Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
24933225 Triptolide: progress on research in pharmacodynamics and toxicology. 2014 Aug 8 ETHNOPHARMACOLOGICAL RELEVANCE: Tripterygium wilfordii Hook. f. (Tripterygium wilfordii), also known as Huangteng and gelsemium elegan, is a traditional Chinese medicine that has been marketed in China as Tripterygium wilfordii glycoside tablets. Triptolide (TP), an active component in Tripterygium wilfordii extracts, has been used to treat various diseases, including lupus, cancer, rheumatoid arthritis and nephritic syndrome. This review summarizes recent developments in the research on the pharmacodynamics, pharmacokinetics, pharmacy and toxicology of TP, with a focus on its novel mechanism of reducing toxicity. This review provides insight for future studies on traditional Chinese medicine, a field that is both historically and currently important. MATERIALS AND METHODS: We included studies published primarily within the last five years that were available in online academic databases (e.g., PubMed, Google Scholar, CNKI, SciFinder and Web of Science). RESULTS: TP has a long history of use in China because it displays multiple pharmacological activities, including anti-rheumatism, anti-inflammatory, anti-tumor and neuroprotective properties. It has been widely used for the treatment of various diseases, such as rheumatoid arthritis, nephritic syndrome, lupus, Behcet׳s disease and central nervous system diseases. Recently, numerous breakthroughs have been made in our understanding of the pharmacological efficacy of TP. Although TP has been marketed as a traditional Chinese medicine, its multi-organ toxicity prevents it from being widely used in clinical practice. CONCLUSIONS: Triptolide, a biologically active natural product extracted from the root of Tripterygium wilfordii, has shown promising pharmacological effects, particularly as an anti-tumor agent. Currently, in anti-cancer research, more effort should be devoted to investigating effective anti-tumor targets and confirming the anti-tumor spectrum and clinical indications of novel anti-tumor pro-drugs. To apply TP appropriately, with high efficacy and low toxicity, the safety and non-toxic dose range for specific target organs and diseases should be determined, the altered pathways and mechanisms of exposure need to be clarified, and an early warning system for toxicity needs to be established. With further in-depth study of the efficacy and toxicity of TP, we believe that TP will become a promising multi-use drug with improved clinical efficacy and safety in the future.
23541481 Assessment of intracellular cytokines and regulatory cells in patients with autoimmune dis 2013 Aug Serum and intracytoplasmic cytokines are mandatory in host defense against microbes, but also play a pivotal role in the pathogenesis of autoimmune diseases by initiating and perpetuating various cellular and humoral autoimmune processes. The intricate interplay and fine balance of pro- and anti-inflammatory processes drive, whether inflammation and eventually organ damage will occur, or the inflammatory cascade quenches. In the early and late, as well as inactive and active stages of autoimmune diseases, different cellular and molecular patterns can dominate in these patients. However, the simultaneous assessment of pro- and anti-inflammatory biomarkers aids to define the immunological state of a patient. A group of the most useful inflammatory biomarkers are cytokines, and with increasing knowledge during the last decade their role have been well-defined in patients with autoimmune diseases and immunodeficiencies. Multiple pathological processes drive the development of autoimmunity and immunodeficiencies, most of which involve quantitative and qualitative disturbances in regulatory cells, cytokine synthesis and signaling pathways. The assessment of these biomarkers does not aid only in the mechanistic description of autoimmune diseases and immunodeficiencies, but further helps to subcategorize diseases and to evaluate therapy responses. Here, we provide an overview, how monitoring of cytokines and regulatory cells aid in the diagnosis and follow-up of patients with autoimmune diseases and immunodeficiencies furthermore, we pinpoint novel cellular and molecular diagnostic possibilities in these diseases.
25568649 Clinical definition of sarcopenia. 2014 Sep Sarcopenia is a condition characterized by loss of skeletal muscle mass and function. Although it is primarily a disease of the elderly, its development may be associated with conditions that are not exclusively seen in older persons. Sarcopenia is a syndrome characterized by progressive and generalized loss of skeletal muscle mass and strength and it is strictly correlated with physical disability, poor quality of life and death. Risk factors for sarcopenia include age, gender and level of physical activity. In conditions such as malignancy, rheumatoid arthritis and aging, lean body mass is lost while fat mass may be preserved or even increased. The loss in muscle mass may be associated with increased body fat so that despite normal weight there is marked weakness, this is a condition called sarcopenic obesity. There is an important correlation between inactivity and losses of muscle mass and strength, this suggests that physical activity should be a protective factor for the prevention but also the management of sarcopenia. Furthermore one of the first step to be taken for a person with sarcopenia or clinical frailty is to ensure that the sarcopenic patient is receiving correct and sufficient nutrition. Sarcopenia has a greater effect on survival. It should be important to prevent or postpone as much as possible the onset of this condition, to enhance survival and to reduce the demand for long-term care. Interventions for sarcopenia need to be developed with most attention on exercise and nutritional interventions.
25365105 The Swedish Rheumatology Quality Register: optimisation of rheumatic disease assessments u 2014 Sep New therapeutic options are constantly emerging for the treatment of rheumatic diseases. To evaluate the safety and efficacy of newly introduced anti-rheumatic treatment alternatives, registers are an important source of information. The Swedish Rheumatology Quality Register (SRQ) collects clinical data on patients with rheumatoid arthritis, as well as other rheumatic diseases, and may be enriched with data on comorbid conditions, prescription drug dispensings, and mortality from national data sources in Sweden. In this setting, many different outcomes can be investigated over a long period of time in a diverse population of patients recruited in daily clinical practice.
25277314 Congenital fulminant Kaposiform hemangioendothelioma of the leg. 2014 Dec Kaposiform hemangioendothelioma is a rare locally aggressive vascular tumor associated with Kasabach Merritt syndrome. We present a case of congenital Kaposiform hemangioendothelioma of the leg in a female infant who was born to a mother treated with various medications including etanercept, a TNF antagonist, due to rheumatoid arthritis. The neonate suffered from a fulminant form of Kasabach Merritt syndrome with disseminated intravascular coagulation (DIC) resulting in multi-organ failure which led to her demise.
25185856 A case of autoimmune urticaria accompanying autoimmune polyglandular syndrome type III ass 2014 We present a case of autoimmune polyglandular syndrome type III (APS III) associated with Hashimoto's disease, type 1 diabetes mellitus, vitiligo and autoimmune urticaria. This rare genetic disorder occurs with unknown frequency in the Polish population. It is characterised by endocrine tissue destruction resulting in the malfunction of multiple organs.Several cases of APS III associated with organ-specific autoimmune diseases such as coeliac disease, hypogonadism and myasthenia gravis, as well as organ-nonspecific or systemic autoimmune diseases such as sarcoidosis, Sjögren syndrome, and rheumatoid arthritis have been described. To the best of our knowledge, we here describe the first case of APS III associated with autoimmune thyroiditis, type 1 diabetes mellitus, vitiligo and autoimmune urticaria in an adult patient.
25102502 Popliteal cysts: a current review. 2014 Aug Baker's cyst, or popliteal cyst, is a fluid-filled mass that is a distention of a preexisting bursa in the popliteal fossa, most commonly the gastrocnemio-semimembranosus bursa. This bursa is unique in that it communicates with the knee joint, unlike other periarticular bursae, via an opening in the joint capsule posterior to the medial femoral condyle. Many have theorized that this opening creates a valve-like mechanism in the presence of effusion that contributes to the formation of these cysts in adults. Popliteal cysts rarely manifest alone and are most often found in conjunction with other intra-articular pathologies and inflammatory conditions, such as osteoarthritis, meniscus tears, and rheumatoid arthritis. In children, popliteal cysts are only occasionally associated with these conditions and are more often an incidental finding discovered during a routine physical examination. Popliteal cysts may present as either a chronically persistent or relapsing condition or as an acute and dramatic condition that can occur in the case of cyst rupture presenting as pseudothrombophlebitis. Ultrasound and magnetic resonance imaging have proven to be consistent and accurate in the confirmation of popliteal cysts, with magnetic resonance imaging becoming the modern imaging modality of choice. This review discusses the anatomy and etiology of popliteal cysts, describes the common clinical presentations, reviews the differential diagnoses, and provides guidance for proper diagnostic imaging. It also provides a comparison of current conservative, minimally invasive, and invasive treatment options, along with a discussion of results. Postoperative rehabilitation depends largely on the condition associated with the popliteal cyst.
24995874 Effects of antibiotics on human microbiota and subsequent disease. 2014 Although antibiotics have significantly improved human health and life expectancy, their disruption of the existing microbiota has been linked to significant side effects such as antibiotic-associated diarrhea, pseudomembranous colitis, and increased susceptibility to subsequent disease. By using antibiotics to break colonization resistance against Clostridium, Salmonella, and Citrobacter species, researchers are now exploring mechanisms for microbiota-mediated modulation against pathogenic infection, revealing potential roles for different phyla and family members as well as microbiota-liberated sugars, hormones, and short-chain fatty acids in regulating pathogenicity. Furthermore, connections are now being made between microbiota dysbiosis and a variety of different diseases such as rheumatoid arthritis, inflammatory bowel disease, type 1 diabetes, atopy, and obesity. Future advances in the rapidly developing field of microbial bioinformatics will enable researchers to further characterize the mechanisms of microbiota modulation of disease and potentially identify novel therapeutics against disease.
24926631 [Doxycycline or how to create new with the old?]. 2014 Mar Tetracyclines are broad-spectrum antibiotics that interfere with protein synthesis. They were first widely prescribed by dermatologists in the early 1950s in the treatment of acne. More recently, their biological actions on inflammation, proteolysis, angiogenesis, apoptosis, metal chelation, ionophoresis, and bone metabolism were studied. Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes that degrade components of the extracellular matrix (ECM). MMPs have direct or indirect effects on the vascular endothelium and the vascular relaxation/contraction system. The therapeutic effects of tetracyclines and analogues were studied in rosacea, bullous dermatoses, neutrophilic diseases, pyoderma gangrenosum, sarcoidosis, aortic aneurysms, cancer metastasis, periodontitis and autoimmune diseases autoimmune diseases such as rheumatoid arthritis and scleroderma. In addition, downregulation of MMP using doxycycline could be beneficial in reducing vascular dysfunction mediated by MMPs and progressive damage of the vascular wall. We review the nonantibiotic properties of doxycycline and its potential clinical applications.
24924729 [Hand ergotherapy for rheumatic diseases and the special importance of hand surgery]. 2014 Jun BACKGROUND: Human hands play an important role in overcoming routine daily life. As a consequence of limitations in the function of the hand due to rheumatic diseases, various manual activities can become an enormous challenge or even become absolutely impossible. MATERIAL AND METHODS: This review article discusses the possibilities of hand ergotherapy and explains the most important assist devices. RESULTS AND CONCLUSION: The main area of occupational and hand therapy interventions in patients with rheumatoid arthritis is the postoperative or conservative treatment of wrist and finger joints. The main areas of concern are to maintain the mobility of the joints, when necessary and possible mobilization of the joints, strengthen the muscles, the prophylaxis or correction of deformities with thermoplastic splints, conservative pain relief and anti-inflammatory treatment, joint protection precautions and teaching of home exercises for prophylaxis of contracture. Further areas of therapy are instruction and provision of adaptive devices for limitations of the upper and/or lower extremities, especially training of activities of daily living (ADL) and patient education.
24695601 Acute pericarditis: diagnosis and management. 2014 Apr 1 Acute pericarditis, inflammation of the pericardium, is found in approximately 5% of patients admitted to the emergency department for chest pain unrelated to acute myocardial infarction. It occurs most often in men 20 to 50 years of age. Acute pericarditis has a number of potential etiologies including infection, acute myocardial infarction, medication use, trauma to the thoracic cavity, and systemic diseases, such as rheumatoid arthritis. However, most etiologic evaluations are inconclusive. Patients with acute pericarditis commonly present with acute, sharp, retrosternal chest pain that is relieved by sitting or leaning forward. A pericardial friction rub is found in up to 85% of patients. Classic electrocardiographic changes include widespread concave upward ST-segment elevation without reciprocal T-wave inversions or Q waves. First-line treatment includes nonsteroidal anti-inflammatory drugs and colchicine. Glucocorticoids are traditionally reserved for severe or refractory cases, or in cases when the cause of pericarditis is likely connective tissue disease, autoreactivity, or uremia. Cardiology consultation is recommended for patients with severe disease, those with pericarditis refractory to empiric treatment, and those with unclear etiologies.
24592325 Idiopathic uveitis and familial mediterranean Fever: is there any relationship? 2014 Introduction. Familial Mediterranean fever (FMF) is an auto-inflammatory disease characterized by attacks of fever and polyserositis. FMF is often associated with other autoimmune diseases such as rheumatoid arthritis, polyarteritis nodosa (PAN), and Behcet. Uveitis is an inflammatory process caused by underlying infectious and inflammatory disorders. This study investigates the probable relationship between idiopathic uveitis and FMF. Methods. Patients with idiopathic uveitis were analyzed for the 12 most common MEFV mutations (P369S, F479L, M680I(G/C), M680I(G/A), I692del, M694V, M694I, K695R, V726A, A744S, R761H, E148Q) by a reverse hybridization assay (FMF StripAssay,Vienna lab,Vienna, Austria). Results. 12 patients with idiopathic uveitis were enrolled in this study. 10 of them were female. The youngest patient was a 7-year-old child and the oldest was 57. The most common complaints of patients were blurred vision and then eye redness. One patient was heterozygous for R761H. Genetic analysis of the 12 most common MEFV mutations in the patients with idiopathic uveitis didnot have any positive results. Conclusion. According to the analysis of the 12 most common MEFV gene mutations, FMF is not an underlying cause of idiopathic uveitis. On the other hand, uveitis merely could not be the first presentation of FMF.
24345205 Cryotherapy in inflammatory rheumatic diseases: a systematic review. 2014 Feb The aim of this article was to review current evidence about cryotherapy in inflammatory rheumatic diseases (therapeutic and biological effects). For therapeutic effects, we performed a systematic review (PubMed, EMBASE, Cochrane Library, LILACS databases, unpublished data) and selected studies including non-operated and non-infected arthritic patients treated with local cryotherapy or whole-body cryotherapy. By pooling 6 studies including 257 rheumatoid arthritis (RA) patients, we showed a significant decrease in pain visual analogic scale (mm) and 28-joint disease activity score after chronic cryotherapy in RA patients. For molecular pathways, local cryotherapy induces an intrajoint temperature decrease, which might downregulate several mediators involved in joint inflammation and destruction (cytokines, cartilage-degrading enzymes, proangiogenic factors), but studies in RA are rare. Cryotherapy should be included in RA therapeutic strategies as an adjunct therapy, with potential corticosteroid and nonsteroidal anti-inflammatory drug dose-sparing effects. However, techniques and protocols should be more precisely defined in randomized controlled trials with stronger methodology.
23843630 Parenting stress among caregivers of children with chronic illness: a systematic review. 2013 Sep To critically review, analyze, and synthesize the literature on parenting stress among caregivers of children with asthma, cancer, cystic fibrosis, diabetes, epilepsy, juvenile rheumatoid arthritis, and/or sickle cell disease. Method PsychInfo, MEDLINE, and Cumulative Index to Nursing and Allied Health Literature were searched according to inclusion criteria. Meta-analysis of 13 studies and qualitative analysis of 96 studies was conducted. Results Caregivers of children with chronic illness reported significantly greater general parenting stress than caregivers of healthy children (d = .40; p = ≤.0001). Qualitative analysis revealed that greater general parenting stress was associated with greater parental responsibility for treatment management and was unrelated to illness duration and severity across illness populations. Greater parenting stress was associated with poorer psychological adjustment in caregivers and children with chronic illness. Conclusion Parenting stress is an important target for future intervention. General and illness-specific measures of parenting stress should be used in future studies.
23606120 Detecting multiple autoantibodies to diagnose autoimmune co-morbidity (multiple autoimmune 2013 Jul In the last 15 years, the estimated prevalence of autoimmune diseases increased from about 4 to 9.4%. Autoimmune co-morbidity (i.e., the association between two or more autoimmune diseases in the same patient) is present in 0.4-0.5% of the worldwide population, more frequently in patients with multiple sclerosis, rheumatoid arthritis, autoimmune thyroid disease, type 1 diabetes, inflammatory bowel disease and vitiligo. The most common associations between autoimmune diseases define two clusters: the multiple autoimmune syndromes and overlap syndromes. This review highlights the importance of multiple antibody assays in the diagnosis of multiple autoimmune and overlap syndromes and summarizes the general conditions of autoantibody detection using the model of the five W's: why, who, what, when and where. These conditions represent a new challenge for clinical and laboratory autoimmunologists, who, in a multidisciplinary arena, cooperate in investigating and treating multiple autoimmune disorders.
23580000 Regulation of inflammation by adenosine. 2013 Adenosine, a purine nucleoside generated by the dephosphorylation of adenine nucleotides, is a potent endogenous physiologic and pharmacologic regulator of many functions. Adenosine was first reported to inhibit the inflammatory actions of neutrophils nearly 30 years ago and since then the role of adenosine and its receptors as feedback regulators of inflammation has been well established. Here we review the effects of adenosine, acting at its receptors, on neutrophil and monocyte/macrophage function in inflammation. Moreover, we review the role of adenosine in mediating the anti-inflammatory effects of methotrexate, the anchor drug in the treatment of Rheumatoid Arthritis and other inflammatory disorders.
23562401 Sulfasalazine-induced linear immunoglobulin A bullous dermatosis with DRESS. 2013 May Linear immunoglobulin (Ig) A dermatosis is an immune-mediated bullous disease characterized by linear deposits of IgA along the basal membrane. While usually idiopathic, it can occasionally be induced by drug exposure. We report the case of a 60-year-old woman with rheumatoid arthritis being treated with sulfasalazine who developed linear IgA dermatosis and drug rash with eosinophilia and systemic symptoms (DRESS). The dermatosis and associated symptoms resolved following withdrawal of the drug and treatment with systemic corticosteroids for 2 months. This is the first report of sulfasalazine-induced linear IgA dermatosis in association with DRESS and we believe that sulfasalazine should be added to the list of drugs that can cause linear IgA dermatosis.
23283607 Three cases of severely disseminated Staphylococcus aureus infection in patients treated w 2013 Jan 2 We report three cases of severe disseminated Staphylococcus aureus infection in patients with rheumatoid arthritis (RA) treated with tocilizumab. Tocilizumab is a new drug, unknown to most internists, and injections given weeks before admission may not be considered by the patient as part of their 'current medical treatment', and the physician may not be aware that the patient is severely immunosuppressed. Severe infections in RA patients treated with tocilizumab may present with mild symptoms despite severe and disseminated infection and, as these patients are severely immunodeficient-intensive diagnostic work-up and early treatment should be performed. Systematic postmarketing studies are needed to clarify if there is a true increased risk of disseminated S aureus infections. We suggest caution when prescribing tocilizumab to patients with prosthetic joints and/or prior invasive S aureus infections and that patients are taught to inform health staff about their medication history and their increased risk of infection.
25431670 A possible molecular mechanism of immunomodulatory activity of bilirubin. 2013 Bilirubin is an endogenous product of heme degradation in mammals. Bilirubin has long been considered as a cytotoxic waste product that needs to be excreted. However, increasing evidence suggests that bilirubin possesses multiple biological activities. In particular, recent studies have shown that bilirubin should be a protective factor for several autoimmune diseases such as rheumatoid arthritis, multiple sclerosis, and systemic lupus erythematosus. Since these autoimmune diseases are closely associated with specific types of human leukocyte antigens (HLAs), we have hypothesized that bilirubin might bind to the antigenic peptide-binding groove of the HLA molecules and exert its immunosuppressive actions. In order to evaluate the hypothesis, theoretical docking studies between bilirubin and the relevant HLA molecules have been undertaken. The in silico studies have clearly shown that bilirubin may bind to the antigenic peptide-binding groove of the HLA molecules relevant to the autoimmune diseases with significant affinity. The bound bilirubin may block the binding of antigenic peptides to be presented to T cell receptors and lead to suppression of the autoimmune responses. Based on this hypothesis new drug discovery research for autoimmune diseases will be conducted.
22490998 Risk factors in lateral epicondylitis (tennis elbow): a case-control study. 2013 Feb Lateral epicondylitis is a common condition, but relatively little is known about its aetiology and associated risk factors. We have undertaken a large case-control study using The Health Improvement Network database to assess and quantify the relative contributions of some constitutional and environmental risk factors for lateral epicondylitis in the community. Our dataset included 4998 patients with lateral epicondylitis who were individually matched with a single control by age, sex, and general practice. The median age at diagnosis was 49 (interquartile range 42-56) years . Multivariate analysis showed that the risk factors associated with lateral epicondylitis were rotator cuff pathology (OR 4.95), De Quervain's disease (OR 2.48), carpal tunnel syndrome (OR 1.50), oral corticosteroid therapy (OR 1.68), and previous smoking history (OR 1.20). Diabetes mellitus, current smoking, trigger finger, rheumatoid arthritis, alcohol intake, and obesity were not found to be associated with lateral epicondylitis.