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Background: Thiol/disulphide homeostasis (TDH) has a critical role in many cellular activities such as antioxidant protection. Alterations of oxidative stress in the transition period play an important role in development of some diseases and disorders in dairy cows., Objectives: The purpose of this study is to assess the total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), total thiol, native thiol, disulphide and lipid profile in Simmental and Montofon dairy cows (aged 2-3) before and after calving., Methods: Blood samples were collected 233-280 days of pregnancy and the 30 days of post-partum. Serum total thiol, native thiol and disulphide levels were determined as well as TAS, TOS and paraoxonase-1 (PON-1) levels were measured using colorimetric assays. Triglycerides (TG), total cholesterol, HDL cholesterol and LDL cholesterol levels were measured with an automatic analyser., Results: Total thiol (p = 0.038) and disulphide (p = 0.015) levels were higher after calving compare to pregnancy in Montofon. TAS was found lower (p < 0.001), and OSI was higher in both breeds (Montofon p = 0.012, Simmental p = 0.028) after calving than in pregnancy. When compared between pregnancy and after calving levels in the same breed, HDL was found to be higher after calving (p < 0.001) and TG was lower after calving (p = 0.020) in Montofon. PON (p = 0.090), HDL (p < 0.001) and cholesterol levels were found higher (p < 0.001) and TG level was lower (p < 0.001) after calving in Simmental., Conclusions: According to our results, we observed different responses between two breeds before and after calving. There are few studies about TDH in animal research, and this is the first study in the literature that evaluates the TDH along with oxidative stress and lipid profiles in dairy cows in the periparturient and post-partum period., (© 2024 The Author(s). Veterinary Medicine and Science published by John Wiley & Sons Ltd.)

Background: Premenstrual syndrome (PMS) characterized by cyclic symptoms during the luteal phase of the menstrual cycle, presents an uncertain etiology in adolescents involving hormonal fluctuations and serotonin-related neurotransmitters with a limited existing literature on the impact of oxidative stress. This study aimed to explore the potential association between PMS and oxidative stress in adolescents., Methods: In a cross-sectional study conducted at a university hospital, involving 45 adolescent girls aged 12 to 18, participants were categorized based on the presence or absence of PMS using the cut-off point of 110 on the PMS Scale developed by Gençdoğan. Oxidative stress was assessed through dynamic thiol-disulfide homeostasis. The shift from the balance towards disulfide form is associated with oxidative stress, whereas towards thiol it shows a greater antioxidant capacity., Results: Thirty out of the forty-five participants were found to have PMS with a mean age of 15.5 years. The PMS group demonstrated a significant increase in antioxidant markers, specifically elevated native (631.6±57.55 vs 598.2±41.08, p=0.048) and total thiol levels (675.15±3.4 vs 639.3±44.9, p=0.031). Despite a significant increase in thiol, thiol to disulfide ratio was not found to be significant (p=0.849)., Conclusion: Contradictory to other studies in adults, we have demonstrated an increase in the antioxidant markers in adolescents with PMS. Elevated antioxidant status in adolescents with PMS may be an adaptive response to acute cyclic inflammation in the adolescent period, which might decrease with the progression of age. Further research is needed to investigate the complex interaction between oxidative stress and PMS across different age groups., Competing Interests: The authors declare that there is no conflict of interest.

This study demonstrates the use of computational methods to simulate the molecular dynamics involved in hemoglobin concentration sensing, utilizing Material Studio and the TCAD Silvaco device simulator. A non-invasive and flexible Graphene/MoS2 heterostructure has been proposed for sensing hemoglobin concentration in blood samples. The findings reveal a notable shift in the wavelength-dependent refractive index and extinction coefficient, as well as significant changes in the absorption coefficient and reflectivity of the Graphene/MoS2 heterostructure in response to different hemoglobin concentrations, specifically within an approximate range of 0.3 μm to 1 μm. Moreover, the spectral response of the heterostructure demonstrates that at a particular wavelength of approximately 600 nm, a maximum response is obtained. This wavelength can be considered optimal for detecting various levels of hemoglobin using this heterostructure. The anticipated outcome is a comprehensive understanding of the fundamental principles, ultimately resulting in the development of an exceptionally sensitive platform for detecting hemoglobin concentration., Competing Interests: The authors have declared that no competing interests exist, (Copyright: © 2024 Kumar et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: This study was designed to compare thiol/disulfide and ischemia-modified albumin (IMA) levels between psoriatic arthritis (PsA) and healthy controls and evaluate the correlation between these molecules and the disease activity scores used in PsA., Methods: A total of 63 PsA patients and 49 healthy volunteers were included in the study. Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), modified disease activity score 28 (DAS28), and Bath Ankylosing Spondylitis Functional Index (BASFI) scores were used as disease activity indices for PsA patients. Calculations of native thiol (-SH), disulfide (-SS), and total thiol (-SH+-SS) molecules were made by the automatic spectrophotometric method, and the albumin cobalt binding test was used to measure IMA levels., Results: In the PsA group, -SS/-SH and -SS/(-SH+-SS) levels were higher and -SH/(-SH+-SS) levels were lower than in controls. In the linear regression analysis, a significant correlation relationship was detected between DAS28-erythrocyte sedimentation rate (ESR) and -SS/(-SH+-SS) (β = 0.795, CI 95%, 0.196-1.395; P = .010), -SH/(-SH+-SS) (β = -0.475, CI 95%, 0.114-0.836; P = .010) and IMA (β = 3.932, CI 95%, 0.859-7.005; P = .013). Additionally, a significant correlation was detected between IMA and BASDAI and BASFI., Conclusion: In PsA, thiol/disulfide homeostasis has shifted in favor of disulfide as an oxidative indicator. Serum thiol/disulfide levels are correlated with PsA disease activity indices., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objective: Thyroid hormones are known to affect the biosynthesis and degradation of antioxidant compounds, suggesting a possible link between hypothyroidism and oxidative stress. However, there is no clear consensus in the literature regarding this association. The aim of this study was to evaluate oxidative stress markers (extracellular thiol-disulfide homeostasis and intracellular glutathione homeostasis) in patients with hypothyroidism due to autoimmune (Hashimoto's thyroiditis) or nonautoimmune thyroid disease rendered euthyroid after levothyroxine replacement., Subjects and Methods: The study included 116 patients admitted to the Taksim Training and Research Hospital (Istanbul, Türkiye). Of these, 50 had hypothyroidism due to Hashimoto's thyroiditis (HT group), 30 had nonautoimmune hypothyroidism (NAIH group), and 36 were healthy controls (control group). All participants were women. Extracellular thiol-disulfide homeostasis and intracellular glutathione homeostasis tests were assessed as oxidative stress markers., Results: Thiol-disulfide homeostasis in both HT and NAIH groups was shifted toward the oxidative spectrum. Compared with the control group, the HT and NAIH groups had lower levels of native (p < 0.001 and p = 0.001, respectively) and total (p = 0.002 and p = 0.012, respectively) thiol, as well as a lower native thiol/total thiol ratio (p < 0.001 for both). The HT group also had higher disulfide levels than the control group (p = 0.027). Reduced glutathione (GSH) and oxidized glutathione (GSSG) values were comparable across all three groups, but the HT and NAIH groups had higher GSSG/GSH (p < 0.001 for both) and GSSG/(GSH+GSSG) ratios (p = 0.003 and p = 0.005, respectively), along with lower GSH/(GSH+GSSG) ratio (p = 0.001 and p = 0.002, respectively) than the control group., Conclusion: Levothyroxine replacement was ineffective in ameliorating oxidative stress in patients with hypothyroidism due to Hashimoto's thyroiditis or nonautoimmune causes, as extracellular thiol-disulfide homeostasis was notably altered in these patients compared with healthy controls. The findings of this study suggest that oxidative stress remains a prevailing issue in patients with autoimmune or nonautoimmune hypothyroidism even after euthyroidism is restored., Competing Interests: Disclosure: no potential conflict of interest relevant to this article was reported.

Background: Oxidative stress results from an imbalance between the induction of reactive oxygen species and the ability of cells to metabolize them. Numerous markers can be used to assess the level of oxidative stress. Thiol-disulfide homeostasis (TDH) and ischemia-modified albumin (IMA) are some of them. The aim of this study is to investigate the role of TDH and IMA, which are indicators of oxidative stress, in older patients with osteosarcopenia (OS)., Methods: The study was conducted cross-sectionally in a geriatrics outpatient clinic. Patients who applied to the outpatient clinic for three months were included in the study. Patients with acute infection, delirium, malignancy, severe liver, heart or kidney dysfunction and who did not give their consent for the study were excluded from the study. The study was conducted with 136 patients. Sarcopenia was diagnosed according to muscle ultrasonography (USG) and handgrip strength (HGS) results. Osteopenia/osteoporosis was diagnosed according to bone mineral densitometry (BMD) results. The combination of osteopenia/osteoporosis and sarcopenia was accepted as OS., Results: Native thiol, total thiol value and nativethiol /totalthiol*100 values were significantly lower in the group with OS (respectively; value = 265 ± 53.8 standard deviation (SD) μmol/L, p =  ≤ 0.001; value = 295.33 ± 55.77 SD μmol/L, p = 0.001; value = 90.06 (2.8) interquartile ranges (IQR), p = 0.033). Disulfide/native thiol*100 and disulfide/total thiol*100 values were significantly higher in the group with OS (respectively; value = 5.5 (1.7) IQR, p = 0.033; value = 4.97 (1.4) IQR, p = 0.034)., Conclusion: In our study, the role of oxidative stress in OS was demonstrated by using TDH as an oxidative stress parameter., (© 2024. The Author(s), under exclusive licence to Royal Academy of Medicine in Ireland.)

We investigated oxidative status in patients with rotator cuff tendinopathy (RCT) and evaluated their relationship with radiological and clinical parameters. In this cross-section study, 88 patients with RCT (59 males and 29 females) and 86 healthy controls (66 males, 20 females) were enrolled. The sample consisted of nontraumatic patients who are suffering from shoulder pain because of rotator cuff disease, which was established by clinical tests and MRI scanning. Oxidative stress in patients with RCT was analyzed via the dynamic thiol/disulfide homeostasis (TDH). Thiol/disulfide homeostasis was measured by a new colorimetric method. Furthermore, oxidative stress was indirectly measured by serum total oxidant status (TOS), oxidative stress index (OSI), and total antioxidant capacity (TAC). Serum disulfide levels and the other oxidative stress parameters of the RCT group were significantly greater than those of the control group (P < .001 for all), whereas the anti-oxidative stress parameters remained unchanged (P > .05 for all). The lowest and highest serum disulfide levels were detected in patients with grades 1 and 3, respectively (P < .001). Furthermore, in a multiple regression analysis, the disulfide/natural thiol ratio (β=-4.886, P = .004) and the MRI grading (β=0.314, P=.001) were independently associated with the Western Ontario Rotator Cuff Index WORC score. We found an association between the levels of various serum markers of oxidative injury, especially serum disulfide levels, and the increasing severity of RCT. Thiol/disulfide homeostasis seems to play a critical role in RCT, both in the beginning and during the progression of disease.

The aim of this study was to analyze the role of thiol/disulfide homeostasis (TDH) parameters as an indicator of oxidative stress in acute appendicitis (AA). PubMed, EMBASE, Web of Science, and Scopus databases were systematically searched. Studies reporting on TDH in AA (both complicated and uncomplicated cases) were included. The comparator group were healthy controls. The TDH domain was compared between the groups using anti-oxidant parameters, namely native thiol and total thiol levels, and native thiol/total thiol ratio; and oxidant parameters, namely disulfide level, disulfide/native thiol ratio, and disulfide/total thiol ratio. The statistical analysis was performed using a random-effects model. The methodological quality of the studies was assessed utilizing the Newcastle-Ottawa scale. Eleven studies with a total of 926 subjects, comprising 457 patients with uncomplicated appendicitis, 147 with complicated appendicitis, and 322 healthy controls were included. Our study demonstrated significantly increased oxidative stress in AA as compared to healthy controls in all TDH parameters and significantly lower total thiol levels in complicated AA as compared to uncomplicated AA. Due to a poor methodological quality in five out of eleven studies, future prospective studies with adequate power are essential to validate these observations and refine the diagnostic approaches to AA., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The aim of this study is to investigate the relationship of the lipid profile, dysfunctional high-density lipoprotein, ischaemia-modified albumin and thiol-disulfide homeostasis with cognitive impairment, fatigue and sleep disorders in patients with multiple sclerosis. The cognitive functions of patients were evaluated with the Brief International Cognitive Assessment for Multiple Sclerosis battery. Fatigue was evaluated with the Fatigue Severity Scale and the Fatigue Impact Scale. The Pittsburgh Sleep Quality Index and the Epworth Sleepiness Scale were used to assess patients' sleep disturbance. Peripheral blood samples were collected, and lipid levels and myeloperoxidase and paraoxonase activity were measured. The myeloperoxidase/paraoxonase ratio, which indicates dysfunctional high-density lipoprotein, was calculated. Thiol-disulfide homeostasis and ischaemia-modified albumin were measured.
We did not identify any relationship between dysfunctional high-density lipoprotein and the physical disability, cognitive decline, fatigue and sleep problems of multiple sclerosis. Thiol-disulfide homeostasis was associated with cognitive scores. The shift of the balance towards disulfide was accompanied by a decrease in cognitive scores. On the other hand, we did not detect any relationship between fatigue and sleep disorders and thiol-disulfide homeostasis. Our findings revealed a possible correlation between cognitive dysfunction and thiol-disulfide homeostasis in multiple sclerosis patients., Competing Interests: No potential conflict of interest relevant to this article was reported.

Objectives: Thiols play an important role in defense against reactive oxygen species. We aimed to evaluate the relation between oxidative stress, glucose tolerance, and sleep quality in kidney transplant recipients without diabetes., Materials and Methods: We enrolled 95 kidney transplant recipients without diabetes from living and deceased donors with stable allograft function and 60 healthy controls. We included recipients who received a kidney from a living donor with a first-degree relation. Insulin resistance was determined using the Homeostasis Model Assessment score. Native thiol, total thiol, and disulfide levels were measured, and disulfide versus native thiol/total thiol ratios were calculated from all patients. We used the Pittsburg Sleep Quality Index to assess sleeping patterns. According to standard cutoff value of the index (≤5 indicates good quality sleep; >5 indicates poor sleep quality), we stratified kidney transplant recipients as group 1 (Pittsburg Sleep Quality Index ≤5; n = 41) and group 2 (Pittsburg Sleep Quality Index >5; n = 54)., Results: In correlation analysis, Pittsburg Sleep Quality Index was positively correlated with age, the Homeostasis Model Assessment score, body mass index, serum disulfide levels, disulfide/total thiol ratio, and native/total thiol ratio. The Pittsburgh Sleep Quality Index was negatively correlated with total thiol levels. In subgroup analysis, the Homeostasis Model Assessment score, disulfide levels, and disulfide/total thiol and native/total thiol ratios were significantly lower in group 1; however, total thiol level was significantly higher in this group. In multivariate regression analysis, age, the Homeostasis Model Assessment score, disulfide/total thiol ratio, and renal resistivity index were detected as predictors of sleep quality score., Conclusions: Sleep quality moderates oxidative stress identified by thiol-disulfide homeostasis and insulin resistance in renal transplant recipients without diabetes.

Objective: We aimed to examine the effect of remission status on thiol-disulfide homeostasis in celiac patients and thus to indirectly determine the effect of oxidative stress and inflammation caused by non-compliance with the diet., Methods: Between February 2019 and December 2021, 117 patients diagnosed with celiac disease were included in this prospective randomized and controlled study. In addition to routine tests of celiac patients, thiol and disulfide measurements were made from the blood both at the beginning of the study and at the end of the first year., Results: While 52 of the patients (44.4%) were in remission, 65 patients (55.6%) were not. There was an evident increase in native thiol levels of the patients who were initially not in remission but went into at the end of the first year (347.4±46.7 μmol/L vs. 365.3±44.0 μmol/L; p=0.001). Mean plasma disulfide levels of patients with celiac going into remission became reduced in the first year from the level of 14.5±5.1 μmol/L down to 8.9±4.2 μmol/L (p<0.001). In celiac patients who entered remission, disulfide and anti-tissue transglutaminase immunoglobulin A levels decreased in a correlation (r=0.526; p<0.001)., Conclusion: Not being in remission in celiac disease leads to increased oxidative stress, and thiol-disulfide homeostasis is an indirect indicator of this. Additionally, providing remission in celiac patients reduces oxidative stress.

Objectives: To examine the influence of hirudotherapy on parameters of oxidative stress., Methods: The cross-sectional study was conducted from March 29 to September 29, 2021, at the Alanya Research and Training Hospital's Traditional and Complementary Medicine Application Centre, Turkey, and comprised adult volunteers of either gender. The participants were subjected to two sessions of hirudotherapy 4 weeks apart. Total antioxidant status, total oxidant status, oxidative stress index values, ischaemia-modified albumin level, paraoxonase 1, disulfide, native thiol, total thiol, and arylesterase levels were assessed at baseline and after the second hirudotherapy session. Data was analysed using SPSS 15., Results: Of the 50 subjects, 30(60%) were females and 20(40%) were males. The overall mean age was 47.10±15.16 years. Oxidative stress, ischaemia-modified albumin and disulfide levels decreased, but not significantly (p>0.05). The reduction in disulfide levels was significant (p=0.021)., Conclusions: Hirudotherapy, within its limitations, could reduce oxidative stress.

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., (© 2024 Japan Society of Obstetrics and Gynecology.)

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.

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., (© 2021. Fondazione Società Italiana di Neurologia.)

The present study focuses on the investigation of the dynamic thiol-disulphide homeostasis in patients with epilepsy and understanding the effects of antiepileptic drugs on thiol levels. A total of 148 participants, 75 of whom had epilepsy and 73 were healthy volunteers, were included in the study. Total thiol and native thiol levels of all epilepsy patients and healthy volunteers were measured. Disulphide level, disulphide/native thiol, disulphide/total thiol and native/total thiol ratios were calculated from these values. The results were compared between epilepsy patients and healthy volunteers. A statistically significant difference was found between native thiol level, total thiol level, disulphide level, disulfide/total thiol, disulphide/native thiol and native/total thiol ratios between patients with epilepsy and healthy volunteers (p = 0.002, p = 0.035, p < 0.001, p < 0.001, p < 0.001, p < 0.001, respectively). The drugs used had a significant effect on disulphide, disulphide/total thiol, native/total thiol levels (p values 0.004, 0.009, 0.009, respectively). Decreased levels of serum native, total thiol and increased disulfide levels as parameters of oxidative stress may be considered as parameters to explain the pathogenesis or consequences of epilepsy., (© 2020. Belgian Neurological Society.)

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., Competing Interests: Declaration of competing interest Tunay Kiremitli, Sevil Kiremitli, Ozcan Erel, Esra Firat Oguz, Kemal Dinc, Umit Arslan Nayki, Cenk Nayki, Can Turkler and Ahmet Kirkinci declare that they have no conflict of interest., (Copyright © 2021. Published by Elsevier B.V.)

We aimed to examine the role of thiol/disulphide homeostasis (TDH) in heart failure and its stages and the prognosis of heart failure. A total of 140 subjects were included in the study. Total and native thiol levels were higher in the control group compared to the patient groups ( p  < .001). While the average disulphide/total thiol ratio was similar in groups 1 and 2, it was found to be significantly lower in the control group compared to other groups and significantly higher in group 3 compared to other groups ( p  < .05). Mean native thiol and total thiol levels were found lower in patients with mortality compared to surviving patients ( p  < .001). In ROC curve analysis, it was determined that the total thiol level had 81.8% sensitivity and 83.1% specificity, and native thiol level had 81.8% sensitivity and 84.3% specificity. We found that TDH was impaired in favour of disulphide in cases of heart failure.

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., (Copyright © 2021. Published by Elsevier B.V.)

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.

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., (Copyright © 2021 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

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., (© 2021 Japan Geriatrics Society.)

Although genetic factors occupy an important place in the development of autism spectrum disorder (ASD), oxidative stress and exposure to environmental toxicants have also been linked to the condition. The aim of this study was to examine dynamic thiol/disulfide homeostasis in children diagnosed with ASD. Forty-eight children aged 3-12 years diagnosed with ASD and 40 age- and sex-matched healthy children were included in the study. A sociodemographic data form was completed for all the cases, and the Childhood Autism Rating Scale (CARS) was applied to the patients. Thiol/disulfide parameters in serum were measured in all cases and compared between the two groups. Mean native thiol, total thiol concentrations (μmol/L), and median reduced thiol ratios were significantly lower in the ASD group than in the control group (p = 0.001 for all). Median disulfide concentrations (μmol/L), redox potential, and median oxidized thiol ratios were significantly higher in the ASD group than in the control group (p = 0.001, p = 0.001, and p = 0.001, respectively). ROC analysis revealed that area under the curve (AUC) values with "excellent discriminatory potential," for native thiol, total thiol, the reduced thiol ration, the oxidized thiol ratio, and redox potential and with "acceptable discriminatory potential" for disulfide were significantly capable of differentiating individuals with ASD from healthy individuals. No correlation was determined between the severity of autism and laboratory parameters. Impaired dynamic thiol/disulfide homeostasis was observed in children with ASD, suggesting that dynamic thiol/disulfide homeostasis in serum may be of diagnostic value in autism.

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.

Purpose: It was aimed to assess the role of thiol-disulphide homeostasis and ischemia-modified albumin (IMA) level in the development of diabetic macular edema (DME) in patients with diabetes mellitus type 2 (T2DM)., Materials and Methods: Sixty-six study patients were divided into two groups. Group I included 43 patients with T2DM and DME, and Group 2 included 23 patients with T2DM without eye involvement. A novel colorimetric method was used to assess thiol-disulphide homeostasis. Between the two groups IMA, total anti-oxidant, and total oxidant levels were measured and compared., Results: In Group 1, total and native thiol levels and disulphide levels were lower compared to Group 2 ( p = .025, p < .001 and p = .013, respectively). Disulphide/native thiol, disulphide/total thiol ratios and native thiol/total thiol were similar between the groups. Total anti-oxidant level (TAL) reduced whereas total oxidant level (TOL) increased in Group 1 compared to Group 2 ( p = .001, p = .002, respectively). Albumin level decreased, whereas IMA level increased in Group 1 compared to Group 2 ( p < .001 for both)., Conclusions: The disruption in thiol/disulphide homeostasis, increased IMA and oxidative stress have an impact on the development of diabetic macular edema.

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., Competing Interests: Declaration of competing interest No authors have any conflict of interest to report., (Copyright © 2021. Published by Elsevier B.V.)

Background: This study aimed to evaluate thiol disulphide volume for the risk of contrast-induced nephropathy ( CIN) in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI)., Methods: A total of 638 patients with ACS were enrolled in the study. CIN was defined as an increase in serum creatinine level of ≥0.5 mg/dL or ≥25% above baseline within 72 h after the procedure. Patients were divided into two groups: patients with and without CIN. Demographics, clinical risk factors, angiographic and laboratory parameters, CIN incidence, thiol, disulphide, and CHA2DS2-VASc score were compared between the two groups., Results: Native thiol, total thiol, and disulphide at baseline were significantly lower in patients who developed CIN compared to those who did not. Also, the CHA2DS2-VASc score was found to be higher in patients with CIN than those without CIN. In receiver operating characteristic analysis showed that at a cutoff of <342.1, the value of native thiol exhibited 82% sensitivity and 80% specificity for detecting CIN. Total thiol< 383.1 calculated on admission had an 80% sensitivity and 80% specificity in predicting CIN., Conclusion: Our study suggested that the thiol disulphide volume on admission was independently associated with the development of CIN after PCI in patients with ACS.

In this work, we utilise the disulphide bond structure of insulin and a new benzothiazole Raman probe for the detection of human insulin using surface-enhanced Raman spectroscopy (SERS). The disulphide bond structure of the insulin was reduced to generate free sulfhydryl terminal groups. When reacted with benzothiazole-functionalised gold nanoparticles, the reduced protein desorbs the Raman probe and causes its Raman signal intensity to quench. Using this approach, insulin was quantified in the concentration range of 1 × 10 -14 -1 × 10 -8 M by SERS quenching. The limit of quantification of insulin by the SERS quenching method was found to be 1 × 10 -14 M (0.01 pM or 58 pg/L), which satisfies the requirements for monitoring its blood concentration in patients. Because many proteins and peptides have disulphide bonds in their molecular structures, the new SERS quenching method has a strong potential for the rapid determination of ultralow concentrations of proteins in formulations and biological fluids., (© 2020 John Wiley & Sons, Ltd.)

Background/aim: The aim of present study was to investigate the dynamic thiol/disulfide homeostasis as oxidative stress marker in diabetic ketoacidosis (DKA)., Materials and Methods: A total of 77 participants consisting of 32 patients with DKA and 45 healthy volunteers were included in the study. Thiol/disulfide homeostasis (TDH) [total thiol-native thiol/disulfide changes] were measured in both groups (patient group and control group) using a brand new method developed by Erel and Neselioglu. Half of the difference between total thiol and native thiol concentrations gives the amount of disulfide bond., Results: Total thiol, native thiol, and disulfide levels in blood were found to be low. The levels of total thiol (P < 0.001) and native thiol (P < 0.001 ) were significantly lower in patients with DKA than in the control group. At the same time, the level of disulfide was nonsignificantly lower in the patient group than the control group (P = 0.388). The level of IMA was higher in the patient group than in the control group (P < 0.001)., Conclusion: The total thiol, native thiol, and disulfide levels in DKA decrease in favor of oxidative stress., Competing Interests: The authors declare that this study received no financial support and there are no conflicts of interest., (This work is licensed under a Creative Commons Attribution 4.0 International License.)

Objective : Hypertension is a multi-factorial process prevalent in developed as well as in developing countries. Urotensin-II, different antioxidants, free radicals, and inflammatory biomarkers play an essential role in the cardiovascular system. The aim of this study is to investigate Urotensin-II, oxidative stress, and inflammation markers in normotensive, hypertensive, and resistant hypertensive patients. Methods : Fifty resistance hypertensive (rHT) patients, 50 hypertensive patients, and 50 age gender matched normotensive controls (NT-control) were enrolled. Urotensin-II (UII), total oxidant status (TOS), total antioxidant status (TAS), native thiol (NT), total thiol (TT), disulfide (DIS), interleukin 1 beta (IL1β), interleukin 6 (IL6), tumor necrosis factor-alpha (TNFα), high sensitive c reactive protein (hsCRP), high-density lipoprotein (HDL) low-density lipoprotein (LDL), and total cholesterol (TC) were evaluated. Results : Serum levels of UII, IL1β, IL6, TNFα, DIS, TOS, and OSI were found higher in rHT and HT as compared to NT-control ( p < .001). On the contrary, serum levels of TT, TAS, and NT were lower in rHT and HT as compared to NT-control ( p < .001). While TC, hsCRP, TOS, OSI, UII, IL1β, IL6, and TNFα levels increase from HT to rHT group ( p < .001); TAS and NT levels decrease from HT to rHT group ( p < .001). Conclusions : UII levels, oxidative stress, and inflammation are higher in rHT and HT, while antioxidants and thiol levels are lower than the NT-control. Our study clearly showed that rHT and HT are more susceptible to impaired states of antioxidants, oxidative stress, and free radicals.

The purpose of this study was to evaluate the relation CC resistant PCOS and the thiol/disulphide homeostasis, used as a marker of OS, by measuring that exchange using a novel technique. Sixty women patients admitted to the infertility clinic were evaluated. The patients were divided into two groups. Group 1 comprised 30 infertile PCOS patients with CC resistance; Group 2 was the control group comprising 30 infertile PCOS patients with CC sensitivity. Serum total thiol ( p  = .024), native thiol ( p  = .0052), disulphide ( p  = .003), index 1 ( p  = .001), index 2 ( p  = .001) and index 3 ( p  = .001), HOMA-IR ( p  < .001) and free testosterone ( p   <  .001) were statistically significant. The independent variables BMI and age effects were adjusted according to the logistic regression method with groups. Significant differences were observed between the two groups in the levels of native thiol ( p * = .0042), total thiol ( p * = .024), disulphide ( p * = .0003), index 1 ( p * = .0001) index 2 ( p *= .0001), index 3 ( p * = .0001), HOMA-IR ( p * = .0044), insulin ( p *= .032) and free testosterone ( p * = .0001) values. The thiol/disulphide homeostasis viewed in favour of OS. Like a reflection of OS in the follicular endocrine microenvironment may be linked with increased thiol/disulphide homeostasis, free testosterone, insulin and HOMA-IR levels.Impact statement What is already known about this subject? In previous studies, thiol/disulphide homeostasis was compared between PCOS and control groups. In this study, serum thiol/disulphide homeostasis was measured in infertile PCOS patients resistant to CC for the first time. What do the results of this study add? Disulphide concentrations were significantly higher in patients with CC resistant patients thanthe control group. This shows us that more OS occurs in the CC-resistant group. What are the implications of these findings for clinical practice and further research? Thiol/disulphide homeostasis will be a guide for PCOS management in patients with CC-resistant PCOS.

Objective: To examine dynamic thiol/disulphide homeostasis metrics as a novel risk factor of oxidative stress in patients with peripheral arterial disease., Methods: One hundred patients with lower extremity peripheral arterial disease (a study group) and 100 control subjects were included in this prospective case-control study. Participants' baseline clinical characteristics and laboratory data including some oxidant/antioxidant status parameters such as albumin, ferroxidase and myeloperoxidase, and thiol/disulphide homeostasis parameters such as native thiol, total thiol and disulphide, as well as native thiol/total thiol, disulphide/native thiol and disulphide/total thiol ratios were all recorded and then compared between the groups., Results: Mean albumin and ferroxidase, and median myeloperoxidase levels were found to be significantly higher in patients with the peripheral arterial disease than in control group ( p  = 0.045, p  = 0.000 and p  = 0.000, respectively). Mean native thiol and total thiol, and median disulphide levels were found to be significantly lower in the study group as compared with the control group ( p  = 0.000, p  = 0.000 and p  = 0.037, respectively). According to the results of logistic regression analysis, systolic blood pressure, ferroxidase and myeloperoxidase levels were detected to be the independent predictors of peripheral arterial disease., Conclusion: Our report is the first one in the literature investigating dynamic thiol/disulphide homeostasis metrics as a novel risk factor of oxidative stress in peripheral arterial disease. Dynamic thiol/disulphide homeostasis metrics may be used as a valuable risk factor of oxidative stress in patients with the peripheral arterial disease since it is readily available, easily calculated and relatively cheap.

Purpose: This research is aimed at determination of total oxidant status, total antioxidant status, serum thiol-disulfide, catalase, albumin, ischemia-modified albumin, and ceruloplasmin in patients suffering from retinitis pigmentosa and drawing a comparison with these parameters determined from healthy controls., Methods: The study involved 35 patients of retinitis pigmentosa and 33 controls who were healthy individuals of comparable gender and age. Native thiol, total thiol, disulfide concentration, disulfide/native thiol, disulfide/total thiol, native thiol/total thiol ratios, total oxidant status, total antioxidant status, catalase, ceruloplasmin, albumin, and ischemia-modified albumin were determined from peripheral blood samples and comparison was drawn between the measurements of retinitis pigmentosa and controls., Results: The two groups were similar in gender and age distributions. It was found that retinitis pigmentosa group demonstrated greater total oxidant status, ischemia-modified albumin, and disulfide concentrations as compared to controls (p < 0.001). However, total antioxidant status, catalase, native thiol, total thiol, albumin, and ceruloplasmin of the two groups did not show statistically significant difference (p > 0.05). Moreover, disulfide/total thiol and disulfide/native thiol ratios of the retinitis pigmentosa group were significantly greater in comparison to controls (p < 0.05)., Conclusion: The researchers reached the conclusion that thiol oxidation in retinitis pigmentosa patients caused the dynamic thiol/disulfide homeostasis to shift toward the generation of disulfide. This is a novel research that involves analysis of thiol/disulfide homeostasis in retinitis pigmentosa patients using a novel automated assay. The researchers identified the cause for persistent oxidative stress and damage reported in retinitis pigmentosa patients. Still, future research is required for analysis of progression of antioxidant-oxidant state through various retinitis pigmentosa stages.

Background: In the presence of advanced age and comorbidities, patients with gallstones may face gangrenous and perforated cholecystitis during their follow-up. In the literature, dynamic thiol/disulfide homeostasis has been shown to play an important role in detoxification, antioxidant protection, regulation of enzymatic reactions, and apoptosis and cellular signaling mechanisms. In this study, we aimed to evaluate the efficacy of IMA and thiol/disulfide homeostasis in the preoperative diagnosis of patients with cholelithiasis, acute/chronic cholecystitis, and perforated gallbladder., Methods: Sixty-six patients that presented to the General Surgery Clinic of Ankara City Hospital for a cholecystectomy operation between February 2019 and May 2020 were included in this study. The patients were divided into three groups depending on the condition for which they were scheduled for surgery: cholelithiasis, cholecystitis, and perforated gallbladder. The demographic data, history of cholecystitis, chronic disease, white blood cell (WBC), amylase, lipase and liver function tests (AST and ALT) were recorded before the operation. Gallbladder appearance was evaluated using hepatobiliary ultrasonography. The duration of surgery, pericholecystic adhesions, hospital stay, body mass index (BMI), postoperative complications, and pathology results of specimens were recorded. In addition, thiol/disulfide and IMA values were analyzed in the blood samples taken from the patients preoperatively., Results: The mean native thiol and total thiol values of the patients with an adhesion score of 0 were significantly higher than those with an adhesion score value of 1, 2 or 3. In addition, the disulfide, disulfide/native thiol, native thiol/total thiol and IMA values of the cases with an adhesion score of 2 or 3 were significantly higher than those with an adhesion score of 0. The native thiol and total thiol averages of the patients with normal cholecystectomy were higher than the others. The disulfide, native thiol/total thiol and IMA averages of those who underwent cholecystectomy due to a perforated gallbladder were also higher than the other groups. The mean preoperative WBC of the patients who underwent cholecystectomy due to a perforated gallbladder was also significantly higher than the other groups. Lastly, the native thiol and total thiol values had a statistically significant negative correlation with age, operation time, and hospital stay, and a statistically significant positive relationship with BMI., Conclusion: We consider that in the preoperative diagnosis of the perforated gallbladder, the evaluation of thiol/disulfide hemostasis and IMA parameters can be used as an effective and reliable method to predict intraoperative difficulties.

Background and Aims: Sterile inflammation is a major clinical concern during ischemia-reperfusion injury (IRI) triggered by traumatic events, including stroke, myocardial infarction, and solid organ transplantation. Despite high-mobility group box 1 (HMGB1) clearly being involved in sterile inflammation, its role is controversial because of a paucity of patient-focused research., Approach and Results: Here, we examined the role of HMGB1 oxidation states in human IRI following liver transplantation. Portal blood immediately following allograft reperfusion (liver flush; LF) had increased total HMGB1, but only LF from patients with histopathological IRI had increased disulfide-HMGB1 and induced Toll-like receptor 4-dependent tumor necrosis factor alpha production by macrophages. Disulfide HMGB1 levels increased concomitantly with IRI severity. IRI + prereperfusion biopsies contained macrophages with hyperacetylated, lysosomal disulfide-HMGB1 that increased postreperfusion at sites of injury, paralleling increased histone acetyltransferase general transcription factor IIIC subunit 4 and decreased histone deacetylase 5 expression. Purified disulfide-HMGB1 or IRI + blood stimulated further production of disulfide-HMGB1 and increased proinflammatory molecule and cytokine expression in macrophages through a positive feedback loop., Conclusions: These data identify disulfide-HMGB1 as a mechanistic biomarker of, and therapeutic target for, minimizing sterile inflammation during human liver IRI., (© 2020 by the American Association for the Study of Liver Diseases.)

We aimed to investigate the role of impaired oxidant-antioxidant homeostasis on the etiopathogenesis of autism with a novel oxidative stress (OS) marker, dynamic thiol/disulfide homeostasis (DTDH), and relationship between the symptom severity and markers. A total of 60 children with ASD aged 3-10 years and 54 unaffected children were investigated for the plasma DTDH parameters. A sociodemographic-data form, K-SADS-PL, Childhood Autism Rating Scale, Abnormal Behavior Checklist, Autism Behavior Checklist, and a developmentally appropriate IQ test were administered to all participants. Distortion of DTDH to the OS-side in the autism group was determined with lower plasma levels of native and total thiol, in contrast to a higher disulfide and thiol oxidation-reduction ratio. However, biomarkers had no correlation with the symptom severity of autism. Cutoff values for each parameter on the ROC curve might be useful to predict ASD and each DTDH biomarker was detected as an independent predictor of ASD. The present study demonstrated a disturbed redox status and absence of an expected compensatory increase in antioxidant response in a pediatric sample of ASD by measuring dynamic oxidation/reduction shifts with a novel, practical and reproducible analytical technique, and contributes to data regarding oxidative hypothesis on autism and raises the question of the place of antioxidants in autism treatment. Our results may suggest predictive usefulness of the plasma DTDH biomarkers in ASD, despite the study being conducted with a modestly small sample size that makes further research with a larger replication sample necessary to substantiate the findings. LAY SUMMARY: Dynamic thiol/disulfide homeostasis is a novel plasma marker used to determine the oxidative stress which is a natural result of disequilibrium between the oxidants and antioxidants in the human body. There is increasing interest regarding a central biological linking role of oxidative stress among the other etiological factors of autism. Our findings on the disturbed plasma dynamic thiol/disulfide homeostasis in children with autism and the absence of an expected antioxidant response against increased oxidative stress supports the data concerning the role of oxidative stress on the etiology of autism and the need of further research on the place of antioxidants in autism treatment., (© 2020 International Society for Autism Research and Wiley Periodicals LLC.)

Plant parasites and soilborne pathogens directly reduce the overall yield of crops, vegetables, and fruits, negatively impacting the market demand for these products and their net profitability. While preplant soil fumigation helps maintain the consistent production quality of high-value cash crops, most soil fumigants are toxic to off-target species, including humans. Dimethyl disulfide (DMDS) has recently been introduced as a relatively low toxicity soil fumigant. Although DMDS exhibits low toxicity compared to other soil fumigants, it is volatile and exposure can cause eye, nasal, and upper respiratory tract irritation, skin irritation, nausea, dizziness, headache, and fatigue. While there is one analysis method available for DMDS from biological matrices, it has significant disadvantages. Hence, in this study, a dynamic headspace gas chromatography-mass spectroscopy (DHS-GC-MS) method was developed for the analysis of DMDS in swine whole blood. This method is highly sensitive and requires only three steps: 1) acid denaturation, 2) addition of internal standard, and 3) DHS-GC-MS analysis. The method produced a wide linear range from 0.1 - 200 µM with an excellent limit of detection of 30 nM. Intra- and interassay accuracy (100±14% and 100±11%, respectively) and precision (<5% and <6% relative standard deviation, respectively) were also excellent. The method worked well to quantify the DMDS levels in the blood of dimethyl trisulfide (DMTS)-treated swine (i.e., DMDS is a byproduct of DMTS treatment) with no interfering substances at or around the retention time of DMDS (i.e., 2.7 min). This simple, rapid, and extremely sensitive method can be used for the quantification of DMDS levels in blood to verify exposure to DMDS or to monitor levels of DMDS following DMTS treatment (e.g., for cyanide poisoning)., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The aim of the current study is to investigate the effect of daily long-term radio-frequency electromagnetic field (RF-EMFs) exposure on thiol/disulphide homeostasis and oxidant-antioxidant status in the serum of rats. Fourteen male Sprague Dawley rats were divided into two equal groups (n = 7). They were grouped as group 1 (sham-control) and group 2 (2100 MHz exposed). Group 2 rats were exposed to GSM-like signals for 5 h/day, 7 days per week for 14 days. In serum of blood samples, the native, total and native/total thiol levels and antioxidant-oxidant parameters were analyzed. The study revealed that the mean serum total thiol levels of GSM exposure group was rather higher than sham-control group ( p = 0,219); the mean serum native thiol levels of GSM exposure group was rather higher than sham-control group ( p = 0,416), and the mean serum disulphide levels of GSM exposure group was rather higher than sham-control group ( p = 0,566). On the other hand, the mean serum total antioxidant status (TAS), total oxidant status (TOS) and oxidative stress index (OSI) of GSM exposure group were higher than sham-control group. There are no data in the literature, that examine the effects of RF-EMFs on thiol/disulphide homeostasis. The results of this study, indicate that RF-EMFs did not cause oxidative stress and statistically changes in thiol/disulphide homeostasis. More sample sizes and longer-term exposures are needed to confirm the results of this study.

Aim: The aim of this study was to investigate the efficacy of thiol disulfide homeostasis and Ischemia Modified Albumin (IMA) values in predicting the technical difficulties that might be encountered during laparoscopic cholecystectomy., Materials and Methods: The study included 65 patients who underwent laparoscopic cholecystectomy due to cholelithiasis at the General Surgery Clinic of Ankara Numune Training and Research Hospital. All patients' demographic data, previous history of cholecystitis, a history of chronic illness, preoperative white blood count (WBC), liver function tests (AST, ALT), amylase and lipase levels, intra-operative adhesion score, the ultrasonographic appearance of gall bladder, duration of hospital stay, duration of operation, thiol disulfide and IMA values were evaluated., Results: Native thiol and total thiol averages were higher in patients without a history of cholecystitis, and on the other hand, disulfide, disulfide/native thiol rate, disulfide/total thiol rate, native thiol/total thiol rate and IMA averages were higher in patients with a history of cholecystitis. While there was a statistically significant negative correlation between native and total thiol values and age, duration of surgery and duration of hospital stay; IMA, disulfide, disulfide/Total thiol, Native/Total thiol and disulfide/Native thiol rates were higher in older patients with a longer duration of surgery and hospital stay. In addition, preoperative IMA, disulfide, disulfide/Total thiol, Native/Total thiol and disulfide/Native thiol were observed to increase as the degree of intraoperative pericholecystic adhesion increased., Conclusion: We believe that the evaluation of thiol disulfide homeostasis and IMA parameters prior to laparoscopic cholecystectomy can be used as an effective method for predicting intraoperative difficulties., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: It is possible that patients with pneumonia may also have sepsis and the separation of these two clinical entities may cause some trouble to clinicians., Objective: In order to separate a patient with pneumonia and a patient with sepsis, we qualify thiol/disulfide homeostasis as a potential biomarker., Methods: This study was designed between February 2018 - February 2019 prospectively. All patients in the intensive care unit with pneumonia and sepsis were enrolled in the study. At the time of hospitalization, thiol/disulfide homeostasis was measured. Patients diagnosed with sepsis and pneumonia were compared, in regards to thiol/disulfide homeostasis., Results: During research period, 103 patients with sepsis and 120 patients with pneumonia were enrolled into the study. When we compared native-thiol, total-thiol, and disulfide levels in both sepsis and pneumonia patients, we had similar results (p>0.05). In sepsis group, index-1 (disulfide/native thiol ratio) and index-2 (disulfide/total thiol ratio) were found to be statistically higher than the pneumonia group, and index-3 (native thiol/total thiol ratio) was statistically lower than the pneumonia group (p=0.020, p= 0.021, p=0.021, respectively)., Conclusion: In this study, we showed that thiol/disulfide homeostasis could be used as new markers in the early period in order to separate patients with sepsis and patients with pneumonia., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Atopic dermatitis (AD) is a chronic disease of infancy and its pathogenesis remains unclear. There are recent studies suggesting that oxidative stress could play a role in the pathophysiology of atopic dermatitis. The aim of this study was to evaluate thiol (SH)-disulfide (SS) hemostasis as a new marker of oxidative stress (OS) in infants with atopic dermatitis. Thirty-one infants with AD and 30 healthy infants were included in a prospective, cross-sectional study. PO-SCORAD Index of infants with atopic dermatitis was calculated at the time of sample collection. Total antioxidant status (TAS), total oxidant status (TOS), native thiol (-SH), total thiol (-SH + -S-S-), and disulfide (SS) were measured in the control and patient groups. SS/SH, SS/total SH, SH/total SH ratios were compared between the groups. Mean native thiol and total thiol concentrations of the patient group were lower than the control group (p = 0.012; 0.047). The mean disulfide concentration of the patient group was significantly higher than the control group (p = 0.025). SS/SH, SS/total SH, and SH/total SH ratios were significantly higher in the patient group than in the control group (p < 0.05). There was a positive correlation between the duration of the breasting of the patients and thiol concentrations (p = 0.000). In our study, we found increased oxidative stress and decreased antioxidant defense mechanisms in infants with AD. Dynamic thiol-disulfide balance in the patient group was weakened and the balance shifted towards the oxidative side. These results may shed light on etiopathogenesis of atopic dermatitis and be useful in the development of new therapeutic methods.

Antrochoanal polyps (ACPs) are benign lesions of the paranasal sinuses. Similarities between ACPs and nasal polyps have been previously investigated. However, oxidative stress has been implicated but not investigated in terms of the etiology of ACPs. Thus, the aim of this study was to investigate oxidative stress in the etiology of ACPs. The study population comprised 93 patients divided into 3 groups. Group 1 consisted of 30 patients with ACPs. Group 2 consisted of 33 patients with nasal septal deviation. Group 3 comprised 30 healthy individuals. Venous blood was taken from all participants, and total thiol, native thiol, disulfide, and ischemic modified albumin (IMA) levels were evaluated. When the values of native thiol ( P = .097), disulfide ( P = .221), total thiol ( P = .140), and IMA ( P = .091) were compared, no significant differences were found among the 3 groups. While many studies have been conducted related to nasal pathologies and the role of oxidative stress in their etiologies, our study concluded that oxidative stress plays no role in ACP etiology.

We aimed to evaluate maternal serum thiol/disulphide homeostasis in pregnancies complicated by fetal distress (FD). A total of 100 patients beyond the 34th week of pregnancy were included in this study, and they were divided into two groups. The study group included 50 patients who had been diagnosed with FD; the control group was composed of 50 patients who had shown no signs of FD and who had undergone an elective (previous) caesarean section (CS). The native thiol, total thiol and native thiol/total thiol (%) concentrations were lower in Group 1 patients than Group 2 patients ( p  < .001). The disulphide, disulphide/native thiol (%) and disulphide/total thiol (%) concentrations were higher in Group 1 patients than Group 2 patients ( p  < .001). This study suggests that maternal thiol/disulphide homeostasis is impaired in pregnancies complicated by FD.IMPACT STATEMENT What is already known about this subject? Oxidative stress (OS) has previously been investigated in FD. This study reports for the first time a new novel and automatic measurement method. What do the results of this study add? This study shows that the thiol balance shifts in the direction of disulphide in the cases of FD. What are the implications of these findings for clinical practice and further research? Thiol balance can be used for the timely diagnosis of FD.

This study aimed to study the dynamic thiol/disulfide homeostasis in pregnant women with gestational diabetes mellitus (GDM). Forty-five pregnant women with GDM and 45 age-matched healthy pregnancies were included in this study. Thiol/disulfide homeostasis was measured using a commercial kit (Rel Assay Diagnostics). The patients with GDM had significantly higher disulfide concentrations than healthy pregnant patients ( p  = .001). Besides, the GDM group had significantly higher disulfide/total thiol, disüplhide/native thiol, and native thiol/total thiol ratio than healthy pregnant patients ( p  = .001, p  = .001 and p  = .001, respectively). The significantly higher concentrations of disulfide, disulfide/total thiol, disüplhide/native thiol, and native thiol/total thiol ratio in women with GDM could be considered as the increased oxidative stress.

We aimed to investigate the impact of oxytocin on serum thiol/disulphide and malonylyldialdehyde (MDA)/glutathione balance under acute stress (AS) and chronic stress (CS) exposure in rats. Animals were allocated into control (C), AS and CS groups, then the groups subdivided as intranasal oxytocin or saline applied groups, randomly. Animals in the AS or CS groups were exposed to combined cold-immobilisation stress. Salivary corticosterone levels and elevated plus maze (EPM) scores were used to assess stress response. MDA, glutathione, thiol-disulphide levels were measured in the serum samples. Oxytocin treatment attenuated stress response regardless of the stress duration verified by lower corticosterone level and favorable profile in EPM parameters measured. Furthermore, oxytocin modulated oxidant profile suggesting lowered oxidant stress with decreased serum MDA/glutathione and disulfide/native thiol ratios. Oxytocin improves the response of organism to stress via both its anxiolytic and antioxidant effects. That's why it can be considered as a protective measure to employ methods to increase endogenous oxytocin and/or to apply exogenous oxytocin to prevent stress-induced increase in oxidant stress, which plays a pivotal role in the pathogenesis of various stress-related diseases.

Aims: This study aimed to compare the serum thiol-disulfide homeostasis, total antioxidant status (TAS), and total oxidant status (TOS) in patients with pseudoexfoliation glaucoma (PEG) patients, primary open-angle glaucoma (POAG) patients, and healthy individuals (control)., Methods: Ninety subjects were included in this study. Three groups were separated as PEG, POAG, and control. All groups were chosen to be similar in terms of age and gender. Blood samples were obtained following an overnight fasting state and were collected on the ice at 4°C. The serum samples were separated from the cells by centrifugation at 3000 rpm for 15 min and were stored at -80°C. Serum samples analyzed for TAS and TOS, native thiol, total thiol, disulfide, and native thiol/disulfide ratio., Results: TAS and TOS levels of PEG patients were 1.2892 ± 0.0905 mmol/L; 5.0191 ± 2.7722 μmol/L, respectively. TAS and TOS levels of POAG patients were 1.2741 ± 0.1252 mmol/L; 4.1674 ± 1.7723 μmol/L, respectively. TAS and TOS levels of the control group were 2.3414 ± 0.1409 mmol/L; 4.0931 ± 0.1107 μmol/L, respectively. The TAS level was significantly lower in PEG and POAG groups compared to control. TOS level showed no significant differ ¬ ence between PEG, POAG, and control groups (P > 0.05). The mean serum total thiol and native thiol levels were significantly lower in patients with PEG compared to POAG and control group; there was no significant difference between the POAG and control group (P > 0.05). The mean serum disulfide level was significantly lower in patients with PEG compared to POAG (P = 0.018)., Conclusion: Low levels of TAS were observed in patients with glaucoma, which was likely a response to the increased oxidative stress observed in these patients. While total thiol and native thiol levels were higher in the PEG group, the disulfide level was higher in the POAG group. TAS and TOS levels showed no significant difference between POAG and PEG groups., Competing Interests: None

Aims: Anethole dithiolethione (ADT) is a marketed drug to treat xerostomia. Its mechanism of action is still unknown, but several preclinical studies indicate that it is able to increase intracellular glutathione (GSH) and protect against oxidative stress. Here, we investigated the molecular mechanisms behind these effects., Results: Oral treatment of rats confirmed the GSH enhancing properties of ADT; among the different organs examined in this study, only the kidney showed a significant GSH increase that was already observed at low-dose treatments. The increase in GSH correlated with a decrease in γ -glutamyltranspeptidase ( γ -GT) activity of the different tissues. In vitro and ex vivo experiments with tubular renal cells and isolated perfused rat kidney showed that the cellular uptake of intact GSH was correlated with the extracellular concentrations of GSH., Conclusion: s. The prominent in vivo pharmacological effect of ADT was a marked increase of GSH concentration in the kidney and a decrease of some systemic and renal biomarkers of oxidative stress. In particular, by inhibition of γ -GT activity, it decreased the production cysteinylglycine, a thiol that has prooxidant effects as the consequence of its autooxidation. The activity of ADT as GSH enhancer in both the circulation and the kidney was long-lasting. All these characteristics make ADT a promising drug to protect the kidney, and in particular proximal tubule cells, from xenobiotic-induced damage., Competing Interests: The authors declare they have not conflicts of interest., (Copyright © 2020 Daniela Giustarini et al.)

Background: The pathogenesis chronic urticaria (CU) hasn't been fully understood. In recent years, it has been shown that thiol-disulphide homoeostasis, as an antioxidant system, plays important roles in both healthy individuals and various diseases. In different ischaemia-reperfusion states, high oxidative stress causes ischaemia-modified albumin (IMA) generation., Aim: To investigate thiol/disulphide balance and IMA level in children with CU and their association with disease severity., Methods: Thirty children with CU and 20 healthy children as controls, aged 1-18 years, were included in this cross-sectional study. In all subjects, total thiol, native thiol, disulphide levels and IMA levels were measured in plasma by spectrophotometry. Disulphide/native thiol, disulphide/total thiol and native thiol/total thiol ratios were calculated. The disease severity was rated by Urticaria Activity Score (UAS)., Results: In the children with CU, the levels of native thiol (375.56 ± 56.22 μmol/L) and total thiol (415.69 ± 54.75 μmol/L) were significantly lower than the control group (475.20 ± 71.87 and 511.20 ± 73.73 μmol/L, respectively) ( p  = 0.000, p  = 0.000). The ratio of native/total thiol * 100 was lower in patients than the control group ( p  = 0.002). IMA was significantly higher in the patient group than control group ( p  = 0.000). No significant correlation was found between UAS and thiol/disulphide homoeostasis ( p  > 0.05). The disulphide levels, disulphide/native thiol and disulphide/total thiol levels were found to be higher in patients with positive family history for autoimmune disorders than those without ( p  < 0.05)., Conclusion: In children with CU, impaired thiol/disulphide homoeostasis and increased IMA suggest that oxidative stress may play role in the disease pathogenesis.

Background/aim: This study aimed to determine plasma thiol, disulphide, and serum ischemia-modified albumin (IMA) levels and ferroxidase activity in patients with ascending aorta dilatation (AAD) in comparison to those without AAD and to evaluate the predictive value of these oxidative stress parameters for AAD., Materials and Methods: This study was designed as a cross-sectional study of 184 patients who applied to our cardiology clinic. Our study population consisted of patients with AAD (n = 85) and without AAD (n = 99). A spectrophotometric method was used to determine plasma thiol, disulphide, and serum IMA levels and ferroxidase activity., Results: The native thiol and the total thiol levels were significantly higher in the control group than the AAD group (P < 0.001), whereas the disulphide and IMA levels and the ferroxidase activity were similar between the groups. The native thiol and the total thiol levels were inversely and significantly correlated with ascending aortic diameter (r = –0.38, P < 0.001; r = –0.39, P < 0.001; respectively). The left ventricle mass and the total thiol levels were independent predictors of ascending aortic diameter (β= 0.223, P = 0.02; β= –0.340, P < 0.001; respectively)., Conclusion: Among oxidative stress parameters including thiols, disulphide, IMA, and ferroxidase activity, only the lower total thiol levels appear to confer a high risk for AAD development. Along with the proven diagnostic imaging methods, thiol levels may be helpful to diagnose and stratify patients with AAD., Competing Interests: All the authors declare no conflict of interest., (This work is licensed under a Creative Commons Attribution 4.0 International License.)

Objective: We aimed to investigate the relationship between oxidative stress (OS) and subclinical atherosclerosis in patients with premature ovarian insufficiency (POI), by analyzing the dynamic thiol/disulfide homeostasis (TDH) parameters as an OS marker and carotid intima-media thickness (CIMT). Materials and methods : A total of 69 women, 34 with POI and 35 healthy controls were included in this prospective cross-sectional study. TDH parameters (plasma native thiol, total thiol, disulfide, disulfide/native thiol, native thiol/total thiol, and disulfide/total thiol ratios) and CIMT were measured and compared between the two groups. Results: In primary ovarian insufficiency group, native thiol ( p =.009) and total thiol ( p =.010) levels were significantly decreased, and CIMT values were significantly increased ( p = <.001). CIMT values were negatively correlated with native thiol ( r =-0.553, p =.001) and total thiol levels ( r =-0.565, p =.001); and positively correlated with age ( r  = 0.457, p =.007), BMI ( r  = 0.408, p =.017), and total cholesterol ( r  = 0.605, p <.001) in POI group. Conclusions: Decreased native thiol and total thiol levels demonstrate the defective anti-oxidant mechanism in POI. Negative correlation between native thiol, total thiol levels, and CIMT means the presence of abnormal anti-oxidant mechanisms may play a role in the development of subclinical atherosclerosis in patients with POI. This is a novel report on the mechanism of subclinical atherosclerosis in women with POI, which needs to be supported with further studies evaluating the pathophysiology of OS.