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Endothelin (ET-1) is a 21-amino acid, vasoconstrictive peptide originally isolated from endothelial cells. It is one member of a class of potent, purportedly paracrine substances that act at receptors in multiple target organs. Antagonists to the receptor subtypes, ETA and ETB, have been designed around the hydrophobic carboxy-terminus of ET-1. The(More)
The 3,5-isoxazolidinediones and 2-isoxazolin-5-ones demonstrated potent cytotoxicity against the growth of human Tmolt3 T cell leukemia, murine P388 and L1210 leukemias, as well as human HeLa-S3 uterine carcinoma and glioma tumor cell growth. The specificity of the 3,5-isoxazolidinedione and 2-isoxazoline-5-one derivatives as cytotoxic agents varied with(More)
A series of 3-imino-1-oxoisoindolines were shown to be potent anti-inflammatory and analgesic agents at 8 mg/kg, intraperitoneally in mice. The compounds were also able to protect against lipopolysaccharide induced endotoxic shock and death better than the current clinical agents. These agents appear to function by blocking the release of TNF alpha and IL-1(More)
2,3-Dihydrophthalazine-1,4-diones were observed to be potent anti-inflammatory agents as well as capable of protecting against endotoxin shock in mice at 8 mg/kg i.p. These agents blocked both locally- and centrally-induced pain at 8 mg/kg i.p. In part they appear to mediate their effects due to their ability to suppress the release of cytokines such as TNF(More)
N-Substituted indazolones were shown to be potent anti-inflammatory and analgesic agents in mice at 8 mg/kg. In addition, the agents were able to protect against death caused by endotoxins similar to those found in chronic infections. In part, the ability of these agents to suppress the inflammatory process is due to their blockage of cytokine release,(More)
In previous in situ and in vivo rat perfusion studies, the intestinal absorption of several low molecular weight drugs was increased by the presence of luminal D-glucose. The intent of this study was to determine the potential of this fed-state effect to improve the intestinal uptake of poorly permeable, small peptide and peptide-like drugs. Jejunal wall(More)
Programmable spatial shapers using liquid-crystal-based spatial-light-modulators in the National Ignition Facility lasers enable spatial shaping of the beam profile so that power delivered to the target can be maximized while maintaining system longevity. Programmable spatial shapers achieve three objectives: Introduce obscurations shadowing isolated flaws(More)
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