Effects of sevoflurane on collagen production and growth factor expression in rats with an excision wound

LEE, H.-J.,KWON, J.-Y.,SHIN, S.-W.,BAEK, S.-H.,CHOI, K.-U.,JEON, Y.-H.,KIM, W.-S.,BAE, J.-H.,CHOI, H.-J.,KIM, H.-K.,BAIK, S.-W. Blackwell Publishing Ltd 2010 Acta anaesthesiologica Scandinavica Vol.54 No.7

<P>Background</P><P>Sevoflurane is a widely used inhalation anesthetic, but there are no studies on its effect on the wound-healing process. This study was undertaken to evaluate the effect of exposure time to sevoflurane on wound healing.</P><P>Method</P><P>Male Sprague–Dawley rats were used. Two circular full-thickness skin defects 8 mm in diameter were made on the dorsum of the rats. The animals were divided into six groups according to exposed gas type and time: S1 (sevoflurane, 1 h), S4 (sevoflurane, 4 h), S8 (sevoflurane, 8 h), O1 (oxygen, 1 h), O4 (oxygen, 4 h), and O8 (oxygen, 8 h). The surface area of the wounds was measured 0, 1, 3, and 7 days after surgery. Separately, the mean blood pressures (MBP) and arterial oxygen pressures (PaO<SUB>2</SUB>) were monitored during the sevoflurane exposure. Collagen type I production and transforming growth factor-β1 (TGF-β1) and basic fibroblast growth factor (bFGF) expression on the wound surface were analyzed. Routine histological analysis was also performed.</P><P>Result</P><P>Exposure duration to sevoflurane had no influence on MBP and PaO<SUB>2</SUB>. The reduction in wound size and collagen type I production was delayed in S8. The expression of TGF-β1 and bFGF on the wound surface in S8 was significantly attenuated in S8. The histology of the S8 demonstrated a delayed healing status.</P><P>Conclusions</P><P>Prolonged exposure to sevoflurane might alter the inflammatory phase of the wound-healing process by attenuation of growth factor expression such as TGF-β1 and bFGF and subsequently by reduced collagen production.</P>

Site-specific mutagenesis of yeast 2-Cys peroxiredoxin improves heat or oxidative stress tolerance by enhancing its chaperone or peroxidase function

Hong, S. H.,Lee, S. S.,Chung, J. M.,Jung, H. s.,Singh, S.,Mondal, S.,Jang, H. H.,Cho, J. Y.,Bae, H. J.,Chung, B. Y. Springer Science + Business Media 2017 Protoplasma Vol.254 No.1

<P>Yeast peroxiredoxin II (yPrxII) is an antioxidant enzyme that plays a protective role against the damage caused by reactive oxygen species (ROS) in Saccharomyces cerevisiae. This enzyme consists of 196 amino acids containing 2-Cys Prx with highly conserved two active cysteine residues at positions 48 and 171. The yPrxII has dual enzymatic functions as a peroxidase and molecular chaperone. To understand the effect of additional cysteine residues on dual functions of yPrxII, S79C-yPrxII and S109C-yPrxII, the substitution of Ser with Cys residue at 79 and 109 positions, respectively, was generated. S109C-yPrxII and S79C-yPrxII showed 3.7- and 2.7-fold higher chaperone and peroxidase activity, respectively, than the wild type (WT). The improvement in enzyme activity was found to be closely associated with structural changes in proteins. S109C-yPrxII had increased beta-sheet in its secondary structure and formed high-molecular-weight (HMW) as well as low-molecular-weight (LMW) complexes, but S79C-yPrxII formed only LMW complexes. HMW complexes predominantly exhibited a chaperone function, and LMW complexes showed a peroxidase function. In addition, transgenic yeast cells over-expressing Cys-substituted yPrxII showed greater tolerance against heat and oxidative stress compared to WT-yPrxII.</P>

Effects of HA and NA glycosylation pattern changes on the transmission of avian influenza A(H7N9) virus in guinea pigs

Park, S.,Lee, I.,Kim, J.I.,Bae, J.Y.,Yoo, K.,Kim, J.,Nam, M.,Park, M.,Yun, S.H.,Cho, W.I.,Kim, Y.S.,Ko, Y.Y.,Park, M.S. Academic Press 2016 Biochemical and biophysical research communication Vol.479 No.2

Avian influenza H7N9 virus has posed a concern of potential human-to-human transmission by resulting in seasonal virus-like human infection cases. To address the issue of sustained human infection with the H7N9 virus, here we investigated the effects of hemagglutinin (HA) and neuraminidase (NA) N-linked glycosylation (NLG) patterns on influenza virus transmission in a guinea pig model. Based on the NLG signatures identified in the HA and NA genetic sequences of H7N9 viruses, we generated NLG mutant viruses using either HA or NA gene of a H7N9 virus, A/Anhui/0½013, by reverse genetics on the 2009 pandemic H1N1 virus backbone. For the H7 HA NLG mutant viruses, NLG pattern changes appeared to reduce viral transmissibility in guinea pigs. Intriguingly, however, the NLG changes in the N9 NA protein, such as a removal from residue 42 or 66 or an addition at residue 266, increased transmissibility of the mutant viruses by more than 33%, 50%, and 16%, respectively, compared with a parental N9 virus. Given the effects of HA-NA NLG changes with regard to viral transmission, we then generated the HA-NA NLG mutant viruses harboring the H7 HA of double NLG addition and the N9 NA of various NLG patterns. As seen in the HA NLG mutants above, the double NLG-added H7 HA decreased viral transmissibility. However, when the NA NLG changes occurred by a removal of residue 66 and an addition at 266 were additionally accompanied, the HA-NA NLG mutant virus recovered the transmissibility of its parental virus. These demonstrate the effects of specific HA-NA NLG changes on the H7N9 virus transmission by highlighting the importance of a HA-NA functional balance.

Phase II study of S-1 combined with oxaliplatin as therapy for patients with metastatic biliary tract cancer: influence of the <i>CYP2A6</i> polymorphism on pharmacokinetics and clinical activity

Kim, K-p,Jang, G,Hong, Y S,Lim, H-S,Bae, K-s,Kim, H-S,Lee, S S,Shin, J-G,Lee, J-L,Ryu, M-H,Chang, H-M,Kang, Y-K,Kim, T W Nature Publishing Group 2011 The British journal of cancer Vol.104 No.4

<P><B>Background:</B></P><P>Advanced biliary cancer is often treated with fluoropyrimidine-based chemotherapy. In this study, we evaluated the efficacy and tolerability of a combination of S-1, an oral fluoropyrimidine prodrug, and oxaliplatin in patients with metastatic biliary cancer.</P><P><B>Methods:</B></P><P>Patients with histologically confirmed metastatic biliary cancer and no history of radiotherapy or chemotherapy were enrolled. Oxaliplatin was administered intravenously (130 mg m<SUP>−2</SUP>), followed by 14-day administration of oral S-1 (40 mg m<SUP>−2</SUP> twice daily) with a subsequent 7-day rest period every 21 days. Pharmacokinetic analysis of S-1 was performed at cycle 1. Patients were genotyped for <I>CYP2A6</I> polymorphisms (<SUP>*</SUP>1, <SUP>*</SUP>4, <SUP>*</SUP>7, <SUP>*</SUP>9 or <SUP>*</SUP>10), and pharmacokinetic and clinical parameters compared according to the <I>CYP2A6</I> genotype.</P><P><B>Results:</B></P><P>In total, 49 patients were evaluated, who received a median of four cycles. The overall response rate was 24.5%. Median progression-free and overall survival was 3.7 and 8.7 months, respectively. The most common haematological grade 3 out of 4 toxicity was neutropenia (14%), while non-hematological grade 3 out of 4 toxicities included anorexia (14%), nausea (12%), asthenia (10%), vomiting (10%), and diarrhoea (4%). Biotransformation of S-1 (AUC<SUB>0−24 h</SUB> of 5-fluorouracil/AUC<SUB>0−24 h</SUB> of tegafur) was 1.85-fold higher for the <I>*1/*1</I> group than for the other groups (90% confidence interval 1.37–2.49). Diarrhoea (<I>P</I>=0.0740), neutropenia (<I>P</I>=0.396), and clinical efficacy (response rate, <I>P</I>=0.583; PFS, <I>P</I>=0.916) were not significantly associated with <I>CYP2A6</I> genotype, despite differences in 5-FU exposure.</P><P><B>Conclusion:</B></P><P>The combination of S-1 and oxaliplatin appears to be active and well tolerated in patients with metastatic biliary cancer, and thus is feasible as a therapeutic modality. <I>CYP2A6</I> genotypes are associated with differences in the biotransformation of S-1. However, the impact of the <I>CYP2A6</I> polymorphism on variations in clinical efficacy or toxicity requires further evaluation.</P>

Structural basis for differential activities of enantiomeric PPARγ agonists: Binding of S35 to the alternate site

Jang, J.Y.,Koh, M.,Bae, H.,An, D.R.,Im, H.N.,Kim, H.S.,Yoon, J.Y.,Yoon, H.J.,Han, B.W.,Park, S.B.,Suh, S.W. Elsevier Science 2017 Biochimica et biophysica acta. Proteins and proteo Vol.1865 No.6

<P>Peroxisome proliferator-activated receptor gamma (PPAR gamma) is a member of the nuclear receptor superfamily. It functions as a ligand-activated transcription factor and plays important roles in the regulation of adipocyte differentiation, type 2 diabetes mellitus, and inflammation. Many PPAR gamma agonists bind to the canonical ligand-binding pocket near the activation function-2 (AF-2) helix (i.e., helix H12) of the ligand-binding domain (LBD). More recently, an alternate ligand-binding site was identified in PPAR gamma LBD; it is located beside the 52 loop between the helices H2 ' and H3. We reported previously that the chirality of two optimized enantiomeric PPAR gamma ligands (S35 and R35) differentiates their PPAR gamma transcriptional activity, binding affinity, and inhibitory activity toward Cdk5 (cyclin-dependent kinase 5)-mediated phosphorylation of PPAR gamma at Ser245 (in PPAR gamma 1 numbering; Ser273 in PPAR gamma 2 numbering). S35 is a PPAR gamma phosphorylation inhibitor with promising glucose uptake potential, whereas R35 behaves as a potent conventional PPAR gamma agonist. To provide a structural basis for understanding the differential activities of these enantiomeric ligands, we have determined crystal structures of the PPAR gamma LBD in complex with either S35 or R35. S35 and R35 bind to the PPAR gamma LBD in significantly different manners. The partial agonist S35 occupies the alternate site near the Omega loop, whereas the full agonist R35 binds entirely to the canonical LBP. Alternate site binding of S35 affects the PPAR gamma transactivation and the inhibitory effect on PPAR gamma Ser245 phosphorylation. This study provides a useful platform for the development of a new generation of PPAR gamma ligands as anti-diabetic drug candidates.</P>

Key Features in the Operation of KSTAR

Jong-Gu Kwak,Oh, Y. K.,Kim, K. P.,Kim, S. W.,Hong, S. H.,Chu, Y.,Lee, H. J.,Kim, Y. O.,Kim, J.,Park, S. L.,Hahn, S. H.,Park, M. K.,Kim, H. K.,Bak, J. G.,Bae, Y. S.,Ko, W. H.,Lee, S. G.,Lee, J. H.,Jung IEEE 2012 IEEE transactions on plasma science Vol.40 No.3

<P>The Korea Superconducting Tokamak Advanced Research (KSTAR) device is aimed at advanced tokamak (AT) research. Three years have passed since it achieved its first plasma in 2008. Because it is a superconducting machine and is working toward AT research, it has unique features in terms of the machine engineering and operation. The toroidal field (TF) magnet coils are made of Nb<SUB>3</SUB>Sn, which provide high TFs up to 3.5 T, and have been fully tested. The poloidal field (PF) magnet coils, consisting of both Nb<SUB>3</SUB>Sn and NbTi, which have a maximum current of 25 kA in their design, were tested up to 15 kA. A thermal hydraulic analysis is being conducted for PF magnet coil operation. All plasma-facing components (PFCs) are equipped with water cooled graphite tiles and have the capability of being baked up to 350°C. A startup scenario, which considered both the effect of the ferromagnetic material in the cable in conduit conductor jacket of the magnet coils as well as a nonferromagnetic up-down asymmetry in the cryostat structure, was developed and demonstrated its effectiveness by the last two year's reliable operations. Passive stabilizers and in-vessel control coils (IVCCs) are key components to realize AT operation in KSTAR. The segmented IVCC coils were connected to form circular coils for internal vertical control in 2010, and diverted plasmas with high elongation (κ~1.8, δ>;0.6) were achieved. A neutral beam injection (NBI) system was developed aiming at 2 MW, 300 s per ion source which meets the long-pulse requirement of KSTAR. An NBI ion source with a power of 1.7 MW at 100 kV has been commissioned for 10 s. Finally, ELMy H-modes were successfully produced with 1.3-MW NBI power at a plasma current of 0.6 MA in the 2010 campaign. The first H-mode discharge (#4200) in KSTAR was achieved one year earlier than officially planned and was done at B<SUB>T</SUB> = 2 T with I<SUB>p</SUB> = 0.6 MA in a well-balanced double null configuration after boronization on the PFC. Successful operations in the early days of KSTAR including H-mode experiments revealed the capability of advanced and steady-state operation which is essential for the international thermonuclear experimental reactor (ITER) and future fusion reactors.</P>

인두편도염 환자와 보균자에서 분리한 Streptococcus pyogenes의 T-protein serotyping 및 항균제 감수성

이영희,황규잠,주영란,박강수,이광준,엄영길,배송미,차성호 국립보건연구원 1998 국립보건원보 Vol.35 No.-

Experimental infection of mandarin duck with highly pathogenic avian influenza A (H5N8 and H5N1) viruses

Kang, H.M.,Lee, E.K.,Song, B.M.,Heo, G.B.,Jung, J.,Jang, I.,Bae, Y.C.,Jung, S.C.,Lee, Y.J. Elsevier Scientific Pub. Co 2017 Veterinary microbiology Vol.198 No.-

<P>A highly pathogenic avian influenza (HPAI) H5N8 virus was first detected in poultry and wild birds in South Korea in January 2014. Here, we determined the pathogenicity and transmissibility of three different clades of 1-15 viruses in mandarin ducks to examine the potential for wild bird infection. H5N8 (Glade 2.3.4.4) replicated more efficiently in the upper and lower respiratory tract of mandarin ducks than two previously identified H5N1 virus clades (clades 2.2 and 2.3.2.1). However, none of the mandarin ducks infected with H5N8 and H5N1 viruses showed severe clinical signs or mortality, and gross lesions were only observed in a few tissues. Viral replication and shedding were greater in H5N8-infected ducks than in H5N1-infected ducks. Recovery of all viruses from control duck in contact with infected ducks indicated that the highly pathogenic H5 viruses spread horizontally through contact. Taken together, these results suggest that H5N8 viruses spread efficiently in mandarin ducks. Further studies of pathogenicity in wild birds are required to examine possible long-distance dissemination via migration routes. (C) 2016 Elsevier B.V. All rights reserved.</P>

H형강 롤포스 예측 모델 개발

정현석(H. S. Jung),위창현(C. H. Wee),문홍길(H. K. Moon),서경호(K. H. Seo),김태형(T. H. Kim),배병철(B. C. Bae),이영석(Y. S. Lee) 한국소성·가공학회 2023 한국소성가공학회 학술대회 논문집 Vol.2023 No.11

원발성 간암에서 PIVKA-II 및 Lens Culinaris Agglutinin-A 반응성 Alpha-fetoprotein(AFP-L3)의 임상적 유용성

배시현,박두호,양진모,박영민,차상복,최종영,성광용,조세현,정규원,선희식,김부성,최상욱,변병훈,한남익 대한간학회 2000 Clinical and Molecular Hepatology(대한간학회지) Vol.6 No.2

Background/Aims: Des-γ-carboxy prothrombin(DCP), a protein induced by vitamin K absence or antagonist-II(PIVKA-II), and Lens culinaris agglutinin-A reactive AFP-L3 have been reported to be useful markers for the diagnosis of hepatocellular carcinoma (HCC). In the present study, both the PIVKA-II and AFP-L3 were analyzed and compared with a conventional AFP to determine its usefulness, specificity and sensitivity in the diagnosis of HCC. Methods: Sera were collected from 108 patients consisting of 17 patients with chronic hepatitis, 22 patients with liver cirrhosis and 69 patients with HCC. The AFP-L3 was determined by an lectin affinity electrophoresis coupled with an antibody-affinity blotting. Level of DCP was measured by an enzyme immunoassay with an anti-DCP monoclonal antibody. Results: The sensitivity and specificity of PIVKA-II and AFP L3 were 49.3% and 89.5%, and 32.5% and 85.7%, respectively. No significant correlation was found between the PIVKA-II or AFP L3 and serum AFP. No correlation was found etween the PIVKA-II or AFP L3 and the characteristics of HCC. Conclusion: The determination of plasma DCP and AFP L3 levels combined with AFP levels may be useful especially for the differential diagnosis between HCC and chronic liver diseases without HCC.(Korean J HepatoBackground/Aims: Des-γ-carboxy prothrombin(DCP), a protein induced by vitamin K absence or antagonist-II(PIVKA-II), and Lens culinaris agglutinin-A reactive AFP-L3 have been reported to be useful markers for the diagnosis of hepatocellular carcinoma (HCC). In the present study, both the PIVKA-II and AFP-L3 were analyzed and compared with a conventional AFP to determine its usefulness, specificity and sensitivity in the diagnosis of HCC. Methods: Sera were collected from 108 patients consisting of 17 patients with chronic hepatitis, 22 patients with liver cirrhosis and 69 patients with HCC. The AFP-L3 was determined by an lectin affinity electrophoresis coupled with an antibody-affinity blotting. Level of DCP was measured by an enzyme immunoassay with an anti-DCP monoclonal antibody. Results: The sensitivity and specificity of PIVKA-II and AFP-L3 were 49.3% and 89.5%, and 32.5% and 85.7%, respectively. No significant correlation was found between the PIVKA-II or AFP-L3 and serum AFP. No correlation was found etween the PIVKA-II or AFP L3 and the characteristics of HCC. Conclusion: The determination of plasma DCP and AFP-L3 levels combined with AFP levels may be useful especially for the differential diagnosis between HCC and chronic liver diseases without HCC.(Korean J Hepatol 2000;6:205-214)l 2000;6:205-214)