Anti-inflammatory drugs with therapeutic effects and drug regulators
Abstract
For prostaglandin production, the enzyme cyclooxygenase (COX) is required. The two COX isoforms are constitutive COX-1 (which is responsible for physiological functions) and inducible COX-2 (involved in inflammation). COX inhibition explains both the medicinal (inhibition of COX-2) and negative effects (inhibition of COX-1) effects of non-steroidal anti-inflammatory medicines (NSAIDs). Nonsteroidal anti-inflammatory medicines (NSAIDs) act by blocking the enzyme cyclooxygenase (COX), which produces prostaglandins (PGs). To a greater or lesser extent, they share similar side effects, such as stomach and renal toxicity. According to a recent study, there are at least two COX isoenzymes. COX-1 is a naturally occurring enzyme that creates prostaglandins (PGs), which protect the stomach and kidneys. Aspirin's well-known anti-cancer impact could also be related to its influence on COX-2, which is expressed in this condition. As a result, selective COX-2 inhibitors may have new therapeutic potential as anticancer drugs, as well as in preventing premature labor and maybe reducing the progression of Alzheimer's disease.
Keywords:
cyclooxygenase, NASIDs, inflammation, colon cancer, anticancer agent
References
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2. Solomon LM, Juhlin L, Kirschenbaum MB. Prostaglandin on cutaneous vasculature. J Invest Dermatol. 1968 Oct;51(4):280-2. PMID: 5676860.
3. Williams TJ, Peck MJ. Role of prostaglandin-mediated vasodilatation in inflammation. Nature. 1977 Dec 8;270(5637):530-2. doi: 10.1038/270530a0. PMID: 593374.
4. Ferreira SH. Prostaglandins, aspirin-like drugs and analgesia. Nat New Biol. 1972 Dec 13;240(102):200-3. doi: 10.1038/newbio240200a0. PMID: 4629913.
5. Saxena PN, Beg MM, Singhal KC, Ahmad M. Prostaglandin-like activity in the cerebrospinal fluid of febrile patients. Indian J Med Res. 1979 Sep;70:495-8. PMID: 535962.
6. Higgs EA, Moncada S, Vane JR. Inflammatory effects of prostacyclin (PGI2) and 6-oxo-PGF1alpha in the rat paw. Prostaglandins. 1978 Aug;16(2):153-62. doi: 10.1016/0090-6980(78)90018-7. PMID: 360302.
7. Wallner BP, Mattaliano RJ, Hession C, Cate RL, Tizard R, Sinclair LK, Foeller C, Chow EP, Browing JL, Ramachandran KL, et al. Cloning and expression of human lipocortin, a phospholipase A2 inhibitor with potential anti-inflammatory activity. Nature. 1986 Mar 6-12;320(6057):77-81. doi: 10.1038/320077a0. PMID: 2936963.
8. Cirino G, Flower RJ. Human recombinant lipocortin 1 inhibits prostacyclin production by human umbilical artery in vitro. Prostaglandins. 1987 Jul;34(1):59-62. doi: 10.1016/0090-6980(87)90262-0. PMID: 2961007.
9. Cirino G, Peers SH, Flower RJ, Browning JL, Pepinsky RB. Human recombinant lipocortin 1 has acute local anti-inflammatory properties in the rat paw edema test. Proc Natl Acad Sci U S A. 1989 May;86(9):3428-32. doi: 10.1073/pnas.86.9.3428. PMID: 2470103; PMCID: PMC287146.
10. Pelt AC. Glucocorticoids: effects, action mechanisms, and therapeutic uses. Hauppauge, N.Y.: Nova Science. 2011; ISBN 978-1617287589.
11. Rhen T, Cidlowski JA. "Antiinflammatory action of glucocorticoids--new mechanisms for old drugs". The New England Journal of Medicine. Oct 2005; 353 (16): 1711–23. doi:10.1056/NEJMra050541
12. Buchanan WW, Kean WF. The treatment of acute rheumatism by salicin, by T.J. Maclagan--The Lancet, 1876. J Rheumatol. 2002 Jun;29(6):1321-3. PMID: 12064852.
13. Van Der Ouderaa FJ, Buytenhek M, Nugteren DH, Van Dorp DA. Acetylation of prostaglandin endoperoxide synthetase with acetylsalicylic acid. Eur J Biochem. 1980 Aug;109(1):1-8. doi: 10.1111/j.1432-1033.1980.tb04760.x. PMID: 6773769.
14. Vane JR, Flower RJ, Botting RM. History of aspirin and its mechanism of action. Stroke. 1990 Dec;21(12 Suppl):IV12-23. PMID: 2124385.
15. Miller TA. Protective effects of prostaglandins against gastric mucosal damage: current knowledge and proposed mechanisms. Am J Physiol. 1983 Nov;245(5 Pt 1):G601-23. doi: 10.1152/ajpgi.1983.245.5.G601. PMID: 6195926.
16. Robert A, Hanchar AJ, Lancaster C, Nezamis JE. Prostacyclin inhibits enteropooling and diarrhea. In: Vane JR, Bergstrom S, eds. Prostacyclin. Raven Press, New York; 1979.
17. Higgs GA, Vane JR, Hart FD, Wojtulewski JA. Effects of anti-inflammatory drugs on prostaglandins in rheumatoid arthritis. In: Robinson HJ, Vane JR, eds. Prostaglandin synthetase inhibitors. Raven Press, New York; 1988.
18. Flower RJ. Drugs which inhibit prostaglandin biosynthesis. Pharmacol Rev. 1974 Mar;26(1):33-67. PMID: 4208101.
19. Vane JR. Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nat New Biol. 1971 Jun 23;231(25):232-5. doi: 10.1038/newbio231232a0. PMID: 5284360.
20. Fu JY, Masferrer JL, Seibert K, Raz A, Needleman P. The induction and suppression of prostaglandin H2 synthase (cyclooxygenase) in human monocytes. J Biol Chem. 1990 Oct 5;265(28):16737-40. PMID: 2120205.
21. Masferrer JL, Zweifel BS, Seibert K, Needleman P. Selective regulation of cellular cyclooxygenase by dexamethasone and endotoxin in mice. J Clin Invest. 1990 Oct;86(4):1375-9. doi: 10.1172/JCI114850. PMID: 2120289; PMCID: PMC296874.
22. Fu JY, Masferrer JL, Seibert K, Raz A, Needleman P. The induction and suppression of prostaglandin H2 synthase (cyclooxygenase) in human monocytes. J Biol Chem. 1990 Oct 5;265(28):16737-40. PMID: 2120205.
23. Xie WL, Chipman JG, Robertson DL, Erikson RL, Simmons DL. Expression of a mitogen-responsive gene encoding prostaglandin synthase is regulated by mRNA splicing. Proc Natl Acad Sci U S A. 1991 Apr 1;88(7):2692-6. doi: 10.1073/pnas.88.7.2692. PMID: 1849272; PMCID: PMC51304.
24. Hemler M, Lands WE. Purification of the cyclooxygenase that forms prostaglandins. Demonstration of two forms of iron in the holoenzyme. J Biol Chem. 1976 Sep 25;251(18):5575-9. PMID: 823151.
25. DeWitt DL. Prostaglandin endoperoxide synthase: regulation of enzyme expression. Biochim Biophys Acta. 1991 May 8;1083(2):121-34. doi: 10.1016/0005-2760(91)90032-d. PMID: 1903657.
26. Ryseck R. Raynoscheck C. Macdonald-Bravo H, Dorfman K. Bravo R. Identification of an immediate early gene, PGHs-6. whose protein product has prostaglandin synthase cyclooxygenase activity. Cell Growth Differ; 1992.
27. Whittle BJ, Higgs GA, Eakins KE, Moncada S, Vane JR. Selective inhibition of prostaglandin production in inflammatory exudates and gastric mucosa. Nature. 1980 Mar 20;284(5753):271-3. doi: 10.1038/284271a0. PMID: 6767192.
28. Vargaftig BB. Salicylic acid fails to inhibit generation of thromboxane A2 activity in platelets after in vivo administration to the rat. J Pharm Pharmacol. 1978 Feb;30(2):101-4. doi: 10.1111/j.2042-7158.1978.tb13171.x. PMID: 24092.
29. Flower RJ, Vane JR. Inhibition of prostaglandin synthetase in brain explains the anti-pyretic activity of paracetamol (4-acetamidophenol). Nature. 1972 Dec 15;240(5381):410-1. doi: 10.1038/240410a0. PMID: 4564318.
30. Brideau C, Kargman S, Liu S, Dallob AL, Ehrich EW, Rodger IW, Chan CC. A human whole blood assay for clinical evaluation of biochemical efficacy of cyclooxygenase inhibitors. Inflamm Res. 1996 Feb;45(2):68-74. doi: 10.1007/BF02265118. PMID: 8907587.
31. Ford-Hutchinson AW. New highly selective COX-2 inhibitors. In: Vane J, Botting J, editors. Selective COX-2 Inhibitors. Pharmacology, Clinical Effects and Therapeutic Potential. London: Kluwer Academic Publishers and William Harvey Press. 1998;117–25.
32. Mitchell JA, Akarasereenont P, Thiemermann C, Flower RJ, Vane JR. Selectivity of nonsteroidal antiinflammatory drugs as inhibitors of constitutive and inducible cyclooxygenase. Proc Natl Acad Sci U S A. 1993 Dec 15;90(24):11693-7. doi: 10.1073/pnas.90.24.11693. PMID: 8265610; PMCID: PMC48050.
33. Cao C, Matsumura K, Yamagata K, Watanabe Y. Cyclooxygenase-2 is induced in brain blood vessels during fever evoked by peripheral or central administration of tumor necrosis factor. Mol Brain Res. 1998; 56:45-56
34. Beiche F, Brune K, Geisslinger G, Goppelt-Struebe M. Expression of cyclooxygenase isoforms in the rat spinal cord and their regulation during adjuvant-induced arthritis. Inflamm Res. 1998 Dec;47(12):482-7. doi: 10.1007/s000110050362. PMID: 9892042.
35. Bennett P, Slater D . COX-2 expression in labor. In: Vane J, Botting J, Botting R (eds) Improved non-steroid anti-inflammatory drugs. COX-2 enzyme inhibitors. Kluwer Academic, Lancaster. 1996; pp 167-188
36. Gibb W, Sun M. Localization of prostaglandin H synthase type 2 protein and mRNA in term human fetal membranes and decidua. J Endocrinol. 1996 Sep;150(3):497-503. doi: 10.1677/joe.0.1500497. PMID: 8882169.
37. Langenbach R, Morham SG, Tiano HF, Loftin CD, Ghanayem BI, Chulada PC, Mahler JF, Lee CA, Goulding EH, Kluckman KD, Kim HS, Smithies O. Prostaglandin synthase 1 gene disruption in mice reduces arachidonic acid-induced inflammation and indomethacin-induced gastric ulceration. Cell. 1995 Nov 3;83(3):483-92. doi: 10.1016/0092-8674(95)90126-4. PMID: 8521478.
38. Brown NL, Alvi SA, Elder MG, Bennett PR, Sullivan MH. A spontaneous induction of fetal membrane prostaglandin production precedes clinical labour. J Endocrinol. 1998 May;157(2):R1-6. doi: 10.1677/joe.0.157r001. PMID: 9659298.
39. McAdam BF, Catella-Lawson F, Mardini IA, Kapoor S, Lawson JA, FitzGerald GA. Systemic biosynthesis of prostacyclin by cyclooxygenase (COX)-2: the human pharmacology of a selective inhibitor of COX-2. Proc Natl Acad Sci U S A. 1999 Jan 5;96(1):272-7. doi: 10.1073/pnas.96.1.272. Erratum in: Proc Natl Acad Sci U S A 1999 May 11;96(10):5890. PMID: 9874808; PMCID: PMC15129.
40. Topper JN, Cai J, Falb D, Gimbrone MA Jr. Identification of vascular endothelial genes differentially responsive to fluid mechanical stimuli: cyclooxygenase-2, manganese superoxide dismutase, and endothelial cell nitric oxide synthase are selectively up-regulated by steady laminar shear stress. Proc Natl Acad Sci U S A. 1996 Sep 17;93(19):10417-22. doi: 10.1073/pnas.93.19.10417. PMID: 8816815; PMCID: PMC38399.
41. Mitchell JA, Akarasereenont P, Thiemermann C, Flower RJ, Vane JR. Selectivity of nonsteroidal antiinflammatory drugs as inhibitors of constitutive and inducible cyclooxygenase. Proc Natl Acad Sci U S A. 1993 Dec 15;90(24):11693-7. doi: 10.1073/pnas.90.24.11693. PMID: 8265610; PMCID: PMC48050.
42. Meade EA, Smith WL, DeWitt DL. Differential inhibition of prostaglandin endoperoxide synthase (cyclooxygenase) isozymes by aspirin and other non-steroidal anti-inflammatory drugs. J Biol Chem. 1993 Mar 25;268(9):6610-4. PMID: 8454631.
43. Lanza FL. A review of gastric ulcer and gastroduodenal injury in normal volunteers receiving aspirin and other non-steroidal anti-inflammatory drugs. Scand J Gastroenterol Suppl. 1989;163:24-31. doi: 10.3109/00365528909091171. PMID: 2683026.
44. Vane JR, Botting RM. Mechanism of action of aspirin-like drugs. Semin Arthritis Rheum. 1997 Jun;26(6 Suppl 1):2-10. doi: 10.1016/s0049-0172(97)80046-7. PMID: 9219313.
45. Thun MJ, Namboodiri MM, Heath CW Jr. Aspirin use and reduced risk of fatal colon cancer. N Engl J Med. 1991 Dec 5;325(23):1593-6. doi: 10.1056/NEJM199112053252301. PMID: 1669840.
46. Luk GD. Prevention of gastrointestinal cancer--the potential role of NSAIDs in colorectal cancer. Schweiz Med Wochenschr. 1996 May 11;126(19):801-12. PMID: 8693304.
47. Gustafson-Svard C, Lilja I, Hallbook 0 , Sjodahl R. Cyclooxygenase-I and cyclooxygenase-2 gene expression in human colorectal adenocarcinomas and in azoxymethane induced colonic tumours in rats. Gut. 1996; 38:79-84
48. Kutchera W, Jones DA, Matsunami N, Groden J, McIntyre TM, Zimmerman GA, White RL, Prescott SM. Prostaglandin H synthase 2 is expressed abnormally in human colon cancer: evidence for a transcriptional effect. Proc Natl Acad Sci U S A. 1996 May 14;93(10):4816-20. doi: 10.1073/pnas.93.10.4816. PMID: 8643486; PMCID: PMC39362.
49. McGeer PL, McGeer EG. The inflammatory response system of brain: implications for therapy of Alzheimer and other neurodegenerative diseases. Brain Res Brain Res Rev. 1995 Sep;21(2):195-218. doi: 10.1016/0165-0173(95)00011-9. PMID: 8866675.
50. Breitner JC. The role of anti-inflammatory drugs in the prevention and treatment of Alzheimer's disease. Annu Rev Med. 1996;47:401-11. doi: 10.1146/annurev.med.47.1.401. PMID: 8712791.
51. Cochran FR, Vitek MP. Neuroinflammatory mechanisms in Alzheimer's disease: new opportunities for drug discovery. Expert Opin Invest Drugs. 1996; 5:449-455
52. Pasinetti GM, Aisen PS. Cyclooxygenase-2 expression is increased in frontal cortex of Alzheimer's disease brain. Neuroscience. 1998 Nov;87(2):319-24. doi: 10.1016/s0306-4522(98)00218-8. PMID: 9740394.
2. Solomon LM, Juhlin L, Kirschenbaum MB. Prostaglandin on cutaneous vasculature. J Invest Dermatol. 1968 Oct;51(4):280-2. PMID: 5676860.
3. Williams TJ, Peck MJ. Role of prostaglandin-mediated vasodilatation in inflammation. Nature. 1977 Dec 8;270(5637):530-2. doi: 10.1038/270530a0. PMID: 593374.
4. Ferreira SH. Prostaglandins, aspirin-like drugs and analgesia. Nat New Biol. 1972 Dec 13;240(102):200-3. doi: 10.1038/newbio240200a0. PMID: 4629913.
5. Saxena PN, Beg MM, Singhal KC, Ahmad M. Prostaglandin-like activity in the cerebrospinal fluid of febrile patients. Indian J Med Res. 1979 Sep;70:495-8. PMID: 535962.
6. Higgs EA, Moncada S, Vane JR. Inflammatory effects of prostacyclin (PGI2) and 6-oxo-PGF1alpha in the rat paw. Prostaglandins. 1978 Aug;16(2):153-62. doi: 10.1016/0090-6980(78)90018-7. PMID: 360302.
7. Wallner BP, Mattaliano RJ, Hession C, Cate RL, Tizard R, Sinclair LK, Foeller C, Chow EP, Browing JL, Ramachandran KL, et al. Cloning and expression of human lipocortin, a phospholipase A2 inhibitor with potential anti-inflammatory activity. Nature. 1986 Mar 6-12;320(6057):77-81. doi: 10.1038/320077a0. PMID: 2936963.
8. Cirino G, Flower RJ. Human recombinant lipocortin 1 inhibits prostacyclin production by human umbilical artery in vitro. Prostaglandins. 1987 Jul;34(1):59-62. doi: 10.1016/0090-6980(87)90262-0. PMID: 2961007.
9. Cirino G, Peers SH, Flower RJ, Browning JL, Pepinsky RB. Human recombinant lipocortin 1 has acute local anti-inflammatory properties in the rat paw edema test. Proc Natl Acad Sci U S A. 1989 May;86(9):3428-32. doi: 10.1073/pnas.86.9.3428. PMID: 2470103; PMCID: PMC287146.
10. Pelt AC. Glucocorticoids: effects, action mechanisms, and therapeutic uses. Hauppauge, N.Y.: Nova Science. 2011; ISBN 978-1617287589.
11. Rhen T, Cidlowski JA. "Antiinflammatory action of glucocorticoids--new mechanisms for old drugs". The New England Journal of Medicine. Oct 2005; 353 (16): 1711–23. doi:10.1056/NEJMra050541
12. Buchanan WW, Kean WF. The treatment of acute rheumatism by salicin, by T.J. Maclagan--The Lancet, 1876. J Rheumatol. 2002 Jun;29(6):1321-3. PMID: 12064852.
13. Van Der Ouderaa FJ, Buytenhek M, Nugteren DH, Van Dorp DA. Acetylation of prostaglandin endoperoxide synthetase with acetylsalicylic acid. Eur J Biochem. 1980 Aug;109(1):1-8. doi: 10.1111/j.1432-1033.1980.tb04760.x. PMID: 6773769.
14. Vane JR, Flower RJ, Botting RM. History of aspirin and its mechanism of action. Stroke. 1990 Dec;21(12 Suppl):IV12-23. PMID: 2124385.
15. Miller TA. Protective effects of prostaglandins against gastric mucosal damage: current knowledge and proposed mechanisms. Am J Physiol. 1983 Nov;245(5 Pt 1):G601-23. doi: 10.1152/ajpgi.1983.245.5.G601. PMID: 6195926.
16. Robert A, Hanchar AJ, Lancaster C, Nezamis JE. Prostacyclin inhibits enteropooling and diarrhea. In: Vane JR, Bergstrom S, eds. Prostacyclin. Raven Press, New York; 1979.
17. Higgs GA, Vane JR, Hart FD, Wojtulewski JA. Effects of anti-inflammatory drugs on prostaglandins in rheumatoid arthritis. In: Robinson HJ, Vane JR, eds. Prostaglandin synthetase inhibitors. Raven Press, New York; 1988.
18. Flower RJ. Drugs which inhibit prostaglandin biosynthesis. Pharmacol Rev. 1974 Mar;26(1):33-67. PMID: 4208101.
19. Vane JR. Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nat New Biol. 1971 Jun 23;231(25):232-5. doi: 10.1038/newbio231232a0. PMID: 5284360.
20. Fu JY, Masferrer JL, Seibert K, Raz A, Needleman P. The induction and suppression of prostaglandin H2 synthase (cyclooxygenase) in human monocytes. J Biol Chem. 1990 Oct 5;265(28):16737-40. PMID: 2120205.
21. Masferrer JL, Zweifel BS, Seibert K, Needleman P. Selective regulation of cellular cyclooxygenase by dexamethasone and endotoxin in mice. J Clin Invest. 1990 Oct;86(4):1375-9. doi: 10.1172/JCI114850. PMID: 2120289; PMCID: PMC296874.
22. Fu JY, Masferrer JL, Seibert K, Raz A, Needleman P. The induction and suppression of prostaglandin H2 synthase (cyclooxygenase) in human monocytes. J Biol Chem. 1990 Oct 5;265(28):16737-40. PMID: 2120205.
23. Xie WL, Chipman JG, Robertson DL, Erikson RL, Simmons DL. Expression of a mitogen-responsive gene encoding prostaglandin synthase is regulated by mRNA splicing. Proc Natl Acad Sci U S A. 1991 Apr 1;88(7):2692-6. doi: 10.1073/pnas.88.7.2692. PMID: 1849272; PMCID: PMC51304.
24. Hemler M, Lands WE. Purification of the cyclooxygenase that forms prostaglandins. Demonstration of two forms of iron in the holoenzyme. J Biol Chem. 1976 Sep 25;251(18):5575-9. PMID: 823151.
25. DeWitt DL. Prostaglandin endoperoxide synthase: regulation of enzyme expression. Biochim Biophys Acta. 1991 May 8;1083(2):121-34. doi: 10.1016/0005-2760(91)90032-d. PMID: 1903657.
26. Ryseck R. Raynoscheck C. Macdonald-Bravo H, Dorfman K. Bravo R. Identification of an immediate early gene, PGHs-6. whose protein product has prostaglandin synthase cyclooxygenase activity. Cell Growth Differ; 1992.
27. Whittle BJ, Higgs GA, Eakins KE, Moncada S, Vane JR. Selective inhibition of prostaglandin production in inflammatory exudates and gastric mucosa. Nature. 1980 Mar 20;284(5753):271-3. doi: 10.1038/284271a0. PMID: 6767192.
28. Vargaftig BB. Salicylic acid fails to inhibit generation of thromboxane A2 activity in platelets after in vivo administration to the rat. J Pharm Pharmacol. 1978 Feb;30(2):101-4. doi: 10.1111/j.2042-7158.1978.tb13171.x. PMID: 24092.
29. Flower RJ, Vane JR. Inhibition of prostaglandin synthetase in brain explains the anti-pyretic activity of paracetamol (4-acetamidophenol). Nature. 1972 Dec 15;240(5381):410-1. doi: 10.1038/240410a0. PMID: 4564318.
30. Brideau C, Kargman S, Liu S, Dallob AL, Ehrich EW, Rodger IW, Chan CC. A human whole blood assay for clinical evaluation of biochemical efficacy of cyclooxygenase inhibitors. Inflamm Res. 1996 Feb;45(2):68-74. doi: 10.1007/BF02265118. PMID: 8907587.
31. Ford-Hutchinson AW. New highly selective COX-2 inhibitors. In: Vane J, Botting J, editors. Selective COX-2 Inhibitors. Pharmacology, Clinical Effects and Therapeutic Potential. London: Kluwer Academic Publishers and William Harvey Press. 1998;117–25.
32. Mitchell JA, Akarasereenont P, Thiemermann C, Flower RJ, Vane JR. Selectivity of nonsteroidal antiinflammatory drugs as inhibitors of constitutive and inducible cyclooxygenase. Proc Natl Acad Sci U S A. 1993 Dec 15;90(24):11693-7. doi: 10.1073/pnas.90.24.11693. PMID: 8265610; PMCID: PMC48050.
33. Cao C, Matsumura K, Yamagata K, Watanabe Y. Cyclooxygenase-2 is induced in brain blood vessels during fever evoked by peripheral or central administration of tumor necrosis factor. Mol Brain Res. 1998; 56:45-56
34. Beiche F, Brune K, Geisslinger G, Goppelt-Struebe M. Expression of cyclooxygenase isoforms in the rat spinal cord and their regulation during adjuvant-induced arthritis. Inflamm Res. 1998 Dec;47(12):482-7. doi: 10.1007/s000110050362. PMID: 9892042.
35. Bennett P, Slater D . COX-2 expression in labor. In: Vane J, Botting J, Botting R (eds) Improved non-steroid anti-inflammatory drugs. COX-2 enzyme inhibitors. Kluwer Academic, Lancaster. 1996; pp 167-188
36. Gibb W, Sun M. Localization of prostaglandin H synthase type 2 protein and mRNA in term human fetal membranes and decidua. J Endocrinol. 1996 Sep;150(3):497-503. doi: 10.1677/joe.0.1500497. PMID: 8882169.
37. Langenbach R, Morham SG, Tiano HF, Loftin CD, Ghanayem BI, Chulada PC, Mahler JF, Lee CA, Goulding EH, Kluckman KD, Kim HS, Smithies O. Prostaglandin synthase 1 gene disruption in mice reduces arachidonic acid-induced inflammation and indomethacin-induced gastric ulceration. Cell. 1995 Nov 3;83(3):483-92. doi: 10.1016/0092-8674(95)90126-4. PMID: 8521478.
38. Brown NL, Alvi SA, Elder MG, Bennett PR, Sullivan MH. A spontaneous induction of fetal membrane prostaglandin production precedes clinical labour. J Endocrinol. 1998 May;157(2):R1-6. doi: 10.1677/joe.0.157r001. PMID: 9659298.
39. McAdam BF, Catella-Lawson F, Mardini IA, Kapoor S, Lawson JA, FitzGerald GA. Systemic biosynthesis of prostacyclin by cyclooxygenase (COX)-2: the human pharmacology of a selective inhibitor of COX-2. Proc Natl Acad Sci U S A. 1999 Jan 5;96(1):272-7. doi: 10.1073/pnas.96.1.272. Erratum in: Proc Natl Acad Sci U S A 1999 May 11;96(10):5890. PMID: 9874808; PMCID: PMC15129.
40. Topper JN, Cai J, Falb D, Gimbrone MA Jr. Identification of vascular endothelial genes differentially responsive to fluid mechanical stimuli: cyclooxygenase-2, manganese superoxide dismutase, and endothelial cell nitric oxide synthase are selectively up-regulated by steady laminar shear stress. Proc Natl Acad Sci U S A. 1996 Sep 17;93(19):10417-22. doi: 10.1073/pnas.93.19.10417. PMID: 8816815; PMCID: PMC38399.
41. Mitchell JA, Akarasereenont P, Thiemermann C, Flower RJ, Vane JR. Selectivity of nonsteroidal antiinflammatory drugs as inhibitors of constitutive and inducible cyclooxygenase. Proc Natl Acad Sci U S A. 1993 Dec 15;90(24):11693-7. doi: 10.1073/pnas.90.24.11693. PMID: 8265610; PMCID: PMC48050.
42. Meade EA, Smith WL, DeWitt DL. Differential inhibition of prostaglandin endoperoxide synthase (cyclooxygenase) isozymes by aspirin and other non-steroidal anti-inflammatory drugs. J Biol Chem. 1993 Mar 25;268(9):6610-4. PMID: 8454631.
43. Lanza FL. A review of gastric ulcer and gastroduodenal injury in normal volunteers receiving aspirin and other non-steroidal anti-inflammatory drugs. Scand J Gastroenterol Suppl. 1989;163:24-31. doi: 10.3109/00365528909091171. PMID: 2683026.
44. Vane JR, Botting RM. Mechanism of action of aspirin-like drugs. Semin Arthritis Rheum. 1997 Jun;26(6 Suppl 1):2-10. doi: 10.1016/s0049-0172(97)80046-7. PMID: 9219313.
45. Thun MJ, Namboodiri MM, Heath CW Jr. Aspirin use and reduced risk of fatal colon cancer. N Engl J Med. 1991 Dec 5;325(23):1593-6. doi: 10.1056/NEJM199112053252301. PMID: 1669840.
46. Luk GD. Prevention of gastrointestinal cancer--the potential role of NSAIDs in colorectal cancer. Schweiz Med Wochenschr. 1996 May 11;126(19):801-12. PMID: 8693304.
47. Gustafson-Svard C, Lilja I, Hallbook 0 , Sjodahl R. Cyclooxygenase-I and cyclooxygenase-2 gene expression in human colorectal adenocarcinomas and in azoxymethane induced colonic tumours in rats. Gut. 1996; 38:79-84
48. Kutchera W, Jones DA, Matsunami N, Groden J, McIntyre TM, Zimmerman GA, White RL, Prescott SM. Prostaglandin H synthase 2 is expressed abnormally in human colon cancer: evidence for a transcriptional effect. Proc Natl Acad Sci U S A. 1996 May 14;93(10):4816-20. doi: 10.1073/pnas.93.10.4816. PMID: 8643486; PMCID: PMC39362.
49. McGeer PL, McGeer EG. The inflammatory response system of brain: implications for therapy of Alzheimer and other neurodegenerative diseases. Brain Res Brain Res Rev. 1995 Sep;21(2):195-218. doi: 10.1016/0165-0173(95)00011-9. PMID: 8866675.
50. Breitner JC. The role of anti-inflammatory drugs in the prevention and treatment of Alzheimer's disease. Annu Rev Med. 1996;47:401-11. doi: 10.1146/annurev.med.47.1.401. PMID: 8712791.
51. Cochran FR, Vitek MP. Neuroinflammatory mechanisms in Alzheimer's disease: new opportunities for drug discovery. Expert Opin Invest Drugs. 1996; 5:449-455
52. Pasinetti GM, Aisen PS. Cyclooxygenase-2 expression is increased in frontal cortex of Alzheimer's disease brain. Neuroscience. 1998 Nov;87(2):319-24. doi: 10.1016/s0306-4522(98)00218-8. PMID: 9740394.
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Paul, P., and M. . “Anti-Inflammatory Drugs With Therapeutic Effects and Drug Regulators”. Himalayan Journal of Health Sciences, Vol. 6, no. 3, Sept. 2021, pp. 30-39, doi:10.22270/hjhs.v6i3.106.
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