We found that QUIN acts as a substrate for NAD(+)
synthesis at very low concentrations (< 50 nM) in both neurons and astrocytes, but is cytotoxic at sub-physiological concentrations (> 150 nM) in both the cell types. We have shown that the GSK1210151A order NMDA ion channel blockers, MK801 and memantine, and the nitric oxide synthase (NOS) inhibitor, L-NAME, significantly attenuate QUIN-mediated PARP activation, NAD(+) depletion, and LDH release in both neurons and astrocytes. An increased mRNA and protein expression of the inducible (iNOS) and neuronal (nNOS) forms of nitric oxide synthase was also observed following exposure of both cell types to QUIN. Taken together these results suggests that QUIN-induced cytotoxic effects on neurons and astrocytes are likely to be mediated by an over activation of an NMDA-like receptor with subsequent induction of NOS and selleck products excessive nitric oxide (NO(aEuro cent))-mediated free radical damage. These results contribute significantly to our understanding of the pathophysiological mechanisms involved in QUIN neuro- and gliotoxicity and are relevant for the development of
therapies for neuroinflammatory diseases.”
“Study Design. Retrospective review of a prospectively accrued patient cohort.
Objective. The ability to treat severe pediatric spinal deformity through an all-posterior vertebral column resection (VCR) has obviated the need for a circumferential approach in both primary and revision settings. We examined indications, correction rates, and complications of this challenging procedure in the pediatric population.
Summary of Background Data. Traditionally,
severe pediatric spinal deformities were treated through a combined anterior/posterior spinal fusion.
Methods. Between 2000 and 2005, 35 consecutive patients underwent a posterior-only VCR by 1 of 2 surgeons at a single institution. Patients were divided into 5 diagnostic categories: (1) severe scoliosis (S) (n = 2; mean, 115; range, 79-150 degrees; average flexibility, 12%); (2) global kyphosis (GK) (n = 3; mean, 101; range, see more 91-113 degrees; average flexibility, 16%); (3) angular kyphosis (AK) (n = 10; mean, 86; range, 45-135 degrees, average flexibility, 23%); (4) kyphoscoliosis (KS) (n = 8; mean kyphosis, 103 degrees/scoliosis 87 degrees; mean combined, 190; range, 144-237 degrees); (5) congenital scoliosis (CS) (n = 12; mean, 43 degrees; range, 23-69 degrees; average flexibility, 20%). There were 20 primary/15 revision surgeries. There were 20 one-level, 11 two-level, and 4 three-level resections.
Results. The major curve correction averaged: Group S = 61 degrees/51%, Group GK = 56 degrees/55%, Group AK = 51 degrees/58%, Group KS = 98 degrees/54%, and Group CS = 24 degrees/60%.