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Abstract Bortezomib has been introduced recently in the therapy of multiple myeloma (MM), a disease that is frequently associated with progressive renal failure. Because bortezomib-based therapy has been reported to lead to a rapid recovery of kidney function in patients with MM, we decided to...
Abstract The present study was designed to compare the anti-inflammatory and antioxidant effects of two antidepressant drugs, desipramine 10,11-dihydro-5-3-(methylamino) propyl-5 H -dibenz- b , f azepine monohydrochloride and fluoxetine N...
Abstract Activation of pancreatic stellate cells (PSCs) is the key process in the development of pancreatic fibrosis, a common feature of chronic pancreatitis and pancreatic cancer. In recent studies, curcumin has been shown to inhibit PSC proliferation via an extracellular signal-regulated...
Abstract Cholestasis causes hepatocyte death, possibly because of mitochondrial injury. This study investigated whether NIM811 ( N -methyl-4-isoleucine cyclosporine), an inhibitor of the mitochondrial permeability transition (MPT), attenuates cholestatic liver injury in vivo. Cholestasis was...
Abstract Elimination of hydrogen sulfide from glutathione (GSH) converts a well known cellular nucleophile to an electrophilic species, γ-glutamyldehydroalanylglycine (EdAG). We have found that a sulfonium metabolite formed from GSH and busulfan undergoes a facile β-elimination reaction to give...
Abstract Recent evidence suggests that the P2X 7 receptor may play a role in the pathophysiology of preclinical models of pain and inflammation. Therefore, pharmacological agents that target this receptor may potentially have clinical utility as anti-inflammatory and analgesic therapy. We...
Abstract We report the first small-molecule protease-activated receptor (PAR) 2 agonists, AC-55541 N -1-(3-bromo-phenyl)-eth-( E )-ylidene-hydrazinocarbonyl-(4-oxo-3,4-dihydro-phthalazin-1-yl)-methyl-benzamide and AC-264613 2-oxo-4-phenylpyrrolidine-3-carboxylic acid 1-(3-bromo-phenyl)-( E / Z...
Abstract Macitentan, also called Actelion-1 or ACT-064992 N -5-(4-bromophenyl)-6-(2-(5-bromopyrimidin-2-yloxy)ethoxy)-pyrimidin-4-yl- N ′-propylaminosulfonamide, is a new dual ET A /ET B endothelin (ET) receptor antagonist designed for tissue targeting. Selection of macitentan was based on...
Abstract Metabotropic glutamate subtype-5 receptors (mGluR5) are implicated in several neuropsychiatric disorders. Positron emission tomography (PET) with a suitable radioligand may enable monitoring of regional brain mGluR5 density before and during treatments. We have developed a new...
Abstract Epoxyeicosatrienoic acids (EETs) are derived from cytochrome P450-catalyzed epoxygenation of arachidonic acid and have emerged as important mediators of numerous biological effects. The major elimination pathway for EETs is through soluble epoxide hydrolase (sEH)-catalyzed metabolism to...
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