• Title/Summary/Keyword: and receptors

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Association of Low Serum Ionized Magnesium Level with Fever-Triggered Seizures in Epileptic Children (소아 뇌전증 환자에서 발열이 동반된 경련을 하는 것과 저 이온화 마그네슘 혈증과의 관련성)

  • Suh, Sunny;Kim, Kyungju;Byeon, Jung Hye;Eun, So-Hee;Eun, Baik-Lin;Kim, Gun-Ha
    • Journal of the Korean Child Neurology Society
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    • v.26 no.4
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    • pp.205-209
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    • 2018
  • Purpose: Several studies have shown that magnesium plays an important role in modulating N-methyl-D-aspartate (NMDA)-related seizures by blocking NMDA ion channel receptors. Clinicians usually measure total serum magnesium levels instead of biologically active ionized magnesium levels. We compared the serum ionized magnesium ($iMg^{2+}$) level between epileptic children with and without a history of fever-triggered seizure (FTS). Methods: All epileptic children who visited the outpatient clinic or pediatric emergency department at Korea University Guro Hospital between January 2015 and July 2017 were included. Only epileptic children aged 1-8 years who were newly diagnosed within 2 years were included. Results: There were 12 children with FTS and 16 without FTS. Median serum $iMg^{2+}$ level was 0.93 (0.85-1.14, quartile) mEq/L. Serum $iMg^{2+}$ level was significantly lower in epileptic children with FTS (0.86 mEq/L) compared to those without FTS (1.10 mEq/L) (P=0.005). No difference was noted in clinical variables between the two groups. Lower serum $iMg^{2+}$ level significantly increased the risk of having FTS in epileptic children based on multivariable logistic regression analysis (odds ratio [OR]=0.028). Conclusion: Serum $iMg^{2+}$ level was significantly lower in epileptic children with FTS than in those without FTS. Measurement of biologically active serum $iMg^{2+}$ level could be considered in epileptic children with recurrent FTS. A large-scale prospective study is warranted.

Sesquiterpenoids Bioconversion Analysis by Wood Rot Fungi

  • Lee, Su-Yeon;Ryu, Sun-Hwa;Choi, In-Gyu;Kim, Myungkil
    • 한국균학회소식:학술대회논문집
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    • 2016.05a
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    • pp.19-20
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    • 2016
  • Sesquiterpenoids are defined as $C_{15}$ compounds derived from farnesyl pyrophosphate (FPP), and their complex structures are found in the tissue of many diverse plants (Degenhardt et al. 2009). FPP's long chain length and additional double bond enables its conversion to a huge range of mono-, di-, and tri-cyclic structures. A number of cyclic sesquiterpenes with alcohol, aldehyde, and ketone derivatives have key biological and medicinal properties (Fraga 1999). Fungi, such as the wood-rotting Polyporus brumalis, are excellent sources of pharmaceutically interesting natural products such as sesquiterpenoids. In this study, we investigated the biosynthesis of P. brumalis sesquiterpenoids on modified medium. Fungal suspensions of 11 white rot species were inoculated in modified medium containing $C_6H_{12}O_6$, $C_4H_{12}N_2O_6$, $KH_2PO_4$, $MgSO_4$, and $CaCl_2$ for 20 days. Cultivation was stopped by solvent extraction via separation of the mycelium. The metabolites were identified as follows: propionic acid (1), mevalonic acid lactone (2), ${\beta}$-eudesmane (3), and ${\beta}$-eudesmol (4), respectively (Figure 1). The main peaks of ${\beta}$-eudesmane and ${\beta}$-eudesmol, which were indicative of sesquiterpene structures, were consistently detected for 5, 7, 12, and 15 days These results demonstrated the existence of terpene metabolism in the mycelium of P. brumalis. Polyporus spp. are known to generate flavor components such as methyl 2,4-dihydroxy-3,6-dimethyl benzoate; 2-hydroxy-4-methoxy-6-methyl benzoic acid; 3-hydroxy-5-methyl phenol; and 3-methoxy-2,5-dimethyl phenol in submerged cultures (Hoffmann and Esser 1978). Drimanes of sesquiterpenes were reported as metabolites from P. arcularius and shown to exhibit antimicrobial activity against Gram-positive bacteria such as Staphylococcus aureus (Fleck et al. 1996). The main metabolites of P. brumalis, ${\beta}$-Eudesmol and ${\beta}$-eudesmane, were categorized as eudesmane-type sesquiterpene structures. The eudesmane skeleton could be biosynthesized from FPP-derived IPP, and approximately 1,000 structures have been identified in plants as essential oils. The biosynthesis of eudesmol from P. brumalis may thus be an important tool for the production of useful natural compounds as presumed from its identified potent bioactivity in plants. Essential oils comprising eudesmane-type sesquiterpenoids have been previously and extensively researched (Wu et al. 2006). ${\beta}$-Eudesmol is a well-known and important eudesmane alcohol with an anticholinergic effect in the vascular endothelium (Tsuneki et al. 2005). Additionally, recent studies demonstrated that ${\beta}$-eudesmol acts as a channel blocker for nicotinic acetylcholine receptors at the neuromuscular junction, and it can inhibit angiogenesis in vitro and in vivo by blocking the mitogen-activated protein kinase (MAPK) signaling pathway (Seo et al. 2011). Variation of nutrients was conducted to determine an optimum condition for the biosynthesis of sesquiterpenes by P. brumalis. Genes encoding terpene synthases, which are crucial to the terpene synthesis pathway, generally respond to environmental factors such as pH, temperature, and available nutrients (Hoffmeister and Keller 2007, Yu and Keller 2005). Calvo et al. described the effect of major nutrients, carbon and nitrogen, on the synthesis of secondary metabolites (Calvo et al. 2002). P. brumalis did not prefer to synthesize sesquiterpenes under all growth conditions. Results of differences in metabolites observed in P. brumalis grown in PDB and modified medium highlighted the potential effect inorganic sources such as $C_4H_{12}N_2O_6$, $KH_2PO_4$, $MgSO_4$, and $CaCl_2$ on sesquiterpene synthesis. ${\beta}$-eudesmol was apparent during cultivation except for when P. brumalis was grown on $MgSO_4$-free medium. These results demonstrated that $MgSO_4$ can specifically control the biosynthesis of ${\beta}$-eudesmol. Magnesium has been reported as a cofactor that binds to sesquiterpene synthase (Agger et al. 2008). Specifically, the $Mg^{2+}$ ions bind to two conserved metal-binding motifs. These metal ions complex to the substrate pyrophosphate, thereby promoting the ionization of the leaving groups of FPP and resulting in the generation of a highly reactive allylic cation. Effect of magnesium source on the sesquiterpene biosynthesis was also identified via analysis of the concentration of total carbohydrates. Our current study offered further insight that fungal sesquiterpene biosynthesis can be controlled by nutrients. To profile the metabolites of P. brumalis, the cultures were extracted based on the growth curve. Despite metabolites produced during mycelia growth, there was difficulty in detecting significant changes in metabolite production, especially those at low concentrations. These compounds may be of interest in understanding their synthetic mechanisms in P. brumalis. The synthesis of terpene compounds began during the growth phase at day 9. Sesquiterpene synthesis occurred after growth was complete. At day 9, drimenol, farnesol, and mevalonic lactone (or mevalonic acid lactone) were identified. Mevalonic acid lactone is the precursor of the mevalonic pathway, and particularly, it is a precursor for a number of biologically important lipids, including cholesterol hormones (Buckley et al. 2002). Farnesol is the precursor of sesquiterpenoids. Drimenol compounds, bi-cyclic-sesquiterpene alcohols, can be synthesized from trans-trans farnesol via cyclization and rearrangement (Polovinka et al. 1994). They have also been identified in the basidiomycota Lentinus lepideus as secondary metabolites. After 12 days in the growth phase, ${\beta}$-elemene caryophyllene, ${\delta}$-cadiene, and eudesmane were detected with ${\beta}$-eudesmol. The data showed the synthesis of sesquiterpene hydrocarbons with bi-cyclic structures. These compounds can be synthesized from FPP by cyclization. Cyclic terpenoids are synthesized through the formation of a carbon skeleton from linear precursors by terpene cyclase, which is followed by chemical modification by oxidation, reduction, methylation, etc. Sesquiterpene cyclase is a key branch-point enzyme that catalyzes the complex intermolecular cyclization of the linear prenyl diphosphate into cyclic hydrocarbons (Toyomasu et al. 2007). After 20 days in stationary phase, the oxygenated structures eudesmol, elemol, and caryophyllene oxide were detected. Thus, after growth, sesquiterpenes were identified. Per these results, we showed that terpene metabolism in wood-rotting fungi occurs in the stationary phase. We also showed that such metabolism can be controlled by magnesium supplementation in the growth medium. In conclusion, we identified P. brumalis as a wood-rotting fungus that can produce sesquiterpenes. To mechanistically understand eudesmane-type sesquiterpene biosynthesis in P. brumalis, further research into the genes regulating the dynamics of such biosynthesis is warranted.

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Evaluation of Liver Function Using $^{99m}-Lactosylated$ Serum Albumin Liver Scintigraphy in Rat with Acute Hepatic Injury Induced by Dimethylnitrosamine (Dimethylnitrosamine 유발 급성 간 손상 흰쥐에서 $^{99m}-Lactosylated$ Serum Albumin을 이용한 간 기능의 평가)

  • Jeong, Shin-Young;Seo, Myung-Rang;Yoo, Jeong-Ah;Bae, Jin-Ho;Ahn, Byeong-Cheol;Hwang, Jae-Seok;Jeong, Jae-Min;Ha, Jeong-Hee;Lee, Kyu-Bo;Lee, Jae-Tae
    • The Korean Journal of Nuclear Medicine
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    • v.37 no.6
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    • pp.418-427
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    • 2003
  • Objects: $^{99m}-lactosylated$ human serum albumin (LSA) is a newly synthesized radiopharmaceutical that binds to asialoglycoprotein receptors, which are specifically presented on the hepatocyte membrane. Hepatic uptake and blood clearance of LSA were evaluated in rat with acute hepatic injury induced by dimethylnitrosamine (DMN) and results were compared with corresponding findings of liver enzyme profile and these of histologic changes. Materials and Methods: DMN (27 mg/kg) was injected intraperitoneally in Sprague-Dawley rat to induce acute hepatic injury. At 3(DMN-3), 8(DMN-8), and 21 (DMN-21) days after injection of DMN, LSA injected intravenously, and dynamic images of the liver and heart were recorded for 30 minutes. Time-activity curves of the heart and liver were generated from regions of interest drawn over liver and heart area. Degree of hepatic uptake and blood clearance of LSA were evaluated with visual interpretation and semiquantitative analysis using parameters (receptor index : LHL3 and index of blood clearance : HH3), analysis of time-activity curve was also performed with curve fitting using Prism program. Results: Visual assessment of LSA images revealed decreased hepatic uptake in DMN treated rat, compared to control group. In semiquantitative analysis, LHL3 was significantly lower in DMN treated rat group than control rat group (DMN-3: 0.842, DMN-8: 0.898, DMN-21: 0.91, Control: 0.96, p<0.05), whereas HH3 was significantly higher than control rat group (DMN-3: 0.731,.DMN-8: 0.654, DMN-21: 0.604, Control: 0.473, p<0.05). AST and ALT were significantly higher in DMN-3 group than those of control group. Centrilobular necrosis and infiltration of inflammatory cells were most prominent in DMN-3 group, and were decreased over time. Conclusion: The degree of hepatic uptake of LSA was inversely correlated with liver transaminase and degree of histologic liver injury in rat with acute hepatic injury.

The 1998, 1999 Patterns of Care Study for Breast Irradiation After Breast-Conserving Surgery in Korea (1998, 1999년도 우리나라에서 시행된 유방보존수술 후 방사선치료 현황 조사)

  • Suh Chang-Ok;Shin Hyun Soo;Cho Jae Ho;Park Won;Ahn Seung Do;Shin Kyung Hwan;Chung Eun Ji;Keum Ki Chang;Ha Sung Whan;Ahn Sung Ja;Kim Woo Cheol;Lee Myung Za;Ahn Ki Jung
    • Radiation Oncology Journal
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    • v.22 no.3
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    • pp.192-199
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    • 2004
  • Purpose: To determine the patterns on evaluation and treatment in the patient with early breast cancer treated with conservative surgery and radiotherapy and to improve the radiotherapy techiniques, nationwide survey was peformed. Materials and Methods: A web-based database system for korean Patterns of Care Study (PCS) for 6 common cancers was developed. Two hundreds sixty-one randomly selected records of eligible patients treated between 1998$\~$1999 from 15 hospitals were reviewed. Results: The patients ages ranged from 24 to 85 years(median 45 years). Infiltrating ductal carcinoma was most common histologic type (88.9$\%$) followed by medullary carcinoma (4.2$\%$) and infiltrating lobular carcinoma (1.5$\%$). Pathologic T stage by AJCC was T1 in 59.7$\%$ of the casses, T2 in 29.5$\%$ of the cases, Tis in 8.8$\%$ of the cases. Axillary lymph node dissection was peformed I\in 91.2$\%$ of the cases and 69.7$\%$ were node negative. AJCC stage was 0 in 8.8$\%$ of the cases, stage I in 44.9$\%$ of the cases, stage IIa in 33.3$\%$ of the cases, and stage IIb in 8.4$\%$ of the cases. Estrogen and progesteron receptors were evaluated in 71.6$\%$, and 70.9$\%$ of the patients, respectively. Surgical methods of breast-conserving surgery was excision/lumpectomy in 37.2$\%$, wide excision in 11.5$\%$, quadrantectomy in 23$\%$ and partial mastectomy in 27.5$\%$ of the cases. A pathologically confirmed negative margin was obtained in 90.8$\%$ of the cases. Pathological margin was involved with tumor in 10 patients and margin was close (less than 2 mm) in 10 patients. All the patients except one recieved more than 90$\%$ of the planned radiotherapy dose. Radiotherapy volume was breast only In 88$\%$ of the cases, breast+supraclavicular fossa (SCL) in 5$\%$ of the cases, and breast+ SCL+ posterior axillary boost in 4.2%$\%$of the cases. Only one patient received isolated internal mammary lymph node irradiation. Used radiation beam was Co-60 in 8 cases, 4 MV X-ray in 115 cases, 6 MV X-ray in 125 cases, and 10 MV X-ray in 11 cases. The radiation dose to the whole breast was 45$\~$59.4 Gy (median 50.4) and boost dose was 8$\~$20 Gy (median 10 Gy). The total radiation dose delivered was 50.4$\~$70.4 Gy (median 60.4 Gy). Conclusion: There was no major deviation from current standard in the patterns of evaluation and treatment for the patients with early breast cancer treated with breast conservation method. Some varieties were identified in boost irradiation dose. Separate analysis for the datails of radiotherapy planning will be followed and the outcome of treatment is needed to evaluate the process.