Prolidase activity in women with polycystic ovarian syndrome undergoing assisted conception.

Background: Prolidase is a manganese (Mn)-dependent cytosolic exopeptidase that degrades imidodipeptides with C-terminal proline or hydroxyproline. Prolidase recycling from imidodipeptides plays a critical role in collagen resynthesis and extracellular matrix (ECM) remodelling. Following an increase in gonadotropins, ovarian and follicular collagen undergo substantial degradation. Abnormal ovarian ECM composition is associated with polycystic ovary syndrome (PCOS). This study aimed to examine prolidase activity in the serum and follicular fluid (FF) of women undergoing in vitro fertilisation/intracytoplasmic sperm injection (IVF/ICSI) treatment, comparing those with PCOS to those with normal ovarian function.Methods: This prospective study enrolled 50 participants, of whom 44 were included. PCOS diagnosis followed the Rotterdam consensus criteria, with 20 patients constituting the study group. The control group comprised 24 individuals with mild-to-moderate male infertility. Prolidase enzyme activity in serum and FF was measured using the Chinard reagent via spectrophotometric analysis and compared between the groups.Results: Serum and FF prolidase levels were significantly lower in patients with PCOS (p < 0.05). A direct correlation was observed between serum and FF prolidase levels (p < 0.05). Although blastocyst quality scoring (BQS) significantly decreased in PCOS patients, no statistical difference was observed in the clinical pregnancy rate between the groups (p < 0.05) (p > 0.05). A negative correlation existed between serum prolidase levels and total antral follicle (AF) count (p < 0.05). Conversely, both serum and FF prolidase levels positively correlated with BQS (r = 0.574)(p < 0.05) (r = 0.650)(p < 0.05).Conclusions: Patients with PCOS showed lower serum and FF prolidase levels, indicating abnormal degradation of ovarian and follicular collagen, potentially causing anovulation.

Polycystic ovary syndrome (PCOS), the most prevalent endocrinopathy among reproductive-aged women, affects approximately 3­15% of this demographic. Long-term disorders such as cardiovascular disease, type 2 diabetes mellitus, obesity, and infertility are commonly associated with PCOS, with approximately 70% of affected women experiencing infertility. Although the aetiology of PCOS remains unclear, complex multigenic disorders and environmental factors such as abnormal ovarian extracellular matrix composition, disruption of the inflammatory pathway, and lifestyle factors have been found to be related.This study addresses the aetiology of PCOS, focusing on the close association between abnormal ovarian extracellular matrix composition and the syndrome, as seen in previous reports. Prolidase is a manganese-dependent cytosolic exopeptidase that degrades imidodipeptides using the C-terminal proline or hydroxyproline. Proline recycling from imidodipeptides by prolidase plays a critical role in the resynthesis of collagen and remodelling of the extracellular matrix. Our aim was to evaluate prolidase activity in the serum and follicular fluid of women diagnosed with PCOS. Our findings revealed a direct correlation between serum and follicular fluid prolidase levels, both of which were diminished in women with PCOS. Furthermore, a negative correlation was observed between serum prolidase levels and total antral follicle count indicating a potential link between prolidase activity and ovarian follicle development. In contrast, both serum and follicular fluid prolidase levels were positively correlated with blastocyst quality. In conclusion, PCOS patients showed lower serum and follicular fluid prolidase levels, indicating abnormal degradation of ovarian and follicular collagen, and potentially causing anovulation. Future studies measuring manganese levels in larger numbers of participants are required.

Heavy Metal and Thiol/Disulfide in Children with Attention-Deficit and Hyperactivity Disorder.

Background: In the etiology of attention-deficit and hyperactivity disorder (ADHD), oxidative stress and heavy metal exposure are still controversial topics. In this study, our goal was to examine heavy metal levels and oxidative balance in newly diagnosed patients with ADHD and reveal whether heavy metal levels have an effect on the oxidation balance. Methods: The study included 35 patients with newly diagnosed ADHD and 31 healthy control groups of similar age and gender. Participants' parents or caregivers completed a semi-structured questionnaire regarding their children's breastfeeding and prenatal and postnatal smoking exposures. The levels of heavy metals lead (Pb), mercury (Hg), and cadmium were measured with inductively coupled plasma optical emission spectroscopy, and a unique automated spectrophotometric approach was used to quantify serum total thiol, native thiol, and disulfide quantities and ratios. Results: The rate of smoking during pregnancy was significantly higher in the ADHD group than in the control group (P = .030). Compared to the control group, the native and total thiol levels of children with ADHD were significantly higher (P < .001). Likewise, the ADHD group had significantly higher Hg levels compared to the control group (P = .002). Cadmium levels were substantially greater in the control group compared to the ADHD group (P < .001). However, there was no significant difference between Pb levels in the ADHD and the control group (P = .844). Conclusion: Exposure to Hg and prenatal smoking may contribute to the development of ADHD in childhood. In response to oxidative stress, the young brains of children with ADHD may enhance their antioxidant levels.

The Effect of Preoperative Carbohydrate-containing Fluid Consumption on Maternal Oxidative Stress Markers During Elective Cesarean Delivery.

PURPOSE: The purpose of this study was to evaluate the effect of carbohydrate loading prior to the cesarean surgery under spinal anesthesia on thiols and ischemia-modified albumin (IMA) levels. DESIGN: Prospective, randomized placebo-controlled study. METHODS: Seventy-nine pregnant women planned for cesarean sections under spinal anesthesia at Karaman Training and Research Hospital were randomized into a control group (group C) (n = 42), and an oral carbohydrate preloading group (group OCH) (n = 37). OCH loading requires consuming 400 mL the night before surgery and 200 mL up to 2 hours before anesthesia. Group OCH consumed an oral carbohydrate-rich beverage (Nutricia-Fantomalt), and group C consumed an equal volume of water. This study investigated thiol-disulfide homeostasis after preoperative carbohydrate consumption. Preoperative gastric fluid, volume, antral cross-sectional area, hypotension following the birth, and fetal blood gas parameters were compared across groups. FINDINGS: Thiols and IMA levels did not differ across groups before and after surgery (P > .05). Gastric ultrasonography showed similar antral cross-sectional area and stomach volume between groups (P = .172, P = .128, respectively). When surgery caused hypotension, group OCH received more ephedrine for surgery-induced hypotension, although this difference is not statistically significant (P = .704). A clustered error bar (95% confidence interval) plot with an interpolation line was used for a time-based comparison of mean differences in heart rate and mean arterial pressure between the groups. CONCLUSIONS: This study supports that mothers' thiols and IMA levels were unaffected by preoperative OCH loading before cesarean surgery. We did not examine thiol and its derivatives in umbilical cord blood; hence, we can not comment on thiol/disulfide homeostasis levels in neonates.

The role of thiol-disulfide homeostasis and ischemia-modified albumin in osteosarcopenia.

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.

Thiol-disulphide Homeostasis in Patients with Schizophrenia: The Potential Biomarkers of Oxidative Stress in Acute Exacerbation of Schizophrenia.

Objective: : Recent evidence suggests that oxidative stress contributes to the pathophysiology of schizophrenia. This study aimed to compare thiol-disulphide homeostasis in acute and stable phases of schizophrenia for the first time. Methods: : Among the patients with schizophrenia, 61 in the acute-phase and 61 in the stable phase of their illness were enrolled in the study. Native thiol (NT), total thiol (TT), disulphide (SS), disulphide/native thiol, disulphide/total thiol, and native thiol/total thiol for thiol-disulphide homeostasis were compared between the groups. The Brief Psychiatric Rating Scale (BPRS), Scale for the Assessment of Positive/Negative Symptoms (SAPS/SANS), Clinical Global Impression-Severity Scale (CGI-S), Barnes Akathisia Rating Scale, and Simpson-Angus Scale were used to assess symptoms. Results: : After controlling for age, sex, body mass index, and smoking status there were significant differences in NT, TT, SS/NT, SS/TT, and NT/TT, but not SS. Thiol/disulphide homeostasis has shifted in favour of the oxidative side in patients with acute-phase compared to that in stable schizophrenia. BPRS, SAPS, and CGI-S scores were significantly correlated with all six thiol-disulphide parameters, but not SANS, when controlling for age and sex. Significant receiver operating characteristic (ROC) curves were obtained for all thiol-disulphide homeostasis parameters. Discriminant analysis was found to be statistically significant in discriminating between groups. Conclusion: : These results show that oxidative status increases thiol-disulphide homeostasis in patients with acute-phase schizophrenia compared to those with stable schizophrenia. These findings suggest that thiol-disulphide parameters can be used as biomarkers for the acute exacerbation of schizophrenia.

Did diet compliance and remission reduce oxidative stress in celiac patients?

SUMMARY 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.

Effect of cardiopulmonary bypass on thiol/disulfide homeostasis in congenital heart surgery.

Background: This study aims to investigate whether thiol/disulfide homeostasis parameters measurements could be used as a new biomarker to predict the pre- and post-cardiopulmonary bypass oxidative status of pediatric patients undergoing congenital heart surgery. Methods: A total of 40 children with congenital heart disease (17 males, 23 females; mean age: 39.6±40.0 months; range, 2 to 216 months) who underwent open-heart surgery were included. The control group consisted of 40 age- and sex-matched healthy children (18 males, 22 females; mean age: 42.8±46.6 months; range, 12 to 156 months). The patients with congenital heart disease were divided into two groups as cyanotic patients (n=18) and acyanotic patients (n=22). Thiol/disulfide parameters were compared among the cyanotic, acyanotic congenital heart disease patients, and control group preoperatively (pre-CPB). The effects of cardiopulmonary bypass on thiol/disulfide parameters, pre-CBP, immediately after cardiopulmonary bypass (post-CPB0), and 24 h after cardiopulmonary bypass (post-CPB24) were investigated. Results: The mean native and total thiol levels in the cyanotic patients were significantly lower than those in the acyanotic patients and control group (p<0.0001). The cyanotic group exhibited higher disulfide levels than the acyanotic group (p<0.01). The mean native thiol and total thiol levels significantly decreased in the post-CPB0 (p<0.0001). The mean disulfide levels significantly increased in the post-CPB0 than the pre-CPB values (p<0.001). Post-CPB24 native and total thiol levels were elevated compared to post-CPB0 (p<0.0001). The mean disulfide levels significantly increased in the post-CPB24 period than the post-CPB0 values (p<0.001). The survivor patients responded better to oxidative stress than non-survivor patients. Conclusion: Thiol/disulfide measurement is a promising biomarker in determining the pre- and post-cardiopulmonary bypass oxidative status of pediatric patients undergoing congenital heart surgery. The interpretation of thiol/disulfide levels, pre- and postoperatively, may be used in predicting mortality and outcomes of these patients earlier.

Investigation of the clinical efficacy of thiol-disulfide homeostasis, delta neutrophil index, and ischemia-modified albumin in cases of incarcerated and strangulated hernia.

BACKGROUND: The treatment of patients presenting with the diagnosis of incarcerated and/or strangulated inguinal hernia is mostly surgery. If strangulation and necrosis are present, the need for laparotomy arises, which may increase the risk of morbidity. Currently, it is not possible to clearly determine whether there is bowel ischemia and necrosis before surgery. In this study, we aimed to investigate the clinical efficacy of the thiol-disulfide homeostasis, delta neutrophil index (DNI), and ischemia-modified albumin (IMA) parameters in incarcerated and strangulated hernia cases. METHODS: Patients that presented to the general surgery outpatient clinic due to inguinal hernia or to the emergency department of the hospital with a preliminary diagnosis of incarcerated and/or strangulated hernia in April 2021-November 2021 were included in the study. The patients were divided into the following four groups: patients that underwent elective repair for inguinal hernia (Group 1), those who were followed up without surgery due to incarcerated hernia (Group 2), those who underwent hernia repair without bowel resection due to incarceration (Group 3), and those who underwent bowel resection due to strangulation (Group 4). Group 1 was defined as the control group, while Groups 2, 3, and Group 4 were evaluated as the incarcerated/strangulated hernia group. The demographic data of the patients, length of hospital stay, body mass index, comorbidities, medical history and physical examina-tion findings, radiological examinations, treatments applied, white blood cell (WBC) count, lactate, and DNI, thiol-disulfide and IMA parameters were evaluated. RESULTS: The WBC count, disulfide/native thiol, disulfide/total thiol, and IMA values were significantly higher in the incarcerated/strangulated hernia group than in the control group, while the native thiol and total thiol values were higher in the latter than in the former (P<0.05). There was no statistically significant difference between the groups in terms of lactate (P>0.05), but the mean WBC count was higher in Group 4 compared to Group 1, and the mean DNI was significantly higher among the patients who underwent bowel resection and anastomosis than in those that were followed up and discharged (P<0.05). CONCLUSION: We consider that the preoperative evaluation of the thiol-disulfide homeostasis, IMA, and DNI parameters in incarcerated/strangulated hernia cases can be an effective and easily applicable method in predicting difficulties that may be encountered intraoperatively and the surgical procedure to be applied to the patient.

Thiol-disulphide homeostasis, ischemia-modified albumin, complete blood count-derived inflammatory markers and C-reactive protein from acute mania to early remission in bipolar disorder.

OBJECTIVES: There is much recent evidence that inflammation contributes to the pathophysiology of acute mania in bipolar disorder (BD). However, no study was evaluated in which the change in thiol-disulphide homeostasis, ischemia-modified albumin (IMA), complete blood count-derived inflammatory markers (CBC-IMs) and C-reactive protein (CRP) levels in bipolar patients was followed-up from acute mania to early remission. METHODS: Seventy-seven bipolar patients in acute mania and ninety-one HC were enrolled. We measured levels of thiol-disulphide parameters, IMA, and CBC-IMs such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), red-cell-distribution-width (RDW)-to-platelet ratio (RPR), systemic immune-inflammatory index (SII), and systemic inflammatory response index (SIRI), CRP and platelet-to-albumin ratio (PAR), after adjusting for age, gender, body-mass index (BMI) and smoking status, during acute mania to subsequent early remission. The results were compared with HC. RESULTS: The levels or ratios of all thiol-disulphide parameters except for disulphide, IMA and CRP of bipolar patients in both acute mania and early remission were significantly different from HC, after adjusting for confounders. The NLR, SII, CRP and PAR values of bipolar patients were significantly higher in only acute mania compared to HC. Significant changes in thiol-disulphide parameters and IMA levels were not found in early remission after acute mania. LIMITATIONS: Short follow-up period and lack of drug-naive patients. CONCLUSIONS: Our results suggest that thiol-disulphide parameters, IMA level and SIRI value might be a trait biomarkers of inflammation in BD. In addition, NLR, SII and PAR values and CRP level might be a state biomarker of inflammation in bipolar patients in a manic phase.

Thiol disulfide homeostasis in ionizing radiation and chemotherapeutic drug exposure.

OBJECTIVE: This study aims to reveal the oxidant and antioxidant status in nurses with chemotheropathic drug exposure and radiology unit workers exposed to ionizing radiation (IR). METHODS: Nineteen radiology unit workers, 14 nurses, and 15 controls were included the study. All of the participants using antioxidants, vitamin supplements, smokers, any therapeutic drugs, and exposed therapeutic or diagnostic X-ray or chemotherapeutic drugs in 12 months were excluded from the study. Total and native thiols, disulfide/native thiol percent ratios (SS/SH), disulfide/total thiol percent ratios, disulfide amounts, and native thiol/total thiol percent ratios, ischemia-modified albumin (IMA) were determined. RESULTS: Disulfide levels, disulfide/total thiol ratio, and disulfide/native thiol ratio of serum samples of both radiology unit workers and nurses were significantly higher and ratio of native thiol/total thiol was lower than the control group. The radiation dose in radiology unit workers was mean±SD: 0.02±0.009, median (min-max): 0.02 (0.001-0.04). Thiol-disulfide homeostasis was disturbed and the balance shifted in the direction of oxidant damage, even at low-dose IR exposure and normal range. CONCLUSION: As far as we know, the current findings first demonstrate an apparent chronic oxidative stress in the subjects who were occupationally exposed to antineoplastic drugs and radiation even if annual radiation exposure dose measurements are normal.

A New Perspective for Potential Organ Damage Due to Iron-Mediated Oxidation in Thalassemia Major Patients.

BACKGROUND: The aim of this study is to develop new perspectives to prevent or reduce potential organ damage due to iron-mediated oxidation in thalassemia major patients. METHODS: Seventy patients were included in this study. Blood samples were taken from the patients before and after transfusion. Total thiol, native thiol, disulfide, disulfide/native thiol percentage ratio, ischemia modified albumin (IMA), total antioxidant status (TAS), total oxidant status (TOS), and ferroxidase levels were determined. Additionally, undepleted thiol level (UTL) was determined as a new parameter associated with organ damage. RESULTS: After transfusion, the levels of native thiol, total thiol, disulfide, TAS, ferroxidase, and TOS were higher, while the IMA levels and disulfide/native thiol percent ratio were lower. Significant correlations were found between antioxidant and oxidant tests before and after transfusion. Additionally, a negative correlation was found between the TOS and UTL levels of the patients measured before the transfusion. CONCLUSION: In the present study, transfusion therapy increased both oxidation and the antioxidant levels. In addition, the term UTL has been introduced as a parameter that enables the determination of the oxidation level that may cause potential organ damage in transfusion-dependent thalassemia patients.

Prolidase as a marker of fibrogenesis in idiopathic primary ovarian insufficiency.

OBJECTIVES: To evaluate the serumlevel of prolidase,which isa marker of fibrogenic activity, in women with idiopathic primary ovarian insufficiency (POI). STUDY DESIGN: This is a prospective case-control study. Serum prolidase level was compared between the study group including 68 women with POI and control group including 65 normally menstruating women. Serum proline and hydroxyproline levels were also compared. Correlation analyses were performed between the prolidase level and POI related parameters including estradiol (E), follicle stimulating hormone (FSH), anti-mullerian hormone (AMH) levels, and presence of POI family history. RESULTS: Serum prolidase and proline level were significantly increased in women with the diagnosis of POI compared to the control group (1082.57 (147.53) vs 981.13 (223.26) U/L, 233.30 (83.16) vs 218.94 (82.59) µmol/L, respectively). Prolidase level found to have significant correlations with AMH, E, FSH levels, and presence of POI family history (r = -0.49, p = 0.001; r = -0.39, p = 0.001; r = 0.42, p = 0.001; r = 0.22, p = 0.01; respectively). In receiver operating characteristics analysis, prolidase was shown to be a discriminative factor for POI at 1031.14 U/L cut-off value with 75 % sensitivity and 65 % specificity. Thearea under curve was 0.71 [(95 % CI: 0.62-0.79), p = 0.001]. CONCLUSION: The current study revealed increased prolidase level in women withPOI. Serum prolidase level was also negatively correlated with the serum AMH level. Considering the present findings,prolidase may be a candidate molecule in assessment of POI cases.

Maternal Serum and Fetal Cord Blood Concentrations of Thiol/ Disulfide and Ischemia-Modified Albumin as Predictors of Neural Tube Defects.

AIM: To investigate the predictive role of thiol/ disulfide homeostasis and Ischemia-modified albumin (IMA) levels for NTDs. MATERIAL AND METHODS: A total of 71 pregnant women (31 with NTD and 42 healthy controls) were enrolled in this study. This prospective case-control study included pregnant women with NTDs as the study group and randomly selected age-matched pregnant women with healthy fetuses as the control group. The two groups were compared on the basis of thiol/disulfide and IMA levels in the maternal and fetal samples. RESULTS: No statistically significant difference in native thiol, total thiol, disulfide, and calculated ratios was observed between the groups. However, maternal IMA values were significantly higher in the study group. The IMA was proven to be a predictor with a sensitivity of 77.4% and specificity of 100% for NTDs at a cut-off value of 1.32. CONCLUSION: The examination of the maternal levels of IMA may be useful in the detection of NTDs.

Dynamic thiol-disulfide homeostasis as an oxidative stress marker in ankylosing spondylitis and undifferentiated spondyloarthropathy.

Background/aim: Seronegative spondyloarthropathies (SpA) are a group of chronic diseases characterized by axial inflammation, oligoarthritis, and enthesitis. Oxidative stress may contribute to a wide range of rheumatologic diseases, including SpA. This prospective case-control study was designed to compare thiol-disulfide levels as a marker of oxidative stress between SpA patients and healthy controls. Materials and methods: A total of 144 patients diagnosed with undifferentiated spondyloarthropathy (USpA, n = 97) or ankylosing spondylitis (AS, n = 47) were included along with 80 healthy controls. Serum native thiol (NT), total thiol (TT), and disulfide (D) levels were measured using the fully automated Erel method. The ratios NT/TT, D/TT, and D/NT were calculated. Thiol-disulfide levels were compared between the SpA groups and the healthy controls. Results: The NT and NT/TT ratios were found to be significantly lower in the SpA group (p < 0.001). The disulfide, D/NT, and D/TT ratios were found to be significantly higher in the SpA group (p < 0.001). In pairwise comparisons between the SpA subgroups, the NT and TT levels were lower in the USpA group than in the AS group (p = 0.021), but serum disulfide levels were higher in the USpA group than in the AS group (p = 0.004). Among the patients with SpA, the group taking antitumor necrosis factor (anti-TNF) had lower TT measurements compared to the group taking conventional disease modifying antirheumatic drugs (DMARD) (p = 0.039). Conclusion: The thiol-disulfide balance is disturbed in favor of disulfide in SpA patients compared to healthy volunteers. Native and total thiol measurements correlate with acute phase reactants and might be used to monitor disease activity. Anti-TNF therapy might control the oxidative degenerative process better than the conventional DMARD in SpA patients.

14-3-3η Proteins as a Diagnostic Marker, Disease Activation Indicator, and Lymphoma Predictor in Patients with Primary Sjögren Syndrome.

BACKGROUND: Primary Sjögren syndrome (PSS) is a chronic, autoimmune, and lymphoproliferative disease of the connective tissue. In patients with PSS, the risk of developing B-cell non-Hodgkin lymphoma (NHL) increases dramatically, with a prevalence of approximately 5%. The 14-3-3 protein isoforms are phospho-serin/phospho-threonine binding proteins associated with many malignant diseases. This study aimed to evaluate the relationship between disease activity parameters and markers predicting lymphoma development in patients with PSS and 14-3-3η proteins. METHODS: This study was designed as an analytical case-control study. A total of 57 PSS patients and 54 healthy volunteers were included in the study. The European League Against Rheumatism (EULAR) Sjögren syndrome disease activity index (ESSDAI) was used to assess systemic disease activity in PSS. Receiver operating characteristic (ROC) analysis was used to test the diagnostic accuracy measures of the analytical results. Multivariable linear regression analysis was used to evaluate the effects of independent variables on the 14-3-3η protein. RESULTS: The 14-3-3η protein serum levels were found to be significantly higher in PSS (2.72 [2.04-4.07]) than healthy controls (1.73 [1.41-2.43]) (P<0.0001). A significant relationship was found between 14-3-3η protein levels and ESSDAI group (ß=0.385, 95%CI=0.318-1.651, P=0.005), hypocomplementemia (C3 or C4) (ß=0.223, 95% CI=0.09-1.983, P=0.048) and purpura (ß=0.252, 95% CI=0.335-4.903, P=0.022), which are accepted as lymphoma predictors. A significant correlation was found between PSS disease activity score ESSDAI and 14-33η protein (ß=0.496, 95% CI=0.079-0.244, P=0.0002). CONCLUSION: 14-3-3η proteins are potential candidates for diagnostic marker, marker of disease activity, and predictor of lymphoma in PSS patients.

Evaluation of Oxidative Stress by Thiol/Disulphide Homeostasis in Patients with Mycosis Fungoides: A Prospective Double-Centre Study.

Background: Mycosis fungoides (MF) is the most common cutaneous T-cell lymphoma with unknown etiopathogenesis. Oxidant and antioxidant balance is important for cell function and normal metabolism. An imbalance between pro-oxidants and antioxidants causes oxidative stress. A recent focus has been on thiol/disulphide homeostasis as a novel marker of oxidative stress. Aims and Objectives: This study aimed to evaluate the role of oxidative stress in MF by analysing thiol/disulphide homeostasis. Materials and Methods: A total of 103 patients (48 female, 55 male) and a control group of 120 healthy individuals (48 female, 72 male) from two tertiary care hospitals were included in our study. Serum native thiol, total thiol and disulphide levels were evaluated using novel method developed by Erel and Neeliolu. Results: Native thiol levels were 340.30 ± 87.44 in the patient group and 401.62 ± 69.45 in the control group. Total thiol value was 374.17 ± 87.78 in the patient group and 428.54 ± 70.05 in the control group. Native thiol and total thiol levels were significantly lower in the patient group compared to the control group (P < 0.001 and P < 0.001). The disulphide value was 16.93 ± 6.46 in the patient group and 13.46 ± 5.06 in the control group. Disulphide levels were found to be significantly higher in the patient group compared to the control group (P < 0.001). Conclusions: In our study, thiol/disulphide balance shifted towards disulphide which indicates the presence of oxidative stress especially in the early stage while 93.2% of our patients had early-stage MF. We think that this may have pathogenetic and prognostic significance.

Association of thiol/disulphide homeostasis with Bethesda classification of thyroid nodules and thyroid cancer.

BACKGROUND: Ultrasonography and fine-needle aspiration biopsy are frequently used to diagnose thyroid cancer. However, supportive data might be required in case of diagnostic difficulty. This study investigated whether there is a relationship between thiol/ disulphide homeostasis and cytological and histopathological diagnosis of thyroid nodules. METHODS: The patient group consisted of 81 individuals with euthyroid nodular (single/multiple) goiter scheduled for thyroidectomy, and the control group consisted of 28 age- and sex-matched healthy volunteers who had no thyroid nodule on ultrasonographic evaluation. All participants were selected among the admissions to the study clinic between June 2017 and June 2018, and venous blood samples were collected. The samples of the patients were taken before surgery. Thiol and disulphide levels were analysed with the automated spectrophotometric method. RESULTS: The mean age of the patient group was 45.66 ± 10.45 years, and the mean age of the control group was 43.53 ± 11.49 years (p = 0.365). The increasing Bethesda categories were positively correlated with the disulphide level (r = 0.281, p = 0.011), disulphide/native thiol ratio (r = 0.241, p = 0.030) and disulphide/total thiol ratio (r = 0.250, p = 0.024). Disulphide/native thiol ratio and disulphide/ total thiol ratio were significantly higher in the histopathologically malignant (euthyroid nodular goiter but final pathology reported malignant) compared to histopathologically benign (euthyroid nodular goiter but final pathology reported benign) (p = 0.012; p = 0.007, respectively) and control groups (p = 0.006; p = 0.004, respectively), but no significant difference was found in these ratios between benign and control group (p = 0.711; p = 0.749, respectively). DISCUSSION: Oxidative stress parameters were significantly higher in thyroid cancer. A positive correlation was detected between Bethesda categories with increased risk of malignancy and the disulphide/native thiol ratio and the disulphide/total thiol ratio.

Oxidative Stress and Thiol/Disulfide Homeostasis in Human Papillomavirus Infections.

Introduction: Viral warts are a group of dermatological diseases caused by human papillomavirus (HPV). Several studies have demonstrated an association between HPV infections and oxidative stress. Thiols are important components of cellular redox homeostasis as antioxidant molecules in the organism. Aim: This study aimed to investigate the role of oxidative stress in patients with HPV infection by analyzing native thiol/disulfide homeostasis. Material and Methods: Forty-two patients with HPV infection and 40 healthy subjects were analyzed for the levels of native thiols, total thiols, and disulfide. Disulfide/native thiol, disulfide/total thiol, and native thiol/total thiol ratios were also calculated. Results: Disulfide and total thiol levels were higher in the patients compared to the healthy controls. The disulfide/native thiol ratio was also higher in the patient group. Native and total thiol levels decreased with the increasing duration of the disease. Conclusion: The native thiol/disulfide homeostasis was shifted toward disulfide in the patients' group, indicating the existence of oxidative stress in HPV infection.

The relationship between thiol-disulfide balance and idiopathic sudden sensorineural hearing loss / Relação entre equilíbrio tiol-dissulfeto e perda auditiva neurossensorial súbita idiopática

Abstract Introduction: Impaired cochlear perfusion is a major etiological factor in idiopathic sudden sensorineural hearing loss. Oxidative stress has been shown to be a risk factor for oxidative damage. Objectives: We investigated the role of oxidative stress in idiopathic sudden sensorineural hearing loss by comparing serum levels of oxidant and antioxidant molecules including thiol/disulfide homeostasis paraoxonase, stimulated thiol/disulfide homeostasis paraoxonase, arylesterase, ceruloplasmin and myeloperoxidase in patients who did and did not recover after treatment. Methods: The amount of dynamic disulfide was calculated by determining half of the difference between the total thiols and native thiols. After the determination of native, total thiol, and disulfide amounts, the disulfide/total thiol percent ratio, native thiol/total thiol ratio and disulfide/native thiol percent ratio were calculated and then compared between the two groups. Additionally, clinical relationship between audiological recovery and native thiol, disulfide, disulfide/native thiol percent ratio, and disulfide/total thiol percent ratio levels was investigated. Blood samples were also analyzed for the assessment of thiol/disulfide homeostasis paraoxonase, stimulated thiol/disulfide homeostasis paraoxonase, arylesterase, ceruloplasmin, and myeloperoxidase levels. Results: A significant difference was found between the two groups with regard to total oxidant status disulfide, disulfide/native thiol percent ratio, disulfide/total thiol percent ratio, and native thiol/total thiol ratio levels (p = 0.001, p = 0.001, p = 0.001, p = 0.003, p = 0.001, p = 0.002, respectively). However, no significant difference was found between the two groups with regard to thiol/disulfide homeostasis paraoxonase, stimulated thiol/disulfide homeostasis paraoxonase, ceruloplasmin, and myeloperoxidase levels (p > 0.05 for all). Conclusion: The results supported the common hypothesis that vascular pathologies are the primary cause of idiopathic sudden sensorineural hearing loss and that other etiological factors ultimately result in vascular pathologies. The oxidant-antioxidant and thiol-disulfide balances were impaired in the idiopathic sudden sensorineural hearing loss group.

Resumo Introdução: A perfusão coclear prejudicada é um fator etiológico importante na perda auditiva neurossensorial súbita idiopática (PANSSI). O estresse oxidativo mostrou ser um fator de risco para danos oxidativos. Objetivos: Investigamos o papel do estresse oxidativo na PANSSI mediante a comparação dos níveis séricos de moléculas oxidantes e antioxidantes, inclusive homeostase de tiol/dissulfeto, paraoxonase, paraoxonase estimulada, arilesterase, ceruloplasmina e mieloperoxidase em pacientes com e sem recuperação após o tratamento. Método: A quantidade de dissulfeto dinâmico foi calculada mediante a determinação de metade da diferença entre os tiois totais e os tiois nativos. Após a determinação das quantidades de tiol nativo, tiol total e dissulfeto, as razões percentuais de dissulfeto/tiol total, tiol nativo/tioltotal e dissulfeto/tiol nativo foram calculadas e depois comparadas entre os dois grupos. Além disso, a relação clínica entre a recuperação audiológica e os níveis de tiol nativo, tiol nativo/tiol total, dissulfeto, dissulfeto/tiol nativo e dissulfeto/tiol total foi investigada. Amostras de sangue também foram analisadas para avaliar os níveis de paraoxonase, paraoxonase estimulada, arilesterase, ceruloplasmina e mieloperoxidase. Resultados: Uma diferença significante foi encontrada entre os dois grupos em relação ao estado oxidante total e aos níveis de dissulfeto, dissulfeto/tiol nativo, dissulfeto/tiol total, tiol nativo/tiol total (p = 0,001, p = 0,001, p = 0,001, p = 0,003, p = 0,001, p = 0,002, respectivamente). Porém, não foi encontrada diferença significante entre os dois grupos em relação aos níveis de paraoxonase, paraoxonase estimulada, ceruloplasmina e mieloperoxidade (p> 0,05 para todos). Conclusão: Os resultados apoiaram a hipótese comum de que as doenças vasculares são a principal causa de PANSSI e que, em última análise, outros fatores etiológicos resultam em doenças vasculares. Os equilíbrios de oxidante-antioxidante e tiol-dissulfeto estavam prejudicados no grupo PANSSI.

Comparison of Thiol-Disulfide Hemostasis With Inflammatory Markers in the Inflammatory Process of Acute Appendicitis.

Background Acute appendicitis is one of the events most frequently encountered by general surgeons. Despite the high incidence, serious problems are experienced in the diagnosis and clinical follow-up. In the pathogenesis of the disease, oxidative stress and impaired antioxidant defense mechanisms created in the body by this stress play an important role. As dynamic thiol-disulfide hemostasis is closely related to oxidative stress and is known to have a crucial role in the pathogenesis of oxidative stress, this study aimed to compare its value with other inflammatory markers in the diagnosis and follow-up of acute appendicitis. Methodology This study included cases admitted for surgery with a diagnosis of acute abdomen at Keçiören Research and Training Hospital General Surgery Clinic between April 2015 and July 2015 who were intraoperatively diagnosed with acute appendicitis and underwent routine appendectomy. In the preoperative period and after clinical healing before discharge, blood samples were obtained to examine white blood cell (WBC), mean platelet volume (MPV), total bilirubin, C-reactive protein (CRP), and thiol-disulfide balance, and the results were recorded. Results A total of 68 cases were operated on for acute appendicitis, and 59 were evaluated comprising 23 (39%) females and 36 (61%) males with a mean age of 35.6 years (range = 19-65 years). The mean duration of hospital stay was two days (range = 1-8 days). The results of the tests performed preoperatively and before discharge and their p-values were as follows: native thiol (-SH) 393.5 ± 9.4 µmol/L and 369.3 ± 9.5 µmol/L (p = 0.04), total thiol 434 ± 9.7 µmol/L and 396.7 ± 10.2 µmol/L (p = 0.03), disulfide (-S-S) 16.8 ± 0.7 µmol/L and 15.7 ± 0.9 µmol/L (p = 0.3), WBC 13.2 ± 0.5 × 10³/mL and 9.2 ± 0.4 × 10³/mL (p = 0.0), CRP 8.17 ± 1.24 mg/L and 7.84 ± 0.82 mg/L (p = 0.17), MPV 7.4 ± 0.37 fL and 7.97 ± 0.19 fL (p = 1.0), and total bilirubin 0.86 ± 0.08 mg/dL and 0.69 ± 0.06 mg/dL (p = 0.08). Conclusions In the clinical follow-up of acute appendicitis patients, the decrease in WBC, total thiol, and native thiol values can be helpful to clinicians as markers of clinical healing. However, CRP may not be a useful marker of clinical healing in acute appendicitis patients who are discharged early.