In an additional DM cohort, insulin therapy was initiated after aneurysm induction. Aneurysmal aortic enlargement progression

PRN1371 research buy was monitored with serial transabdominal ultrasound measurements. At sacrifice, AAA cellularity and proteolytic activity were evaluated by immunohistochemistry and substrate zymography, respectively. Influences of serum glucose levels on macrophage migration were examined in separate models of thioglycollate-induced murine peritonitis.

Results: At 14 days after PPE infusion, AAA enlargement in hyperglycemic mice (serum glucose a 300 mg/dL) was less than that in euglycemic mice (PPE-DM: 54% +/- 19% vs PPE: 84% +/- 24%, P < .0001). PPE-DM mice also demonstrated reduced aortic mural macrophage infiltration (145 87 vs 253 119 cells/cross-sectional area, SBI-0206965 P = .0325), elastolysis (% residual elastin: 20% +/- 7% vs 12% +/- 6%, P = .0209), and neovascularization (12 +/- 8 vs 20 +/- 6 vessels/high powered field, P = .0229) compared with PPE mice. Hyperglycemia limited AAA enlargement after ANG infusion in ApoE(-/-)mice

(ANG-DM: 38% +/- 12% vs ANG: 61% +/- 37% at day 28). Peritoneal macrophage production was reduced in response to thioglycollate stimulation in hyperglycemic mice, with limited augmentation noted in response to vascular endothelial growth factor administration. Insulin therapy reduced serum glucose levels and was associated

with AAA enlargement rates intermediate between euglycemic and hyperglycemic mice (PPE: 1.21 +/- 0.14 mm vs PPE-DM: 1.00 +/- 0.04 mm vs PPE-DM + insulin: 1.14 +/- 0.05 mm).

Conclusions: Hyperglycemia reduces progression of experimental AAA disease; lowering of serum glucose levels with insulin treatment diminishes this protective effect. Identifying mechanisms of hyperglycemic aneurysm inhibition may accelerate development of novel clinical therapies for AAA disease. (J Vase Surg 2010;52:975-83.)”
“The alpha-synuclein protein is a major component of Lewy bodies found in the brains of patients with Parkinson’s disease (PD). Recently, alpha-synuclein 98 (alpha-syn98), a small isoform of the wild type protein PDK4 was isolated. The neurotoxicity of this protein was assessed by over-expressing alpha-syn98 in dopaminergic cells. Enhanced expression of alpha-syn98 was insufficient to adversely affect the survival of neurons or to promote aggregation of the protein. However, when exposed to rotenone, alpha-syn98 over-expressing dopaminergic cells demonstrated significantly increased cytotoxicity and aggregate formation. Furthermore, we found enhanced basal ROS production and MDA levels in alpha-syn98 over-expressing neurons.