Increased maternal leptin levels may be an indicator of subclinical hypothyroidism in a newborn.

Background: Several factors may influence newborn thyroid-stimulating hormone (TSH) concentrations and cause subclinical hypothyroidism in a newborn. A sufficient level of leptin signalling is needed for the normal production of TSH and thyroid hormones by the thyroid gland. Our study aimed to investigate the correlation between maternal serum leptin concentration during the third trimester of pregnancy and newborn screening-TSH levels. Methods: This prospective cross-sectional study was conducted in obstetrics and gynaecology clinics of a state hospital between June and August 2013. Maternal venous blood samples were collected from 270 healthy pregnant women in the third trimester just before delivery. Measurements of maternal fT3, fT4, TSH, anti-thyroid peroxidase (TPO), and anti-thyroglobulin (anti-Tg) antibodies from serum samples were performed by chemiluminescence immunoassay. Maternal serum leptin levels were determined by ELISA. Dried capillary blood spots were used to measure newborn TSH levels. Results: Subjects were divided into two groups according to the neonatal TSH levels using a cut-point of 5.5 mIU/L. Median maternal serum leptin levels were significantly higher in newborns whose TSH levels were higher than >5.5 mIU/L [13.2 µg/L (1.3 - 46.5) vs 19.7 µg/L (2.4 - 48.5), p<0.05]. Serum leptin levels showed a negative correlation with maternal fT4 (r=0.32, p<0.05), fT3 (r=0.23, p<0.05), and a positive correlation with BMI (r=0.30, p<0.05). Conclusions: Our results suggest that high leptin levels in the third trimester of pregnancy influence maternal thyroid functions and might cause an increase in newborn TSH levels. Detection of high maternal serum leptin levels may be a reason for subclinical hypothyroidism.

An Assessment of HbA1c in Diabetes Mellitus and Pre-diabetes Diagnosis: a Multi-centered Data Mining Study.

HbA1c test has been widely used to evaluate glycemic control in patients with diabetes. However, there are controversial results regarding the value of HbA1c in the diagnosis of diabetes mellitus (DM). The present study investigates the diagnostic effectiveness of HbA1c in a large patient group. The oral glucose tolerance test and HbA1c results of 6551 patients (4704 healthy, 1345 pre-diabetes, 502 DM) in 12 different medical centers in Turkey between 2010 and 2016 were examined to understand the effectiveness of HbA1c in the diagnosis of DM. Different Roche systems were used for measuring HbA1c via the immunoturbidimetric method. The DM ROC curves revealed the diagnostic sensitivity, specificity, and AUC of 74.5%, 87.1%, and 0.866 (CI 95% 0.858-0.875), respectively, for HbA1c (at the cut-off 41 mmol/mol, 5.9%). For HbA1c at the universal diagnostic decision value of 48 mmol/mol (6.5%), the sensitivity and specificity were determined as 32.4% and 99.9%, respectively. The ROC curves for fasting plasma glucose (FPG) revealed the diagnostic sensitivity, specificity, and AUC of 71.3%, 85.3%, and 0.853 (CI 95% 0.844-0.861), respectively. However, the ROC curve results for pre-diabetes (HbA1c at the cut-off value of 39 mmol/mol, 5.7%) revealed the diagnostic sensitivity, specificity, and AUC of 45.7%, 76.4%, and 0.641, respectively. Furthermore, it was shown that the changes in HbA1c values due to gender and age had no clinical effect on the diagnosis. According to our results, it remains challenging to suggest HbA1c measurements can have a significant contribution to the FPG measurements. It was found that the sensitivity is specifically low in the assessment of the pre-diabetes data. Additionally, considering the problems associated with Hb1Ac measurements, further studies conducted in different regions by using different methods are required.

I405V and TaqIB polymorphisms of the cholesteryl ester transfer protein and their relation to serum lipid and lipoprotein levels in a Turkish population.

Cholesteryl ester transfer protein (CETP) plays a central role in high-density lipoprotein (HDL) metabolism. Genetic polymorphisms of the CETP gene can influence levels of serum lipoproteins. It has been reported that mean HDL-cholesterol (HDL-C) concentrations are low in Turkish population. Thus, we investigated the frequencies of the common I405V and TaqIB polymorphisms of the CETP gene and their relation to serum lipid and lipoprotein levels in a Turkish population. The variant allele frequencies of I405V and TaqIB polymorphisms of the CETP gene were found to be 0.38 and 0.46, respectively and similar to some of the European populations. Subjects for the VV genotype of I405V polymorphism had higher HDL-C levels than did II subjects. The covariance analysis showed that gender and triglyceride (TG) levels have an effect on the association of HDL-C and I405V polymorphism. In conclusion, our results indicate that I405V polymorphism may affect the HDL-C levels in Turkish population. The association of this polymorphism and HDL-C levels could be modified by other factors, such as gender and TG levels.

Single nucleotide polymorphisms in base-excision repair genes hOGG1, APE1 and XRCC1 do not alter risk of Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder with a poorly understood etiology. There is considerable evidence that oxidative stress occurs in AD and increased DNA damage has been found in brain tissues and leukocytes of AD patients. Base excision repair (BER) is the major pathway responsible for removing oxidative DNA damage. Polymorphisms in DNA-repair genes have been associated with the increased risk of several age-related disorders including various types of cancer and could also be related to the etiology of AD. We conducted a case-control study including 91 patients with AD and age- and sex-matched 93 control subjects to examine the role of single nucleotide polymorphisms of BER genes, hOGG1 (Ser326Cys), APE1 (Asp148Glu) and XRCC1 (Arg280His and Arg399Gln) as a risk factor for AD. The frequencies of the hOGG1-Ser326Cys, APE1-Asp148Glu and XRCC1-Arg280His and XRCC1-Arg399Gln variant alleles in our control group were 0.23, 0.31, 0.10 and 0.33, respectively. No significant association was observed between the variant alleles of hOGG1-Ser326Cys (OR=1.32, 95% CI=0.83-2.11), APE1-Asp148Glu (OR=1.08, 95% CI=0.70-1.68), XRCC1-Arg280His (OR=0.53, 95% CI=0.24-1.14) and XRCC1-Arg399Gln (OR=1.05, 95% CI=0.68-1.63) and AD. Our results suggest that the polymorphic variants of these BER genes are not independent risk factors for AD.

Effect of taurine treatment on pro-oxidant-antioxidant balance in livers and brains of old rats.

The effect of taurine treatment on antioxidant defense in liver and brain tissues of old rats was investigated. Endogenous malondialdehyde (MDA) and diene conjugate (DC), ascorbic acid (AA)- and NADPH-induced lipid peroxide levels as well as non-enzymatic (glutathione--GSH, vitamin E and vitamin C) and enzymatic antioxidants (superoxide dismutase, glutathione peroxidase and glutathione transferase) were determined in livers and brains of young (5 months), old (22 months), and taurine-treated old rats. Taurine (2%, w/v; in drinking water) was administered to old rats for 6 weeks. Taurine levels decreased in the liver and brain of old rats compared to young rats.MDA and DC levels increased, GSH levels decreased, but induced lipid peroxidation remained unchanged in livers of aged rats. Oxidative stress parameters did not change in brains of aged rats. Taurine treatment resulted in significant increases in taurine levels, decreases in MDA and DC levels and increases in GSH levels in livers of old rats. Taurine treatment also increased brain taurine levels. However, no significant changes were detected in lipid peroxidation and antioxidant system in brains of old rats following taurine treatment. Accordingly, in old rats the liver seems more susceptible to age-related lipid peroxidation increases and taurine level changes than the brain. Thus, taurine supplementation seems to be useful for decreasing hepatic oxidative stress in aging.

Nitrotyrosine formation and heme oxygenase-1 expression in endotoxemic cirrhotic rats.

BACKGROUND: Endotoxemia increases hepatic toxicity and mortality in cirrhosis. Because the mechanism of augmented hepatotoxicity in endotoxemic cirrhotic rats is still unclear, we wanted to investigate whether oxidative and nitrosative stress play a causative role in lipopolysaccharide (LPS)-treated cirrhotic rats. METHODS: Liver cirrhosis was produced by the administration of thioacetamide (0.3 g/L of tap water) for a period of 3 months in rats. At the end of this period, cirrhotic rats were sacrificed 6 h after LPS injection (5 mg/kg, intraperitoneally). Serum transaminase activities, plasma total nitrite and nitrotyrosine (NT) levels as well as hepatic lipid peroxides, NT formation and heme oxygenase 1 (HO-1) expression were determined. RESULTS: LPS administration to cirrhotic rats caused further increases in serum transaminase activities, and plasma total nitrite and NT levels as well as hepatic lipid peroxide levels as compared to cirrhotic rats. Hepatic NT formation and HO-1 expression were also found to be increased in LPS-injected cirrhotic rats. CONCLUSIONS: Our results indicate that increased oxidative and nitrosative stress may have a synergistic effect in LPS-augmented hepatotoxicity in cirrhotic rats.

Polymorphisms in the DNA repair genes XPD (ERCC2) and XPF (ERCC4) are not associated with sporadic late-onset Alzheimer's disease.

Nucleotide excision repair (NER) is the most versatile mechanism of DNA repair, recognizing and dealing a variety of helix-distorting lesions. Xeroderma pigmentosum group D (XPD) and group F (XPF) are essential participants in NER pathway. There is evidence that two common polymorphisms of XPD gene (g.22541C>A; exon 6 and g.35931A>C; Lys>Gln; exon 23) may be associated with differential DNA repair activities. Alzheimer's disease (AD) is characterized by progressive neuronal loss correlated in time with the symptoms of disease considered. Although deficient DNA repair was proposed in the etiology of AD by several researchers, polymorphisms of DNA repair genes have not been studied in AD yet. We conducted a case-control study including 97 patients with AD and age- and sex-matched 101 control subjects to examine the role of genetic polymorphisms of XPD and XPF (g.30028T>C; exon 11) as a risk factor for AD. The frequencies of the XPD/exon 6, XPD/exon 23, and XPF/exon 11 variant alleles in our control group were 0.41, 0.35, and 0.35, respectively. No significant association was observed between the variant alleles of XPD/exon 6 (OR=0.94, 95% CI=0.63-1.41), XPD/exon 23 (OR=1.24, 95% CI=0.82-1.86) and XPF/exon 11 (OR=1.08, 95% CI=0.72-1.64) and AD. Our results suggest that the polymorphic variants of these NER genes do not contribute to the risk of developing AD.

Effects of carnosine on prooxidant-antioxidant status in heart tissue, plasma and erythrocytes of rats with isoproterenol-induced myocardial infarction.

Rats were injected with isoproterenol (ISO; 110 mg/kg, ip, 2 doses, 24 h interval) to induce acute myocardial infarction (AMI) and were sacrificed 6 and 24 h after the last ISO injection. The heart tissue, plasma and erythrocytes of these rats were evaluated for cardiac markers and oxidative stress parameters. Levels of cardiac troponin T (cTnT) and the activities of creatine kinase (CK), lactate dehydrogenase (LDH), and aspartate aminotransferase (AST) in plasma were increased 6 and 24 h after ISO treatment. The levels of malondialdehyde (MDA), diene conjugate (DC), and protein carbonyl (PC) were increased in heart tissue and plasma, while levels of erythrocyte MDA and glutathione (GSH) and plasma ferric reducing antioxidant power (FRAP) were also increased. However, GSH levels and the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) decreased in heart tissue of rats with AMI. We also investigated the effects of carnosine (CAR) treatment on these parameters 24 h after the last ISO injection. CAR (250 mg/kg/day; ip) treatments were carried out either 10 days before ISO injection or 2 days concomitant with ISO. Pretreatment with CAR decreased plasma LDH and AST activities and ameliorated cardiac histopathological changes in ISO-treated rats. Cardiac MDA, DC and PC levels decreased, but GSH levels and SOD and GSH-Px activities increased. However, the increases in plasma MDA and PC levels as well as erythrocyte H(2)O(2)-induced MDA and GSH levels did not change due to CAR pretreatment. In conclusion, our findings indicate that CAR pretreatment may have protective effects on ISO-induced cardiac toxicity by decreasing oxidative stress.

Spectral effect: each population must have its own normal midnight salivary cortisol reference values determined.

INTRODUCTION: The mesurement of midnight salivary cortisol provides the most sensitive method for screening of Cushing's sendrome. However the clinical significance of spectral error is the requirement for determination of normal reference values in each population for each test, which will be used as the diagnostic method. Salivary cortisol levels may be affected by individual factors such as nutrition, sleep, medication, activity, and gender. Being a non-invasive method, midnight salivary cortisol (MSC) has been used as a valuable indicator of free plasma cortisol. MATERIAL AND METHODS: Midnight salivary cortisol was assessed in randomly selected 100 Turkish patents who underwent to a detailed physical examination. Saliva samples were collected at 00:00 to plastic tubes with the help of plastic pipettes, without brushing their teeth, but after rinsing their mouth. Salivary cortisol was measured with luminescense immunoassay kit. Differences and correlations were analysed. RESULTS: The mean midnight salivary cortisol of the healthy population was 0.21 ±0.03 µg/dl. Body mass index, age, sex, smoking, exercise, educational status alcohol, had no effect on the MSC. CONCLUSIONS: Consequently, normal salivary cortisol reference ranges must be used for different assays and different populations in order to evaluate more accurately pituitary-adrenal axis pathology in clinical practice.