were complicated with preeclampsia and IUGR had elevated levels of TOS and TAS when compared with healthy pregnant women (median TOS values: 9.73, 10.6 and 8.06, P = 0.001; median TAS values: 1. 77, 1.54 and 1.44, P < 0.001, respectively). The frequencies of SCE were only found to be increased in women with IUGR fetus compared with healthy pregnant women (8.81 vs 7.5, respectively, P = 0.02). Multivariable linear regression analysis for both TOS and TAS showed a significant relation between these variables and uric acid. CONCLUSION: Increased oxidative stress and antioxidative defense mechanisms may contribute to disease processes both in preeclampsia and IUGR.

Serum thyroid hormone levels in preterm infants born before 33 weeks of gestation and association of transient hypothyroxinemia with postnatal characteristics.

BACKGROUND: Fetal thyroid function and the hypothalamopituitary-thyroid axis continue to mature throughout pregnancy. Therefore, thyroid hormone levels of premature infants differ from those of mature ones. Our primary objective was to evaluate the reference values of serum thyroid hormones in preterm infants born before 33 wk gestation. The second objective was to define a cut-off value for transient hypothyroxinemia of prematurity (THOP) according to gestational age and association of THOP with postnatal characteristics in these infants. SUBJECTS AND METHODS: We recruited a cohort of 200 infants (26-32 wk gestation) admitted to neonatal intensive care units (NICU) between March 2008 and February 2009. We assessed serum levels of thyroid hormones and thyrotropin (TSH), at 1st, 2nd, and 3rd-4th wk of life. Thyroid-binding globulin (TBG), thyroglobulin (Tg), and urinary iodine values were also measured at the 1st wk of life. The infants were divided into two groups according to gestational ages; group 1: 26-29 wk and group 2: 30-32 wk. Association of THOP with postnatal characteristics of these infants were evaluated. RESULTS: TT4 and TT3 values steadily increased from 1st wk to 3rd-4th wk while FT4 value did not significantly changed. FT3 value slightly decreased from 1st wk to 2nd wk and not significantly changed after this period. TSH value steadily decreased from 1st wk to 3rd-4th wk. For all postnatal ages, TT4, TT3, and FT3 values were lower in the lower gestational age group, while there was no significant difference for FT4 and TSH values between two gestational age groups. THOP rate decreased from first wk (24.0%, n=47) to 3rd-4th (14.0%, n=24) in all infants. When adjusted for age, THOP was associated with need for mechanical ventilation (P=0.03, OR:0.65, CI 95% 0.4-0.9) and for having respiratory distress syndrome (RDS) (P=0.02, OR:0.61 CI95%: 0.4-0.9). Longer hospital stay (P=0.006, OR:0.96, CI 95% 0.94-0.99) was also found to be associated with THOP. CONCLUSIONS: In preterm infants below 30 wk, thyroid hormones were lower and urinary iodine values were higher compared to infants with older gestational age. THOP at the first wk of life may convey important prognostic information about neonatal morbidity and length of hospitalization stay.

Maternal plasma total antioxidant status in preterm labor.

AIM: To investigate the role of oxidative stress and antioxidant status in preterm labor. METHODS: Twenty-five cases diagnosed with preterm labor were included in the study group, whereas 25 women with uncomplicated pregnancies at similar stages of pregnancy were included in the control group. Total antioxidant status was measured in maternal plasma using a Hitachi 911 auto analyzer and a total antioxidant status kit (Randox Laboratories, UK) in mmol/L. RESULTS: Mean serum antioxidant status were lower in patients (1.002 ± 0.177 mmol/L) than in controls (1.258 ± 0.147 mmol/L) (P < 0.001). CONCLUSION: Women with preterm labor have decreased total antioxidant status compared with uncomplicated pregnancies in similar gestational weeks. Future work should clarify whether decreased total antioxidant status precedes preterm labor in a prospective cohort study.

Asymmetric dimethylarginine concentrations are elevated in women with gestational diabetes.

As shown in the previous studies, asymmetric dimethylarginine (ADMA) is related to endothelial dysfunction, whereas high-sensitive C-reactive protein (hCRP) is the marker of inflammation. In our study, we investigated ADMA, hCRP, and homocysteine concentrations in women with gestational diabetes mellitus (GDM) and normal glucose tolerance (NGT) during late pregnancy. Fifty-four women with GDM and 69 women with NGT between 32 and 39 weeks of gestation were included in this study. ADMA, hCRP, homocysteine, lipid parameters, glycated hemoglobin (HbA1c) levels, insulin, and homeostasis model assessment for insulin resistance (HOMA-IR) were measured. The plasma ADMA concentrations were significantly higher in GDM patients than in NGT subjects (P = 0.03) and the hCRP levels were also significantly increased in GDM group when compared with those in the NGT group (P = 0.008). However, plasma homocysteine levels did not differ between the groups (P = 0.4), while HOMA-IR, insulin, and triglyceride levels were higher in the GDM group than in the NGT group (P = 0.001, 0.002, and 0.02, respectively). The ADMA concentrations in the third trimester were positively correlated with the glucose levels the 50-g glucose challenge test (GCT) during 24-28 weeks in the whole group (r = 0.21, P = 0.02). Our results demonstrate that ADMA and hCRP are elevated in women with GDM during late pregnancy. Further studies are needed to clarify the significance and the underlying mechanisms of the elevated ADMA and hCRP levels in women with GDM.

A long-standing incomprehensible matter of obstetrics: meconium-stained amniotic fluid, a new approach to reason.

OBJECTIVE: We sought to determine whether meconium-stained amniotic fluid is based on chronic hypoxia or not? In case of chronic hypoxia, higher red blood cell (Rbc) count and/or total hemoglobin levels (Hgb) and/or higher fetal hemoglobin (HbF) and/or lower adult hemoglobin (HbA) levels were expected when compared with controls. DESIGN: Case-control study. SETTING: Obstetric unit of a tertiary ministry of health hospital. SAMPLE: Fifty singleton pregnancies with meconium-stained amniotic fluid and 50 singleton pregnancies with clear amniotic fluid at all stages of labor. METHODS: Umbilical cord blood samples were collected for determination of total blood parameters and hemoglobin electrophoresis. MAIN OUTCOME MEASURES: Red blood cell count, total hemoglobin, fetal and adult hemoglobin contents (HbF and HbA). RESULTS: Red blood cell count, total hemoglobin, fetal hemoglobin (HbF) and adult hemoglobin (HbA) contents were not different between meconium stained and clear amniotic fluid groups. CONCLUSION: These results suggest that meconium passage may not be associated with chronic fetal hypoxia as demonstrated by similar red blood cell count, total hemoglobin values and fetal hemoglobin (HbF) and adult hemoglobin (HbA) contents.