20-Hydroxyeicosatetraenoic acid (20-HETE) contributes to the migration and proliferation of vascular smooth muscle cells (VSMC) in vitro, but there are few studies that address its effects on vascular remodeling in vivo. The present study determined whether inhibition of 20-HETE production attenuates intimal hyperplasia (IH) and vascular remodeling after balloon injury (BI). Sprague Dawley rats underwent BI of the common carotid artery and were treated with vehicle, 1-aminobenzotriazole (ABT, 50 mg/kg i.p. once daily), or HET0016 (N-hydroxy-N9-(4-butyl-2-methylphenyl)-formamidine) (2 mg/kg s.c. twice daily) for 14 days. Fourteen days after BI and treatment, the animals underwent carotid angiography, and the arteries were harvested for morphometric, enzymatic and immunohistochemical analysis. There was a 96% reduction of angiographic stenosis in the rats treated with 1-ABT. There was a 61 and 66% reduction of the intima/media area ratios in the 1-ABT and HET0016 treated rats compared with the vehicle-treated group. 20-HETE levels were elevated in BI carotid arteries, and the levels were markedly suppressed in the groups treated with 1-ABT and HET0016 (P , 0.001). Immunostaining revealed that the expression of CYP4A enzyme was markedly increased in the neointima of BI arteries, and it colocalized with the expression of smooth musclespecific actin, indicating increased proliferation of VSMC. An increase in the expression of CYP4A and the production of 20-HETE contributes to neointimal growth in BI rat carotid arteries. Systemic administration 1-ABT or HET0016 prevents the increase in 20-HETE levels and attenuates VSMC migration and proliferation, resulting in a marked reduction in IH and vascular remodeling after endothelial injury.
The authors describe the unique presentation of Balamuthia mandrillaris encephalitis in a kidney donor and two recipients. All three patients suffered acute clinical deterioration, with radiological or clinical evidence of intracranial hypertension. Brain autopsy in the donor and an urgent brain biopsy in a recipient established the diagnosis. First-tier therapy, with mannitol and CSF drainage, successfully treated the intracranial hypertension in both recipients, while administration of a combination of antiamebic drugs was associated with survival in the second recipient. For both recipients, neurosurgical management played a critical role in the rapid diagnosis and treatment of Balamuthia mandrillaris encephalitis.
Onyx embolization under balloon catheter flow arrest allows for greater nidal penetration of embolic material and improved reflux control. The technique is limited by the current deliverability of balloon catheters and the potential risk for earlier embolization of dangerous anastomosis.
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