Thiol-disulfide homeostasis: an integrated approach with biochemical and clinical aspects

Dynamic thiol-disulfide homeostasis (TDH) is a new area has begun to attract more scrutiny. Dynamic TDH is reversal of thiol oxidation in proteins and represents the status of thiols (-SH) and disulfides (-S-S-). Organic compounds containing the sulfhydryl group is called thiol, composed of sulfur and hydrogen atoms. Disulfides are the most important class of dynamic, redox responsive covalent bonds build in between two thiol groups. For many years, thiol levels were analyzed by several methods. During last years, measurements of disulfide levels have been analyzed by a novel automated method, developed by Erel and Neselioglu. In this method, addition to thiol (termed as native thiol) levels, disulfide levels were also measured and sum of native thiol and disulfide levels were termed as total thiol. Therefore, TDH was begun to be understood in organism. In healthy humans, TDH is maintained within a certain range. Dysregulated dynamic TDH has been implicated several disorders with unknown etiology. A growing body of evidence has demonstrated that the thiol-disulfide homeostasis is involved in variety diseases, such as diabetes mellitus, hypertension, nonsmall cell lung cancer, familial Mediterranean fever (FMF), inflammatory bowel diseases, occupational diseases, gestational diabetes mellitus and preeclampsia. These results may elucidate some pathogenic mechanism or may be a predictor indicating diagnostic clue, prognostic marker or therapeutic sign. In conclusion, protection of the thiol-disulfide homeostasis is of great importance for the human being. Evidence achieved so far has proposed that thiol-disulfide homeostasis is an important issue needs to elucidate wholly.

A new potential biomarker in early diagnosis of firefighter lung function impairment: dynamic thiol/disulphide homeostasis.

OBJECTIVES: The aim of this study was to investigate the associations between urinary arsenic, oxidative stress, assessed by thiol/disulphide homeostasis, and lung diseases in firefighters. METHODS: The study conducted among the municipality-based male firefighters (n = 100) who were admitted to occupational diseases clinic for periodic medical examination. The control group consisted of non-exposed male office workers (n = 50). Urinary arsenic levels, thiol/disulphide homeostasis parameters of participants were determined. Also, lung diseases were assessed by chest X-ray and pulmonary function tests. RESULTS: The mean age and work year did not differ in the study and control group. The median urinary arsenic concentration of firefighters was significantly higher than in the control group: 15.65 (2.5-246) µg/L and 3 (0.10-6) µg/L, respectively (p < 0.001). The parameters of pulmonary function tests (PFT) FVC (%), FEV1 (%), FEV1/FVC ratio and FEF 25-75 (%) were all significantly lower in firefighters compared to controls. A significant increase in mean serum disulphide concentration (17.10 ± 8.31 µmol/L vs. 7.48 ± 5.91) (Fig. 1) and disulphide/native thiol % ratio: 3.63 (0.53-11.43) vs. 1.51 (0.03-7.65) (p < 0.001) were found between exposed group and controls. The Spearman's correlation analysis revealed a positive correlation between urinary arsenic and disulphide (r = 0.422, p < 0.001), disulphide/native thiol % ratio (r = 0.409, p < 0.001). Nevertheless, urinary arsenic correlated negatively with all PFT parameters including FVC (%), FEV1 (%), FEV1/FVC and FEF 25-75 (%) (p < 0.001). CONCLUSION: We showed the arsenic-induced oxidative stress in firefighters with impairments of several lung functions determined by thiol/disulphide homeostasis using a novel method.

The effects of transport by car on coagulation tests.

BACKGROUND: This research investigated the effects of the transport of blood samples between centers/laboratories by car on coagulation tests. METHODS: Five tubes of blood samples were taken from 20 healthy volunteers. The samples consisted of a baseline (control) group, centrifuged and noncentrifuged transported samples; centrifuged and noncentrifuged untransported samples. The groups of centrifuged and noncentrifuged samples were transported by car for 2 h. The centrifuged and noncentrifuged untransported samples were incubated in the laboratory until the transported samples arrived. Prothrombin time (PT) and activated partial thromboplastin time (APTT) tests were conducted for all samples. RESULTS: Significant differences between the baseline group and the centrifuged and noncentrifuged transported samples and the noncentrifuged untransported samples were found for APTT levels (p<0.05, for all). In addition, significant mean percentage differences in PT values were found between the baseline group and the noncentrifuged transported samples (p<0.001) and the noncentrifuged untransported samples (p=0.005). The mean level of PT in the noncentrifuged transported samples was outside the upper limit of the clinical decision level. CONCLUSIONS: Noncentrifuged transported samples showed clinically significant differences in PT test results that may have stemmed from mechanical agitation during transportation. Therefore, we recommend not transporting noncentrifuged specimens for PT testing by car.

An evaluation of thiol/disulphide homeostasis in patients with psoriasis.

INTRODUCTION: The role of oxidative stress in the pathogenesis of psoriasis has been investigated in previous studies with conflicting results. On the other hand, well-established treatments currently used in psoriasis exert their effects via a boost of oxidative stress. Recently, a strong positive association between psoriasis, metabolic syndrome and dyslipidemia has also been described showing the complex nature of the disease. AIM: To examine thiol/disulphide homeostasis, a newly developed homeostasis assay in psoriasis and evaluate the possible association between thiol/disulphide homeostasis and dyslipidemia in psoriasis. MATERIAL AND METHODS: The study population included 92 psoriasis patients and 71 healthy subjects. Serum native thiol, total thiol and disulphide levels were investigated in patients with psoriasis and in healthy subjects. In addition, lipid profile (serum total cholesterol, triglyceride, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol) levels were investigated in both groups. The association between thiol-disulphide parameters and dyslipidemia was also evaluated. RESULTS: Serum total cholesterol and triglyceride levels were found to be higher in patients with psoriasis than in the healthy group. Lower plasma disulphide and higher native thiol levels were found in patients with psoriasis indicating an antioxidant status. CONCLUSIONS: To our knowledge, this is the first study showing the shift of dynamic thiol/disulphide homeostasis towards the thiol form in psoriasis which indicate higher antioxidant status.

Inflammation and chemerin in colorectal cancer.

Chemerin is expressed mainly in the adipose tissue. It is an agonist of chemokine-like receptor-1, which is expressed by the immune system cells. Chemerin stimulates the chemotaxis of the immune system cells, and this indicates the function of chemerin and chemokine-like receptor-1 in the immune response. The tumor microenvironment is very important for determining cancer cell growth and spreading. Therefore, we aimed to investigate the association between colorectal cancer, inflammation, and adipokines including chemerin, adiponectin, and vaspin. The study group consisted of patients with colon cancer, whereas the control subjects consisted of patients with benign conditions, diagnosed with colonoscopy. The two groups were compared in terms of the C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), fibrinogen, adiponectin, chemerin, and vaspin. A total of 41 (28 men, 13 women) patients with confirmed colon cancer, and 27 (15 men, 12 women) controls without, confirmed by colonoscopy, were enrolled. The median chemerin levels were found significantly higher in the study group than the controls (390 vs. 340 ng/mL, p = 0.032), whereas the mean vaspin and adiponectin levels were not significantly different. The median values for the CRP, fibrinogen, and ESR were significantly higher in the patients with colon cancer, when compared to the control group (6.08 vs. 1.4 mg/L, p < 0.0001; 408 vs. 359 mg/dL, p = 0.002; and 30 vs. 8 mm/h, p < 0.0001, respectively). Our results show that higher levels of circulating chemerin, CRP, fibrinogen, and ESR are associated with an increased risk of developing colorectal cancer.

Serum vaspin and adiponectin levels in patients with prolactinoma.

BACKGROUND: Studies investigating serum vaspin and adiponectin levels in patients with prolactinoma are inconclusive. The aim of this study was to evaluate serum vaspin and adiponectin levels in patients with prolactinoma and healthy controls. METHODS: A total of 42 prolactinoma patients (Group 1, 21 patients; Group 2, 21 patients) and 30 healthy controls were enrolled in the study. Group 1 consisted of newly diagnosed patients who were never treated or had not received a dopamine agonist (DA) within 6 months prior to screening. Group 2 consisted of prolactinoma patients who were on DA treatment for at least 6 months at the time of screening. The control group (group 3) consisted of healthy controls. RESULTS: Patients with prolactinoma had higher homeostasis model assessment of insulin resistance and lower quantitative insulin sensitivity check index values in comparison to healthy controls (p < 0.001 for both). Serum levels of adiponectin and vaspin were also significantly lower in prolactinoma patients when compared to the control group (p < 0.01 and p < 0.001, respectively). Following adjustment for confounding factors, the respective odds ratios for prolactinoma in patients in the lower subgroup compared with those in the higher subgroup for adiponectin and vaspin were 2.733 (0.621-12.035; p > 0.05) and 5.041 (1.191-21.339; p < 0.05). CONCLUSION: This is the first study to demonstrate the presence of low vaspin levels in patients with prolactinomas. Further studies are needed to help establish the roles of vaspin and adiponectin in prolactinoma patients.

Augmentation of ADAMTS9 gene expression by IL-1ß is reversed by NFκB and MAPK inhibitors, but not PI3 kinase inhibitors.

The pathways involved in the regulation of a disintegrin and metalloproteinase with thrombospondin motifs 9 (ADAMTS9) expression have not yet been elucidated. Therefore, the aim of this study was to investigate the involvement of nuclear factor-κB (NF-κB), mitogen activated protein kinases (MAPK) and Phosphatidylinositol 3-kinase (PI3 kinase) in ADAMTS9 gene regulation, with special focus on the involvement of NF-κB in IL-1ß-induced ADAMTS9 expression. The OUMS-27 chondrosarcoma cells were exposed to IL-1ß. They were pretreated with 20 µM PD98059 (specific inhibitor of p44/42 kinase), 10 µM SB203580 (specific inhibitor of p38 kinase), 20 µM SB600125 (MAPK inhibitor), and 1 µM Wortmannin and 10 µM LY294002 (specific inhibitors of PI3 kinase) for 30 min and subsequently incubated with IL-1ß. For the effects of NF-κB and IκB inhibitors, cells were pretreated with curcumin or BAY117085 for 30 min and subsequently incubated with IL-1ß. BAY117085 and different concentrations of curcumin were applied to the cells just after the first experiment to determine their concentration effect on ADAMTS9 gene expression. After total RNA was extracted, they were reversely transcribed with random primers and then real-time polymerase chain reaction (PCR) was performed on cDNA samples. There was a significant difference between control and stimulated cells in terms of ADAMTS9/ß-actin ratio. Wortmannin and LY294002 did not have any repressive effect on the OUMS-27 whereas SB203580 and SP600125 were found to decrease the expression of ADAMTS9 gene. BAY 117085 and curcumin, which are two NF-κB inhibitors, led to a decrease in the ratio of ADAMTS9/ß-actin. As a conclusion, the pathways MAPK and NF-κB were thought to be responsible pathways for the induction of ADAMTS9 gene.

The diagnostic value of non-invasive tests for the evaluation of liver fibrosis in chronic hepatitis B patients.

BACKGROUND: Liver biopsy, which is considered the gold standard for the evaluation of hepatic fibrosis in patients with chronic hepatitis B (CHB), has certain limitations. The aim of this study was to investigate the diagnostic performance of non-invasive markers of hepatic fibrosis as potential alternatives to liver biopsy. METHODS: The medical records of 221 patients with a diagnosis of CHB who underwent a liver biopsy were reviewed. Indirect indicators of fibrosis were calculated for each patient based on previously described formulas [Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio (AAR), age-platelet index (API), cirrhosis discriminant score (CDS), AST-platelet ratio index (APRI), Forns index, FIB-4, Pohl score, AAR-platelet score (AARP), fibro-quotient (FibroQ), AST/platelet/Gammaglutamyl transpeptidase (GGT)/Alphafetoprotein (AFP) (APGA) index, Platelet/Age/Phosphatase (ALP)/AFP/AST (PAPAS) index, Lok's model, Goteborg University Cirrhosis Index (GUCI)]. Diagnostic adequacy of these indices was evaluated by receiver operating characteristic curve analysis. RESULTS: Area under the receiver operating characteristic curves for the FIB-4, Forns, GUCI, APRI, PAPAS, APGA and FibroQ indices were 0.701, 0.680, 0.670, 0.670, 0.639, 0.638 and 0.588, respectively. The AAR, API, CDS and AARP indices, Pohl score and Lok's model were all deemed diagnostically inadequate. FIB-4 had the best diagnostic adequacy whereas AAR had the worst. CONCLUSIONS: Our results suggest that out of the 13 indices evaluated, only FIB-4 index may be useful in estimating the extent of fibrosis in patients with CHB. There is a need for more comprehensive prospective studies to help determine the diagnostic value of non-invasive tests for liver fibrosis.

Evaluation of cases with impaired state of consciousness: Gaziantep Children's Hospital experience.

The aim of this study was to characterize the etiology, course and prognosis in children admitted to a pediatric intensive care unit (PICU) of Gaziantep Children's Hospital for impaired state of consciousness. Three hundred and eighty cases were evaluated. Convulsions (44%; n=170) were the leading cause of the impaired state of consciousness followed by poisonings, envenomation, infection, metabolic disease, electrical injury, hepatic encephalopathy, intracranial hemorrhage, brain tumor, and drowning. The diagnosis was definite in 95% (n=359) and probable in 5% (n=21) of cases. Twenty-seven (7%) patients died with impaired state of consciousness. We suggest that defining the causes of impaired state of consciousness in a specific region will help physicians to evaluate the patients faster and in a more systemic manner. Since most of the causes seem to be preventable, appropriate education programs and policies should be provided for improving sanitation and socioeconomic conditions.

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.

Evaluation of gastric emptying rate in patients with fibromyalgia: a case control study.

Fibromyalgia (FM) is a chronic pain illness with unknown etiology, and it generally affects women. These patients also have gastrointestinal symptoms and signs. In this study, we aimed to evaluate the gastric emptying rate in patients with newly diagnosed FM by using the radionuclide method. Investigation of the differences in gastric emptying rate, the number of pain points, and Fibromyalgia Impact Questionnaire (FIQ) scores between premenopausal and postmenopausal FM patients was planned as secondary goal of this study. Fifteen female patients (ages 17-68 years) with FM and 15 age-matched healthy women (ages 20-65 years) as a control group participated in the study. Exponential gastric emptying rate at 30, 60, 90 min and duration of the lag phase were calculated. There was no statistically significant difference in the mean age or in the gastric emptying rates at 30, 60, and 90 min between these two groups (p > 0.05). Mean time of the lag phase of the FM group was significantly longer than that of the control group (p < 0.05). Average age at menopause in the FM group was also significantly lower than that of patients in the control group (p < 0.05). When FM patients were divided into the two subgroups of menopausal and premenopausal patients, there was no significant difference in gastric emptying rate, duration of the lag phase, the number of pain points, and FIQ scores between these two groups (p > 0.05). Although gastric emptying rate was not affected in patients with FM, grinding was prolonged. This result can be explained as one of the causes of gastrointestinal complaints of FM patients. In addition there was no determined influence of menopause on prolonged grinding. However, further studies are needed to elucidate the relationship between clinical findings and gastrointestinal functions and complaints of FM patients.

Dynamic Thiol/Disulfide Balance in Patients with Seborrheic Dermatitis: A Case-Control Study.

BACKGROUND: Seborrheic dermatitis is a chronic, inflammatory skin disease, in which many endogenous and exogenous factors play a role. Recent studies have shown that oxidative stress increases in these patients. The role of the dynamic thiol/disulfide homeostasis, an important component of the oxidative stress, in the pathogenesis of seborrheic dermatitis has not yet been investigated. OBJECTIVES: The objective was to investigate the relationship between the dynamic thiol/disulfide balance in the plasma of seborrheic dermatitis patients and disease severity. METHODS: In this case-control study, 70 seborrheic dermatitis patients and 61 age- and sex-matched healthy controls were included. Thiol/disulfide homeostasis was calculated from venous blood samples, and tests were performed by automated spectrophotometric method. The thiol/disulfide balance between the patient and control groups was compared. In addition, disease severity and other demographic characteristics and thiol/disulfide balance parameters were compared. RESULTS: Native and total thiols were significantly higher in the patient group than that in the control group (P < 0.001). Disulfide levels were nonsignificantly lower in the patient group than controls (P = 0.821). Patients' age and age at the onset of disease were found to have a negative correlation with native and total thiol levels. CONCLUSION: Higher levels of thiols in the serum may be responsible for the increased proliferation of seborrheic dermatitis lesions. To the best of the authors' knowledge, this is the first report on the correlation between thiol/disulfide homeostasis in patients with seborrheic dermatitis.

Is Thiol/Disulphide homeostasis important in prostate cancer diagnosis? / Es importante la homeostasis del Tiol/Disulfito en el diagnóstico del cáncer de próstata?

OBJECTIVES: To assess the relationship between prostate cancer and thiol/disulphide homeostasisas an important indicator of oxidative stress. METHODS: After ethics committee approval (546/2015); 388 patients aged between 46-75 years who underwent transrectal ultrasound guided prostatebiopsy in three different centers between July 2015-2016 owing to serum prostate specific antigen (PSA) levels ≥2.5 ng/ml and/or abnormal digital rectal examination were involved in this study. The plasma levels of thiol/disulphide homeostasis parameters were compared in patients with and without prostate cancer. RESULTS: The mean age of the patients was 62.9±7 years. In patients with prostate cancer (n=130, 33.5% ) the mean plasma levels of native thiol and total thiol were lower (332.9 vs 362.1 µmol/L and 363 vs 392.6 µmol/L, p=0.001). Plasma disulphide levels were not statistically different between the groups (15 vs 15.3 µmol/L, p=0.936). In prostate cancer group; patients with Gleason score ≥7 had lower plasma native thiol levels than patients with Gleason score<7 (321.3  vs 342.6 µmol/L, p=0.029) while there were no significant differences in total thiol and disulphide levels (352.3 vs 371.9 µmol/L, ptotal Thiol =0.064 and 15.5 vs 14.6 µmol/L, pdisulphide =0.933). CONCLUSIONS: Lower plasma levels of thiol in patients with prostate cancer and high Gleason score is an oteworthy result. We believe that our results should be supported by further studies.

OBJETIVOS: Establecer la relación entre cáncer de próstata y la homeostasis del tiol/disulfito como un importante indicador de estrés oxidativo.MÉTODOS: Con la aprobacion del comité ético (546/2015), 388 pacientes entre 46 y 75 años que recibieron una biopsia transrectal prostática ecoguiada en diferentes centros entre julio 2015 y 2016 por un PSA superior a 2,5 ng/ml o tacto rectal anómalo, fueron incluidos en este estudio. Los niveles plasmáticos de la homeostasis de tiol/disulfito se compararon en pacientes con y sin cáncer de próstata. RESULTADOS: La edad media de los pacientes fue de 62,9 =/- 7 años. En pacientes con cáncer de próstata (n=130, 33,5%) el nivel plasmático de tiol nativo y tiol total fue menor (332,9 vs 362,1 µmol/L y 363 vs 392,6 µmol/L, p=0,001). Los niveles de disulfito en plasma no fueron estadísticamente diferentes entre los grupos (15 vs 15,3 µmol/L, p=0,936). En el grupo con cáncer de próstata; pacientes con Gleason 7 o más tuvieron niveles menores de tiol nativo en relación a los pacientes con Gleason menor de 7 (321,3 vs 342,6 µmol/L, p=0,029), mientras no hubo diferencias en eltiol total y los disulfitos (352,3 vs 371,9 µmol/L, ptotaltiol =0,064 y 15,5 vs 14,6 µmol/L, pdisulfito =0,933). CONCLUSIONES: Niveles bajos de tiol en pacientes con cáncer de próstata y Gleason alto es un resultado notable. Creemos que nuestros resultados deberian tenerse en cuenta para otros estudios.

Clinical and laboratory features of COVID-19: Predictors of severe prognosis.

BACKGROUND: Coronavirus disease 2019 (COVID-19) emerged first in December 2019 in Wuhan, China and quickly spread throughout the world. Clinical and laboratory data are of importance to increase the success in the management of COVID-19 patients. METHODS: Data were obtained retrospectively from medical records of 191 hospitalized patients diagnosed with COVID-19 from a tertiary single-center hospital between March and April 2020. Prognostic effects of variables on admission among patients who received intensive care unit (ICU) support and those who didn't require ICU care were compared. RESULTS: Patients required ICU care (n = 46) were older (median, 71 vs. 43 years), with more underlying comorbidities (76.1% vs. 33.1%). ICU patients had lower lymphocytes, percentage of large unstained cell (%LUC), hemoglobin, total protein, and albumin, but higher leucocytes, neutrophils, neutrophil-lymphocyte ratio (NLR), monocyte-lymphocyte ratio (MLR), platelet-lymphocytes ratio (PLR), urea, creatinine, aspartate amino transferase (AST), lactate dehydrogenase (LDH), and D-dimer when compared with non-critically ill patients (p < 0.001). A logistic regression model was created to include ferritin, %LUC, NLR, and D-dimer. %LUC decrease and D-dimer increase had the highest odds ratios (0.093 vs 5.597, respectively) to predict severe prognosis. D-dimer, CRP, and NLR had the highest AUC in the ROC analysis (0.896, 0.874, 0.861, respectively). CONCLUSIONS: The comprehensive analysis of clinical and admission laboratory parameters to identify patients with severe prognosis is important not only for the follow-up of the patients but also to identify the pathophysiology of the disease. %LUC decrease and D-dimer, NLR, and CRP increases seem to be the most powerful laboratory predictors of severe prognosis.

Thiol Disulfide Homeostasis in Schizophrenic Patients Using Atypical Antipsychotic Drugs.

OBJECTIVE: Schizophrenia is a severe, debilitating mental disorder characterized by behavioral abnormalities. Although several studies have investigated the role of oxidative stress and the effects of antipsychotic drugs on oxidative markers in schizophrenia, adequate information is not available on these issues. The aim of this study is to determine the changes in oxidative status and thiol disulfide homeostasis in schizophrenic patients using atypical antipsychotic drugs. METHODS: Thirteen schizophrenic patients using atypical antipsychotic drugs and 30 healthy controls were included this study. The concentrations of total oxidant status (TOS), total antioxidant status (TAS), native thiol, total thiol, and disulfide levels were determined in the study population. RESULTS: The TAS (p=0.001), total thiol, and native thiol levels (p＜0.001) were higher in the patients compared to the controls, whereas the TOS and disulfide levels were lower in the patients than in the controls (p＜0.001). CONCLUSION: These results may suggest that atypical antipsychotic drugs have a useful therapeutic effect by reducing oxidative stress via the inhibition of the formation of disulfide bonds. The study population number was one of the limitations of this study. Therefore, further studies are needed to establish the association between thiol disulfide homeostasis in schizophrenic patients using atypical antipsychotic drugs.

Melatonin ameliorates blood-brain barrier permeability, glutathione, and nitric oxide levels in the choroid plexus of the infantile rats with kaolin-induced hydrocephalus.

Hydrocephalus is a disabling disease for children, but current data concerning the effects of melatonin on ventricular enlargement are still limited. We have investigated the changes in the choroid plexuses (CPs) of ventricles and blood-brain barrier (BBB) of hydrocephalic rats. Forty-five Swiss Albino rats at age 2 weeks were divided into three equal groups: control, hydrocephalus, and melatonin-treated hydrocephalus groups. Hydrocephalus was induced by kaolin injection into the cisterna magna of all pups except control group and melatonin was given at a daily dose of 0.5 mg/100 g body weight for 4 weeks. At the end of the study, one animal from each group was examined using a gamma camera to study the disruption of BBB due to hydrocephalus. All animals were then killed for assay of glutathione (GSH) and nitric oxide (NO), as well as histological study of the CPs during the hydrocephalus. We observed an increased BBB activity was found in hydrocephalus group, while melatonin reversed these changes. It was found that NO concentration was elevated in hydrocephalus group and melatonin partly abolished the increased levels of NO. In contrast, GSH levels were significantly decreased in hydrocephalus group, while melatonin increased the tissue GSH level (p<0.01). Histologically, there was a significant alteration in the CPs of the ventricles of hydrocephalic animals, but it was regressed after melatonin treatment in consistent with the gross morphological changes related to hydrocephalus. In conclusion, our results clearly demonstrated for the first time the neuroprotective effects of melatonin upon hydrocephalus-induced CP changes in infantile rats, but further studies are needed to suggest melatonin as a candidate protective drug in children.

Thiol/disulfide parameters as a novel oxidative marker in medical labor induction with oxytocin.

BACKGROUND: The aim of this study was to analyze the alterations in thiol levels among mothers and neonates who were prone to medical oxytocin induction. MATERIALS AND METHODS: A total of 40 pregnant women who underwent medical labor induction with oxytocin (Group A) were compared with 53 women whose labor progressed spontaneously without any kind of induction (Group B). We measured the thiol/disulfide homeostasis parameters (native thiol, total thiol, disulfide, disulfide/total thiol, disulfide/native thiol) of maternal and cord blood. RESULTS: There were no statistically significant differences with respect to the maternal and cord blood thiol/disulfide homeostasis between the two groups. CONCLUSION: Being an artificial intervention during labor, oxytocin induction has been found to be safe in terms of oxidative stress (OS) according to the results of this study. Both the maternal and the fetal sides were safe in this molecular manner against oxytocin infusion.

Thiol/disulfide homeostasis: A prognostic biomarker for patients with advanced non-small cell lung cancer?

BACKGROUND: The aim of this study was to investigate oxidative stress and thiol/disulfide status with a novel automated homeostasis assay in advanced non-small cell lung cancer (NSCLC). METHODS: Thirty-five patients with advanced NSCLC, who had been newly diagnosed and previously untreated, and 35 healthy subjects were chosen for the study. We measured plasma total thiol (-SH+-S-S-), native thiol (thiol) (-SH), and disulfide (-S-S-) levels in the patients with NSCLC and the healthy subjects. The thiol/disulfide (-SH/-S-S-) ratio was also calculated. RESULTS: Statistically significant differences between the patient group and the control group were detected for the thiol/disulfide parameters. The mean native thiol, total thiol, and disulfide levels were significantly lower in the group with advanced stage NSCLC. The cut-off value was 313 and 13.8 for native thiol and disulfide, respectively. Median overall survival (OS) was significantly shorter in patients with low native thiol and disulfide levels according to the cut-off value (respectively, P = 0.001; P = 0.006). Native thiol, total thiol, and disulfide levels were correlated with Karnofsky performance status (KPS), OS, and age. Additionally, hierarchical regression analyses showed gender, KPS, lung metastases, and plasma native thiol levels were the determinants of OS in the final model. CONCLUSION: These results suggest that in advanced stage NSCLC, the native thiol, total thiol, and disulfide levels decrease, while the native thiol/disulfide ratio does not change. Low levels of thiol/disulfide parameters are related to tumor aggressiveness and may predict a poor outcome for patients with NSCLC.

The role of reactive oxygen species and oxidative stress in carbon monoxide toxicity: an in-depth analysis.

The underlying mechanism of the central nervous system (CNS) injury after acute carbon monoxide (CO) poisoning is interlaced with multiple factors including apoptosis, abnormal inflammatory responses, hypoxia, and ischemia/reperfusion-like problems. One of the current hypotheses with regard to the molecular mechanism of CO poisoning is the oxidative injury induced by reactive oxygen species, free radicals, and neuronal nitric oxide. Up to now, the relevant mechanism of this injury remains poorly understood. The weakening of antioxidant systems and the increase of lipid peroxidation in the CNS have been implicated, however. Accordingly, in this review, we will highlight the relationship between oxidative stress and CO poisoning from the perspective of forensic toxicology and molecular toxicology.