Effect of <i>CYP3A5*3</i> genotype on serum carbamazepine concentrations at steady-state in Korean epileptic patients

Park, P.-W.,Seo, Y. H.,Ahn, J. Y.,Kim, K.-A.,Park, J.-Y. Blackwell Publishing Ltd 2009 Journal of clinical pharmacy and therapeutics Vol.34 No.5

<P>Abstract</P><P>Background and Objective: </P><P>Carbamazepine (CBZ) is metabolized mainly by the CYP3A family of enzymes, which includes CYP3A4 and CYP3A5. Several studies have suggested that the <I>CYP3A5*3</I> genotype influences the pharmacokinetics of CYP3A substrates. The present study aimed to assess the effect of the <I>CYP3A5*3</I> genotype on serum concentration of CBZ at the steady-state in Korean epileptic patients.</P><P>Method: </P><P>The serum concentrations of CBZ in 35 Korean epileptic patients were measured and their <I>CYP3A5</I> genotype was determined. Fourteen patients were <I>CYP3A5</I> expressors (two for <I>CYP3A5*1/*1</I> and 12 for <I>CYP3A5*1/*3</I>) and 21 patients were <I>CYP3A5</I> non-expressors (<I>CYP3A5*3/*3</I>). Dose-normalized concentrations (mean ± SD) of CBZ were 9·9 ± 3·4 ng/mL/mg for <I>CYP3A5</I> expressors and 13·1 ± 4·5 ng/mL/mg for <I>CYP3A5</I> non-expressors (<I>P</I> = 0·032). The oral clearance of CBZ was significantly higher in <I>CYP3A5</I> non-expressors than that of <I>CYP3A5</I> expressors (0·056 ±0·017 L/h/kg vs. 0·040 ± 0·014 L/h/kg, <I>P</I> = 0·004). The <I>CYP3A5</I> genotype affected the CBZ concentrations in Korean epileptic patients and is a factor that may contribute to inter-individual variability in CBZ disposition in epileptic patients.</P>

Clinical efficacy and safety of abatacept in methotrexate-naive patients with early rheumatoid arthritis and poor prognostic factors

Westhovens, R,Robles, M,Ximenes, A C,Nayiager, S,Wollenhaupt, J,Durez, P,Gomez-Reino, J,Grassi, W,Haraoui, B,Shergy, W,Park, S-H,Genant, H,Peterfy, C,Becker, J-C,Covucci, A,Helfrick, R,Bathon, J BMJ Group 2009 Annals of the Rheumatic Diseases Vol.68 No.12

<P><B>Objectives:</B></P><P>To assess the efficacy and safety of abatacept in methotrexate-naive patients with early rheumatoid arthritis (RA) and poor prognostic factors.</P><P><B>Methods:</B></P><P>In this double-blind, phase IIIb study, patients with RA for 2 years or less were randomly assigned 1 : 1 to receive abatacept (∼10 mg/kg) plus methotrexate, or placebo plus methotrexate. Patients were methotrexate-naive and seropositive for rheumatoid factor (RF), anti-cyclic citrullinated protein (CCP) type 2 or both and had radiographic evidence of joint erosions. The co-primary endpoints were the proportion of patients achieving disease activity score in 28 joints (DAS28)-defined remission (C-reactive protein) and joint damage progression (Genant-modified Sharp total score; TS) at year 1. Safety was monitored throughout.</P><P><B>Results:</B></P><P>At baseline, patients had a mean DAS28 of 6.3, a mean TS of 7.1 and mean disease duration of 6.5 months; 96.5% and 89.0% of patients were RF or anti-CCP2 seropositive, respectively. At year 1, a significantly greater proportion of abatacept plus methotrexate-treated patients achieved remission (41.4% vs 23.3%; p<0.001) and there was significantly less radiographic progression (mean change in TS 0.63 vs 1.06; p = 0.040) versus methotrexate alone. Over 1 year, the frequency of adverse events (84.8% vs 83.4%), serious adverse events (7.8% vs 7.9%), serious infections (2.0% vs 2.0%), autoimmune disorders (2.3% vs 2.0%) and malignancies (0.4% vs 0%) was comparable for abatacept plus methotrexate versus methotrexate alone.</P><P><B>Conclusions:</B></P><P>In a methotrexate-naive population with early RA and poor prognostic factors, the combination of abatacept and methotrexate provided significantly better clinical and radiographic efficacy compared with methotrexate alone and had a comparable, favourable safety profile.</P>

Golimumab, a human antibody to tumour necrosis factor α given by monthly subcutaneous injections, in active rheumatoid arthritis despite methotrexate therapy: the GO-FORWARD Study

Keystone, E C,Genovese, M C,Klareskog, L,Hsia, E C,Hall, S T,Miranda, P C,Pazdur, J,Bae, S-C,Palmer, W,Zrubek, J,Wiekowski, M,Visvanathan, S,Wu, Z,Rahman, M U BMJ Publishing Group 2009 Annals of the Rheumatic Diseases Vol.68 No.6

<P><B>Objective:</B></P><P>The phase III GO-FORWARD study examined the efficacy and safety of golimumab in patients with active rheumatoid arthritis (RA) despite methotrexate therapy.</P><P><B>Methods:</B></P><P>Patients were randomly assigned in a 3 : 3 : 2 : 2 ratio to receive placebo injections plus methotrexate capsules (group 1, n  =  133), golimumab 100 mg injections plus placebo capsules (group 2, n  =  133), golimumab 50 mg injections plus methotrexate capsules (group 3, n  =  89), or golimumab 100 mg injections plus methotrexate capsules (group 4, n  =  89). Injections were administered subcutaneously every 4 weeks. The co-primary endpoints were the proportion of patients with 20% or greater improvement in the American College of Rheumatology criteria (ACR20) at week 14 and the change from baseline in the health assessment questionnaire-disability index (HAQ-DI) score at week 24.</P><P><B>Results:</B></P><P>The proportion of patients who achieved an ACR20 response at week 14 was 33.1% in the placebo plus methotrexate group, 44.4% (p = 0.059) in the golimumab 100 mg plus placebo group, 55.1% (p = 0.001) in the golimumab 50 mg plus methotrexate group and 56.2% (p<0.001) in the golimumab 100 mg plus methotrexate group. At week 24, median improvements from baseline in HAQ-DI scores were 0.13, 0.13 (p = 0.240), 0.38 (p<0.001) and 0.50 (p<0.001), respectively. During the placebo-controlled portion of the study (to week 16), serious adverse events occurred in 2.3%, 3.8%, 5.6% and 9.0% of patients and serious infections occurred in 0.8%, 0.8%, 2.2% and 5.6%, respectively.</P><P><B>Conclusion:</B></P><P>The addition of golimumab to methotrexate in patients with active RA despite methotrexate therapy significantly reduced the signs and symptoms of RA and improved physical function.</P>

Foxp3 is a key downstream regulator of p53-mediated cellular senescence

Kim, J-E,Shin, J-S,Moon, J-H,Hong, S-W,Jung, D-J,Kim, J H,Hwang, I-Y,Shin, Y J,Gong, E-Y,Lee, D H,Kim, S-M,Lee, E Y,Kim, Y S,Kim, D,Hur, D,Kim, T W,Kim, K-p,Jin, D-H,Lee, W-J Macmillan Publishers Limited 2017 Oncogene Vol.36 No.2

<P>The downstream events and target genes of p53 in the process of senescence are not fully understood. Here, we report a novel function of the forkhead transcription factor Foxp3, which is a key player in mediating T-cell inhibitory functions, in p53-mediated cellular senescence. The overexpression of Foxp3 in mouse embryonic fibroblasts (MEFs) accelerates senescence, whereas Foxp3 knockdown leads to escape from p53-mediated senescence in p53-expressing MEFs. Consistent with these results, Foxp3 expression resulted in the induction of senescence in epithelial cancer cells, including MCF7 and HCT116 cells. Foxp3 overexpression also increased the intracellular levels of reactive oxygen species (ROS). The ROS inhibitor N-acetyl-L-cysteine rescued cells from Foxp3-expression-induced senescence. Furthermore, the elevated ROS levels that accompanied Foxp3 overexpression were paralleled by an increase in p21 expression. Knockdown of p21 in Foxp3-expressing MEFs abrogated the Foxp3-dependent increase in ROS levels, indicating that Foxp3 acts through the induction of p21 and the subsequent ROS elevation to trigger senescence. Collectively, these results suggest that Foxp3 is a downstream target of p53 that is sufficient to induce p21 expression, ROS production and p53-mediated senescence.</P>

Photoswitching and photocatalytic functions of Sn_xCu_1−xS nanostructures

Ilanchezhiyan, P.,Kumar, G. Mohan,Siva, C.,Venkatasubbu, G. Devanand,Kang, T.W.,Kim, D.Y. Elsevier 2019 APPLIED SURFACE SCIENCE - Vol.489 No.-

<P><B>Abstract</B></P> <P>Ultra-thin semiconducting nanostructures are garnering strategic importance in energy and environment remediation applications. In this regard, Sn<SUB>x</SUB>Cu<SUB>1−x</SUB>S nanostructures were processed through an eco-friendly chemical route and investigated in detail for photoswitching and photocatalytic functions. X-ray diffraction, FT-IR, Raman, UV–vis absorbance and high-resolution microscopic tools were initially used to examine the physico-chemical traits of Sn<SUB>x</SUB>Cu<SUB>1−x</SUB>S nanostructures. Ambiguous evidence for the substitution of Sn ions in place of Cu ions was attained through X-ray photoelectron spectroscopy. The photocatalytic performance of Sn<SUB>x</SUB>Cu<SUB>1−x</SUB>S systems was investigated through effective remediation of organic dye molecules under visible light. Scavenger based photocatalytic experiments were additionally carried out to infer the degradation mechanism. Type II <I>p-n</I> Sn<SUB>x</SUB>Cu<SUB>1−x</SUB>S/In<SUB>2</SUB>S<SUB>3</SUB> heterojunction diodes were also demonstrated for the first time with improved electrical conductivity and photoelectrical performances. The rectification ratio, forward current values and photo switching capabilities of these diodes were noted to improve in the Current vs. Voltage (I-V) and Current vs. Time (I-T) curves as a function of Sn composition and applied bias potential. The excellent photo switching stability augments the photo generated carriers to be effectively separated along the p-n junctions. The enhanced photoelectronic and photocatalytic functionalities in Sn<SUB>x</SUB>Cu<SUB>1−x</SUB>S has finally been reasoned to the improved charge transfer kinetics in the respective architectures, resulting from the effective Sn interaction in hexagonal host lattice.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Sn<SUB>x</SUB>Cu<SUB>1−x</SUB>S nanostructures were fabricated by hydrothermal route. </LI> <LI> The nanostructures exhibited excellent photocatalytic activity under visible light. </LI> <LI> Sn interaction in hexagonal host lattice promoted their photocatalytic performance. </LI> <LI> p-Sn<SUB>x</SUB>Cu<SUB>1−x</SUB>S/n-In<SUB>2</SUB>S<SUB>3</SUB> diodes demonstrated improved photoswitching performance. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

면양(緬羊)에 의한 Formaldehyde 처리 Alfalfa 엽(葉) 분미의 단백질 가치평가에 관한 연구

강희신,R. H. Weston,J. R. Ashes,P. Davis,R. W. Edols 한국낙농학회 1985 韓國酪農學會誌 Vol.7 No.4

低質 粗飼科 밀짚으로 飼育되는 交雜種 緬羊 6頭를 供試하며 alfalfa 葉 粉末, 當年葉, 貯藏葉, 2% HCHO處理 當年葉 및 4% HCHO處理貯藏葉을 供試 飼料로 하고 밀짚 基本飼料 700g 및 alfalfa 粉末 補充飼料 300g 計 1.0㎏를 日量 飼料로 連續 給餌器에서 3시간 間隔으로 1日 8回 給與하며 20日間씩의 代謝試驗을 4回 實施하였다. ^(51)Cr-EDTA 및 ^(103)Ru-phe의 二重 標識物質을 使用하여 腸內 內容物의 通過量 및 滯在時間反芻胃 溶量, 有機物 및 窒素의 利用性을 測定한 結果 다음과 같은 結果를 얻었다. 1. 反芻胃 溶液中의 NH₃態 窒素 濃度는 貯藏葉이 當年葉보다 17.5% 높으며(P<.01) 2% HCHO處理 當年葉은 그 無處理보다 7% 程度 減少되고 4% HCHO處理 貯藏葉은 無處理보다 34.0% 程度 減少(P<.01)되었다. 2. 反芻胃로부터 流入되는 NH₃態 窒素 量은 當年葉보다 貯藏葉이 18% 增加(P<.01)되고 2% HCHO處理 當年葉은 無處理보다 6% 減少 (P<.05)되며, 4% HCHO處理 貯藏葉은 無處理보다 32% 減少(P<.01)를 나타내었다. 3. 第4胃內 NAN含量은 當年葉이 貯藏葉보다 6% 增加되며 2% HCHO處理 當年葉은 無處理보다 5.6%의 增加(P<.05) 4% HCHO處理 貯藏葉은 그 無處理보다 17% 程度의 增加(P<.01)를 나타내었다. 4. 第4胃로부터 排出되어 小腸에 流入되는 NAN의 量은 當年葉보다 貯藏葉이 9.0% 더 流入되며(P<.05) 2% HCHO 處理 當年葉은 그 無處理보다 6% 程度 增加(P<.05) 流人되었다. 5. 飼料源 室素 100g 攝取量當 NAN의 小腸內 消化量은 當年葉보다 貯藏葉이 10% 程度 消化가 增進(P<.05)되며 2% HCHO 處理 當年葉은 無處理보다 6% 程度 消化가 增進(P<.05)되었다. 6. 飼料源 室素 100g 攝取量 當 糞中 窒素의 排泄量은 當年葉보다 貯藏葉이 8% 정도(P<.01), 2% HCHO處理 當年葉은 無處理보다 6% 程度(P<.05) 더 排泄되었으며 4% HCHO處理葉은 그 無處理에 比하여 2% 程度 더 排泄되었으나 有意差는 認定되지 않았다. 7. 反芻胃液(Y, ㎎ N%)과 第4胃 濾液(X, ㎎ N%)中의 NH₃態 室素 濃度와의 關係는 다음 回歸 方程式으로 表示되었다. Y = 3.981 + 1.2783(±0.3736)X (r = 0.59, n-2=22) 8. 飼料 窒素 攝取量에 對한 補充飼料 alfalfa 葉 粉末의 小腸內 流入 NAN의 百分比는 當年葉, 2% HCHO處理 當年葉 및 無處理 貯藏葉의 順으로 각각 57.0%, 68.0% 및 65%로 推定되었다. 따라서 小腸內 流入 NAN은 2% HCHO處理 當年葉이 無處理보다 19%, 貯藏葉은 當年葉 無處理보다 14% 程度 增加된 것으로 推定된다. 9. 貯藏葉 補充時 音機物 消化率은 當年葉을 補充할 때 보다 約 1% 減少되고 當年葉 및 貯藏葉에 HCHO處理는 葉中 有機物의 排泄量을 0∼3.4% 程度 增加시키는 傾向이었으나 有意差는 當年葉과 貯藏葉 間에만 認定되었다. 10. 反芻胃液 및 第4胃液의 各 腸器 通過率, 反芻胃 容量 및 그 內容物의 滯在時間은 處理間有意差가 認定되지 않았다. 1. The OM out-put in the faeces was about 3% unit higher with the Old than that with the New, while with the HCHO treated meals there was only a slightly and insignificantly increasing tendency in the OM out-put. 2. No significant differences in the liquor flow rate of the rumen and the abomasum fluid, and in the rumen volume and retention time were found between the treatments. 3. The ruminal NH₃-N concentration in the Old was about 17.5% unit higher (P<0.01) than that in the New, while the New + 2% HCHO was about 7.0% unit (P<0.10) and the Old + 4% HCHO was about 34% lower (P<0.01) than those in the untreated-New and Old. 4. The amount of NH₃-N excreted from the rumen in the Old was 18% unit higher (P<0.01) than that in the New, and that in the New + 2% HCHO about 6% unit was lower, though insignificant, than that in the New, while that in the Old + 4% HCHO was about 32% unit lower (P<0.01) than that in the Old. 5. The NAN content of the intestine in the New was about 6% unit higher (P<0.10) than that in the Old, while in the New + 2% HCHO and the Old + 4% HCHO about 6% unit (P<0.05) and 17% unit (P<0.01) were higher than those in the New and the Old, respectively. 6. The amount of NAN excreted from the abomasum in the Old was about 9% unit higher (P<0.05) than that in the New, while the New + 2% HCHO resulted about 6% unit higher (P<0.01) NAN excretion than the New. 7. The NAN digested in the intestine per 100g of dietary nitrogen intake in the Old was about 10% unit higher (P<0.10) than that in the New, while in the New + 2% HCHO about 6% unit was higher (P<0.05) than that in the New. 8. The fecal nitrogen output per 100g of dietary nitrogen intake in the Old was about 8% unit (P<0.01), in the New + 2% HCHO was about 6% unit and in the Old + 4% HCHO about 2.4% unit was higher (P<0.10) than in the New and the Old. 9. The significant correlation between the concentrations of NH₃-N in the abomasal filtrates and those in the ruminal fluids permitted to draw a predictive equation by regression analysis as follows: y = 3.981 + 1.2783(+0.3736) X, where, Y = Ruminal NH₃-N concentration (㎎ N%) X= NH₃-N concentration in abomasal filtrates (㎎ N%), (n-2=22) and (r=0.59) 10. The percent of NAN entered the intestines over supplemental leaf meal nitrogen intake in the New, the New + 2% HGHO and the Old were 57.0, 68.0 and 65%, respectively. The NAN entered the intestine in the New + 2% HCHO and the Old were 19% and 14% higher than those in the New, respectively.

Identification of a novel <i>FAM83H</i> mutation and microhardness of an affected molar in autosomal dominant hypocalcified amelogenesis imperfecta

Hyun, H.-K.,Lee, S.-K.,Lee, K.-E.,Kang, H.-Y.,Kim, E.-J.,Choung, P.-H.,Kim, J.-W. Blackwell Publishing Ltd 2009 International endodontic journal Vol.42 No.11

<P>Abstract</P><P>Aim </P><P>To determine the underlying molecular genetic aetiology of a family with the hypocalcified form of amelogenesis imperfecta and to investigate the hardness of the enamel and dentine of a known <I>FAM83H</I> mutation.</P><P>Methodology </P><P>Mutational screening of the <I>FAM83H</I> on the basis of candidate gene approach was performed. All exons and exon–intron boundaries was amplified and sequenced. A microhardness test was performed to measure the Vickers microhardness value.</P><P>Results </P><P>A novel nonsense mutation (c.1354C>T, p.Q452X) was identified in the last exon of <I>FAM83H</I>, which resulted in soft, uncalcified enamel. The affected enamel was extremely soft (about 17% of the normal control), but the underlying dentine was as hard as the normal control.</P><P>Conclusions </P><P>Mutational analysis revealed a novel mutation in <I>FAM83H</I> gene. Hardness of dentine was not affected by the mutation, whilst the enamel was extremely soft.</P>

국내이용 말사료의 영양적 가치와 YEAST CULTURE 첨가시 소화율 , 광물질 이용율 및 혈액성상에 미치는 영향

김성민(S . M . Kim),김종민(C . M . Kim),이현기(H . K . Lee),박원표(W . P . Park),임영재(Y . J . Lim),김병진(B . J . Kim),정태영(T . Y . Chung) 한국영양사료학회 1991 韓國營養飼料學會誌 Vol.15 No.5

Report of the CCQM-K97: measurement of arsenobetaine standard solution and arsenobetaine content in fish tissue (tunafish)

Ma, L D,Wang, J,WEI, C,Kuroiwa, T,Narukawa, T,Ito, N,HIOKI, A,CHIBA, K,Yim, Y H,Lee, K S,Lim, Y R,Turk, G C,Davis, C W,Mester, Z,Yang, L,McCooeye, M,Maxwell, P,Cankur, O,Tokman, N,Coskun, F G BUREAU INTERNATIONAL DES POIDS ET MESURES 2017 METROLOGIA -BERLIN- Vol.54 No.-

<P></P> <P>The CCQM-K97 key comparison was organized by the inorganic analysis working group (IAWG) of CCQM as a follow-up to completed pilot study CCQM-P96 and P96.1 to test the abilities of the national metrology institutes to accurately quantitate the mass fraction of arsenobetaine (AsB) in standard solution and in fish tissue. A pilot study CCQM-P133 was parallelized with this key comparison. National Institute of Metrology (NIM), China and National Metrology Institute of Japan (NMIJ) acted as the coordinating laboratories.</P> <P>Six NMIs participated in CCQM-K97 and two institutes participated in CCQM-P133, and all of them submitted the results. Some NMIs submitted more than one results by different methods. The results were in excellent agreement with each other, and obviously better than those of previous P96 and P96.1. Therefore the calibrant which each NMI used was comparable. It shows that the capabilities of some of the participants have been improved after the previous pilot studies.</P> <H2>Main text</H2> <P> To reach the main text of this paper, click on <A HREF='http://www.bipm.org/utils/common/pdf/final_reports/QM/K97/CCQM-K97.pdf'>Final Report</A>. Note that this text is that which appears in Appendix B of the BIPM key comparison database <A HREF='http://kcdb.bipm.org/'>kcdb.bipm.org/</A>.</P> <P>The final report has been peer-reviewed and approved for publication by the CCQM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).</P>

High performance photodiodes based on chemically processed Cu doped SnS₂ nanoflakes

Mohan Kumar, G.,Xiao, Fu,Ilanchezhiyan, P.,Yuldashev, Sh.,Madhan Kumar, A.,Cho, H.D.,Lee, D.J.,Kang, T.W. Elsevier 2018 APPLIED SURFACE SCIENCE - Vol.455 No.-

<P><B>Abstract</B></P> <P>In this work, Cu doped SnS<SUB>2</SUB> nanoflakes were synthesized through a simple hydrothermal method. The influence of Cu doping on the structural, optical and electrical properties of SnS<SUB>2</SUB> were investigated in detail. Optical properties explores the Cu doping in SnS<SUB>2</SUB> crystal lattice to result with a red-shift in absorption spectrum, which benefits visible-light absorption. Photodiodes were further fabricated by spin coating Cu doped SnS<SUB>2</SUB> nanoflakes on p-type silicon (Si). Electrical and photoelectrical parameters of Cu doped SnS<SUB>2</SUB> nanoflakes were determined by studying their impedance and current–voltage (I–V) characteristics, respectively. The diodes were found to exhibit excellent rectifying behavior and good sensitivity on par to pristine photodiodes. Impedance results identified the resistance of device to reduce considerably on Cu doping. The enhanced photoelectrical properties of the heterojunctions has been ascribed to Cu ions, which act as effective dopant and contribute to the varied carrier concentration in SnS<SUB>2</SUB>. Finally the obtained results suggest the potential of Cu-doped SnS<SUB>2</SUB> for application in photodetection and sensors applications.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Cu doped SnS<SUB>2</SUB> nanoflakes were synthesized in hexagonal phase. </LI> <LI> Nature of charge carriers/carrier density was determined using Mott-Schottky plots. </LI> <LI> Photodiode based on Cu doped SnS<SUB>2</SUB> nanoflakes were fabricated on p-Si substrate. </LI> <LI> Photodiode revealed improved photocurrent and responsitivity values under illumination. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>