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BACKGROUND Traumatic brain injury (TBI) with its associated morbidity is a major area of unmet medical need that lacks effective therapies. TBI initiates a neuroinflammatory cascade characterized by activation of astrocytes and microglia, and increased production of immune mediators including proinflammatory cytokines and chemokines. This inflammatory(More)
INTRODUCTION The purpose of this study was to compare urate-lowering (UL) efficacy and safety of daily febuxostat and allopurinol in subjects with gout and serum urate (sUA) > or = 8.0 mg/dL in a six-month trial. METHODS Subjects (n = 2,269) were randomized to febuxostat 40 mg or 80 mg, or allopurinol 300 mg (200 mg in moderate renal impairment).(More)
We tested the hypothesis that TREK-1, a two-pore domain K channel, is involved with dilations in arteries. Because there are no selective activators or inhibitors of TREK-1, we generated a mouse line deficient in TREK-1. Endothelium-mediated dilations were not different in arteries from wild-type (WT) and TREK-1 knockout (KO) mice. This includes dilations(More)
Obstructive sleep apnea (OSA), a condition in which the upper airway collapses during sleep, is strongly associated with metabolic and cardiovascular diseases. Little is known how OSA affects the cerebral circulation. The goals of this study were 1) to develop a rat model of chronic OSA that involved apnea and 2) to test the hypothesis that 4 wk of apneas(More)
Slow afterhyperpolarizations (sAHPs) play an important role in establishing the firing pattern of neurons that in turn influence network activity. sAHPs are mediated by calcium-activated potassium channels. However, the molecular identity of these channels and the mechanism linking calcium entry to their activation are still unknown. Here we present several(More)
Two-pore domain K(+) (K(2P)) channels are a new channel family. The goal of this study was to determine if K(2P) channels are activated by the nitric oxide (NO)/cGMP/PKG pathway in vascular smooth muscle. Relative levels of message for K(2P) channels were assessed in rat middle cerebral arteries (MCAs) using quantitative RT-PCR, and K(+) currents were(More)
BACKGROUND Angiotensin receptor blockers (ARBs) are preferred antihypertensive therapies in patients with type 2 diabetes mellitus (T2DM). Azilsartan medoxomil (AZL-M) is a potent ARB for the treatment of stages 1-2 hypertension. We compared the efficacy, safety, and metabolic effects of AZL-M to both valsartan (VAL) and olmesartan (OLM), separately in(More)
A phase 3, 26-week, open-label, titrate-to-target study (n=418) assessed the safety of azilsartan medoxomil (AZL-M) alone and with chlorthalidone (CLD), followed by a 6-week, double-blind, placebo-controlled reversal phase with change in clinic diastolic blood pressure (DBP) as the primary endpoint. Target blood pressure (BP) was <140/90 mm Hg (<130/80 mm(More)
A new rodent model for obstructive sleep apnea: effects on ATP-mediated dilations in cerebral arteries. Obstructive sleep apnea (OSA), a condition in which the upper airway collapses during sleep, is strongly associated with metabolic and cardio-vascular diseases. Little is known how OSA affects the cerebral circulation. The goals of this study were 1) to(More)
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