allopurinol and Infant--Newborn--Diseases

Neonatal hypoxia ischemia is characterized by inadequate blood perfusion of a tissue or a systemic lack of oxygen. This condition is thought to cause/exacerbate well documented neonatal disorders including neurological impairment. Decreased adenosine triphosphate production occurs due to a lack of oxidative phosphorylation. To compensate for this energy deprived state molecules containing high energy phosphate bonds are degraded. This leads to increased levels of adenosine which is subsequently degraded to inosine, hypoxanthine, xanthine, and finally to uric acid. The final two steps in this degradation process are performed by xanthine oxidoreductase. This enzyme exists in the form of xanthine dehydrogenase under normoxic conditions but is converted to xanthine oxidase (XO) under hypoxia-reperfusion circumstances. Unlike xanthine dehydrogenase, XO generates hydrogen peroxide as a byproduct of purine degradation. This hydrogen peroxide in combination with other reactive oxygen species (ROS) produced during hypoxia, oxidizes uric acid to form allantoin and reacts with lipid membranes to generate malondialdehyde (MDA). Most mammals, humans exempted, possess the enzyme uricase, which converts uric acid to allantoin. In humans, however, allantoin can only be formed by ROS-mediated oxidation of uric acid. Because of this, allantoin is considered to be a marker of oxidative stress in humans, but not in the mammals that have uricase. We describe methods employing high pressure liquid chromatography (HPLC) and gas chromatography mass spectrometry (GCMS) to measure biochemical markers of neonatal hypoxia ischemia. Human blood is used for most tests. Animal blood may also be used while recognizing the potential for uricase-generated allantoin. Purine metabolites were linked to hypoxia as early as 1963 and the reliability of hypoxanthine, xanthine, and uric acid as biochemical indicators of neonatal hypoxia was validated by several investigators. The HPLC method used for the quantification of purine compounds is fast, reliable, and reproducible. The GC/MS method used for the quantification of allantoin, a relatively new marker of oxidative stress, was adapted from Gruber et al. This method avoids certain artifacts and requires low volumes of sample. Methods used for synthesis of MMDA were described elsewhere. GC/MS based quantification of MDA was adapted from Paroni et al. and Cighetti et al. Xanthine oxidase activity was measured by HPLC by quantifying the conversi

Topics: Chromatography, High Pressure Liquid; Gas Chromatography-Mass Spectrometry; Humans; Hypoxia; Infant, Newborn; Infant, Newborn, Diseases; Malondialdehyde; Purines; Xanthine Oxidase

The reactions reflecting adaptation may assume pathological traits under certain conditions. It is necessary to have reliable predictors that characterize adaptive processes. As this criterion, it is expedient to use the most important marker of free radical oxidation, such as xanthine oxidase (XO) activity. On the basis of the authors' findings, it can be said that it is advisable to apply this test to the screening of the course of adaptation within the first days after birth and to the detection of neonatal infants who require more scrupulous attention.

Topics: Adaptation, Biological; Biomarkers; Female; Free Radicals; Humans; Infant, Newborn; Infant, Newborn, Diseases; Male; Xanthine Oxidase

Topics: Amino Acid Metabolism, Inborn Errors; Female; Humans; Infant, Newborn; Infant, Newborn, Diseases; Lens Subluxation; Metabolism, Inborn Errors; Molybdenum; Oxidoreductases; Oxidoreductases Acting on Sulfur Group Donors; Xanthine Oxidase; Xanthines