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Dynamic thiol/disulphide homeostasis in acute pancreatitis.
Köseoğlu, H, Alışık, M, Başaran, M, Tayfur Yürekli, Ö, Solakoğlu, T, Tahtacı, M, Ersoy, O, Erel, Ö
The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology. 2018;(3):348-353
Abstract
BACKGROUND/AIMS: The dynamic thiol/disulfide homeostasis plays pivotal roles in many physiological mechanisms in an organism. We aimed to investigate whether dynamic thiol/disulfide homeostasis changes among patients with acute pancreatitis. MATERIALS AND METHODS This prospective trial contained 45 patients with acute pancreatitis and 45 sex-and age-matched healthy volunteers as control group. Thiol/disulfide homeostasis parameters were measured by a novel and automated assay, and detected results were compared between the two groups. RESULTS Disulfide/total thiol percent ratio and disulfide/native thiol percent ratios were significantly higher in acute pancreatitis group; besides the native thiol, total thiol levels and native thiol/total thiol percent ratios were significantly lower (for all p < 0.001). CONCLUSION The thiol/disulfide homeostasis is impaired in acute pancreatitis with a shift toward the oxidative status, and this deficiency might be a pathogenic factor in acute pancreatitis. The correction of this thiol/disulfide imbalance may be a new target in the management of acute pancreatitis.
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2.
An alternative method for measuring oxidative stress in intrahepatic cholestasis of pregnancy: thiol/disulphide homeostasis.
Sanhal, CY, Daglar, K, Kara, O, Yılmaz, ZV, Turkmen, GG, Erel, O, Uygur, D, Yucel, A
The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians. 2018;(11):1477-1482
Abstract
PURPOSE The aim of our study was to evaluate the oxidative stress (OS) in pregnant women with intrahepatic cholestasis of pregnancy (ICP) by evaluating thiol/disulphide homeostasis using an alternative technique. METHODS A total of 57 pregnant women with ICP were compared with 50 gestational age and body mass index matched controls. A recently defined method was used for the measurement of plasma native-total thiol and disulphide levels. The independent two-sample t test, Mann-Whitney-U test, Chi-square test, binary logistic regression with backward elimination and receiver operating characteristic (ROC) curve was performed for statistical analyses. RESULTS Pregnant women with ICP (n = 57) versus controls (n = 50) had significantly lower serum levels of native thiol (233.8 ± 47.4 μmol/L vs. 308.5 ± 51.7 μmol/L, p < .001), total thiol (258.4 ± 46.5 μmol/L vs. 328.0 ± 52.0 μmol/L, p < .001) and higher levels of disulphide (12.3 ± 3.6 μmol/L vs. 9.7 ± 3.4 μmol/L, p < .001). Binary logistic regression showed that the most important variables related to ICP were native thiol and total thiol. According to the ROC curve, the optimal cut-off level for native thiol was 280.0 μmol/L (sensitivity: 86%, specificity: 84.2%, area under the curve (AUC):0.896, 95% CI: 0.831-0.962, p < .001), and the optimal cut-off level for total thiol was 300.0 μmol/L (sensitivity: 86%, specificity: 80.7%, AUC: 0.883, 95% CI: 0.815-0.951, p < .001). CONCLUSIONS To our knowledge, this is the first study in the literature exploring thiol/disulphide balance in ICP. We found that thiol/disulphide balance indicate OS in pregnant woman with ICP.
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3.
Effects of Hemodialysis on Thiol-Disulphide Homeostasis in Critically Ill Pediatric Patients with Acute Kidney Injury.
Ayar, G, Sahin, S, Yazici, MU, Neselioglu, S, Erel, O, Bayrakcı, US
BioMed research international. 2018;:1898671
Abstract
AIM: To evaluate thiol/disulphide homeostasis as a new indicator of oxidative stress in AKI patients and to determine the effect of HD on antioxidant balance and oxidative stress through plasma thiols. METHODS This study was performed in patients aged between 12 months and 18 years prospectively who underwent hemodialysis due to AKI and were followed up for a year in a 22-bed tertiary pediatric intensive care unit. 20 patients and 39 controls were included. RESULTS No difference was present between the groups in terms of age and gender. Median values of plasma native thiol, total thiol, and percent thiol were significantly lower in AKI group both before and after dialysis when compared to control group. The median dynamic disulphide values were significantly lower in the AKI group of predialysis compared to the controls. When pre- and postdialysis values were compared, disulphide values were statistically higher after dialysis. When pre- and postdialysis native thiol, dynamic disulphide, total thiol, and percent thiol median values were compared, postdialysis values were significantly higher than the predialysis values. There was a positive correlation between albumin, total thiol, and native thiol values before dialysis in the patient group. CONCLUSION AKI patients have low levels of thiol species showing the presence of oxidative stress and hemodialysis has a positive effect on thiol/disulphide balance. This new method may be an inexpensive and simple tool suitable for clinical studies and can be used in routine screening as a useful indicator to show oxidative stress.
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Vitamin D supplementation does not improve plasma thiol/disulfide homeostasis.
Mertoglu, C, Siranli, G, Topal, I, Gok, G, Erel, O
Pediatrics international : official journal of the Japan Pediatric Society. 2018;(11):1008-1013
Abstract
BACKGROUND Impairment of thiol/disulfide homeostasis, as well as vitamin D deficiency, are responsible for the pathophysiology of many acute and chronic diseases. This study examined the relationship between thiol/disulfide homeostasis and vitamin D level and supplementation. METHODS A total of 203 healthy children were included in the study. The participants were divided into four groups according to 25-hydroxyvitamin D (25(OH)D) level: group 1, severe deficiency (<10 ng/mL); group 2, deficiency (10-20 ng/mL); group 3, insufficiency (20-30 ng/mL); and group 4, sufficiency (≥30 ng/mL). Furthermore, group 5 was defined as being on vitamin D supplementation. RESULT Native thiol was lower in group 5 than in groups 2-4 (P = 0.003). Disulfide was higher in groups 1, 4 and 5 than groups 2 and 3 (P < 0.001). Total thiol was lower in group 5 than in group 4 (P = 0.032). The ratio of native thiol/total thiol was lower in groups 1 and 5 compared with groups 2 and 3, and in group 4 compared with group 3 (P < 0.001). The ratios of disulfide/total thiol and disulfide/native thiol were higher in groups 1 and 5 than in groups 2 and 3 whereas only the disulfide/total thiol ratio was higher in group 4 than in group 3 (P < 0.001). CONCLUSIONS In healthy children, severe deficiency of vitamin D causes impairment of thiol/disulfide homeostasis and increases protein oxidation, which cannot be reversed by external vitamin D supplementation.
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Thiol/disulfide homeostasis in predicting adverse perinatal outcomes at 24-28 weeks of pregnancy in gestational diabetes.
Ozler, S, Oztas, E, Caglar, AT, Uygur, D, Ergin, M, Erel, O, Danisman, N
The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians. 2016;(22):3699-704
Abstract
OBJECTIVE The main aim of this study was to investigate thiol/disulfide homeostasis at 24-28 weeks of pregnancy and to evaluate whether it is predictive for adverse perinatal outcomes or not in gestational diabetes mellitus (GDM). METHODS A total of 110 pregnant women at 24-28 weeks of pregnancy (74 GDM patients and 36 age- and BMI-matched healthy pregnant women) were enrolled in this prospective case-control study. Thiol/disulfide homeostasis was evaluated with a novel spectrophotometric method to determine if there is an association with adverse perinatal outcomes in GDM, by using logistic regression analysis. RESULTS GDM patients, with decreased native thiol levels at 24-28 weeks (OR: 4.890, 95% CI: 1.355-5.764, p = 0.015) and with higher pre-pregnancy BMI (OR: 1.280, 95% CI: 1.072-1.528, p = 0.006), were found to be at increased risk of adverse perinatal outcomes in GDM. There were no statistically significant differences in thiol/disulfide homeostasis between diet- and insulin-treated GDM subgroups. Additionally, 1-h and 2-h glucose levels on 100 g OGTT were found to be predictive for the insulin need in achieving good glycemic control in GDM (OR: 1.022, 95% CI: 1.005-1.038, p = 0.010 and OR: 1.019, 95% CI: 1.004-1.035, p = 0.015). CONCLUSIONS GDM patients, with decreased native thiol levels at 24-28 weeks of pregnancy and with higher pre-pregnancy BMI, have an increased risk of possible adverse perinatal outcomes. Also, increased 1-h and 2-h glucose levels on 100 g OGTT can predict the need for insulin treatment for GDM.
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Disulfide-mediated apoptosis of human T-lymphotrophc virus type-I (HTLV-I)-infected cells in patients with HTLV-I-associated myelopathy/tropical spastic paraparesis.
Nishiura, Y, Nakamura, T, Fukushima, N, Nakamura, H, Ida, H, Aramaki, T, Eguchi, K
Antiviral therapy. 2009;(4):533-42
Abstract
BACKGROUND This study was conducted to construct a basis for a therapeutic strategy against human T-lymphotropic virus type-I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) using a compound that contained a disulfide moiety, prosultiamine, which is a homologue of allithiamine originally synthesized by allicin and thiamine-thiol, for the targeting of HTLV-I-infected cells. METHODS First, we analysed the apoptotic pathway in allicin or prosultiamine treatment against an HTLV-I-infected T-cell line (HCT-1), derived from an HAM/TSP patient, by flow cytometry and western blot. Second, we evaluated the effect of targeting HTLV-I-infected cells in a prosultiamine in vitro treatment and in a clinical trial in HAM/TSP patients by quantitative PCR analysis of HTLV-I proviral load. RESULTS Prosultiamine, like allicin, induced caspase-dependent apoptosis against HCT-1 cells. The fact that the loss of mitochondrial membrane potential was recovered in z-VAD-fmk-pretreated HCT-1 cells with prosultiamine treatment suggested that prosultiamine can induce caspase-dependent apoptosis through the mitochondrial pathway. On the basis of data showing that prosultiamine in vitro treatment against peripheral blood CD4(+) T-cells of HAM/TSP patients induced a significant decrease of HTLV-I proviral copy numbers by apoptosis of HTLV-I-infected cells, we treated six HAM/TSP patients with intravenous administration of prosultiamine for 14 days. As a result of this treatment, the copy numbers of HTLV-I provirus in peripheral blood decreased to approximately 30-50% of their pretreatment levels with some clinical benefits in all patients. CONCLUSIONS Our results suggest that prosultiamine has the potential to be a new therapeutic tool that targets HTLV-I-infected cells in HAM/TSP.
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A clinical investigation on garlicin injectio for treatment of unstable angina pectoris and its actions on plasma endothelin and blood sugar levels.
Li, G, Shi, Z, Jia, H, Ju, J, Wang, X, Xia, Z, Qin, L, Ge, C, Xu, Y, Cheng, L, et al
Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan. 2000;(4):243-6
Abstract
To investigate the therapeutic effects and mechanisms of garlicin for treatment of unstable angina pectoris (UAP), garlicin injectio was intravenously dripped 60 mg/day in 34 cases for 10 days. Nitroglycerine was used in 21 cases of the control group. The results showed that the total effective rates in improving symptoms and electrocardiogram after garlicin treatment were respectively 82% and 62%, and that the plasma endothelin and blood sugar levels were markedly lowered in cases with hyperglycemia.