Serum interleukin-6 levels are increased in HIV-infected patients that develop autoimmune disease during long-term follow-up

Background: Elevated IL-6 levels have been associated with both autoimmune diseases and treated HIV-seropositive (HIV+) subjects. However, few data on classic and trans-signaling IL-6 in autoimmune thyroid diseases and HIV+ subjects developing autoimmune disorders are currently available. Materials and methods: A total of 102 patients were included in the study. They were subdivided into two groups. Group A consisted in 51 HIV+ patients, who were followed-up for a period of five years in search of possible occurrence of autoimmune diseases. Ten of them, treated with antiretroviral therapy (ART), developed an autoimmune disorder, namely Hashimoto's thyroiditis, and psoriasis. Group B consisted in 51 patients affected by Hashimoto's thyroiditis (HT). Serum levels of the free form of IL-6 were analyzed by ELISA in all patients and for HIV+ patients at the beginning of the follow-up, before initiation of ART. Results: Mean serum levels of IL-6 were similar in Group A and in Group B. In Group B, IL-6 levels showed a 5.8% increase compared with assay minimum detectable dose corresponding to 1% of full serum IL-6 level. However, serum levels of free IL-6 were increased in those HIV+ patients who developed autoimmune disorders (5.8 ± 2.8 pg/ml) and in these patients, the highest levels of free IL-6 correlated with age and CD4 cellular counts. Conclusions: The present study indicates a correlation between serum free IL-6 levels and the occurrence of autoimmune disease in HIV+ population, treated with ART during a long-term follow-up. The increased levels of serum free IL-6 were observed before ART treatment was initiated, indicating that IL-6 measurement in such patients may represent an early predictor of development of autoimmune disease

Favorable effects of myo-inositol, selenomethionine or their combination on the hydrogen peroxide-induced oxidative stress of peripheral mononuclear cells from patients with Hashimoto's thyroiditis: preliminary in vitro studies

OBJECTIVE: The aim of this study was to assess whether blood mononuclear cells (PBMC) from Hashimoto's thyroiditis (HT) and control women, were protected from in vitro H2O2-induced oxidative stress after addition of antioxidants. PATIENTS AND METHODS: PBMC, from 8 HT women and 3 healthy women (controls), were cultured in the presence of 200 µM H2O2 alone, with subsequent addition of myo-inositol (Myo) (0.25, 0.5, 1.0 µM), selenomethionine (SelMet) (0.25, 0.5, 1.0 µM), or their combination (0.25+0.25, 0.5+0.5, 1.0+1.0 µM). PBMC proliferation, vitality, genotoxicity (Comet score) and secretion in the medium of the chemokines CXCL10 [IP10], CCL2 e CXCL9 [MIG] were the indices measured. RESULTS: PBMC proliferation was decreased by H2O2 alone, and it decreased further and dose-dependently in either group (greatest decrease with Myo+SelMet in HT). H2O2 alone decreased vitality by 5% in controls and 10% in the HT group, but vitality was rescued by the three additions. The addition of H2O2 alone increased the Comet score at +505% above baseline in controls and +707% in HT women. In either group, each addition dose-dependently contrasted genotoxicity. Concentrations of chemokines in the medium were increased by H2O2 alone, and in HT women more than in controls. Each addition dose-dependently decreased these concentrations in either group, and often below baseline levels, with Myo+SelMet being the most potent addition (up to approximately -80% of baseline). CONCLUSIONS: The tested antioxidants exert beneficial effects on PBMC exposed in vitro to H2O2-induced oxidative stress in both control and HT women. Particularly, the association Myo+SelMet is the most effective. After the demonstration of a favorable in vitro outcomes in a large cohort of HT patients, we could predict favorable in vivo outcomes given by the same supplement. Thus, one can select HT patients with a high chance of benefit from supplementation

Influence of Dietary Habits on Oxidative Stress Markers in Hashimoto's Thyroiditis

Background: There is a growing awareness that nutritional habits may influence risk of several inflammatory and immune-mediated disorders, including autoimmune diseases, through various mechanisms. The aim of the present study was to investigate dietary habits and their relationship with redox homeostasis in the setting of thyroid autoimmunity. Materials and Methods: Two hundred subjects (173 females and 27 males; median age, 37 years) were enrolled. None were under any pharmacological treatment. Exclusion criteria were any infectious/inflammatory/autoimmune comorbidity, kidney failure, diabetes, and cancer. In each subject, serum thyrotropin (TSH), free thyroxine, antithyroid antibodies, and circulating oxidative stress markers were measured. A questionnaire on dietary habits, evaluating the intake frequencies of food groups and adherence to the Mediterranean diet, was submitted to each participant. Results: Among the 200 recruited subjects, 81 (71 females and 10 males) were diagnosed with euthyroid Hashimoto's thyroiditis (HT); the remaining 119 (102 females and 17 males) served as controls. In questionnaires, HT subjects reported higher intake frequencies of animal foods (meat, p = 0.0001; fish, p = 0.0001; dairy products, p = 0.004) compared with controls, who reported higher intake frequencies of plant foods (legumes, p = 0.001; fruits and vegetables, p = 0.030; nuts, p = 0.0005). The number of subjects who preferentially consumed poultry instead of red/processed meat was lower in HT subjects than in controls (p = 0.0141). In logistic regression analysis, meat consumption was associated with increased odds ratio of developing thyroid autoimmunity, while the Mediterranean diet traits were protective. In HT subjects, serum advanced glycation end products (markers of oxidative stress) were significantly higher (p = 0.0001) than in controls, while the activity of glutathione peroxidase and thioredoxin reductase, as well as total plasma antioxidant activity, were lower (p = 0.020, p = 0.023, and p = 0.002, respectively), indicating a condition of oxidative stress. Stepwise regression models demonstrated a significant dependence of oxidative stress parameters on consumption of animal foods, mainly meat. Conclusions: The present study suggests a protective effect of low intake of animal foods toward thyroid autoimmunity and a positive influence of such nutritional patterns on redox balance and potentially on oxidative stress-related disorders

MicroRNAs expression in pituitary tumors: differences related to functional status, pathological features, and clinical behavior

BACKGROUND: MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene expression at post-transcriptional level, having a role in many biological processes, such as control of cell proliferation, cell cycle, and cell death. Altered miRNA expression has been reported in many neoplasms, including pituitary adenomas (PAs). PURPOSE: In this study, we aimed to evaluate the expression of 20 miRNAs involved in pathways relevant to pituitary pathophysiology, in PAs and normal pituitary tissue and to correlate their expression profile with clinical and pathological features. METHODS: Pituitary tumor samples were obtained during transphenoidal surgery from patients with non-functioning (NFPA, n = 12) and functioning (n = 11, 5 GH-, 3 ACTH-, 3 PRL-omas) PAs. The expression of selected miRNAs in PAs and in normal pituitary was analyzed by RT-qPCR. miRNAs expression was correlated with demographic, clinical, and neuroradiological data and with histopathological features including pituitary hormones immunostaining, Ki-67 proliferation index, and p53 immunohistochemistry evaluation. RESULTS: All evaluated miRNAs except miR-711 were expressed in both normal and tumor pituitary tissue. Seventeen miRNAs were significantly down-regulated in pituitary tumors compared to normal pituitary. miRNAs were differentially expressed in functioning PAs or in NFPAs, as in the latter group miR-149-3p (p = 0.036), miR-130a-3p (p = 0.014), and miR-370-3p (p = 0.026) were significantly under expressed as compared to functioning tumors. Point-biserial correlation analysis demonstrated a negative correlation between miR-26b-5p and Ki-67 (p = 0.031) and between miR-30a-5p and 'atypical' morphological features (p = 0.038) or cavernous sinus invasion (p = 0.049), while 508-5p was inversely correlated with clinical aggressiveness (p = 0.043). CONCLUSIONS: In this study, we found a significant down-regulation of 17 miRNAs in PAs vs normal pituitary, with differential expression profile related to functional status and tumor aggressiveness

Impact of prosthesis-patient mismatch on early and late mortality after aortic valve replacement

<p>Background: The influence of prosthesis-patient mismatch (PPM) on survival after aortic valve replacement (AVR) remains controversial. In this study, we sought to determine the effect of PPM on early (30 days) after AVR or AVR combined with coronary artery bypass grafting (AVR with CABG).</p><p>Methods: Between January 1998 and March 2012, 2976 patients underwent AVR (n= 1718) or AVR with CABG (n=1258) at a single institution. PPM was defined as an indexed effective orifice area (EOAI)</p><p>Results: Early mortality was 6.7% in the PPM group vs 4.7% in the group with no PPM (p=0.013). Late mortality for the PPM group at 1, 5 and 10 years was 4%, 16% and 43%, respectively. Late mortality for the group with no PPM at 1, 5 and 10 years was 4%, 15% and 33% respectively. Independent predictors of early mortality included age, severely impaired left ventricular (LV) function, endocarditis, renal dysfunction, chronic obstructive pulmonary disease (COPD) and cardiopulmonary bypass (CPB) time. Multivariate independent predictors of late mortality included age, severely impaired LV function, diabetes, peripheral vascular disease (PVD), renal dysfunction, history of a cerebrovascular accident (CVA), CPB time and a history of previous cardiac surgery. PPM was not an independent predictor of early or late mortality.</p><p>Conclusion: PPM is not an independent predictor of both early and late mortality after AVR or AVR combined with CABG.</p>