Biomedical subjects

Catherine A Best

Publications and source records attributed to Catherine A Best.

8 recordsLinked to original sources

PubMed2006

Method to assess fatty acid ethyl ester binding to albumin.

AIMS: To develop a method to assess the relative binding of fatty acid ethyl esters (FAEE) and free fatty acids (FFA) to albumin, and to determine if binding affinity is related to fatty acid chain length and or degree of saturation. METHODS: Radiolabelled ethyl-[14C] oleate bound to albumin was challenged with various ratios of FFA to FAEE. The displacement of ethyl-[14C] oleate by FFA was visualized and quantitated through a combination of native-PAGE, autoradiography, and liquid scintillation counting (LSC). RESULTS: As the ratio of FFA to FAEE increased from 0:1 to 12:1, for all fatty acids tested (myristate, palmitate, stearate, oleate, linoleate, and arachidonate), ethyl-[14C] oleate displacement increased, when expressed as radioactivity (in DPM) as a percentage of control. In contrast, ethyl oleate did not displace stearate or oleate from albumin at molar ratios up to 5:1 (FAEE:FFA). CONCLUSIONS: The method developed gave reproducible visualization of noncovalent binding of radiolabelled FAEE to albumin. The combination of native-PAGE and autoradiography LSC works well in assessing the binding properties of albumin and radiolabelled FAEE. The data indicate preferential binding of FFA over FAEE to albumin with six different FFA displacing FAEE to an approximately equal extent.

Albumins↗

PubMed2006

Increased plasma fatty acid ethyl ester levels following inhibition of oxidative metabolism of ethanol by 4-methylpyrazole treatment in human subjects.

BACKGROUND: Recent experimental evidence suggests that fatty acid ethyl esters (FAEE), nonoxidative metabolites of ethanol, mediate ethanol-induced organ damage. A direct association between pancreas-specific toxicity and increased levels of FAEE following inhibition of the oxidative metabolism of ethanol by 4-methylpyrazole (4-MP) has previously been shown in studies with rats. METHODS: We obtained plasma samples from 32 healthy human volunteers who drank ethanol following 4-MP or placebo ingestion to determine whether in vivo inhibition of oxidative metabolism of ethanol causes a shift to nonoxidative metabolism of ethanol and the subsequent production of increased levels of FAEE. Plasma FAEE were isolated by solid-phase extraction and quantified by gas chromatography-mass spectrometry (GC-MS). RESULTS: Plasma FAEE levels in subjects receiving 4-MP treatment before ethanol consumption were elevated compared with plasma FAEE concentrations taken from control subjects who received a placebo before ethanol ingestion. Increased FAEE levels in the 4-MP treatment group occurred after peak blood ethanol, and peak FAEE levels were achieved. There was a correlation between the blood ethanol and the plasma FAEE levels, and the correlation persisted in the presence or absence of 4-MP. The peak FAEE values were greater in men than in women, with or without 4-MP treatment. CONCLUSIONS: Our results indicate that the in vivo inhibition of the oxidative metabolism of ethanol using 4-MP results in an increased circulating concentration of FAEE, products of the nonoxidative metabolism of ethanol.

Adult↗

PubMed2006

Rapid fatty acid ethyl ester synthesis by porcine myocardium upon ethanol infusion into the left anterior descending coronary artery.

Fatty acid ethyl esters (FAEEs), nonoxidative metabolites of ethanol, have been implicated in ethanol-induced heart injury. To assess the in vivo production of FAEEs by myocardial tissue, we used a modified ethanol ablation procedure in pigs. A controlled 60-minute ethanol infusion was administered into the distal left anterior descending coronary artery in seven swine; serial blood sampling of the coronary sinus and peripheral vein before, during, and after infusion allowed measurement of FAEE production and ethanol levels in the coronary sinus and the peripheral circulation. In a single animal, FAEEs were also quantified from nine different sites within the myocardium. FAEEs were produced by the heart within 5 minutes of exposure to ethanol, with very high concentrations of FAEEs detected in coronary sinus blood. Significant variability in amounts of FAEEs was detected in different regions of the heart tissue. A strong correlation was found between coronary sinus FAEEs and ethanol concentration (r = 0.9241, P < 0.00001). FAEE production by the heart after delivery of ethanol into the left anterior descending coronary artery was rapid, reaching levels in the coronary sinus blood 4 to 10 times greater than that found in peripheral blood after ethanol intake. These data demonstrate that FAEEs may be mediators of ethanol-induced cardiotoxicity.

Animals↗

PubMed2003

Red blood cell fatty acid ethyl esters: a significant component of fatty acid ethyl esters in the blood.

Although alcohol abuse is known to cause an array of ethanol-induced red blood cell (RBC) abnormalities, the underlying molecular mechanisms remain poorly understood. Fatty acid ethyl esters (FAEEs) are toxic, nonoxidative ethanol metabolites that have been found in blood, plasma, and tissues. Because FAEEs have been shown to be incorporated into phospholipid bilayers, we conducted a controlled ethanol intake study to test the hypothesis that FAEEs accumulate and persist within RBCs following ethanol ingestion. We demonstrated that RBC FAEEs account for approximately 5% to 20% of total whole-blood FAEEs, and that the fatty acid composition of FAEEs in RBCs and plasma are different and vary differently over time. These data indicate that a significant percentage of FAEEs in the blood is associated with RBCs and that the metabolism of RBC FAEEs and that of plasma FAEEs (bound to albumin or lipoproteins) are largely independent.

Adult↗

PubMed2003

Fatty acid ethyl esters: toxic non-oxidative metabolites of ethanol and markers of ethanol intake.

This report describes the biochemistry of fatty acid ethyl esters (FAEE), non-oxidative metabolites of ethanol, and their clinical significance. We review information regarding the enzymes responsible for FAEE synthesis and degradation, and the mechanisms involved with the intracellular and extracellular transport of FAEE and FAEE-mediated cytotoxicity. Also a summary of reports on the emerging clinical significance and diagnostic utility of FAEE as short and long-term markers of alcohol consumption, and the methodological aspects of FAEE assessment is included.

Alcohol Drinking↗

PubMed2003

Fatty acid ethyl esters. Ethanol metabolites that reflect ethanol intake.

Fatty acid ethyl esters (FAEEs) are nonoxidative ethanol metabolites that have been implicated as mediators of alcohol-induced organ damage. FAEEs are detectable in the blood after ethanol ingestion, and on that basis represent markers of ethanol intake. FAEEs have also been quantitated in human liver and adipose tissue and have been shown to be postmortem markers of premortem ethanol intake. A substantial difference in FAEE concentration was found in liver and adipose tissue of patients with detectable blood ethanol at the time of autopsy vs those with no detectable blood ethanol, who were either chronic alcoholics or social drinkers. Most currently available diagnostic markers for chronic alcoholism have limited clinical utility. Data in this report demonstrate that the amount or type of FAEEs can be used to differentiate a chronic alcoholic from an episodic heavy drinker (binage drinker) at or near peak blood ethanol concentrations and approximately 24 hours after discontinuation of ethanol. Thus, FAEEs are markers of ethanol intake in blood and tissues and can be useful in distinguishing chronic alcoholics from binge drinkers.

Alcoholic Intoxication↗

PubMedDate not supplied

Fatty acid ethyl esters: recent observations.

Fatty acid ethyl esters (FAEE), esterification products of fatty acids and ethanol, have been shown to be mediators of ethanol-induced cell injury and their presence in the blood and tissues is a marker of ethanol intake. Recently, it has been shown that FAEE are produced within seconds of infusion of ethanol into the heart, when using a protocol similar to that used for myocardial ablation. This raises the possibility that the mechanism for the death of myocytes in cardiac ablation involves the generation of toxic FAEE. It has also been recently demonstrated that chronic alcoholics have a high concentration of a specific FAEE species--ethyl oleate. The use of the serum ethyl oleate concentration may be helpful in differentiating binge drinkers from chronic alcoholics.

Alcoholism↗

PubMedDate not supplied

Erythrocyte structure and dynamics quantified by Hilbert phase microscopy.

We present a new quantitative method for investigating red blood cell morphology and dynamics. The instrument integrates quantitative phase microscopy with an inverted microscope, which makes it particularly suitable for the noninvasive assessment of live erythrocytes. In particular, we demonstrate the ability of this approach to quantify noninvasively cell volume and dynamic morphology. The subnanometer path-length sensitivity at the millisecond time scales is exemplified by measuring the hemoglobin flow out of the cell during hemolysis.

Cell Size↗