跳到主要內容

臺灣博碩士論文加值系統

(34.204.172.188) 您好!臺灣時間:2023/09/27 19:33
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果 :::

詳目顯示

我願授權國圖
: 
twitterline
研究生:陳煒堯
研究生(外文):Wei-Yao Chen
論文名稱:開環透明質酸攜帶瘦肉精緩釋用於高脂餵食的肥胖小鼠治療
論文名稱(外文):The Study of Oxidized Hyaluronic Acid Hydrogels as a Carrier for Constant-Release Clenbuterol against High-Fat Diet-Induced Obesity in Mice
指導教授:林峯輝
指導教授(外文):Feng-Huei Lin
口試委員:曾厚陳敏弘丁詩同董國忠
口試委員(外文):How TsengMing-Hong ChenShih-Torng DingGuo-Chung Dong
口試日期:2023-01-16
學位類別:博士
校院名稱:國立臺灣大學
系所名稱:生物科技研究所
學門:生命科學學門
學類:生物科技學類
論文種類:學術論文
論文出版年:2023
畢業學年度:111
論文頁數:90
中文關鍵詞:肥胖克倫特羅緩釋萊克多巴胺水凝膠
外文關鍵詞:ObesityClenbuterolConstant releaseRactopamineHydrogel
DOI:10.6342/NTU202300245
相關次數:
  • 被引用被引用:0
  • 點閱點閱:14
  • 評分評分:
  • 下載下載:0
  • 收藏至我的研究室書目清單書目收藏:0
全球肥胖患病率逐年遞增,肥胖及肥胖相關疾病的治療及控制的醫療成本隨之增加。儘管治療肥胖的方法很多,如:物理性的飲食控制或運動、化學性的健康食品攝取、藥理性使用減肥藥、或是最激烈的手術,上述沒有一種策略既安全有效又易於維持。瘦肉精一直是充滿爭議的藥物,由於其副作用(特別是肝腎毒性),克倫特羅在健美運動中的使用和職業運動員的使用存在爭議,受限於副作用及有效窗口僅在某些地區被准許用在氣喘治療上。這項研究以顯著低於安全水平劑量給予克崙特羅的原位注射脂肪組織緩釋作為治療肥胖的療法研究。研究顯示在更低的劑量和原位注射脂肪組織緩釋的方式下,能降低副作用發生的風險,提高安全性,對於克崙特羅真正使用在對抗肥胖方面的應用上相當有幫助。本研究以開環玻尿酸的溫感水凝膠為載體,負載克倫特羅以實現緩釋的效果。本實驗分為三個部分:材料合成、體外測試與動物實驗。在材料合成的實驗裡,利用傅立葉轉換紅外光譜確認玻尿酸確實開環後,加入高碘酸鈉氧化後的克倫特羅以製作含有克倫特羅的緩釋溫感水凝膠。在合成含有克倫特羅的緩釋溫感水凝膠後,使用流變儀確認在標準溫度及體溫下的成膠時間,並確認溶脹率與降解時間符合安全性及有效性需求。此外,利用可見光分光光度計檢測溫感水膠緩釋平台中的克倫特羅釋放曲線。在體外研究中,新開發的系統顯示在以開環玻尿酸的溫感水凝膠為載體的攜帶的克崙特羅,不僅對3T3-L1細胞無細胞毒性,並且可有效抑制體外培養細胞內的脂肪生成。在動物研究中,小鼠被餵食高脂肪飲食,並通過口服克崙特羅或定期注射攜帶克倫特羅的透明質酸溫感水凝膠 (HAC) 進行治療。實驗顯示全身、內臟和性腺脂肪含量和體重都有所下降。在使用脂肪模式和水模式下的 MRI比對成像分析腹部脂肪,我們發現脂肪內注射 HAC 的小鼠的腹部脂肪比率在試驗組中最低,甚至接受正常飲食治療的小鼠,而用高脂肪飲食 (HFD) 治療的小鼠顯示出 53.78% 的最高值。在血球和血清學分析中,確認了克倫特羅口服給藥造成的急性與慢性體內毒性在HAC組別試驗中並無觀察到,證明了有別於傳統口服給藥,每天 2 μg – 10 μg 克倫特羅的控釋注射劑是安全的。這項研究開發了一種新的和有潛力的抗肥胖治療方法,使用每月脂肪內控釋注射 HAC水凝膠。新研發的鹽酸克倫特羅配方不僅有效降低體重和體脂含量,還能抑制內臟組織的脂肪生成,減少性腺周圍的脂肪組織。本研究未觀察到傳統口服克崙特羅引起的副作用;這項研究極有可能成為未來肥胖治療甚至是第二型糖尿病的有效治療手段,而無需擔心安全問題。
The prevalence of obesity around the world is rising yearly, as are the associated costs. Although there are many ways to combat obesity, there isn't a single strategy that is both secure and effective. The use of Clenbuterol in bodybuilding and by professional athletes is controversial owing to its side effects, including hepatotoxicity. This study administered Clenbuterol at a much lower dose than the established safety level, and rather than through oral administration, the treatments were delivered through controlled-release intra-adipose injection; and a thermo-sensitive hydrogel was used as the carrier uploaded with Clenbuterol to achieve controlled-release. On the other hand, this study also demonstrates that Clenbuterol which at the different dosing and mode of administration will lower the risk of side effects, increase the safety profile, and could facilitate use in the anti-obesity market. A thermo-sensitive hydrogel was used as the carrier uploaded with Clenbuterol to achieve controlled-release.
The HAC hydrogel was prepared and then checked using Fourier-transform infrared spectroscopy (FTIR), and rheometer to confirm functional groups, and gelation time and temperature, respectively. The release profile in vitro was used to soak HAC in PBS solution for some time and then check the Clenbuterol level in the supernatant by UV-Vis. Then, the results of the following: cell viability, cytotoxicity, lipolysis on a cellular level, chronic toxicity, body weight control, whole-body adipose tissue, gonadal fat tissue, blood analysis, serological analysis, and sectioning examination of internal organs. These would be used to evaluate the safety and efficacy of the synthesized HAC, both in vitro and in vivo. The HAC group was not cytotoxic to 3T3-L1 cells and could inhibit lipogenesis effectively. In the animal study, the mice were fed a high-fat diet and treated with Clenbuterol by oral administration or injected with Clenbuterol-modified hyaluronate hydrogel (HAC) regularly. The HAC group showed reduction in whole-body, visceral, and gonadal fat contents and body weight. The abdominal fat was analyzed using MRI imaging in adipose mode and water mode. The abdominal fat ratio in the mice treated with normal diet and those given intra-adipose injections with HAC had the lowest value among the test groups. The mice treated with high-fat diet (HFD) showed the highest value of 53.78 %. The chronic toxicity in-vivo tests proved that controlled-release injections of 2 g – 10 g Clenbuterol daily were safe, as demonstrated in the blood elements and serological analyses. This study developed a new and promising method for anti-obesity treatment, using a monthly intra-adipose controlled-release injection of HAC hydrogel. The developed new treatment of Clenbuterol only effectively decreased body weight and body fat content but also inhibited lipogenesis on the harvested visceral tissue and reduced adipose tissue around the gonadal area. The side effects induced by traditional oral administration of Clenbuterol was not observed in this research; this has excellent potential to be a useful tool for future obesity treatment without safety concerns.
口試委員會審定書 i
誌謝 ii
中文摘要 iii
Abstract v
List of Figure x
List of Table xi
1. Introduction 1
1.1 Obesity and overweight 2
1.2 Body fat composition and adipose tissue distribution 5
1.3 Obesity therapies 9
2. Theoretical basis 11
2.1 Adrenergic receptor 12
2.2 Beta-adrenergic agonists 14
2.3 Receptor sequestration 16
2.4 Clenbuterol 17
2.5 Ractopamine 19
2.6 Dosage and Administration 21
2.7 Hyaluronate 23
2.8 propose of study 25
3. Materials and methods 27
3.1 The preparation of injectable Clenbuterol-modified hyaluronate hydrogel (HAC) and Ractopamine hyaluronate hydrogel (HAR) 28
3.2 Fourier transform infrared (FTIR) 29
3.3 Rheological Evaluation of the oxi-HA/ADH Hydrogel 29
3.4 In Vitro Degradation of the oxi-HA/ADH Hydrogel 30
3.5 In Vitro Swelling Index of the oxi-HA/ADH Hydrogel 30
3.6 UV-vis spectrophotometer 31
3.7 In vitro release profile 31
3.8 Cell culture and differentiation 32
3.9 Cell viability and cytotoxicity 33
3.10 Oil-Red-O 35
3.11 Animal study 36
3.12 Magnetic Resonance Imaging (MRI) 37
3.13 The calculation of body weight gain 38
3.14 Percentage of body fat 38
3.15 Measurement of organ weight 39
3.16 Histological analysis 39
3.17 Serological analysis and blood element analysis 39
3.18 Statistical methods 39
4. Result 41
4.1 FTIR 42
4.2 Rheological Evaluation 43
4.3 Swelling Index 45
4.4 UV-Vis and in vitro release profile 47
4.5 Cell viability and cytotoxicity 48
4.6 Oil-Red-O 50
4.7 The measurement of body weight 51
4.8 Body fat analysis 53
4.9 MRI analysis 55
4.10 Organ weight analysis 58
4.11 Fat tissue weight analysis 60
4.12 The blood element and serological analysis 63
4.13 Histological analysis 67
5. Discussion 70
5.1 The COVID-19 Pandemic's effect on Lifestyle 71
5.2 The evolution in healthcare models under COVID-19 72
5.3 The medicine selection utilizes on people or animals. 73
5.4 In vitro study of lipogenesis 75
5.5 Differences in toxicity caused by different administration methods in in vivo study 76
5.6 The difficulty of localized fat weight loss and possibilities 78
6. Conclusion 81
7. References 83
1.Muuronen AT, Taina M, Hedman M, Marttila J, Kuusisto J, Onatsu J, et al. Increased visceral adipose tissue as a potential risk factor in patients with embolic stroke of undetermined source (ESUS). PLoS One. 2015;10(3):e0120598. Epub 2015/03/11. doi: 10.1371/journal.pone.0120598. PubMed PMID: 25756793; PubMed Central PMCID: PMCPMC4354901.
2.Madrigal L, Brady J, Raxter M, Ruiz E, Otarola F, Blell M. Obesity, hypertension, and migration: a meta-analysis of populations of the South Asian diaspora. Hum Biol. 2011;83(1):71-86. Epub 2011/04/02. doi: 10.3378/027.083.0105. PubMed PMID: 21453005.
3.Apovian CM. Obesity: definition, comorbidities, causes, and burden. Am J Manag Care. 2016;22(7 Suppl):s176-85. Epub 2016/06/30. PubMed PMID: 27356115.
4.Naja F, Hwalla N, Itani L, Karam S, Sibai AM, Nasreddine L. A Western dietary pattern is associated with overweight and obesity in a national sample of Lebanese adolescents (13-19 years): a cross-sectional study. Br J Nutr. 2015;114(11):1909-19. doi: 10.1017/S0007114515003657. PubMed PMID: 26431469; PubMed Central PMCID: PMCPMC4635384.
5.Hussain A, Mahawar K, Xia Z, Yang W, El-Hasani S. Obesity and mortality of COVID-19. Meta-analysis. 2020(1871-403X (Print)).
6.Blüher M. Obesity: global epidemiology and pathogenesis. 2019(1759-5037 (Electronic)).
7.Ward Lc Fau - Müller MJ, Müller MJ. Bioelectrical impedance analysis. 2013(1476-5640 (Electronic)).
8.Di Vincenzo O, Marra M, Di Gregorio A, Pasanisi F, Scalfi L. Bioelectrical impedance analysis (BIA) -derived phase angle in sarcopenia: A systematic review. 2020(1532-1983 (Electronic)).
9.Ballesteros-Pomar MD, González-Arnáiz E, Pintor-de-la Maza B, Barajas-Galindo D, Ariadel-Cobo D, González-Roza L, et al. Bioelectrical impedance analysis as an alternative to dual-energy x-ray absorptiometry in the assessment of fat mass and appendicular lean mass in patients with obesity. 2022(1873-1244 (Electronic)).
10.Fukuda T, Bouchi RA-O, Takeuchi T, Tsujimoto K, Minami I, Yoshimoto T, et al. Sarcopenic obesity assessed using dual energy X-ray absorptiometry (DXA) can predict cardiovascular disease in patients with type 2 diabetes: a retrospective observational study. 2018(1475-2840 (Electronic)).
11.Katzer K, Hill JA-O, McIver KB, Foster MA-O. Lipedema and the Potential Role of Estrogen in Excessive Adipose Tissue Accumulation. LID - 10.3390/ijms222111720 [doi] LID - 11720. 2016(1422-0067 (Electronic)).
12.Luo L, Liu M. Adipose tissue in control of metabolism. J Endocrinol. 2016;231(3):R77-R99. Epub 2016/12/10. doi: 10.1530/JOE-16-0211. PubMed PMID: 27935822; PubMed Central PMCID: PMCPMC7928204.
13.Nakamura MT, Yudell BE, Loor JJ. Regulation of energy metabolism by long-chain fatty acids. Prog Lipid Res. 2014;53(1873-2194 (Electronic)):124-44. Epub 2013/12/24. doi: 10.1016/j.plipres.2013.12.001. PubMed PMID: 24362249.
14.Rebuffe-Scrive M. Steroid hormones and distribution of adipose tissue. Acta Med Scand Suppl. 1988;723(0365-463X (Print)):143-6. Epub 1988/01/01. doi: 10.1111/j.0954-6820.1987.tb05937.x. PubMed PMID: 2839955.
15.Saxton SA-O, Clark BJ, Withers SB, Eringa EC, Heagerty AM. Mechanistic Links Between Obesity, Diabetes, and Blood Pressure: Role of Perivascular Adipose Tissue. 2019(1522-1210 (Electronic)).
16.Cypess AM, Lehman S, Williams G, Tal I, Rodman D, Goldfine AB, et al. Identification and importance of brown adipose tissue in adult humans. N Engl J Med. 2009;360(15):1509-17. Epub 2009/04/10. doi: 10.1056/NEJMoa0810780. PubMed PMID: 19357406; PubMed Central PMCID: PMCPMC2859951.
17.Ibrahim MM. Subcutaneous and visceral adipose tissue: structural and functional differences. Obes Rev. 2010;11(1):11-8. Epub 2009/08/07. doi: 10.1111/j.1467-789X.2009.00623.x. PubMed PMID: 19656312.
18.Reyes-Farias M, Fos-Domenech J, Serra D, Herrero L, Sanchez-Infantes D. White adipose tissue dysfunction in obesity and aging. Biochem Pharmacol. 2021;192(1873-2968 (Electronic)):114723. Epub 2021/08/09. doi: 10.1016/j.bcp.2021.114723. PubMed PMID: 34364887.
19.Vishvanath L Fau - Gupta RK, Gupta RK. Contribution of adipogenesis to healthy adipose tissue expansion in obesity. 2019(1558-8238 (Electronic)).
20.de Almeida Marques Bernabé R, de Souza Vieira M, Felício de Souza V, Gomes Fontana L, Albergaria BH, Marques-Rocha JL, et al. Muscle strength is associated with fracture risk obtained by fracture risk assessment tool (FRAX) in women with breast cancer. 2022(1471-2407 (Electronic)).
21.Quail DF, Dannenberg AJ. The obese adipose tissue microenvironment in cancer development and progression. Nat Rev Endocrinol. 2019;15(3):139-54. Epub 2018/11/22. doi: 10.1038/s41574-018-0126-x. PubMed PMID: 30459447; PubMed Central PMCID: PMCPMC6374176.
22.Zhang F, Hao G, Shao M, Nham K, An Y, Wang Q, et al. An Adipose Tissue Atlas: An Image-Guided Identification of Human-like BAT and Beige Depots in Rodents. Cell Metab. 2018;27(1):252-62 e3. Epub 2018/01/11. doi: 10.1016/j.cmet.2017.12.004. PubMed PMID: 29320705; PubMed Central PMCID: PMCPMC5764189.
23.Anders S, Schroeter C. The impact of nutritional supplement intake on diet behavior and obesity outcomes. PLoS One. 2017;12(10):e0185258. Epub 2017/10/11. doi: 10.1371/journal.pone.0185258. PubMed PMID: 28991921; PubMed Central PMCID: PMCPMC5633155.
24.Kanauchi O, Deuchi K, Imasato Y, Shizukuishi M, Kobayashi E. Mechanism for the inhibition of fat digestion by chitosan and for the synergistic effect of ascorbate. Biosci Biotechnol Biochem. 1995;59(5):786-90. Epub 1995/05/01. doi: 10.1271/bbb.59.786. PubMed PMID: 7787293.
25.Zhang W-S, An Pan LY, Cai Y-Y, Liu B-L, Li P, Qi L-W, et al. American Ginseng and Asian Ginseng Intervention in Diet-Induced Obese Mice: Metabolomics Reveals Distinct Metabolic Profiles. The American Journal of Chinese Medicine. 2017;4.
26.Iannelli A, Dainese R, Piche T, Facchiano E, Gugenheim J. Laparoscopic sleeve gastrectomy for morbid obesity. World J Gastroenterol. 2008;14(6):821-7. Epub 2008/02/02. doi: 10.3748/wjg.14.821. PubMed PMID: 18240338; PubMed Central PMCID: PMCPMC2687048.
27.Santoro S, Malzoni CE, Velhote MC, Milleo FQ, Santo MA, Klajner S, et al. Digestive Adaptation with Intestinal Reserve: a neuroendocrine-based operation for morbid obesity. Obes Surg. 2006;16(10):1371-9. Epub 2006/10/25. doi: 10.1381/096089206778663841. PubMed PMID: 17059749.
28.Yu SS, Lefkowitz RJ, Hausdorff WP. Beta-adrenergic receptor sequestration. A potential mechanism of receptor resensitization. J Biol Chem. 1993;268(1):337-41. Epub 1993/01/05. PubMed PMID: 8380158.
29.Doronin S, Shumay E, Wang HY, Malbon CC. Akt mediates sequestration of the beta(2)-adrenergic receptor in response to insulin. J Biol Chem. 2002;277(17):15124-31. Epub 2002/01/26. doi: 10.1074/jbc.M108771200. PubMed PMID: 11809767.
30.Iwatsubo K, Toya Y, Fujita T, Ebina T, Schwencke C, Minamisawa S, et al. Ischemic preconditioning prevents ischemia-induced beta-adrenergic receptor sequestration. J Mol Cell Cardiol. 2003;35(8):923-9. Epub 2003/07/25. doi: 10.1016/s0022-2828(03)00173-1. PubMed PMID: 12878479.
31.Prezelj A, Obreza A, Pecar S. Abuse of clenbuterol and its detection. Curr Med Chem. 2003;10(4):281-90. Epub 2003/02/07. doi: 10.2174/0929867033368330. PubMed PMID: 12570701.
32.Spann C, Winter ME. Effect of clenbuterol on athletic performance. 1995(1060-0280 (Print)).
33.Liu J, Zeng L, Li Z, Gao F, Huang X, Li F, et al. Solid substrate-room temperature phosphorimetry for the determination of residual clenbuterol hydrochloride based on the catalysis of sodium periodate oxidizing eosine Y. Anal Chim Acta. 2009;638(1):69-74. Epub 2009/03/21. doi: 10.1016/j.aca.2009.02.007. PubMed PMID: 19298881.
34.Kintz P, Gheddar L, Ameline A, Dumestre-Toulet V, Verschoore M, Comte J, et al. Complete Post-mortem Investigations in a Death Involving Clenbuterol After Long-term Abuse. J Anal Toxicol. 2019;43(8):660-5. Epub 2019/08/23. doi: 10.1093/jat/bkz058. PubMed PMID: 31436794.
35.Ip EJ, Doroudgar S, Lau B, Barnett MJ. Anabolic steroid users' misuse of non-traditional prescription drugs. Res Social Adm Pharm. 2019;15(8):949-52. Epub 2019/07/16. doi: 10.1016/j.sapharm.2018.07.003. PubMed PMID: 31303195.
36.Valachova K, Volpi N, Stern R, Soltes L. Hyaluronan in Medical Practice. Curr Med Chem. 2016;23(31):3607-17. Epub 2016/08/25. doi: 10.2174/0929867323666160824162133. PubMed PMID: 27554806.
37.The Biological Role of Hyaluronic Acid. Hyaluronic Acid. p. 9-75.
38.Hu MH, Yang KC, Sun YH, Chen YC, Yang SH, Lin FH. In situ forming oxidised hyaluronic acid/adipic acid dihydrazide hydrogel for prevention of epidural fibrosis after laminectomy. Eur Cell Mater. 2017;34:307-20. Epub 2017/11/14. doi: 10.22203/eCM.v034a19. PubMed PMID: 29130237.
39.Su WY, Chen YC, Lin FH. Injectable oxidized hyaluronic acid/adipic acid dihydrazide hydrogel for nucleus pulposus regeneration. Acta Biomater. 2010;6(8):3044-55. doi: 10.1016/j.actbio.2010.02.037. PubMed PMID: 20193782.
40.Chen YC, Su WY, Yang SH, Gefen A, Lin FH. In situ forming hydrogels composed of oxidized high molecular weight hyaluronic acid and gelatin for nucleus pulposus regeneration. Acta Biomater. 2013;9(2):5181-93. doi: 10.1016/j.actbio.2012.09.039. PubMed PMID: 23041783.
41.Shoham N, Sasson AL, Lin FH, Benayahu D, Haj-Ali R, Gefen A. The mechanics of hyaluronic acid/adipic acid dihydrazide hydrogel: towards developing a vessel for delivery of preadipocytes to native tissues. J Mech Behav Biomed Mater. 2013;28:320-31. Epub 2013/09/12. doi: 10.1016/j.jmbbm.2013.08.009. PubMed PMID: 24021174.
42.Liu J, Liu Z-b, Huang Q, Lin C-Q, Lin X. Highly Sensitive Fluorescent Probe for Clenbuterol Hydrochloride Detection Based on its Catalytic Oxidation of Eosine Y by NaIO4. Journal of Fluorescence. 2014;24(5):1495-501. doi: 10.1007/s10895-014-1435-7.
43.Wang CY, Liao JK. A mouse model of diet-induced obesity and insulin resistance. Methods Mol Biol. 2012;821:421-33. doi: 10.1007/978-1-61779-430-8_27. PubMed PMID: 22125082; PubMed Central PMCID: PMCPMC3807094.
44.Yang Y, Smith DL, Jr., Keating KD, Allison DB, Nagy TR. Variations in body weight, food intake and body composition after long-term high-fat diet feeding in C57BL/6J mice. Obesity (Silver Spring). 2014;22(10):2147-55. doi: 10.1002/oby.20811. PubMed PMID: 24942674; PubMed Central PMCID: PMCPMC4180788.
45.Hong J, Stubbins RE, Smith RR, Harvey AE, Nunez NP. Differential susceptibility to obesity between male, female and ovariectomized female mice. Nutr J. 2009;8:11. doi: 10.1186/1475-2891-8-11. PubMed PMID: 19220919; PubMed Central PMCID: PMCPMC2650703.
46.Simchick G, Yin A, Yin H, Zhao Q. Fat spectral modeling on triglyceride composition quantification using chemical shift encoded magnetic resonance imaging. Magn Reson Imaging. 2018;52:84-93. Epub 2018/06/22. doi: 10.1016/j.mri.2018.06.012. PubMed PMID: 29928937; PubMed Central PMCID: PMCPMC6537901.
47.Johnson DH, Narayan S, Wilson DL, Flask CA. Body composition analysis of obesity and hepatic steatosis in mice by relaxation compensated fat fraction (RCFF) MRI. J Magn Reson Imaging. 2012;35(4):837-43. Epub 2011/11/19. doi: 10.1002/jmri.23508. PubMed PMID: 22095745; PubMed Central PMCID: PMCPMC3288219.
48.Lee MR, Kim JE, Choi JY, Park JJ, Kim HR, Song BR, et al. Anti-obesity effect in high-fat-diet-induced obese C57BL/6 mice: Study of a novel extract from mulberry (Morus alba) leaves fermented with Cordyceps militaris. Exp Ther Med. 2019;17(3):2185-93. Epub 2019/03/15. doi: 10.3892/etm.2019.7191. PubMed PMID: 30867704; PubMed Central PMCID: PMCPMC6395968.
49.Betzel B, Cooiman MI, Aarts EO, Janssen IMC, Wahab PJ, Groenen MJM, et al. Clinical follow-up on weight loss, glycemic control, and safety aspects of 24 months of duodenal-jejunal bypass liner implantation. Surg Endosc. 2019. Epub 2019/03/17. doi: 10.1007/s00464-019-06752-8. PubMed PMID: 30877567.
50.Su WY, Chen Kh Fau - Chen Y-C, Chen Yc Fau - Lee Y-H, Lee Yh Fau - Tseng C-L, Tseng Cl Fau - Lin F-H, Lin FH. An injectable oxidated hyaluronic acid/adipic acid dihydrazide hydrogel as a vitreous substitute. 2011(1568-5624 (Electronic)).
51.Mills G. Assessing the impact of Covid-19 on pets. Vet Rec. 2022;191(1):5. Epub 2022/07/09. doi: 10.1002/vetr.1983. PubMed PMID: 35802095; PubMed Central PMCID: PMCPMC9349665.
52.Zhou Y, Chi J, Lv W, Wang YA-OX. Obesity and diabetes as high-risk factors for severe coronavirus disease 2019 (Covid-19). 2019(1520-7560 (Electronic)).
53.Lan K, Saheba A, Mathew P. Low Dose Clenbuterol Toxicity: Case Report and Review of Literature. HCA Healthcare Journal of Medicine. 2020;1(4). doi: 10.36518/2689-0216.1086.
54.Schifano F, Chiappini S, Corkery JM, Guirguis A. Abuse of Prescription Drugs in the Context of Novel Psychoactive Substances (NPS): A Systematic Review. Brain Sci. 2018;8(4). Epub 2018/04/25. doi: 10.3390/brainsci8040073. PubMed PMID: 29690558; PubMed Central PMCID: PMCPMC5924409.
55.Li C, Adhikari BK, Gao L, Zhang S, Liu Q, Wang Y, et al. Performance-Enhancing Drugs Abuse Caused Cardiomyopathy and Acute Hepatic Injury in a Young Bodybuilder. Am J Mens Health. 2018;12(5):1700-4. Epub 2018/06/22. doi: 10.1177/1557988318783504. PubMed PMID: 29926766; PubMed Central PMCID: PMCPMC6142118.
56.Courcier EA, O'Higgins R, Mellor DJ, Yam PS. Prevalence and risk factors for feline obesity in a first opinion practice in Glasgow, Scotland. Journal of Feline Medicine and Surgery. 2010;12(10):746-53. doi: 10.1016/j.jfms.2010.05.011. PubMed PMID: 20685143.
57.Hassan BB, Elshafae SM, Supsavhad W, Simmons JK, Dirksen WP, Sokkar SM, et al. Feline Mammary Cancer. Vet Pathol. 2017;54(1):32-43. Epub 2016/06/10. doi: 10.1177/0300985816650243. PubMed PMID: 27281014; PubMed Central PMCID: PMCPMC7212821.
58.Porcellato I, Menchetti L, Brachelente C, Sforna M, Reginato A, Lepri E, et al. Feline Injection-Site Sarcoma. Vet Pathol. 2017;54(2):204-11. Epub 2016/12/23. doi: 10.1177/0300985816677148. PubMed PMID: 28005492.
59.Ganguly B, Das U, Das AK. Canine transmissible venereal tumour: a review. Vet Comp Oncol. 2016;14(1):1-12. Epub 2013/08/29. doi: 10.1111/vco.12060. PubMed PMID: 23981098.
60.Zhu Y, Kruglikov IL, Akgul Y, Scherer PE. Hyaluronan in adipogenesis, adipose tissue physiology and systemic metabolism. Matrix Biol. 2019;78-79(1569-1802 (Electronic)):284-91. Epub 2018/02/20. doi: 10.1016/j.matbio.2018.02.012. PubMed PMID: 29458140; PubMed Central PMCID: PMCPMC6534160.
61.Nadra K, Andre M, Marchaud E, Kestemont P, Braccini F, Cartier H, et al. A hyaluronic acid-based filler reduces lipolysis in human mature adipocytes and maintains adherence and lipid accumulation of long-term differentiated human preadipocytes. J Cosmet Dermatol. 2021;20(5):1474-82. Epub 2020/11/06. doi: 10.1111/jocd.13794. PubMed PMID: 33150734; PubMed Central PMCID: PMCPMC8246837.
62.Blanco A, Artacho-Perula E, Flores-Acuna R, Aguera E, Monterde JG. Quantitative modification of the testicular structure in pigs fed with anabolic doses of clenbuterol. Vet Res. 2002;33(1):47-53. Epub 2002/03/05. doi: 10.1051/vetres:2001005. PubMed PMID: 11873818.
63.Karastergiou K, Smith SR, Greenberg AS, Fried SK. Sex differences in human adipose tissues - the biology of pear shape. Biol Sex Differ. 2012;3(1):13. Epub 2012/06/02. doi: 10.1186/2042-6410-3-13. PubMed PMID: 22651247; PubMed Central PMCID: PMCPMC3411490.
64.Swainson MG, Batterham AM, Tsakirides C, Rutherford ZH, Hind K. Prediction of whole-body fat percentage and visceral adipose tissue mass from five anthropometric variables. PLoS One. 2017;12(5):e0177175. Epub 2017/05/12. doi: 10.1371/journal.pone.0177175. PubMed PMID: 28493988; PubMed Central PMCID: PMCPMC5426673.
65.Meister JA-O, Bone DA-O, Knudsen JA-OX, Barella LA-O, Velenosi TA-O, Akhmedov D, et al. Clenbuterol exerts antidiabetic activity through metabolic reprogramming of skeletal muscle cells. 2022(2041-1723 (Electronic)).
連結至畢業學校之論文網頁點我開啟連結
註: 此連結為研究生畢業學校所提供,不一定有電子全文可供下載,若連結有誤,請點選上方之〝勘誤回報〞功能,我們會盡快修正,謝謝!
QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top