Angiotensin-(1-7) via the mas receptor alleviates the diabetes-induced decrease in GFAP and GAP-43 immunoreactivity with concomitant reduction in the COX-2 in hippocampal formation: an immunohistochemical study.

We have previously shown that chronic treatment with angiotensin-(1-7) [Ang-(1-7)] can prevent diabetes-induced cardiovascular dysfunction. However, effect of Ang-(1-7) treatment on diabetes-induced alterations in the CNS is unknown. The aim of this study was to test the hypothesis that treatment with Ang-(1-7) can produce protection against diabetes-induced CNS changes. We examined the effect of Ang-(1-7) on the number of cyclooxygenase-2 (COX-2) immunoreactive neurons and the glial fibrillary acidic protein (GFAP)-immunoreactive astrocytes and assessed the changes in the neuronal growth-associated protein-43 (GAP-43) of the hippocampal formation in streptozotocin-induced diabetes in rats. Animals were sacrificed 30 days after induction of diabetes and/or treatment with Ang-(1-7). Ang-(1-7) treatment significantly prevented diabetes-induced decrease in the number of GFAP immunoreactive astrocytes and GAP-43 positive neurons in all hippocampal regions. Co-administration of A779, a selective Ang-(1-7) receptor antagonist, inhibited Ang-(1-7)-mediated protective effects indicating that Ang-(1-7) produces its effects through activation of receptor Mas. Further, Ang-(1-7) treatment through activation of Mas significantly prevented diabetes-induced increase in the number of the COX-2 immunolabeled neurons in all sub-regions of the hippocampus examined. These results show that Ang-(1-7) has a protective role against diabetes-induced changes in the CNS.

Thioredoxin and thioredoxin reductase expression in thyroid cancer depends on tumour aggressiveness.

Thyroid cancer is the second most common malignancy following breast cancer in Arab females. Thioredoxin (TRX) is a small multi-functional redox protein with both intracellular and extracellular functions. The protein exists in either a reduced form (thioredoxin-SH2) or an oxidized form (thioredoxin-S2). TRX acts as an enhancement for growth factors and stimulates the growth of cancer cells. In this study of thyroid neoplasms, involving 121 female and 62 male patients, expression of TRX and TRX-R was studied using purified mouse anti-human TRX monoclonal antibody and anti-human TRX-R antiserum from rabbits, respectively. In order to delineate tumour cell growth, proliferating cell nuclear antigen (PCNA) polyclonal antibody was used. Compared to normal thyroid tissue, expression of TRX and TRX-R was increased in the cytoplasm and nuclei of thyroid cancer cells. Furthermore, TRX expression correlated with that of TRX-R. Of the 183 thyroid neoplasms investigated, overexpression of TRX-R was found in different types of neoplasms. The majority of carcinomas showed a correlation between strongly positive TRX and TRX-R expression and neoplastic cellular proliferation, as measured by PCNA. This indicates that increased TRX and TRX-R expression may be associated with tumourigenesis by acting as an autocrine growth stimulus. This study suggests that TRX immunoreactivity in thyroid tumours is a function of malignancy and cancer progression. In addition, secreted TRX can also act as an extracellular growth factor for both normal and tumour cells and enhance the sensitivity of the cells. Furthermore, this study emphasizes the potential benefits of anti-TRX/TRX-R agents in cancer therapeutics in the treatment of thyroid cancer.