Severe Forms Of Rheumatoid Arthritis Research Articles

The Many Lives of Auranofin: How an Old Anti-Rheumatic Agent May Become a Promising Antimicrobial Drug.

Auranofin (AF) is a gold-based compound with a well-known pharmacological and toxicological profile, currently used in the treatment of some severe forms of rheumatoid arthritis. Over the last twenty years, AF has also been repurposed as antiviral, antitumor, and antibacterial drug. In this review we focused on the antibacterial properties of AF, specifically researching the minimal inhibitory concentrations (MIC) of AF in both mono- and diderm bacteria reported so far in literature. AF proves to be highly effective against monoderm bacteria, while diderm are far less susceptible, probably due to the outer membrane barrier. We also reported the current mechanistic hypotheses concerning the antimicrobial properties of AF, although a conclusive description of its antibacterial mode of action is not yet available. Even if its mechanism of action has not been fully elucidated yet and further studies are required to optimize its delivery strategy, AF deserves additional investigation because of its unique mode of action and high efficacy against a wide range of pathogens, which could lead to potential applications in fighting antimicrobial resistance and improving therapeutic outcomes in infectious diseases.

Association of HLA-DRB1 alleles with rheumatoid arthritis in Split-Dalmatia County in southern Croatia.

The aim of this study was to investigate the distribution of HLA-DRB1 alleles in patients with rheumatoid arthritis (RA) in the Sinj Region (SR) and the rest of the Split-Dalmatia County (SDC) in Croatia and to determine their relationship with disease severity. Atotal of 74RA patients and 80healthy controls from the SR, and 74RA patients and 80healthy controls from the rest of the SDC were genotyped using sequence-specific oligonucleotide primed PCR. High-resolution typing of HLA-DRB1*04 alleles was performed using the single specific primed polymerase chain reaction (PCR-SSP) method. Serum anti-CCP, rheumatoid factor, C‑reactive protein, and erythrocyte sedimentation rate were measured in all RA patients, whereas disease activity was assessed by DAS-28 and functional status by the Health Assessment Questionnaire Disability Index. The HLA-DRB1*04 allele was more frequent in patients with RA from the SR than that in patients from the rest of the SDC (18.2% vs. 9.5%; P = 0.014), whereas the HLA-DRB1*15 allele was more frequent in patients with RA from the rest of the SDC than in patients from the SR (16.2% vs. 7.4%; P = 0.010). Shared epitope (SE) positive patients from the SR had significantly higher serum anti-CCP and RF antibody levels (P = 0.014 and P = 0.004, respectively), higher disease activity (P = 0.043), and worse functional status (P < 0.001), than SE-positive patients from the rest of the SDC. The observed higher incidence of more severe forms of RA in the SR in comparison to the rest of the SDC might be associated with the higher incidence of HLA-DRB1*04 allele in the SR.

ПРИМЕНЕНИЕ БИОТЕХНОЛОГИЧЕСКИХ ЛЕКАРСТВЕННЫХ СРЕДСТВ В ПЕДИАТРИЧЕСКОЙ ПРАКТИКЕ РЕСПУБЛИКИ БЕЛАРУСЬ

The article deals with the use of biotechnological drugs (BTLG) in the treatment of children of the Republic of Belarus, mainly suffering from rheumatoid arthritis. This group of drugs is a new, very promising and insufficiently studied group in the world pediatric practice. The work assessed the effectiveness of the use of BTLG, taking into account the indications in pediatric practice. The results of studying the structure of patients receiving BTLG depending on the nosological unit of the disease, age, sex, place of residence of patients are presented; analyzes the effectiveness of de-escalation of therapy, switching to another drug, “escape” of the effect when using BTLG. The authors substantiate the need for a further differentiated approach to the use of the BTLG group in the treatment of severe forms of rheumatoid arthritis in children, the need to take into account the effects of the therapy.

Unexpected Diagnosis of Schizophrenia in Young Woman with Severe form of Rheumatoid Arthritis

Unexpected Diagnosis of Schizophrenia in Young Woman with Severe form of Rheumatoid Arthritis

Is Cyclosporine Ototoxic?

Cyclosporine was discovered in 1970, it was isolated from the fungus Tolypocladium inflatum in Switzerland (1). Soon after, an immunosuppressive property was suggested, and by 1978, it was used for the first time in human kidney transplantation to treat organ rejection post-transplant (2). It is now used as a treatment for solid organ, as well as bone marrow transplantation. Its immunomodulatory capacity has extended its use to other immune-mediated diseases such as severe forms of rheumatoid arthritis and psoriasis, steroid-dependent, frequently relapsing or steroid-resistant nephrotic syndrome, graft vs. host disease, refractory posterior uveitis/Behcet disease and amyotrophic lateral sclerosis (2, 3).

Etanercept administration prevents the inflammatory response induced by carrageenan in the murine air pouch model.

Rheumatoid arthritis (RA) is one of several inflammatory and autoimmune diseases that affect approximately 1% of world's population. The development of TNF inhibitors in the last decade represents a great advance in the treatment of mild and severe forms of RA. Etanercept is one of these drugs that is useful for RA treatment, but the mechanism of inhibition of the signaling pathway of inflammation was not completely elucidated. This study was conducted to evaluate the anti-inflammatory effect of etanercept in comparison to reference drugs (dexamethasone and indomethacin). Inflammation was induced by subcutaneal administration of carrageenan in the Swiss albino mice using the murine air pouch model. Exudation; leukocytes; myeloperoxidase (MPO); adenosine deaminase (ADA); nitric oxide metabolites (NOx); tumor necrosis factor (TNF); interferon gamma (IFN-γ); interleukins (IL) IL-6, IL-17, IL-10, IL-4, and IL-2; nuclear transcription factor kappa B (NF-κB) activation and apoptosis were evaluated 24 h after the induction of inflammation. Treatment with etanercept significantly inhibited exudate concentrations; leukocyte count; MPO and ADA activities; NOx, TNF, IFN-γ, and IL-17 levels; and NF-kappa B activation (p < 0.05). Etanercept induced apoptosis, reducing the number of viable neutrophils without increasing necrosis (p < 0.05). Our results suggest that the anti-inflammatory mechanism of action of etanercept may be via decrease of NF-κB activation. This effect promoted the reduction of pro-inflammatory cytokines and NOx and the induction of neutrophil apoptosis. The effect of etanercept upon neutrophils apoptosis may indicate the use of this drug therapy in the early stage of rheumatoid arthritis disease.

Cost-effectiveness analysis of tocilizumab in combination with methotrexate for rheumatoid arthritis: A Markov model based on data from Serbia, country in socioeconomic transition

Recent studies have shown that biological treatments for rheumatoid arthritis can change the course of rheumatoid arthritis and improve functional ability of patients with rheumatoid arthritis. In spite of this fact, use of biological therapy is still limited by high prices of these medicines, especially in countries in socioeconomic transition. The aim of our study was to compare cost-effectiveness of a combination of tocilizumab and methotrexate with methotrexate alone for rheumatoid arthritis in Serbia, a country in socioeconomic transition. For the purpose of our study we designed a Markov model using data on therapy efficacy from the available literature, and data on the costs of health states calculated from records of actual patients treated in the Clinical Center Kragujevac, Serbia. The duration of one cycle in our model was set at one month, and the time horizon was 480 months (40 years). The study was done from the social perspective, and all the costs and outcomes were discounted for 3% per year. Treating rheumatoid arthritis with disease-modifying antirheumatic drugs (DMARDs) alone was more cost-effective in comparison with a combination of biologic treatment with tocilizumab and DMARDs. The total costs for treating a patient with DMARDs for one year were on average 261,945.42 RSD, or 2,497.70 Euro and the total costs for treatment with tocilizimab plus DMARDs were on average 1,959,217.44 RSD, or 18,659.20 Euro. However, these results are susceptible to changes in costs and treatment effects of tocilizumab in patients with more severe forms of rheumatoid arthritis. Our results show that the use of tocilizumab for rheumatoid arthrits in economic environment of Serbia is not cost-effective. Use of tocilizumab for treating rheumatoid arthritis can become affordable, if costs of its use become lower. In order to start using expensive biologic medicines in patients in transitional countries, special strategy and pricing policy of international pharmaceutical companies are necessary, which would include calculation of prices of biologic medicines on the basis of local pharmacoeconomic studies.

Anti-cyclic citrullinated peptide antibodies do not reflect self-reported disability and physical health in patients with rheumatoid arthritis of less than 5 years of duration

It is well accepted that patients with antibodies against cyclic citrullinated peptides (anti-CCP) and rheumatoid arthritis (RA) suffer from more severe forms of RA in terms of clinical presentation and radiographic destruction at long term compared to anti-CCP-negative patients. The purpose of this cross-sectional study was to investigate whether the measures of self-reported health among patients with RA of <5 years of duration are influenced by anti-CCP status. Additionally, we aimed to determine whether the measures of self-reported health among the two patient groups differ from those of a control group. Telephone interviews were conducted with 464 patients with RA and 637 population controls, who reported educational level, income, smoking habits and lifestyle 10 years before the interview and completed the Health Assessment Questionnaire and the Short-Form Health Survey Questionnaire, version 2 (SF-36v2); 424 (91%) patients submitted a blood sample for analysis. Patients with anti-CCP-positive and anti-CCP-negative RA showed no significant differences in self-reported disability and physical health after adjustment for age, gender, socioeconomic factors, lifestyle and disease-related variables (p > 0.05). Both groups of RA patients reported significantly more physical disabilities in everyday life and significantly poorer physical health than the controls (both p < 0.001). A similar pattern was seen for self-reported mental health (both p < 0.05). Patients with RA of <5 years of duration report significantly more disability and poorer physical health than the general population of Denmark, but these reports were independent of anti-CCP status.

Cellular factor XIII and peptidylarginine deiminase-catalysed citrullination in rheumatoid arthritis

Antibodies against citrullinated proteins (ACPA) have been reported in the order of 70% of all cases with rheumatoid arthritis (RA). The authors and other groups have also shown that approximately...

The Cataract Blindness Challenge Innovations Case Discussion: Aravind Eye Care System)

world,” accompanied by a prize of Euro 1 million, was given in 2007 to the Aravind Eye Hospitals in Tamil Nadu, India. They could not have made a better choice. Aravind Eye Hospitals are the highest volume cataract surgery facility in the world. Their five hospitals examined over 2.3 million people and performed over 270,000 surgeries in 2006. Aravind is not only the highest volume cataract surgery system in the world but also a trendsetter that has lifted the quality of cataract surgery in India and set a new paradigm for delivering high volume, high-quality surgery to the poor in a self sustaining manner. The founding genius was a spiritual guru for all who now work in international eye care. Dr. Govindappa Venkataswamy, affectionately known by family and friends as “Dr. V,” passed away at age 87 in July 2006. He was born in 1918 in a poor farming village. There was no school in his village. After tending the water buffalo in the mornings, he would walk more than three miles to school every day. When a school finally came to his community, there were no writing materials and the students learned to write with sticks in the sand on the floor of their thatched roofed schoolroom. Despite these obstacles, the brilliant young Venkataswamy earned a scholarship to Stanley Medical College in Madras. Because of three cousins who died during childbirth, he chose to specialize in obstetrics. In his final year of training Dr. V was stricken with a severe form of rheumatoid arthritis. The young Venkataswamy was hospitalized for nearly two years. Agonized by constant, severe, physical pain he watched helplessly as his fingers twisted and deformed to the point where he knew he would be unable to work as an obstetrician, delivering babies. He sought spiritual solace through the philosoGeoffrey Tabin

A new classification of HLA–DRB1 alleles differentiates predisposing and protective alleles for rheumatoid arthritis structural severity

A new classification of HLA-DRB1 alleles supporting the shared epitope hypothesis of rheumatoid arthritis (RA) susceptibility was recently introduced. We investigated the relevance of this classification in terms of the structural severity of RA. The study group comprised 144 patients who were included in a prospective longitudinal cohort of French Caucasoid patients with early RA. Progression of the total radiographic damage score (Sharp/van der Heijde method) was used to quantify the structural severity of RA after 4 years of followup. HLA-DRB1 typing and subtyping were performed by polymerase chain reaction, using a panel of sequence-specific oligonucleotide probes. HLA-DRB1 alleles were classified according to the above-mentioned new system. The association between the HLA-DRB1 allele groups (S1, S2, S3P, S3D, and X) and the structural severity of RA was analyzed with nonparametric statistical tests. The presence of S2 alleles (HLA-DRB1*0401 and HLA-DRB1*1303) was associated with severe forms of RA (P = 0.004); a significant dose effect was observed (P = 0.01). The presence of S3D alleles (HLA-DRB1*11001, HLA-DRB1*1104, HLA-DRB1*12, and HLA-DRB1*16) was associated with benign forms of RA (P < 0.0001), and a significant dose effect was observed (P < 0.01). The studied classification of HLA-DRB1 alleles is relevant in terms of RA outcomes. Compared with a previously described classification system, this system differentiates predisposing (S2) and protective (S3D) alleles for RA structural severity, which, respectively, correspond to KRRAA and DRRAA amino acid patterns at position 70-74 of the third hypervariable region of the HLA-DRbeta chain.

A Deiminated Viral Peptide to Detect Antibodies in Rheumatoid Arthritis

The data presented suggest that a deiminated viral peptide is specifically recognized by antibodies contained in rheumatoid arthritis (RA) sera. Antipeptide antibodies are not associated with the presence or severity of specific manifestations of RA, but are more frequent in subjects with erosive arthritis. Taking into account the association with rheumatoid factor and with erosive arthritis, we can conclude that antipeptide antibodies are markers of severe forms of RA. Our data also show familial aggregation of anticitrullinated peptide antibodies.

The immunogenetic component of susceptibility to rheumatoid arthritis.

The precise nature of the HLA element associated with rheumatoid arthritis has been identified as a short sequence of amino acids on the alpha helix of a range of DR beta alleles. Recently the range of alleles known to bear this sequence and to be associated with rheumatoid arthritis has increased considerably. Although these findings lend further weight to the validity of the original hypothesis, they have also made it very difficult to propose a mechanism for the association. It has also become clear that the simple model of dominant susceptibility is unsatisfactory. Patients with early disease show little or no association with any HLA alleles, whereas patients with severe forms of rheumatoid arthritis are frequently homozygous for DR4, showing a disproportionate tendency toward compound heterozygocity--expressing two different molecules sharing the conserved sequence.

Diminished incidence of severe rheumatoid arthritis associated with oral contraceptive use

It has been suggested that the negative association between rheumatoid arthritis (RA) and oral contraceptive (OC) use might be limited to the more severe forms of RA. To investigate this further, we studied 121 consecutive female patients with definite RA, 52 female patients with probable RA, and 378 female controls. All patients had RA symptoms of recent onset. After a mean followup period of 6 years, patients with definite RA were classified as having either a severe disease course (n = 76) or a mild disease course (n = 45). The negative association between OC use prior to the onset of RA symptoms and the development of RA was limited to those patients with definite RA who had a severe disease course. We therefore conclude that OC use prior to the onset of RA symptoms is only associated with a reduction in the incidence of severe RA. This may explain the divergent results of previous studies.

Association of MHC antigens with susceptibility to and severity of rheumatoid arthritis in multicase families.

A study of HLA association with rheumatoid arthritis (RA) in multicase families has been performed in north east England. Two hundred and nineteen individuals from 13 families were assessed for the presence of RA, and all were HLA typed. Thirty-nine were found to have classical or definite RA by American Rheumatism Association (ARA) criteria. Thirty-five (90%) of these possess HLA-DR4, confirming the previously reported association of RA with DR4. A further 19 individuals were found to have probable RA or gave a convincing history of previous inflammatory polyarthritis. Thirteen (68%) of these possess HLA-DR4, and this is not significantly different from non-affected family members of whom 63% possess DR4. These results suggest that HLA-DR4 is associated only with the more severe forms of RA. Homozygosity for HLA-DR4 was not associated with either earlier onset or more severe disease when compared with heterozygous DR4. Possession of the haplotype most commonly inherited with the RA in individual families was not associated with earlier onset but may be associated with more severe disease. The severity of RA appears to be influenced by the major histocompatibility complex (MHC) in these families.

Bf and C3 complement types in rheumatoid arthritis.

Bf and C3 complement types were studied in 100 male and 100 females patients from northern Sweden with erosive rheumatoid arthritis (RA) and compared with population controls. A significantly decreased frequency of the Bf FS phenotype was found particularly in males and in patients with a family history of polyarthritis. Significant Bf associations were also found with a more severe form of RA (functional classes III and IV) and with high titers of the rheumatoid factor. No significant difference with respect to C3 phenotype and gene frequencies was found between RA patients and controls. Thus, the association between RA and C3F found in some previous investigations was not confirmed.