Objective: This is a secondary analysis of a randomized controlled trial that aimed to assess subclinical atherosclerosis in patients with rheumatoid arthritis (RA) by measuring carotid artery intima-media thickness (CIMT) and correlating it with disease activity and inflammatory markers (including levels of matrix metalloproteinase-3(MMP-3) and matrix metalloproteinase-9 (MMP-9)) and to detect the effectiveness of agents that inhibit matrix metalloproteinases (MMPs) as doxycycline in RA therapy. Methods: One hundred and sixty RA patients were assigned in a randomized clinical trial (clinicaltrial.gov NCT03194204). Disease activity score 28(DAS28), laboratory markers including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), MMP-3, and MMP-9 were done and mean CIMT was measured. Subjects were allocated randomly into one of two treatment arms either methotrexate (MTX) only or MTX with doxycycline 200mg per day orally. Follow up ESR, CRP, DAS28, MMP-3, and MMP-9 levels were re-evaluated after 3 months. Results: There were positive significant correlations between CIMT and disease duration (r = 0.461, p = 0.001), age (r=0.459, p= 0.001), DAS28 score (r= 0.547, p = 0.001), ESR (r =0.413, p = 0.001), CRP (r= 0.281, p = 0.001), MMP-3(r = 0.476, p =0.001), and MMP-9 (r= 0.593, p =0.001). Patients treated with MTX and doxycycline showed lower levels of DAS28, ESR, CRP, MMP-3 and MMP-9 and this was statistically significant. Conclusion: CIMT seems to be the ultimate method to screen for subclinical atherosclerosis in RA patients. MMP-3 and 9 play a key role in both RA synovitis and cardiovascular changes making them important therapeutic targets especially with safe and cost-effective agents like doxycycline.

Patients with rheumatoid arthritis (RA) have a higher risk of cardiovascular disease (CVD) compared to the general population, which leads to increased morbidity and mortality. Inflammation is the key in RA and CVD. Our study aimed to refine cardiovascular (CV) risk assessment in RA patients by using carotid intima-media thickness (cIMT) as a marker of subclinical atherosclerosis. We also explored whether proinflammatory cytokines represented by tumor necrosis factor-alpha (TNF-α) and high-sensitivity cardiac troponin I (hs-cTnI), a biomarker of myocardial injury, could be correlated in RA patients. The study included 80 RA patients and 80 control subjects. TNF-α and hs-cTnI levels were measured. Subclinical atherosclerosis was evaluated by cIMT by means of carotid ultrasound. Disease activity score 28 (DAS28) was used to evaluate disease activity. hs-cTnI and TNF-α serum levels were higher in RA patients compared to controls (p=0.001). There was a significant difference in the median of cIMT between cases and controls (median (IQR) 0.9 (0.2) for cases, 0.7 (0.1) for controls, (p=0.001). A significant correlation was found between the level of TNF-α and hs-cTnI (p=0.002). Also, there was a significant correlation between the cIMT level and TNF-α and hs-cTnI (p=0.003 and p=0.002, respectively). Significant correlation was found between cIMT, TNF-α, and hs-cTnI in relation to the DAS28 score (p<0.001, p<0.001, and p=0.001, respectively). In conclusion, patients with RA are more likely to develop subclinical atherosclerosis, as reflected in increased cIMT. Higher levels of hs-cTnI in RA patients may correlate with the presence of occult cardiovascular disease. TNF-α and hs-cTnI correlations can reveal the interplay between disease activity and CVD. Thus, inflammation must be the primary target of various therapeutic approaches.

Background This single-center randomized open-label clinical trial evaluates the effectiveness of doxycycline as a combination therapy for active rheumatoid arthritis (RA) with methotrexate (MTX). Materials and methods One hundred and sixty RA patients were recruited who fulfilled the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria. Subjects were randomly allocated in a 1:1 ratio into one of two treatment arms; one group was maintained on MTX alone and the other group on MTX together with doxycycline orally 200 mg daily. Follow-up clinical response, erythrocyte sedimentation rate (ESR), levels of C-reactive protein (CRP), and disease activity score 28 (DAS28-CRP) after 3 months were done. Results There was a significant difference regarding DAS28-CRP between the two groups (median (IQR) 4.26 (3.6–5) for those treated with MTX alone compared with 2.8 (2.37–3.5) for those treated with MTX together with doxycycline) (p = 0.005). A higher number of patients treated with doxycycline in combination with MTX achieved remission (40.5%) compared to patients who received MTX alone (13.5%). The levels of ESR and CRP were lower in patients treated with MTX and doxycycline and this was statistically significant (p = 0.005, p = 0.003 respectively). Conclusion Doxycycline as a cost-effective combination therapy with MTX can achieve higher rates of remission than MTX alone in RA patients without causing increase in the adverse events profile. Trial registration Clinical Trials.gov, NCT03194204. Registered on 21 June 2017

Lipases are enzymes which have numerous applications in many industries like leather, soaps and detergents, pharmaceuticals, biofuel, food, textile etc. Many organisms like plants, fungi, bacteria are known to produce lipase. Lipolytic bacteria were isolated from Egyptian animal fats and grown on tributyrin media. Among the isolates from Egyptian animal fats three strains identified to be Lactobacillus suebicus DSM 5008 DSM, Pseudomonas oryzihabitans DSM 6835 THAM and Staphylococcus epidermidis 4b_r ESL. These strains were evaluated for potential probiotic properties. Absence of haemolytic activity and antibiotic resistance is considered as a safety prerequisite for the selection of a probiotic strains. One strain was γ-haemolytic (i.e. no haemolysis) and other were αhemolysis. All of the strains were recorded highly lipolytic activity on Tributyrin agar base plates The highest lipase activity (651.9 µg/ml/min) was observed in Pseudomonas oryzihabitans DSM 6835 THAM but the lowest activity was recorded in Staphylococcus epidermidis 4b_r ESL (151.3 µg/ml/ min). On the other hand, Lactobacillus suebicus DSM 5008 DSM tested gave (337.9 µg/ml/min).