Nos

Clinical Endocrinology 2006; 64: 703–710
Objective. Nitric oxide (NO) and endothelin-1 (ET-1) are involved
in carcinogenesis. Overexpression of the ET-1 axis has been demonstrated in papillary thyroid carcinoma (PTC). This study investigated the expression of NO synthases (NOS) and their relationship with expression of ET-1 and angiogenic markers in PTC.
Design and Patients. Expression of NOS, angiogenic markers
[vascular endothelial growth factor (VEGF), angiopoietin-1 and
angiopoietin-2] and their receptors was studied in surgical thyroid samples obtained from 22 patients aged 15–68 years. Three groups were constituted: normal thyroid (n = 5), Hashimoto’s thyroiditis (n = 9) and PTC (n = 8).
Results. Immunohistochemistry disclosed NOS2 and NOS3
immunoreactivity in PTC cells, the percentage of positive cells being greater than normal (P < 0·02). Real-time quantitative polymerase chain reaction (RTQ-PCR) showed that NOS2 and NOS3 mRNA levels were, respectively, increased (P < 0·02) by 2·6 ± 0·6 and 4·2 ± 1·1 times in PTC. RTQ-PCR demonstrated that VEGF, its receptors VEGFR-1 and VEGFR-2, and angiopoietin-2 and its receptor (Tie2) were also overexpressed (P < 0·05) in PTC. Correlations were found between ET-1 expression and that of NOS2, angiopoietin-1 and -2 (P < 0·05). NOS2 mRNA levels also correlated with those
of NOS3 and angiopoietin-2 (P < 0·05). In thyroiditis, NOS2 immunoreactivity was observed in inflammatory cells whereas NOS2 mRNA levels were 12·1 ± 1·6 times higher than normal (P < 0·005).
Conclusions. This study revealed an activation of the NO pathway in thyroid carcinoma, which is interrelated to the ET-1 axis, both systems being overexpressed in concert with angiogenic factors. This global system might play a role in carcinogenesis and constitutes a potential target for anticancer therapy.

Chronic hyperglycemia has been associated with increased oxidative stress in skeletal muscle and sympathetic nerve dysfunction. We investigated the effect of chronic hyperglycemia on the myocardium of patients with uncontrolled diabetes (UD) compared with patients with well-controlled diabetes (CD) and patients without diabetes (ND) after cardioplegic cardiopulmonary bypass (CP/CPB) with acute intraoperative glycemic control. Atrial tissue and serum were collected from 47 patients (ND=18 with glycated hemoglobin [HbA1c] of 5.8±0.2; CD=8 with HbA1c of 6.1±0.1; with UD=21 with HbA1c=9.6±0.5) before and after CP/CPB for immunoblotting, protein oxidation assays, immunohistochemical evaluation, and microarray analysis. The uncontrolled group had increased total protein oxidation (p&lt;0.05) and decreased levels of antioxidative enzyme manganese superoxide dismutase (MnSOD) (p&lt;0.05) after CP/CPB compared with the controlled group. Collagen staining revealed increased fibrosis in patien...