• Title/Summary/Keyword: purine metabolism

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PREVENTION OF SELF-MUTILATION IN PATIENT WITH LESCH-NYHAN SYNDROME: A CASE REPORT (Lesch-Nyhan 증후군 환아의 자해 예방)

  • Lee, Ji-Hyun;Kim, Ji-Hoon;Kim, Jae-Moon;Kim, Shin;Jeong, Tae-Sung
    • Journal of the korean academy of Pediatric Dentistry
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    • v.32 no.2
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    • pp.306-311
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    • 2005
  • Lesch-Nyhan syndrome is a rare disorder of purine metabolism, first described in 1964. The incidence is estimated to be 1:100,000 birth. It is an X-linked recessive disorder in which affected males have a virtually complete deficiency of the enzyme hypoxanthine guanine phosphorybosyl transferase(HGPT). This enzyme deficiency gives rise to excessive uric acid production and consequent hyperuricemia. Lesch-Nyhan syndrome is clinically characterized by mental retardation, choreoathetosis, spastic cerebral palsy, and severe self-mutilation behavior. Patient with Lesch-Nyhan syndrome mostly bite their lip, tongue and finger. In severe cases, partial or total amputation of the lip and tongue is common. Self-inflicted bites are often further complicated by secondary infection to injuried site as well as pain. And tissue loss by biting results in esthetic problems. This report presents a Lesch-Nyhan syndrome patient with self-mutilation, who have a destruction of perioral tissue, especially the lower lip. He was treated successfully with soft mouthguard, psychological and pharmacological method.

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Influence of the Novel Urease Inhibitor Hydroquinone on Growing Lamb Nitrogen Utilization

  • Zhang, Y.G.;Shan, A.S.;Bao, J.
    • Asian-Australasian Journal of Animal Sciences
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    • v.15 no.7
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    • pp.992-997
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    • 2002
  • Two in vivo experiments were conducted to evaluate the effect of novel urease inhibitor hydroquinone (HQ) on ammonia release rate from urea hydrolysis, nitrogen balance, nutrient digestibility and efficiency of microbial protein synthesis. In Exp. 1, twelve crossbred cannulated lambs were randomly assigned within initial body weight block to one of four HQ treatments, which included 0 (control), 30, 60 or 80 mg HQ/kg DM intake. Ammonia concentration and pH of ruminal fluid were immediately measured at 0, 2, 4, 6 and 8 h after feeding. Increasing the dose of HQ tended (p<0.15) to linearly decrease NH3 formation. The ammonia peak concentration (2 h post-feeding) in animals receiving HQ was approximately one-half of that in animals not receiving HQ (p<0.01), and a relatively sustained ammonia release could be obtained at the dose of 30 or 60 mg HQ/kg DM. In Exp. 2, sixteen intact crossbred lambs (weight $40{\pm}0.8kg$) were used in a $2{\times}2$ factorial design experiment. The four rations consisting of soybean meal-based (SBM) or urea-based (Urea) nitrogen source with or without HQ (S1, S0, U1 and U0) were fed in digestion and N balance trials. Apparent digestibility of major nutrients except that of ADF was not affected by either nitrogen source or addition of HQ. Regardless of nitrogen source, supplementation of HQ significantly improved ADF digestibility (p<0.05). The various ration had no effects on N metabolism in the presence of HQ. There was significant difference between total purine derivatives (PD), estimated efficiency of microbial N synthesis (p<0.05) and urea-N excretion (p<0.01) in the urine for the SBM ration and for the Urea ration. However, HQ had little influence on efficiency of microbial N synthesis as proportion of daily intake of total tract digestible OM (p>0.05). No interactions between main nitrogen source and HQ were measured throughout the trial. Results of this study suggest that addition of HQ to ration may improve ADF digestion with having no negative effect on N metabolism and microbial protein production.

Proteomic Analysis of Protein Expression in Streptococcus pneumoniae in Response to Temperature Shift

  • Lee Myoung-Ro;Bae Song-Mee;Kim Tong-Soo;Lee Kwang-Jun
    • Journal of Microbiology
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    • v.44 no.4
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    • pp.375-382
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    • 2006
  • From its initial colonization to causation of disease, Streptococcus pneumoniae has evolved strategies to cope with a number of stressful in vivo environmental conditions. In order to analyze a global view of this organism's response to heat shock, we established a 2-D electrophoresis proteome map of the S. pneumoniae D39 soluble proteins under in vitro culture conditions and performed the comparative proteome analysis to a 37 to $42^{\circ}C$ temperature up-shift in S. pneumoniae. When the temperature of an exponentially growing S. pneumoniae D39 culture was raised to $42^{\circ}C$, the expression level of 25 proteins showed changes when compared to the control. Among these 25 proteins, 12 were identified by MALDI-TOF and LC-coupled ESI MS/MS. The identified proteins were shown to be involved in the general stress response, energy metabolism, nucleotide biosynthesis pathways, and purine metabolism. These results provide clues for understanding the mechanism of adaptation to heat shock by S. pneumoniae and may facilitate the assessment of a possible role for these proteins in the physiology and pathogenesis of this pathogen.

Dendropanax morbifera and Rubus coreanus Miq. Extracts Inhibits the Formation of Uric Acid Crystal by Reducing Xanthine Oxidase Activity

  • Hurh, Joon;Simu, Shakina Yesmin;Han, Yaxi;Ahn, Jong-Chan;Yang, Deok-Chun
    • Proceedings of the Plant Resources Society of Korea Conference
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    • 2018.04a
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    • pp.95-95
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    • 2018
  • Uric acid is the end product of purine metabolism in human body, originating from hypoxanthine after enzyme catalysis by Xanthine oxidase (XOD). Hyperuricemia results as a result of either over-generation of uric acid or a reduction in its excretion. In silico modelling methods such as Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET) prediction, Autodock 4.2.6 program were used to study the potential inhibitory compounds of XOD. Also we investigated the inhibition of XOD activity by using the extracts of Dendropanax morbifera and Rubus coreanus Miq spectrophotometrically. According to ADMET data, several compounds from D. morbifera and R. coreanus plants, were found to be more potent in inhibiting the XOD activity than allopurinol. XOD inhibitory activity is evaluated by quantifying the formation of uric acid by measuring the absorbance at 290 m ($A_{290}$).D. morbifera extract inhibited XOD activity at $250{\mu}g/ml$, however the extracts from R. coreanus has inhibited XOD activity at $25{\mu}g/ml$. The major compound of R. coreanus, ellagic acid significantly increased the inhibition rate from $9{\mu}g/ml$ and showed a 71% suppression rate at $15{\mu}g/ml$. Finally, these results suggested a potential inhibitory activities of the extracts from D. morbifera and R. coreanus Miq, but further research is needed to validate to ensure their safe usage as drug.

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LAB Fermentation Improves Production of Bioactive Compounds and Antioxidant Activity of Withania somnifera Extract and Its Metabolic Signatures as Revealed by LC-MS/MS

  • Yu, Jinhui;Geng, Yun;Xia, Han;Ma, Deyuan;Liu, Chao;Wu, Rina;Wu, Junrui;You, Shengbo;Bi, Yuping
    • Journal of Microbiology and Biotechnology
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    • v.32 no.4
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    • pp.473-483
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    • 2022
  • In this study we investigated the effect of lactic acid bacteria (LAB) fermentation on the ingredients and anti-oxidant activity of Withania somnifera extract. Four strains of LAB could proliferate normally in medium containing W. somnifera extract after the pH reached 3.1~3.5. LAB fermentation increased the content of alcohols and ketones, endowing the extract with the characteristic aroma of fermentation. Compared to the control, the DPPH and ABTS free radical scavenging rates in the fermented samples were significantly improved, ranging from 48.5% to 59.6% and 1.2% to 6.4%. The content of total phenols was significantly increased by 36.1% during the fermentation of mixed bacteria. Moreover, the original composition spectrum of the extract was significantly changed while the differentially accumulated metabolites (DAMs) were closely related to bile secretion, tryptophan metabolism and purine metabolism. Therefore, LAB fermentation can be used as a promising way to improve the flavor and bioactivity of the extracts of W. somnifera, making the ferments more attractive for use as functional food.

Role of Kupffer Cells in Cold/warm Ischemia-Reperfusion Injury or Rat Liver

  • Lee, Young-Goo;Lee, Sang-Ho;Lee, Sun-Mee
    • Archives of Pharmacal Research
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    • v.23 no.6
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    • pp.620-625
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    • 2000
  • The mechanisms of liver injury from cold storage and reperfusion are not completely under-stood. The aim of the present study was to investigate whether the inactivation of Kupffer cells (KCs) by gadolinium chloride ($GdCl_3$) modulates ischemia-reperfusion injury in the rat liver. Hepatic function was assessed using an isolated perfused rat liver model. In livers subjected to cold storage at $4^{\circ}C$ in University of Wisconsin solution for 24 hrs and to 20 min rewarm-ing ischemia, oxygen uptake was markedly decreased, Kupffer cell phagocytosis was stimulated, releases of purine nucleoside phosphorylase and lactate dehydrogenase were increased as compared with control livers. Pretreatment of rats with $GdCl_3$) , a selective KC toxicant, suppressed kupffer cell activity, and reduced the grade of hepatic injury induced by ischemia-reperfusion. While the initial mixed function oxidation of 7-ethoxycoumarin was not different from that found in the control livers, the subsequent conjugation of its meta-bolite to sulfate and glucuronide esters was suppressed by ischemia-reperfusion, CdCl$_3$restored sulfation and glucuronidation capacities to the level of the control liver. Our findings suggest that Kupffer cells could play an important role in cold/warm ischemia-reperfusion hepatic injury.

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Characterization and Evaluation of a Distinct Fusion Ability in the functionally Related Cyclic Amidohydrolase Family Enzymes

  • Kim, Hak-Sung;Lee, Dong-Eun;Kim, Geun-Joong
    • Biotechnology and Bioprocess Engineering:BBE
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    • v.7 no.3
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    • pp.155-162
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    • 2002
  • The cyclic amidohydrolase family enzymes, which include allantoinase, dihydroorotase, dihydropyrimidinase and (phenyl)hydantoinase, are metal-dependent hydrolases and play a crucial role in the metabolism of purine and pyrimidine in vivo. Each enzyme has been independently characterized, and thus well documented, but studies on the higher structural traits shared by members of this enzyme family are rare due to the lack of comparative study. Here, we report upon the expression in E. coli cells of maltose-binding protein (MBP)- and glutathione S-transferase (GST)-fused cyclic amidohydrolase family enzymes, facilitating also for both simple purification and high-level expression. Interestingly, the native quaternary structure of each enzyme was maintained even when fused with MBP and GST. We also found that in fusion proteins the favorable biochemical properties of family enzymes such as, their optimal pHs, specific activities and kinetic properties were conserved compared to the native enzymes. In addition, MBP-fused enzymes showed remarkable folding ability in-vitro. Our findings, therefore, suggest that a previously unrecognized trait of this family, namely the ability to functional fusion with some other protein but yet to retain innate properties, is conserved. We described here the structural and evolutionary implications of the properties in this family enzyme.

Antiinflammatory, Analgesic and Antihyperuricemic Effects of 'Gyejakjimo-Tang' in Rats (계작지모탕(桂芍知母湯)의 소염.진통작용 및 Alcohol성 고뇨산혈증(高尿酸血症)에 미치는 영향)

  • Kim, Soon-Shin;Kim, Hye-Kyung;Choi, Jong-Won;Lee, Chung-Kyu
    • Korean Journal of Pharmacognosy
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    • v.26 no.1
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    • pp.66-73
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    • 1995
  • 'Gyejakjimo-Tang(桂芍知母湯)', which is composed of Cinnamon bark(桂枝), Peony root(芍藥), Anemarrhena root(知母) and other seven herbs, is described as antipyretic, diuretic and analgesic prescription in traditional medical literatures including Geumgwe-Yoryak(金櫃要略). So it is being used in the treatment of gout clinically in oriental region. As the results of the pharmacological and biochemical trials of the prescription, it was found to have antiinflammatory and significant analgesic effects indicated by carrageenin edema, dye permeabilities and writhing behavior. And it potentiated the output of uric acid in blood and the increase of uric acid in urine of alcohol-toxicated rats, which mean the decrease of uric acid level only by excretion procedure. But the prescription didn't show any effects on the activities of adenine/guanine deaminase, purine nucleoside phosphorylase, xanthine oxidase or uricase, which are related with formation and metabolism of uric acid.

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Evaluation of Genotoxicity of Three Antimalarial Drugs Amodiaquine, Mefloquine and Halofantrine in Rat Liver Cells

  • Farombi E. Olatunde
    • Environmental Mutagens and Carcinogens
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    • v.25 no.3
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    • pp.97-103
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    • 2005
  • The genotoxic effect of antimalarial drugs amodiaquine (AQ), mefloquine (MQ) and halofantrine (HF) was investigated in.at liver cells using the alkaline comet assay. AQ, MQ and HF at concentrations between $0-1000{\mu}mol/L$ significantly increased DNA strand breaks of rat liver cells dose-dependently. The order of induction of strand breaks was AQ>MQ>HF. The rat liver cells exposed to AQ and HF (200 and 400 ${\mu}mol/L$) and treated with (Fpg) the bacterial DNA repair enzyme that recognizes oxidized purine showed greater DNA damage than those not treated with the enzyme, providing evidence that AQ and HF induced oxidation of purines. Such an effect was not observed when MQ was treated with the enzyme. Treatment of cells with catalase, an enzyme inactivating hydrogen peroxide, decreased significantly the extent of DNA damage induced by AQ, and HF but not the one induced by MQ. Similarly quercetin, an antioxidant flavonoid at $50{\mu}mol/L$ attenuated the extent of the formation of DNA strand breaks by both AQ and HE. Quercetin, however, did not modify the effects of MQ. These results indicate the genotoxicity of AQ, MQ and HF in rat liver cells. In addition, the results suggest that reactive oxygen species may be involved in the formation of DNA lesions induced by AQ and HF and that, free radical scavengers may elicit protective effects against genotoxicity of these antimalarial drugs.

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Effect of condensed tannins from Ficus infectoria and Psidium guajava leaf meal mixture on nutrient metabolism, methane emission and performance of lambs

  • Pathak, A.K.;Dutta, Narayan;Pattanaik, A.K.;Chaturvedi, V.B.;Sharma, K.
    • Asian-Australasian Journal of Animal Sciences
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    • v.30 no.12
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    • pp.1702-1710
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    • 2017
  • Objective: The study examined the effect of condensed tannins (CT) containing Ficus infectoria and Psidium guajava leaf meal mixture (LMM) supplementation on nutrient metabolism, methane emission and performance of lambs. Methods: Twenty four lambs of ~6 months age (average body weight $10.1{\pm}0.60kg$) were randomly divided into 4 dietary treatments (CT-0, CT-1, CT-1.5, and CT-2 containing 0, 1.0, 1.5, and 2.0 percent CT through LMM, respectively) consisting of 6 lambs each in a completely randomized design. All the lambs were offered a basal diet of wheat straw ad libitum, oat hay (100 g/d) along with required amount of concentrate mixture to meet their nutrient requirements for a period of 6 months. After 3 months of experimental feeding, a metabolism trial of 6 days duration was conducted on all 24 lambs to determine nutrient digestibility and nitrogen balance. Urinary excretion of purine derivatives and microbial protein synthesis were determined using high performance liquid chromatography. Respiration chamber study was started at the mid of 5th month of experimental feeding trial. Whole energy balance trials were conducted on individual lamb one after the other, in an open circuit respiration calorimeter. Results: Intake of dry matter and organic matter (g/d) was significantly (p<0.05) higher in CT-1.5 than control. Digestibility of various nutrients did not differ irrespective of treatments. Nitrogen retention and microbial nitrogen synthesis (g/d) was significantly (p<0.01) higher in CT-1.5 and CT-2 groups relative to CT-0.Total body weight gain (kg) and average daily gain (g) were significantly (linear, p<0.01) higher in CT-1.5 followed by CT-1 and CT-0, respectively. Feed conversion ratio (FCR) by lambs was significantly (linear, p<0.01) better in CT-1.5 followed by CT-2 and CT-0, respectively. Total wool yield (g; g/d) was linearly (p<0.05) higher for CT-1.5 than CT-0. Methane emission was linearly decreased (p<0.05) in CT groups and reduction was highest (p<0.01) in CT-2 followed by CT-1.5 and CT-1. Methane energy (kcal/d) was linearly decreased (p<0.05) in CT groups. Conclusion: The CT supplementation at 1% to 2% of the diet through Ficus infectoria and Psidium guajava LMM significantly improved nitrogen metabolism, growth performance, wool yield, FCR and reduced methane emission by lambs.