Enantioseparation of Mandelic Acid Enantiomers With Magnetic Nano‐Sorbent Modified by a Chiral Selector

In this study, R(+)‐α‐methylbenzylamine‐modified magnetic chiral sorbent was synthesized and assessed as a new enantioselective solid phase sorbent for separation of mandelic acid enantiomers from aqueous solutions. The chemical structures and magnetic properties of the new sorbent were characterized by vibrating sample magnetometry, transmission electron microscopy, Fourier transform infrared spectroscopy, and dynamic light scattering. The effects of different variables such as the initial concentration of racemic mandelic acid, dosage of sorbent, and contact time upon sorption characteristics of mandelic acid enantiomers on magnetic chiral sorbent were investigated. The sorption of mandelic acid enantiomers followed a pseudo‐second‐order reaction and equilibrium experiments were well fitted to a Langmuir isotherm model. The maximum adsorption capacity of racemic mandelic acid on to the magnetic chiral sorbent was found to be 405 mg g^?1. The magnetic chiral sorbent has a greater affinity for (S)‐(+)‐mandelic acid compared to (R)‐(?)‐mandelic acid. The optimum resolution was achieved with 10 mL 30 mM of racemic mandelic acid and 110 mg of magnetic chiral sorbent. The best percent enantiomeric excess values (up to 64%) were obtained by use of a chiralpak AD‐H column. Chirality 27:835–842, 2015. © 2015 Wiley Periodicals, Inc.     

A retrospective controlled study of thiol disulfide homeostasis as a novel marker in Crimean Congo hemorrhagic fever

Objectives: Crimean Congo hemorrhagic fever (CCHF) is the second most common hemorrhagic fever worldwide. This study aimed to evaluate the oxidant–antioxidant balance of patients with CCHF by detecting dynamic thiol disulfide homeostasis (TDH), which is a novel oxidative stress marker, and other molecules, including paraoxonase (PON), arylesterase (ARES), ceruloplasmin (CLP), myeloperoxidase (MPO), and catalase.

Methods: This retrospective, cross-sectional, controlled study, which involved patients with CCHF and healthy volunteers, measured dynamic TDH using a novel automated method developed by Erel.

Results: We recruited 69 adult patients with CCHF (31 females, 38 males, median age 46 years). The case fatality rate was 1.49% (1/69). Increased disulfide/native thiol and disulfide/total thiol ratios, decreased total antioxidant status (TAS), and increased total oxidant status (TOS) were found in patients with CCHF. TAS, PON, and ARES values were found to be positively correlated with both native and total thiol levels, whereas TOS and CLP were negatively correlated with both, at a significant level. MPO activity was similar in both groups.

Discussion: This is the first study in the literature to evaluate dynamic TDH in CCHF. TDH shifts to the oxidative side in patients with CCHF, leading to an increase in TOS.     

Whole genome sequencing of Turkish genomes reveals functional private alleles and impact of genetic interactions with Europe,Asia and Africa

Background

Turkey is a crossroads of major population movements throughout history and has been a hotspot of cultural interactions. Several studies have investigated the complex population history of Turkey through a limited set of genetic markers. However, to date, there have been no studies to assess the genetic variation at the whole genome level using whole genome sequencing. Here, we present whole genome sequences of 16 Turkish individuals resequenced at high coverage (32 × -48×).

Results

We show that the genetic variation of the contemporary Turkish population clusters with South European populations, as expected, but also shows signatures of relatively recent contribution from ancestral East Asian populations. In addition, we document a significant enrichment of non-synonymous private alleles, consistent with recent observations in European populations. A number of variants associated with skin color and total cholesterol levels show frequency differentiation between the Turkish populations and European populations. Furthermore, we have analyzed the 17q21.31 inversion polymorphism region (MAPT locus) and found increased allele frequency of 31.25% for H1/H2 inversion polymorphism when compared to European populations that show about 25% of allele frequency.

Conclusion

This study provides the first map of common genetic variation from 16 western Asian individuals and thus helps fill an important geographical gap in analyzing natural human variation and human migration. Our data will help develop population-specific experimental designs for studies investigating disease associations and demographic history in Turkey.

Electronic supplementary material

The online version of this article (doi:10.1186/1471-2164-15-963) contains supplementary material, which is available to authorized users.     

The Antioxidant Vitamin E Modulates Amyloid β-Peptide-Induced Creatine Kinase Activity Inhibition and Increased Protein Oxidation: Implications for the Free Radical Hypothesis of Alzheimer's Disease

Amyloid -peptide (A), the main constituent of senile plaques in Alzheimer's disease (AD) brain, is hypothesized to be a key factor in the neurodegeneration seen in AD. Recently it has been shown by us and others that the neurotoxicity of A occurs in conjunction with free radical oxidative stress associated with the peptide. A(1–40) and several other fragments of the A sequence are associated with free radicals in solution that are detectable using electron paramagnetic resonance spectroscopy. These free radicals were shown to attack brain cell membranes, initiate lipid peroxidation, increase Ca²⁺ influx and damage membrane and cytosolic proteins. In AD brain obtained under rapid autopsy protocol, the activity of the oxidatively-sensitive enzyme creatine kinase was shown to be significantly reduced. We reasoned that A-associated free radical-induced modification of creatine kinase activity and other markers of cellular damage might be modulated by free radical scavengers. Accordingly, this study demonstrates that vitamin E can modulate A(25–35)-induced oxidative damage to creatine kinase and cellular proteins in cultured embryonic hippocampal neurons. These results, consistent with the hypothesis of free radical-mediated A toxicity in AD, are discussed with deference to potential free radical scavengers as therapeutic agents for slowing the progression of AD.     

Analysis of the Influences of Short-Term Levosimendan Exposure on Oxidant/Antioxidant Status and Trace-Element Levels in the Physiological Status of the Thoracic Aorta of Rats

The objective of this study was to evaluate the effect of levosimendan (chemical formula C₁₄H₁₂N₆O) exposure on oxidant/antioxidant status and trace-element levels in the thoracic aorta of rats. Eighteen male Wistar albino rats were randomly divided into two groups of eight animals each. Group 1 was not exposed to levosimendan and served as a control. Levosimendan (12???g/kg) diluted in 10 ml 0.5?% dextrose was administered intraperitoneally to group 2. Animals of both groups were killed after 3?days, and their thoracic aortae were harvested for determination of changes in tissue oxidant/antioxidant status and trace-element levels. The animals in both groups were killed 72?h after levosimendan exposure, and thoracic aortae were harvested for determination of the lipid peroxidation product MDA and antioxidant GSH levels and the activities of antioxidant enzymes such as SOD, GSH-Px and CAT. It was found that MDA, GSH and CAT enzyme levels increased in thoracic aortae of rats after levosimendan administration. SOD and CA enzyme activities and the level of antioxidant GSH decreased in thoracic aortae of rats after levosimendan treatment. Pb, Cd and Fe levels of thoracic aortae were significantly higher (P?<?0.001) and Mg, Mn, Zn and Cu were significantly lower (P?<?0.001) in the levosimendan group compared to the control group. These results suggest that short-term levosimendan treatment caused an increase in free radical production and a decrease in antioxidant enzyme activity in thoracic aortae of levosimendan-treated rats. It also causes a decrease or increase in many mineral levels of the thoracic aorta, which is an undesirable condition for normal pharmacological function.     

Takayasu's arteritis is associated with HLA-B*52, but not with HLA-B*51, in Turkey

Introduction

HLA-B*51 and HLA-B*52 are two close human leukocyte antigen (HLA) allele groups with minor amino acid differences. However, they are associated with two different vasculitides (HLA-B*51 in Behçet's disease and HLA-B*52 in Takayasu's arteritis (TAK)) and with major clinical and immunological differences. In this study, we aimed to screen a large cohort of TAK patients from Turkey for the presence of HLA-B*51 and HLA-B*52 as susceptibility and severity factors.

Methods

TAK patients (n = 330) followed at a total of 15 centers were included in the study. The mean age of the patients was 37.8 years, and 86% were women. DNA samples from the patients and healthy controls (HC; n = 210) were isolated, and the presence of HLA-B*51 or HLA-B*52 was screened for by using PCR with sequence-specific primers.

Results

We found a significant association of HLA-B*52 with TAK (20.9% vs HC = 6.7%, P = 0.000, OR = 3.7, 95% CI = 2.02 to 6.77). The distribution of HLA-B*51 did not differ between TAK patients and HCs (22.7% vs 24.8%, OR = 0.9, 95% CI = 0.60 to 1.34). The presence of HLA-B*52 decreased in late-onset patients (> 40 years of age; 12.0%, P = 0.024, OR = 0.43, 95% CI = 0.20 to 0.91). Patients with angiographic type I disease with limited aortic involvement also had a lower presence of HLA-B*52 compared to those with all other disease subtypes (13.1% vs 26%, P = 0.005, OR = 0.43, 95% CI = 0.23 to 0.78).

Conclusions

In this study, the previously reported association of TAK with HLA-B*52 in other populations was confirmed in patients from Turkey. The functional relevance of HLA-B*52 in TAK pathogenesis needs to be explored further.     

Ghrelin and adipokines as circulating markers of disease activity in patients with Takayasu arteritis

Introduction

The current markers of disease activity in Takayasu arteritis (TA) are insufficient for proper assessment. We investigated circulating levels of unacylated and acylated ghrelin, leptin and adiponectin and their relationships with disease activity in patients with TA.

Methods

This study included 31 patients with TA and 32 sex-, age- and body mass index-matched healthy controls. Disease activity was assessed in TA patients using various tools, including Kerr''s criteria, disease extent index-Takayasu, physician''s global assessment, radiological parameters, and laboratory markers. Plasma unacylated and acylated ghrelin, and serum leptin and adiponectin levels were measured using an enzyme-linked immunosorbent assay.

Results

Unacylated and acylated ghrelin levels were found to be significantly lower in TA patients than that in healthy controls. Patients with active disease had lower unacylated ghrelin levels than those with inactive disease and had lower acylated ghrelin levels than healthy controls. Ghrelin levels were negatively correlated with various parameters of disease activity. The leptin/ghrelin ratio was significantly higher in TA patients than controls. It was positively correlated with disease activity. There was a positive correlation between unacylated and acylated ghrelin and a negative correlation between leptin and ghrelin. There was no statistical difference in adiponectin levels between TA patients and controls. The radiological activity markers were positively correlated with other parameters of disease activity.

Conclusions

This study suggests that plasma unacylated and acylated ghrelin levels may be useful in monitoring disease activity and planning treatment strategies for patients with TA. The serum leptin level and leptin/ghrelin ratio may also be used to help assess the disease activity.     

Effects of shock waves on oxidative stress and some trace element levels of rat liver and diaphragm muscles

This study was designed to investigate whether the short-term extracorporeal shockwave lithotripsy (ESWL) exposure to kidney produces an oxidative stress and a change in some trace element levels in liver and diaphragm muscles of rats. Twelve male Wistar albino rats were divided randomly into two groups, each consisting of six rats. The animals in the first group did not receive any treatment and served as control group. The right-side kidneys of animals in group 2 were treated with two-thousand 18 kV shock waves while anesthetized with 50 mg kg(-1) ketamine. The localization of the right kidney was achieved after contrast medium injection through a tail vein under fluoroscopy control. The animals were killed 72 h after the ESWL treatment, and liver and diaphragm muscles were harvested for the determination of tissue oxidative stress and trace element levels. Although the malondialdehyde level increased, superoxide dismutase and glutathione peroxidase enzyme activities decreased in the livers and diaphragm muscles of ESWL-treated rats. Although glutathione level increased in liver, it decreased in diaphragm muscles of ESWL-treated animals. Fe, Mg and Mn levels decreased, and Cu and Pb levels increased in the livers of ESWL-treated animals. Fe and Cu levels increased, and Mg, Pb, Mn and Zn levels decreased in the diaphragm muscles of ESWL-treated animals. It also causes a decrease or increase in many mineral levels in liver and diaphragm muscles, which is an undesirable condition for the normal physiological function of tissues.     

Evaluation of cryopreserved stallion semen from Tori and Estonian breeds using CASA and flow cytometry

Methods to evaluate the quality of frozen-thawed stallion semen are still needed, particularly those considering the sperm function. The present study evaluated sperm motility, membrane and acrosome integrity and the capacitation status of frozen-thawed spermatozoa from seven Tori and six Estonian breed stallions by way of computer assisted sperm analysis (CASA), a triple fluorophore stain combination and Merocyanine 540, respectively, the latter ones using flow cytometry. Two ejaculates from each stallion were cryopreserved using the Hannover method in 0.5 ml plastic straws. Two straws per ejaculate per stallion were thawed at 37 degrees C for 30s. Motility was analysed with CASA immediately after thawing, while for flow cytometry spermatozoa were cleansed by 70:40% Percoll discontinuous density gradient separation before analysed for sperm viability, acrosome integrity (stained with SNARF, PI and FITC-PSA) and capacitation status (stained with Merocyanine 540/Yo-Pro-1). Results (as least square means) were as follows: the motility of frozen-thawed semen was 43.4% for Tori stallions and 42.3% for Estonian stallions (P>0.05). After Percoll separation 79.3% of the spermatozoa from Tori stallions had intact acrosomes and 1.7% of them showed early signs of capacitation. The same parameters for Estonian stallions were 84.5 and 2.3%, respectively. There were no statistically significant differences between breeds or ejaculates within breed for any evaluated parameter. We conclude that triple staining and flow cytometry are valuable techniques to evaluate frozen-thawed stallion spermatozoa, and that no differences in quality of frozen semen were registered between Tori and Estonian breed stallions, allowing implementation of this technology in the Estonian horse population.