The I{kappa}B kinase inhibitor nuclear factor-{kappa}B essential modulator-binding domain peptide for inhibition of injury-induced neointimal formation.

OBJECTIVE: The activation of nuclear factor-κB (NF-κB) is a crucial step in the arterial wall's response to injury. The identification and characterization of the NF-κB essential modulator-binding domain (NBD) peptide, which can block the activation of the IκB kinase complex, have provided an opportunity to selectively abrogate the inflammation-induced activation of NF-κB. The aim of the present study was to evaluate the effect of the NBD peptide on neointimal formation. METHODS AND RESULTS: In the rat carotid artery balloon angioplasty model, local treatment with the NBD peptide (300 µg/site) significantly reduced the number of proliferating cells at day 7 (by 40%; P<0.01) and reduced injury-induced neointimal formation (by 50%; P<0.01) at day 14. These effects were associated with a significant reduction of NF-κB activation and monocyte chemotactic protein-1 expression in the carotid arteries of rats treated with the peptide. In addition, the NBD peptide (0.01 to 1 µmol/L) reduced rat smooth muscle cell proliferation, migration, and invasion in vitro. Similar results were observed in apolipoprotein E(-/-) mice in which the NBD peptide (150 µg/site) reduced wire-induced neointimal formation at day 28 (by 47%; P<0.01). CONCLUSIONS: The NBD peptide reduces neointimal formation and smooth muscle cell proliferation/migration, both effects associated with the inhibition of NF-κB activation.

Retrospective characterization of coma and stupor in dogs and cats presenting to a multicenter out-of-hours service (2012-2015): 386 animals.

OBJECTIVE: To describe the signalment, etiology, and short-term outcome of dogs and cats presenting in a coma or stupor. DESIGN: Retrospective study conducted between May 2012 and February 2015. SETTING: Multicenter out-of-hours emergency service provider. ANIMALS: Three hundred eighty-six patients presenting in a coma or stupor to a multicenter out-of-hours emergency care provider. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Records were reviewed to determine the most likely etiology of coma or stupor. Short-term outcomes were defined as deceased (died or euthanized) or transferred (case handed over to a daytime clinic or discharged). There were 168 dogs (coma n = 112, stupor n = 56) and 218 cats (coma n = 148, stupor n = 70) identified. Coma and stupor were more prevalent in cats compared to dogs, and Chihuahuas were over represented. Blood glucose concentrations were frequently outside established reference intervals. Excluding undetermined causes, the most common causes in dogs included traumatic brain injury (TBI) 16.0% (n = 27, deceased n = 22), hypoglycemia 10.7% (n = 18, deceased n = 8), shock 10.1% (n = 17, deceased n = 16), seizure 9.5% (n = 16, deceased n = 13), and renal or hepatic dysfunction 5.3% (n = 9, deceased n = 7). For cats, the most common causes included TBI 21.6% (n = 47, deceased n = 38), renal or hepatic dysfunction 13.3% (n = 29, deceased n = 25), intoxication 10.1% (n = 22, deceased n = 18), hypoglycemia 6.0% (n = 13, deceased n = 4), and shock 5.0% (n = 11, deceased n = 8). When treatment was attempted, 46.0% of dogs (n = 44/96) and 41.2% of cats (n = 35/85) survived to be transferred. Compared to all other etiologies, death was less likely when coma or stupor was attributed to hypoglycemia. CONCLUSION: In cases where a cause was determined, TBI was the predominant etiology of coma and stupor for both species. With the exception of coma and stupor attributed to hypoglycemia, the overall short-term prognosis was poor.