Алфлутоп – в современной симптом-модифицирующей терапии остеоартрита
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Drozdov V.N., Shikh E.V., Serebrova S.Y., et al. Alflutop – in modern symptom-modifying osteoarthritis therapy. Therapeutic Archive. 2019; 91 (5): 134–140. DOI: 10.26442/00403660.2019.05.000169
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Ключевые слова: остеоартрит, терапия, потребность в нестероидных противовоспалительных препаратах, комплексная терапия.
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One of the serious problems during the treatment of osteoarthritis (OA) is the developing of adverse drug events during therapy. Nonsteroidal anti-inflammatory drugs (NSAIDs) are the first drugs with the high incidence and severity of adverse events. This article describes OA treatment strategies approaches for OA are presented using the complex drug Alflutop, which has a composition similar to the human hyaline cartilage. The drug has anti-inflammatory and analgesic effects, normalizes the function of the affected joints, improves the quality of patients’ life, also has a structure-modifying effect. Such therapy is safe, well tolerable for patients, and can be used used as a starting complex OA treatment.
Keywords: osteoarthritis, therapy, daily consumption of nonsteroidal anti-inflammatory drugs, complex therapy.
2. Bassleer C, Rovati LC, Franchimont P. Glucosamine sulfate stimulates proteoglycan production in human chondrocytes in vitro. Osteoarthritis Cartilage. 1998;6:427-34. https://doi.org/10.1053/joca.1998.0146
3. Piperno M, Reboul P, Helio Le, Graverand MP, Peschard MJ, Annefeld M, Richard M, et al. Glucosamine sulfate modulates dysregulated activities of human osteoarthritic chondrocytes in vitro. Osteoarthritis Cartilage. 2000;8:207-12. https://doi.org/10.1053/joca.1999.0291
4. Dodge GR, Jimenez SA. Glucosamine sulfate modulates the levels of aggrecan and matrix metalloproteinase-3 synthesized by cultured human osteoarthritis articular chondrocytes. Osteoarthritis Cartilage. 2003;11:424-32. https://doi.org/10.1016/s1063-4584(03)00052-9
5. Mroz PJ, Silbert JE. Use of 3H-glucosamine and 35S-sulfate with cultured human chondrocytes to determine the effect of glucosamine concentration on formation of chondroitin sulfate. Arthritis Rheum. 2004;50:3574-9. https://doi.org/10.1002/art.20609
6. Biggee BA, Blinn CM, McAlindon TE, Nuite M, Silbert JE. Low levels of human serum glucosamine after ingestion of glucosamine sulfate relative to capability for peripheral effectiveness. Ann Rheum Dis. 2006;65:222-6. https://doi.org/10.1136/ard.2005.036368
7. Varghese S, Theprungsirikul P, Sahani S, Hwang N, Yarema KJ, Elisseeff JH. Glucosamine modulates chondrocyte proliferation, matrix synthesis, and gene expression. Osteoarthritis Cartilage. 2007;15:59-68. https://doi.org/10.1016/ j.joca.2006.06.008
8. Gouze JN, Bordji K, Gulberti S, Terlain B, Netter P, Magdalou J, et al. Interleukin-1beta down-regulates the expression of glucuronosyltransferase I, a key enzyme priming glycosaminoglycan biosynthesis: influence of glucosamine on interleukin-1beta-mediated effects in rat chondrocytes. Arthritis Rheum. 2001;44:351-60. https://doi.org/10.1002/1529-0131(200102)44:2%3C351:: aid-anr53%3E3.0.co;2-m
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13. Jomphe C, Gabriac M, Hale TM, Heroux L, Trudeau LE, Deblois D, et al. Chondroitin sulfate inhibits the nuclear translocation of nuclear factor-kappaB in interleukin-1beta- stimulated chondrocytes. Basic Clin Pharmacol Toxicol. 2008;102:59-65. https://doi.org/10.1111/j.1742-7843.2007.00158.x
14. Caraglia M, Beninati S, Giuberti G, D’Alessandro AM, Lentini A, Abbruzzese A, et al. Alternative therapy of earth elements increases the chondroprotective effects of chondroitin sulfate in mice. Exp Mol Med. 2005;37:476-81. https://doi.org/10.1038/emm.2005.58
15. Bassleer CT, Combal JP, Bougaret S, Malaise M. Effects of chondroitin sulfate and interleukin-1 beta on human articular chondrocytes cultivated in clusters. Osteoarthritis Cartilage. 1998;6:196e204. https://doi.org/10.1053/joca.199 8.0112
16. Uebelhart D, Thonar EJ, Zhang J, Williams JM. Protective effect of exogenous chondroitin 4,6-sulfate in the acute degradation of articular cartilage in the rabbit. Osteoarthritis Cartilage. 1998;6(Suppl A):6-13. https://doi.org/10.1016/ s1063-4584(98)80005-8
17. Wang L, Wang J, Almqvist KF, Veys EM, Verbruggen G. Influ- ence of polysulphated polysaccharides and hydrocortisone on the extracellular matrix metabolism of human articular chondrocytes in vitro. Clin Exp Rheumatol. 2002;20:669-76. https://doi.org/10.1016/s1063-4584(03)00168-7
18. Orth MW, Peters TL, Hawkins JN. Inhibition of articular cartilage degradation by glucosamine HCl and chondroitin sulphate. Equine Vet J Suppl. 2010;34:224-9. https://doi.org/10.1111/j.2042-3306.2002.tb05423.x
19. Chan PS, Caron JP, Orth MW. Effect of glucosamine and chondroitin sulfate on regulation of gene expression of proteolytic enzymes and their inhibitors in interleukin-1- challenged bovine articular cartilage explants. Am J Vet Res. 2005;66:1870-6. https://doi.org/10.2460/ajvr.2005.66.1870
20. Chou MM, Vergnolle N, McDougall JJ, Wallace JL, Marty S, Teskey V, et al. Effects of chondroitin and glucosamine sulfate in a dietary bar formulation on inflammation, interleukin- 1beta, matrix metalloprotease-9, and cartilage damage in arthritis. Exp Biol Med. 2005;230:255-62. https://doi.org/10.1177/153 537020523000405
21. Monfort J, Nacher M, Montell E, Vila J, Verges J, Benito P. Chondroitin sulfate and hyaluronic acid (500e730 kDa) inhibit stromelysin-1 synthesis in human osteoarthritic chondrocytes. Drugs Exp Clin Res. 2005;31:71-6. https:// doi.org/10.1016/s1699-258x(05)72734-0
22. Baici A, Bradamante P. Interaction between human leukocyte elastase and chondroitin sulfate. Chem Biol Interact. 1984;51:1-11. https://doi.org/10.10 16/0009-2797(84)90015-2
23. Baici A, Lang A. Cathepsin B secretion by rabbit articular chondrocytes: modulation by cycloheximide and glycosami- noglycans. Cell Tissue Res. 1990;259:567-73. https://doi.org/10.1007/bf01740785
24. Verbruggen G, Veys EM. Influence of sulphated glycosamino- glycans upon proteoglycan metabolism of the synovial lining cells. Acta Rhumatol Belg. 1977;1:75-92.
25. Nishikawa H, Mori I, Umemoto J. Influences of sulfated glycosaminoglycans on biosynthesis of hyaluronic acid in rabbit knee synovial membrane. Arch Biochem Biophys. 1985;240:146-53. https://doi.org/10.1016/0003-9861(85) 90017-7
26. Nishikawa H, Mori I, Umemoto J. Glycosaminoglycan polysulfate- induced stimulation of hyaluronic acid synthesis in rabbit knee synovial membrane: involvement of binding protein and calcium ion. Arch Biochem Biophys. 1988;266:201-9. https://doi.org/10.1016/0003-9861(88)90251-2
27. Chan PS, Caron JP, Rosa GJ, Orth MW. Glucosamine and chondroitin sulfate regulate gene expression and synthesis of nitric oxide and prostaglandin E(2) in articular cartilage explants. Osteoarthritis Cartilage. 2005;13:387-94. https://doi.org/10.1016/j.joca.2005.01.003
28. Chan PS, Caron JP, Orth MW. Short-term gene expression changes in cartilage explants stimulated with interleukin beta plus glucosamine and chondroitin sulfate. J Rheumatol. 2006;33:1329-40.
29. Tat SK, Pelletier JP, Vergés J, Montell E, Lajeunesse D, Fahmi H, et al. Chondroitin and glucosamine sulfate in combination decrease the pro-resorptive properties of human osteoarthritis subchondral bone osteoblasts. Arthritis Res Ther. 2007;9:R117. https://doi.org/10.1186/ar2325
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1. Noyszewski EA, Wroblewski K, Dodge GR, Kudchodkar S, Beers J, Sarma AV, et al. Preferential incorporation of glucosamine into the galactosamine moieties of chondroitin sulfate in articular cartilage explants. Arthritis Rheum. 2001;44:1089-95. https://doi.org/10.1002/1529-0131(200105)44:5<1089::AID-ANR189>3.0.CO;2-9
2. Bassleer C, Rovati LC, Franchimont P. Glucosamine sulfate stimulates proteoglycan production in human chondrocytes in vitro. Osteoarthritis Cartilage. 1998;6:427-34. https://doi.org/10.1053/joca.1998.0146
3. Piperno M, Reboul P, Helio Le, Graverand MP, Peschard MJ, Annefeld M, Richard M, et al. Glucosamine sulfate modulates dysregulated activities of human osteoarthritic chondrocytes in vitro. Osteoarthritis Cartilage. 2000;8:207-12. https://doi.org/10.1053/joca.1999.0291
4. Dodge GR, Jimenez SA. Glucosamine sulfate modulates the levels of aggrecan and matrix metalloproteinase-3 synthesized by cultured human osteoarthritis articular chondrocytes. Osteoarthritis Cartilage. 2003;11:424-32. https://doi.org/10.1016/s1063-4584(03)00052-9
5. Mroz PJ, Silbert JE. Use of 3H-glucosamine and 35S-sulfate with cultured human chondrocytes to determine the effect of glucosamine concentration on formation of chondroitin sulfate. Arthritis Rheum. 2004;50:3574-9. https://doi.org/10.1002/art.20609
6. Biggee BA, Blinn CM, McAlindon TE, Nuite M, Silbert JE. Low levels of human serum glucosamine after ingestion of glucosamine sulfate relative to capability for peripheral effectiveness. Ann Rheum Dis. 2006;65:222-6. https://doi.org/10.1136/ard.2005.036368
7. Varghese S, Theprungsirikul P, Sahani S, Hwang N, Yarema KJ, Elisseeff JH. Glucosamine modulates chondrocyte proliferation, matrix synthesis, and gene expression. Osteoarthritis Cartilage. 2007;15:59-68. https://doi.org/10.1016/ j.joca.2006.06.008
8. Gouze JN, Bordji K, Gulberti S, Terlain B, Netter P, Magdalou J, et al. Interleukin-1beta down-regulates the expression of glucuronosyltransferase I, a key enzyme priming glycosaminoglycan biosynthesis: influence of glucosamine on interleukin-1beta-mediated effects in rat chondrocytes. Arthritis Rheum. 2001;44:351-60. https://doi.org/10.1002/1529-0131(200102)44:2%3C351:: aid-anr53%3E3.0.co;2-m
9. Chiusaroli R, Piepoli T, Zanelli T, Ballanti P, Lanza M, Rovati LC, et al. Experimental pharmacology of glucosamine sulfate. Int J Rheumatol. 2011: 939265 [Epub]. https://doi.org/10.1155/2011/939265
10. Imagawa K, deAndrés MC, Hashimoto K, Pitt D, Itoi E, Goldring MB, et al. The epigenetic effect of glucosamine and a nuclear factor-kappa B (NF-kB) inhibitor on primary human chondrocytes – implications for osteoarthritis. Biochem Biophys Res Commun. 2011;405:362-7. https://doi.org/10.1016/j.bbrc. 2011.01.007
11. Maneiro E, Fernández Sueiro J, Lema D, de Toro F, Galdo F, Blanco F. Efecto del condroitín sulfato sobre la producción de óxido nítrico por los condrocitos humanos artrósicos. Rev Esp Reumatol. 2001;28:12-7. https://doi.org/10.39 89/mc.1961.v11.i103.1883
12. Vergés J, Montell E, Martinez G, Heroux L, du Souich P. Chon- droitin sulfate reduces nuclear translocation factor NF-kappaB and does not modify the activation state of activating protein-1 (AP-1) (Abstract). Osteoarthritis Cartilage. 2004;12:194. https://doi.org/10.1016/s1063-4584(08)60572-5
13. Jomphe C, Gabriac M, Hale TM, Heroux L, Trudeau LE, Deblois D, et al. Chondroitin sulfate inhibits the nuclear translocation of nuclear factor-kappaB in interleukin-1beta- stimulated chondrocytes. Basic Clin Pharmacol Toxicol. 2008;102:59-65. https://doi.org/10.1111/j.1742-7843.2007.00158.x
14. Caraglia M, Beninati S, Giuberti G, D’Alessandro AM, Lentini A, Abbruzzese A, et al. Alternative therapy of earth elements increases the chondroprotective effects of chondroitin sulfate in mice. Exp Mol Med. 2005;37:476-81. https://doi.org/10.1038/emm.2005.58
15. Bassleer CT, Combal JP, Bougaret S, Malaise M. Effects of chondroitin sulfate and interleukin-1 beta on human articular chondrocytes cultivated in clusters. Osteoarthritis Cartilage. 1998;6:196e204. https://doi.org/10.1053/joca.199 8.0112
16. Uebelhart D, Thonar EJ, Zhang J, Williams JM. Protective effect of exogenous chondroitin 4,6-sulfate in the acute degradation of articular cartilage in the rabbit. Osteoarthritis Cartilage. 1998;6(Suppl A):6-13. https://doi.org/10.1016/ s1063-4584(98)80005-8
17. Wang L, Wang J, Almqvist KF, Veys EM, Verbruggen G. Influ- ence of polysulphated polysaccharides and hydrocortisone on the extracellular matrix metabolism of human articular chondrocytes in vitro. Clin Exp Rheumatol. 2002;20:669-76. https://doi.org/10.1016/s1063-4584(03)00168-7
18. Orth MW, Peters TL, Hawkins JN. Inhibition of articular cartilage degradation by glucosamine HCl and chondroitin sulphate. Equine Vet J Suppl. 2010;34:224-9. https://doi.org/10.1111/j.2042-3306.2002.tb05423.x
19. Chan PS, Caron JP, Orth MW. Effect of glucosamine and chondroitin sulfate on regulation of gene expression of proteolytic enzymes and their inhibitors in interleukin-1- challenged bovine articular cartilage explants. Am J Vet Res. 2005;66:1870-6. https://doi.org/10.2460/ajvr.2005.66.1870
20. Chou MM, Vergnolle N, McDougall JJ, Wallace JL, Marty S, Teskey V, et al. Effects of chondroitin and glucosamine sulfate in a dietary bar formulation on inflammation, interleukin- 1beta, matrix metalloprotease-9, and cartilage damage in arthritis. Exp Biol Med. 2005;230:255-62. https://doi.org/10.1177/153 537020523000405
21. Monfort J, Nacher M, Montell E, Vila J, Verges J, Benito P. Chondroitin sulfate and hyaluronic acid (500e730 kDa) inhibit stromelysin-1 synthesis in human osteoarthritic chondrocytes. Drugs Exp Clin Res. 2005;31:71-6. https:// doi.org/10.1016/s1699-258x(05)72734-0
22. Baici A, Bradamante P. Interaction between human leukocyte elastase and chondroitin sulfate. Chem Biol Interact. 1984;51:1-11. https://doi.org/10.10 16/0009-2797(84)90015-2
23. Baici A, Lang A. Cathepsin B secretion by rabbit articular chondrocytes: modulation by cycloheximide and glycosami- noglycans. Cell Tissue Res. 1990;259:567-73. https://doi.org/10.1007/bf01740785
24. Verbruggen G, Veys EM. Influence of sulphated glycosamino- glycans upon proteoglycan metabolism of the synovial lining cells. Acta Rhumatol Belg. 1977;1:75-92.
25. Nishikawa H, Mori I, Umemoto J. Influences of sulfated glycosaminoglycans on biosynthesis of hyaluronic acid in rabbit knee synovial membrane. Arch Biochem Biophys. 1985;240:146-53. https://doi.org/10.1016/0003-9861(85) 90017-7
26. Nishikawa H, Mori I, Umemoto J. Glycosaminoglycan polysulfate- induced stimulation of hyaluronic acid synthesis in rabbit knee synovial membrane: involvement of binding protein and calcium ion. Arch Biochem Biophys. 1988;266:201-9. https://doi.org/10.1016/0003-9861(88)90251-2
27. Chan PS, Caron JP, Rosa GJ, Orth MW. Glucosamine and chondroitin sulfate regulate gene expression and synthesis of nitric oxide and prostaglandin E(2) in articular cartilage explants. Osteoarthritis Cartilage. 2005;13:387-94. https://doi.org/10.1016/j.joca.2005.01.003
28. Chan PS, Caron JP, Orth MW. Short-term gene expression changes in cartilage explants stimulated with interleukin beta plus glucosamine and chondroitin sulfate. J Rheumatol. 2006;33:1329-40.
29. Tat SK, Pelletier JP, Vergés J, Montell E, Lajeunesse D, Fahmi H, et al. Chondroitin and glucosamine sulfate in combination decrease the pro-resorptive properties of human osteoarthritis subchondral bone osteoblasts. Arthritis Res Ther. 2007;9:R117. https://doi.org/10.1186/ar2325
30. Zhang W, Doherty M, Arden N, et al. EULAR evidence based recommendations for the management of hip osteoarthritis: report of a task force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT). Ann Rheum Dis. 2005;64:669-81. https://doi.org/10. 1136/ard.2004.028886
31. Zhang W, Moskowitz RW, Nuki G, et al. OARSI recommendations for the man- agement of hip and knee osteoarthritis, part II: OARSI evidence-based, expert consensus guidelines. Osteoarthritis Cartilage. 2008;16:137-62. https://doi.org/10.1016/j.joca.2008.04.019
32. Zhang W, Moskowitz RW, Nuki G, et al. OARSI recommendations for the man- agement of hip and knee osteoarthritis. Part I: Critical appraisal of existing treatment guidelines and systematic review of current research evidence. Osteoarthritis Cartilage. 2007;15:981-1000. https://doi.org/10.1016/j.joca.20 08.04.019
33. Zhang W, Nuki G, Moskowitz RW, et al. OARSI recommendations for the man- agement of hip and knee osteoarthritis. Part III: changes in evidence following systematic cumulative update of research published through January 2009. Osteoarthritis Cartilage. 2010;18:476-99.
34. Hochberg MC, Altman RD, April KT, et al. American College of Rheumatology 2012 recommendations for the use of nonpharmacologic and pharmacologic therapies in osteoarthritis of the hand, hip, and knee. Arthritis Care Res (Hobo-ken). 2012;64:465-74. https://doi.org/10.1002/acr.21596
35. McAlindon TE, Bannuru RR, Sullivan MC, et al. OARSI guidelines for the non-surgical management of knee osteoarthritis. Osteoarthritis Cartilage. 2014;22(3):363-88. https://doi.org/10.1016/ j.joca.2014.01.003
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ФГАОУ ВО «Первый Московский государственный медицинский университет им. И.М. Сеченова» Минздрава России (Сеченовский Университет), кафедра клинической фармакологии и пропедевтики внутренних болезней лечебного факультета, Москва, Россия
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V.N. Drozdov, E.V. Shikh, S.Y. Serebrova, A.G. Abrosimov, A.K. Starodubtsev
Сlinical pharmacology and internal medicine propaedeutics of I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), Department of general medicine, Moscow, Russia