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1. Safety and Effectiveness of Naltrexone-Bupropion in Korean Adults with Obesity: Post-Marketing Surveillance Study

Author

Lyu YS, Ahn H, Hong S, and Park CY

Subjects
naltrexone-bupropion, obesity management, post-marketing survey, weight loss efficacy, adverse events, Therapeutics. Pharmacology, RM1-950
Abstract

Young Sang Lyu,1 Hongyup Ahn,2 Sangmo Hong,3 Cheol-Young Park4 1Division of Endocrinology and Metabolism, Department of Internal Medicine, Chosun University Hospital, Gwangju, Republic of Korea; 2Department of Statistics, Dongguk University, Seoul, Republic of Korea; 3Department of Internal Medicine, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Republic of Korea; 4Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of KoreaCorrespondence: Cheol-Young Park, Division of Endocrinology and Metabolism, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 29 Saemunan-ro,Jongno-gu, Seoul, 03181, Republic of Korea, Email cydoctor@skku.eduPurpose: To investigate the safety and effectiveness of naltrexone-bupropion in Korean adults with obesity.Patients and methods: This was a prospective, observational multicenter study from April 29, 2016, to April 28, 2022. Individuals with obesity with a body mass index of ≥ 30 kg/m2 or ≥ 27 kg/m2 who had obesity-related comorbidities were included. The naltrexone-bupropion dose was gradually titrated weekly from 8/90 to 32/360 mg and maintained at the maximum tolerated dose. In total, 612 and 300 individuals were evaluated for safety and effectiveness, respectively.Results: In total, 41.34% individuals reported drug-related adverse reactions, such as nausea (19.12%), headache (7.68%), and dizziness (5.23%). Older age and comorbidities were significantly associated with adverse events. At 12 weeks after reaching the maintenance dose, naltrexone-bupropion 32/360 mg resulted in the greatest weight reduction (− 7.21%) compared with other doses, which persisted at week 24 (− 7.69%). The naltrexone-bupropion 16/180 mg resulted in significant weight reduction, achieving − 5.99% and − 9.18% reductions at weeks 12 and 24, similar to that with naltrexone-bupropion 32/360 mg. Young age and no comorbidities were significantly associated > 5% weight reduction.Conclusion: Naltrexone-bupropion demonstrated marked stability and weight loss effectiveness, particularly in young individuals with obesity without comorbidities. Therefore, individualized treatment is necessary when prescribing naltrexone-bupropion.Keywords: naltrexone-bupropion, obesity management, post-marketing survey, weight loss efficacy, adverse events

Published
2024

2. Progranulin and Breast Cancer Mortality: 13-Year Follow-Up of a Cohort Study

Author

Koo DH, Lee KS, Sim SH, Chae H, Lee EG, Han JH, Jung SY, Lee S, Kang HS, Lee ES, Park CY, and Oh SW

Subjects
breast cancer, progranulin, mortality, long-term follow-up, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Dong-Hoe Koo,1,* Keun Seok Lee,2,* Sung Hoon Sim,2 Heejung Chae,2 Eun-Gyeong Lee,2 Jai Hong Han,2 So-Youn Jung,2 Seeyoun Lee,2 Han-Sung Kang,2 Eun Sook Lee,2 Cheol-Young Park,1,* Sang Woo Oh3,* 1Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; 2Center for Breast Cancer, Research Institute and Hospital, National Cancer Center, Goyang-si, Gyeonggi-do, Republic of Korea; 3Department of Family Medicine, Center for Obesity, Metabolism, and Nutrition, Dongguk University Ilsan Hospital, Goyang-si, Gyeonggi-do, Republic of Korea*These authors contributed equally to this workCorrespondence: Cheol-Young Park, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 29 Saemunan-ro, Jongno-gu, Seoul, 03181, Republic of Korea, Tel +82-2-2001-1869, Fax +82-2-2001-1588, Email cydoctor@chol.com Sang Woo Oh, Center for Obesity, Nutrition, and Metabolism, Department of Family Medicine, Dongguk University Ilsan Hospital, Dongguk University College of Medicine, 27 Donggung-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do, 10326, Republic of Korea, Tel +82-31-961-7000, Email osw6021@gmail.comBackground: We have reported that serum progranulin (PGRN) levels are clinically significant in predicting recurrence in patients with HR-positive breast cancer. The aim of the present study was to examine whether PGRN levels might be associated with breast cancer mortality.Methods: This was a cohort study of 695 newly diagnosed breast cancer patients who underwent curative surgery between 2001 and 2004. The relationship between breast cancer mortality and pre-operative serum PGRN levels in these patients with a median follow-up of 12.7 years was evaluated until May 2020.Results: A total of 118 (17%) deaths were identified in the cohort. According to the HR status, (10, 15, and 20)-year overall survival (OS) rates were (91.4, 81.1, and 75.9) % for HR-positive patients, and (76.5, 74.2, and 69.8) % for HR-negative patients, respectively (p = 0.003). Higher levels of PGRN were significantly associated with poor OS in the HR-positive group (p for trend = 0.001). In particular, hazard ratios for PGRN quartiles suggested a dose–response relationship, with the highest quartile having the worst OS in the HR-positive group (highest vs lowest: 15-year OS, (68.3 vs 90.0) %; 20-year OS, (62.3 vs 84.8) %, even after adjusting for age, tumor stage, and metabolic confounders.Conclusion: Pre-operative serum PGRN levels had clinical significance for predicting cancer mortality in breast cancer patients independent of tumor stage and metabolic parameters, especially in HR-positive tumors.Keywords: breast cancer, progranulin, mortality, long-term follow-up

Published
2023

4. Identification of MiR-205 As a MicroRNA That is highly expressed in medullary thymic epithelial cells

Author

Erle, David, Anderson, Mark, McManus, Thomas, Khan, IS, Park, CY, Mavropoulos, A, Shariat, N, Pollack, JL, Barczak, AJ, Erle, DJ, McManus, MT, Anderson, MS, and Jeker, LT

Abstract

© 2015 Khan et al.Thymic epithelial cells (TECs) support T cell development in the thymus. Cortical thymic epithelial cells (cTECs) facilitate positive selection of developing thymocytes whereas medullary thymic epithelial cells (mTECs) facilitate the dele

Published
2015

5. Partially Penetrant Postnatal Lethality of an Epithelial Specific MicroRNA in a Mouse Knockout

Author

McManus, Thomas, Farmer, DT, Shariat, N, Park, CY, Liu, HJ, Mavropoulos, A, and McManus, MT

Abstract

MicroRNAs are small noncoding RNAs thought to have pivotal roles in numerous diseases and developmental processes. However, a growing body of literature indicates that in vivo elimination of these tiny RNAs usually has little to no observable consequence,

Published
2013

7. Differing spatial patterns of the urban heat exposure of elderly populations in two megacities identifies alternate adaptation strategies

Author

Park, CY, Park, CY, Thorne, JH, Hashimoto, S, Lee, DK, Takahashi, K, Park, CY, Park, CY, Thorne, JH, Hashimoto, S, Lee, DK, and Takahashi, K

Abstract

Mapping the elderly population exposure to heat hazard in urban areas is important to inform adaptation strategies for increasingly-deadly urban heat under climate change. However, fine-scale mapping is lacking, because global climate change projections have not previously been integrated with urban heat island effects especially with urban three-dimensional characteristics for within-city heat risk analyses. This study compared the spatial patterns of deadly heat exposure for elderly populations in two East Asian megacities, Seoul and Tokyo, using current climate (2006–2015) and two future periods (2040s and 2090s). We integrated global warming projections (the Shared Socioeconomic Pathway 5 based on Representative Concentration Pathway 8.5) with local urban characteristics and demographics. We found that, for the historical period, the overall hotspots of elderly population exposure to urban heat was larger in Tokyo because of relatively higher maximum air temperatures and lack of green spaces, whereas in the future periods, Seoul will have larger hotspots because the elderly population density will have increased. About 20% of the area in Seoul and 0.3–1% of Tokyo will be hotpots in the 2040s, and the size of these hotspots increases to 25–26% and 2–3%, respectively, in the 2090s. The spatial patterns of hotspots identify different types of priority areas and suggest that alternative adaptation strategies for two cities are appropriate. The approach introduced here will be useful for identifying sustainable thermal environments in other cities with high density elderly population and severe heat hazard.

Published
2021

8. K-EmoCon, a multimodal sensor dataset for continuous emotion recognition in naturalistic conversations.

Author

Park, CY, Cha, N, Kang, S, Kim, A, Khandoker, AH, Hadjileontiadis, L, Oh, A, Jeong, Y, Lee, U, Park, CY, Cha, N, Kang, S, Kim, A, Khandoker, AH, Hadjileontiadis, L, Oh, A, Jeong, Y, and Lee, U

Abstract

Recognizing emotions during social interactions has many potential applications with the popularization of low-cost mobile sensors, but a challenge remains with the lack of naturalistic affective interaction data. Most existing emotion datasets do not support studying idiosyncratic emotions arising in the wild as they were collected in constrained environments. Therefore, studying emotions in the context of social interactions requires a novel dataset, and K-EmoCon is such a multimodal dataset with comprehensive annotations of continuous emotions during naturalistic conversations. The dataset contains multimodal measurements, including audiovisual recordings, EEG, and peripheral physiological signals, acquired with off-the-shelf devices from 16 sessions of approximately 10-minute long paired debates on a social issue. Distinct from previous datasets, it includes emotion annotations from all three available perspectives: self, debate partner, and external observers. Raters annotated emotional displays at intervals of every 5 seconds while viewing the debate footage, in terms of arousal-valence and 18 additional categorical emotions. The resulting K-EmoCon is the first publicly available emotion dataset accommodating the multiperspective assessment of emotions during social interactions.

Published
2020

9. Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy

Author

Perkovic, V., Jardine, M. J., Neal, B., Bompoint, S., Heerspink, H. J. L., Charytan, D. M., Edwards, R., Agarwal, R., Bakris, G., Bull, S., Cannon, C. P., Capuano, G., Chu, P. -L., De Zeeuw, D., Greene, T., Levin, A., Pollock, C., Wheeler, D. C., Yavin, Y., Zhang, H., Zinman, B., Meininger, G., Brenner, B. M., Mahaffey, K. W., Perkovic, V, Mahaffey, Kw, Agarwal, R, Bakris, G, Brenner, Bm, Cannon, Cp, Charytan, Dm, de Zeeuw, D, Greene, T, Jardine, Mj, Heerspink, Hjl, Levin, A, Meininger, G, Neal, B, Pollock, C, Wheeler, Dc, Zhang, H, Zinman, B, Mcguire, Dk, Holman, R, Home, P, Scharfstein, D, Parfrey, P, Shahinfar, S, August, P, Chang, T, Sinha, Ad, Januzzi, J, Kolansky, D, Amerena, J, Hillis, G, Gorelick, P, Kissela, B, Kasner, S, Lindley, R, Fulcher, G, Ounadjela, S, Hufert, K, von Ingersleben, G, Gaglia, J, Harris, R, Hudson, M, Turchin, A, Cheifetz, A, Sheth, S, Feuerstein, J, Cohen, S, Jardine, M, Li, N, Kolesnyk, I, Aizenberg, D, Pecoits-Filho, R, Cherney, D 3rd, Obrador, G, Chertow, G, Hawley, C, Ji, L, Wada, T, Jha, V, Lim, Sk, Lim-Abrahan, Ma, Santos, F, Chae, Dw, Hwang, Sj, Vazelov, E, Rychlík, I, Hadjadj, S, Krane, V, Rosivall, L, De Nicola, L, Dreval, A, Nowicki, M, Schiller, A, Distiller, L, Górriz, Jl, Kolesnyk, M, Morren, F, Goykhman, S, David, C, Yost, L, Wang, H, Hettiarachchi, M, Thimmaiah, R, Koppolu, D, George, S, Schmidt, M, Ignjatovic, J, Chapin, L, Travis, K, Destree, M, Sood, V, Coffee, L, De Brouwer, K, Zaviriukha, V, Starzec, A, Koizumi, M, Lin, G, Chen, E, Lin, P, Leia, C, Mascaro, D, Amigo, A, Limos, A, Abrahamsen, I, Jaffer, S, Ahuad Guerrero RA, Albisu, Jp, Alvarisqueta, A, Bartolacci, I, Berli, Ma, Bordonava, A, Calella, P, Cantero, Mc, Cartasegna, Lr, Cercos, E, Coloma, Gc, Colombo, H, Commendatore, V, Cuadrado, J, Cuneo, Ca, Cusumano, Am, Douthat, Wg, Dran, Rd, Farias, E, Fernandez, Mf, Finkelstein, H, Fragale, G, Fretes, Jo, Garcia, Nh, Gastaldi, A, Gelersztein, E, Glenny, Ja, Gonzalez, Jp, Gonzalez Colaso PDC, Goycoa, C, Greloni, Gc, Guinsburg, A, Hermida, S, Juncos, Li, Klyver, Mi, Kraft, F, Krynski, F, Lanchiotti, Pv, Leon de la Fuente RA, Marchetta, N, Mele, P, Nicolai, S, Novoa, Pa, Orio, Si, Otreras, F, Oviedo, A, Raffaele, P, Resk, Jh, Rista, L, Rodriguez Papini, N, Sala, J, Santos, Jc, Schiavi, Lb, Sessa, H, Smith Casabella, T, Ulla, Mr, Valdez, M, Vallejos, A, Villarino, A, Visco, Ve, Wassermann, A, Zaidman, Cj, Cheung, Nw, Droste, C, Fraser, I, Johnson, D, Mah, Pm, Nicholls, K, Packham, D, Proietto, J, Roberts, A, Roger, S, Tsang, V, Raduan, Ra, Alves da Costa FA, Amodeo, C, Andreotti Turatti LA, Bregman, R, Camelo Sanches FC, Canani, Lh, Chacra, Ar, Cunha Borges JL, Cunha Vêncio SA, da Silva Franco RJ, D'Avila, D, de Souza Portes, E, de Souza, P, Deboni, Lm, Filho, Ff, Geloneze Neto, B, Gomes, M, Kohara, Sk, Keitel, E, Kerr Saraiva JF, Kurtz Lisboa HR, de Carvalho Contieri FL, Milagres, R, Montenegro Junior, R, Moreira de Brito, C, Nazzer Hissa, M, Nazario Sabbag ÂR, Noronha, I, Panarotto, D, Pecoits Filho, R, Pereira, Ma, Saporito, W, Scotton, As, Schuch, T, Simões de Almeida, R, Slompo Ramos, C, Soares Felício, J, Thomé, F, Tibes Hachmann JC, Yamada, S, Yoiti Hayashida, C, Zanata Petry TB, Zanella, Mt, Andreeva, V, Angelova, A, Dimitrov, S, Genadieva, V, Genova-Hristova, G, Hristozov, K, Kamenov, Z, Koundurdjiev, A, Lozanov, L, Margaritov, V, Nonchev, B, Rangelov, R, Shinkov, A, Temelkova, M, Velichkova, E, Yakov, A, Aggarwal, N, Aronson, R, Bajaj, H, Chouinard, G, Conway, J, Cournoyer, S, Daroza, G, De Serres, S, Dubé, F, Goldenberg, R, Gupta, A, Gupta, M, Henein, S, Khandwala, H, Leiter, L, Madore, F, Mcmahon, A, Muirhead, N, Pichette, V, Rabasa-Lhoret, R, Steele, A, Tangri, N, Torshizi, A, Woo, V, Zalunardo, N, Fernández Montenegro MA, Godoy Jorquera JG, Medina Fariña, M, Saavedra Gajardo, V, Vejar, M, Chen, N, Chen, Q, Gan, S, Kong, Y, Li, D, Li, W, Li, X, Lin, H, Liu, J, Lu, W, Mao, H, Ren, Y, Song, W, Sun, J, Sun, L, Tu, P, Wang, G, Yang, J, Yin, A, Yu, X, Zhao, M, Zheng, H, Accini Mendoza JL, Arcos, E, Avendano, J, Diaz Ruiz JEA, Garcia Ortiz LH, Gonzalez, A, Hernandez Triana, E, Higuera, Jd, Malaver, N, Molina de Salazar DI, Rosero, R, Terront Lozano MA, Valderrama Cometa, L, Valenzuela, A, Vargas Alonso RD, Villegas, I, Yupanqui, H, Bartaskova, D, Barton, P, Belobradkova, J, Dohnalova, L, Drasnar, T, Ferkl, R, Halciakova, K, Klokocnikova, V, Kovar, R, Lastuvka, J, Lukac, M, Pesickova, S, Peterka, K, Pumprla, J, Rychlik, I, Saudek, F, Tesar, V, Valis, M, Weiner, P, Zemek, S, Alamartine, E, Borot, S, Cariou, B, Dussol, B, Fauvel, Jp, Gourdy, P, Klein, A, Le Meur, Y, Penfornis, A, Roussel, R, Saulnier, Pj, Thervet, E, Zaoui, P, Burst, V, Faghih, M, Faulmann, G, Haller, H, Jerwan-Keim, R, Maxeiner, S, Paschen, B, Plassmann, G, Rose, L, Gonzalez Orellana RA, Haase, Fp, Moreira Diaz JP, Ramirez Roca LA, Sánchez Arenales JA, Sanchez Polo JV, Turcios Juarez, E, Csecsei, G, Csiky, B, Danos, P, Deak, L, Dudas, M, Harcsa, E, Keltai, K, Keresztesi, S, Kiss, K, Konyves, L, Major, L, Mileder, M, Molnar, M, Mucsi, J, Oroszlan, T, Ory, I, Paragh, G, Peterfai, E, Petro, G, Revesz, K, Takacs, R, Vangel, S, Vasas, S, Zsom, M, Abraham, O, Bhushan, Rs, Deepak, D, Edwin, Fm, Gopalakrishnan, N, Gracious, N, Hansraj, A, Jain, D, Keshavamurthy, Cb, Khullar, D, Manisha, S, Peringat, J, Prasad, N, Satyanarayana, Rk, Sreedhar, R, Sreelatha, M, Sudhakar, B, Vyasam, Rc, Bonadonna, R, Castellino, P, Ceriello, A, Chiovato, L, De Cosmo, S, Derosa, G, Di Carlo, A, Di Cianni, G, Frascà, G, Fuiano, G, Gambaro, G, Garibotto, G, Giorda, C, Malberti, F, Mandreoli, M, Mannucci, E, Orsi, E, Piatti, P, Santoro, D, Sasso, Fc, Serviddio, G, Stella, A, Trevisan, R, Veronelli, Am, Zanoli, L, Akiyama, H, Aoki, H, Asano, A, Iitsuka, T, Kajiyama, S, Kashine, S, Kawada, T, Kodera, T, Kono, H, Koyama, K, Kumeda, Y, Miyauchi, S, Mizuyama, K, Niiya, T, Oishi, H, Ota, S, Sakakibara, T, Takai, M, Tomonaga, O, Tsujimoto, M, Wakasugi, M, Wakida, Y, Watanabe, T, Yamada, M, Yanagida, K, Yanase, T, Yumita, W, Gaupsiene, E, Kozloviene, D, Navickas, A, Urbanaviciene, E, Abdul Ghani, R, Abdul Kadir, K, Ali, N, Che Yusof MD, Gan, Cl, Ismail, M, Kong, Wy, Lam, Sw, Lee, Ly, Loh, Cl, Manocha, Ab, Ng, Ks, Nik Ahmad NNF, Ratnasingam, V, Bin Shudim SS, Vengadasalam, P, Abraira Munoz LD, Salazar, Ma, Cruz, Jb, Soto, Mb, Ramos, Jc, Wong, Ac, Correa Rotter JR, Diaz Escalante, T, Enriquez Sosa FE, Flores Lozano, F, Flota Cervera LF, Frenk Baron, P, Garcia Ballesteros, C, Gomez Rangel JD, Herrera Jimenez LE, Irizar Santana SS, Jimenez Florez, F, Laviada Molina, H, Luna Ceballos RI, Martin Del Camp Blanco, B, Morales Franco, G, Moreno Loza OT, Mustieles Rocha, C, Obrador Vera, G, Orozco Castellanos, R, Peralta Calcaneo, J, Reyes Rosano MA, Rodriguez Pattzi, H, Rosas Guzman, J, Rucker Joerg IE, Saaveddra Sanchez SB, Sanchez Mijangos JH, Serrano Sanson, P, Tamayo, Y Orozco JA, Tellez Chavez, E, Valdes Depeda, A, Venegas Carrillo, L, Villagordoa Mesa, J, Zamarripa Escobedo, R, Baker, J, Noonan, P, Scott, R, Walker, R, Watson, E, Williams, M, Young, S, Abejuela, Z, Agra, J, Aquitania, G, Caringal, C, Comia, Rs, Delos Santos, L, Gomez, O, Jimeno, C, Tan, G, Tolentino, M, Yao, C, Yap, Ye, Ygpuara, Mdl, Bijata-Bronisz, R, Hotlos, L, Januszewicz, A, Kaczmarek, B, Kaminska, A, Lazuka, L, Madej, A, Mazur, S, Mlodawska-Choluj, D, Orlowska-Kowalik, G, Popenda, G, Rewerska, B, Sowinski, D, Angelescu, Lm, Anghel, V, Avram, Ri, Busegeanu, Mm, Cif, A, Cosma, D, Crisan, C, Demian, Ld, Ferariu, Ie, Halmagyi, I, Hancu, N, Munteanu, M, Negru, D, Onaca, Ag, Petrica, L, Popa, Ar, Ranetti, Ae, Serafinceanu, C, Toarba, C, Agafyina, A, Barbarash, O, Barysheva, O, Chizhov, D, Dobronravov, V, Glinkina, I, Grineva, E, Khirmanov, V, Kolmakova, E, Koroleva, T, Kvitkova, L, Marasaev, V, Mkrtumyan, A, Morugova, T, Nagibovich, G, Nagibovich, O, Nedogoda, S, Osipova, I, Raskina, T, Samoylova, Y, Sazonova, O, Shamkhalova, M, Shutemova, E, Shwartz, Y, Uriasyev, O, Vorobyev, S, Zateyshchikova, A, Zateyshshikov, D, Zykova, T, Antic, S, Djordjevic, M, Kendereski, A, Lalic, K, Lalic, N, Popovic-Radinovic, V, Babikova, J, Benusova, O, Buganova, I, Culak, J, Dzupina, A, Dzuponova, J, Fulop, P, Ilavska, A, Martinka, E, Ochodnicka, Z, Pella, D, Smatanova, I, Ahmed, F, Badat, A, Breedt, J, Govender, V, Govender, R, Joshi, M, Jurgens, J, Latiff, G, Lombard, L, Mookadam, M, Ngcakani, N, Nortje, H, Oosthuizen, H, Pillay-Ramaya, L, Prozesky, H, Reddy, J, Rheeder, P, Seeber, M, Cho, Ym, Jeong, Ik, Kim, Sg, Kim, Yh, Kwon, Hs, Kwon, Mj, Lee, Bw, Lee, J, Lee, Mk, Nam, Ms, Oh, Kh, Park, Cy, Park, Sh, Yoon, Kh, Alvarez Garcia, P, Asmarats Mercadal, L, Barrios, C, Cereto Castro, F, Cigarran Guldris, S, Dominquez Lopez, M, Egido de Los Rios, J, Fernandez Fresnedo, G, Galan Serrano, A, Garcia, I, Gonzalez Martinez FJ, Jodar Gimeno JE, Muñoz Lopez Mendoza, M, Malek Marin, T, Morales Portillo, C, Munar Vila MA, Muñoz Torres, M, Nieto Iglesias, J, Pantoja Perez, J, Perez Vera, M, Portoles Perez JM, Quesada Simón MA, Simo Canonge, R, Soto Gonzalez, A, Terns Riera, M, Tinahones Madueno FJ, Plaza, Mv, Chang, Ct, Chuang, Lm, Hsia, Tl, Hsieh, Ch, Lin, Cc, Lu, Yc, Sheu, Wh, Barna, O, Bilyk, Sd, Botsyurko, V, Dudar, I, Fushtey, I, Godlevska, O, Golovchenko, O, Gyrina, O, Kazmirchuk, A, Komisarenko, I, Korzh, O, Kravchun, N, Legun, O, Mankovskyy, B, Martynyuk, L, Mostovoy, Y, Pashkovska, N, Pererva, L, Pertseva, T, Samoylov, O, Smirnov, I, Svyshchenko, Y, Tomashkevych, H, Topchii, I, Tryshchuk, N, Tseluyko, V, Vizir, V, Vlasenko, M, Zlova, T, Zub, L, Abusnana, S, Railey, M, Abouglila, K, Ainsworth, P, Ali, Z, Arutchelvam, V, Barnard, M, Bellary, S, Davies, E, Davies, M, Davies, S, Dawson, A, El Kossi, M, English, P, Fraser, D, Gnudi, L, Gunstone, A, Hall, T, Hanif, W, Jackson, A, Johnson, A, Joseph, F, Krishnan, S, Kumwenda, M, Macdougall, I, Nixon, P, O'Hare, J, Philip, S, Ramtoola, S, Saxena, M, Sennik, D, Simon, G, Singh, B, Stephens, J, Strzelecka, A, Symonds, R, Turner, W, Wahba, M, Wakeling, J, Wheeler, D, Winocour, P, Abdallah, J, Abdullah, R, Abramowitz, M, Acosta, I, Aiello, J, Akright, L, Akyea-Djamson, A, Alappan, R, Alicic, R, Al-Karadsheh, A, Allison, Dc, Arauz-Pacheco, C, Arfeen, S, Arif, A, Arvind, M, Atray, N, Awad, A, Barnhill, P, Barranco, E, Barrera, C, Beacom, M, Behara, V, Belo, D, Bentley-Lewis, R, Berenguer, R, Bermudez, L, Bernardo, M, Biscoveanu, M, Bowman-Stroud, C, Brandon, D, Brusco, O, Busch, R, Canaan, Y, Chilito, A, Christensen, T, Christiano, C, Christofides, E, Chuateco, C, Cohen, K, Cohen, R, Cohen-Stein, D, Cook, C, Coyne, D, Daboul, N, Darwish, R, Daswani, A, Deck, K, Desouza, C, Dev, D, Dhillon, M, Dua, S, Eder, F, Elosegui, Am, El-Shahawy, M, Ervin, J, Esquenazi, A, Evans, J, Fishbane, S, Frias, J, Galindo-Ramos, E, Galphin, C, Ghazi, A, Gonzalez, E, Gorson, D, Gowda, A, Greco, B, Grubb, S, Gulati, R, Hammoud, J, Handelsman, S, Hartman, I, Hershon, K, Hiser, D, Hon, G, Jacob, R, Jaime, M, Jamal, A, Kaupke, C, Keightley, G, Kern, E, Khanna, R, Khitan, Z, Kim, S, Kopyt, N, Kovesdy, C, Krishna, G, Kropp, J, Kumar, A, Kumar, J, Kumar, N, Kusnir, J, Lane, W, Lawrence, M, Lehrner, L, Lentz, J, Levinson, D, Lewis, D, Liss, K, Maddux, A, Maheshwari, H, Mandayam, S, Marar, I, Mehta, B, Middleton, J, Mordujovich, J, Moreda, R, Moustafa, M, Mujica 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Subjects
Aged, Canagliflozin, Cardiovascular Diseases, Creatinine, Diabetes Mellitus, Type 2, Diabetic Nephropathies, Double-Blind Method, Female, Follow-Up Studies, Glomerular Filtration Rate, Humans, Kidney Failure, Chronic, Male, Middle Aged, Sodium-Glucose Transporter 2 Inhibitors, Type 2 diabetes, 030204 cardiovascular system & hematology, Diabetic nephropathy, Kidney Failure, chemistry.chemical_compound, 0302 clinical medicine, 030212 general & internal medicine, 03.02. Klinikai orvostan, Dapagliflozin, Chronic, 11 Medical and Health Sciences, EMPAGLIFLOZIN, General Medicine, Life Sciences & Biomedicine, Type 2, medicine.drug, medicine.medical_specialty, Nephropathy, 03 medical and health sciences, Medicine, General & Internal, Internal medicine, Diabetes mellitus, General & Internal Medicine, CREDENCE Trial Investigators, medicine, Diabetes Mellitus, Science & Technology, business.industry, urogenital system, diabetic nephropathy, Type 2 Diabetes Mellitus, KIDNEY-DISEASE, medicine.disease, chemistry, business, Kidney disease
Abstract

BACKGROUND: Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium-glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS: In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to 300 to 5000) and were treated with renin-angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of

Published
2019

10. The Canagliflozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) Study Rationale, Design, and Baseline Characteristics

Author

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Yoiti Hayashida C, Yoon KH, Young S, Yu X, Yumita W, Yupanqui H, Zaidman CJ, Zamarripa Escobedo R, Zanata Petry TB, Zanella MT, Zaoui P, Zavaroni I, Zemek S, Zhang H, Zhao M, Zheng H, Zlova T, Zsom M, Zykova T., Groningen Kidney Center (GKC), Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), Abdallah, J, Abdul Ghani, R, Abdul Kadir, K, Abdullah, R, Abejuela, Z, Abraham, O, Abramowitz, M, Abusnana, S, Accini Mendoza, Jl, Acosta, I, Agafyina, A, Aggarwal, N, Ahmed, F, Ahuad Guerrero, Ra, Aiello, J, Ainsworth, P, Aizenberg, D, Akiyama, H, Akright, L, Akyea-Djamson, A, Alamartine, E, Alappan, R, Ali, N, Ali, Z, Alicic, R, Al-Karadsheh, A, Alpizar Salazar, M, Alvarez Garcia, P, Alvarisqueta, A, Amodeo, C, Andreeva, V, Andreotti Turatti, La, Angelescu, Lm, Angelova, A, Anghel, V, Antic, S, Aoki, H, Aquitania, G, Arauz-Pacheco, C, Arce-Nunez, E, Arcos Palma, Eg, Arfeen, S, Arif, A, Aronson, R, Arutchelvam, V, Asano, A, Atray, N, Avram, Ri, Awad, A, Baas 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Borges, Jl, Cunha Vêncio, Sa, Cusumano, Am, da Silva Franco, Rj, Daboul, N, Danos, P, Daroza, G, Davies, E, Davies, M, Davies, S, Dawson, A, De Cosmo, S, De Nicola, L, De Serres, S, de Souza Portes, E, Deak, L, Deck, K, Deepak, D, Derosa, G, Desouza, C, Dev, D, Dhillon, M, DI CARLO, Alfonso, Di Cianni, G, Diaz Escalante, T, Dimitrov, S, Distiller, L, Djordjevic, M, Dobronravov, V, Dohnalova, L, Dominguez Lopez, M, Douthat, Wg, Dran, Rd, Drasnar, T, Dreval, A, Droste, C, Dua, S, Dube, F, Dudar, I, Dudas, M, Dussol, B, Dzupina, A, Eder, F, Egido de Los Rios, J, El Kossi, M, El-Shahawy, M, English, P, Enriquez Sosa, Fe, Ervin, J, Esquenazi, A, Evans, J, Faghih, M, Farias, E, Faulmann, G, Fauvel, Jp, Ferariu, Ie, Fernandez, Mf, Fernandez Fresnedo, G, Fernandez Montenegro, Ma, Finkelstein, H, Flores Lozano, F, Flota Cervera, L, Fraige Filho, F, Fraser, D, Frenk Baron, P, Fretes, Jo, Frias, J, Fuiano, G, Fulop, P, Fushtey, I, Galan Serrano, A, Galphin, C, Gan, S, Gan, Cl, Garcia, Nh, Garcia, I, Garcia Ballesteros, C, Garcia Ortiz, Lh, Garrido, N, Gastaldi, A, Gelersztein, E, Geloneze Neto, B, Genadieva, V, Genova-Hristova, G, Genovese, S, Ghazi, A, Giorda, C, Glenny, Ja, Glinkina, I, Godlevska, O, Godoy Jorquera, Jg, Goldenberg, R, Golovchenko, O, Gomes Bastos, M, Gomez, O, Gomez Rangel, Jd, Gonzalez, E, Gonzalez Dorado, A, Gonzalez Martinez, Fj, Gonzalez Orellana, Ra, Gopalakrishnan, N, Gorriz, Jl, Gorson, D, Govender, V, Gracious, N, Greco, B, Gregar, R, Greloni, Gc, Grineva, E, Guinsburg, A, Gulati, R, Gunstone, A, Gupta, A, Gupta, M, Gyrina, O, Hadjadj, S, Halciakova, K, Hall, T, Haller, H, Halmagyi, I, Hammoud, J, Hancu, N, Hanif, W, Hansraj, A, Hawley, C, Henein, S, Hermida, S, Hernandez Triana, E, Herrera Jimenez, Le, Hershon, K, Higuera Cobos, Jd, Hiser, D, Hocking, S, Hon, G, Hristozov, K, Hsieh, Ch, Hura, C, Hwang, Sj, Ilavska, A, Irizar Santana, S, Ismail, M, Jackson, A, Jain, D, Jamal, A, Januszewicz, A, Jeong, Ik, Jha, V, Jimenez Flores, F, Jodar Gimeno, Je, Johnson, A, Joseph, F, Joshi, M, Juncos, Li, Jurgens, J, Kajiyama, S, Kaminska, A, Kashine, S, Kaupke, C, Kawada, T, Keiko Kohara, S, Keitel, E, Keltai, K, Kendereski, A, Keresztesi, S, Kern, E, Kerr Saraiva, Jf, Keshavamurthy, Cb, Khandwala, H, Khanna, R, Khitan, Z, Khullar, D, Kim, Sg, Kim, Yh, Kim, S, Kiss, K, Klein, A, Klyver, Mi, Kodera, T, Kolesnyk, M, Kolmakova, E, Komisarenko, I, Kong, Y, Kong, Wy, Kono, H, Konyves, L, Kopyt, N, Korzh, O, Kovar, R, Kovesdy, C, Koyama, K, Kozloviene, D, Kraft, F, Krane, V, Kravchun, N, Krishna, G, Krishnan, S, Kropp, Jj, Kumar, A, Kumar, J, Kumeda, Y, Kumwenda, M, Kurtz Lisboa, Hr, Kvitkova, L, Kwon, H, Kwon, Mj, Lalic, K, Lalic, N, Lanchiotti, Pv, Lastuvka, J, Laviada Molina, H, Lawrence, M, Le Meur, Y, Lee, Ly, Lee, Bw, Lee, J, Lee, Mk, Legun, O, Leiter, L, Lentz, J, Leon de la Fuente, Ra, Levin, A, Lewis, D, Li, D, Li, W, Li, X, Lim, Sk, Lin, H, Lin, Cc, Liss, K, Liu, J, Loh, Cl, Lombard, L, Lopez Mendoza, M, Lopez Tarabay, C, Lorenzoni d'avila, Do, Loss de Carvalho Contieri, F, Lu, W, Lu, Yc, Luna Ceballos, R, M., Edwin F, Macdougall, I, Macedo de Souza, Pa, Madej, A, Madore, F, Magalhaes Montenegro Junior, R, Mah, Pm, Maheshwari, H, Major, L, Malberti, F, Malek Marin, T, Mandayam, S, Mandreoli, M, Manisha, S, Mankovskyy, B, Mannucci, E, Manocha, Ab, Mao, H, Marar, I, Marasaev, V, Marchetta, N, Martin Del Campo Blanco, B, Martinka, E, Martynyuk, L, Maxeiner, S, Mazur, S, Mcmahon, A, Medina Farina, M, Mehta, B, Middleton, J, Mileder, M, Miyauchi, S, Mizuyama, K, Mkrtumyan, A, Mlodawska-Choluj, D, Molina de Salazar, Di, Molnar, M, Mookadam, M, Morales Franco, G, Morales Portillo, C, Mordujovich, J, Moreira de Brito, C, Moreira Diaz, Jp, Moreno Loza, Ot, Mostovoy, Y, Moustafa, M, Muirhead, N, Mujica Trenche, S, Munar Vila, Ma, Munoz Torres, M, Munteanu, M, Mustieles Rocha, C, Nagibovich, G, Nam, M, Narvarte, J, Nasser Hissa, M, Navickas, A, Nazario Sabbag, Âr, Nedogoda, S, Negru, D, Newman, G, Ng, K, Ngcakani, N, Nicholls, K, Nicol, P, Nieto Iglesias, J, Niiya, T, Nik Ahmad, Nnf, Nisnisan, J, Nonchev, B, Noronha, Il, Nortje, H, Nossuli, Ak, Nowicki, M, Obialo, C, Obrador Vera, G, Ochodnicka, Z, Oh, Kh, Oishi, H, Olelewe, S, Oliver, M, Oosthuizen, H, Orio, Si, Orlowska-Kowalik, G, Oroszlan, T, Orozco Castellanos, R, Orsi, E, Ory, I, O'Shaughnessy, A, Ota, S, Otreras, F, Oviedo, A, Packham, D, Padron, J, Panarotto, D, Pankhaniya, R, Pantoja Perez, J, Paragh, G, Park, Cy, Park, Sh, Pashkovska, N, Patel, D, Patel, G, Pavon, H, Pei, D, Pella, D, Penfornis, A, Peralta Calcaneo, J, Pereira, Ma, Pererva, L, Perez Vera, M, Peringat, J, Pertseva, T, Pesickova, S, Peterfai, E, Peterka, K, Petrica, L, Petro, G, Pettis, K, Pharr, W, Philip, S, Phillips, A, Piatti, P, Pichette, V, Pontiroli, A, Popa, Ar, Popenda, G, Popovic-Radinovic, V, Portoles Perez, Jm, Prasad, N, Proietto, J, Prozesky, H, Pumprla, J, Purighalla, R, Quesada Simon, Ma, Quesada-Suarez, L, Rabasa-Lhoret, R, Ramirez Roca, La, Ramtoola, S, Ranetti, Ae, Rangelov, R, Ranjan, R, Raskina, T, Rastogi, S, Ratnasingam, V, Reddy, J, Ren, Y, Resk, Jh, Rewerska, B, Reyes Rosano, Ma, Rich, L, Rista, L, Roberts, A, Robinson, M, Rodelo, J, Rodriguez, H, Rodriguez Papini, N, Roger, S, Rosas, S, Rosas Guzman, J, Rosivall, L, Roussel, R, Rucker Joerg, Ie, Rychlik, I, Saavedra Gajardo, V, Saavedra Sanchez, Sb, Sala, J, Samoylov, O, Samoylova, Y, Sanchez Arenales, Ja, Sanchez Mijangos, Jh, Sanchez Polo, Jv, Sankaram, R, Santoro, D, Santos, Jc, Santos, F, Sarin, R, Saudek, F, Saumell, F, Saxena, M, Sazonova, O, Schiavi, Lb, Schiller, A, Schuch, T, Scott, R, Scott, D, Seeber, M, Seiji Yamada, S, Sekkarie, M, Sensenbrenner, J, Serafinceanu, C, Serrano Sanson, P, Sessa, H, Shakeel, M, Shamkhalova, M, Shanik, M, Shaw, S, Sheu, Wh, Shinkov, A, Shutemova, E, Silva Pecoits Filho, Rf, Simo Canonge, R, Simoes de Almeida, R, Simon, G, Singh, B, Slompo Ramos, C, Smatanova, I, Smirnov, I, Smith, S, Smith Casabella, T, Soares Felicio, J, Soler Romeo, Mj, Solomon, R, Song, W, Soto Gonzalez, A, Sowinski, D, Sprague, A, Sree Bhushan, R, Sreedhar, R, Sreelatha, M, Steele, A, Spedding, Stephen John, Strzelecka, A, Suchinda, P, Sudhakar, B, Sun, J, Sun, L, Surampudi, P, Sussman, S, Svyshchenko, Y, Symonds, R, Szlachcic, Y, Takacs, R, Takai, M, Tamayo Y., Orozco J, Tan, G, Tellez Chavez, E, Temelkova, M, Terns Riera, M, Terront Lozano, Ma, Tesar, V, Thompson, M, Tibes Hachmann, Jc, Tinahones Madueno, Fj, Tolentino, M, Tomashkevych, H, Tomonaga, O, Topchii, I, Torshizi, A, Trespalacios, F, Trevisan, R, Trueba, P, Tryshchuk, N, Tseluyko, V, Tsujimoto, M, Tu, P, Turcios Juarez, E, Turner, W, Twahirwa, M, Ulla, Mr, Updegrove, J, Urbanaviciene, E, Valderrama Cometa, L, Valdes Cepeda, A, Valenzuela, A, Valis, M, Vallejos, A, Vangel, S, Vannorsdall, M, Vargas Alonso, Rd, Varghese, F, Vasas, S, Vazelov, E, Vejar, M, Velasquez-Mieyer, P, Velichkova, E, Velo, M, Venegas Carrillo, L, Vengadasalam, P, Ventrapragada, S, Villagordoa Mesa, J, Villarino, Aa, Villegas, I, Visco, Ve, Vizir, V, Vlasenko, M, Vyasam, Rc, Wada, T, Wadud, K, Wahba, M, Wakasugi, M, Wakeling, J, Wakida, Y, Walker, JOHN RICHARD, Wang, G, Warren, M, Wassermann, A, Watanabe, T, Watson, E, Watts, R, Weiner, P, Weiner, D, Welsh, J, Wheeler, D, Williams, M, Winocour, P, Woo, V, Yamada, M, Yanagida, K, Yanase, T, Yang, J, Yao, C, Yap, Ye, Ygpuara, Mdl, Yin, A, Yoiti Hayashida, C, Yoon, Kh, Young, S, Yu, X, Yumita, W, Yupanqui, H, Zaidman, Cj, Zamarripa Escobedo, R, Zanata Petry, Tb, Zanella, Mt, Zaoui, P, Zavaroni, I, Zemek, S, Zhang, H, Zhao, M, Zheng, H, Zlova, T, Zsom, M, and Zykova, T.

Subjects
medicine.medical_specialty, ALBUMINURIA, Urology, Renal function, 030209 endocrinology & metabolism, PROGRESSION, Type 2 diabetes, Diabetic nephropathy, 030204 cardiovascular system & hematology, GLOMERULAR-FILTRATION-RATE, CARDIOVASCULAR OUTCOMES, Nephropathy, 03 medical and health sciences, 0302 clinical medicine, Diabetes mellitus, Chronic kidney disease, medicine, 03.02. Klinikai orvostan, Renal outcome, Canagliflozin, Science & Technology, ATRIAL-NATRIURETIC-PEPTIDE, IRBESARTAN, GFR DECLINE, business.industry, 1103 Clinical Sciences, KIDNEY-DISEASE, Urology & Nephrology, medicine.disease, Renal outcomes, Nephrology, COLLABORATIVE METAANALYSIS, Albuminuria, Original Report: Patient-Oriented, Translational Research, LOSARTAN, medicine.symptom, business, Life Sciences & Biomedicine, CREDENCE study investigators, medicine.drug, Kidney disease
Abstract

Background: People with diabetes and kidney disease have a high risk of cardiovascular events and progression of kidney disease. Sodium glucose co-transporter 2 inhibitors lower plasma glucose by reducing the uptake of filtered glucose in the kidney tubule, leading to increased urinary glucose excretion. They have been repeatedly shown to induce modest natriuresis and reduce HbA1c, blood pressure, weight, and albuminuria in patients with type 2 diabetes. However, the effects of these agents on kidney and cardiovascular events have not been extensively studied in patients with type 2 diabetes and established kidney disease. Methods: The Canagliflozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) trial aims to compare the efficacy and safety of canagliflozin ­versus placebo at preventing clinically important kidney and cardiovascular outcomes in patients with diabetes and established kidney disease. CREDENCE is a randomized, double-blind, event-driven, placebo-controlled trial set in in 34 countries with a projected duration of ∼5.5 years and enrolling 4,401 adults with type 2 diabetes, estimated glomerular filtration rate ≥30 to 2, and albuminuria (urinary albumin:creatinine ratio >300 to ≤5,000 mg/g). The study has 90% power to detect a 20% reduction in the risk of the primary outcome (α = 0.05), the composite of end-stage kidney disease, doubling of serum creatinine, and renal or cardiovascular death. Conclusion: CREDENCE will provide definitive evidence about the effects of canagliflozin on renal (and cardiovascular) outcomes in patients with type 2 diabetes and established kidney disease. Trial Registration: EudraCT number: 2013-004494-28; ClinicalTrials.gov identifier: NCT02065791.

Published
2017

11. Dose-related effect of urinary cotinine levels on pulmonary function among Korean women

Author

Jang Tw, Park Cy, Jun-Pyo Myong, Koo Jw, Kim Hr, Kim Ky, and Hye-Eun Lee

Subjects
Adult, Pulmonary and Respiratory Medicine, Spirometry, Nicotine, medicine.medical_specialty, Urinary system, Vital Capacity, Population, Pulmonary function testing, Decile, chemistry.chemical_compound, FEV1/FVC ratio, Forced Expiratory Volume, Surveys and Questionnaires, Internal medicine, Republic of Korea, Humans, Medicine, Nicotinic Agonists, Information bias, Cotinine, education, Lung, Aged, education.field_of_study, Dose-Response Relationship, Drug, medicine.diagnostic_test, business.industry, Smoking, Middle Aged, Health Surveys, Respiratory Function Tests, Cross-Sectional Studies, Infectious Diseases, chemistry, Female, business, Biomarkers
Abstract

SETTING Country-wide general population in South Korea. BACKGROUND The dose-response relationship between smoking and pulmonary function in women may have been significantly over-estimated by studies that employed a self-reporting questionnaire. OBJECTIVE To evaluate whether this relationship was still observed among Korean women when smoking levels were determined by urinary cotinine measurements. DESIGN A total of 4584 Korean women from the spirometry data set of the Korean National Health and Nutrition Examination Surveys IV and V (2008-2010) were included. Analysis of covariance was performed to estimate the dose-related effect of urinary cotinine levels on pulmonary function after adjusting for covariates in this country-wide cross-sectional study. RESULTS Compared to urinary cotinine levels (cut-off 50 ng/ml), the false-positive rate of self-reported smoking was 53.2%. After the smokers were divided into deciles, the regression coefficients for percentage forced expiratory volume in 1 second (FEV₁%) and percentage forced expiratory volume/forced volume capacity (FEV₁/FVC) ratio (FEV1/FVC%) were -0.2903 and -0.2680 (%/decile), respectively (both P < 0.001). CONCLUSION It is necessary to use objective methods when determining the smoking status of Korean women. Even after reducing information bias, smoking affected pulmonary function in a dose-dependent manner.

Published
2014

12. Latrophilin receptors: novel bronchodilator targets in asthma

Author

Faiz, A, Donovan, C, Nieuwenhuis, MAE, van den Berge, M, Postma, DS, Yao, S, Park, CY, Hirsch, R, Fredberg, JJ, Tjin, G, Halayko, AJ, Rempel, KL, Ward, JPT, Lee, T, Bosse, Y, Nickle, DC, Obeidat, M, Vonk, JM, Black, JL, Oliver, BG, Krishnan, R, McParland, B, Bourke, JE, Burgess, JK, Faiz, A, Donovan, C, Nieuwenhuis, MAE, van den Berge, M, Postma, DS, Yao, S, Park, CY, Hirsch, R, Fredberg, JJ, Tjin, G, Halayko, AJ, Rempel, KL, Ward, JPT, Lee, T, Bosse, Y, Nickle, DC, Obeidat, M, Vonk, JM, Black, JL, Oliver, BG, Krishnan, R, McParland, B, Bourke, JE, and Burgess, JK

Abstract

BACKGROUND: Asthma affects 300 million people worldwide. In asthma, the major cause of morbidity and mortality is acute airway narrowing, due to airway smooth muscle (ASM) hypercontraction, associated with airway remodelling. However, little is known about the transcriptional differences between healthy and asthmatic ASM cells. OBJECTIVES: To investigate the transcriptional differences between asthmatic and healthy airway smooth muscle cells (ASMC) in culture and investigate the identified targets using in vitro and ex vivo techniques. METHODS: Human asthmatic and healthy ASMC grown in culture were run on Affymetrix_Hugene_1.0_ST microarrays. Identified candidates were confirmed by PCR, and immunohistochemistry. Functional analysis was conducted using in vitro ASMC proliferation, attachment and contraction assays and ex vivo contraction of mouse airways. RESULTS: We suggest a novel role for latrophilin (LPHN) receptors, finding increased expression on ASMC from asthmatics, compared with non-asthmatics in vivo and in vitro, suggesting a role in mediating airway function. A single nucleotide polymorphism in LPHN1 was associated with asthma and with increased LPHN1 expression in lung tissue. When activated, LPHNs regulated ASMC adhesion and proliferation in vitro, and promoted contraction of mouse airways and ASMC. CONCLUSIONS: Given the need for novel inhibitors of airway remodelling and bronchodilators in asthma, the LPHN family may represent promising novel targets for future dual therapeutic intervention.

Published
2017

13. Evaluation of 3D printed PCL/PLGA/β-TCP versus collagen membranes for guided bone regeneration in a beagle implant model

Author

Geunseon Ahn, Won-Soo Yun, Jin-Hyung Shim, Dong-Woo Cho, Kim C, Ji-Hyeon Bae, Dong-Hyuk Lim, Joo-Yun Won, Park Cy, and Jung-Bo Huh

Subjects
Calcium Phosphates, Male, X-ray microtomography, Materials science, Bone Regeneration, Biocompatibility, Polyesters, Biomedical Engineering, Bioengineering, Biocompatible Materials, macromolecular substances, 02 engineering and technology, Bone and Bones, Biomaterials, 03 medical and health sciences, chemistry.chemical_compound, Mice, 0302 clinical medicine, Dogs, Polylactic Acid-Polyglycolic Acid Copolymer, In vivo, Osteogenesis, Tensile Strength, Animals, Lactic Acid, Postoperative Period, Bone regeneration, Cell Proliferation, Tissue Scaffolds, technology, industry, and agriculture, Cell Differentiation, 030206 dentistry, X-Ray Microtomography, Fibroblasts, 021001 nanoscience & nanotechnology, Staining, PLGA, Membrane, chemistry, Polycaprolactone, Bone Substitutes, Printing, Three-Dimensional, NIH 3T3 Cells, Collagen, Stress, Mechanical, 0210 nano-technology, Polyglycolic Acid, Biomedical engineering
Abstract

Here, we compared 3D-printed polycaprolactone/poly(lactic-co-glycolic acid)/β-tricalcium phosphate (PCL/PLGA/β-TCP) membranes with the widely used collagen membranes for guided bone regeneration (GBR) in beagle implant models. For mechanical property comparison in dry and wet conditions and cytocompatibility determination, we analyzed the rate and pattern of cell proliferation of seeded fibroblasts and preosteoblasts using the cell counting kit-8 assay and scanning electron microscopy. Osteogenic differentiation was verified using alizarin red S staining. At 8 weeks following implantation in vivo using beagle dogs, computed tomography and histological analyses were performed after sacrifice. Cell proliferation rates in vitro indicated that early cell attachment was higher in collagen than in PCL/PLGA/β-TCP membranes; however, the difference subsided by day 7. Similar outcomes were found for osteogenic differentiation, with approximately 2.5 times greater staining in collagen than PCL/PLGA/β-TCP, but without significant difference by day 14. In vivo, bone regeneration in the defect area, represented by new bone formation and bone-to-implant contact, paralleled those associated with collagen membranes. However, tensile testing revealed that whereas the PCL/PLGA/β-TCP membrane mechanical properties were conserved in both wet and dry states, the tensile property of collagen was reduced by 99% under wet conditions. Our results demonstrate in vitro and in vivo that PCL/PLGA/β-TCP membranes have similar levels of biocompatibility and bone regeneration as collagen membranes. In particular, considering that GBR is always applied to a wet environment (e.g. blood, saliva), we demonstrated that PCL/PLGA/β-TCP membranes maintained their form more reliably than collagen membranes in a wet setting, confirming their appropriateness as a GBR membrane.

Published
2016

14. In-Situ Synchrotron Radiation Photoemission Spectroscopy Study of the Initial Atomic Layer Deposition of Al2O3 Film on Si(001) Substrate

Author

An Ks, Hwang Hn, Jeong Min Baik, Kim Sh, Lee Ss, Park Cy, Jeon C, Hwang Cc, Lee J, and Bong-Ki Lee

Subjects
Materials science, Photoemission spectroscopy, Binding energy, Biomedical Engineering, Analytical chemistry, Synchrotron radiation, Bioengineering, General Chemistry, Substrate (electronics), Electronic structure, Condensed Matter Physics, Atomic layer deposition, Chemical species, Band bending, General Materials Science
Abstract

In-situ synchrotron radiation photoemission spectroscopy and X-ray photoemission spectroscopy have been used to investigate the initial stages of Al2O3 growth on a Si(001) substrate by atomic layer deposition (ALD). The core level spectra of Si 2p, O 1s, and Al 2p as well as the valence band spectra were measured at every half reaction in the trimethylaluminum (TMA)-H2O ALD process. The line shape changes and binding energy shifts of the core level spectra reveal that Al2O3 is predominantly formed with a small amount of Si oxide in the initial stages without the formation of Al silicate. All core level spectra were alternately shifted toward higher and lower binding energies sides at every half ALD reaction. This can be explained by the band bending effect induced by different chemical species on the surface during the TMA-H2O ALD reaction. The valence band spectra showed that four cycles of ALD reactions were necessary to complete the electronic structure of the Al2O3 film with a valence band offset of 3.73 eV.

Published
2011

15. CD19-CD45 low/- CD38 high/CD138+ plasma cells enrich for human tumorigenic myeloma cells.

Author

Kim D, Park CY, Medeiros BC, Weissman IL, Kim, D, Park, C Y, Medeiros, B C, and Weissman, I L

Abstract

Multiple myeloma is a hematological neoplasm characterized by the accumulation of clonal plasma cells in the bone marrow. Its frequent relapse following achievement of clinical remissions implicates the existence of therapy-resistant myeloma-initiating cells. To date, results on the identity of myeloma-initiating cells have differed. Here, we prospectively identified a myeloma-initiating population by fractionating and transplanting patient bone marrow cells into human bone-bearing immunocompromised mice. Xenotransplantation of fractionated CD138(+)/CD38(high) cells from 40% of patients (8/20) led to a repopulation of CD19(+)CD38(low) or CD138(+)CD38(+) B-lineage cells in human bone grafts; and these grafts were clonally derived from patient myeloma cells. Meanwhile, CD19(+)CD38(low) xenografts were detected in human bone-bearing mice transplanted with CD19(+)CD38(low/-) B cells from 8 of 22 samples but were not clonally related to patient myeloma cells. Further fractionation and xenotransplantation of CD138(+)CD38(high) cells demonstrated that (CD45(low/-) or CD19(-)) CD38(high)/CD138(+) plasma cells, but not (CD45(high) or CD19(+)) CD38(high)/CD138(+) plasmablasts enrich for myeloma-initiating cells. Quantitative reverse transcription-PCR of two serially transplantable xenografts, which were CD19(-)CD138(+), revealed that they were Pax5 (a B-cell-specific transactivator)-negative. These results suggest that CD19(-)CD45(low/-) fully differentiated plasma cells enrich for long-lived and tumor-initiating cells whereas B cells or plasmablasts do not. [ABSTRACT FROM AUTHOR]

Published
2012
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16. Daily supplementation with 25 μg cholecalciferol does not increase calcium absorption or skeletal retention in adolescent girls with low serum 25-hydroxyvitamin D.

Author

Park CY, Hill KM, Elble AE, Martin BR, Dimeglio LA, Peacock M, McCabe GP, Weaver CM, Park, Clara Y, Hill, Kathleen M, Elble, Ann E, Martin, Berdine R, DiMeglio, Linda A, Peacock, Munro, McCabe, George P, and Weaver, Connie M

Abstract

In healthy adolescents, cross-sectional studies show either no or negative relationships between serum 25-hydroxyvitamin D [25(OH)D] and calcium (Ca) absorption. Using a 2-period metabolic balance study, the effect of vitamin D supplementation on Ca absorption and retention in adolescent girls was investigated. Eleven girls aged 12-14 y with a mean entry serum 25(OH)D of 35.1 nmol/L consumed a controlled intake (providing 5 μg vitamin D and 1117 mg Ca/d) for two 3-wk metabolic balance periods separated by a 1-wk washout period. Sunlight exposure was minimized by sunscreen with a sun protection factor ≥ 15. After the first metabolic balance period, participants received 25 μg/d cholecalciferol supplementation for 4 wk. Fractional Ca absorption was measured in each metabolic balance period using a stable Ca isotope method. All urine and fecal samples were collected and analyzed to measure net Ca absorption and Ca retention. Paired t tests and correlations were used to analyze the data. Daily supplementation with 25 μg vitamin D resulted in a mean increase in serum 25(OH)D of 13.3 nmol/L (P < 0.01) but a decrease in fractional Ca absorption of 8.3% (P < 0.05) and no significant change in fasting serum 1,25-dihydroxyvitamin D, parathyroid hormone, net Ca absorption, or Ca skeletal retention. In pubertal girls with vitamin D status considered insufficient in adults, vitamin D supplementation of 25 μg/d for 4 wk did not improve fractional Ca absorption, net Ca absorption, or Ca retention. [ABSTRACT FROM AUTHOR]

Published
2010
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17. Cancer stem cells: on the verge of clinical translation.

Author

Chao MP, Weissman IL, and Park CY

Abstract

Researchers have long studied malignant tumors using experimental techniques that assume that cancers are composed of identical cells; however, growing evidence indicates that cancers are composed of functionally heterogeneous cells maintained by a stem cell-like population. Identification of tumor-initiating, or cancer stem cells, has been largely guided by principles established for normal stem cells. Cancer stem cells must be capable of initiating tumors when transplanted into immunodeficient mice, and the resulting tumors must replicate the heterogeneity of the original tumor. Demonstration of the ability to self-renew, a key feature of stem cells, is achieved through serial passage of tumors in xenohosts. Given their potential roles in tumor initiation, maintenance, and metastasis, the impact of cancer stem cells on the practice of medicine is likely to be profound. [ABSTRACT FROM AUTHOR]

Published
2008
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18. Combined effect of nonalcoholic fatty liver disease and impaired fasting glucose on the development of type 2 diabetes: a 4-year retrospective longitudinal study.

Author

Bae JC, Rhee EJ, Lee WY, Park SE, Park CY, Oh KW, Park SW, Kim SW, Bae, Ji Cheol, Rhee, Eun Jung, Lee, Won Young, Park, Se Eun, Park, Cheol Young, Oh, Ki Won, Park, Sung Woo, and Kim, Sun Woo

Abstract

Objective: To evaluate whether there is a difference in the association between nonalcoholic fatty liver disease (NAFLD) and incident diabetes based on the presence of impaired fasting glucose.Research Design and Methods: A total of 7,849 individuals (5,409 men and 2,440 women) without diabetes, who underwent comprehensive health check-ups annually for 5 years, were categorized into four groups by the presence of impaired fasting glucose and NAFLD at baseline. The association between NAFLD and incident diabetes was evaluated separately in groups with normal and impaired fasting glucose.Results: For 4 years, the incidence of diabetes in the NAFLD group was 9.9% compared with 3.7% in the non-NAFLD group, with multivariable-adjusted hazard ratio of 1.33 (95% CI 1.07-1.66). However, this higher risk for diabetes only existed in the impaired fasting glucose group.Conclusions: Our study suggests that NAFLD has an independent and additive effect on the development of diabetes under conditions of impaired insulin secretion. [ABSTRACT FROM AUTHOR]

Published
2011
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