Evaluation of maternal serum thiol and ischemia-modified albumin levels in cases of placenta previa: A case-control study in a tertiary center.

AIM: We aim to compare the maternal serum thiol and ischemia-modified albumin (IMA) levels between pregnant women with placenta previa and those with uncomplicated pregnancies and to determine whether changes in these levels were useful in predicting cases of abnormally invasive placenta (AIP). METHODS: Fifty-five pregnant women diagnosed with placenta previa according to the diagnostic criteria (case group) were compared to 100 women with uncomplicated pregnancies of similar demographic characteristics (control group). The patients with placenta previa were further divided into two subgroups: AIP (n = 20) and placenta previa without invasion (n = 35). The maternal serum native thiol, total thiol, disulfide, and IMA levels of the groups were evaluated. RESULTS: The native thiol, total thiol, and IMA values were significantly lower in the case group than in the control group (p < 0.001). The disulfide values were similar between the study and control groups (p = 0.488). When the AIP and placenta previa without invasion groups were compared, the levels of native thiol, total thiol, disulfide, and IMA were similar (p > 0.05). CONCLUSIONS: Maternal serum thiol and IMA levels were lower in placenta previa cases compared to the control group. However, these parameters were not useful in predicting AIP cases.

Evaluation of IL-10, IFN-γ, and thiol-disulfide homeostasis in patients with drug-resistant epilepsy.

AIM: This study compared dynamic thiol-disulfide homeostasis (an oxidative stress marker), anti-inflammatory interleukin-10 (IL-10) levels, and proinflammatory interferon gamma (IFN-γ) levels in drug-resistant epilepsy patients with those in patients with well-controlled epilepsy and healthy controls. METHOD: This prospective cross-sectional study enrolled 89 people: 27 with drug-resistant epilepsy, 30 with well-controlled epilepsy, and 32 healthy controls matched in demographic characteristics. RESULTS: The mean serum IL-10 levels were significantly lower and the mean serum IFN-γ levels significantly higher in the drug-resistant epilepsy patients compared to the well-controlled epilepsy and healthy control groups. The mean serum native thiol (SH) and total thiol (TT) levels were significantly lower, and the disulfide (SS) levels were significantly higher in the drug-resistant group than in the other two groups. CONCLUSIONS: The significant differences in thiol-disulfide homeostasis and IL-10 and IFN-γ levels in the drug-resistant epilepsy group suggest that these markers indicate a poor prognosis in epilepsy.

An Evaluation of Oxidative Stress With Thiol/Disulfide Homeostasis in Patients With Persistent Allergic Rhinitis.

BACKGROUND: We evaluated the efficacy of medical treatment on thiol-disulfide balance despite ongoing allergic stimulation. METHODS: The research design was a prospective observational study that included 35 persistent allergic rhinitis (AR) patients. All patients who were diagnosed with persistent AR were included. A skin prick test was applied to all patients, and the Sino-nasal Outcome Test-22 was used to evaluate sinonasal symptoms. Thiol/disulfide homeostasis balance parameters were measured using a novel automatic and spectrophotometric method and compared statistically. Serum total thiol (TT), native thiol (SH), disulphide (SS), disulphide/native thiol (SS/SH), disulphide/total thiol (SS/TT), and native thiol/total thiol (SH/TT) ratios were measured after the second month of the treatment. RESULTS: The 35 patients included 20 (58%) females and 15 (42%) males. The mean age of the patients was 33.17 ± 9.9 years. Disulphide, SS/SH, and SS/TT ratios decreased significantly after the treatment (P < .05), while SH and SH/TT increased significantly (P < .05). The mean SH measurement increased significantly in the second month (P = .001), but TT mean measurements showed no difference after the treatment (P = .058). The mean SS measurements, on the other hand, decreased significantly in the second month (P = .003). CONCLUSION: Thiol/disulfide homeostasis may be used as a marker to evaluate the efficacy of persistent AR treatments. After the treatment, the increase in SH levels suggested the decrease in oxidative stress, even though allergen exposure continued.

Dynamic thiol/disulphide homeostasis and ischemic modified albumin levels in isolated oligohydramnios.

OBJECTIVE: Oligohydramnios is defined as amniotic fluid index in ultrasonographic measurement is less than 5 percentile according to gestational age, the amniotic fluid volume is ≤ 5 cm, or if the single deepest dial is < 2 cm. The condition of oligohydramnios that not with fetal structural/chromosomal abnormalities, intrauterine growth retardation, intrauterine infection and maternal disease is described as isolated oligohydramnios (IO). The aim of this study is to examine whether oxidative stress and reactive oxygen species (ROS) have a place in the pathophysiology of IO. MATERIALS AND METHODS: In this prospective case-control study, a total of 126 participants were included. The patient group consisted of 65 patients who were diagnosed IO, and the control group consisted of 61 healthy normal pregnants. Native thiol (-SH), total thiol (-SH + -SS), dynamic disulfide (-SS), IMA values from maternal serum were measured and compared between groups. RESULTS: Maternal serum -SH and -SH + -SS values were significantly lower in the IO group than in the control group (409.47 ± 55.36 µmol/L vs. 437.40 ± 48.68 µmol/L, p = 0.03 and 457.40 ± 63.01 µmol/L vs. 484.59 ± 52.75 µmol/L, p = 0.01). In the IO group when -SS/-SH and -SS/-SH + -SS ratio was found to be statistically significantly higher than control group (5.84 ± 1.1 vs 5.41 ± 0.71, p = 0.01 and 5.2 ± 0.88 vs 4.8 ± 0.58, p = 0.01), -SH/-SH + -SS ratio was significantly lower (89.56 ± 1.7 vs 90.24 ± 1.16, p = 0.01). There was no significant difference in terms of -SS value (p = 0.66). IMA value was significantly higher in the IO group than control group (0.76 ± 0.10 ABSU vs 0.68 ± 0.06, p < 0.01). It is seen as a result of ROC analysis that -SH, -SH + -SS, -SS/-SH, -SS/-SH + -SS, -SH/-SH + -SS and IMA values have a diagnostic value for IO (p < 0.05). CONCLUSION: The thiol/disulfide balance shifted towards oxidative stress in IO compared to control group. So oxidative stress and ROS have a place in the pathophysiology of IO.

Intermediate Cu(II)-Thiolate Species in the Reduction of Cu(II)GHK by Glutathione: A Handy Chelate for Biological Cu(II) Reduction.

Gly-His-Lys (GHK) is a tripeptide present in the human bloodstream that exhibits a number of biological functions. Its activity is attributed to the copper-complexed form, Cu(II)GHK. Little is known, however, about the molecular aspects of the mechanism of its action. Here, we examined the reaction of Cu(II)GHK with reduced glutathione (GSH), which is the strongest reductant naturally occurring in human plasma. Spectroscopic techniques (UV-vis, CD, EPR, and NMR) and cyclic voltammetry helped unravel the reaction mechanism. The impact of temperature, GSH concentration, oxygen access, and the presence of ternary ligands on the reaction were explored. The transient GSH-Cu(II)GHK complex was found to be an important reaction intermediate. The kinetic and redox properties of this complex, including tuning of the reduction rate by ternary ligands, suggest that it may provide a missing link in copper trafficking as a precursor of Cu(I) ions, for example, for their acquisition by the CTR1 cellular copper transporter.

Se-modified gold nanorods for enhancing the efficiency of photothermal therapy: avoiding the off-target problem induced by biothiols.

Tumor-targeting gold nanorods (AuNRs) assembled through Au-S bonds have been widely used for photothermal therapy (PTT) via intravenous injection. However, with extended in vivo circulation times, biothiols can replace some S-modified targeting ligands on the surface of the AuNRs, which lowers their targeting efficacy towards cancer cells, resulting in a non-ideal PTT effect. To address this problem, herein, we utilized Se-modified AuNRs to establish a dual functional nanoprobe (Casp-RGD-Se-AuNRs) for improving the therapeutic effect and real-time monitoring of Caspase-9 levels to indicate the degree of cell apoptosis. The experiments demonstrated that the Casp-RGD-Se-AuNRs are better at avoiding interference from biothiols than the S-modified nanoprobe (Casp-RGD-S-AuNRs) for extended blood-circulation times after intravenous injection, significantly improving the PTT efficacy via more effectively targeting cancer cells. Simultaneously, the change of Caspase-9 levels visually shows the degree of apoptosis. Moreover, an in vivo study showed that, compared with the S-modified nanoprobe, the Se-modified nanoprobe exhibits a higher delivery efficiency to the tumor region after intravenous injection (accumulation in the tumor increased by 87%) and a better anticancer efficacy under NIR light irradiation (the tumor inhibition rate increased 6-fold). This work provides a valuable strategy to overcome the off-target problem, and new ideas for avoiding interference by biomolecules during blood circulation.

Oxidative stress biomarkers in fetal growth restriction with and without preeclampsia.

INTRODUCTION: Oxidative stress as observed in fetal growth restriction (FGR) and preeclampsia (PE) can be identified by decreased levels of systemic free thiols (FT) and increased levels of plasma ischemia-modified albumin (IMA), which may serve as biomarkers in maternal blood for pregnancy complications. We evaluate the performance of oxidative stress-associated potential biomarkers for FGR and PE, and their relationship with clinical characteristics. METHODS: A prospective clinical pilot study was performed in healthy controls and women with pregnancies complicated by severe FGR with or without PE. Blood samples were taken directly after inclusion and analyzed for FT; IMA; soluble FMS-like tyrosine kinase-1 (sFlt-1); placenta growth factor (PlGF); and biomarkers like leptin and soluble receptors for advanced glycation end products (sRAGE). Placentas were examined microscopically. Descriptive statistics and receiver operating characteristics statistics were performed. RESULTS: Mothers with both severe FGR and PE had significantly reduced FT levels (p < 0.001) and PlGF levels (p < 0.001), and increased levels of plasma IMA (p < 0.05), sFlt (p < 0.001), leptin (p < 0.05) and sRAGE (p < 0.01) compared to women with FGR only. Systemic FT levels were significantly inversely associated with blood pressure (p < 0.01) and plasma IMA (p < 0.001), leptin (p = 0.01) and sRAGE (p < 0.001). Systemic FT and leptin showed significant discriminative ability to differentiate mothers with both FGR and PE from mothers with uncomplicated pregnancies or pregnancies complicated by FGR only. DISCUSSION: There is a significant discriminative capacity of FT, IMA, leptin and sRAGE that harbor potential as biomarkers of pregnancies complicated by combined FGR and PE.

Extracellular cystine influences human preadipocyte differentiation and correlates with fat mass in healthy adults.

Plasma cysteine is associated with human obesity, but it is unknown whether this is mediated by reduced, disulfide (cystine and mixed-disulfides) or protein-bound (bCys) fractions. We investigated which cysteine fractions are associated with adiposity in vivo and if a relevant fraction influences human adipogenesis in vitro. In the current study, plasma cysteine fractions were correlated with body fat mass in 35 adults. Strong positive correlations with fat mass were observed for cystine and mixed disulfides (r ≥ 0.61, P < 0.001), but not the quantitatively major form, bCys. Primary human preadipocytes were differentiated in media containing cystine concentrations varying from 10-50 µM, a range similar to that in plasma. Increasing extracellular cystine (10-50 µM) enhanced mRNA expression of PPARG2 (to sixfold), PPARG1, PLIN1, SCD1 and CDO1 (P = 0.042- < 0.001). Adipocyte lipid accumulation and lipid-droplet size showed dose-dependent increases from lowest to highest cystine concentrations (P < 0.001), and the malonedialdehyde/total antioxidant capacity increased, suggesting increased oxidative stress. In conclusion, increased cystine concentrations, within the physiological range, are positively associated with both fat mass in healthy adults and human adipogenic differentiation in vitro. The potential role of cystine as a modifiable factor regulating human adipocyte turnover and metabolism deserves further study.

A Dual-emitting Two-dimensional Nickel-based Metal-organic Framework Nanosheets: Eu3+/Ag+ Functionalization Synthesis and Ratiometric Sensing in Aqueous Solution.

Using two-dimensional (2D) nickel-based metal organic framework (Ni-MOF) nanosheets as a matrix, Eu3+ and Ag+ were incorporated to synthesize Ag/Eu@Ni-MOF with double luminescence centers of Eu3+ ion (615 nm) and organic ligand (524 nm). And a ratiometric luminescence sensor is constructed based on Ag/Eu@Ni-MOF for sensitive detection of biothiols in aqueous solutions. The dual-emissive fluorescence properties can be tuned by changing the amounts of Ag+ ions doping. The results of temperature and pH effects on the fluorescence of Ag/Eu@Ni-MOF indicates that the Ag/Eu@Ni-MOF is a temperature-sensitive material and the fluorescence of Ag/Eu@Ni-MOF can keep stable over a wide pH range. Due to the binding of -SH in cysteine (Cys) and glutathione (GSH) with Ag+, the ligand luminescence was significantly inhibited by weakening the Ag + influence on the energy transfer process in the MOFs. Therefore, ratiometric fluorescent sensing of biomolecular thiols was realized based on the dual-emission Ag/Eu@Ni-MOF. More importantly, the fluorescence color change can be observed with naked eyes to realize visual detection. The ratiometric fluorescent sensor exhibits high performance for Cys and GSH detection with a wide linear range of 5-250 µM and a relatively low detection limit of 0.20 µM and 0.17 µM, respectively. Furthermore, the biothiols content in human serum was determined with satisfactory results. It proves the Ni-MOF nanosheets can be used as a stable matrix for construction luminescent MOFs for the first time, and validate the great potential of Ag/Eu@Ni-MOF as a ratiometric fluorescent probe for point-of-care testing (POCT) in disease diagnosis.

Alteration of serum biomarkers in patients with hypertrophic cardiomyopathy with and without atrial fibrillation.

Aim: We sought to determine the relationship between presence of atrial fibrillation (AF) and serum biomarkers, including native thiol (antioxidant), disulphide/native thiol ratio, Hs-CRP and high-sensitivity Troponin-I (Hs-TnI) in hypertrophic cardiomyopathy (HCM). Materials & methods: We enrolled consecutive 121 HCM outpatients without AF and 40 HCM outpatients with AF. A 12-lead electrocardiogram, transthoracic echocardiography and 24/48-h ambulatory rhythm monitoring were performed for all patients. Fasting venous blood samples were taken from all study patients to measure serum thiol-disulphide homeostasis, Hs-CRP and Hs-TnI. Results: Serum-native thiol was lower and disulphide/native thiol ratio was more oxidized in HCM patients with AF (p < 0.001). Also, HCM patients with AF had higher Hs-TnI and Hs-CRP than no-AF HCM patients. Disulphide/native thiol ratio, serum-native thiol, age, NYHA functional class≥III, and advanced diastolic dysfunction were independently associated with the presence of AF in HCM. Conclusion: In addition to clinical and echocardiographic findings, oxidative stress is also associated with AF in HCM patients.

Elevated plasma free thiols are associated with early and one-year graft function in renal transplant recipients.

BACKGROUND: Reduced free thiols in plasma are indicative of oxidative stress, which is an important contributor to ischaemia-reperfusion injury (IRI) in kidney transplantation leading to kidney damage and possibly delayed graft function (DGF). In a post-hoc, exploratory analysis of the randomised controlled CONTEXT trial, we investigated whether higher (i.e. less oxidised) plasma levels of free thiols as a biomarker of reduced oxidative stress are associated with a better initial graft function or a higher GFR. METHODS: Free thiol levels were measured in plasma at baseline, 30 and 90 minutes after reperfusion of the kidney as well as at Day 1, Day 5 and twelve months after kidney transplantation in 217 patients from the CONTEXT study. Free thiol levels were compared to the kidney graft function measured as the estimated time to a 50% reduction in plasma creatinine (tCr50), the risk of DGF and measured GFR (mGFR) at Day 5 and twelve months after transplantation. RESULTS: Higher levels of free thiols at Day 1 and Day 5 are associated with higher mGFR at Day 5 (p<0.001, r2adj. = 0.16; p<0.001, r2adj. = 0.25), as well as with mGFR at twelve months (p<0.001, r2adj. = 0.20; p<0.001, r2adj. = 0.16). However, plasma levels of free thiols at 30 minutes and 90 minutes, but not Day 1, were significantly higher among patients experiencing DGF. CONCLUSION: Higher levels of plasma free thiols at Day 1 and Day 5, which are reflective of lower levels of oxidative stress, are associated with better early and late graft function in recipients of a kidney graft from deceased donors. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01395719.

Inhibition of an organophosphate-detoxifying bacterial phosphotriesterase by albumin and plasma thiol components.

The phosphotriesterase of the bacterium Brevundimonas diminuta (BdPTE) is a naturally occurring enzyme that catalyzes the hydrolysis of organophosphate (OP) nerve agents as well as pesticides and offers a potential treatment of corresponding intoxications. While BdPTE mutants with improved catalytic efficiencies against several OPs have been described, unexpectedly, less efficient breakdown of an OP was observed upon application in an animal model compared with in vitro measurements. Here, we describe detailed inhibition studies with the high-activity BdPTE mutant 10-2C3(C59M/C227A) by human plasma components, indicating that this enzyme is inhibited by serum albumin. The inhibitory activity is mediated by depletion of crucial zinc ions from the BdPTE active site, either via the known high-affinity zinc binding site of albumin or via chemical complex formation with its free thiol side chain at position Cys34. Albumin pre-charged with zinc ions or carrying a chemically blocked Cys34 side chain showed significantly reduced inhibitory activity; in fact, the combination of both measures completely abolished BdPTE inhibition. Consequently, the available zinc ion concentration in blood plays an important role for BdPTE activity in vivo and should be taken into account for therapeutic development and application of a catalytic OP scavenger.

Effects of antiviral drug therapy on dynamic thiol/disulphide homeostasis and nitric oxide levels in COVID-19 patients.

The novel coronavirus disease 2019 (COVID-19) has led to a serious global pandemic. Although an oxidative stress imbalance occurs in COVID-19 patients, the contributions of thiol/disulphide homeostasis and nitric oxide (NO) generation to the pathogenesis of COVID-19 have been poorly identified. Therefore, the aim of this study was to evaluate the effects of antiviral drug therapy on the serum dynamics of thiol/disulphide homeostasis and NO levels in COVID-19 patients. A total of 50 adult patients with COVID-19 and 43 sex-matched healthy control subjects were enrolled in this prospective study. Venous blood samples were collected immediately on admission to the hospital within 24 h after the diagnosis (pre-treatment) and at the 15th day of drug therapy (post-treatment). Serum native thiol and total thiol levels were measured, and the amounts of dynamic disulphide bonds and related ratios were calculated. The average pre-treatment total and native thiol levels were significantly lower than the post-treatment values (P < 0.001 for all). We observed no significant changes in disulphide levels or disulphide/total thiol, disulphide/native thiol, or native thiol/total thiol ratios between pre- and post-treatments. There was also a significant increase in serum NO levels in the pre-treatment values when compared to control (P < 0.001) and post-treatment measurements (P < 0.01). Our results strongly suggest that thiol/disulphide homeostasis and nitrosative stress can contribute to the pathogenesis of COVID-19. This study was the first to show that antiviral drug therapy can prevent the depletion in serum thiol levels and decrease serum NO levels in COVID-19 patients.

Redox index of Cys-thiol residues of serum apolipoprotein E and its diagnostic potential.

BACKGROUND: The redox modulation of Cys-thiol participates in various pathophysiological processes. We explored the proper index for estimating the redox status of Cys-thiol of serum apolipoprotein E (apoE), named "redox-IDX-apoE," which is necessary to understand the redox biology of age-related diseases. METHODS: The fractions of the reduced form (red-), reversible oxidized form (roxi-), and irreversibly oxidized form (oxi-) apoE in serum, obtained from the patients with no apparent disease (controls, n=192) and with atherosclerosis and type 2 diabetes (patients, n=16), were measured by a band-shift assay using a maleimide compound. Redox-IDX-apoE candidates were determined by calculating the values of these fractions and the total apoE concentration. RESULTS: Cys number of apoE significantly increased for the ratio of roxi-apoE to total-apoE (roxi/total) (E2/E3>E3/E3>E3/E4) but decreased for the ratios of red-apoE to roxi-apoE (red/roxi) and [red-apoE + oxi-apoE] to roxi-apoE ([red + oxi]/roxi) (E2/E3

Plasma thiol and disulphide levels and their relationship with left ventricular systolic functions: A propensity score matching analysis.

OBJECTIVE: Left ventricular (LV) systolic function measured through LV ejection fraction (LVEF) has prognostic implications in patients with cardiac and non-cardiac conditions. The balance of thiol and disulphide levels reflects oxidative status in the body. In this study, we aimed to investigate the relationship between plasma thiol and disulphide levels, and LVEF calculated by transthoracic echocardiography (TTE). METHODS: This retrospective study included 1,048 patients referred for TTE examination and biochemical analyses, including plasma thiol and disulphide levels. After the application of exclusion criteria, the remaining 611 patients were included in the statistical analysis. Patients were classified into two groups, namely normal LVEF (n-LVEF) (n=446) and low LVEF (l-LVEF) (n=165) according to a cut-off level of LVEF 50%. To reduce sample selection bias and adjust for the influence of differences in patient characteristics on LVEF and oxidative status, 1: 1 propensity score matching analysis was applied. RESULTS: Propensity score matching analysis yielded 125 patients in both groups with comparable demographics, medications, and blood parameters. Native thiol and total thiol levels were lower in l-LVEF patients than in n-LVEF patients (p<0.001 for both), whereas disulphide levels were higher in l-LVEF group (p=0.008). Native thiol (r=0.384, p<0.001), total thiol (r=0.35, p<0.001), and disulphide levels (r=-0.129, p=0.004) significantly correlated with LVEF. CONCLUSION: Plasma thiol levels decrease and disulphide levels increase suggesting the presence of oxidative stress in patients with l-LVEF. Significant correlation between oxidative stress and LVEF sheds light about the possible pathogenetic role of thiol and disulphide in heart failure.

Thiol-disulfide homeostasis and ischemia-modified albumin as a marker of oxidative stress in patients with sarcopenia.

AIM: Sarcopenia is characterized by progressive and generalized loss of skeletal muscle mass and strength. Chronic inflammatory conditions and increased oxidative stress are in the pathogenesis of sarcopenia. Our aim was to evaluate the relationship between sarcopenia and thiol-disulfide homeostasis and ischemia-modified albumin levels as an oxidative stress marker. METHODS: Patients aged ≥65 years were recruited in this study. Sarcopenia was diagnosed according to the European Working Group on Sarcopenia in Older People criterion. Total thiol, native thiol, disulfide and ischemia-modified albumin levels were measures according to clinical and laboratory features. Patients were divided into two groups according to their sarcopenia presence; thiol-disulfide homeostasis and ischemia-modified albumin levels were evaluated between these groups. RESULTS: Overall, 94 patients were analyzed. The mean age was 75.0 ± 6.71 years. A total of 39% of the patients were diagnosed as probable sarcopenia, 3.2% had sarcopenia, 6.4% had severe sarcopenia and 51.1% were diagnosed as normal. The levels of native thiol, total thiol, disulfide level and disulfide-native thiol, native thiol-total thiol and disulfide-total thiol ratios were similar in patients with sarcopenia when compared with the control group. In addition, there were no differences between albumin and ischemia-modified albumin levels. In univariate regression analysis, handgrip strength was found to be an independent predictor of native thiol and total thiol, and disulfide levels. CONCLUSION: This is the first study in the literature that evaluates the thiol-disulfide homeostasis and ischemia-modified albumin levels in sarcopenic older patients. Long-term studies are warranted to confirm the relationship between oxidative stress markers and sarcopenia. Geriatr Gerontol Int 2021; 21: 584-589.

The relationship between serum thiol levels and thiol/disulfide homeostasis in women with tubal ectopic pregnancy.

OBJECTIVE: The aim of this study was to investigate the thiol/disulfide homeostasis in tubal ectopic pregnancies in terms of early diagnosis of the disease. DESIGN: A prospective case-control study was carried out between June 2017-February 2018 in the Gynaecology Department of Umraniye Medical and Research Hospital. MATERIALS AND METHODS: A total of 42 women with ectopic pregnancy were compared with 44 healthy women who have intrauterine first trimester pregnancies. The thiol/disulfide homeostasis is evaluated with the spectrophotometric measurement method that was recently developed by Erel&Neselioglu. RESULTS: Disulfide/native thiol and disulfide/total thiol ratios were increased (p = 0.018 and p = 0.023 respectively), while native thiol/total thiol ratios and native thiol levels were decreased in tubal ectopic pregnancy group according to control group (p = 0.023). Between control and tubal ectopic pregnancy groups no differences were measured in disulfide levels (p = 0.350). The area under curve for native thiol and total thiol were 0.937 and 0.927, respectively. The optimum cut off value for native thiol was 379.95 µmol/l with a sensitivity of 90% and specificity of 81%. The optimum cut off value for total thiol was 432.5 µmol/l had 92% sensitivity and 79% specificity. LIMITATIONS: In the study, whether intrauterine pregnancies resulted in miscarriage or delivery can be examined. CONCLUSION: Increased disulfide/native thiol levels, disulfide/total-thiol ratio and decreased native/total thiol ratio were found to be significantly associated with the presence of tubal ectopic pregnancy which can be useful for the early diagnosis of the disease.

Erythrocyte reduced/oxidized glutathione and serum thiol/disulfide homeostasis in patients with rheumatoid arthritis.

BACKGROUND: Chronic inflammation and oxidative stress are the most known mechanisms in Rheumatoid Arthritis (RA) pathophysiology, which is still not fully elucidated. In this study, we evaluated oxidative status by determining intracellular reduced/oxidized glutathione (GSH/GSSG) homeostasis and serum thiol/disulfide (SH/SS) homeostasis in RA patients. METHODS: A total of 152 RA patient and 89 healthy controls were included in the study. RA patients were subdivided according to disease activity score-28 (DAS-28) as active RA and remission RA. Intracellular GSH/GSSG and serum SH/SS homeostasis parameters were analyzed. RESULTS: Median (1st-3rd quartile values) SS/SH and GSSG/GSH percent ratio levels were significantly higher in RA patients (6.94 (6.02-8.54) and 69.8 (44.05-85.29); respectively) compared to controls (4.62 (4.15-5.46) and 34.9 (22.43-62.2); respectively) (p < 0.05 for all). SS/SH and GSSG/GSH percent ratio levels were significantly higher in active RA patients when compared to remission RA patients and controls (p < 0.05 for all). SS/SH and GSSG/GSH percent ratios were significantly increased in remission RA group compared to controls (p < 0.05 for all). DAS28 scores were positively correlated with SS/SH and GSSG/GSH percent ratios (rho = 0.259 and 0.296; respectively). CONCLUSIONS: These findings suggest that active intracellular and extracellular thiol group oxidation process might play a role in RA pathogenesis and further work in these areas may be warranted to show potential value of evaluating intracellular GSSG/GSH and serum SH/SS balances together in disease monitoring.

Serum Sulfhydryl Groups, Malondialdehyde, Uric Acid, and Bilirubin as Predictors of Adverse Outcome in Heart Failure Patients due to Ischemic or Nonischemic Cardiomyopathy.

Oxidative stress plays a significant role in the pathogenesis of heart failure (HF). The aim of the study was to investigate the prognostic value of oxidation-reduction (redox) markers in patients with HF due to ischemic and nonischemic cardiomyopathy. The study included 707 patients of HF allocated into two groups depending on ethology: ischemic cardiomyopathy (ICM) (n = 435) and nonischemic cardiomyopathy (nICM) (n = 272), who were followed up for one year. The endpoint occurrence (mortality or heart transplantation) in a 1-year follow-up was similar in the ICM and nICM group. The predictive value of endpoint occurrence of oxidative stress biomarkers such as the serum protein sulfhydryl groups (PSH), malondialdehyde (MDA), uric acid (UA), bilirubin, and MDA/PSH ratio and other clinical and laboratory data were assessed in both groups (ICM and nICM) separately using univariate and multivariate Cox regression analyses. In multivariate analysis, the higher concentrations of UA (p = 0.015, HR = 1.024, 95% CI (1.005-1.044)) and MDA (p = 0.004, HR = 2.202, 95% CI (1.296-3.741)) were significantly associated with adverse prognosis in patients with ICM. Contrastingly, in patients with nICM, we observed that higher bilirubin concentration (p = 0.026, HR = 1.034, 95% CI (1.004-1.064)) and MDA/PSH ratio (p = 0.034, HR = 3.360, 95% CI (1.096-10.302)) were significantly associated with increased risk of death or HT. The results showed the association of different oxidative biomarkers on the unfavorable course of heart failure depending on etiology.

Comparison of serum human Klotho levels and thiol/disulfide homeostasis in women with polycystic ovary syndrome and in healthy women.

OBJECTIVES: Women with polycystic ovary syndrome (PCOS) have an increased cardiometabolic risk. Similarly, it was previously shown that atherosclerotic and cardiovascular risk is increased in the general population with lower serum Klotho levels. The aim of this study was to investigate the lotho and thiol/disulfide levels in women with non-obese PCOS compared to healthy controls and also to investigate the relationship of serum Klotho and thiol/disulfide homeostasis with cardiometabolic risk factors. MATERIALS AND METHODS: In this prospective case control study, human serum alpha Klotho levels and thiol/disulfide homeostasis of women with PCOS aged between 19-33 were compared to their age and BMI matched non - PCOS healthy controls. In addition, the correlation of these molecules with other metabolic markers/measurements were also investigated. RESULTS: Metabolic parameters such as mean waist circumference, lipid accumulation product, visceral adiposity index, fasting insulin, homeostasis model assessment of insulin resistance and triglyceride values were higher in the PCOS group (p = 0.038, p = 0.008, p = 0.001, p = 0.001, p = 0.002 and p = 0.002, respectively) compared to controls. However, mean serum Klotho and native thiol levels (respectively p < 0.0001 and p = 0.038) were lower compared to controls. Correlation analysis revealed that serum Klotho levels were negatively correlated with BMI, waist circumference, disulphide/total thiol, disulphide/native thiol, HOMA-IR and LAP-index. CONCLUSIONS: Findings of decreased serum Klotho and native thiol values of the PCOS group compared to controls and the negative correlation of serum Klotho levels with metabolic markers supports the idea that decreased Klotho may be another mechanism by which cardiovascular risk is increased in women with PCOS.