• Genomics & Informatics
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• v.4 no.1
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• pp.16-22
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• 2006

The KFDA (Korea Food & Drug Administration) has performed a collaborative toxicogenomics project since 2003. Its aim is to construct a toxicology database of 12 compounds administered to mice at initial phase. We chose 6-MP (6-mercaptopurine) which has been used in the treatment of childhood leukemia. It was administered at low (0.224 mg/kg) and at high (2.24 mg/kg) dose (5 mice per group) intraperitonealy to the postnatal 6 weeks mice, then the serum and liver were collected at the indicated time (6, 24 and 72 h) after scarification. Serum biochemical markers for liver toxicity were measured and histopathologic studies also were carried out. The gene expression profiling was carried out by using Applied Biosystems 1700 Full Genome Expression Mouse. By self-organization maps (SOM), we identified groups with unique gene expression patterns, some of them are supposed to be related to 6-MP induced toxicity, including lipid metabolism abnormality, inflammatory response, oxidative stress, ATP depletion and cell death. The potential toxic effects appearing as gene expression changes are dependent of the time of 6-MP but independent of the dosage of it. This study would contribute to establishment of international database as well as national one about hepatotoxicity.

• Annals of Pediatric Endocrinology and Metabolism
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• v.23 no.4
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• pp.226-228
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• 2018

Various endocrine dysfunctions occur during chemotherapy, including hypoglycemia. However, reports of hypoglycemia associated with 6-mercaptopurine (6-MP) are rare. Herein, we report an 8-year-old boy with severe symptomatic hypoglycemia likely due to 6-MP during chemotherapy. He had been diagnosed with acute lymphoblastic leukemia 3 years previously and was in the maintenance chemotherapy period. Treatment included oral dexamethasone, methotrexate, and 6-MP, of which only 6-MP was administered daily. Hypoglycemic symptoms appeared mainly at dawn, and his serum glucose dropped to a minimum of 37 mg/dL. Laboratory findings showed nothing specific other than increased serum cortisol, free fatty acids, ketone, alanine aminotransferase, and aspartate aminotransferase. Under the hypothesis of hypoglycemia due to chemotherapy drugs, we changed the time of 6-MP from evening to morning and recommended him to ingest carbohydrate-rich foods before bedtime. Hypoglycemia improved dramatically, and there was no further episode during the remaining maintenance chemotherapy period. To the best of our knowledge, this is the first report of this type of hypoglycemia occurring in an Asian child including Korean.

• Analytical Science and Technology
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• v.23 no.6
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• pp.579-586
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• 2010

Commercially widely used antitumor agents such as hydroxy urea, 6-mercaptopurine monohydrate, cytosine arabinoside, cyclophosphamide monohydrate and uracil were reacted with 3-(triethoxysilyl)propyl isocyanate and the product hydrolyzed to give silica nanoparticles bound antitumor agents ranging from 10 nm to micron-sized aggregates. The silyl isocyanate derivative was also reacted neat with water to give hybrid organicsilicananoparticles containing $-CH_2-CH_2-CH_2-NH-COOH$ or the corresponding decarboxylated propylamine groups depending on solvent and temperature employed. In vitro tests these functionalized silica nanoparticles were effective in the treatment of malignant tumor cells but had little or no effect on normal cells. Malignant human lung, ovarian, melanoma, CNS(Central nervous system) and colon tumor cells were used in this research. The use of silica as a carrier medium in the present research serves as a model material due to its ready functionalization via silation. The proof of concept established by the results suggests that the technique may be applied to other, more biocompatible carrier nanoparticles.

• Korean Journal of Animal Reproduction
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• v.20 no.4
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• pp.427-432
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• 1997

These studies were performed to approach the precise pathway inducing the meiotic inhibitory action of hypoxanthine on mouse follicular oocytes and to identify the cause of detrimental effect of hypoxanthine on viability of the oocyte in vitro. In addition, a correlation between the meiotic inhibitory effect and the detrimental effect of hypoxanthine was investigated. Mouse follicular oocytes at germinal vesicle(GV) stage were collected from the ovaries of ICR mice by puncturing the antral follicles with a fine needle, at 48 hours after PMSG injection. Oocytes were cultured in Modified Whittingham's T6 media containing hypoxanthine and several materials that involved in metabolism of hypoxanthine, and the effects of the materials on the actions of hypoxanthine were investigated by observing germinal vesicle breake down (GVBD), 1st polar body (PB) extrusion and viability of the oocytes. Phophodiesterase significantly reduced the meiotic inhibitory effect of dbcAMP but did not influence on the inhibitory effect of hypoxanthine. Allopurinol and 6-MP significantly enhanced the meiotic inhibitory effect of hypoxanthine, but the materials themselves also showed the meiotic inhibitory action like hypoxanthine. Hypoxanthine-guanine phosphoribosyltransferase significantly enhanced the meiotic inhibitory effect of hypoxanthine, on the contrary HGPRT itself promoted meiotic resumption of the oocytes. Catalase did not induce any change in the meiotic inhibitory effect of hypoxanthine, but SOD increased the GVBD rate suppressed by hypoxanthine. The detrimental effect of hypoxanthine on viability of the oocytes was significantly reduced by allopurinol and catalase, but SOD increased the GVBD rate suppressed by hypoxanthine. The detrimental effect of hypoxanthine on viability of the oocytes was significantly reduced by allopurinol and catalase, but SOD did not reduce the deterimental effect of hypoxanthine. In conclusion, the meiotic inhibtory effect of hypoxanthine may be caused by guanyl dervartives converted from hypoxanthine via salvage pathway, and superoxide anion may partially participate in the inhibitory effect of hypoxanthine. The detrimental effect of hypoxanthine on viability of the oocytes be cused by hydrogen peroxide produced during the metabolism of hypoxanthine.

• Korean Journal of Microbiology
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• v.31 no.2
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• pp.148-156
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• 1993

Kinetic parameters of purine nucleoside phosphorylase (PNP) from Saccharomyces cerevisiae were measured. The Michaelis constants determined for substrates of the enzyme were $ 2.0 * 10^{-4}$ M for inosine, $2.0 *10^{-3}$ M for deoxyinosine, $ 2.0 * 10^{-5}$ M for guanosine and $2.0 10 ^{-5}$ M for deoxyguanosine. According to the ratio of relative $K_{cat}$Km, substrate specificity of each nucleoside was in the order of guanosine or deoxyguanosine, inosine and deoxyinosine. Cosubstrate, phosphate, revealed downward curvature in Lineweaver-Burk plot at high concentrations, indicating a negative cooperativity between subunits. The inhibition constants for purine analogs were measured to be $ 6 * 10^{-4}$ M for formycin B as the competitive inhibitor of inosine, $ 9 * 10^{-6}$ M for guanine as the competitive inhibitor of guanosine, $2 * 10^{-4}$ M for hypoxanthine as the non competitive inhibitor of guanosine and $4.5 * 10 ^{-4}$ M for 6-mercaptopurine as the non competitive inhibitor of guanosine. Alternative substrates, guanosine, deoxyguanosine and adenosine were found to act as competitive inhibitors with Ki values o $f^ 2.0 * 10 {-5}$ M, $2.6 * 10^{-5}$ M and $8.5 * 10 ^{-4}$ M, respectively, when inosine was the variable substrate. Guanosine and deoxyguanosine were also observed as competitive inhibitors with the Ki values of $1.8 * 10^{-5}$ M and $ 3.0 * 10^{-5}$ M, respectively, when deoxyinesine was the variable substrate. The results of alternative substrate sstudies suggested that a single enzyme acted on different nucleosides, inosine, deoxyinosine, adenosine, guanosine and deoxyguanosine.e.

• Toxicological Research
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• v.23 no.3
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• pp.231-238
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• 2007

Evaluation of potentials of chemicals to alter expression of genes that are involved in carcinogenesis may serve useful tools in toxicological research. In this investigation, we developed reporter cell lines that expressed luciferase in response to transactivation of hypoxia inducible factor-1, P53 tumor suppressor and Nur77 of which roles have been well established in cancer development and progression. Whereas these reporter cell lines displayed low constitutive backgrounds, the reporter activities were significantly enhanced in response to $desferriosamine/CoCl_2$, adriamycin or 6-mercaptopurine, which are hypoxia mimicking chemicals, P53 activator or Nur77 inducer, respectively. The activation of the reporter was time- and dose-dependent. Known tumor initiators and promoters, such as phorbol 12-myristate 13-acetate and phorbol 12, 13-dicaprinate induced the reporter activity at as low as 10nM in these stable cell lines. Further, known anti-tumor promoters, such as ascorbic acid and ${\beta}-carotene$ repressed the reporter activities. These results indicate that our stable reporter cell lines could serve as a useful system for rapid assessment of carcinogenicity of toxic chemicals.

• Journal of Korean Public Health Nursing
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• v.16 no.1
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• pp.176-189
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• 2002

The purpose of this study were to illustrate the various medication error types and causes and identified to related drugs to provide basic data for preventing nurses' medication error by analysing 73 cases of AJN 'medication Error' column(1993, Oct -2000, Nov). Nurses' types of medication error were classified into 7 types. The most frequent error types are wrong medication$(21.9\%)$ and the wrong dose$(21.9\%)$ together. The others are wrong $time(4.1\%)$, $omission(2.7\%)$, mechanical $error(2.7\%)$, incorrect IV $rate(1.4\%)$. wrong route $administration(1.4\%)$ in order. Nurses' causes of medication error were 9 kinds. The most frequent type is confusing between similar drug shape, color, size, name, injection devices and patient's $name(43.9\%)$ and the others are lack of knowledge about $drugs(26.8\%),\; slips(7.3\%),\; miscalculating\;dose(4.9\%)$, incorrect adjusts $devices(4.9\%)$, difficulty to read or illegible decimal $point(4.9\%),$ $abbreviation(2.4\%)$, fatigue with $overwork(2.4\%)$ and no communication with $patient(2.4\%)$ in order. Related drugs with medication error are as follows. - dose unit(IU. minims. mcg/min. mEq) : Heparin. insulin. synthetic calcitonin, some enzymes and hormones, vitamins, some antibiotics, tuberculin injection. MgSO4 injection. nitroglycerin - similar size, color and shape drug : $0.9\%$ N/S and acetic acid $0.25\%$ for irrigation. premixed 2mg lidocaine sol. and $0.9\%$ N/S, gentamycin 20mg/2mL for children and 80mg/2mL for adult, dextroamphetamine 5mg and 10mg capsule. sedatives chloral hydrate 250mg/5mL and 500mg/5mL - similar name :Aredia(pamidronate disodium) and Adriamycin(doxorubicin), Lamictal (lamotrigine) and Lamisil 250mg. Elderpryl and enalapril, cefotaxime and cefoxitin, carboplatin and cisplatin, sumatriptan and zolmitriptan, Celebrex and Celexa, Humulin and Humalog, Percodan and Percocet, Diabeta and Diabinese, Epivir and Retrovir, Xanax(alprazolam) and Zantac(ranitidine) - decimal point : low molecular weight warfarin, methotrexate - unfamiliar drug uses of familiar drug ; methotrexate. droperidol, imipramine, propranolol - number of drug name(misleading chemical name) : 6-thioguanine, 6-mercaptopurine, 5-fluorouracil - type of administration route : Oxycodone(OxyContin). - administration time : acarbose(Precose). - injection way (Z-track method): hydroxyzine - epidural cathether : LMWHs(enoxaparin, dalteparin), - ADD Vantage self contained delivery system : ceftriaxone(Rocephin)