This study investigated the effects of the peroxisome proliferator-activated receptor-gamma agonist rosiglitazone (RGZ) on cardiac fibroblast proliferation, nitric oxide content and connective tissue growth factor (CTGF) expression following incubation with advanced glycation end-products (AGEs). Cultured neonatal rat cardiac fibroblasts were incubated with various concentrations of AGEs for 48 h. Cells were also incubated with 200 mg/l AGEs plus various concentrations of RGZ. Cardiac fibroblast proliferation and cell cycle status were detected using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry. Western blotting was used to measure the expression of CTGF and nitric oxide content was evaluated using a nitrate reductase assay. AGEs significantly accelerated proliferation, increased CTGF expression and decreased nitric oxide production in cardiac fibroblasts. These effects of AGEs were inhibited by RGZ in a dose-dependent manner. Treatment with RGZ could be a valuable therapeutic approach in diabetic patients with myocardial fibrosis.

Lymphedema is a well-known complication of Noonan syndrome (NS) but the lymphatic malformations in NS are poorly understood. We report clinical, genetic, and imaging information about a boy and girl with NS and late-onset lower extremity lymphedema. A de novo mission mutation of RIT1 (NM_006912.5) c.246T>A, p.Phe82Leu was identified in the girl, who also showed systemic lymphatic hyperplasia and dysfunction. Magnetic resonance lymphangio-graphy (MRL) of the boy clearly demonstrated segmental dilated and hyperplastic lymphatics with impaired transport function in an affected limb and pelvic region. Indocyanine green lymphography (ICGL) showed delayed and partial enhancement of the lymph vessels in the affected limb but no lymph reflux was detected. No causative mutation was identified in the second case. Lymphoscintigraphy (LSG) failed to show lymph vessels in either of the children. Our study showed that MRL is a reliable and accurate test that can be used to demonstrate morpho-logical and functional defects of the lymphatic system. Moreover, ICGL is sufficiently sensitive to determine the functional condition of peripheral lymph vessels. The combined use of imaging modalities can give an accurate diagnosis of complex lymphatic system anomalies in NS and other syndromic diseases.

No abstract