Fatigue in Multiple Sclerosis: Is it related to cytokines and hypothalamic-pituitary-adrenal axis?

BACKGROUND: Fatigue is a common symptom of Multiple Sclerosis (MS) that diminishes the quality of life of patients, but its exact mechanism remains poorly understood. There is not a generally adopted scale to determine MS fatigue. Studies that investigated physiopathology of fatigue symptom have shown dysregulation of hypothalamic-pituitaryadrenal (HPA) axis. In the current study, we aimed to compare the results obtained with two separate scales, namely the Fatigue Severity Scale (FSS) and the Neurological Fatigue Index-Multiple Sclerosis (NFI-MS), and assess the relationship between fatigue and serum IL-1ß, TNF-α, IL-35, IL-2, IL-10, ACTH, cortisol, α-MSH, ß-MSH, γ-MSH and CLIP (Corticotropinlike intermediate lobe peptide) in MS patients categorized as fatigued and non-fatigued on the basis of FSS scores. METHODS: For the study, a total of 54 (29 females, 25 males) patients diagnosed with RRMS including 26 with fatigue symptom (48.1%), and 26 healthy controls (13 females, 13 males) were enrolled. A FSS score ≥36 was considered as cut-off score to separate fatigued patients from nonfatigued patients. RESULTS: A significant positive correlation was determined between FSS score and NFI-MS scale, NFI-MS 1, NFI-MS 2, NFI-MS 3 and NFI-MS 4 scores. IL-1ß, IL-10 and TNF-α levels did not differ between patient and control groups. IL-35 and IL-2 levels were significantly higher among MS patients (p<0.01). However, no difference was observed between fatigued and nonfatigued patients in the cytokines and HPA parameters studied. ACTH, cortisol and α-MSH were significantly higher in MS group (p=0.02, p<0.01 and p<0.01, respectively). CLIP level was significantly low in MS patient group (p<0.01). CONCLUSION: NFI-MS scale is equally sensitive as FSS scale for assessment of MS fatigue; thus, it may also be widely used to evaluate that symptom. Generally HPA axis is hyperactive in MS patients, but it is not correlated with fatigue in our study. For the first time, levels of CLIP (a type of melanocortin) are studied, and determined to be lower among MS patients. Elevated levels of IL-35 and IL-2 suggest that these cytokines may have a prominent role in MS pathophysiology and can be investigated as potential targets for development of novel therapies.

Evaluation of Serum S100A8/S100A9 Levels in Patients with Autoimmune Thyroid Diseases.

BACKGROUND: The correlation of S100A8/S100A9 with various inflammatory conditions, including autoimmune diseases have been reported. There is no study investigating the levels of S100A8/S100A9 in autoimmune thyroid diseases (AITD). AIMS: We aimed to evaluate the level of serum S100A8/S100A9 in AITD. STUDY DESIGN: Case control study. METHODS: Fifty patients with AITD (25 Hashimoto's thyroiditis (HT) and 25 Graves' disease (GD)) were included in the study. Twenty seven healthy subjects participated as a control group. Blood samples were obtained in the 3 months after the initiation of medical treatment. Serum levels of total antioxidant status (TAS), total oxidative status (TOS), total free sulfhydryl (SH), lipid hydroperoxide (LOOH) and S100A8/S100A9 were analyzed. RESULTS: The patients with AITD had significantly higher S100A8/S100A9, OSI, LOOH and TOS levels than the healthy control group. There was no significant difference between GD and HT patients in terms of S100A8/S100A9, TOS and OSI levels. S100A8/S100A9 level was positively correlated with LOOH, TOS and OSI levels but negatively correlated with -SH level in the patients with AITD. CONCLUSION: Serum S100A8/S100A9 levels were increased in patients with AITD and positively correlated with LOOH, TOS and OSI whereas negatively correlated with SH.

Association between red blood cell distribution width and disease activity in patients with Behçet's disease.

OBJECTIVES: To examine associations between red blood cell distribution width (RDW) and organ involvement and disease activity in patients with Behçet's disease. METHODS: Haematological and inflammatory parameters including RDW, high-sensitivity C-reactive protein (hsCRP) and erythrocyte sedimentation rate (ESR) were examined in patients with Behçet's disease and in healthy controls. Patients were divided into those with active or inactive disease. RESULTS: Data from 236 patients with Behçet's disease (77 with active and 159 with inactive disease) and 72 controls were analysed. RDW, ESR and hsCRP were significantly higher in patients with Behçet's disease than in controls, and in those with active disease compared with inactive disease or controls. In addition, ESR and hsCRP were significantly higher in those with inactive disease than controls. No correlations were found between hsCRP, ESR and RDW. No differences were observed in RDW, ESR or hsCRP between patients with or without ocular or vascular involvement. Multivariate logistic regression analysis revealed that RDW was significantly higher in active disease compared with inactive disease. CONCLUSIONS: RDW was increased in active disease compared with inactive disease. No relationships were found between organ involvement and RDW. RDW may be a cost-effective, novel potential parameter to evaluate disease activity in Behçet's disease.

Maternal Iron Deficiency Anemia as a Risk Factor for the Development of Retinopathy of Prematurity.

BACKGROUND: Retinopathy of prematurity is a proliferative vascular disease affecting premature newborns and occurs during vessel development and maturation. The aim of this study was to evaluate the maternal iron deficiency anemia as possible risk factors associated with the development of retinopathy of prematurity among premature or very low birth weight infants. METHODS: In this study, mothers of 254 infants with retinopathy of prematurity were analyzed retrospectively, and their laboratory results of medical records during pregnancy were reviewed for possible iron deficiency anemia. RESULTS: In a cohort of 254 mothers of premature infants with retinopathy of prematurity, 187 (73.6%) had iron deficiency, while the remaining 67 (26.4%) mothers had no deficiency. Babies born to mothers with iron deficiency anemia with markedly decreased hemoglobin, hematocrit, mean corpuscular volume, serum iron, and ferritin levels were more likely to develop retinopathy of prematurity. CONCLUSIONS: Our results are the first to suggest that maternal iron deficiency is a risk factor for the development of retinopathy of prematurity. Our data suggest that maternal iron supplementation therapy during pregnancy might lower the risk of retinopathy of prematurity.

Is calprotectin a novel biomarker of neuroinflammation in diabetic periferal neuropathy?

BACKGROUND: In the present study, we aimed to investigate serum calprotectin levels in patients with diabetic peripheral neuropathy, and possible role of this molecule in the disease pathogenesis. METHOD: Twenty nine patients with diabetic peripheral neuropathy, 30 type 2 diabetic patients without neuropathy, and 40 healthy controls were enrolled in the study. Fasting plasma glucose (FPG), high-density lipoprotein- cholesterol (HDL-C), low-density lipoprotein- cholesterol (LDL-C), total cholesterol, triglyceride, HbA1c, calprotectin and hsCRP levels were measured in diabetic and healthy control groups. RESULTS: Serum calprotectin and hsCRP levels were significantly higher in patients with and without neuropathy than healthy controls (p < 0.001, p = 0.017, p < 0.001 and p = 0.001, respectively). Serum calprotectin and hsCRP levels were higher in diabetics with neuropathy than the ones without (p = 0.021 and p < 0.001, respectively). The positive correlation was detected between calprotectin levels and hsCRP and HbA1c in Spearman correlation analysis (r = 0.510, p < 0.001; r = 0.437, p < 0.001 respectively). The results of multiple logistic regression analysis demonstrated the important association between neuropathy development and hsCRP and serum calprotectin levels in diabetic individuals. CONCLUSION: Seum calprotectin levels were increased in diabetic peripheral neuropathy. It may have a role in the pathogenesis of the disease.

Investigation of the role of 8-OHdG and oxidative stress in papillary thyroid carcinoma.

The aim of this study was to determine levels of serum 8-hydroxy-2'-deoxyguanosine (8-OHdG) as an indicator of oxidant-induced DNA damage and oxidant status in patients with papillary thyroid carcinoma before and after surgery. This study included 25 patients with papillary thyroid carcinoma and age-matched 27 healthy controls. Total antioxidant status (TAS), total oxidant status (TOS), lipid hydroperoxide (LOOH), and 8-OHdG levels were measured. 8-OHdG levels were significantly higher in the preoperative papillary thyroid carcinoma (PTC) group compared with the healthy control group (p < 0.001) and were significantly lower after operation in patients with papillary thyroid carcinoma (p = 0.004). Oxidative stress index (OSI) levels were significantly higher in both preoperative and postoperative PTC patients compared with the healthy control group (p < 0.001 and p < 0.001, respectively). TOS levels were higher in the preoperative and postoperative PTC groups compared to the healthy control group (p < 0.001 and p < 0.001, respectively). TAS levels was lower in the preoperative PTC groups compared to the healthy control group (p = 0.011). Serum LOOH levels were higher in both preoperative and postoperative PTC groups compared to the healthy control group (p < 0.001 and p < 0.001, respectively). Correlation analysis yielded that serum 8-OHdG levels were positively correlated with OSI and LOOH levels in patients with PTC before surgery (r = 0.668, p < 0.001; r = 0.446, p = 0.025, respectively) and had a negative correlation with TAS levels (r = -0.616, p = 0.001). We have shown severe oxidative DNA damage and impaired antioxidant status in papillary thyroid carcinoma.

QT dispersion in the risk stratification of patients with unstable angina: correlation with clinical course, troponin T and scintigraphy.

OBJECTIVE: This study sought to evaluate the potential prognostic usefulness of QT dispersion (QTd) in patients with unstable angina. METHODS AND RESULTS: QTd was calculated and plasma troponin T (TnT) level was measured and rest perfusion imaging with Tc-99m sestamibi was performed in 62 patients admitted with chest pain at rest. All patients had a follow-up during one month in order to assess cardiac events. Cardiac events occurred in 41 patients (no deaths, 11 myocardial infarctions (MI), 4 urgent and 26 planned revascularizations). The mean QTd in patients with cardiac events was significantly higher than in those without cardiac events (68 +/- 28 vs. 54 +/- 14 ms; p = 0.01). When patients were divided into subgroups according to the cardiac events, the mean QTd in MI and revascularization were 90 +/- 25 ms and 60 +/- 25 ms, respectively. QTd in patients with MI was higher than in patients without cardiac events (p = 0.001). There was no significant difference in QTd between the revascularization subgroup and patients without cardiac events. Nineteen patients with elevated TnT had a greater QTd compared to patients with normal TnT (74 +/- 29 vs. 56 +/- 20 ms; p = 0.008). Additionally, the mean QTd in 46 patients with perfusion defects was slightly higher than in patients without (66 +/- 27 vs. 53 +/- 17 ms; p = 0.03). There was also a moderate correlation between QTd and the number of perfusion defects (r = 0.31, p = 0.01). On the other hand, most of the patients who had a MI or urgent revascularization had a QTd greater than 75 ms. CONCLUSION: The measurement of QTd in patients with unstable angina may help to stratify patients at high risk for cardiac events, in particular MI and urgent revascularization.