In order to examine the neurotoxic mechanism of oxygen radicals on cultured bovine oligodendrocytes, cytoxic effect of oxygen radicals was examined when cultures were treated with various concentrations of xanthine oxidase (XO) and hypoxanthine (HX) in culture medium. In addition, the neuroprotective effect of iron-chelators against the neurotoxicity induced by oxygen radicals was evaluated by MTT assay. Cell viability was remarkably decreased in a time-dependent manner after exposure of cultured bovine oligodendrocytes to 20mU/ml XO and 0.1mM HX for 4 hours. In the neuroprotective effect of iron-chelators on oxidant-induced neurotoxicity, tetrakis (2-pyridylmethyl)ethylenediamine (TPEN) blocked the neurotoxicity induced by oxygen radicals, while DFX was not effective in blocking oxidant-induced neurotoxicity in these cultures. These results suggest that oxygen radicals are toxic in cultured bovine oligodendrocytes, and also selective iron-chelators such as TPEN are effective in blocking the neurotoxicity induced by oxygen radicals.
Allopurinol* ; Cell Survival ; Hypoxanthine ; Neuroprotective Agents ; Oligodendroglia ; Reactive Oxygen Species ; Xanthine Oxidase

Deficiency of hypoxanthine-guanine phosphoribosyltransferase is a purine nucleotide disorder and is the most common genetic cause of uric acid overproduction. This disease has a wide range of spectrum with regard to neurological features depending on the extent of the enzymatic deficiency. Complete deficiency of hypoxanthine-guanine phosphoribosyltransferase, called Lesch-Nyhan syndrome, is presented with hyperuricemia and characteristic neurological manifestation and self-mutilation. Partial hypoxanthine-guanine phosphoribosyltransferase--deficient patients are presented with a various intensities of the aforementioned symptoms, from almost normal neurologic manifestation to a severe form along with hyperuricemia. We report a twenty-year-old man with complete hypoxanthine-guanine phosphoribosyltransferase mutation and Lesch-Nyhan sydrome, who manifested gouty arthritis without neurologic symptom.
Arthritis, Gouty* ; Humans ; Hyperuricemia ; Hypoxanthine Phosphoribosyltransferase ; Lesch-Nyhan Syndrome* ; Neurologic Manifestations* ; Uric Acid

OBJECTIVE: It has been known that the enzyme deficiency associated with uric acid production is the minor cause of gout. The purpose of this study is to evaluate the role of hypoxanthine- guanine phosphoribosyltransferase (HGPRT) activity deficiency in the development of gout. METHODS: Assay of HGPRT activity was performed on 38 gout patients and 107 controls compromising 82 men and 25 women. In the patients with gout, age of onset, sex, family history of gout, duration of disease, serum uric acid level, and uric acid concentration of 24-hour urine were analyzed. RESULTS: In gout patients and control male group, the HGPRT activity was lowest in the age of forties. But, in female, there was no decreasing tendency with aging. In 4 gout patients, HGPRT activities were severely deficient and their ages of onset were less than 30 years old, and all have a family history of gout. CONCLUSION: In men, the lowest HGPRT activity in the age of forties could be one of the factors that make the onset of gout is highest in the fifth decade of age. The deficiency of HGPRT enzyme and family history of gout are the important factors in the pathogenesis of early onset gout.
Adult ; Age of Onset ; Aging ; Female ; Gout* ; Humans ; Hypoxanthine Phosphoribosyltransferase* ; Male ; Uric Acid

The purpose of this study is to obtain the clinicopathological characteristics of replication error-positive (RER ) gastric adenocarcinoma in Korean, and to identify the significance of RER in adenoma stage of gastric carcinogenesis. Microsatellite instability was examined at D2S71, D2S119, D3S1067, D6S87, D11S905, DM, AR, VWF, HPRT, and BAT-26 loci. Frameshift mutation of BAX gene was analyzed in RER tumors. Normal and tumor DNA of 76 cases of gastric carcinoma and 25 cases of adenoma were examined. RER was found in 8 of 76 cases (10.5%), and it was more frequently found in adenocarcinoma of female (17.7%) than those of male (4.8%). The frequency of RER was not different between the histologic types, age of the patient, anatomical location of the carcinoma, and the stage. The RER found in adenoma suggests that RER contributes to the malignant transformation early in the adenoma stage of the gastric carcinogenesis. None of the RER tumors revealed frameshift mutation of the BAX gene.
Adenocarcinoma* ; Adenoma ; Carcinogenesis ; DNA ; Female ; Frameshift Mutation ; Humans ; Hypoxanthine Phosphoribosyltransferase ; Male ; Microsatellite Instability

OBJECTIVEUsing HPLC To determine hypoxanthine in co-hirudo injection for establishing its HPLC fingerprint, and evaluating its internal quality.

METHODThe chromatographic separation was performed on a Kromasil C18 column (4.6 mm x 250 mm,5 microm). A linear gradient elution with A (0.01 mol x L(-1) x KH2PO4) and B (50% methanol) was used, the flow rate was 0.8 mL x min(-1), the detection wavelength was set at 254 nm, and the column temperature was at normal.

RESULTHypoxanthine was used as the reference substance in the fingerprint of co-hirudo injection, it showed 15 common peaks and theirs similarity threshod was 0.97.

CONCLUSIONThis method was accurate, repeatable and useful for the quality control of co-hirudo injection.

Animals ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; chemistry ; Hypoxanthine ; chemistry ; Leeches ; chemistry ; Reproducibility of Results

Allopurinol(4-hydroxypyrazolo[3, 4-d]pyrimidine) is an analog of hypoxanthine, widely used in the treatment of gout and in some patients develop the allopurinol hypersensitivity syndrome. Allopurinol hypersensitivity syndrome is characterized by multiple symptoms and signs such as fever, rash, decreased renal function, hepatocellular injury, leukocytosis, and eosinophilia. Herein reported is a 44 year-old male patient who developed generalized erythematous skin eruption with severe hepatotoxicity 3 weeks after taking allopurinol medication. The patient improved by dropping the allopurinol medication, which was consistent with the allopurinol hypersensitivity syndrome.
Adult ; Allopurinol* ; Eosinophilia ; Exanthema ; Fever ; Gout ; Humans ; Hypersensitivity* ; Hypoxanthine ; Leukocytosis ; Male ; Skin

OBJECTIVETo establish a RP-HPLC method for simultaneous determination of thymine, hypoxanthine and uracil contents in medical pipefish.

METHODSamples were extracted with distilled water by ultrasonic wave and separated on Waters C18 column eluted with a mobile phase of 0.05 mol x L(-1) KFI2PO4-acetonitrile (97:3). The flow rate was 0.6 mL x min(-1). The determination wavelength was 260 nm and the column temperature was set at 40 degrees C.

RESULTThe method had good linearity in the range of 0.033-0.660 (r = 0.9996), 0.620-12.400 (r = 0.9999), 0.048-0.960 microg (r = 0.9995), with average recoveries of 98.67% (RSD 1.6%), 99.03% (RSD 0.74%), 98.65% (RSD 1.8%), for thymine, hypoxanthine and uracil respectively.

CONCLUSIONThe simultaneous determination method of thymine, hypoxanthine and uracil in medical pipefish is established by RP-HPLC for the first time. The contents of the three constituents in different kinds of medical pipefish are significantly different. The method is simple, rapid and sensitive, and can be used for control the quality of medical pipefish.

Animals ; Chromatography, High Pressure Liquid ; methods ; Hypoxanthine ; analysis ; Medicine, Chinese Traditional ; Smegmamorpha ; Thymine ; analysis ; Uracil ; analysis

PURPOSE: Patients show variable responses to chemoradiotherapy (CRT), which is generally administered before surgery for locally advanced rectal cancer (LARC). The aim of this study was to identify molecular markers predictive of CRT responses by analysis of low-mass ions (LMIs) in serum of LARC patients. MATERIALS AND METHODS: LMIs (< 1,000 m/z) in serum obtained before CRT from 73 LARC (cT3-4) patients were profiled using matrix-assisted laser desorption/ionization mass spectrometry. LMIs with higher weighting factors in discriminating CRT responses were selected using principal components analysis and discriminant analysis. Selected LMIs were identified using the Human Metabolome Database. The concentrations of identified LMIs were determined by colorimetric enzyme assay, and compared according to post-CRT pathological stage (ypStage) or Dworak's tumor regression grade (TRG). RESULTS: The nine highest-ranking LMIs were selected. Among them, two LMIs with 137.08 and 169.04 m/z were identified as hypoxanthine (HX) and phosphoenolpyruvic acid (PEP), respectively. Higher HX concentration was observed in patients with ypStage 0-1 compared to ypStage 2-4 (p=0.034) or ypStage 3-4 (p=0.030); a similar difference was observed between TRG 4-3 and TRG 1 (p=0.035). HX > 16.0 muM showed significant association with ypStage 0-1 or TRG 4-3 than ypStage 3-4 (p=0.009) or TRG 1 (p=0.024), respectively. In contrast, a significantly lower concentration of PEP was observed in TRG 4-3 compared with TRG 2-1 (p=0.012). CONCLUSION: Findings of this study demonstrated that serum concentrations of HX and PEP, identified using LMI profiling, may be useful for predicting the CRT response of LARC patients before treatment.
Biological Markers* ; Chemoradiotherapy* ; Enzyme Assays ; Humans ; Hypoxanthine* ; Ions ; Mass Spectrometry ; Metabolome ; Phosphoenolpyruvate ; Rectal Neoplasms*

PURPOSE: To investigate the protective effects of hyaluronic acid with glutathione and ascorbic acid on corneal endothelial function against free-radical damage. METHODS: bovine corneal endothelial(BCEN) cells were treated with a flux of chemically generated superoxide anion produced by the combination of 1 mM hypoxanthine and 0.06 U/ml xanthine oxidase(HX-XO) for 10 minutes, and rabbit corneas were mounted in the dual-chamber specular microscope and perfused with bicarbonate Ringer(BR) solution for one hour and their endothelial surface was exposed to HX-XO for five minutes, and then perfused with glutathione, hyaluronic acid, or ascorbic acid in BR solution for three hours. BCEN cells was observed using MTT assay and rabbit corneal thickness was measured every 15 minutes and corneal swelling rates were calculated by linear regression analysis. Also, corneal endothelial permeability was measured using carboxyfluorescein and fluorometer. RESULTS: MTT assay showed less cytotoxicity in the cells treated with glutathione, hyaluronic acid, or ascorbic acid compared to HX-XO alone. Glutathione, hyaluronic acid, or ascorbic acid reduced the rabbit corneal swelling caused by HX-XO. Corneal endothelial permeability(Pac) increased in corneas perfused with HX-XO(7.88 x 10 cm/min) while those with BR had Pac of 4.54 x 10 cm/min. Following treatment with glutathione, hyaluronic acid, or ascorbic acid, Pac decreased to 4.96, 6.81, and 5.25 respectively(p<0.05). CONCLUSIONS: In conclusion, these data suggest that hyaluronic acid scavenges HX-XO-generated oxyradicals as well as glutathione and less likely ascorbic acid.
Ascorbic Acid ; Cornea ; Endothelium, Corneal ; Free Radicals ; Glutathione ; Hyaluronic Acid* ; Hypoxanthine ; Linear Models ; Permeability ; Superoxides ; Xanthine

OBJECTIVETo examine the quality of Whitmania pigra from the different populations to provide the basis for new species selection.

METHODThe contents of the moisture, alcohol extractive, total ash, acid-insoluble ash, and the activity of antiplatelet aggregation enzyme of wild and the breeding W. pigra were determined by the methods were determined in Chinese Pharmacopoeia (2005 edition). The contents xanthine and hypoxanthine by HPLC.

RESULTIt showed that the contents of the alcohol extractive, total ash, acid-insoluble ash, antiplatelet aggregation enzyme, and xanthine and hypoxanthine content of the breeding population in Nanjing are lations. Many quality indexes of the breeding in Zhejiang Tongxiang base were beffer than the wild.

CONCLUSIONThe breeding W. pigra are good in quality, It suggested large-scale promotion of aquaculture.

Animals ; Breeding ; Female ; Hypoxanthine ; analysis ; Leeches ; chemistry ; physiology ; Male ; Xanthine ; analysis