Kanchan Vohra

Effect of spironolactone on endothelial dysfunction in rheumatoid arthritis

Objective: Chronic inflammation in rheumatoid arthritis (RA) is associated with vascular endothelial dysfunction. The aim of this study was to determine the effect of spironolactone on endothelial function in anti‐tumour necrosis factor (TNF)‐naive RA patients. Methods: Twenty‐four anti‐TNF‐naive RA patients (mean age 49±1.8 years; disease duration 8.5±5.8 years) with high disease activity [Disease Activity Score including a 28‐joint count (DAS28>5.1)] despite treatment with stable doses of conventional disease‐modifying anti‐rheumatic drugs (DMARDs) were investigated. Inflammatory disease activity [DAS28 and Health Assessment Questionnaire‐Disability Index (HAQ‐DI) scores, erythrocyte sedimentation rate (ESR), and C‐reactive protein (CRP)], serum markers of endothelial dysfunction, serum nitrite concentration, and endothelium‐dependent and ‐independent vasodilation of the brachial artery were measured before and after 12 weeks of therapy with oral spironolactone 2 mg/kg/day. Results: After treatment with spironolactone, flow‐mediated vasodilation (FMD) improved from 3.18±0.46% to 3.95±0.49% (p<0.001) whereas there was no significant change in endothelium‐independent vasodilation with nitroglycerin and baseline diameter (18.4±1.15% vs. 18.3±1.13%, p = 0.046, and 3.5±0.1 vs. 3.52±0.1 mm, p = 0.952, respectively); serum nitrite concentration was reduced significantly from 6.9±0.34 to 6.8±0.33 µmol/L (p<0.001), ESR from 59.90±4.86 to 51.22±4.26 mm in the first hour (p<0.001), and CRP level from 15.2±3.8 to 9.4±2.6 mg/dL (p = 0.019). DAS28 and HAQ‐DI scores were significantly reduced, from 6.9±0.25 to 4.1±0.31 (p<0.05) and from 1.47±0.09 to 0.69±0.1 (p<0.05), respectively. Conclusions: The study suggests that, in RA, endothelial dysfunction is part of the disease process and treatment with spironolactone improves both endothelial dysfunction and inflammatory disease activity in RA.

Advanced glycation end-products inhibition improves endothelial dysfunction in rheumatoid arthritis

Aim:  Chronic inflammation in rheumatoid arthritis is associated with vascular endothelial dysfunction. The objective was to study the efficacy and safety of advanced glycation end products (AGEs) inhibitor (benfotiamine 50 mg + pyridoxamine 50 mg + methylcobalamin 500 μg, Vonder® (ACME Lifescience, Baddi, Himachal Pradesh, India)) on endothelial function in rheumatoid arthritis (RA).

Efficacy and tolerability of advanced glycation end-products inhibitor in osteoarthritis: a randomized, double-blind, placebo-controlled study.

Objectives:Advanced glycation end-products (AGEs) play an important role in pathogenesis of osteoarthritis (OA). The objective of this study was to evaluate the efficacy and tolerability of AGEs inhibitor (benfotiamine [50 mg]+pyridoxamine [50 mg]+methylcobalamin [500 µg]; Vonder [Cosme Farma Laboratories Limited, Goa, India]) in OA patients. Methods:A 24-week, double-blind, randomized placebo-controlled study in primary OA patients (n=30 [F/M=26/4; mean age, 57.26±2.16 y]) meeting the classification criteria of American College of Rheumatology, was conducted. Inflammatory disease activity scores on the Western Ontario and McMaster University (WOMAC) Osteoarthritis Index, Lequesne Index, and Pain scores were analyzed. Biomarkers: serum nitrite, AGEs, thiobarbituric acid reactive substances, C-reactive protein, erythrocyte sedimentation rate, were also measured. Time taken to walk 20 m was also recorded. Patients were randomized to either AGEs inhibitor or placebo tablets as thrice-daily regimen. Results:At 24 weeks, net decrease in pain score, −6.64±2.71 versus −8.20±1.28, P=0.003; total WOMAC score, −5.88±0.84 versus −8.26±1.24, P=0.013; Lequesne Index score, −0.60±0.06 versus −0.84±0.09, P=0.05; time taken for 20-m walk test, −5.0±1.39 versus −5.0±0.92 s, P=1.00, were observed in the placebo versus drug group, respectively. Net change in serum nitrite, −0.15±0.01 versus −0.79±0.12 µmol/L, P<0.001; AGEs, −0.12±0.02 versus −0.99±0.09, arbitrary florescence units, P=0.001; thiobarbituric acid reactive substances, −0.69±0.12 versus −1.80±0.12 nmol/L, P<0.01; C-reactive protein, −0.12±0.35 versus −2.45±0.60 mg/L, P<0.01, were observed in the placebo versus drug group, respectively. Discussion:This study shows the efficacy of an AGE inhibitor on decreasing pain and inflammation, and increasing daily activity and mobility in OA patients.

Exploring the potential of low dose sulfasalazine in stable coronary artery disease patients: randomized, double blind, placebo controlled study

Recent statistics reports by Centre for Disease Control and Prevention (CDC) and World Health Organization (WHO) have presented the facts that cardiovascular disease (CVD) accounts for 30% of all deaths.1 Genetic polymorphism, age, gender, smoking, inflammation, systolic blood pressure (SBP), cholesterol, physical inactivity, low socio-economic status, and psychosocial risk factors contribute to development of CVD.2 Inflammation-induced cardiac and vascular remodelling, oxidative stress, unregulated synthesis of nitric oxide, impaired immune cells signalling, and cytokines cascade contribute to cardiovascular damage. Sulfasalazine, an anti-cytokine drug, is reasonably accepted clinically for its efficacy in inflammatory diseases due to potential NF-kB and TNF-α inhibitory activity.3 However, none of the anti-cytokine drugs has been incorporated in a standard regimen for treatment of coronary artery disease (CAD). Our study aimed at controlling inflammation using sulfasalazine 500 mg, once a day for 24 weeks in stable CAD patients. A randomized, double-blind, placebo-controlled, parallel group study was carried out, under the Department of Pharmaceutical Sciences and Drug Research, after due approval from Institutional Ethics Committee of Punjabi University, Patiala. The study was performed in accordance with the declaration of Helsinki and the code of Good Clinical Practice. Written informed consent was obtained from each patient prior to recruitment in the study. Inclusion criteria were: male/female patients ( n = 50, ≥18 years …