Default Normal Template Original Article Oxidative Stress & C – Reactive Protein In Patients With Arthritis Imad A. Thanoon*Ph.D Nahla O. Tawfik** Farhad N. Hussin*** Summary: Back ground: Oxidative damage has been suggested to play a key role in accelerating inflammation and to be involved in the pathogenesis of rheumatoid arthritis (RA) and osteoarthritis (OA). Many studies had shown that those patients have low antioxidants level and are at risk of increased oxidative stress. Objective: This study was designed to examine the levels of serum Total Antioxidant Status (TAS). Malondialdehyde (MDA) as index of lipid peroxidation and C–Reactive Protein (CRP) as a marker of oxidative stress in patients with RA and OA and compared them with healthy control. J Fac Med Baghdad 2007; Vol. 49, No.2 Received Jan.2007 Accepted April 2007 Method: Serum TAS , MDA and CRP levels were measured in 16 RA and 24 OA patients and compare with those obtained from 25 healthy controls. Results: Serum TAS were significantly lower in RA group than in the OA and control groups (P < 0.05). Serum MDA and CRP levels were significantly higher in patients with RA than in those with OA and healthy subjects (P< 0.05). There were significant negative correlations between TAS and MDA, CRP levels (r = -0.850; p < 0.001) and ( r = -0.498; P < 0.05) respectively and a positive correlation between MDA and CRP levels in the RA group (r = 0.686; P < 0.01) . In OA group, the level of CRP was significantly increased (P< 0.05) and there was significant positive correlation between age and MDA level (r = 0.553; P < 0.01). Conclusion: Our results demonstrated that levels of lipid peroxidation are increased in patients with RA compared to controls and patients with OA , In addition serum TAS levels were decreased in RA. Serum TAS levels may be used as a routine and rapid test to verify the levels of oxidative stress in RA. Furthermore correlating TAS and MDA levels with a cute phase reactants such as CRP may give some clues about disease activity in RA . __________________________________________________________________________________________ Introduction:_______________________________ There has been great interest among researchers in the past 20 years for the role of oxidative stress in the development of arthritis(1). Evans and Halliwell stated that the damaging oxidative species (reactive oxygen, nitrogen and others) arise as byproducts of metabolism and as a physiological mediators and singling molecules (2). The levels of these oxidative intermediates are held in cheek by the anti- oxidant defense system, the component of this defense system are micronutrients like vitamin C and E(3). A deficiency in these micronutrients leads to oxidative stress which leaves the body tissue open to the damaging effects of the oxidative intermediates which may accompany inflammatory and immunological process seen in RA patients(4,5). In addition many studies have suggested the major role of these intermediates in altering chondrocyte (cartilage cells) function in OA(6). _________________________________________ *Assistant Professor, College of Medicine- University of Mosul **Lecturer, College of Dentistry – University of Mosul *** lecturer, College of Medicine- University of Saladin Oxygen free radicals have been suggested to exert their cytotoxic effect by causing oxidation of membrane phospholipids ( i.e. lipid peroxidation)(7). Many products of lipid peroxidation are not overtly toxic or are minor products of major toxicological interest one of them is malondialdehyde (MDA)(8),a major reactive aldehyde and is used as an indicator of tissue damage(9). Elevated levels of serum MDA were observed in RA patients which suggested that there is an increase in oxidant stress in those patients(10,11,12). It is now widely accepted that inflammation and oxidative stress are two important processes integrally involved in the development and progression of arthritis(13), C–reactive protein (CRP) is a well established marker of inflammation and is classified as an acute phase reactant(14) often showing coordinated response with interleukin 6(15), CRP measurement served mostly in diagnostic, albeit non – specific one , and in monitoring role in such fields of infections and rheumatology(16). Kumon et. al.(17) found that serum CRP was significantly higher in RA than in OA, and correlated with erythrocyte sedimentation rate (ESR) in arthritis patients, he concluded that higher levels of CRP seems to reflect greater degree of joint inflammation in RA and OA patients. J Fac Med Baghdad Vol. 49 , No. 2 , 2007 227 Simpo PDF Merge and Split Unregistered Version - http://www.simpopdf.com Oxidative Stress & C – Reactive Protein In Patients With Arthritis IMAD Nahla Farhad The purpose of the present study was to examine the levels of lipid peroxidation (MDA), CRP, and TAS in patients with RA and OA and to Compared that with healthy control subjects. J Fac Med Baghdad 228 Vol. 49 , No. 2 , 2007 Patients and Method: Sixteen RA patients all fulfilling the American rheumatism criteria for RA(18) and, twenty four OA patients of the same age group were included . All patients had early active disease and were on non steroidal anti– inflammatory drugs as maintenance therapy. No prior treatment with second line anti rheumatic medication . The data collected include age, sex , weight and height. Body mass index (BMI) was calculated with patient clothed without shoes and expressed in Kg/m2 . The control group consisted of twenty five healthy individuals of the same age group . All of the subjects in this study were non – smoker. Blood samples were collected from the antecubital vein into plain tubes. MDA levels were assayed in serum as described by Ohkawa (19). TAS level were estimated using commercial assay kit obtained from Randox(20). Serum CRP concentration were measured by nephlometric immunoassay(21). Results were expressed as mean ± standard deviation (SD) . Differences in mean values of serum variables between healthy controls and arthritis patients were analyzed with the Students – t – test. P value of < 0.05 was considered significant. Pearson correlation coefficient was done to calculate the r value between the parameters analyzed in the serum. Results: Patients characteristics are given in table (1), the levels of antioxidant and markers of oxidative stress are given in table (2). Table (1) Base line characteristics of arthritis and control groups Characteristics Control N= 25 RA group N=16 OA group N= 24 Male : Female 11 : 14 7 : 9 10 : 14 Age (years) 49.12 ± 4.25 49 ± 3.72 52.08 ± 3.32 BMI kg/m2 24.36 ± 1.32 22.24 ± 2.18 23.06 ± 2.09 N= Number of patients Data are presented as mean ± SD. Table (2) Serum TAS, MDA and CRP levels in RA, OA and control groups Subject Croup N TAS (mmol/L) MDA (μ mol/L) CRP (mg/L) Control group 25 1.44±0.19 1.08±0.21 2.875±0.52 RA group 16 1.06±0.21* 2.01±0.26** 23.61±10.43*** OA group 24 1.43±0.20 1.19±0.36 5.50±0.83* N= Number of patients Data are presented as mean ± SD. * p<0.05, ** p<0.01, *** p<0.001 vs. the control group. In RA patients, mean values of TAS were significantly lower by – 25.35% (P< 0.05) from the control group while MDA and CRP mean levels are significantly increased by 85.32% (P< 0.01) and 723.0 % (P< 0.001) respectively when compared with health control subject. Serum levels of MDA and CRP where significantly higher (P< 0.05) in patients with RA that those with OA while the TAS level was significantly lower (P< 0.05). Pearson correlation showed that there were significant positive correlation between MDA and CRP level (r = 0.686 ; P< 0.01) (Fig. 1). while there were significant negative correlation between TAS and CRP (r = -0.498; P < 0.05) (Fig. 2) and between TAS and MDA levels (r = -0.850; p < 0.001) as shown in (Fig. 3). In OA group, the level of CRP was significantly increase (P< 0.05) and the percentage of increment was 91.64 % when compared with control group, no significant differences were observed between TAS and MDA levels on comparison with control. There were no significant correlation between these parameters in OA patients, the only significant correlation was between age and MDA level (r = 0.553 ; P < 0.05) as shown in (Fig. 4). Figure (1): Correlaion betwee n M DA &CRP le ve ls in rheumatoid arthritis patients y = 0.0174x + 1.6046 r = 0.686(sig.)** 0 0.5 1 1.5 2 2.5 3 0 10 20 30 40 50 60 CRP (m g/L) M D A ( µ m o l/L ) Simpo PDF Merge and Split Unregistered Version - http://www.simpopdf.com Oxidative Stress & C – Reactive Protein In Patients With Arthritis IMAD Nahla Farhad J Fac Med Baghdad 229 Vol. 49 , No. 2 , 2007 Discussion: Rheumatoid arthritis and osteoarthritis are the most common inflammatory diseases worldwide. In the present study serum TAS levels were significantly lower in the RA group than the OA and control groups, while serum MDA and CRP concentrations were significantly higher in patients with RA than those with OA and healthy subjects. These results are consisted with many studies (5,11,13), were an increased levels of lipid peroxidation reaction and lower TAS level in RA patients as compared to healthy subjects were reported. Figure (2): Corre lation be twe e n TAS & CRP le v e ls in rhe umatoid arthritis patie nts y = -24.51x + 49.737 r = -0.498 (sig.)* 0 10 20 30 40 50 60 0 0.5 1 1 TAS ( mmol/L ) C R P Our previous study (12) had shown a decreased antioxidant level (glutathione) and an increase in the MDA level in erythrocyte and plasma of patients with active RA compared with healthy subjects. Antioxidants hypothesized to provide protection against RA, was 400mg of vitamin E and 100mg vitamin C given twice daily and were significantly effective in reducing duration of morning stiffness, Ritchie joint index, ( patient and physician global assessment of disease activity parameters in RA patients). Wang et. al.(4) found that dietary supplementation with vitamin E alone reduces the base line inflammatory status, that is indicated by CRP concentration in healthy baboon. .5 ( m g/ L ) Figure (3): Corre lation be twe e n TAS & M DA le v e ls in rhe umatoid arthritis patie nts y = -0.68x + 2.4362 r = -0.850(sig.)** 0 0.5 1 1.5 0 1 2 3 TAS( m m ol/L) M D A ( µ m o l/L ) A significant increase in MDA and a decrease in TAS levels in the present study reveals that there is an increase in the oxidative stress in RA. The negative correlation between MDA, CRP and TAS parameters can be explained by the impairment of the antioxidant defense mechanisms due to excess utilization by the inflamed tissue to scavenge the excessive lipid peroxide that are generated at the inflammatory site or to scavenge accumulated lipid peroxides in the plasma(22). Increase in the in vivo generation of oxidants and lipid peroxidation product was demonstrated in plasma of RA patients which correlated with the antioxidant level (14). This may indicate evidence of oxidative stress in those patients and that it plays an important role in the pathogenesis of the disease(1). CRP was positively associated with MDA and this could give a clue the extent and rate of tissue damage due to increase oxidative stress and increased lipid peroxidation. Sukkar and Rossi (25) had supposed that oxidative stress may trigger inflammatory activity and therefore it may induce a flare of the disease. Figure (4): Correlation between Age & MDA levels in osteo arthritis patients y = 0.0605x - 1.9584 r= 0.553(sig.)** 0 0.5 1 1.5 2 0 20 40 60 80 Age ( Year ) M D A m o l/L ) µ Many studies have reported higher oxidative stress in OA (23,24) and this is in accordance with our results, where the only significant increase was in the CRP level. This increase combined with haemostatic and haemodynamic reaction to the stress task could give an indication to the disease activity in OA patients(6). Kumon et.al. (17) found ( Simpo PDF Merge and Split Unregistered Version - http://www.simpopdf.com Oxidative Stress & C – Reactive Protein In Patients With Arthritis IMAD Nahla Farhad J Fac Med Baghdad 230 Vol. 49 , No. 2 , 2007 that serum and synovial CRP levels were significantly higher in RA than OA patients, and it correlate with ESR in all arthritis patients. In this study MDA levels were significantly correlated with age in OA patients. Our results are consisted with the hypothesis that with age the prevalence of OA increases and the efficacy of articular cartilage repair decrease(26). It was suggested that in vivo chondrocyte essences contributes to the age related increase in the prevalence of OA and decrease in the efficacy of cartilage repair. Kehan and Archer(6) found that articular cartilage is susceptible to many forms of injury some of which may lead to secondary arthritis at much later time. Numerous medical studies (22,25) concluded that oxidative stress is the root cause of arthritis when the antioxidant defense system is over whelmed, this oxidative stress within the joint causes damage to the surrounding cartilage (4). In OA and RA, there is a focal loss of cartilage resulting from catabolic pathway in the joint over production of free radicals and lack of oxygen processing enzymes and free radical scavenging molecules can lead to inflammation. Inflammatory products like phagocytosis from neutrophils create even more free radicals (2).it is this viscious low grade inflammatory response that leads to the destruction f the joint and this may contribute to the pathogenesis of the disease (24,25). Increasing numbers of health care recognizes the need for diagnostic laboratory tests that measure oxidative damage and the status of the individuals antioxidant defenses. Given the multiplicity of antioxidant and the influences of life style and nutritional supplements on an individuals antioxidant capacity, it is important to be able to quantitively measure the total antioxidant capacity of the antioxidant power within biological specimens and use it as a routine work to detect the level and to correlate it with the disease activity for patients at various stages of the disease. References: 1- Aaseth J, Haugen M, Forre O. Rheumatoid arthritis and metal compounds. Perspective on the role of oxygen radical detoxification. Analys 1998;123:36-44. 2- Evans P, Halliwell B. Micronutrient: oxidant/ antioxidant stuatus. Br J Nutr 2001;85: 67-74. 3- Hamilton JMJ, Gilmore WS, Benzie IFF, Mulholland CW. Interactions between vitamins C and E in human subjects. British journal of nutrition 2000;84: 261-267. 4- Wang L, Rainwater DL, Mohaney MC, Stocker R. Co supplementation with vitamin E and coenzyme Q10 reduces circulating markers of inflammation in baboons. Am J Clin. Nutr. 2004; 80: 649-655. 5- Vansanthi P, Ganesan N, Hariprasad C, Rajesekhan G, Meera S. Plasma lipophilic antioxidant and pro-oxidant levels in rheumatoid arthritis. J Indian Rheumatol Assoc. 2004:12:40-42. 6- Khan IM, Archer CW. Oxidative stress induce expression of markers of early osteoarthritis and chondrocyte terminal differentiation in cultured bovine explants. European cell and mineral 2006; 12(3),36. 7- Sarban S, KocyigitA, Yazar M, Isikan UE. Plasma total antioxiddnt capacity, lipid peroxidation and erythrocyte antioxidant enzyme activities in patients with rheumatoid arthritis and osteoarthritis. Clin. Biochem. 2005; 38: 981986. 8- Mayes PA. Structure and function of lipid-soluble vitamins In: Harpers Biochemistry, 25th ed., Murray RK, Granner DK, Mayes PA, Rodwell VW (eds). Appleton and Lange, Standford, Connecticut :219-223. 9- Dezwart LL, Neerman JHN, Commandeur INM, Vermeulen NPE. Biomarkers of free radicals damage applications in experimental animals and in humans. Free Radic Biol. Med. 1999; 26: 202-226. 10- Stock J, Dormandy TL. The autoxidation of human red cell lipids induced by hydrogen peroxide. Br J Haem 1971; 20-95-111. 11- Gambhir JK, Lali P, Jain AK. Correlation between blood antioxidant levels and lipid peroxidation in rheumatoid arthritis. Clin Biochem. 1997; 30: 200-204. 12- Tawfik NOM. The role of antioxidant and non steroidal anti inflammatory drugs in the management of patients with rheumatoid arthritis Ph. D. thesis college of Medicine- University of Mosul 2004. 13- Vijaya Kumar D, Suresh K, Monaharan S. Lipid peroxidation and antioxidant status in blood of rheumatoid arthritis patients. Indian J of clinical biochemistry 2005; 21: 104-108. 14- Nagler RM, Salameh F, Reznick AZ, Livshits V, Nahir AM. Salivary gland involvement in rheumatoid arthritis and its relationship to induced oxidative stress. Rheumatology 2003; 42: 1234-1241. 15- Sac KE. Evaluation of patients C: laboratory assessment. In: Primer on the rheumatoid disease, 12th ed., Klipped JH, Crofford LJ. Ston JH, Weyand CM (eds.). Arthritis foundation, Atlanta Georgia, 2001; 218-225. 16- Crockson RA, Crockson AP. Relationship of the erythrocyte sedimentation rate to viscosity and plasma proteins in rheumatoid arthritis. Ann Rheum. Dis. 1974; 33:53-56. 17- Kumon Y, Suehiro T, Nishia K, Hashimoto K Nakatani K, Sipe JD. Ferritin accelerates with C-reactive protein and acute phase serum amyloid. Amyloid 1999; 6:130- 135. 18- Arnett FC, Edworthy SM, Bloch DA, et. al. The American Rheumatism Association 1987 Revised Criteria for the Classification of Rheumatoid Arthritis. Arthritis. Rheum 1988; 31: 315-325. 19- Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animals tissues by thiobarituric acid reaction. Analytic Biochem. 1979; 95:351-358. 20- Miller NJ, Rice Evance C, Duvies MJ, Gopinathan V, Milner A. Total antioxidant status by colorimetric method- clinical science. 1993; 84:407-412. 21- Wener MH, Daum PR, McQuillan C. The influence of age, sex and race on the upper reference limit of serum C-reactive protein concentration. J Rheumat 2000; 27:2351-2359. 22- Halliwell B, Hoult HR, Blake DR. Oxidants inflammation and anti inflammatory drugs ASEBJ- 1988; 2: 2867-2873. 23- Maneesh M, Jayalekshmi H, Sama T, Chatterjee S, Chakrabati A, Sigh TA. Evidence for oxidative stress in osteoarthritis. Indian J of clinical Biochemistry 2005; 20 :129- 130. 24- Yudoh K, Trieu NV, Nakamura H, Kato KT and Nishioka K. Potential involvement of oxidative stress in cartilage senescence and development of osteoarthritis. Arthritis Res Ther 2005; 7: 380-383. 25- Suckker YG, Rossi E. Oxidative stress and nutritional prevention in autoimmune rheumatic disease. Autoimmunity Review 2004; 3:199-206. 26- Mortin JA, Buckwalter JA. The role of chondrocyte senescence in the pathogenesis of osteoarthritis and in limiting cartilage repair. J of Bone and Joint Surgery 2003; 85: 106-110. Simpo PDF Merge and Split Unregistered Version - http://www.simpopdf.com 1.DOC 2.doc References List all authors when six or less; when seven or more, list only first three and add et al. Tables Submission of manuscripts Mail the required number of manuscript copies in a heavy-paper envelope, enclosing the manuscript copies and figures in cardboard. Manuscripts should be accompanied by a covering letter from the author who will be responsible for correspondence regarding the manuscript. The covering letter should contain a statement that the manuscript has been seen and approved by all authors. 3.doc Modified Sugiura Operation for Portal Hypertension and Bleeding Esophageal Varices 172 Omar S. Khattab,Samie B. Safar Post-Surgical Loco Regional Recurrence Of Breast Carcinoma In Iraq 193 Ali M. Al-saiegh 4.doc 5.doc Modified Sugiura Operation for Portal Hypertension and Bleeding Esophageal Varices Omar S. Khattab*, M.B.Ch.B , H.D.S , H.D.L.M , F.I.C.M.S, C.A.B.S Samie B. Safar, M.B.Ch.B , F.R.C.P, F.R.C.S, F.A.C.S 6.doc Introduction:______________________________ Types of Incisional hernias: - _________________________________________ Clinical types of Incisional hernias: - Patients And Methods: Discussion Conclusions References 7.doc 8.doc 9.doc Post-Surgical Loco Regional Recurrence Of Breast Carcinoma In Iraq Ali M. Al-saiegh * M.B.CH.B. D.S F.I.C.M.S. Summary Conclusion: Carcinoma of the breast affecting Iraqi females at younger ages in a high & increasing rate than other studies with a higher Loco-regional recurrence rate. Significant association were found regarding latency period, staging, histopathology & grading of primary tumour . Aims Of Study: 1. To assess the incidence of post operative loco regional recurrence of breast carcinoma in Iraqi female patients. 2. To determine the significance of certain variables that may affect the loco regional recurrence rate . Introduction:______________________________ * Head of Department of surgery- medical college Kufa university Results: Discussion: Conclusion References 10.doc 11.doc 12.doc 13.doc 14.doc 15.doc 16.doc Back ground: Oxidative damage has been suggested to play a key role in accelerating inflammation and to be involved in the pathogenesis of rheumatoid arthritis (RA) and osteoarthritis (OA). Many studies had shown that those patients have low antioxidants level and are at risk of increased oxidative stress. Objective: This study was designed to examine the levels of serum Total Antioxidant Status (TAS). Malondialdehyde (MDA) as index of lipid peroxidation and C–Reactive Protein (CRP) as a marker of oxidative stress in patients with RA and OA and compared them with healthy control. __________________________________________________________________________________________ Introduction:_______________________________ **Lecturer, College of Dentistry – University of Mosul Patients and Method: Results: 17.doc 18.doc 19.doc HLA -A HLA-B Total Increased frequency Study groups Blood groups 20.doc Subject and Methods: - 21.doc 22.doc 23.doc 24.doc 25.doc 26.doc Rabab .N. AL-Saadi.* FICMS Back ground: Psoriasis is a chronic relapsing disorder with no life long cure, many systemic and topical modalities are available, one of these topical modalities is the vitamin D analogue (calcipotriene) which is widely used recently to treat psoriasis and many other skin problems. 27.doc 28.doc 29.doc 30.doc 31.DOC 16.pdf Back ground: Oxidative damage has been suggested to play a key role in accelerating inflammation and to be involved in the pathogenesis of rheumatoid arthritis (RA) and osteoarthritis (OA). Many studies had shown that those patients have low antioxidants level and are at risk of increased oxidative stress. Objective: This study was designed to examine the levels of serum Total Antioxidant Status (TAS). Malondialdehyde (MDA) as index of lipid peroxidation and C–Reactive Protein (CRP) as a marker of oxidative stress in patients with RA and OA and compared them with healthy control. __________________________________________________________________________________________ Introduction:_______________________________ **Lecturer, College of Dentistry – University of Mosul Patients and Method: Results: 166.pdf Back ground: Oxidative damage has been suggested to play a key role in accelerating inflammation and to be involved in the pathogenesis of rheumatoid arthritis (RA) and osteoarthritis (OA). Many studies had shown that those patients have low antioxidants level and are at risk of increased oxidative stress. Objective: This study was designed to examine the levels of serum Total Antioxidant Status (TAS). Malondialdehyde (MDA) as index of lipid peroxidation and C–Reactive Protein (CRP) as a marker of oxidative stress in patients with RA and OA and compared them with healthy control. __________________________________________________________________________________________ Introduction:_______________________________ **Lecturer, College of Dentistry – University of Mosul Patients and Method: Results: