Accelerated kynurenine pathway downregulates immune activation in patients with axial spondyloarthritis.

Various studies reported that the kynurenine (Kyn) pathway plays a pivotal role in regulating the balance between activation and inhibition of the immune system. Proinflammatory cytokines can accelerate the Kyn pathway by altering indoleamine (2, 3)- dioxygenase (IDO) allosteric enzyme activity. Excessive cytokine release and immune system activation have essential roles in the pathogenesis of axial spondyloarthritis (axSpA). We aimed to investigate the relationship of the Kyn pathway with proinflammatory cytokines and with the severity of the disease in patients with axSpA. The study included 104 patients with axSpA and 54 healthy volunteers. The severity of the disease was determined by Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). The Kyn pathway was evaluated by IDO activity calculated with Kyn/Tryptophan (Trp) ratio. Plasma Trp and Kyn concentrations were measured with tandem mass spectrometry. Serum IL 17/23 and IFN-γ concentrations were measured with ELISA. These groups were compared in terms of IDO, IL-17, IL-23, IFN-γ, and BASDAI. Plasma IDO activity was significantly increased, however, serum IL-17, IL-23, and IFN-γ levels were significantly decreased in patients compared to healthy volunteers. While IFN-γ was positively correlated with the severity of the disease (p = 0.02), it also had a significant inverse correlation with IDO activity (p < 0.001). However, these correlations are weak. As a result of this study, the Kyn pathway is accelerated and proinflammatory cytokine levels are decreased in patients with axSpA. All of these results with an indirect weak negative association between high IDO and low disease activity suggest that an accelerated Kyn pathway may limit the immune system activation in axSpA disease.

Thiol/Disulfide Homeostasis in Bipolar and Unipolar Depression.

OBJECTIVE: Bipolar disorder and unipolar depressive disorder are complex phenotypes. There appear to be phenotypical, mechanistic, and therapeutic differences between bipolar depression (BD) and unipolar depression (UD). There is a need for understanding the underlying biological variation between these clinical entities. The role of oxidative processes underlying bipolar disorder and depression has been demonstrated. Thiol-disulfide homeostasis (TDH) is a recent oxidative stress marker. In this study, we aimed to inspect patients with bipolar depression and unipolar depression in terms of thiol-disulfide balance and to compare them with healthy controls. METHODS: Patients admitted to the outpatient clinic of Ankara Numune Training and Research Hospital and diagnosed either as a depressive episode with bipolar disorder (n = 37) or unipolar depression (n = 24) according to DSM-5 criteria, along with healthy controls (HC) (n = 50), were included in the study. Native thiol, total thiol, and disulfide levels were compared across the groups. RESULTS: In comparison to HC, both BD and UD groups had higher disulfide levels, disulfide/native thiol ratio, and disulfide/total thiol ratio. No significant differences between BD and UD were detected in terms of disulfide level, disulfide/ native thiol ratio, and disulfide/total thiol ratio. CONCLUSION: Increased levels of disulfide, native thiol, and disulfide/total thiol ratios compared to healthy controls in both UD and BD groups may be indicative of the presence of oxidative damage in these two clinical conditions. To clarify the role of oxidative stress in the pathophysiology of depressive disorders and investigate TDH, longitudinal studies in patients with medication-free UD and BD are required.

The Variation of Disulfides in the Progression of Type 2 Diabetes Mellitus.

AIM: The purpose of this study was to examine thiol-disulfide balance in patients with type 2 diabetes mellitus. METHODS: This study included 32 subjects with known type 2 diabetes mellitus without complications, 30 patients with type 2 diabetes mellitus with complications, 28 newly diagnosed patients with type 2 diabetes mellitus, and 45 healthy individuals. Thiol-disulfide profile tests were quantified in all groups. RESULTS: Compared to the control group, patients in each of the diabetic groups had significantly lower native and total thiol levels, higher disulfide levels, and higher disulfide/native thiol and disulfide/total thiol ratios (p<0.05 for all). Disulfide levels were significantly lower in the newly diagnosed group than in other diabetic groups (p<0.05). There were significant associations between glycemic parameters and thiol-disulfide tests (p<0.05). CONCLUSIONS: A disequilibrium between thiol-disulfide pairs occurs in patients with type 2 diabetes mellitus, and a gradual increase to disulfide levels may contribute to the disease's severity. Deteriorated thiol-disulfide homeostasis may be relevant to the pathophysiology of type 2 diabetes mellitus.

Does extracorporeal shockwave lithotripsy therapy affect thiol-disulfide homeostasis?

OBJECTIVE: Extracorporeal Shockwave Lithotripsy (ESWL) is a non-invasive method that is effective at crushing stones in the upper urinary tract. Disturbance of the thiol/disulfide homeostasis, in favor of the disulfide, has been shown to be involved in the disease pathogenesis. METHODS: A total of 36 individuals that underwent ESWL had blood samples collected before ESWL (0hrs), 6hrs, and one week after the ESWL. Sera native and total as wells as disulfide amount was measured using an automated method sodium borohydrate (NaBH4) reduction. In addition, Ischemia Modified Albumin (IMA) levels were measured using colorimetric assay method. RESULTS: Native thiol level was reduced at the 6th hour following ESWL compared to baseline. While the ratios of disulfide level, Disulfide/Total Thiol (DTT), Disulfide/Native Thiol (DNT) and IMA level were increased at the 6th hour following ESWL compared to baseline, they were found to be similar with their baseline values at the end of 1st week. Total thiol and native /total thiol did not show any significant change. CONCLUSIONS: ESWL treatment disrupts thiol/disulfide homeostasis and the structure of albumin at the acute term. Therefore, it increases protein oxidation and leads to increased oxidative stress. However, this state is transient and returns to normal within the proceeding days.