The netrin-1 receptor, deleted in colorectal cancer (DCC), is upregulated by repeated amphetamine treatment selectively in the ventral tegmental area (VTA) of adult rats and wild-type mice. Furthermore, adult dcc heterozygous mice fail to show amphetamine-induced
increases in VTA DCC expression JPH203 mw and do not develop sensitization to this drug.
Objectives The effects of netrin-1 receptor signaling on mesocorticolimbic dopamine system function change across development. However, the effects of AMPH on DCC receptor regulation and behavioral sensitization before puberty have not been determined. Here we examined whether (1) repeated amphetamine treatment would also alter DCC expression in juvenile rats and wild-type mice, and (2) dcc heterozygotes treated with amphetamine during the juvenile period (PND 22-32) would develop behavioral sensitization to this drug.
Results Repeated amphetamine downregulates DCC expression selectively
in the VTA of juvenile rodents. Moreover, the behavioral phenotype of adult dcc heterozygous mice is not present before puberty and is abolished by amphetamine treatment during the juvenile period. Remarkably, adult dcc heterozygotes pretreated with amphetamine as juveniles no longer exhibit reduced DCC expression in the VTA compared to wild-type controls.
Conclusions Our results indicate that netrin-1 receptor signaling may be a key factor in determining individual differences in vulnerability to the behaviorally sensitizing effects of amphetamine at different ages. Moreover, they suggest that the juvenile period marks a window of vulnerability during which exposure to stimulant drugs can reverse the behavioral Combretastatin A4 phenotype of adult dcc heterozygous mice.”
“Objective: This multicenter, prospective, nonrandomized trial was undertaken to evaluate the first-in-human experience with the INCRAFT endograft
(Cordis Corporation, Bridgewater, NJ), an ultralow-profile ZD1839 trimodular bifurcate device for the repair of abdominal aortic aneurysms.
Methods: Patients with asymptomatic infrarenal abdominal aortic aneurysms were eligible for enrollment in the trial. Anatomic eligibility criteria included a proximal aortic neck at least 15 mm in length and up to 27 mm in diameter, and an aortic bifurcation >= 18 mm in diameter. Iliofemoral access vessels were required to be large enough to accept the 14F (4.7 mm) outer diameter of the delivery system. The primary efficacy end point was technical success, defined by successful device deployment during the conclusion of the procedure at the desired location without a type I, III, or IV endoleak. The primary safety end point was defined by the absence of a type I, III, or IV endoleak or a device-or procedure-related major adverse event at the 1-month follow-up point.
Results: Over a 16-month period divided into two different phases, 57 men and three women with a mean age of 74.4 +/- 6.9 years were enrolled at three German and three Italian centers.