A5048499581- Drug Transport and Resistance Mechanisms
- Cholesterol and Lipid Metabolism
- Pediatric Hepatobiliary Diseases and Treatments
- Liver Disease Diagnosis and Treatment
- Metabolism and Genetic Disorders
- Steroid Chemistry and Biochemistry
- Hormonal Regulation and Hypertension
- Neonatal Health and Biochemistry
- Estrogen and related hormone effects
- Liver Diseases and Immunity
- Cancer, Lipids, and Metabolism
- Hormonal and reproductive studies
- Peroxisome Proliferator-Activated Receptors
- Gallbladder and Bile Duct Disorders
- Liver Disease and Transplantation
- Pharmacogenetics and Drug Metabolism
- Lipid metabolism and biosynthesis
- Drug-Induced Hepatotoxicity and Protection
- Gastroesophageal reflux and treatments
- Congenital Anomalies and Fetal Surgery
- Receptor Mechanisms and Signaling
- Antibiotics Pharmacokinetics and Efficacy
- Analytical Chemistry and Chromatography
- Inflammatory mediators and NSAID effects
- Folate and B Vitamins Research
New York University
2010-2023
NYU Langone Health
1989-2021
University of Kentucky
2019
National University of Rosario
2019
Columbia University Irving Medical Center
1993-2007
National Institutes of Health
2001-2007
Eunice Kennedy Shriver National Institute of Child Health and Human Development
2002-2007
ICU Medical (United States)
2007
Health and Human Development (2HD) Research Network
2003
University of Minnesota
2002
BACKGROUNDMirabegron is a β3-adrenergic receptor (β3-AR) agonist approved only for the treatment of overactive bladder. Encouraging preclinical results suggest that β3-AR agonists could also improve obesity-related metabolic disease by increasing brown adipose tissue (BAT) thermogenesis, white (WAT) lipolysis, and insulin sensitivity.METHODSWe treated 14 healthy women diverse ethnicities (27.5 ± 1.1 years age, BMI 25.4 1.2 kg/m2) with 100 mg mirabegron (Myrbetriq extended-release tablet,...
Sodium taurolithocholate and sodium taurocholenate were infused intravenously into rats hamsters. Each bile acid salt was given alone or in combination with varying amounts of a primary salt, either taurocholate taurochenodeoxycholate. Bile flow, total excretion, the excretion quantitatively determined. In addition, mannitol determined at various flow rates. found to be rapidly excreted concentrations greater than its aqueous solubility. When endogenous rate infusion less molar amount...
Steroidogenic acute regulatory protein (StAR) plays a key role in steroid hormone synthesis by enhancing the metabolism of cholesterol into pregnenolone. We determined organization StAR structural gene, mapped to 8p11.2. The gene spans 8 kb and consists seven exons interrupted six introns. 1.3 DNA upstream from transcription start site directed expression luciferase reporter mouse Y-1 adrenal cortical tumor cells but not BeWo choriocarcinoma cells. Reporter was increased more than 2-fold...
The pathways of bile acid synthesis in man were evaluated by studying the metabolism 7alpha-hydroxycholesterol-4-(14)C and 26-hydroxycholesterol-16, 22-(3)H administered parenterally to individuals requiring external biliary drainage. Techniques for identification metabolites thin-layer chromatography, column gas-liquid chromatography with stream splitting, crystallization constant specific activity. It was found that both compounds rapidly metabolized acids excreted bile. Of total...
Accumulation of very long chain fatty acids in X-linked and neonatal forms adrenoleukodystrophy (ALD) appears to be a consequence deficient oxidation acids, function that has been attributed peroxisomes. Peroxisomes were readily identified liver biopsies taken from patient having the disorder. However, neonatal-onset ALD, hepatocellular peroxisomes greatly reduced size number, sedimentable catalase was markedly diminished. The presence increased concentrations serum pipecolic acid bile...
Two major modifications of existing methods for the quantitative estimation serum bile salts by gas–liquid chromatography have been made. A new protein precipitation step using 2,2-dimethoxypropane gives almost complete recovery added salts. purification thin-layer good mono-, di-, and tri-hydroxy acids. Overall is greater than 70%. The procedure reduces time required salt analysis.
Bile acid synthesis from cholesterol can occur via two pathways, one initiated by sterol 27-hydroxylase activity or that of 7 alpha-hydroxylase. In contrast to alpha-hydroxylase, which is found in the liver, a widely distributed mitochondrial enzyme with high vascular endothelial cells. Although both pathways lead production chenodeoxycholic and cholic acids, key step, alpha-hydroxylation, governed different enzymes. Both 27-hydroxycholesterol 3 beta-hydroxy-5-cholestenoic acid, metabolites...
We attempted to quantitate production of bile acid via the 27-hydroxylation pathway in six human subjects. After bolus intravenous injection known amounts [24-14C]cholic and [24-14C]chenodeoxycholic acid, each subject underwent a constant infusion mixture [22,23-3H]-27-hydroxycholesterol [2H]-27-hydroxycholesterol for 6–10 h. Production rate 27-hydroxycholesterol was calculated from serum ratio deuterated/protium 27-hydroxycholesterol, which reached plateau level by 4 h infusion. Conversion...
Using isotope dilution mass spectrometry, 26-hydroxycholesterol was identified in the serum of normal adults. Total values ranged from 9.2 to 25.6 micrograms/100 ml which 31-35% free sterol. Density gradient ultracentrifugation indicates that steroid is distributed among low and high density lipoproteins.
Osteoporosis is an important clinical problem, affecting more than 50% of people over age 50 yr. Estrogen signaling critical for maintaining proper bone density, and the identification endogenous selective estrogen receptor (ER) modulator, 27-hydroxycholesterol (27HC), suggests a mechanism by which nutritional/metabolic status can influence biology. With its levels directly correlated with cholesterol, new possibility emerges wherein 27HC links cholesterol to homeostasis. In these studies,...
Abstract The Clemmensen reduction procedure has been adapted for the tritiation of kryptogenin to obtain cholest-5-ene-3β, 26-diol-3H. Intravenous administration cholest-5-ene-3β,26-diol bile fistula rat and hamster was followed by rapid excretion acid metabolites in bile. Cholic identified as a metabolite reverse isotope dilution five hamsters three rats. In addition, monohydroxy acid, 3β-hydroxy-5-cholenoic cholest-5-ene-3β,26-diol. It seems possible, therefore, that pathway from...
Oxysterol 7α-hydroxylase has broad substrate specificity for sterol metabolites and may be involved in many metabolic processes including bile acid synthesis neurosteroid metabolism. The cloned human oxysterol (CYP7B1) cDNA encodes a polypeptide of 506 amino residues that shares 40% sequence identity to cholesterol (CYP7A1), the rate-limiting enzyme conversion acids liver. In contrast liver-specific expression CYP7A1, CYP7B1 mRNA transcripts were detected tissues steroid genesis (brain,...
In humans, the biotransformation of cholesterol and its hydroxylated metabolites (oxysterols) by sulfonation is a fundamental process great importance. Nevertheless, sulfotransferase enzyme(s) that carries out this function has never been clearly identified. Cholesterol relatively poor substrate for previously cloned hydroxysteroid (HST), i.e. dehydroepiandrosterone (DHEA) (HST1). Recently, cloning single human gene encodes two proteins related to HST1 was reported. These newly...
Oxysterols constitute a class of cholesterol derivatives that exhibit broad biological effects ranging from cytotoxicity to regulation nuclear receptors. The role oxysterols such as 7-ketocholesterol (7-KC) in the development retinal macular degeneration and atheromatous lesions is particular interest, but little known their metabolic fate. We establish steroid/sterol sulfotransferase SULT2B1b, efficiently sulfonate cholesterol, also effectively sulfonates variety oxysterols, including 7-KC....
The use of 2-hydroxypropyl-~-cyclodextrin as a vehicle for solubilizing cholesterol and 27-hydroxycholestero1 has led to study their rates 7a-hydroxylation in microsomal preparations from hamster liver HepG2 cells.Addition the alone 7a-hydroxylase assay always caused several-fold increase activity.Preloading with further augmented rate 7a-hydroxycholesterol formation.Preloading 27-hydroxycholesterol or 27-hydroxycholestanol (molar ratio 1/1.2) minimally decreased activity (-12%), compared...