Evaluation of microparticle chemically bonded reversed-phase packings in the high-pressure liquid chromatographic analysis of nucleosides and their bases

Hartwick, Richard A.; Brown, Phyllis R.

doi:10.1016/s0021-9673(01)84111-x

Cited by 186 publications

(37 citation statements)

References 33 publications

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“…Fluorimetry (30, 3 1) and high-performance liquid chromatography (HPLC) (28,(32)(33)(34)(35) provide methods with greater sensitivity. Although several other methods have been described, pOz, fluorimetric, or HPLC methods are the most generally used.…”

Section: Methodsmentioning

confidence: 99%

Hypoxanthine as an Indicator of Hypoxia: Its Role in Health and Disease through Free Radical Production

Saugstad¹

1988

Pediatr Res

379

206

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Hypoxia is a common insult during the perinatal and neonatal period. New and better ways to evaluate hypoxia are needed. In 1975 we demonstrated high concentrations of the purine metabolite hypoxanthine in umbilical cord plasma after intrauterine hypoxia and proposed that hypoxanthine could be used as an indicator of hypoxia (1). Since then a large number of studies have been published dealing with different aspects of hypoxanthine in hypoxia. However, investigators in this field have encountered several methodologic problems: 1) Hypoxanthine leaks rapidly from erythrocytes (2, 3); if plasma is not separated promptly from red cells, falsely elevated plasma hypoxanthine concentrations will be found. 2) There are large variations in purine metabolism among species. 3) No clear definition of clinical hypoxia is available. Many authors do not distinguish between the terms hypoxemia and hypoxia, which adds to the confusion. We define tissue hypoxia as: "oxygen deficiency resulting in altered or interrupted energy metabolism" (4). It is important to be aware that hypoxia has two stages. In the first stage it is compensated because the cells are able to meet energy demands through anaerobic metabolism and other mechanisms. (We are not dealing with physiologic adaptation to hypoxia.) In the second stage of hypoxia or uncompensated hypoxia, energy demands are not met and cell injury ensues. At present there are no techniques for distinguishing between these two stages in clinical medicine, and such a distinction would be useful. Theoretically hypoxanthine should only be elevated in uncompensated hypoxia, while pH and lactate changes occur in compensated hypoxia. It seems, however, that hypoxanthine is also elevated to some extent in uncompensated hypoxia.Renewed interest in hypoxanthine developed when it was realized that hypoxanthine is a potential free radical generator (5, 6). Hypoxanthine seems to play a role in posthypoxic reoxygenation cell injury through oxygen radical production (7) and is therefore involved in the pathogenesis of a number of diseases. Hypoxanthine also modulates a number of other processes because it reacts with benzodiazepine receptors (8) and inhibits phosphodiesterase in the brain (9). Hypoxanthine inhibits the effect of several cytotoxic drugs and may therefore influence treatment with such drugs (10).Herein we summarize the extensive literature on hypoxanthine published during the last decade and try to answer the question: How useful in clinical medicine are hypoxanthine measurements in plasma and other body fluids? Is hypoxanthine a better marker of hypoxia than lactate or pH? Further, we discuss the significance of hypoxanthine as a potential oxygen radical generator and put forward a hypothesis for the pathogenesis of an "oxygen radical disease in neonatology". In hypoxia there is an accelerated breakdown of AMP to hypoxanthine. Figure 1 illustrates several important aspects of hypoxanthine metabolism in hypoxia. Normally about 90% of the hypoxanthine formed is reutilized through the sa...

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Section: Methodsmentioning

confidence: 99%

Hypoxanthine as an Indicator of Hypoxia: Its Role in Health and Disease through Free Radical Production

Saugstad¹

1988

Pediatr Res

379

206

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“…Plasma and urinary nucleosides and purine bases were determined by high pressure liquid chromatography (21). Purine compounds were identified by their specific retention times and the enzymatic peak-shift technique (22,23). Hypoxanthine and adenine phosphoribosyltransferases were determined by radiochemical methods (24).…”

Section: Methodsmentioning

confidence: 99%

Hereditary xanthinuria. Evidence for enhanced hypoxanthine salvage.

Mateos¹,

Puig²,

Jiménez³

et al. 1987

J. Clin. Invest.

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We tested the hypothesis that there is an enhanced rate of hypoxanthine salvage in two siblings with hereditary xanthinuria. We radiolabeled the adenine nucleotide pool with 18-'4Cladenine and examined purine nucleotide degradation after intravenous fructose. The cumulative excretion of radioactivity during a 5-d period was 9.7% and 9.1% of infused radioactivity in the enzymedeficient patients and 6.0±0.7% (mean±SE) in four normal subjects. Fructose infusion increased urinary radioactivity to 7.96 and 9.16 X 106 cpm/g creatinine in both patients and to 4.73±0.69 X 106 cpm/g creatinine in controls. The infusion of fructose increased total urinary purine excretion to a mean of 487% from low-normal baseline values in the patients and to 398±86% in control subjects. In the enzyme-deficient patients, the infusion of fructose elicited an increase of plasma guanosine from undetectable values to 0.7 and 0.9 gM. With adjustments made for intestinal purine loss, these data support the hypothesis that there is enhanced hypoxanthine salvage in hereditary xanthinuria. Degradation of guanine nucleotides to xanthine bypasses the hypoxanthine salvage pathway and may explain the predominance of this urinary purine compound in xanthinuria.

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“…Samples were immediately centrifuged in order to eliminate any red blood cell contamination. They were then frozen at -70°C until assayed for adenosine and adenosine metabolites concentration by HPLC (Hartwick and Brown, 1976).…”

Section: Csf Adenosine Concentrationsmentioning

confidence: 99%

The Role of Adenosine in the Vascular Adaptation of Neonatal Cerebral Blood Flow during Hypotension

Laudignon

Beharry

Farri

et al. 1991

J Cereb Blood Flow Metab

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Summary: This study investigated the potential role of adenosine in cerebral blood flow (CBF) regulation in the neonate during moderate and severe hypotension. Exper iments were done in anesthetized, 1-to 3-day-old piglets. Regional CBF (determined by radio labeled microsphere technique) and cerebral metabolic rate for Oz (CMROz) were measured (a) during normotension and (b) during a 3-min period of moderate (58 ± 9 mm Hg) or severe (36 ± 7 mm Hg) hypotension produced by the inflation of a balloon catheter placed in the aortic root. Measurements of CBF and CMROz were performed successively after intracerebroventricular (i. c. v. ) injections of vehicle (n = 17), the adenosine receptor blocker 8-phenyltheophylline (8-PT, 10 /Lg, n = 14), and the A2-receptor agonist 5'-N-(ethylcarboxamide)adenosine (NECA, 2 ng, n = 8).After i. c. v. administration of vehicle, none of the param eters studied was significantly altered by moderate hy potension, but severe hypotension decreased the total Autoregulation (i.e., the maintenance of a con stant cerebral blood flow (CBF) over a range of systemic blood pressure) exists in the neonates (Hernandez et aI., 1980; Laptook et aI., 1982 Laptook et aI., , 1983 Papile et aI., 1985; Leffler et aI., 1986) albeit at a narrower range relative to adults. It is due to an adaptation of the cerebral resistance vessels that constrict in response to an increase in cerebral per fusion pressure and dilate in response to a decrease Received March 3, 1990; revised November 5, 1990; accepted November 9, 1990.Address correspondence and reprint requests to Dr. N. Lau dignon at Department of Pharmacology and Therapeutics, The Montreal Children's Hospital, Room A-604, 2300 Tupper Street, Montreal, Quebec, H3H IP3, Canada.Abbreviations used: CO, cardiac output; COD, cerebral oxy gen delivery; CVR, cerebral vascular resistance; EHNA, erythro-9-(2-hydroxy-3-nonyl)adenine; i. c. v. , intracerebro ventricular; NECA, 5'-N-(ethylcarboxamide)adenosine; 8-PT, 8-phenyltheophylline. 424CBF (mean ± SD) from 86 ± 24 to 40 ± 15 ml min -I 100 g-l and CMROz from 3. 2 ± 0. 8 to 1. 8 ± 1. 0 ml min -I 100 g-I (p < 0. 05). Administration of 8-PT did not alter these parameters during normotension, but significantly de creased CBF during moderate hypotension compared to postvehicle values (53 ± 11 versus 81 ± 12 ml min -I 100 g-l, P < 0. 05). This loss of autoregulation was com pletely reversed by NECA. During severe hypotension, 8-PT altered the CBF redistribution towards the brain stem. Mean normotensive CSF concentrations of adeno sine (0. 76 ± 0. 26 /LM) increased during moderate (l.40 ± 1. 78 /LM) and severe (2. 60 ± 2. 56/LM, p < 0.05) hypoten sion. These data suggest that, in the newborn, adenosine is an important mediator of the cerebral adaptive re sponse to hypotension, even within the range of autoreg ulation.

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Evaluation of microparticle chemically bonded reversed-phase packings in the high-pressure liquid chromatographic analysis of nucleosides and their bases

Cited by 186 publications

References 33 publications

Hypoxanthine as an Indicator of Hypoxia: Its Role in Health and Disease through Free Radical Production

Hypoxanthine as an Indicator of Hypoxia: Its Role in Health and Disease through Free Radical Production

Hereditary xanthinuria. Evidence for enhanced hypoxanthine salvage.

The Role of Adenosine in the Vascular Adaptation of Neonatal Cerebral Blood Flow during Hypotension

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