Δ8(14)-Ergostenol Glycoside Derivatives Inhibit the Expression of Inflammatory Mediators and Matrix Metalloproteinase

Arthritis is a chronic inflammatory disease accompanied by pathological reactions such as swelling, redness, fever, and pain in various joint areas. The drugs currently available to treat arthritis are associated with diverse side-effects. Therefore, there is a need for safer and more effective treatments to alleviate the inflammation of arthritis with fewer side-effects. In this study, a new sterol, Δ⁸⁽¹⁴⁾-ergostenol, was discovered, and its glycosides were synthesized and found to be more efficient in terms of synthesis or anti-inflammatory activity than either spinasterol or 5,6-dihydroergosterol is. Among these synthetic glycosides, galactosyl ergostenol inhibited the expression of inflammatory mediators in TNF-α-stimulated FLS and TNF-α-induced MMPs and collagen type II A1 degradation in human chondrocytes. These results suggest the new galactosyl ergostenol as a treatment candidate for arthritis.     

3.0 T MR investigation of CLIPPERS: Role of susceptibility weighted and perfusion weighted imaging

For the first time we describe and interpret Susceptibility Weighted Imaging (SWI) and Perfusion Weighted Imaging (PWI) findings in a case of Chronic Lymphocytic Inflammation with Perivascular Pontine Enhancement Responsive to Steroids (CLIPPERS). The diagnosis of the disease was formulated on the basis of typical Magnetic Resonance (MR) findings and its responsiveness to steroids in a 40-year-old man with acute onset of dizziness, ataxia and diplopia. The patient underwent a 3 tesla (T) MR examination including SWI and PWI sequences. SWI revealed prominent veins and multiple hypointense lesions of different size widely distributed in brainstem and cerebellum, which could be expression of iron deposition or cellular infiltrates. PWI demonstrated global infratentorial hypoperfusion. SWI and PWI provide new information on CLIPPERS that might be helpful to understand the physiopathology of the disease. Further observations are needed to evaluate if these findings are peculiar for CLIPPERS and if they might have a role in a non-invasive diagnosis of the disease.     

Novel calorimetric properties of human cartilage samples in rheumatoid arthritis

During recent years, knowledge of rheumatoid arthritis has increased, and management of the disease has improved. A limited number of papers have been published before on the subject of thermal analysis of degenerative cartilage but rheumatoid arthritis (RA) has not been studied previously. A new protocol had to be established before the investigation. The purpose of this study was to further characterize the altered metabolism in human RA cartilage that promotes disease progression. Previously, these methods have not been used for this purpose. The use of thermal analysis could be an effective method for controlling the relationship between biomarkers and disease progression.     

Network Modeling of Inflammatory Dynamics Induced by Biomass Smoke Leading to Chronic Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disorder characterized by airflow obstruction and progressive damage of lung tissues. As currently more than 3 billion people use biomass fuel for cooking and heating worldwide, exposure to biomass smoke (BS) is recognized as a significant risk factor for COPD. Recent clinical data have shown that BS-COPD patients have a Th2-type inflammatory profile significantly different from that in COPD induced by cigarette smoke. As COPD is essentially proinflammatory, however, the mechanism underlying this Th2-type anti-inflammatory profile remains elusive. In this work, a network model is applied to study BS-induced inflammatory dynamics. The network model involves several positive feedback loops, activations of which are responsible for different mechanisms by which clinical phenotypes of COPD are produced. Our modeling study in this work has identified a subset of BS-COPD patients with a mixed M1-and Th2-type inflammatory profile. The model's prediction is in good agreement with clinical experiments and our in silico knockout simulations have demonstrated several important network components that play an important role in the disease. Our modeling study provides novel insight into BS-COPD progression, offering a rationale for targeted therapy and personalized medicine for treatment of the disease in future.     

Direct determination of selenium in whole blood by anodic stripping voltammetry

Trace quantities of selenium can be determined in the presence of iron, copper and lead using anodic stripping voltammetry, depositing at –0.60 V in 0.1M HClO₄ and stripping in the anodic direction. Two separate peaks are observed at –0.25 V and –0.10 V belonging to copper and selenium, respectively. Sometimes one peak may be observed for both copper and selenium. In this case one more stripping (without deposition) must be done to obtain separate peaks. After standard addition, two strippings have to be done also. With this proposed method, 10^–7 M selenium could be determined as (1.09±0.03) × 10^–7 M with a 90% confidence interval in blood samples without any separation.Presented at Xth National Chemistry Congress, Bursa, Turkey, September 19–21, 1994     

Simultaneous determination of leflunomide and its active metabolite,A77 1726, in human plasma by high-performance liquid chromatography

The isoxazol derivative leflunomide [N-(4'-trifluoromethylphenyl)-5-methylisoxazole-4-carboxamide] is an inhibitor of de novo pyrimidine synthesis used for the treatment of rheumatoid artrithis. In the present study, a liquid-liquid extraction-based reversed-phase HPLC method with UV detection was validated and applied for the analysis of leflunomide and its active metabolite, A77 1726, in human plasma. The analytes were separated using a mobile phase, consisting of acetonitrile, water and formic acid (40/59.8/0.2, v/v), at a flow rate of 0.5 mL/min, and UV detection at 261 nm. The retention times for A77 1726, leflunomide and warfarin (internal standard) were 8.2, 16.2 and 12.2 min, respectively. The validated quantification range of the method was 0.05-100 micro g/mL for leflunomide and 0.1-100 micro g/mL for A77 1726. The developed procedure was applied to assess steady-state plasma concentrations of A77 1726 in patients with rheumatoid arthritis treated with 10 or 20 mg leflunomide per day.     

A review on the therapeutic applications of aptamers and aptamer-conjugated nanoparticles in cancer,inflammatory and viral diseases

The advancement in early diagnosis and precise treatments options result in more predictable and powerful health care modalities. Aptamers are known as nucleic acid structures with three-dimensional conformation to selectively bind a target site. Physicochemical properties of aptamers, their conjugation with nanoparticles (NPs) in theranostics applications and their internalization have been found to be of interest in development of aptamer-based drug delivery systems. Therefore, we aimed to present an overview on the structure and generation of aptamers followed by advantages of aptamers-conjugated NPs and their theranostics applications in various diseases such as oncology, inflammatory diseases and viral diseases. Afterward, we discussed several reports on the internalization approaches of aptamers, efficiency of aptamers vs. their analogous, and implications of aptamers in clinical trials. Finally, we discussed the current challenges and future perspectives of actively targeted aptamers for clinical application. In conclusion, this review may hold a great promise for development of aptamer-based therapeutic platforms in clinical trials.     

Label-free Electrochemical Immunosensor for Sensitive Detection of Rheumatoid Arthritis Biomarker Anti-CCP-ab

The accurate and sensitive analysis of rheumatoid arthritis(RA) trace biomarkers is essential for early warning and diagnosis of RA, while anti-cyclic citrullinated peptide antibody (anti-CCP-ab) is a specific one. In this study, a simple label-free electrochemical immunosensor for the detection of anti-CCP-ab was constructed with nitrogen-doped graphene (N−G) and gold nanoparticles (AuNPs). The proposed non-enzyme immunosensor had exhibited high specificity, selectivity, and stability in the linear calibration curve range from 0.125∼2000 pg mL-1 and has been successfully used in the detection of anti-CCP-ab in human serum, providing a new idea for the early diagnosis of RA.