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DENEYSEL AKUT ÜLSERATİF KOLİT MODELİNDE infliksimab ve allopurinol’ün ETKİLERİNİN İNCELENMESİ

INVESTIGATION OF THE EFFICACY OF infliksimab and allopurinol IN EXPERİMENTAL ACUTE ULCERATIVE COLITIS MODEL

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Abstract (2. Language): 
Purpose: In this study, our purpose was to compare the efficacy of infliximab and allopurinol seperatly and in combined usage in ulcerative colitis. Material and Methods: 30 Wistar albino rats were used and divided into 5 groups. GROUP I: 1 cc of 4% acetic acid was applied. GROUP II: Similarly, SF solution was applied, GROUP III: After acetic acid application, intraperitoneal infliximab was used, GROUP IV: After acetic acid application, intraperitoneal Allopurinol was used, GROUP V: After acetic acid application, intraperitoneal infliximab+Allopurinol were used. When the rats were under a slight ether anesthesia, a 6-milimetre catheter was placed through anus and 1 cc of 4% acetic acid and SF was applied. The rats in all these groups were sacrificed 48 hours after the procedure. Results: Significant difference (p<0,001) among the groups in terms of their macroscopic and microscopic evaluation was observed. Myeloperoxidase (MPO) scores in infliximab, allopurinol, and combined medicine use groups were close to each other and that they were higher in sham and colitis groups. Malondialdehide (MDA) scores did not show any important difference among the groups. Conclusion: When we consider the macroscopic and microscopic scoring, we believe that the efficiency of allopurinol and infliximab in experimental acute colitis model are close to each other, but lower than the combined medicine use group. Therefore, we suppose that the decrease in macroscopic and microscopic scores caused by combined medicine use in creases the anti-inflammatory efficacy and that this treatment can be used in the future.
Abstract (Original Language): 
Amaç: Bu çalışmadaki amacımız infliximab ve allopurinol’ün ülseratif kolitteki ayrı ayrı ve birlikte kullanıldıklarındaki etkilerini araştırmaktır. Materyal ve Metod: Çalışmaya 30 adet wistar albino rat alındı ve 5 gruba ayrıldılar. Grup I’e 1 cc %4’lük asetik asid rektal yolla verildi, Grup II’ye aynı mitarda SF verildi, Grup III’e asetik asid ve infliximab verildi, Grup IV’e asetik asid ve allopurinol verildi, Grup V’e asetik asid ve infliximab + allopurinol verildi. Asetik asid ile SF denekler eter anestezisi altındayken rektal yolla sokulan bir kateter aracılığıyla verildi. İlaçlar periton içine enjekte edildiler. Ratlar işlemden 48 saat sonra sakrifiye edildiler. Bulgular: Makroskopik ve mikroskopik incelem sonucu elde edilen skorlar ilaç kullanılan gruplarda anlamlı olarak daha iyi idiler. En iyi sonuç kombine ilaç grubunda bulundu. Miyeloperoksidaz (MPO) değerleri de ilaç kullanılan gruplarda kontrol ve deney grubuna göre anlamlı olarak daha yüksek bulundu. Malondialdehit (MDA) değerleri ise gruplar arasında anlamlı farklılık göstermedi. Sonuç: Mikroskopik ve makroskopik skorlar dikkate alındığı zaman infliximab ve allopurinol’ün deneysel akut ülseratif kolitte düzelme sağladığı ve sonuçların birbirine yakın olduğu gözlendi. Kombine ilaç kullanımının daha etkin bir düzelme sağladığı ve bu yöntemin ülseratif kolit’in tedavisinde kullanılabileceği kanaatine varıldı.
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REFERENCES

References: 

1. Jewell DP. Ulcerative colitis. Feldman M,
Scharschmidt BF, SIeisenger MH. Sleisenger and
Fordtran’s Gastrointestinale and liver diseases. 5th
ed. Volum 2. Philadelphia, 1993: 1305-1330
2. Lashner BA. Epidemiology of inflammatory bowel
disease. Gastroenterol. Clin. North Am. l995: 24(3);
467-74.
3. Kirsner JB, Shorter RG. Recent development in “nonspecific” inflammatory bowel disease. N Engl J Med
1982; 306: 775-784.
4. Donaldson RM. Crohn’s disease. In: Sleisenger MH,
Fordtran JS, eds. Gastrointestinal disease. 4th ed.
Philadelphia : Saunders, 1989: 1327-1358.
5. Wright JP, Mee S., Parfitt A., Marks I..N., et al.: Vitamin A therapy in patients with Crohn’s disease.
Gastroenterology, 88(2): 512-514,1985.
6. Ahnfelt-Ronne I, Nielson O.H.: The antiinflammatory moiety of sulfasalazine, 5-ASA, is a radical
scavenger. Agents Actions, 21(1-2):191-194,1987.
7. Ahnfelt-Ronne I., Haagen Nielsen O., Christensen A., Langholz E., Binder V., Riis P.: Clinical
evidence supporting the scavenger mechanism of
5- aminosalicyclic acid. Gastroenterology, 98: 1162-
1169,1990
8. Fedorak RN,Empey LR,Mc Arthur C,Jevell LD:Misoprostol provides colonic mucosal protective effect
during acetic acid induced colitis in rats.Gastroenterology J.98;615-625,1990
9. Dhawan V, Mohamed A, Fedorak RN. Exercise and
inflammatory bowel disease. Can J Gastroenterol.
2009 Jan;23(1):19-22. Review.
10. Fedorak RW,Empley LR,Walker K. Verapamil alters
eicosanoid synthesis and accelerates healing during experimental colitis in rats.Gastroenterology
1992;102:1229-35
11. Okhawa H.,Ohishi N.,Yagi K.:assay for lipid peroxides in animal tissues by thiobarbituric acid reaction.
Analytical Biochemistry,95,351-358 (1979).
12. Tianhong Zhang et al;The prophylactic and therapeutic effects of cholinolytics on perfluoroisobutylene inhalation induced acute lung injury.J Occup
Health 2005;47(4):277-285
13. Barkin JS, Green JA.İnflammatory bowel disease:
medical management. In: Berk JE. Haubrich WS,
Kalser MH, Roth JLA, Shaffner F.eds. Bockus gastroenterology. Vol 2.5thed. Philadelphia: J.B.Lippincott,
1994; 1374-81.
14. Farmer RG, Easley KA, Farmer JM. Assessing quality
of life for patients with inflammatory bowel disease.
Cleve Clin J Med 1992:58;7-15.
15. Gerald P., Beck PL, Wallace JL, Fallone CA.: Animal
models and pathogenesis of inflammatory bowel
disease. Ed: Szabo S, Tache Y, Neuroendocrinology of Gastrointestinal- Ulceration. Vol 2, 73- 92,
Plenium Press, New York, 1995.
16. Watss JN,Dombal FT,Watkinson G;Golghe JC:Early
course of ulcerative colitis.Gut 7:16-31,1966
17. Fabia R, Willen R, Ar’Rajab A, Anderson R, Ahren B,
Bengmark S.: Acetic acid induced colitis in rat:a reproducible xeperimental model for acute ulcerative
colitis.Eur surg Res. 1992;24(4):211-25
18. Hommes DW, Radema S, Jansen J, Smit F, Zhao
YC, Fockens P: Production and cellular source
of interleukin-8 in inflammatory bowel disease.
İnflammatory Bowel Diseases, 1:108-16, 1995.
19. Armuzzi A,De Pascalis B,lupascu A,Fedeli p,leo
D,Mentella MC,Vincenti F,Melina D,Gasbarrini
G,Pola ,Gasbarrini A.:Infliximab in treatment of
steroid-dependent olerative colits.Eur Rev Med
Pharnmacol Sci.2004 Sep-Oct;8(5):231-3
20. Lee KM, Kim JS, Shin DH, Cheong JY, Yoo BM, Kim
JK, Lee KJ, Hahm KB, Kim JH, Cho SW.: Effect of
infliximab in the treatment of refractory inflamatorry
bowel disease with complication.Korean J Gastroenterol .2004 Nov;44(5):259-66
21. Oschenkühn T,Sackman M,Göke B.:Infliximab for
acute,nonsteroide-refractory ulcerative colitis: a
randomized pilot study.eur J Gastroenterol hepatol.2004 Nov;16(11):1167-71.
22. Tilg H, Feichtenschlager T, Knoflach P,Petritsch W,
Schöfl R,Vogelsang H;Reinisch W.:Use of infliximab
in ulcerative colitis. Z Gastroneterol. 2007 Aug;45(8):
907-11.
23. Kohn A, Daperno M, Armuzzi A, Capello M,Biancone
L ,Orlando A,Viscido A, Annese V, Riegler G, Meucci
G,Marollo M, Sostegni R, Gasbarrini A, Peralta S,
Prantera C.:İnfliximab in severe ulcerative colitis:
short- term results of different infusion regimens
and long- term follow-up.Aliment Pharmacol
Ther.2007 Sep 1;26(5):747-56.
24. Hassan C, Ierardi E, Burattini O, De Francesco V,
Zullo A, Stoppino G, Panella C, Morini S: Tumour
necrosis factor alpha down-regulation parallels
inflammatory regression in ulcerative colitis patients treated with infliximab. Dig Liver Dis.2007
Sep;39(9):811-7
25. Feagan BG, Reinisch W, Rutgeerts P, Sandborn WJ,
Yan S, Eisenberg D, Bala M, Hanauer SB.: The effects of infliximab therapy on health-related quality
of life in ulcerative colitis patients.Am JGastroenterol
2007 Apr;102(4):794-802.
26. Jarnerot G,Hertervig E, Friis-Liby I, Blomquist L,
Karlen P, Grannö C, Vilien M, Ström M, Danielsson
A, Verbaan H, Hellström PM, Magnuson A, Curman B. İnfliximab as rescue therapy in severe to
moderately severe ulcerative colitis:a randomized,
placebo-controlled study.Gastroenterology. 2005
Jun;128(79:1805-11.
27. Sener G, Aksoy H, Sehirli O, Yüksel M, Aral C, Gedik
N, Cetinel S, Yeğen BC.: Erdosteine prevents colonic
inflammation through its antioxidant and free radical scavenging activities. Dig Dis Sci. 2007 Sep;52(9):
2122-32.
28. Cakir B, Bozkurt A, Ercan F, Yeğen BC.: The antiinflammatory effect of leptin on experimental colitis:
involvement of endogenous glucocorticoids. Peptides. 2004 Jan;25(1):95-104.
29. Bozkurt A, Cakir B, Ercan F, Yeğen BC.: Anti-inflammatory effects of leptin and cholecystokinin on
acetic acid-induced colitis in rats: role of capsaicinsensitive vagal afferent fibers. Regul Pept. 2003 Nov
15;116(1-3):109-18.
30. Jahovic N, Gedik N, Ercan F, Sirvanci S, Yüksel M,
Sener G, Alican I.: Effects of statins on experimental
colitis in normocholesterolemic rats. Scand J Gastroenterol. 2006 Aug; 41(8): 954-62
31. Granger DN, Hollwarth E, Parks DA: Ischemia-reperfusion injury: role of oxygen-derived free radicals.
Açta Physiol Scand (Suppl) 548:47-63, 1986.
32. Pokorny AT, Bright DA, Cummings CW: The effects
of allopurinol and superoxide dismutase in a rat
model of skin flap necrosis. Arch Otolaryngol Head
Neck Surg 115:207-212, 1989
33. Lansek R, Packham D, Aspey BS. Harrison MJG:
An assesment of the possible protective effect of
allopurinol in acute stroke. J Neurol Neurosurg Psychi 49:585-587, 1986. meyabolites in experimental
colitis.Gut. 1990 Jul,31(7):786-90.
34. Millar AD,Rampton Ds,Chander CI,Claxson Aw,
Blades S,Coumbe A,Panetta JMorris CJ,Blake Dr.:
evaluating the antioxidant potential of new treatments for inflammatory bowel disease using a rat
model of colitis.Gut.1996 Sep:39(3):407-15
35. Dinda PK, Kossev P, Beck IT, Buell MG. Role of
xanthine oxidase-derived oxidants and leucocytes
in ethanol-induced jejunal mucosal in jury.Dig Dis
Sci.1996 dec,41(12).2462-70
36. Klein AS, joh JW, Rangan U, Wang D, Bulkley
GB. Allopurinol: discrimination of antioxidant
from enzyme inhibitory activities. Free Radic Biol
Med.1996;21(5):713-7
37. Sparrow MP, Hande SA, Fiedman S, Cao D, Hanauer SB. Effect of allopurinol on clinical outcomes in
inflammatory bowel disease nonresponders to azathiopurine or mercaptopurine. Clin Gastroenterol
Hepatol. 2007 Feb;5(2).209-14
38. Reynolds PD, Rheinius ST, Hunter JO. Xanthine
oxidase activity is not incresed inthe colonic mucosa
of ulcerative colitis.Alimentary Pharmacology and
Therapeutics.10(5):737-41, October 1996
39. Keshavarzian A, Morgan G, Sedghi S, Gordon JH,
Doria M. Role of reactive oxygen metabolites in
experimental colitis. Gut.1990 Jul, 31(7):786-90
40. Pacifici RE, Davies KJ. Protein, lipid and DNA repair
system in oxidative stres: The free radical-theory of
aging revisited. Gerontolgy 1991;31:166

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