. Two clinical trials were performed to test the hypothesis that CVT-1, a potent inhibitor of pancreatic cholesterol esterase, reduces percent cholesterol absorption and LDL cholesterol in humans. Measurements of cholesterol absorption were made with deuterated cholesterol tracers given orally and intravenously and detected in plasma by a new technique using negative ion mass spectrometry. Study 1 was a randomized, double-blind parallel study of CVT-1 treatment at doses of 0, 300, 1500, and 3000 mg/day in 19 subjects. Percent cholesterol absorption measured at baseline and again after 2 and 6 weeks showed no treatment effect and LDL cholesterol was unchanged. Study II was a randomized open-label crossover comparison between CVT-1 given as 1000 mg three times daily for 2 weeks and 187.5 mg hourly 16 hours/day for 2 weeks. Percent cholesterol absorption and plasma LDL cholesterol were not different between periods. We conclude that cholesterol esterase is not requir ed for unesterified cholesterol absorption in human subjects.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR000954-25
Application #
6486752
Study Section
Project Start
2001-08-01
Project End
2002-07-31
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
25
Fiscal Year
2001
Total Cost
$157,506
Indirect Cost
Name
Washington University
Department
Type
DUNS #
062761671
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Yue, Xuyi; Dhavale, Dhruva D; Li, Junfeng et al. (2018) Design, synthesis, and in vitro evaluation of quinolinyl analogues for ?-synuclein aggregation. Bioorg Med Chem Lett 28:1011-1019
Cade, W Todd; Levy, Philip T; Tinius, Rachel A et al. (2017) Markers of maternal and infant metabolism are associated with ventricular dysfunction in infants of obese women with type 2 diabetes. Pediatr Res 82:768-775
Lucey, Brendan P; Mawuenyega, Kwasi G; Patterson, Bruce W et al. (2017) Associations Between ?-Amyloid Kinetics and the ?-Amyloid Diurnal Pattern in the Central Nervous System. JAMA Neurol 74:207-215
Ohlemacher, Shannon I; Giblin, Daryl E; d'Avignon, D André et al. (2017) Enterobacteria secrete an inhibitor of Pseudomonas virulence during clinical bacteriuria. J Clin Invest 127:4018-4030
Lin, Xiaobo; Racette, Susan B; Ma, Lina et al. (2017) Endogenous Cholesterol Excretion Is Negatively Associated With Carotid Intima-Media Thickness in Humans. Arterioscler Thromb Vasc Biol 37:2364-2369
Ovod, Vitaliy; Ramsey, Kara N; Mawuenyega, Kwasi G et al. (2017) Amyloid ? concentrations and stable isotope labeling kinetics of human plasma specific to central nervous system amyloidosis. Alzheimers Dement 13:841-849
Wei, Xiaochao; Song, Haowei; Yin, Li et al. (2016) Fatty acid synthesis configures the plasma membrane for inflammation in diabetes. Nature 539:294-298
Shields-Cutler, Robin R; Crowley, Jan R; Miller, Connelly D et al. (2016) Human Metabolome-derived Cofactors Are Required for the Antibacterial Activity of Siderocalin in Urine. J Biol Chem 291:25901-25910
Mertins, Philipp; Mani, D R; Ruggles, Kelly V et al. (2016) Proteogenomics connects somatic mutations to signalling in breast cancer. Nature 534:55-62
Murata, Takahiro; Dietrich, Hans H; Horiuchi, Tetsuyoshi et al. (2016) Mechanisms of magnesium-induced vasodilation in cerebral penetrating arterioles. Neurosci Res 107:57-62

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