Diabetes augments cognitive dysfunction in chronic cerebral hypoperfusion by increasing neuronal cell death: Implication of cilostazol for diabetes mellitus-induced dementia

Kwon, K.J.,Lee, E.J.,Kim, M.K.,Kim, S.Y.,Kim, J.N.,Kim, J.O.,Kim, H.J.,Kim, H.Y.,Han, J.S.,Shin, C.Y.,Han, S.H. Blackwell Science ; Academic Press 2015 Neurobiology of disease Vol.73 No.-

Many patients with diabetes are at increased risk of cognitive dysfunction and dementia. Diabetes mellitus is a vascular risk factor that may increase the risk of dementia through its associations with vascular dementia. We tested whether cognitive impairment could be exacerbated in combined injury using a rat model of chronic cerebral hypoperfusion with diabetes. We also determined whether a potent inhibitor of type III phosphodiesterase could prevent the cognitive decline caused by this combined injury. We used Otsuka Long-Evans Tokushima Fatty (OLETF) rats as a model of type II diabetes (T2DM) and Long-Evans Tokushima Otsuka (LETO) rats as a control. Chronic cerebral hypoperfusion was modeled by permanent bilateral common carotid artery occlusion (BCCAO). At 24weeks, the non-diabetic and T2DM rats were randomly assigned into groups for the following experiments: analysis I (1) sham non-diabetic rats (n=8); (2) hypoperfused non-diabetic rats (n=9); (3) sham T2DM rats (n=8); (4) hypoperfused T2DM rats (n=9); analysis II- (1) sham T2DM rats without treatment (n=8); (2) cilostazol-treated T2DM rats (n=8); (3) hypoperfused T2DM rats (n=9); and (4) hypoperfused T2DM rats and cilostazol treatment (n=9). The rats were orally administered cilostazol (50mg/kg) or vehicle once a day for 2weeks after 24weeks. Rats performed Morris water maze tasks, and neuronal cell death and neuroinflammation were investigated via Western blots and histological investigation. Spatial memory impairment was exacerbated synergistically in the hypoperfused T2DM group compared with the hypoperfused non-diabetic group and sham T2DBM group (P<0.05). Compared with the control group, neuronal cell death was increased in the hippocampus of the hypoperfused T2DM group. Cilostazol, a PDE-3 inhibitor, improved the memory impairments through inhibition of neuronal cell death, activation of CREB phosphorylation and BDNF expression in the hypoperfused T2DM group. Our experimental results support the hypothesis that there are deleterious interactions between chronic cerebral hypoperfusion and T2DM. That is, metabolic diseases such as diabetes may exacerbate cognitive impairment in a rat model of vascular dementia. We also suggest that surprisingly, the phosphodiesterase III inhibitor, cilostazol may be useful for the treatment of cognitive impairment in diabetes mellitus-induced dementia. In conclusion, diabetes can aggravate cognitive dysfunction in vascular dementia, and PDE-3 inhibitors, such as cilostazol, may form the basis of a novel therapeutic strategy for diabetes-associated cognitive impairment or vascular dementia.

N-BACK 프로그램이 뇌졸중 환자의 인지, 시지각, 우울, 불안과 일상생활활동에 미치는 효과

김소영(S. Y. Kim),권상남(S. N. Kwon),김지훈(J. H. Kim) 한국재활복지공학회 2015 재활복지공학회논문지 Vol.9 No.3

본 연구의 목적은 임상에서 사용하고 있는 뇌 자극 훈련인 N-BACK 프로그램을 뇌졸중 환자들에게 적용하여 인지, 시지각, 우울, 불안과 일상생활활동에 미치는 임상적 효과를 증명하고자 하는 것이다. 이를 증명하기 위해 뇌졸중으로 진단받고 유병기간이 6개월 이상인자로 한국판 정신상태판별검사(MMSE-K)에서 18∼23점으로 인지기능 손상이 의심되는 자로써 무작위로 실험군과 대조군 각각 10명씩 선정하였다. 연구자 1인의 진행 하에 임상경력 5년 이상의 숙련된 치료사 8명에 의해 연구가 진행되었으며, 4주간 주 5회 1일 30분, 총 20회를 실시하였다. 그 결과 뇌졸중 환자에게 뇌 자극 훈련인 N-BACK 프로그램을 적용한 실험군이 대조군보다 인지, 시지각, 우울, 불안과 일상생활활동 기능 향상에 긍정적인 결과를 보였다. 이 연구로부터 얻은 결과들은 뇌졸중 환자의 인지, 시지각, 우울 및 불안의 향상을 위해 N-BACK 프로그램을 적용하면 환자의 재활에 긍정적인 효과가 있음을 기대할 수 있고, 그로 인해 일상생활 활동이 보다 독립적으로 향상될 것으로 기대할 수 있다. The purpose of this study was to demonstrate clinical effects on cognition, visual perception, depression, anxiety, and activities of daily living by applying the N-BACK program, a brain stimulated training program, which is used for the clinical purpose. To prove this, subjects suspected of cognitive impairment with 18-23 points in a Korean version of mental status examination (MMSE-K) were recruited among the population who had been diagnosed with stroke duration and suffered from it for six months of duration, and 10 of the subjects were selected into the experimental group and the control group, respectively. A total of 20 sessions were carried out for 30 minutes per day 5 times for 4 weeks. As a result, the experimental group who has been applied the N-BACK program showed positive results in the improvement of cognition, visual perception, depression, anxiety, and daily living skills. The results obtained from this study expect us that applying the N-BACK program for the improvement of cognition, visual perception, depression, and anxiety to stroke patients has a positive effect on the rehabilitation of patients and will lead them to improve daily living activities more independently.

Molecular, structural, and functional comparison of N lobe and C lobe of the transferrin from rock bream, <i>Oplegnathus fasciatus,</i> with respect to its immune response

Perera, N.C.N.,Godahewa, G.I.,Hwang, Jee Youn,Kwon, Mun Gyeong,Hwang, Seong Don,Lee, Jehee Elsevier 2017 Fish & shellfish immunology Vol.68 No.-

<P><B>Abstract</B></P> <P>The iron-withholding strategy of innate immunity is an effective antimicrobial defense mechanism that combats microbial infection by depriving microorganisms of Fe<SUP>3+</SUP>, which is important for their growth and propagation. Transferrins (Tfs) are a group of iron-binding proteins that exert their antimicrobial function through Fe<SUP>3+</SUP> sequestration. The current study describes both structural and functional characteristics of a transferrin ortholog from rock bream <I>Oplegnathus fasciatus</I> (RbTf). The RbTf cDNA possesses an open reading frame (ORF) of 2079 bp encoding 693 amino acids. It has a molecular mass of approximately 74 kDa and an isoelectric point of 5.4. <I>In silico</I> analysis revealed that RbTf has two conserved domains: N-terminal domain and C-terminal domain. Pairwise homology analysis and phylogenetic analysis revealed that RbTf shared the highest identity (82.6%) with <I>Dicentrarchus labrax</I> Tf. According to the genomic analysis, RbTf possesses 17 exons and 16 introns, similar to the other orthologs. Here, we cloned the N terminal and C terminal domains of RbTf to evaluate their distinct functional features. Results obtained through the CAS (chrome azurol S) assay confirmed the iron-binding ability of the RbTf, and it was further determined that the iron-binding ability of rRbTfN was higher than that of rRbTfC. The antimicrobial functions of the rRbTfN and the rRbTfC were confirmed via the iron-dependent bacterial growth inhibition assay. Tissue distribution profiling revealed a ubiquitous expression with intense expression in the liver. Temporal assessment revealed that <I>RbTf</I> increased after stimulation of LPS, <I>Edwardsiella tarda,</I> and <I>Streptococcus iniae</I> post injection (p.i.). These findings demonstrated that RbTf is an important antimicrobial protein that can combat bacterial pathogens.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Transferrin was identified from rock bream (<I>RbTf</I>). </LI> <LI> N terminal and C terminal domains of RbTf was separately cloned and evaluated their distinct functional features. </LI> <LI> CAS (chrome azurol S) assay confirmed the iron-binding ability of the RbTf. </LI> <LI> Transcriptional level of <I>RbTf</I> was modulated by pathological stress. </LI> </UL> </P>

Cr-Si Schottky Nano-Diodes Utilizing Anodic Aluminum Oxide Templates

Kwon, N.,Kim, K.,Heo, J.,Chung, I. American Scientific Publishers 2014 Journal of Nanoscience and Nanotechnology Vol.14 No.4

We have fabricated Cr nanodot Schottky diodes utilizing AAO templates formed on n-Si substrates. The diameters of the diodes were 75.0, 57.6, and 35.8 nm. Cr nanodot Schottky diodes with smaller diameters yield higher current densities than those with larger diameters due to an enhanced tunnel current contribution, which is attributed to a reduction in the barrier thickness. The diameters of Cr nanodots smaller than the Debye length (156 nm) play an important role in the reduction of barrier thickness. Also, we have fabricated Cr-Si nanorod Schottky diodes with three different lengths (130, 220, and 330 nm) by dry etching of n-Si substrate. Cr Si nanorod Schottky diodes with longer nanorods yield higher reverse current than those with shorter nanorods due to the enhanced electric field, which is attributed to a high aspect ratio of Si nanorod.

Fragilariopsis kerguelensis response to iron enrichment regarding its growth, uptake of nutrients and trace metals, and changes in CO2, CH4, and N2O

Kwon, Y. S.,Rhee, T. S.,Kim, S. Y.,Kim, M. S.,Choi, M. S.,Yang, E. J.,Kim, Y. N. Korean Ocean Research & Development Institute and 2014 OCEAN SCIENCE JOURNAL Vol.49 No.4

케블라 / 에폭시 프리프레그의 경화특성에 관한 연구

제갈영순(Y . S . Gal),이원철(W . C . Lee),권오혁(O . H . Kwon),윤남균(N . G . Yoon),임길수(K . S . Lhim),안종기(J . K . Ahn),박경준(K . J . Park) 한국복합재료학회 2001 Composites research Vol.14 No.2

N/A N/A

측완피판(Lateral upper arm free flap)을 이용한 구강내 결손부의 재건

권대근(Tae Geon Kwon),이상한(Sang Han Lee),R Schmelzeisen,N-C.Gellrich 대한구강악안면외과학회 1999 대한구강악안면외과학회지 Vol.25 No.3

1997년 4월부터 1998년 8월까지 독일 Freiburg 대학에서 행하여진 20증례의 측완피판(Lateral upper arm free flap)을 대상으로 수술증 임상적 소견과 피판생존률, 술후 합병증등의 술후 경과를 관찰하여 다음과 같은 결과를 얻었다. 1. 한 증례의 피판의 완전괴사와 한 증례의 부분괴사를 제외하고 측완피판은 구강내 결손부 재건에 수혜부와 양호한 적합을 이루었으며 저작, 연하등의 기능적 재건에 적합한 정도의 두께와 크기를 제공하였다. 2. 공여부의 감각이상을 보인 증례가 전체의 40%를 차지하였으나 이로인한 불편감을 호소하는 환자는 없었으며 Radial n. 의 손상이나 심한 반흔을 보이지 않았다. 3. 측완피판은 과거 구강악안면부위 결손부의 수복에 주로 이용된 전완피판의 새로운 대안이 될 수 있으나 혈관경의 직경이 작아 수술에 다소의 숙련도를 요하는 것으로 사료된다. Thin and pliable fasciocutaneous free flap is recommended to reconstruct the intraoral defects of intraoral mobile structures to maintain function at optimum. Recently, radial forearm free flap is one of the popular flaps for intraoral reconstruction for these reasons. However, donor site morbidity such as necessary skin grafting and esthetic compromise was the problems of this flap. In this point of view, lateral upper arm free flap(LUFF) has many advantages include relatively simple vascular anatomy and very low doner site morbidity. The purpose of this study is to investigate the 20 consecutive LUFF and evaluate the surgical procedure and postoperative results. The lateral arm flap provided a good functional and esthetic result except for one case of complete flap necrosis because of vascular insufficiency of the supplying vessel of the neck. Although post-operative lower arm partial sensory deficit is a possible disadvantage of this flap, it is a highly reliable method for oral reconstruction with minimal complication.

Role of CH2F2 and N-2 Flow Rates on the Etch Characteristics of Dielectric Hard-mask Layer to Extreme Ultra-violet Resist Pattern in CH2F2/N2/Ar Capacitively Coupled Plasmas

B. S. Kwon,J. H. Lee,N. E. Lee 한국진공학회 2011 한국진공학회 학술발표회초록집 Vol.40 No.0

Essential Role of YIMPO1, a Novel Yarrowia lipolytica Homologue of Saccharomyces cerevisiae MNN4, in Mannosylphosphorylation of N- and O-Linked Glycans

Park, J.-N.,Song, Y.,Cheon, S.A.,Kwon, O.,Oh, D.-B.,Jigami, Y.,Kim, J.-Y.,Kang, H.A. AMERICAN SOCIETY FOR MICROBIOLOGY 2011 Applied and environmental microbiology Vol.77 No.4

Jacobi–Stirling numbers, Jacobi polynomials, and the left-definite analysis of the classical Jacobi differential expression

Everitt, W.N.,Kwon, K.H.,Littlejohn, L.L.,Wellman, R.,Yoon, G.J. Koninklijke Vlaamse Ingenieursvereniging 2007 Journal of computational and applied mathematics Vol.208 No.1

<P><B>Abstract</B></P><P>We develop the left-definite analysis associated with the self-adjoint Jacobi operator Ak(α,β), generated from the classical second-order Jacobi differential expression<SUB>ℓα,β,k</SUB>[y](t)=1<SUB>wα,β</SUB>(t)((-(1-t<SUP>)α+1</SUP>(1+t<SUP>)β+1</SUP><SUP>y′</SUP>(t)<SUP>)′</SUP>+k(1-t<SUP>)α</SUP>(1+t<SUP>)β</SUP>y(t))(t∈(-1,1)),in the Hilbert space Lα,β2(-1,1)≔<SUP>L2</SUP>((-1,1);<SUB>wα,β</SUB>(t)), where <SUB>wα,β</SUB>(t)=(1-t<SUP>)α</SUP>(1+t<SUP>)β</SUP>, that has the Jacobi polynomials {Pm(α,β)}m=0∞ as eigenfunctions; here, α,β>-1 and <I>k</I> is a fixed, non-negative constant. More specifically, for each n∈N, we explicitly determine the unique left-definite Hilbert–Sobolev space Wn,k(α,β)(-1,1) and the corresponding unique left-definite self-adjoint operator Bn,k(α,β) in Wn,k(α,β)(-1,1) associated with the pair (Lα,β2(-1,1),Ak(α,β)). The Jacobi polynomials {Pm(α,β)}m=0∞ form a complete orthogonal set in each left-definite space Wn,k(α,β)(-1,1) and are the eigenfunctions of each Bn,k(α,β). Moreover, in this paper, we explicitly determine the domain of each Bn,k(α,β) as well as each integral power of Ak(α,β). The key to determining these spaces and operators is in finding the explicit Lagrangian symmetric form of the integral composite powers of <SUB>ℓα,β,k</SUB>[·]. In turn, the key to determining these powers is a double sequence of numbers which we introduce in this paper as the <I>Jacobi–Stirling numbers</I>. Some properties of these numbers, which in some ways behave like the classical Stirling numbers of the second kind, are established including a remarkable, and yet somewhat mysterious, identity involving these numbers and the eigenvalues of Ak(α,β).</P>