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Generation of double knockout cattle via CRISPR-Cas9 ribonucleoprotein(RNP)electroporation

Journal of Animal Science and Biotechnology 2024年第1期15卷 456-462页

作者： Gyeong-Min Gim Kyeong-Hyeon Eom Dong-Hyeok Kwon Dae-Jin Jung Dae-Hyun Kim Jun-Koo Yi Jae-Jung Ha Ji-Hyun Lee Seong-Beom Lee Woo-Jae Son Soo-Young Yum Won-Wu Lee goo jang Laboratory of Theriogenology and Biotechnology Department of Veterinary Clinical ScienceCollege of Veterinary Medicine and the Research Institute of Veterinary ScienceSeoul National UniversitySeoulRepublic of Korea LARTBio Co. Ltd.SeoulRepublic of Korea Gyeongsangbukdo Livestock Research Institute YeongjuRepublic of Korea Comparative Medicine Disease Research Center Seoul National UniversitySeoulRepublic of Korea

Background Genome editing has been considered as powerful tool in agricultural ***,genome editing progress in cattle has not been fast as in other mammal species,for some disadvantages including long gestational periods,single pregnancy,and high raising ***,technically demanding methods such as microinjection and somatic cell nuclear transfer(SCNT)are needed for gene editing in *** this point of view,electroporation in embryos has been risen as an *** First,editing efficiency of our electroporation methods were tested for *** of mutation on embryo was confirmed by T7E1 *** first combination,mutation rates for MSTN and PRNP were 57.6%±13.7%and 54.6%±13.5%,*** case of MSTN/BLG,mutation rates were 83.9%±23.6%for MSTN,84.5%±18.0%for ***,the double-KO embryos were transferred to surrogates and mutation rate was identified in resultant calves by targeted deep *** recipients were transferred for MSTN/PRNP,4 calves were delivered,and one calf underwent an induction for double *** surrogates were given double-KO embryos for MSTN/BLG,and four of the six calves that were born had mutations in both *** These data demonstrated that production of genome edited cattle via electroporation of RNP could be effectively ***,MSTN and PRNP from beef cattle and MSTN and BLG from dairy cattle have been born and they will be valuable resources for future precision breeding.

关键词： Beta-lactoglobulin Cattle CRISPR-Cas9 Electroporation Knockout MSTN PRNP

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Development of genome engineering technologies in cattle: from random to specific

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Journal of Animal Science and Biotechnology 2018年第2期9卷 285-293页

作者： Soo-Young Yum Ki-Young Youn Woo-Jae Choi goo jang Department of Veterinary Clinical Science College of Veterinary Medicine and the Research Institute of Veterinary Science Seoul National University Farm Animal Clinical Training and Research Center Institute of Green Bio Science Technology Seoul National University Emergence Center for Food-Medicine Personalized Therapy System Advanced Institutes of Convergence Technology Seoul National University College of Veterinary Medicine Seoul National University

The production of transgenic farm animals(e.g., cattle) via genome engineering for the gain or loss of gene functions is an important undertaking. In the initial stages of genome engineering, DNA micro-injection into one-cell stage embryos(zygotes) followed by embryo transfer into a recipient was performed because of the ease of the ***, as this approach resulted in severe mosaicism and has a low efficiency, it is not typically employed in the cattle as priority, unlike in mice. To overcome the above issue with micro-injection in cattle, somatic cell nuclear transfer(SCNT) was introduced and successfully used to produce cloned livestock. The application of SCNT for the production of transgenic livestock represents a significant advancement, but its development speed is relatively slow because of abnormal reprogramming and low gene targeting efficiency. Recent genome editing technologies(e.g.,ZFN, TALEN, and CRISPR-Cas9) have been rapidly adapted for applications in cattle and great results have been achieved in several fields such as disease models and bioreactors. In the future, genome engineering technologies wil accelerate our understanding of genetic traits in bovine and wil be readily adapted for bio-medical applications in cattle.

关键词： Cattle CRISPR-Cas9 Genome engineering technologies Transgenesis Transposon

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Efficacy of 0.5-L vs 1-L polyethylene glycol containing ascorbic acid as additional colon cleansing methods for inadequate bowel preparation as expected by last stool examination before colonoscopy

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World Journal of Clinical Cases 2019年第1期7卷 39-48页

作者： Joon Hyun Cho Eun Joo goo Kyeong Ok Kim Si Hyung Lee Byung Ik jang Tae Nyeun Kim Division of Gastroenterology and Hepatology Department of Internal Medicine Yeungnam University College of Medicine

BACKGROUND No consensus has been reached in patients suspected of having inadequate bowel preparation regarding optimal salvage methods, which negatively affects the efficacy and quality of colonoscopy. The most ideal and reasonable rescue option involves early suspicion and identification of patients with inadequate preparation before sedation, additional oral ingestion of a suitable preparation formulation, and same-day *** To compare 0.5-L and 1-L polyethylene glycol containing ascorbic acid(PEG +Asc) as additional bowel cleansing methods after a 2-L split-dose PEG + Asc regimen in patients with expected inadequate bowel preparation before *** Individuals with expected inadequate bowel preparation based on last stool form, such as turbid liquid, particulate liquid, or liquid with small amounts of feces, were randomized to either a 0.5-L PEG + Asc group or a 1-L PEG + Asc group. The primary endpoint was bowel preparation as assessed using the Aronchick bowel preparation scale(ABPS) and Boston bowel preparation scale(BBPS) scores. The secondary endpoints were cecal intubation time, withdrawal time, polyp detection rate(PDR), adenoma detection rate(ADR), individual compliance with additional PEG + Asc, and patient *** Initially, 98 patients were included, but 8 were later excluded due to withdrawal of consent to participate in the study. Adequate bowel preparation(as assessed by ABPS) was observed in 80.9%(38/47) of subjects in the 0.5-L group and in88.4%(38/43) of subjects in the 1-L group(P = 0.617). Mean total BBPS was 6.7 points in the 0.5-L group and 7.0 points in the 1-L group(P = 0.458). ADRs and PDRs were similar in the two groups, and cecal intubation and withdrawal times were not significantly different. However, mean patient satisfaction score was significantly higher in the 0.5-L group(P = 0.041).CONCLUSION The bowel cleaning efficacy of additional 0.5-L PEG + Asc was not inferior to that of 1-L PEG + Asc. Add

关键词： Inadequate bowel preparation Additional colon cleansing Colonoscopy Polyethylene glycol

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Characterization of smooth muscle, enteric nerve, interstitial cells of Cajal, and fibroblast-like cells in the gastric musculature of patients with diabetes mellitus

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World Journal of Gastroenterology 2016年第46期22卷 10131-10139页

作者： Kyung Sik Park Kwang Bum Cho Il Seon Hwang Jae Hyung Park Byung Ik jang Kyeong Ok Kim Sung Woo Jeon Eun Soo Kim Chang Sik Park Joong goo Kwon Department of Internal Medicine Keimyung University School of Medicine Department of Pathology Keimyung University School of Medicine Department of Physiology Keimyung University School of Medicine Department of Internal Medicine Youngnam University College of Medicine Department of Internal Medicine Kyungpook National University School of Medicine Department of Advanced Materials Convergence Korea Institute of Ceramic Engineering and Technology Department of Internal Medicine Catholic University of Daegu School of Medicine

AIM To investigate histologic abnormalities in the gastric smooth muscle of patients with diabetes mellitus(DM).METHODS Full-thickness gastric specimens were obtained from patients undergoing surgery for gastric cancer. H&E stain and Masson's Trichrome stain were performed to assess the degree of fibrosis. Immunohistochemical staining using various antibodies was also performed [antibodies against protein gene product 9.5(PGP9.5), neuronal nitric oxide synthase(n NOS), vasoactive intestinal peptide(VIP), neurokinin-1(NK1) receptor, c-Kit, and platelet-derived growth factor receptor-alpha,(PDGFRα)]. Immunofluorescent staining and evaluation with confocal microscopy were also *** Twenty-six controls and 35 diabetic patients(21 shortduration patients and 14 long-duration patients) were included. There were no significant differences in basic demographics between the two groups except in mean body mass index(BMI)(higher in the DM group). Proportions of moderate-to-severe intercellular fibrosis in the muscle layer were significantly higher in the DM group than in the control group(P < 0.01). On immunohistochemical staining, c-Kit- and PDGFRα-positive immunoreactivity were significantly decreased in the DM group compared with the control group(P < 0.05). There were no statistically significant differences in PGP9.5, n NOS, VIP, and neurokinin 1 expression. On immunofluorescent staining, cellularity of interstitial cells of Cajal(ICC) was observed to decrease with increasing duration of *** Our study suggests that increased intercellular fibrosis, loss of ICC, and loss of fibroblast-like cells are found in the smooth muscle of DM patients. These abnormalities may contribute to changes in gastric motor activity in patients with DM.

关键词：糖尿病 mellitus Cajal 的空隙的房间像成纤维细胞的房间 Gastroparesis 伤寒神经系统

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Retinoic acid enhances lactoferrin-induced IgA responses by increasing betaglycan expression

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Cellular & Molecular Immunology 2016年第6期13卷 862-870页

作者： Jeong-Min Lee Young-Saeng jang Bo-Ra Jin Sun-Jin Kim Hyeon-Jin Kim Bo-Eun Kwon Hyun-Jeong Ko Sung-il Yoon Geun-Shik Lee Woan-Sub Kim goo-Young Seo Pyeung-Hyeun Kim Department of Molecular Bioscience School of Biomedical Science Kangwon National University Chuncheon Republic of Korea Laboratory of Microbiology and Immunology College of Pharmacy Kangwon National University Chuncheon Republic of Korea Department of Systems Immunology College of Biomedical Science Kangwon National University Chuncheon 200-701 Republic of Korea College of Veterinary Medicine Kangwon National University Chuncheon Gangwon 200-701 Republic of Korea Department of Animal Life and Environmental Science College of Agriculture and Life Science Hankyong National University Anseong-si 456-749 Republic of Korea

Lactoferrin （LF） and retinoic acid （RA） are enriched in colostrum, milk, and mucosal tissues. We recently showed that LF-induced IgA class switching through binding to betaglycan （transforming growth factor-beta receptor III, TpRIII） and activation of canonical TGF-p signaling. We investigated the combined effect of LF and RA on the overall IgA response. An increase in IgA production by LF was further augmented by RA. This combination effect was also evident in Ig germ-line α （GLa） transcription and GLa promoter activity, indicating that LF in cooperation with RA increased IgA isotype switching. We subsequently found that RA enhanced TβRIII expression and that this increase contributed to LF-stimulated IgA production. In addition to the IgA response, LF and RA in combination also enhanced the expression of the gut-homing molecules C-C chemokine receptor 9 （CCR9） and a4β7 on B cells. Finally, peroral administration of LF and RA enhanced the frequency of CCR9＋ IgA＋ plasma cells in the lamina propria. Taken together, these results suggest that LF in cooperation with RA can contribute to the establishment of gut IgA responses.

关键词： gut homing molecule IgA lactoferrin retinoic acid TGF-β receptor

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Randomized controlled trial to evaluate the efficacy and safety of fexuprazan compared with esomeprazole in erosive esophagitis

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World Journal of Gastroenterology 2022年第44期28卷 6294-6309页

作者： Kang Nyeong Lee Oh Young Lee Hoon Jai Chun Jin Il Kim Sung Kook Kim Sang Woo Lee Kyung Sik Park Kook Lae Lee Suck Chei Choi Jae-Young jang Gwang Ha Kim In-kyung Sung Moo In Park Joong goo Kwon Nayoung Kim Jae Jun Kim Soo Teik Lee Hyun Soo Kim Ki Bae Kim Yong Chan Lee Myung-Gyu Choi Joon Seong Lee Hwoon-Yong Jung Kwang Jae Lee Jie-Hyun Kim Hyunsoo Chung Department of Internal Medicine Hanyang University College of MedicineSeoul 04763South Korea Department of Internal Medicine Korea University Anam HospitalSeoul 02841South Korea Department of Internal Medicine The Catholic University of KoreaYeouido ST.Mary’s HospitalSeoul 07260South Korea Department of Internal Medicine Kyungpook National University HospitalDaegu 41944South Korea Department of Internal Medicine Korea University Ansan HospitalAnsan-si 15355South Korea Department of Internal Medicine Keimyung University Dongsan HospitalDaegu 42601South Korea Department of Internal Medicine Seoul Metropolitan Government Seoul National University Boramae Medical CenterSeoul 07061South Korea Department of Internal Medicine Wonkwang University HospitalIksan 54538South Korea Department of Internal Medicine KyungHee University Medical CenterSeoul 02447South Korea Department of Internal Medicine Pusan National University School of Medicine and Biomedical Research InstitutePusan National University HospitalBusan 47241South Korea Department of Internal Medicine KKonkuk University Medical CenterSeoul 05030South Korea Department of Internal Medicine Kosin University Gaspel HospitalBusan 49267South Korea Department of Internal Medicine Daegu Catholic University Medical CenterDaegu 42471South Korea Department of Internal Medicine Seoul National University Bundang HospitalSeongnam-si 13620Gyeonggi-doSouth Korea Department of Internal Medicine Samsung Medical CenterSeoul 06351South Korea Department of Internal Medicine Chonbuk National University HospitalJeonju-si 54907South Korea Department of Internal Medicine Chonnam National University HospitalGwangju 61469South Korea Department of Internal medicine Chungbuk National University School of MedicineCheong Ju 28644South Korea Department of Internal Medicine Severance HospitalSeoul 03722South Korea Department of Internal Medicine The Catholic University of KoreaSeoul ST.Mary’s HospitalSeoul 06591South Korea Digestive Disease Center Soon

BACKGROUND Fexuprazan,a novel potassium-competitive acid blocker,reversibly suppresses the K+/H+-ATPase enzyme in proton pumps within gastric parietal ***’s suppression of gastric acid was maintained in healthy individuals for 24 h in a dose-dependent *** To compare fexuprazan to esomeprazole and establish its efficacy and safety in patients with erosive esophagitis(EE).METHODS Korean adult patients with endoscopically confirmed EE were randomized 1:1 to receive fexuprazan 40 mg or esomeprazole 40 mg once daily for eight *** primary endpoint was the proportion of patients with healed EE confirmed by endoscopy at week *** secondary endpoints included the healing rate of EE at week 4,symptom response,and quality of life *** profiles and serum gastrin levels were compared between the *** Of the 263 randomized,218 completed the study per protocol(fexuprazan 40 mg,n=107;esomeprazole 40 mg,n=111).Fexuprazan was non-inferior to esomeprazole regarding the healing rate at week 8[99.1%(106/107)vs 99.1%(110/111)].There were no between-group differences in the EE healing rate at week 4[90.3%(93/103)vs 88.5%(92/104)],symptom responses,and quality of life ***,serum gastrin levels at weeks 4 and 8 and drug-related side effects did not significantly differ between the *** Fexuprazan 40 mg is non-inferior to esomeprazole 40 mg in EE healing at week *** suggest that fexuprazan is an alternative promising treatment option to PPIs for patients with EE.

关键词： Gastroesophageal reflux Esophagitis Proton pump inhibitors Heartburn Quality of life

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Comparison of hepatic venous pressure gradient and endoscopic grading of esophageal varices

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World Journal of Gastroenterology 2016年第11期22卷 3212-3219页

作者： Eun Ji Lee Yong Jae Kim Dong Erk goo Seung Boo Yang Hyun-Joo Kim Jae Young jang Soung Won Jeong Department of Radiology Soonchunhyang University Seoul Hospital Department of Radiology Soonchunhyang University Gumi Hospital Department of Gastroenterology Soonchunhyang University Seoul Hospital

AIM: To determine the correlation between the hepatic venous pressure gradient and the endoscopic grade of esophageal ***: From September 2009 to March 2013, a total of 176 measurements of hepatic venous pressure gradient(HVPG) were done in 146 patients. Each transjugular HVPG was measured twice, first using an end whole catheter(EH-HVPG), and then using a balloon catheter(B-HVPG). The HVPG was compared with the endoscopic grade of esophageal varices(according to the general rules for recording endoscopic findings of esophagogastric varices), which was recorded within a month of the measurement of ***: The study included 110 men and 36 women, with a mean age of 56.1 years(range, 43-76 years). The technical success rate of the pressure measurements was 100% and there were no complication related to the procedures. Mean HVPG was 15.3 mm Hg as measured using the end hole catheter method and 16.5 mm Hg as measured using the balloon catheter method. Mean HVPG(both EHHVPG and B-HVPG) was not significantly different among patients with different characteristics, including sex and comorbid factors, except for cases with hepatocellular carcinoma(B-HVPG, P = 0.01; EH-HVPG, P = 0.02). Portal hypertension(> 12 mm Hg HVPG) occurred in 66% of patients according to EH-HVPG and 83% of patients according to B-HVGP, and significantly correlated with Child's status(B-HVPG, P < 0.000; EHHVGP, P < 0.000) and esophageal varies observed upon endoscopy(EH-HVGP, P = 0.003; B-HVGP, P = 0.006). One hundred and thirty-five endoscopies were performed, of which 15 showed normal findings, 27 showed grade 1 endoscopic esophageal varices, 49 showed grade 2 varices, and 44 showed grade 3 varices. When comparing endoscopic esophageal variceal grades and HVPG using univariate analysis, the P value was 0.004 for EH-HVPG and 0.002 for B-HVPG. CONCLUSION: Both EH-HVPG and B-HVPG showed a positive correlation with the endoscopic grade of esophageal varices, with B-HVPG showing a stron

关键词： Hepatic venous pressure gradient Liver cirrhosis Esophageal varices Endoscopic grade of esophageal v

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Validation of pharmacodynamic assessment method after administration of voglibose in healthy subjects

Validation of pharmacodynamic assessment method after admini...

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第十五届国际药理学大会

作者： Tae Yu-Mi Kim Jung - Ryul Lim Kyoung Soo Kim JaeWoo Kim Bo-Hyung Jeon Ji - Young Cho Joo - Youn Yu Kyung - Sang jang In - Jin Shin Sang-goo Department of Pharmacology and Clinical Pharmacology Unit Seoul National University College of Medicine and Hospital Seoul Republic of Korea Department of Pharmacology and Clinical Pharmacology Unit Seoul National University College of Medicine and Hospital Seoul Republic of Korea Department of Pharmacology and Clinical Pharmacology Unit Seoul National University College of Medicine and Hospital Seoul Republic of Korea Department of Pharmacology and Clinical Pharmacology Unit Seoul National University College of Medicine and Hospital Seoul Republic of Korea Department of Pharmacology and Clinical Pharmacology Unit Seoul National University College of Medicine and Hospital Seoul Republic of Korea Department of Pharmacology and Clinical Pharmacology Unit Seoul National University College of Medicine and Hospital Seoul Republic of Korea Department of Pharmacology and Clinical Pharmacology Unit Seoul National University College of Medicine and Hospital Seoul Republic of Korea Department of Pharmacology and Clinical Pharmacology Unit Seoul National University College of Medicine and Hospital Seoul Republic of Korea Department of Pharmacology and Clinical Pharmacology Unit Seoul National University College of Medicine and Hospital Seoul Republic of Korea Department of Pharmacology and Clinical Pharmacology Unit Seoul National University College of Medicine and Hospital Seoul Republic of Korea

＜正＞ BACKGROUND Voglibose is an alpha- glucosidase inhibitor. Due to negligible oral absorption, measuring drug concentration in the blood is impractical. So we proposed a pharmacodynamic assessment method to reflect drug effect, and this study aimed to validate this *** A placebo - controlled, selective two - period clinical study was conducted in 20 healthy male subjects. Period Ⅰ: On day 1. subjects received a placebo and a sucrose - rich fluid meal 20 min after dosing. Blood samples were taken during 3 hours. On day 2. subjects received 0.3 mg voglibose instead of *** Ⅱ: 9 subjects in whom effects of drug were observed in Period Ⅰ participated in a multiple dose study （placebo: 8. 11 pm on day - 1. and 9 am on day 1 / voglibose: 2. 8. 11 pm on day 1. and 9 am on day 2）. RESULTS The average percent decreases of AUEClh （area under the serum glucose level- time curve to 1h） and Gmax （maximum serum glucose level） were 19.6% （P＜0.001） and 22.2% （P＜0.001）. respectively. CONCLUSIONS Significant drug effects of voglibose were revealed after multiple doses. Changes of AUEClh and Gmax compared to placebo may be alternative parameters to AUC and Cmax for an equivalence study.

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Risk factors of biliary intervention by imaging after livingdonor liver transplantation

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World Journal of Gastroenterology 2016年第7期22卷 2342-2348页

作者： Soon Kyu Lee Jong Young Choi Dong Myung Yeo Young Joon Lee Seung Kew Yoon Si Hyun Bae Jeong Won jang Hee Yeon Kim Dong goo Kim Young Kyoung You Division of Hepatology Department of Internal MedicineCollege of MedicineThe Catholic University of KoreaSeoul 06591South Korea Department of Radiology College of MedicineThe Catholic University of KoreaSeoul 06591South Korea Department of Surgery College of MedicineThe Catholic University of KoreaSeoul 06591South Korea

AIM:To determine the risk factors of biliary intervention using magnetic resonance cholangiopancreatography(MRCP) after living donor liver transplantation(LDLT).METHODS: We retrospectively enrolled 196 patients who underwent right lobe LDLT between 2006 and 2010 at a single liver transplantation center. Direct duct-to-duct biliary anastomosis was performed in all 196 patients. MRCP images routinely taken 1 mo after LDLT were analyzed to identify risk factors for biliary intervention during follow-up, such as retrograde cholangiopancreatography or percutaneous transhepatic biliary drainage. Two experienced radiologists evaluated the MRCP findings, including the anastomosis site angle on three-dimensional images, the length of the filling defect on maximum intensity projection, bile duct dilatation, biliary stricture, and ***: Eighty-nine patients underwent biliary intervention during follow-up. The anastomosis site angle [hazard ratio(HR) = 0.48; 95% confidence interval(CI), 0.30-0.75, P < 0.001], a filling defect in the anastomosis site(HR = 2.18, 95%CI: 1.41-3.38,P = 0.001), and biliary leakage(HR = 2.52, 95%CI: 1.02-6.20, P = 0.048) on MRCP were identified in the multivariate analysis as significant risk factors for biliary intervention during follow-up. Moreover, a narrower anastomosis site angle(i.e., below the median angle of 113.3°) was associated with earlier biliary intervention(38.5 ± 4.2 mo vs 62. 1 ± 4.1 mo, P < 0.001). Kaplan-Meier analysis comparing biliary intervention-free survival according to the anastomosis site angle revealed that lower survival was associated with a narrower anastomosis site angle(36.3% vs 62.0%, P < 0.001).CONCLUSION: The biliary anastomosis site angle in MRCP after LDLT may be associated with the need for biliary intervention.

关键词： Magnetic resonance cholangiopancreatography Liver transplantation Living donor Biliary intervention Endoscopic retrograde cholangiopancreatography Percutaneous transhepatic biliarydrainage

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SAFETY, TOLERABILITY, AND PHARMACOKINETICS OF CKD- 501,A NOVEL PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR ALPHA/GAMMA DUAL AGONIST

SAFETY, TOLERABILITY, AND PHARMACOKINETICS OF CKD- 501,A NOV...

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第十五届国际药理学大会

作者： Shin Sang-goo Kim Jung-Ryul Cho Joo-Youn Lim Kyoung Soo Kim JaeWoo Kim Bo-Hyung Shin Hyun Suk Yu Kyung-Sang Shin Jae-Soo Ahn Soon-Kil jang In-Jin Department of Pharmacology Seoul National University College of MedicineKorea. Department of Pharmacology Seoul National University College of MedicineKorea. Department of Pharmacology Seoul National University College of MedicineKorea. Department of Pharmacology Seoul National University College of MedicineKorea. Department of Pharmacology Seoul National University College of MedicineKorea. Department of Pharmacology Seoul National University College of MedicineKorea. Department of Pharmacology Seoul National University College of MedicineKorea. Department of Pharmacology Seoul National University College of MedicineKorea. Chong Kun Dang Pharm. Korea. Chong Kun Dang Pharm. Korea. Department of Pharmacology Seoul National University College of Medicine Korea.

＜正＞ CKD-501 is a novel peroxisome proliferator-activated receptor α/γ dual agonist for the treatment of diabetes mellitus. This study aimed to investigate safety, tolerability, and pharmacokinetics of CKD-501 in healthy volunteers. A randomized, placebo-controlled, double-blind, parallel-group, dose-rising study was performed. Thirty-six healthy male subjects received single oral doses ranging from 0.5-8 mg CKD- 501 or placebo. In the multipledose study, 24 subjects received 1-4 mg once daily for 7 days. Serial blood and urine samples were collected. No serious adverse events （AEs） were observed and AEs reported were all of mild severity. In the single-dose study, mean Cmax and AUCinf increased linearly up to the 8 mg dose *** and t1/2 ranged from 0.5-4 h and 7.8-9.8 h. respectively. Less than 1 % CKD-501 was excreted in urine. After multiple dosing, accumulation index was around 1.2. Mean apparent clearance, Tmax and t1/2 in steady state were independent of dose and time. Single oral doses up to 8 mg CKD- 501 and multiple doses up to 4 mg were safe and well tolerated. Mean Cmax and AUCinf were dose proportional and there was no remarkable accumulation after multiple dosing.

关键词： PPAR clinical trial

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