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Fulltext DNA methylation mediates genotype and smoking interaction in the development of anti-citrullinated peptide antibody-positive rheumatoid arthritis

Meng W, Zhu Z, Jiang X, Too CL, Uebe S, Jagodic M, et al.

Arthritis Res Ther, 2017 03 29;19(1):71.
PMID: 28356135 DOI: 10.1186/s13075-017-1276-2

BACKGROUND: Multiple factors, including interactions between genetic and environmental risks, are important in susceptibility to rheumatoid arthritis (RA). However, the underlying mechanism is not fully understood. This study was undertaken to evaluate whether DNA methylation can mediate the interaction between genotype and smoking in the development of anti-citrullinated peptide antibody (ACPA)-positive RA.

METHODS: We investigated the gene-smoking interactions in DNA methylation using 393 individuals from the Epidemiological Investigation of Rheumatoid Arthritis (EIRA). The interaction between rs6933349 and smoking in the risk of developing ACPA-positive RA was further evaluated in a larger portion of the EIRA (1119 controls and 944 ACPA-positive patients with RA), and in the Malaysian Epidemiological Investigation of Rheumatoid Arthritis (MyEIRA) (1556 controls and 792 ACPA-positive patients with RA). Finally, mediation analysis was performed to investigate whether DNA methylation of cg21325723 mediates this gene-environment interaction on the risk of developing of ACPA-positive RA.

RESULTS: We identified and replicated one significant gene-environment interaction between rs6933349 and smoking in DNA methylation of cg21325723. This gene-smoking interaction is a novel interaction in the risk of developing ACPA-positive in both Caucasian (multiplicative P value = 0.056; additive P value = 0.016) and Asian populations (multiplicative P value = 0.035; additive P value = 0.00027), and it is mediated through DNA methylation of cg21325723.

CONCLUSIONS: We showed that DNA methylation of cg21325723 can mediate the gene-environment interaction between rs6933349 and smoking, impacting the risk of developing ACPA-positive RA, thus being a potential regulator that integrates both internal genetic and external environmental risk factors.

Matched MeSH terms: Arthritis, Rheumatoid/genetics*; Arthritis, Rheumatoid/immunology
Fulltext Occupational exposure to textile dust increases the risk of rheumatoid arthritis: results from a Malaysian population-based case-control study

Too CL, Muhamad NA, Ilar A, Padyukov L, Alfredsson L, Klareskog L, et al.

Ann Rheum Dis, 2016 06;75(6):997-1002.
PMID: 26681695 DOI: 10.1136/annrheumdis-2015-208278

OBJECTIVES: Lung exposures including cigarette smoking and silica exposure are associated with the risk of rheumatoid arthritis (RA). We investigated the association between textile dust exposure and the risk of RA in the Malaysian population, with a focus on women who rarely smoke.

METHODS: Data from the Malaysian Epidemiological Investigation of Rheumatoid Arthritis population-based case-control study involving 910 female early RA cases and 910 female age-matched controls were analysed. Self-reported information on ever/never occupationally exposed to textile dust was used to estimate the risk of developing anti-citrullinated protein antibody (ACPA)-positive and ACPA-negative RA. Interaction between textile dust and the human leucocyte antigen DR β-1 (HLA-DRB1) shared epitope (SE) was evaluated by calculating the attributable proportion due to interaction (AP), with 95% CI.

RESULTS: Occupational exposure to textile dust was significantly associated with an increased risk of developing RA in the Malaysian female population (OR 2.8, 95% CI 1.6 to 5.2). The association between occupational exposure to textile dust and risk of RA was uniformly observed for the ACPA-positive RA (OR 2.5, 95% CI 1.3 to 4.8) and ACPA-negative RA (OR 3.5, 95% CI 1.7 to 7.0) subsets, respectively. We observed a significant interaction between exposure to occupational textile dust and HLA-DRB1 SE alleles regarding the risk of ACPA-positive RA (OR for double exposed: 39.1, 95% CI 5.1 to 297.5; AP: 0.8, 95% CI 0.5 to 1.2).

CONCLUSIONS: This is the first study demonstrating that textile dust exposure is associated with an increased risk for RA. In addition, a gene-environment interaction between HLA-DRB1 SE and textile dust exposure provides a high risk for ACPA-positive RA.

Matched MeSH terms: Arthritis, Rheumatoid/etiology*; Arthritis, Rheumatoid/genetics
Fulltext One-Year Tuberculosis Risk in Rheumatoid Arthritis Patients Starting Their First Tumor Necrosis Factor Inhibitor Therapy from 2008 to 2012 in Taiwan: A Nationwide Population-Based Cohort Study

Lim CH, Lin CH, Chen DY, Chen YM, Chao WC, Liao TL, et al.

PLoS One, 2016;11(11):e0166339.
PMID: 27832150 DOI: 10.1371/journal.pone.0166339

OBJECTIVE: To investigate the risk of tuberculosis (TB) among rheumatoid arthritis (RA) patients within 1 year after initiation of tumor necrosis factor inhibitor (TNFi) therapy from 2008 to 2012.
METHODS: We used the 2003-2013 Taiwanese National Health Insurance Research Database to identify RA patients who started any RA-related medical therapy from 2008 to 2012. Those who initiated etanercept or adalimumab therapy during 2008-2012 were selected as the TNFi group and those who never received biologic disease-modifying anti-rheumatic drug therapy were identified as the comparison group after excluding the patients who had a history of TB or human immunodeficiency virus infection/acquired immune deficiency syndrome. We used propensity score matching (1:6) for age, sex, and the year of the drug index date to re-select the TNFi group and the non-TNFi controls. After adjusting for potential confounders, hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated to examine the 1-year TB risk in the TNFi group compared with the non-TNFi controls. Subgroup analyses according to the year of treatment initiation and specific TNFi therapy were conducted to assess the trend of 1-year TB risk in TNFi users from 2008 to 2012.
RESULTS: This study identified 5,349 TNFi-treated RA patients and 32,064 matched non-TNFi-treated controls. The 1-year incidence rates of TB were 1,513 per 105 years among the TNFi group and 235 per 105 years among the non-TNFi controls (incidence rate ratio, 6.44; 95% CI, 4.69-8.33). After adjusting for age, gender, disease duration, comoridities, history of TB, and concomitant medications, TNFi users had an increased 1-year TB risk (HR, 7.19; 95% CI, 4.18-12.34) compared with the non-TNFi-treated controls. The 1-year TB risk in TNFi users increased from 2008 to 2011 and deceased in 2012 when the Food and Drug Administration in Taiwan announced the Risk Management Plan for patients scheduled to receive TNFi therapy.
CONCLUSION: This study showed that the 1-year TB risk in RA patients starting TNFi therapy was significantly higher than that in non-TNFi controls in Taiwan from 2008 to 2012.

Matched MeSH terms: Arthritis, Rheumatoid/complications*; Arthritis, Rheumatoid/drug therapy*
Java Tea (Orthosiphon stamineus) protected against osteoarthritis by mitigating inflammation and cartilage degradation: a preclinical study

Bokhari RA, Tantowi NACA, Lau SF, Mohamed S

Inflammopharmacology, 2018 Aug;26(4):939-949.
PMID: 29380171 DOI: 10.1007/s10787-017-0432-2

The effect of Orthosiphon stamineus aqueous (OSA) extract against osteoarthritis (OA) was investigated in explant cartilage culture and in postmenopausal OA rat model. Female rats were bilaterally ovariectomized (OVX). Osteoarthritis was induced after surgical recovery, by intra-articular injection of monosodium iodoacetate (MIA) into the right knee. Rats were grouped (n = 8) into: healthy sham control; non-treated OA; OA + diclofenac (positive control 5 mg/kg); and two doses OSA (150-300 mg/kg). After 4 weeks' treatment, rats were evaluated for OA-related parameters and biomarkers. The OSA reduced proteoglycan and ROS release from the cartilage explants under inflammatory (IL-1b) conditions. In the OA-induced rats' cartilages, the OSA downregulated the mRNA expressions for IL-1β, IL-6, IL-10, TNF-α, NF-κβ, NOS2, PTGS2, PTGER2, ACAN, COL2A1, MMP1, MMP13, ADAMTS4, ADAMTS5 and TIMP1, mostly dose-dependently. The OSA reduced the OA rats' serum levels for PGE2, CTX-II, TNF-α, MMP1, MMP13, PIINP, OPG, RANKL, OC and BALP, but not dose-dependently. The OSA contained polyphenols and flavonoids (tetramethoxyflavone). The OSA alleviated articular cartilage degradation, inflammation, collagenase/aggrecanase activities, to improve joint and subchondral bone structure. O. stamineus mitigated osteoarthritis by downregulating inflammation, peptidases and aggrecanases, at a dose equivalent to about 30 mg/kg for humans.

Matched MeSH terms: Arthritis, Experimental/drug therapy*; Arthritis, Experimental/pathology
CXCL 9 and CXCL 10 as Sensitive markers of disease activity in patients with rheumatoid arthritis

Kuan WP, Tam LS, Wong CK, Ko FW, Li T, Zhu T, et al.

J Rheumatol, 2010 Feb;37(2):257-64.
PMID: 20032101 DOI: 10.3899/jrheum.090769

OBJECTIVE:
To assess whether serum levels of CC and CXC chemokines correlate with disease activity in patients with rheumatoid arthritis (RA), and to determine whether these effects predict clinical response.

METHODS:
Serum levels of the chemokines CC (CCL2, CCL5) and CXC (CXCL8, CXCL9, CXCL10) were quantified at baseline and after 12 weeks of treatment with disease-modifying antirheumatic drugs or biologic agents in 28 patients using flow cytometry. Serum from 40 healthy individuals was collected for comparison at baseline. Response to treatment was classified according to the European League Against Rheumatism (EULAR) response criteria. Remission of disease was defined as a Disease Activity Score < 2.6.

RESULTS:
The baseline serum concentrations of CC and CXC chemokines were significantly elevated in patients with active RA compared to healthy controls (p < 0.05) except for CCL2. Significant improvement in all disease activity measurements was observed after 12 weeks of treatment. Seventeen (60.7%) patients achieved good to moderate response based on the EULAR response criteria, and 5 (17.9%) patients achieved remission. The improvement in clinical activity in patients with RA was accompanied by a significant reduction in the serum concentration of CXCL9 and CXCL10 (p < 0.001). A significant reduction in the serum level of CXCL10 was also observed in the group that achieved EULAR response. Serum concentration of CCL5 remained significantly elevated in patients with RA (n = 5) who achieved remission compared to the healthy controls (p < 0.05).

CONCLUSION:
Serum concentration of CXCL9 and CXCL10 may serve as sensitive biomarkers for disease activity in patients with RA.
Study done in Hong Kong

Matched MeSH terms: Arthritis, Rheumatoid/blood*; Arthritis, Rheumatoid/therapy
Fulltext Reiter's syndrome postintravesical Bacillus Calmette-Guérin instillations

Ng KL, Chua CB

Asian J Surg, 2017 Apr;40(2):163-165.
PMID: 25183290 DOI: 10.1016/j.asjsur.2014.01.016

Intravesical Bacillus Calmette-Guérin (BCG) has been a proven and effective immunotherapy treatment for superficial transitional cell carcinoma (TCC) of the bladder, especially for high-grade tumors and carcinoma in situ. Nevertheless, significant side effects are associated with BCG instillations, including fever, myalgia, malaise, dysuria, hematuria, and irritable lower urinary tract symptoms. We herein report the case of a patient who developed Reiter's syndrome following intravesical BCG instillations. A 39-year-old Chinese man presented with a 3-week history of dysuria, suprapubic pain, and pain at the tip of the penis postmicturition. Initial investigations revealed that he had microhematuria, and an ultrasound with computed tomography scan of the abdomen showed a bladder mass. Transurethral resection of the bladder tumor was performed and the patient received a single dose of intravesical mitomycin postoperatively. Results of histopathological examination revealed high-grade bladder TCC (G3pT1), and the patient was managed with intravesical BCG for 2 weeks following the surgery. Four weekly cycles of BCG were administered uneventfully; however, before the fifth instillation, the patient complained of urethral discharge, bilateral conjunctivitis, and low back pain. Reiter's syndrome was diagnosed as a rare but known complication of BCG instillation and the BCG immunotherapy was withheld. The patient was treated with nonsteroidal antiinflammatory drugs (for back pain) and eye ointment (for conjunctivitis) and his condition improved. This case report of Reiter's syndrome should be highlighted as a rare but significant complication of BCG immunotherapy and urologists should have a high index of suspicion to diagnose this rare complication.

Matched MeSH terms: Arthritis, Reactive/chemically induced*; Arthritis, Reactive/physiopathology; Arthritis, Reactive/therapy*
Fulltext Melioidosis: a case report

Barman P, Sidhwa H, Shirkhande PA

J Glob Infect Dis, 2011 Apr;3(2):183-6.
PMID: 21731307 DOI: 10.4103/0974-777X.81697

Burkhloderia pseudomallei has recently gained importance as an emerging pathogen in India. It causes various clinical manifestations like pneumoniae, septicaemia, arthritis, abscess etc. Cases have been reported from Southeast Asia mainly Thailand, Malaysia, Vietnam, etc. In India, few cases have been reported mainly from the southern part of the country. Patient was a 65-year-old male and presented with fever 1 month back, cough and breathlessness for same period, swelling on both ankles from 7 days. B. pseudomallei was isolated from endotracheal secretions, blood cultures, leg wound. He was successfully treated with Imipenem and Doxycycline and put on maintenance therapy now, and is currently doing well.

Matched MeSH terms: Arthritis
Fulltext Severe psoriatic acroosteolysis in the absence of psoriatic arthropathy

Sakthiswary R, Naicker AS, Htwe O, Shahrir MS, Sazliyana SS

BMJ Case Rep, 2011;2011.
PMID: 22669957 DOI: 10.1136/bcr.09.2011.4794
Matched MeSH terms: Arthritis, Psoriatic
Fulltext Antiarthritic activity of a polyherbal formulation against Freund's complete adjuvant induced arthritis in Female Wistar rats

Petchi RR, Parasuraman S, Vijaya C, Gopala Krishna SV, Kumar MK

J Basic Clin Pharm, 2015 Jun;6(3):77-83.
PMID: 26229343 DOI: 10.4103/0976-0105.160738

OBJECTIVES:
To formulate a polyherbal formulation and evaluate its antiarthritic activity against Freund's complete adjuvant induced arthritis in Female Wistar rats.

MATERIALS AND METHODS:
Glycosmis pentaphylla, Tridax procumbens, and Mangifera indica are well-known plants available throughout India and they are commonly used for the treatment of various diseases including arthritis. The polyherbal formulation was formulated using the ethanol extracts of the stem bark of G. pentaphylla , whole plant of T. procumbens, and leaves of M. indica. The polyherbal formulation contains the ethanol extracts of G. pentaphylla, T. procumbens, and M. indica in the ratio of 2:2:1. The quality of the finished product was evaluated as per the World Health Organization's guidelines for the quality control of herbal materials. Arthritis was induced in female Wistar rats using Freund's complete adjuvant (FCA), and the antiarthritic effect of polyherbal formulation was studied at doses of 250 and 500 mg/kg. The effects were compared with those of indomethacin (10 mg/kg). At the end of the study, blood samples were collected for biochemical and hematological analysis. The radiological examination was carried out before terminating the study.

RESULTS:
Polyherbal formulation showed significant antiarthritic activity at 250 and 500 mg/kg, respectively, and this effect was comparable with that of indomethacin. The antiarthritic activity of polyherbal formulation is supported by biochemical and hematological analysis.

CONCLUSION:
The polyherbal formulation showed signinicant antiarthritic activity against FCA-induced arthritis in female Wistar rats.

KEYWORDS:
Arthritis; Fingerprint analysis; Glycosmis pentaphylla; Mangifera indica; Tridax procumbens

Matched MeSH terms: Arthritis
Fulltext Early results of total knee replacements: "a clinical and radiological evaluation"

Dhillon KS, Jamal A, Bhupinderjeet S

Med J Malaysia, 1993 Dec;48(4):427-35.
PMID: 8183167

From March 1986 to June 1992, 100 primary total knee arthroplasties were done in 69 patients. The demographic data and complications were analysed in these 69 patients. The first 50 knees with a minimal follow-up of one year (range 1-6 years) were analysed in more detail according to the International Knee Society Rating System. Detailed radiological evaluation was also carried out to assess positioning of the components. There were 79 knees with osteoarthritis, 20 knees with rheumatoid arthritis and one with Systemic Lupus Erythromatosus (SLE). The knee score was poor in all knees pre-operatively. Post-operatively 78% had good to excellent score and the other 22% had fair knee score. However the functional score remained poor in 50% of the knees. Ideal tibio-femoral alignment was obtained in 68% of the knees. Twenty four percent of the knees had 0.4 degrees of varus and eight percent had 10-12 degrees valgus. Complication rate was low with 1% of infection (one knee). Overall early results were satisfactory.
Study site; University Hospital Kuala Lumpur (University Malaya Medical Centre)

Matched MeSH terms: Arthritis, Rheumatoid
Fulltext Vertebrae Destruction with Cauda Equina Syndrome Secondary to Spinal Gouty Arthritis: A Case Report

Thuraikumar K, Wan KL, Ong KL, Lim SW

Malays Orthop J, 2020 Jul;14(2):141-144.
PMID: 32983391 DOI: 10.5704/MOJ.2007.024

Gouty arthritis commonly affects peripheral joints and is associated with hyperuricaemia. Spinal manifestations of gouty arthritis are not common, and majority of published articles worldwide were case reports. This is a case report of spinal gouty arthritis that presented with spinal vertebrae destruction and cauda equina syndrome. The magnetic resonance imaging (MRI) showed destruction of L5/S1end plates with cystic collection mimicking infective changes. The tissue histological examination confirmed presence of urate crystal needles that displayed negative double refraction on light microscopy. Spinal gouty arthritis is part of the differential diagnoses in gouty arthritis patients.

Matched MeSH terms: Arthritis, Gouty
Fulltext Health benefits and potential risk of tropical herbs from the leguminosae family: a review

Fatin Afifah Rosli, Mohd Rahman Omar, Abdul Aziz Marwan, Ummu Aiman Faisal, Hana Maizuliana Solehan, Ummi Affah Mahamad, et al.

Malaysian Journal of Medicine and Health Sciences, 2019;15(106):59-59.
MyJurnal

Introduction:Tropical herbs are used as a medicine long before the introduction of modern medicine, especially by traditional healers. However, its’ scientific benefits are not widely investigated. There is a belief that the use of tradi-tional herbs potentially causing health deterioration due to its unknown mechanism of actions and interactions, and the nature of its unregulated processing as a health supplement. Parkia speciosa (local: petai) and Pithecellobium jir-inga (local: jering) are two tropical herbs from the Leguminosae family that are widely used raw as salads with many perceived health benefits and harms. We reviewed both species, looking into scientific pieces of evidence supporting the belief. Methods: The databases of MEDLINE, PubMed, EBSCOhost, and Google Scholars were systematically searched for both in vitro and in vivo effects of both species with no language restriction. Data were extracted using standardised fashioned. Results:P speciosa has pharmacological properties including antioxidant and anti-inflam-mation. It has shown to have antibacterial properties and glucose-lowering activity. P jiringa contains known an-tioxidant metabolites such as flavonoids, phenolics and terpenoids. It also contains antiangiogenic properties with potential use in retinopathy, cancer, and Rheumatoid arthritis. However, both herbs have potentially harmful effects which include liver injuries. Large consumption of P jiringa leads to acute kidney injury. Conclusion: Consumption of both P speciosa and P jiringa has medicinal properties as well as health harm. If taken as a supplement, rigorous clinical trials are needed to delineate benefit vs harm effect of both herbs.

Matched MeSH terms: Arthritis, Rheumatoid
Fulltext Salivary and serum levels of Ca and Zn in periodontitis with or without rheumatoid arthritis

Jazli Aziz, Zamri Radzi, Rathna Devi Vaithilingam, Mohammad Tariqur Rahman

Malaysian Journal of Medicine and Health Sciences, 2019;15(108):32-32.
MyJurnal

Introduction: While sharing a common causal link, both rheumatoid arthritis (RA) and periodontitis (PD) manifest similar inflammatory responses. With the progression of severity, both diseases result in bone loss. Hence, Ca and Zn, as structural components of the bones, are expected to be altered in saliva and serum in PD and RA respectively. Zinc and calcium concentrations have been studied previously in patients with PD or RA, with PD patients exhibiting increased salivary Ca and decreased Zn concentrations in serum, while RA patients have been reported to express low plasma concentrations of both Zn and Ca. The aim of this study is to evaluate the saliva and serum levels of Ca and Zn in PD patients with or without RA. Methods: Serum and saliva samples were collected from 82 patients from the Faculty of Dentistry, University of Malaya and the University Malaya Medical Centre rheumatoid clinic. Patients were grouped according to their periodontal health and RA status (healthy n=21; PD n=21; RA n=21; RAPD n=19). Results: Zinc concentration in serum was significantly higher (p

Matched MeSH terms: Arthritis, Rheumatoid
Anti-CCP antibodies: A better diagnostic tool for rheumatoid arthritis

Dollah R, Yaacob A, Ismail AH, Che Hussin CM

International Medical Journal (Tokyo), 2011;18(1):53-57.

Objective: The assay for anti-cyclic citrullinated peptide (anti-CCP) antibody is a recent test of interest due to low diagnostic specificity of rheumatoid factor in the diagnosis of rheumatoid arthritis. To determine the sensitivity and specificity of anti-CCP antibodies in rheumatoid arthritis patients using American College of Rheumatology (ACR) criteria as a gold standard.
Design: A cross sectional study was conducted from January 2008 to December 2008 on 100 patients with rheumatoid arthritis and 153 patients with arthritis or arthralgia but not fulfilling ACR criteria for rheumatoid arthritis.
Materials and Methods: Serum from each subject was tested for anti-CCP antibodies and IgM rheumatoid factor (IgM RF) by an enzyme linked immunosorbent assay (ELISA). Sensitivity and specificity of the tests were evaluated using the ACR criteria as the gold standard. Data was analyzed using SPSS version 12.0 software. The association between the two categorical variables were tested using chi-square test. The differences between the two groups were tested using independent t-test. Results: The sensitivity of anti-CCP antibodies was 71% with 94.8% of specificity. For rheumatoid factor the sensitivity was 85% and the specificity was 74.5%. Positive predictive value for anti-CCP antibodies was 89.9% whereas for rheumatoid factor it was 68.5%. The sensitivity of ACR criteria with inclusion of anti- CCP antibodies was 100% and specificity of 94.8% (95%CI: 91.3%, 98.2%).
Conclusion: Anti-CCP antibody has a higher diagnostic accuracy compared to the RF. Anti-CCP antibody is a useful laboratory marker to support the diagnosis of rheumatoid arthritis and to differentiate patients with rheumatoid arthritis from rheumatoid arthritis-like symptoms. Therefore, it is suggested that anti-CCP antibodies should be included as another laboratory supportive criterium besides RF test in ACR criteria in the diagnosis of RA.
Study site: family medicine clinic, rheumatology clinic and immunology laboratory of Hospital Universiti Sains Malaysia (HUSM), Kubang Kerian, Kelantan, Malaysia

Matched MeSH terms: Arthritis, Rheumatoid
Association of HLA class II antigens with clinical manifestations in malays with systemic lupus erythematosus

Yahya NK, Afzal N, Daud KM

International Medical Journal (Tokyo), 2009;16(1):3-7.

Objectives: To evaluate the frequency of HLA Class II antigens in Malays with SLE in order to determine their role in disease susceptibility and association with clinical manifestations.
Design: Cross-sectional study
Methods: Fifty-four SLE patients from Malay ethnic attending Physician Clinic at Hospital Universiti Sains Malaysia were enrolled into the study. Demographic and clinical findings were obtained from medical records. HLA typing of class II antigens were carried out using MicroSSP Class II generic (DRB/ DQB) from One Lambda Inc. Controls were from ethnically matched healthy individuals.
Results: A univariate analysis confirmed the association between HLA-DR15 with SLE compared to healthy control group; and was maintained using multiple logistic regression model (P corr = 0.002, adjusted OR = 5.513). There was a weak decrease of HLA-DR4 which was not significant after corrections for multiple comparisons made. DR7 was found to be significantly increased in patients with malar rash. There was positive association of DR15 with arthritis in patients compare to those without.
Conclusion: Our data support the role of HLA Class II genes in conferring SLE susceptibility.
Study site: Physician Clinic, Hospital Universiti Sains Malaysia (HUSM), Kelantan, Malaysia

Matched MeSH terms: Arthritis
Evaluation of antiarthritic activity of nimbolide against Freund's adjuvant induced arthritis in rats

Cui X, Wang R, Bian P, Wu Q, Seshadri VDD, Liu L

Artif Cells Nanomed Biotechnol, 2019 Dec;47(1):3391-3398.
PMID: 31394949 DOI: 10.1080/21691401.2019.1649269

Nimbolide, a triterpenoid isolated from flower of neem tree possess various therapeutic properties. The objective of the study was to assess the anti-arthritic activity of nimbolide in arthritis induced rats. Nimbolide (20 mg/kg per day) was given orally to arthritic rats induced with Complete Freund's Adjuvant and changes in paw volume, body weight, organ indices (thymus and spleen), arthritic score, biochemical parameters and proinflammatory cytokines levels were determined. Histopathological analysis was also performed. Western blot analysis was also performed. Rats treated with nimbolide displayed marked reduction in arthritic score, organ indices, volume of paw, edema formation, along with substantial enhancement in body weight. Histopathological findings showed significant reduction in destruction of joints and inflammation following nimbolide treatment. The protective action of arthritic rats treated with nimbolide was also substantiated by molecular and biochemical studies. The results of the study show that nimbolide treatment has markedly enhanced health and reduced inflammation via lessening the proinflammatory cytokines expression in arthritic rats. Hence, nimbolide may be used as a potent therapeutic drug in treating rheumatoid arthritis.

Matched MeSH terms: Arthritis, Experimental/drug therapy*; Arthritis, Experimental/metabolism; Arthritis, Experimental/pathology
To compare ESR and CRP as predictors of disease activity in rheumatoid arthritis patients in Hospital Seremban. [Abstract]

Gun SC, Loh YL, Das Gupta E

APLAR Journal of Rheumatology, 2006;9 Suppl 1:A185.

Background: Rheumatoid arthritis (RA) is an inflammatory disease. Predictors of disease activity include presence of joint inflammation, blood investigations such as erythrocyte sedimentation rate (ESR) and c-reactive protein (CRP). ESR is said to be imprecise as it is affected by aging, female sex, obesity, pregnancy, anaemia and polycythaemia. But it is inexpensive and easy to perform. CRP is produced as an acute phase reactant by the liver in response to interleukin 6 and other cytokines. CRP is more specific but costs more than ESR. Both tests are done in the rheumatology clinic of Hospital Seremban. Objective: To compare the usefulness of ESR and CRP as a predictor of disease activity in rheumatoid arthritis (RA) patients. Method: This was a retrospective study. The medical records of 248 RA patients who attended the rheumatology clinic, Hospital Seremban between 1 January 2004 and 31 Dec 2004 were reviewed. The following data were obtained: joint swelling and tenderness, other clinical features which indicate inflammation secondary to infection or trauma and inflammation of soft tissue, ESR, CRP, FBC and UFEME. Results: Data was analysed and the results showed that a total number of 248 patients were seen. There were 13 defaulters. Of the 248 patients there were 929 patients' visits. Of the total number of patients' visits where patients clinically had active disease, 80.2% had raised ESR while 88.8% had raised CRP. As for visits where patients had quiescent disease clinically, 57.3% had normal ESR and 36.5% had normal CRP. Conclusion: CRP is more sensitive but less specific than ESR. This suggests that we still should use both tests as they complement each other. ESR can serve as a countercheck for CRP and vice versa.

Matched MeSH terms: Arthritis, Rheumatoid
Prevalence and correlates of self-reported depression in Malaysian patients with rheumatoid arthritis

Chow SK, Guan YK, Chong HY, Zainal NZ, Yeap SS

Malaysian Journal of Psychiatry, 2002;10(2):9-14.

Objectives: To determine the prevalence of self-reported depression among Malaysian patients with rheumatoid arthritis (RA) and to study the correlates and independent predictors for depression. Methods: The Hospital Anxiety and Depression Scale (HADS) questionnaire wasused to assess depressive symptoms. Disease activity was determined by theduration of morning stiffness, visual analogue scale for pain and fatigue, numberof swollen/tender joint and the modified disease activity score (DAS). The Health Assessment Questionnaire (HAQ) was used to assess the patients' functionalstatus. Results: Depression was recorded in 17.2% of the 93 patients. Painful joints(p<0.001), active disease (p<0.001) and poor joint function (p<0.001) correlatedsignificantly with depression. Poor functional status assessed by the HAO was themost significant Independent predictor for depression in RA patients, (OR=5.4,p=0.028). Conclusion: The prevalence of depression In this cohort of Asian RA patients was17.2%. Painful joints and functional disability were associated with a higherIncidence of depression. RA Patients with severe functional disability should beassessed for depression that may need to be treated Independently.

Matched MeSH terms: Arthritis, Rheumatoid
Fulltext Blau Syndrome Associated with Nucleotide-binding Oligomerization Domain Containing 2 Mutation in a Baby from Malaysia

Leong KF, Sato R, Oh GGK, Surana U, Pramono ZAD

Indian J Dermatol, 2019 9 24;64(5):400-403.
PMID: 31543536 DOI: 10.4103/ijd.IJD_44_18

Blau syndrome (BS) is a very rare autosomal dominant juvenile inflammatory disorder caused by mutation in nucleotide-binding oligomerization domain containing 2 (NOD2). Usually, dermatitis is the first symptom that appears in the 1st year of life. About 220 BS cases with confirmed NOD2 mutation have been reported. However, the rarity and lack of awareness of the disease, especially in the regions where genetic tests are very limited, often result in late diagnosis and misdiagnosis. Here, we report a de novo BS case from Malaysia, which may be the first report from southeast Asia. PCR and DNA sequencing of peripheral blood mononuclear cells were performed to screen the entire coding region of NOD2 gene. A heterozygous c.1000C>T transition in exon 4, p. R334W, of the NOD2 gene was identified in the patient. This report further reaffirms the ubiquitousness of the disease and recurrency of p. R334W mutation.

Matched MeSH terms: Arthritis
Fulltext Epstein-Barr Virus- (EBV-) Immortalized Lymphoblastoid Cell Lines (LCLs) Express High Level of CD23 but Low CD27 to Support Their Growth

Yap HY, Siow TS, Chow SK, Teow SY

Adv Virol, 2019;2019:6464521.
PMID: 31049064 DOI: 10.1155/2019/6464521

Epstein-Barr virus (EBV) is one of the common human herpesvirus types in the world. EBV is known to infect more than 95% of adults in the world. The virus mainly infects B lymphocytes and could immortalize and transform the cells into EBV-bearing lymphoblastoid cell lines (LCLs). Limited studies have been focused on characterizing the surface marker expression of the immortalized LCLs. This study demonstrates the generation of 15 LCLs from sixteen rheumatoid arthritis (RA) patients and a healthy volunteer using B95-8 marmoset-derived EBV. The success rate of LCL generation was 88.23%. All CD19+ LCLs expressed CD23 (16.94-58.9%) and CD27 (15.74-80.89%) on cell surface. Our data demonstrated two distinct categories of LCLs (fast- and slow-growing) (p<0.05) based on their doubling time. The slow-growing LCLs showed lower CD23 level (35.28%) compared to fast-growing LCLs (42.39%). In contrast, the slow-growing LCLs showed higher percentage in both CD27 alone and CD23+CD27+ in combination. Overall, these findings may suggest the correlations of cellular CD23 and CD27 expression with the proliferation rate of the generated LCLs. Increase expression of CD23 may play a role in EBV immortalization of B-cells and the growth and maintenance of the EBV-transformed LCLs while CD27 expression might have inhibitory effects on LCL proliferation. Further investigations are warranted to these speculations.

Study site: Sunway Medical Centre, Malaysia

Matched MeSH terms: Arthritis, Rheumatoid

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