Нестероидные противовоспалительные препараты в лечении остеоартрита: проблема выбора с учетом безопасности и влияния на хрящ

1. Bijlsma JW, Berenbaum F, Lafeber FP. Osteoarthritis: an update with relevance for clinical practice. Lancet 2011; 377: 2115–26.
2. Dawson JILI, Linsell L, Zondervan K et al. Impact of persistent hip or knee pain overall health status in elderly People: a longitudinal population study. Arthr Rheum 2005; 53: 368–74.
3. Bruyere O, Cooper CC, Pelletier J-P et al. An algorithm recommendation for the management of knee osteoarthritis in Europe and internationally: A report from a task force of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO). Sem Arthr Rheum 2014; 44: 252–63.
4. Adams PF, Hendershot GE, Marano MA. Current estimates from the National Health Interview Survey, 1996. Vital Health Stat 10 1999.
5. Ruoff G. Management of pain in patients with multiple health problems: a guide for the practicing physician. Am J Med 1998; 105 (1B): 53S–60S.
6. Janssen M, Dijkmans B, van der Sluijs FA. Upper gastrointestinal complaints and complication in chronic rheumatic patients in comparison with other chronic diseases. Br J Rheum 1992; 31: 747–52.
7. Насонова В.А., Сигидин Я.А. Патогенетическая терапия ревматических заболеваний. М., 1985; с. 58–63. / Nasonova V.A., Sigidin Ia.A. Patogeneticheskaia terapiia revmaticheskikh zabolevanii. M., 1985; s. 58–63. [in Russian]
8. Haskisson EC. Clinical aspects of chondroprotection. Sem Arthr Rheum 1990; 19: 30–2.
9. Doherty M. Chondroprotection by nonsteroidal anti-inflammatory drugs. Ann Rheum Dis 1989; 48: 619–21.
10. Brandt KD. The mechanism of action of nonsteroidal anti-inflammatory drugs. J Rheum 1991; 18: 120–1.
11. Ostensen M. Cartilage changes in arthritis do non-steroidal antiphlogistics have positive or negative effects? Tiddsskr-Nor-Laegeforen 1991; 111: 838–40.
12. Manicourt DH, Pita JC. Progressive depletion of hyaluronic acid in early experimental osteoarthritis in dogs. Arthr Rheum 1988; 31: 538–44.
13. Sweet MB, Thonar EJ, Immelman AR, Solomon L. Biochemical changes in progressive osteoarthrosis. Ann Rheum Dis 1977; 36: 387–98.
14. Thonar EJ, Sweet MB, Immelman AR, Lyons G. Hyaluronate in articular cartilage: age-related changes. Calcif Tissue Res 1978; 26: 19–21.
15. Rizkalla G, Reiner A, Bogoch T, Poole AR. Studies of the articular cartilage proteoglycan aggrecan in health and osteoarthritis. Evidence of molecular heterogeneity and extensive molecular changes in disease. J Clin Res 1992; 90: 2268–77.
16. Holmes MW, Bayliss MT, Muir H. Hyaluronic acid in human articular cartilage. Age-related changes in content and size. Biochem J 1988; 250: 435–41.
17. Meyer-Carrive I, Ghosh P. Effects of tiaprofenic acid (Surgam) on cartilage proteoglycans in the rabbit joint immobilization model. Ann Rheum Dis 1992; 51: 448–55.
18. Vries BJ, Van der Berg W. Impact of NSAIDS on murine antigen induced arthritis. A light microscopic investigation of anti-inflammatory and bone protective effects. J Rheum 1990; 17: 295–303.
19. Osteoarthritis. Clinical and Experimental aspects. Ed. J.-E.Reginster, J.-P.Pelletier, Y.Henrotin. Springer, 1999.
20. Haskinsson EC, Berry H, Gishen P et al. Effects of anti-inflammatory drugs on the progression of osteoarthritis of the knee. J Rheum 1995; 22: 1941–6.
21. Rashad S, Revell P, Hemingway A et al. Effect of non-steroidal anti-inflammatory drugs on the course of osteoarthritis. Lancet 1989; I: 519–22.
22. Howell DS, Pita JC, Muller FJ et al. Treatment of OA with tiaprofenic acid: biochemical and histological protection against cartilage breakdown in the Pond-Nuki canine model. J Rheum 1991; 18 (Suppl. 27): 138–42.
23. Blot L, Marcelis A, Devogelaer JP, Manicourt DH. Effects of diclofenac, aceclofenac and meloxicam on the metabolism of proteoglycans and hyaluronan in osteoarthritic human articular cartilage. Br J Pharmacol 2000; 131: 1413–21.
24. Ding C. Do NSAIDs affect the progression of osteoarthritis? Inflammation 2002; 131: 1413–21.
25. Dingle JT. The effect of nonsteroidal anti-inflammatory drugs on human articular cartilage glycosaminoglycan synthesis. Osteoarthritis Cartilage 1999, 7: 313–4.
26. Henroitin Y, Reginster JY. In-vitro differences among nonsteroidal anti-inflammatory drugs in their activities related to osteoarthritis pathophysiology. Ostearthritis Cartilage 1999, 7: 355–7.
27. Makherje P, Rachita C, Aisen PS, Pasinetti GM. Non-steroidal anti-inflammatory drugs protect against chondrocyte apoptotic death. Clin Exp Rheimatol 2001; 19: S7–S11.
28. Fernandes JC, Caron JP, Martel-Pelletier J et al. Effects of tenidap on the progression of osteoarthritic lesions in a canine experimental model. Suppression of metalloprotease and interleukin-1 activity. Arthr Rheum 1997; 40: 284–94.
29. Pelletier JC, Lajeunesse D, Jovanovic DV et al. Carprofen simultaneously reduces progression on morphological changes in cartilage and subchondral bone in experimental dog osteoarthritis. J Rheumatol 2000; 27: 2893–902.
30. Ratcliffe A, Azzo W, Saed-Nejad F et al. In vivo effects of naproxen on composition, proteoglycan metabolism, and matrix metalloproteinase activities in canine articular cartilage. J Orthop Res 1993; 11: 163–71.
31. Serni U, Manoni A, Benucci M. Is there preliminary in-vivo evidence for an influence of nonsteroidal anti-inflammatory drugs on progression in osteoarthritis? Part II-evidence from animal models. Osteoarthritis Cartilage 1999; 7: 351–2.
32. Mastbergen SC, Lafeber FP, Bijlsma JW. Selective COX-2 inhibition prevents proinflammatory cytokine-induced cartilage damage. Rheumatologe (Oxf) 2002; 41: 801–8.
33. Hajjaji EI, Marcells A, Devogelaer JP, Manicourt DH. Celecoxib has a positive effect on the overall metabolism of hyaluronan and proteoglycans in human osteoarthritic cartilage. J Rheumatol 2003; 30: 2444–51.
34. Mastbergen SC, Bijlsma JW, Lafeber FP. Selective COX-2 inhibition is favorable to human early and late-atage osteoarthritis: a human in vitro study. Osteoarthritis Cartilage 2005; 13: 519–26.
35. Mastbergen SC, Jansen NW, Bijlsma JW, Lafeber FP. Differetial direct effects of cyclo-oxygenase-1/2 inhibition on proteoglycan turnover of human osteoarthritic cartilage: an in vitro study. Arthritis Res Therapy 2006; 8: R2. DOI: 10.1186/ar1846
36. Collier S, Ghosh P. Comparison of the effects of non-steroidal anti-inflammatory drugs (NSAIDs) on proteiglican synthesis by articular cartilage explant and chondrocytemonolayer cultures. Biochem Pharmacol 1991; 41: 1375–84.
37. Smith RL, Kajiyama G, Lane NE. Nonsteroidal anti-inflammatory drugs: effects on normal and interleukin 1 treated human articular chondrocyte metabolism in vitro. J Rheumatol 1995; 22: 1131–7.
38. David MJ, Vignon E, Peschard MJ et al. Effect of non-steroidal anti-unflammatory drugs (NSAIDs) on glycosyltransferase activity from human osteoarthritic cartilage. Br J Rheumatol 1992; 31 (Suppl. 1): 13–7.
39. Bort R, Ponsoda X, Carrasco E et al. Metabolism of aceclofenac in humans. Drug Metab Dispos 1996; 24: 834–41.
40. Henrotin Y, de Leval X, Mathy-Harlet M et al. In vitro effects of aceclofenac and its metabolites on the production by chondrocyres of inflammatory mediators. Inflamm Res 2001; 50: 391–9.
41. Hinz B, Rau T, Auge D et al. Aceclofenac spares cyclooxygenase 1 as a result of limited but sustained biotransformation to diclofenac. Clin Pharmacol Ther 2003; 74: 222–35.
42. Yamazaki R, Kawai S, Matsuzaki T et al. Aceclofenac blocks prostaglandine E2 production following its intracellular conversion into cyclooxygenase inhibitors. Eur J Pharmaсol 1997; 328: 181–7.
43. Diaz C, Rodriguez de la Serna A, Geli C et al. Efficacy and tolerability of aceclofenac versus diclofenacin the treatment of knee osteoarthritis: a multicenter study. Eur J Rheumatol Inflamm 1996; 16: 17–22.
44. Busquier PM, Calero E, Rodriguez M et al. Comparison of aceclofenac with piroxicam in the treatment osteoarthritis. Clin Rheum 1997; 16: 154–9.
45. Torri G, Vignati C, Agrifoglio E et al. Aceclofenac versus piroxicam in the management of osteoarthritis of knee: a double-blind controlled study. Curr Ther Res 1994; 55: 576–83.
46. Ward DE, Veys EM, Bowdler JM et al. Comparison of aceclofenac with diclofenac in the treatment of osteoarthritis. Clin Rheum 1995; 14: 656–62.
47. Kornasoff D, Frerick H, Bowdler JM et al. Aceclofenac as a well-tolerated alternative to naproxen in the treatment of osteoarthritis. Clin Rheum 1997; 16: 32–8.
48. Lidburg PS, Vojnovic J, Warner TD. COX2/COX1 selectivity of aceclofenac in comparison with celecoxib and rofecoxob in the human whole blood assay. Fifth world Congress of the OARSI, Barselona, Spain, 4–6 October. 2000; 8 (Suppl. B): Th053.
49. Peris F, Bird HA, Srni U et al. Treatment compliance and safety of aceclofenac versus standart NSAIDs in patients with common arthritis disorders: a meta-analysis. Eur J Rheum Inflamm 1996; 16 (1): 37–45.
50. Castellsague J, Riera-Guardia N, Calingaert D et al. Individual NSAIDs and Upper Gastrointestinal Complications A Systematic Review and Meta-Analysis of Observational Studies (the SOS Project). Drug Saf 2012; 35 (12): 1127–46. DOI: 0114-916/12/0012-1127
51. Patel PB, Patel TK. Efficacy and safety of aceclofenac in osteoarthritis: a meta-analysis of randomized controlled trials. Eur J Rheumatol 2017; 4: 11–8. DOI: 10.5152/eurjrheum.2017.160080
52. Huskisson EC, Irani M, Murray F. A large prospective open-label, multicenter SAMM study, comparing the safety of aceclofenac with diclofenac in patients with rheumatic disease. Eur J Rheumatol Inflamm 2000; 17 (1): 1–7.
53. Llorente MJ. Specific types of non-steroidal anti-inflammatory drugs and relative risk of upper gastrointestinal bleeding [abstract]. Br J Rheumatol 1998; 37 (Suppl. 1): 115.
54. Yanagawa A, Endo T, Kusakari K et al. Endocopic evaluation of aceclofenac-induced gastrointestinal mucosal damage: a double-blind comparison with sodium diclofenac and placebo. Jpn J Rheum 1998; 8: 249–59.
55. Martel-Рelletier J, Cloutier J-M, Pelletier J-P. Effect of aceclofenac and diclofenac on synovial inflammatory factors in human osteoarthritis. Clin Drug Invest 1997; 14: 226–32.
56. Henrotin Y, de Laval X, Mathy-Hartet M et al. In vitro effects of aceclofenac and its metabolites on the production by chondrocytes of inflammatory mediators. Inflamm Res 1997; 25: 314–9.
57. Gonsalez E, de la Cruz C, de Nicola’s R et al. Long-term effect of nonsteroidal anti-inflammatory drugs on the production of cytokines and other inflammatory mediators by blood cells of patients with osteoarthritis. Agents Actions 1994; 41: 171–8.
58. Blanco FJ, Maneiro E, de Toro FJ et al. Effect of NSAIDs on synthesis of IL-1 receptor antagonist (IL-Ra) by human articular chondrocytes [abstr.]. Osteoarthritis Cartilage 2000; 8 (Suppl. S27).
59. Akimoto H, Yamazaki R, Hashimoto S et al. 4-Hydroxy aceclofenac suppressed the interleukin-1-induced production of promatrix metalloproteases and release of sulfated-glycosaminoglycans from rabbit articular chondrocytes. Eur J Pharmacol 2000; 401: 429–36.
60. Yamazaki R, Kawai S, Mizushima Y et al. A mayor metabolite of aceclofenac, 4-hydroxy aceclofenac, suppressed the production of interstitial pro-collafenase|proMMP-1 and pro-stromelysin-1|proMMP-3 human rheumatoid synovial cells. Inflamm Res 2000; 49: 133–8.

________________________________________________

1. Bijlsma JW, Berenbaum F, Lafeber FP. Osteoarthritis: an update with relevance for clinical practice. Lancet 2011; 377: 2115–26.
2. Dawson JILI, Linsell L, Zondervan K et al. Impact of persistent hip or knee pain overall health status in elderly People: a longitudinal population study. Arthr Rheum 2005; 53: 368–74.
3. Bruyere O, Cooper CC, Pelletier J-P et al. An algorithm recommendation for the management of knee osteoarthritis in Europe and internationally: A report from a task force of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO). Sem Arthr Rheum 2014; 44: 252–63.
4. Adams PF, Hendershot GE, Marano MA. Current estimates from the National Health Interview Survey, 1996. Vital Health Stat 10 1999.
5. Ruoff G. Management of pain in patients with multiple health problems: a guide for the practicing physician. Am J Med 1998; 105 (1B): 53S–60S.
6. Janssen M, Dijkmans B, van der Sluijs FA. Upper gastrointestinal complaints and complication in chronic rheumatic patients in comparison with other chronic diseases. Br J Rheum 1992; 31: 747–52.
7. Nasonova V.A., Sigidin Ia.A. Patogeneticheskaia terapiia revmaticheskikh zabolevanii. M., 1985; s. 58–63. [in Russian]
8. Haskisson EC. Clinical aspects of chondroprotection. Sem Arthr Rheum 1990; 19: 30–2.
9. Doherty M. Chondroprotection by nonsteroidal anti-inflammatory drugs. Ann Rheum Dis 1989; 48: 619–21.
10. Brandt KD. The mechanism of action of nonsteroidal anti-inflammatory drugs. J Rheum 1991; 18: 120–1.
11. Ostensen M. Cartilage changes in arthritis do non-steroidal antiphlogistics have positive or negative effects? Tiddsskr-Nor-Laegeforen 1991; 111: 838–40.
12. Manicourt DH, Pita JC. Progressive depletion of hyaluronic acid in early experimental osteoarthritis in dogs. Arthr Rheum 1988; 31: 538–44.
13. Sweet MB, Thonar EJ, Immelman AR, Solomon L. Biochemical changes in progressive osteoarthrosis. Ann Rheum Dis 1977; 36: 387–98.
14. Thonar EJ, Sweet MB, Immelman AR, Lyons G. Hyaluronate in articular cartilage: age-related changes. Calcif Tissue Res 1978; 26: 19–21.
15. Rizkalla G, Reiner A, Bogoch T, Poole AR. Studies of the articular cartilage proteoglycan aggrecan in health and osteoarthritis. Evidence of molecular heterogeneity and extensive molecular changes in disease. J Clin Res 1992; 90: 2268–77.
16. Holmes MW, Bayliss MT, Muir H. Hyaluronic acid in human articular cartilage. Age-related changes in content and size. Biochem J 1988; 250: 435–41.
17. Meyer-Carrive I, Ghosh P. Effects of tiaprofenic acid (Surgam) on cartilage proteoglycans in the rabbit joint immobilization model. Ann Rheum Dis 1992; 51: 448–55.
18. Vries BJ, Van der Berg W. Impact of NSAIDS on murine antigen induced arthritis. A light microscopic investigation of anti-inflammatory and bone protective effects. J Rheum 1990; 17: 295–303.
19. Osteoarthritis. Clinical and Experimental aspects. Ed. J.-E.Reginster, J.-P.Pelletier, Y.Henrotin. Springer, 1999.
20. Haskinsson EC, Berry H, Gishen P et al. Effects of anti-inflammatory drugs on the progression of osteoarthritis of the knee. J Rheum 1995; 22: 1941–6.
21. Rashad S, Revell P, Hemingway A et al. Effect of non-steroidal anti-inflammatory drugs on the course of osteoarthritis. Lancet 1989; I: 519–22.
22. Howell DS, Pita JC, Muller FJ et al. Treatment of OA with tiaprofenic acid: biochemical and histological protection against cartilage breakdown in the Pond-Nuki canine model. J Rheum 1991; 18 (Suppl. 27): 138–42.
23. Blot L, Marcelis A, Devogelaer JP, Manicourt DH. Effects of diclofenac, aceclofenac and meloxicam on the metabolism of proteoglycans and hyaluronan in osteoarthritic human articular cartilage. Br J Pharmacol 2000; 131: 1413–21.
24. Ding C. Do NSAIDs affect the progression of osteoarthritis? Inflammation 2002; 131: 1413–21.
25. Dingle JT. The effect of nonsteroidal anti-inflammatory drugs on human articular cartilage glycosaminoglycan synthesis. Osteoarthritis Cartilage 1999, 7: 313–4.
26. Henroitin Y, Reginster JY. In-vitro differences among nonsteroidal anti-inflammatory drugs in their activities related to osteoarthritis pathophysiology. Ostearthritis Cartilage 1999, 7: 355–7.
27. Makherje P, Rachita C, Aisen PS, Pasinetti GM. Non-steroidal anti-inflammatory drugs protect against chondrocyte apoptotic death. Clin Exp Rheimatol 2001; 19: S7–S11.
28. Fernandes JC, Caron JP, Martel-Pelletier J et al. Effects of tenidap on the progression of osteoarthritic lesions in a canine experimental model. Suppression of metalloprotease and interleukin-1 activity. Arthr Rheum 1997; 40: 284–94.
29. Pelletier JC, Lajeunesse D, Jovanovic DV et al. Carprofen simultaneously reduces progression on morphological changes in cartilage and subchondral bone in experimental dog osteoarthritis. J Rheumatol 2000; 27: 2893–902.
30. Ratcliffe A, Azzo W, Saed-Nejad F et al. In vivo effects of naproxen on composition, proteoglycan metabolism, and matrix metalloproteinase activities in canine articular cartilage. J Orthop Res 1993; 11: 163–71.
31. Serni U, Manoni A, Benucci M. Is there preliminary in-vivo evidence for an influence of nonsteroidal anti-inflammatory drugs on progression in osteoarthritis? Part II-evidence from animal models. Osteoarthritis Cartilage 1999; 7: 351–2.
32. Mastbergen SC, Lafeber FP, Bijlsma JW. Selective COX-2 inhibition prevents proinflammatory cytokine-induced cartilage damage. Rheumatologe (Oxf) 2002; 41: 801–8.
33. Hajjaji EI, Marcells A, Devogelaer JP, Manicourt DH. Celecoxib has a positive effect on the overall metabolism of hyaluronan and proteoglycans in human osteoarthritic cartilage. J Rheumatol 2003; 30: 2444–51.
34. Mastbergen SC, Bijlsma JW, Lafeber FP. Selective COX-2 inhibition is favorable to human early and late-atage osteoarthritis: a human in vitro study. Osteoarthritis Cartilage 2005; 13: 519–26.
35. Mastbergen SC, Jansen NW, Bijlsma JW, Lafeber FP. Differetial direct effects of cyclo-oxygenase-1/2 inhibition on proteoglycan turnover of human osteoarthritic cartilage: an in vitro study. Arthritis Res Therapy 2006; 8: R2. DOI: 10.1186/ar1846
36. Collier S, Ghosh P. Comparison of the effects of non-steroidal anti-inflammatory drugs (NSAIDs) on proteiglican synthesis by articular cartilage explant and chondrocytemonolayer cultures. Biochem Pharmacol 1991; 41: 1375–84.
37. Smith RL, Kajiyama G, Lane NE. Nonsteroidal anti-inflammatory drugs: effects on normal and interleukin 1 treated human articular chondrocyte metabolism in vitro. J Rheumatol 1995; 22: 1131–7.
38. David MJ, Vignon E, Peschard MJ et al. Effect of non-steroidal anti-unflammatory drugs (NSAIDs) on glycosyltransferase activity from human osteoarthritic cartilage. Br J Rheumatol 1992; 31 (Suppl. 1): 13–7.
39. Bort R, Ponsoda X, Carrasco E et al. Metabolism of aceclofenac in humans. Drug Metab Dispos 1996; 24: 834–41.
40. Henrotin Y, de Leval X, Mathy-Harlet M et al. In vitro effects of aceclofenac and its metabolites on the production by chondrocyres of inflammatory mediators. Inflamm Res 2001; 50: 391–9.
41. Hinz B, Rau T, Auge D et al. Aceclofenac spares cyclooxygenase 1 as a result of limited but sustained biotransformation to diclofenac. Clin Pharmacol Ther 2003; 74: 222–35.
42. Yamazaki R, Kawai S, Matsuzaki T et al. Aceclofenac blocks prostaglandine E2 production following its intracellular conversion into cyclooxygenase inhibitors. Eur J Pharmaсol 1997; 328: 181–7.
43. Diaz C, Rodriguez de la Serna A, Geli C et al. Efficacy and tolerability of aceclofenac versus diclofenacin the treatment of knee osteoarthritis: a multicenter study. Eur J Rheumatol Inflamm 1996; 16: 17–22.
44. Busquier PM, Calero E, Rodriguez M et al. Comparison of aceclofenac with piroxicam in the treatment osteoarthritis. Clin Rheum 1997; 16: 154–9.
45. Torri G, Vignati C, Agrifoglio E et al. Aceclofenac versus piroxicam in the management of osteoarthritis of knee: a double-blind controlled study. Curr Ther Res 1994; 55: 576–83.
46. Ward DE, Veys EM, Bowdler JM et al. Comparison of aceclofenac with diclofenac in the treatment of osteoarthritis. Clin Rheum 1995; 14: 656–62.
47. Kornasoff D, Frerick H, Bowdler JM et al. Aceclofenac as a well-tolerated alternative to naproxen in the treatment of osteoarthritis. Clin Rheum 1997; 16: 32–8.
48. Lidburg PS, Vojnovic J, Warner TD. COX2/COX1 selectivity of aceclofenac in comparison with celecoxib and rofecoxob in the human whole blood assay. Fifth world Congress of the OARSI, Barselona, Spain, 4–6 October. 2000; 8 (Suppl. B): Th053.
49. Peris F, Bird HA, Srni U et al. Treatment compliance and safety of aceclofenac versus standart NSAIDs in patients with common arthritis disorders: a meta-analysis. Eur J Rheum Inflamm 1996; 16 (1): 37–45.
50. Castellsague J, Riera-Guardia N, Calingaert D et al. Individual NSAIDs and Upper Gastrointestinal Complications A Systematic Review and Meta-Analysis of Observational Studies (the SOS Project). Drug Saf 2012; 35 (12): 1127–46. DOI: 0114-916/12/0012-1127
51. Patel PB, Patel TK. Efficacy and safety of aceclofenac in osteoarthritis: a meta-analysis of randomized controlled trials. Eur J Rheumatol 2017; 4: 11–8. DOI: 10.5152/eurjrheum.2017.160080
52. Huskisson EC, Irani M, Murray F. A large prospective open-label, multicenter SAMM study, comparing the safety of aceclofenac with diclofenac in patients with rheumatic disease. Eur J Rheumatol Inflamm 2000; 17 (1): 1–7.
53. Llorente MJ. Specific types of non-steroidal anti-inflammatory drugs and relative risk of upper gastrointestinal bleeding [abstract]. Br J Rheumatol 1998; 37 (Suppl. 1): 115.
54. Yanagawa A, Endo T, Kusakari K et al. Endocopic evaluation of aceclofenac-induced gastrointestinal mucosal damage: a double-blind comparison with sodium diclofenac and placebo. Jpn J Rheum 1998; 8: 249–59.
55. Martel-Рelletier J, Cloutier J-M, Pelletier J-P. Effect of aceclofenac and diclofenac on synovial inflammatory factors in human osteoarthritis. Clin Drug Invest 1997; 14: 226–32.
56. Henrotin Y, de Laval X, Mathy-Hartet M et al. In vitro effects of aceclofenac and its metabolites on the production by chondrocytes of inflammatory mediators. Inflamm Res 1997; 25: 314–9.
57. Gonsalez E, de la Cruz C, de Nicola’s R et al. Long-term effect of nonsteroidal anti-inflammatory drugs on the production of cytokines and other inflammatory mediators by blood cells of patients with osteoarthritis. Agents Actions 1994; 41: 171–8.
58. Blanco FJ, Maneiro E, de Toro FJ et al. Effect of NSAIDs on synthesis of IL-1 receptor antagonist (IL-Ra) by human articular chondrocytes [abstr.]. Osteoarthritis Cartilage 2000; 8 (Suppl. S27).
59. Akimoto H, Yamazaki R, Hashimoto S et al. 4-Hydroxy aceclofenac suppressed the interleukin-1-induced production of promatrix metalloproteases and release of sulfated-glycosaminoglycans from rabbit articular chondrocytes. Eur J Pharmacol 2000; 401: 429–36.
60. Yamazaki R, Kawai S, Mizushima Y et al. A mayor metabolite of aceclofenac, 4-hydroxy aceclofenac, suppressed the production of interstitial pro-collafenase|proMMP-1 and pro-stromelysin-1|proMMP-3 human rheumatoid synovial cells. Inflamm Res 2000; 49: 133–8.

Н.В.Чичасова

ФГАОУ ВО «Первый Московский государственный медицинский университет им. И.М.Сеченова» Минздрава России. 119991, Россия, Москва, ул. Трубецкая, д. 8, стр. 2
kafedrarheum@yandex.ru

________________________________________________

N.V.Chichasova

I.M.Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation. 119991, Russian Federation, Moscow, ul. Trubetskaia, d. 8, str. 2
kafedrarheum@yandex.ru