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Biomedical subjects

G Dunea

Publications and source records attributed to G Dunea.

At least 19 recordsLinked to original sources

A study of xanthopterin in chronic renal failure.

Xanthopterin, a metabolic end product of the nonconjugated pterins dihydrobiopterin and tetrahydrobiopterin, is present in many organs and is known to inhibit the proliferation and growth of conconavalin-stimulated lymphocytes. We have developed a simple fluorometric method to measure xanthopterin in the blood and have validated the method by high pressure liquid chromatography (HPLC). Serum levels were 14 +/- 7 nmol/l in normal subjects and 141 +/- 51 nmol/l in hemodialysis patients (p < 0.02). Intermediate levels from patients with renal insufficiency not on dialysis correlated with serum creatinine levels (p < 0.001). Xanthopterin (MW 179) was cleared by hemodialysis at a slightly lower rate than creatinine. It is bound to protein, but the binding, 90 +/- 5% in normal subjects, is decreased in uremia to 60 +/- 15%, p < 0.01. Red cell levels of xanthopterin were five times higher than those of plasma in normal subjects (69 +/- 15 vs. 14 +/- 7 nmol/l, p < 0.001), but uremic patients had lower levels in red cells than in plasma (101 +/- 24 vs. 141 +/- 51 nmol/l, p < 0.05). Slight or moderate hemolysis induced by mechanical stress increased plasma xanthopterin levels by 35%, the effect being more pronounced when hemolysis was severe. We conclude that xanthopterin is increased and its binding to protein is decreased in chronic renal failure. The altered ratio of red cell/plasma xanthopterin levels may reflect an abnormality of the red cell membrane in uremia. We are conducting further studies to amplify our preliminary findings that xanthopterin inhibits cellular growth in vitro.

Chromatography, High Pressure Liquid

Purification and biochemical characterization of xanthopterin from patients with chronic renal failure. I. Isolation, purification and preliminary characterization.

We describe the purification and initial characterization of a hitherto unrecognized fluorescence (excitation/emission maxima at 380/440 nm and 400/460 nm) reported from this laboratory in patients with chronic renal failure (Clin Chem 31: 1988, 1985). Purification was achieved using Sephadex G-10 gel chromatography combined with reverse phase and ion exchange high-performance liquid chromatography (HPLC). Purity of the "blue-green" fluorescent compound was determined to be greater than 99% by HPLC, and two-dimensional thin layer chromatography using an acidic and basic solvent system. The excitation/emission maxima were shown to be 390 nm/456 nm, and ultraviolet scans, at pH 1.0, 7.0, and 13.0, gave absorbance optima at 261 nm/356 nm, 278 nm/390 nm, and 255 nm/394 nm, respectively. The isoelectric point of 4.05 in conjunction with the fluorescent and ultraviolet spectra suggests that the fluorophore belongs to the class of compounds known as pteridines.

Chromatography, High Pressure Liquid

Purification and biochemical characterization of xanthopterin from patients with chronic renal failure. II. Biochemical elucidation and structural analysis.

We have identified the primary endogenous fluorescent substance, which has characteristic excitation/emission maxima at 380/440 nm and 400/460 nm, found in the sera of patients with chronic renal failure (Clin Chem 32: 1276, 1988). Preliminary studies, using thin layer chromatography (with cellulose) in conjunction with pteridine standards, indicated that the compound is an unconjugated pteridine. Characterization by gas chromatography-mass spectrometry (electron impact), direct probe-mass spectrometry (electron impact/chemical ionization), and Fourier Transform Infrared analysis showed this compound to be xanthopterin (2-amino 4,6 pteridinedione), an unconjugated pteridine known to be present in man in trace quantities. An authentic sample of this compound had a retention time with high-performance liquid chromatography (HPLC) identical to that of the purified fluorophore. The physiological role of xanthopterin in the pathogenesis of uremia has yet to be elucidated.

Chromatography, Thin Layer

Generic acrimony.

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Drug Industry

Healing by touching.

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American Medical Association

Chromatographic studies of uremic plasma.

In order to characterize the spectrum of possibly toxic retention compounds in uremia we have developed a simple reproducible method of separating fractions of uremic serum by Sephadex G-15 column chromatography. This technique, which requires no prior deproteinisation and is carried out at ambient temperatures, allowed the separation of uremic serum into several well defined fractions. Subsequent thin layer chromatography (TLC) showed that each peak represented a mixture of peptides, and that there were qualitative and quantitative differences between the plasma of normal and uremic patients as well as between patients with acute renal failure and chronic renal failure.

Acute Kidney Injury

Continuing education.

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Attitude of Health Personnel