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Abstract A drug targeting both the inflammatory initiators (lipopolysaccharide; LPS) and mediators tumor necrosis factor-α (TNF-α) should have advantage over a “single-factor targeting strategy” in sepsis prevention trials. We have prepared conjugates of polymyxin B (PMB) and the cytokine...
Abstract “Dopamine stabilizers” are a new class of compounds that have the ability to reverse both hypo- as well as hyperdopaminergia in vivo. This class, exemplified by the phenylpiperidines ( S )-(-)-3-(3-methanesulfonyl-phenyl)-1-propyl-piperidine (-)-OSU6162 and...
Abstract This study first investigates the anticancer effect of plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone) in human nonsmall cell lung cancer cells, A549. Plumbagin has exhibited effective cell growth inhibition by inducing cancer cells to undergo G 2 /M phase arrest and apoptosis....
Abstract Vascular endothelial cells (ECs), which regulate vascular tonus, serve as a barrier at the interface of vascular tissue. It is generally believed that alteration of this barrier is correlated with diabetic complications; however, a detailed mechanism has not been elucidated. This study...
Abstract Here, the ligand binding, activation, and tissue distribution of the orphan G protein-coupled receptor (GPCR) GPR92 were studied. GPR92 binds and is activated by compounds based on the lysophosphatidic acid (LPA) backbone. The binding of LPA to GPR92 was of high affinity ( K D = 6.4 ±...
Abstract Intoxication with γ-hydroxybutyrate (GHB) is associated with coma, seizure, and death; treatment of overdoses is symptomatic. Previous studies in our laboratory have demonstrated that l -lactate and pyruvate treatment can increase the renal clearance of GHB and increase its elimination...
Abstract Therapeutic strategies focused on kinase inhibition rely heavily on surrogate measures of kinase inhibition obtained from in vitro assay systems. There is a need to develop methodology that will facilitate measurement of kinase inhibitor activity or specificity in tissue samples from...
Abstract The present study determined the effects of the angiotensin-converting enzyme (ACE) inhibitor captopril and angiotensin II receptor subtype 1 (AT 1 -R) antagonist losartan on the internal anal sphincter pressures (IASP) in spontaneously hypertensive rats (SHR) versus normotensive...
Abstract The excitatory neurotransmitter glutamate has been implicated in both migraine and persistent pain. The identification of the kainate receptor GLU K5 in dorsal root ganglia, the dorsal horn, and trigeminal ganglia makes it a target of interest for these indications. We examined the in...
Abstract We recently demonstrated that endoxifen (4-hydroxy- N -desmethyl-tamoxifen), a pharmacogenetically regulated metabolite of tamoxifen, is equipotent to 4-hydroxy-tamoxifen (4-OH-Tam) with respect to estrogen receptor binding and inhibition of 17β-estradiol (E 2 )-induced cell...
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