Levothyroxine Replacement Improves Oxidative Status in Primary Hypothyroidism.

Objective: Although hypothyroidism has been linked to oxidative stress, data regarding the relationship between thyroid hormone levels and oxidative stress is still inconsistent. This study was designed to evaluate the effect of levothyroxine replacement on oxidative stress in women with primary hypothyroidism. Design: A total of 25 female patients with primary hypothyroidism were included. Oxidative stress markers were measured before and after levothyroxine replacement treatment in all patients. Methods: Oxidative stress was evaluated through the measurement of oxidants (thiobarbituric acid reactive substances [TBARS] and nitrite/nitrate levels), and antioxidants (superoxide dismutase and catalase activity). Results: Antioxidant catalase activity (63.77 ± 23.8 vs. 50.12 ±12.75 atv/min; p = 0.03) was significantly increased and the levels of TBARS (3.02 ± 0.86 vs. 3.55 ± 0.87 µM; p = 0.03) were significantly decreased in the state of euthyroidism after levothyroxine replacement compared to the hypothyroidism before levothyroxine treatment. No significant change in neither nitrite/nitrate concentration (p = 0.18) nor in superoxide dismutase activity (p = 0.93) after L-T4 adjustment was found. Conclusions: Our data demonstrate that levothyroxine replacement improved oxidative status in patients with primary hypothyroidism, indexed by the significantly decreased levels of malonaldehyde (MDA) and increased catalase (CAT) activity.

Myelodysplastic syndrome patients present more severe respiratory muscle impairment and reduced forced vital capacity: Is disordered inflammatory signaling the culprit?

BACKGROUND/OBJECTIVES: The ageing process is associated with gradual decline in respiratory system performance. Anemia is highly prevalent among older adults and usually associated with adverse outcomes. Myelodysplastic syndromes (MDS) are a heterogeneous group of hematologic malignancies with increasing incidence with age and characterized by anemia and other cytopenias. The main objectives of this study were to evaluate respiratory muscle strength and lung function in elderly patients with anemia, compare data between myelodysplastic syndromes and non-clonal anemias and evaluate the influence of serum IL-8 level and NF-kB activity on deteriorate pulmonary function in this specific population. PARTICIPANTS: Individuals aged 60 and older with anemia secondary to MDS, non-clonal anemia and healthy elderly individuals. MEASUREMENTS: Forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and FEV1/ FVC ratio were measured by spirometry. Respiratory muscle strength was evaluated by maximal static respiratory pressures measurement. IL-8 analysis was performed by ELISA and activity of NF-kB by chemiluminescent assay. RESULTS: Mean Hb concentration was comparable between patients with anemia. Significant differences were detected between all patients with anemia and controls for maximum-effort inspiratory mouth pressure (PImax) and also for maximum-effort expiratory mouth pressure (PEmax). The MDS group recorded a significantly lower PImax and PEmax percent predicted when compared to non-clonal anemia group. For FVC and FEV1, a significant difference was found in anemic patients, with even significantly lower values for FVC and FEV1 in MDS group. No significant differences were detected for PImax and PEmax and spirometry parameters when anemic patients were stratified according to the degree of anemia. A significant negative impact in FVC (% pred), PImax (% pred) and PEmax (% pred) was observed in patients with MDS and higher levels of IL-8 or increased activity of NF-kB. CONCLUSION: A negative impact of anemia, independent of its degree, was demonstrated in respiratory muscle strength and lung function particularly in MDS. The well known elevated proinflammatory cytokines in MDS patients were proposed to play a role as was demonstrated by detrimental effect of higher IL-8 and NF-kB in pulmonary function tests in this population.

Interleukin-8 and nuclear factor kappa B are increased and positively correlated in myelodysplastic syndrome.

The pathogenesis of myelodysplastic syndromes (MDS) is complex and depends on the interaction between aberrant hematopoietic cells and their microenvironment, probably including aberrations in cytokines and their signaling pathways. To evaluate interleukin-8 (IL-8) plasma levels and nuclear factor kappa B (NF-kB) in patients with MDS and to test possible correlation between IL-8 and NF-Kb, a total of 45 individuals were analyzed: 25 consecutive adult de novo MDS patients and 20 sex and age-matched healthy elderly volunteers. IL-8 analysis was performed by ELISA and activity of NF-kB by chemiluminescent assay. MDS patients showed higher level of IL-8 when compared to controls (p = 0.006). Patients aged 75 and above showed even higher levels (p = 0.035). NF-kB activity was significantly elevated in MDS patients when compared to controls (p < 0.0001) and higher in patients older than 75 years (p = 0.047). NF-kB activity was associated with higher serum ferritin (p = 0.042) and higher percentage of blasts (p = 0.028). A significant positive correlation between IL-8 and NF-kB was demonstrated (r = 0.480; p = 0.015). Many pathways involved in pathophysiology of MDS have been recently described, suggesting that an inflammatory process may act as a pathogenic driver. In this study, significantly elevated levels of IL-8 and NF-kB were demonstrated in MDS patients, with positive association of NF-kB with some markers of poor prognosis. A positive correlation between IL-8 and NF-kB suggests they cooperate as part of a complex networking of immune and inflammatory factors involved in MDS.