RESULTS: The majority (88.74%) of California’s CES patients received surgery within the recommended 48-hour window after diagnosis. The incidence of CES in surgically treated degenerative lumbar disk patients was 1.51% with an average of 397 cases per year in California. CES patients had worse outcomes and used more healthcare resources than other surgically treated degenerative lumbar disk patients; this disparity was more pronounced for patients with advanced CES. CES patients treated after 48 hours had 3 times the odds of a nonroutine discharge as patients treated within 48 hours (odds ratio = 3.082; P < .001).

CONCLUSION:

In California, patients are being treated within the recommended 48-hour time frame.”
“Objective: The

present study was aimed at developing a new cell-permeant peptide inhibitor (MK2i) of the kinase that phosphorylates selleck chemicals llc Dasatinib concentration and activates heat-shock protein (HSP)27 (MAPKAP kinase II), and evaluating the ability of this peptide to inhibit HSP27 phosphorylation and intimal thickening.

Methods: The ability of MK2i to reduce HSP27 phosphorylation and cell migration was evaluated in A7R5 cells stimulated with arsenite or lysophosphatidic acid. Stable isotopic labeling using amino acids in cell culture, in combination with liquid chromatography mass spectrometry, was used to characterize the effect of MK2i on global protein expression in fibroblasts. The effect of MK2i on intimal thickening and connective tissue growth factor expression was evaluated in human saphenous vein (HSV) rings maintained with 30% fetal bovine serum for 14 days by light microscopy and immunoblotting.

Results: Pretreatment of cells

with MK2i (10 mu M) prior to arsenite Terminal deoxynucleotidyl transferase or lysophosphatidic acid stimulation decreased phosphorylation of HSP27 (36% +/- 9% and 33% +/- 10%, respectively) compared with control (not pretreated) cells. MK2i also inhibited A7R5 migration, and downregulated the transforming growth factor-induced expression of collagen and fibronectin in keloid cells, two major matrix proteins involved in the development of intimal hyperplasia. Treatment of HSV segments with MK2i enhanced relaxation, reduced HSP27 phosphorylation (40% +/- 17%), connective tissue growth factor expression (17% +/- 5%), and intimal thickness (48.2% +/- 10.5%) compared with untreated segments. On the other hand, treatment with a recombinant fusion protein containing a cell-permeant peptide attached to the HSP27 sequence increased intimal thickness of HSV segments by 48% +/- 14%.

Conclusion: Our results suggest that HSP27 may play a role in the development of processes leading to intimal hyperplasia in HSV, and reduction of HSP27 phosphorylation by MK2i may be a potential strategy to inhibit the development of intimal hyperplasia in HSV to prevent the autologous vascular graft failure. ( J Vase Surg 2010;52:1596-1607.