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Abstract The CC chemokine, eotaxin1 (CCL11) is an important regulator of eosinophil function. A marked accumulation of eosinophils in tissues has been correlated with the up-regulation of eotaxin1 expression in several diseases. The potential therapeutic value of neutralizing the effects of...
Abstract The mutation in the α 1A subunit gene of the P/Q-type (Ca v 2.1) Ca 2+ channel present in tottering ( tg ) mice causes ataxia and motor seizures that resemble absence epilepsy in humans. P/Q-type Ca 2+ channels are primarily involved in acetylcholine (ACh) release at mammalian...
Abstract The pharmacokinetics (PK) and pharmacodynamics (PD) of recombinant human erythropoietin (rHuEPO) were studied in rats after single i.v. and s.c. administration at three dose levels (450, 1350, and 4050 IU/kg). The plasma concentrations of rHuEPO and its erythropoietic effects including...
Abstract Methylphenidate (MPH) and other psychostimulants are highly effective in the treatment of attention deficit hyperactivity disorder (ADHD). Evidence indicates the therapeutic actions of stimulants in ADHD probably involve the locus coeruleus (LC)-norepinephrine system. LC neurons display...
Abstract Previous studies reported the ability of raloxifene to acutely relax arterial and venous vessels, but the underlying mechanisms are controversial. Anti-inflammatory effects of the drug have been reported in nonvascular tissues. Therefore, the aim of this study was to investigate the...
Abstract Prostaglandin E 2 (PGE 2 ) is both an inflammatory mediator released at the site of tissue inflammation and a neuromodulator that alters neuronal excitability and synaptic processing. The effects of PGE 2 are mediated by four G-protein-coupled EP receptors (EP1-EP4). Here we show that...
Abstract The antioxidant α-lipoic acid (LA) is a naturally occurring compound that has been shown to possess promising anticancer activity because of its ability to preferentially induce apoptosis and inhibit proliferation of cancer cells relative to normal cells. However, the molecular...
Abstract ATP-sensitive P2X 7 receptors are localized on cells of immunological origin including glial cells in the central nervous system. Activation of P2X 7 receptors leads to rapid changes in intracellular calcium concentrations, release of the proinflammatory cytokine interleukin-1β...
Abstract Accumulation of amyloid β-peptide (Aβ) is considered a key step in the etiology of Alzheimer's disease. Aβ is produced by sequential cleavage of the amyloid precursor protein by β- and γ-secretase enzymes. Consequently, inhibition of γ-secretase provides a promising therapeutic...
Abstract 7-But-2-ynyl-9-(6-methoxy-pyridin-3-yl)-6-piperazin-1-yl-7,9-dihydro-purin-8-one (ER-319711) is a novel dipeptidyl peptidase (DPP)-IV inhibitor discovered in our laboratories. In this study, we have characterized this DPP-IV inhibitor in vitro and in vivo as an antidiabetic agent. The...
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