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Cytokines in rheumatoid arthritis and osteoarthrosis
Petrovi?-Rackov Ljiljana
Medicinski Pregled , 2005, DOI: 10.2298/mpns0506245p
Abstract: The aim of this research was to determine the clinical significance of tumor necrosis factor-alpha (TNF-alpha), IL-12, IL-15 and IL-18 in evaluation of the activity of rheumatoid arthritis. Cytokine concentrations in serum samples and synovial fluid were measured by immnnoenzymatic methods using kits for human interleukins and the Disease Activity Score 28 in 64 patients with active disease. The control group consisted of 25 subjects with arthritis of the knee and osteoarthrosis. Patients with rheumatoid arthritis have significantly high (p<0.01) concentrations of examined cytokines in relation to patients with osteoarthritis. By comparing concentrations in 30 patients with high, 14 patients with moderate and 20 patients with mild activity of rheumatoid arthritis, it was established that patients with high degree of disease activity have significantly high (p<0.01; p<0.05) concentrations of examined cytokines in the blood and synovial fluid in relation to patients with moderate and mild disease. We have concluded that cytokine concentrations are good indicators of the degree of rheumatoid arthritis activity. This research is a contribution to understanding the insufficiently known pathogenetic mechanisms of cytokines, especially IL-18, in active disease. .
Evaluation of the degree of clinical rheumatoid arthritis activity based on the concentrations of cytokines TNF-alpha, IL-12, IL-15, and IL-18 in serum and synovial fluid
Petrovi?-Rackov Ljiljana
Vojnosanitetski Pregled , 2006, DOI: 10.2298/vsp0601021p
Abstract: Bacground/Aim. Experimental in vitro and in vivo investigations in a mouse model have proved that TNF-alpha, IL-12, IL- 15 and IL-18 participate in the pathogenesis of erosive inflammatory arthritis. The aim of this research was to determine the clinical significance of cytokines in the evaluation of the activity of rheumatoid arthritis (RA). Methods. Inside a 4-year period we followed-up 64 patients with RA as newly occurred or in the phase of worsening. We observed the clinical manifestation of the disease upon wluch we divided the patients in to 3 groups: the patients with low active RA, patients with moderate active RA, and the patients with wild active RA. The control group (n = 25 patients) included the patients with osteoarthrosis (OA), and arthritis of the knee. In the samples of serum of all of the patients the concentrating of cytokines TNF-alpha, IL-12, IL-15, and IL-18 were determined using the immunoenzymatic methods in mice for human interleukines. By comparing the concentrations in 30 patients with the high, 14 patients with moderate, and 20 patients with the mild activity of RA it was determined that the patients with the high degree of the disease activity, had significantly high (p < 0.01; p < 0.05) concentrations of the examined cytokines in blood and synovial fluid as compared to the patients with the moderate and mild active disease. There was a relationship (p < 0.01) between the concentrations of cytokines in blood and synovial fluid with the quantity of the Disease Activity Score in 28 joints. Conclusions. Cytokines concentrations could be good indicators of the degree of the general activity of RA. This research could contribute to the interpretation of insufficiently well known views of the pathogenesis role and significance of citokines in an active disease.
Therapeutic approach to progressive Takayasu's arteritis
Petrovi?-Rackov Ljiljana
Vojnosanitetski Pregled , 2006, DOI: 10.2298/vsp0606615p
Abstract: Background. Takayasu's arteritis (TA) is a nonspecific autoimmune inflammation manifested with systemic large vessel vasculitis which affects predominantly the aorta and its main branches. Case report. We presented a 40-year-old woman with a two-year history of the symptoms of compromised circulation in the head, the neck, the upper extremities and the right leg, followed by claudications in the left leg, numbness in the left hand and stenocardia. Aortic arch angyography revealed occlusion of the right subclavian artery stenosis of the right vertebral artery (20 30%) and the right iliac artery. Anti-inflammatory agents had no satisfactory effect and due to the discase progression first aorto-bifemoral bypass grafting, and 10 months later left carotid-axillary bypass grafting were performed which led to the restoration of circulation in the lower extremities and the left arm. Conclusion. This case suggested that a surgical therapy should be applied in the cases with progressive Takayasu's arteritis, particularly in the absence of a response to the conventional immunosupressive therapy to prevent eventual fatal complications.
Detection of bone erosions in knee osteoarthrosis by serum biomarkers
?ivanovi? Sandra,Petrovi?-Rackov Ljiljana,Jevti? Milorad
Srpski Arhiv za Celokupno Lekarstvo , 2010, DOI: 10.2298/sarh1002062z
Abstract: Introduction. Osteoarthrosis (OA) is a degenerative chronic disease characterized by destruction of joint articular cartilage and subchondral bone with formation of osteophytes and usuries on joint surface. Quantitative and dynamic changes in remodeling of joint tissue reflect matrix molecules that dismiss as fragments in joint liquid, blood and urine where they can be detected. Human cartilage glycoprotein (YKL-40) is synthesised by chondrocytes and synovial cells and plays a significant role in remodel tissue. Objective. The aim of the paper was the parallel analysis and determination of the degree of correlation between ultrasound indicators destruction of joints, bone erosion (usuries), and serum YKL-40 concentrations in patients with primary osteoarthrosis of the knee. Methods. The analysis included 88 patients with the diagnosis of knee OA. Ultrasound review of knees was done by two rheumatologists. The analysis of serum samples determined the concentration of YKL40 by ELISA method. Results. The average age of patients was 69.97±9.37 years, duration of knee OA 6.46±6.73 years. The mean value of age in 59 patients with usuries was 72.05±7.74, at 29 without usuries 65.75±11.00 (p=0.003). The average value (median) thickness cartilage in medial condyl femur (front access) in patients with usuries was 1.25 mm (1.12-1.36 mm), without usuries 1.35 mm (1.20-1.51 mm) (p=0.016). The central YKL40 value of biomarkers in the patients without usuries was 81 ng/ml (46.5-120.5 ng/ml), with usuries the medial condyil 138 ng/ml (89.5-175.0 ng/ml), the lateral 106 ng/ml (63.0-201.5 ng/ml) and both condyl 86 ng/ ml (69.75-140.5 ng/ml) (p=0.004). The central value YKL40 after 5 year-duration of disease was 83.68±33.65 ng/ml, after 10 years 138.22±48.88 ng/ml, after 15 years 209.30±79.36 ng/ml, and after 20 years 218.50±106.51 ng/ml (p=0.000). The biomarker YKL 40 may be a marker for usuries (area 0.691, p=0.004; confidence interval 0.574-0.808). If you took the optimal cut-off of 84.5 ng/ml, then YKL40 sensitivity to the usuries was 69.5%, and specificity 51.7%. Conclusion. Increased concentrations of biomarkers YKL40 may be an indicator of the degree of destructive changes in the knee osteoarthrosis.
Arthrosonography and biomarkers in the evaluation of destructive knee cartilage osteoarthrosis
?ivanovi? Sandra,Petrovi?-Rackov Ljiljana,?ivanovi? Aleksandar
Srpski Arhiv za Celokupno Lekarstvo , 2009, DOI: 10.2298/sarh0912653z
Abstract: Introduction. Knee osteoarthrosis (OA) is a degenerative disease with progressive loss of cartilage of joints and bone destruction. During this process, the release of fragments of connective tissue matrix is detected in the biological fluids such as human cartilage glycoprotein (YKL-40), cartilage oligomeric matrix protein (COMP) and collagen type I C terminal telopeptid (CTX-I). Objective. The aim of the study was to determine the degree of connection cartilage thickness measured by ultrasound with serum concentrations of biomarkers YKL-40, COMP and CTX-I in patients with primary knee OA. Methods. The analysis included 88 patients with the diagnosis of knee OA. Ultrasound examination of knees were done by two rheumatologists. The analysis of serum samples determined the concentration of COMP, YKL-40 and CTX-I by the ELISA method. Results. The average age of patients was 69.97±9.37 years and the duration of knee OA 6.46±6.73 years. The average cartilage thickness of the femoral condyle was 1.33±0.20 mm; of the medial condyle (MC) (front access) 1.30±0.23 mm, (rear access) 1.30±0.29 mm and lateral condyli (LC) (front access) 1.39±0.27 mm. The average cartilage thickness of MC (front access) was 1.27 mm (0.98-1.42 mm), (rear access) 1.27 mm (0.84-1.46 mm) and LC (front access) 1.36 mm (1.01-1.57 mm) (p=0.002). There was a significant connection in the negative direction between the patients' age and the cartilage thickness of MC (front and rear access) and LC (front access) (r=-0.253; p=0.017). There was a significant negative direction of interrelationship between the cartilage thickness of MC (front access) (r=-0.259; p=0.015) and LC (front access) and the disease duration (r=-0.259; p=0.015). In patients with knee OA lasting for 5 years the measured cartilage thickness was 1.27 mm (1.16-1.49 mm), and 0.99 mm (0.94-1.23 mm) (p=0.007) in those lasting for 20 years. There was a significant relationship in a negative direction between the concentration of YKL-40 and cartilage thickness of MC (front access) (r=-0.249; p=0.019). Conclusion. The progressive loss of cartilage during the long-term evolution of osteoarthrosis is most extensive in the femoral MC. The increased serum levels of YKL-40 can be a good indicator of joint cartilage destruction.
Immune Complexes and Complement in Serum and Synovial Fluid of Rheumatoid Arthritis Patients
Zoran Miju kovi , Ljiljana Rackov, Janko Pejovi , Sandra ivanovi , Jelica Stojanovi , Zoran Kova evi
Journal of Medical Biochemistry , 2009, DOI: 10.2478/v10011-009-0016-9
Abstract: Rheumatoid arthritis (RA) is predominantly an intraarticular inflammatory and autoimmune disease that involves different autoantibodies and effector mechanisms. The aim of the study was to determine the utility of Circulating Immune Complexes (CIC) and complement components (C3c, C4) as possible markers for the disease activity in laboratory diagnostics. In a cross-section study 59 patients, according to the clinical criteria, were categorized into two groups: group with moderate (MA, n=24), and group with severe activity (SA, n=35) of RA. The concentration of CIC, C3c and C4 in sera (S) and synovial fluids (SF) was examined by an immunonephelometric method in both groups and compared with values in the control group (n=15) of patients with lesions of the menisci. Obtained results showed that there was no statistical significance in the values of C3c and C4, in both biological fluids, among all tested groups. Significant differences were found in the levels of CIC in both fluids, while testing the parameters (× ± SD, IU/mL) in the sera of groups with SA and MA of RA: 7.43 ± 13.40; 3.01 ± 2.92 (p<0.05) and SF: 13.47 ± 21.1, 5.33 ± 7.53 (p<0.001), respectively. These differences were higher between the group with SA and CG. Results for the concentrations of CIC were significantly higher in SF compared to sera: in the RA group with SA by 77% and group with MA by about 82%. These data could provide a confirmation of the hypothesis about local, intraarticular autoantibodies and subsequent CIC production. It can be concluded that the examination of CIC concentration in serum, and where it is possible in SF, is a useful marker of disease activity in RA patients, in contrast to the tested components of the complement. This statement does not exclude their consumption within immune effector mechanisms, but elicits the possibility that lower molecular fragments (C3d, C4d), as well as the novel activation products, could be better disease activity markers in RA patients.
Arthrosonography and the Biomarker Cartilage Oligomeric Matrix Protein in the Detection of Knee Osteoarthrosis Effusion
Sandra ivanovi , Ljiljana Petrovi Rackov, Du an Vu eti , Zoran Miju kovi
Journal of Medical Biochemistry , 2009, DOI: 10.2478/v10011-009-0005-z
Abstract: Osteoarthrosis of the knee is a degenerative disease with inflammatory episodes objectively shown by arthrosonography. Cartilage Oligomeric Matrix Protein - COMP is a useful biomarker for early cartilage destruction. The aim of this paper is a comparative analysis of the clinical, arthrosonographic findings and the COMP concentration in the sera of patients for the detection of joint inflammation. The analysis included 88 patients with knee OA. Clinical examination determined the outflow, arthrosonography the size of synovitis and effusion, and serum analysis the COMP concentration (ng/ml). Minimum outflow had 34.1% of patients, moderate 22.7%, and significant 4.5%. Sensitivity of the clinical diagnosis of outflow is 73%, and specificity 73% (p=0.000). Seventy five percent of patients had effusion; 28.4% of patients in the suprapatellar recessus (SR), 27.3% in the medial (MR), and 62.5% in the lateral (LR). In SR, effusion was 10.13±4.35 mm, MR 8.53±2.27 mm, LR 11.38±4.44 mm. Synovitis was found in 67% of patients, in SR the size of 4.84±3.57 mm, in MR 3.15±1.86 mm, in LR 6.09±2.80 mm. The average value of the size of effusion in patients with significant outflow in SR was 13.85 (10.36-17.43) mm (p=0.000), MR 4.9 (0-10.22) mm (p=0.008), LR 12.0 (11.34-14.50) mm (p=0.000), in LR with moderate outflow 6.94 (1.16-8.13) mm and minimum outflow 4.9 (0-7.25) mm. There is a significant correlation between the size of synovitis and effusion in the SR, MR and LR (p=0.000). The average value of the concentration of COMP in patients without effusion was 54 (44.5-58) ng/ml, with effusion 57 (48.75-64.25) ng/ml (p=0.030). Arthrosonography and the determination of the COMP concentration are sensitive methods for diagnosing joint effusion.
Efficacy and safety of once monthly ibandronate treatment in patients with reduced bone mineral density: Esther study
Vujasinovi?-Stupar Nada,Mili? Nata?a,Petrovi?-Rackov Ljiljana,Prodanovi? Nenad
Srpski Arhiv za Celokupno Lekarstvo , 2010, DOI: 10.2298/sarh1002056v
Abstract: Introduction. Osteoporosis usually affects post-menopausal women. Treatment is individualized and requires an approach that will provide long-term compliance to prevent fractures. Studies conducted so far suggest inadequate compliance and persistence in weekly bisphosphonate treatment (under 43% after a year of treatment). Ibandronate, as a powerful bisphosphonate, has made it possible for the first time to treat osteoporosis with a single tablet per month. Objective. Study of efficacy, safety and tolerance of ibandronate applied once a month in female patients with decreased bone mineral density (BMD). Methods. The prospective study was conducted in 34 centres in Serbia covering the total of 370 women with reduced BMD with ibandronate once a month. Demographic data, risk factors for osteoporosis, mode of diagnosis establishment, previous treatment for osteoporosis and concomitant diseases were investigated. Efficacy of the treatment was evaluated by T-score value after 12 months versus the baseline values. Tolerance of the treatment, compliance and adverse effects were recorded. Results. The sample included 97.5% post-menopausal women, 92.7% with osteoporosis. In 80% of the cases, the diagnosis was established by DXA measurement. In more than 90% of the sample, the level of physical activity was unsatisfactory, and 70% had an accompanying risk factor for osteoporosis in addition to menopause. After 12 months of treatment, 100% compliance was recorded in 84% of the patients and significant reduction (p<0.0001) of the bone mineral loss, regardless of the previous aminobisphosphonate treatment. The treatment was tolerated well, with no serious adverse reactions. Some, mainly gastrointestinal complaints, registered in the first month (6%), were significantly relieved (p<0.0001) after 12 months of treatment (1%). Conclusion. Ibandronate manifested significant improvement of the BMD after 12 months of treatment of patients with decreased BMD, with good tolerance and excellent treatment compliance.
Improving Influenza Vaccination Rates— A Straightforward Task or a Multifaceted Challenge?  [PDF]
Ljiljana Trtica-Majnaric
World Journal of Vaccines (WJV) , 2013, DOI: 10.4236/wjv.2013.32010

Annual vaccination with trivalent inactivated vaccines has been proven as safe and efficacious in preventing influenza and its complications. It is recommended especially to the elderly (>65) and other people at high risk for influenza complications and death such as patients with chronic medical conditions. Healthcare workers, who are considered to transmit infection to patients, or reciprocally, can be infected during encounters with patients, are also strongly advised to regularly receive vaccines. In order to improve influenza vaccination rates in countries in Europe, health authorities set targets for vaccination coverage by 2010. Despite the substantial efforts done, coverage rates maintain low. It is considered that informed decisions, based on existing evidence, are likely to cope with improving vaccination rates. Intention of this manuscript is to address some important issues connected with influenza vaccination which, to be able to aid the evidence, need to be further clearified. To support the debate, the author presented some dubious facts from the own practice experiences. As a long-lasting solution to improve vaccination practice strategies, strengthening programed vaccination is suggested. This concept would include implementation of nationwide vaccination protocols and their harmonization by the common logistics, and standardized data collection based on installation of E-health records. This strategy would allow data comparison among different populations. As based on this debate, improving influenza vaccination rates is not likely to be easy to perform straightforward task, but a multifaceted, long term challenge.

Fractal Dimension in Animal Model of Alzheimer’s Dementia  [PDF]
Ljiljana Marta?, Slobodan Sekuli?
Journal of Behavioral and Brain Science (JBBS) , 2018, DOI: 10.4236/jbbs.2018.89031
Abstract: The aim of this study was to qualitatively described effect of the oxidative stress, neurotransmission change and the neurodegeneration in animal model of chronic intoxication by aluminum. Electrocortical brain activity of animal model of stress and neurodegeneration is comparable with Alzheimer’s Dementia (AD). We used adult animals, during 6 weeks intraperitoneally treated with aluminum. Both animals and patients with Alzheimer’s Dementia have increased relative spectral power in delta range. By fractal analysis we described changes in electrocortical activity of aluminum intoxication animals compare to physiological control. We used change in delta range to calculate fractal dimension for the pathophysiological state of disease. We evaluate effect of stress and neurodegeneration, oxidative stress and accumulation of beta amyloid and neurofibrillary tangles as change in fractal dimension (FD). We conclude that change in fractal dimension could be used for prognosis of AD. Results show that decrease in fractal dimension could be used for evaluation of changes in neural activity in occurrence of AD.
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