Enrico Di Stasio

In the recent decades, oxidative stress has become focus of interest in most biomedical disciplines and many types of clinical research. Increasing evidence from research on several diseases show that oxidative stress is associated with the pathogenesis of diabetes, obesity, cancer, ageing, inflammation, neurodegenerative disorders, hypertension, apoptosis, cardiovascular diseases, and heart failure. Based on this research, the emerging concept is that oxidative stress is the "final common pathway", through which risk factors of several diseases exert their deleterious effects. Oxidative stress causes a complex dysregulation of cell metabolism and cell-cell homeostasis. In this review, we discuss the role of oxidative stress in the pathogenesis of insulin resistance and beta-cell dysfunction. These are the two most relevant mechanisms in the pathophysiology of type 2 diabetes, and in the pathogenesis of diabetic vascular complications, the leading cause of death in diabetic patients.

Hepatitis C virus (HCV) is a major human pathogen causing chronic liver disease. We have recently found that the large extracellular loop (LEL) of human CD81 binds HCV. This finding prompted us to assess the structure-function features of HCV-CD81 interaction by using recombinant E2 protein and a recombinant soluble form of CD81 LEL. We have found that HCV-E2 binds CD81 LEL with a K(d) of 1.8 nM; CD81 can mediate attachment of E2 on hepatocytes; engagement of CD81 mediates internalization of only 30% of CD81 molecules even after 12 h; and the four cysteines of CD81 LEL form two disulfide bridges, the integrity of which is necessary for CD81-HCV interaction. Altogether our data suggest that neutralizing antibodies aimed at interfering with HCV binding to human cells should have an affinity higher than 10(-9) M, that HCV binding to hepatocytes may not entirely depend on CD81, that CD81 is an attachment receptor with poor capacity to mediate virus entry, and that reducing environments do not favor CD81-HCV interaction. These studies provide a better understanding of the CD81-HCV interaction and should thus help to elucidate the viral life cycle and to develop new strategies aimed at interfering with HCV binding to human cells.

BACKGROUND: Image-guided laser ablation therapy (LAT) of benign thyroid nodules demonstrated favorable results in randomized trials with fixed modalities of treatment. The aim of this retrospective multicenter study was to assess the effectiveness, tolerability, and complications of LAT in a large consecutive series of patients from centers using this technique in their routine clinical activity. PATIENTS: Clinical records of 1534 consecutive laser-treated nodules in 1531 patients from eight Italian thyroid referral centers were assessed. Inclusion criteria were as follows: solid or mixed nodules with fluid component up to 40%; benign cytological findings; and normal thyroid function. METHODS: LAT was performed with a fixed-power protocol, whereas the number of applicators and illumination times were different according to target size. From one to three illuminations with pullback technique and with a total energy delivery based on the nodule volume were performed during the same session. Patients were evaluated during LAT, within 30 days, and 12 months after the procedure. RESULTS: Total number of treatments was 1837; 1280 (83%) of nodules had a single LAT session. Mean nodule volume decreased from 27 ± 24 mL at baseline to 8 ± 8 mL 12 months after treatment (P < .001). Mean nodule volume reduction was 72% ± 11% (range 48%-96%). This figure was significantly greater in mixed nodules (79% ± 7%; range 70%-92%) because they were drained immediately before laser illumination. Symptoms improved from 49% to 10% of cases (P < .001) and evidence of cosmetic signs from 86% to 8% of cases (P < .001). Seventeen complications (0.9%) were registered. Eight patients (0.5%) experienced transitory voice changes that completely resolved at the ear-nose-throat examination within 2-84 days. Nine minor complications (0.5%) were reported. No changes in thyroid function or autoimmunity were observed. CONCLUSIONS: Real practice confirmed LAT as a clinically effective, reproducible, and rapid outpatient procedure. Treatments were well tolerated and risk of major complications was very low.

BACKGROUND: The aim of the present trial on ultrasound (US)-guided laser ablation therapy (LAT) of solid thyroid nodules is to assess long-term clinical efficacy, side effects, and predictability of outcomes in different centers operating with the same procedure. PATIENTS: Two hundred consecutive patients were randomly assigned to a single LAT session (group 1, 101 cases) or to follow-up (group 2, 99 cases) at four thyroid referral centers. Entry criteria were: solid thyroid nodule with volume of 6-17 mL, repeat benign cytological findings, normal thyroid function, no autoimmunity, and no thyroid gland treatment. METHODS: Group 1: LAT was performed in a single session with two optical fibers, a 1064 nm Nd-YAG laser source, and an output power of 3 W. Volume and local symptom changes were evaluated 1, 6, 12, 24, and 36 months after LAT. Side effects and tolerability of treatment were registered. Group 2: Follow-up with no treatment. RESULTS: One patient was lost to follow-up in each group. Group 1: Volume decrease after LAT was -49 ± 22%, -59 ± 22%, -60 ± 24%, and -57 ± 25% at 6, 12, 24, and 36 months, respectively (P < .001 vs baseline). LAT resulted in a nodule reduction of >50% in 67.3% of cases (P < .001). Local symptoms decreased from 38 to 8% of cases (P = .002) and cosmetic signs from 72 to 16% of cases (P = .001). Baseline size, presence of goiter (P = .55), or US findings (fluid component ≤ 20% [P = .84], halo [P = .46], vascularization [P = .98], and calcifications [P = .06]) were not predictive factors of a volume decrease > 50%. The procedure was well tolerated in most (92%) cases. No changes in thyroid function or autoimmunity were observed. In group 2, nodule volume increased at 36 months (25 ± 42%; P = .04). The efficacy and tolerability of the procedure were similar in different centers. CONCLUSIONS: A single LAT treatment of solid nodules results in significant and persistent volume reduction and local symptom improvement, in the absence of thyroid function changes.