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

ID PMID Title PublicationDate abstract
24280676 Involvement of Multiple Transporters-mediated Transports in Mizoribine and Methotrexate Ph 2012 Aug 10 Mizoribine is administered orally and excreted into urine without being metabolized. Many research groups have reported a linear relationship between the dose and peak serum concentration, between the dose and AUC, and between AUC and cumulative urinary excretion of mizoribine. In contrast, a significant interindividual variability, with a small intraindividual variability, in oral bioavailability of mizoribine is also reported. The interindividual variability is mostly considered to be due to the polymophisms of transporter genes. Methotrexate (MTX) is administered orally and/or by parenteral routes, depending on the dose. Metabolic enzymes and multiple transporters are involved in the pharmacokinetics of MTX. The oral bioavailability of MTX exhibits a marked interindividual variability and saturation with increase in the dose of MTX, with a small intraindividual variability, where the contribution of gene polymophisms of transporters and enzymes is suggested. Therapeutic drug monitoring of both mizoribine and MTX is expected to improve their clinical efficacy in the treatment of rheumatoid arthritis.
23216081 Are there new emerging drugs for ankylosing spondylitis or spondyloarthritis? 2013 Mar New emerging drugs in the treatment of ankylosing spondylitis (AS), and spondyloarthritis in general, should be compared to anti-TNF agents, which provided clear evidence of efficacy in these conditions. To date, other biologic agents used in rheumatoid arthritis failed to demonstrate efficacy in AS, even in anti-TNF naïve patients. Some new potential options may target cytokines such as IL-17, or molecules involved in entheseal ossification or signaling pathways, but need confirmatory evaluation.
22961090 Leflunomide: friend or foe for systemic lupus erythematosus? 2013 Feb Leflunomide is a new immunosuppressive medicine that has been effectively used in the therapy of rheumatoid arthritis and subsequently used with success in animal models and patients with systemic lupus erythematosus (SLE). However, its use has also been associated with significant and serious adverse reactions involving hematological, hepatic, immune, dermatological and respiratory systems. In the current review, we attempt to describe the two sides of this drug in the treatment of SLE.
22825877 Abductor pollicis longus tendon division with swan neck thumb deformity. 2012 Aug Swan neck thumb deformity can be caused by osteoarthritis, rheumatoid arthritis, systemic lupus erythematosus, tendon transfers and paralytic diseases. Abductor pollicis longus is one of the major stabilizing tendon of the carpometacarpal joint of thumb. To the best of our knowledge, swan neck thumb deformity owing to division of abductor pollicis longus tendon is rare. In this article, we describe a case of isolated division of abductor pollicis longus tendon presenting with swan-neck deformity of thumb and discuss the mechanism, management and outcome. The patient was treated by repair of the divided tendon using palmaris longus tendon graft. At approximately 107 weeks following treatment, the patient was having full range of thumb movement and the deformity completely disappeared. We also describe the unusual mechanism whereby an isolated division of abductor pollicis longus tendon results in swan neck thumb deformity. Level of clinical evidence IV.
22802024 [Janus kinase inhibitors]. 2012 Aug Janus protein tyrosine kinase (JAK) inhibitors are new therapeutic targets in the treatment of rheumatoid arthritis. Tofacitinib has shown good clinical efficacy in phase II and III studies with American College of Rheumatology (ACR) 20 response rates over 50% for monotherapy and in combination with methotrexate (MTX). Also the safety profile shows similar infection rates as observed with known biologicals. The crude rate of serious infection events was 3/100 patient-years. Often reported adverse events are infections of the upper respiratory tract and urogenital infections.
22474574 The autoimmune tautology: an in silico approach. 2012 There is genetic evidence of similarities and differences among autoimmune diseases (AIDs) that warrants looking at a general panorama of what has been published. Thus, our aim was to determine the main shared genes and to what extent they contribute to building clusters of AIDs. We combined a text-mining approach to build clusters of genetic concept profiles (GCPs) from the literature in MedLine with knowledge of protein-protein interactions to confirm if genes in GCP encode proteins that truly interact. We found three clusters in which the genes with the highest contribution encoded proteins that showed strong and specific interactions. After projecting the AIDs on a plane, two clusters could be discerned: Sjögren's syndrome-systemic lupus erythematosus, and autoimmune thyroid disease-type1 diabetes-rheumatoid arthritis. Our results support the common origin of AIDs and the role of genes involved in apoptosis such as CTLA4, FASLG, and IL10.
30736113 Molecular mechanisms of cachexia in chronic disease. 2012 Jan Cachexia is a metabolic syndrome that manifests with excessive weight loss and disproportionate muscle wasting. It is related to many different chronic diseases, such as cancer, infections, liver disease, inflammatory bowel disease, cardiac disease, chronic obstructive pulmonary disease, chronic renal failure and rheumatoid arthritis. Cachexia is linked with poor outcome for the patients. In this article, we explore the role of the hypothalamus, liver, muscle tissue and adipose tissue in the pathogenesis of this syndrome, particularly concentrating on the role of cytokines, hormones and cell energy-controlling pathways (such as AMPK, PI3K/Akt and mTOR). We also look at possible future directions for therapeutic strategies.
22080212 Effects of dialysis on the pharmacokinetics of salazosulfapyridine. 2013 Feb There was no standard or report for the treatment of rheumatoid arthritis (RA) patients on hemodialysis with Salazosulfapyridine (SASP). We examined the pharmacokinetics of SASP and its metabolites in RA patient on hemodialysis. Hemodialysis was started 2 h after administration of SASP at a dose of 250 or 500 mg. Blood samples were took 8 times during the observation period. The concentration of SASP and its metabolites (SP, Ac-SP) in blood sample were measured. There was no difference for the concentration of SASP before and after hemodialysis. Results showed SASP was nondialyzable, but SP and AC-SP were dialyzable. At a dose of 500 mg, AUC0-∞ of SASP and SP were higher than healthy volunteer. Therapy with SASP for hemodialysis RA should be started at a lower dose for adverse event risk.
22078355 Amyloidosis of the nasopharynx: an unexpected cause of unilateral middle ear effusion. 2011 Nov Amyloidosis is an idiopathic disease that is characterized by the extracellular deposition of fibrillar proteins. The disease can be categorized as primary or secondary where deposits occur in conjunction with chronic diseases such as rheumatoid arthritis or tuberculosis. The deposits can be localized or systemically distributed. It can mimic, and also be associated with underlying malignancy. Primary amyloidosis is a rare cause of a nasopharyngeal lesion, and less so of a secondary middle ear effusion. Its association with underlying chronic and malignant disease must not be over-looked if serious complications are to be avoided. It is, therefore, important to consider this as a differential diagnosis in such patients.
21978345 Painful numb hands. 2011 Oct 3 Carpal tunnel syndrome, resulting from median nerve compression at the wrist, is a common and often disabling mononeuropathy. Risk factors include female sex, family history, repetitive hand use, obesity, pregnancy and a variety of medical comorbidities including diabetes mellitus, rheumatoid arthritis, and other connective tissue diseases. In many cases, an accurate diagnosis can be reached on the basis of clinical history and supportive examination findings alone. Neurophysiological investigations are essential for confirming the diagnosis, assessing severity and excluding more generalised neuropathies, as well as providing a baseline preoperative index of median nerve function. Wrist splinting and local corticosteroid injection are effective treatments in the short term, but long-term data are lacking. Surgical (endoscopic or open) carpal tunnel release is effective and nearly always required to enable a return to work for patients with occupationally induced carpal tunnel syndrome.
21897499 Anesthesia for joint replacement surgery: Issues with coexisting diseases. 2011 Jul The first joint replacement surgery was performed in 1919. Since then, joint replacement surgery has undergone tremendous development in terms of surgical technique and anesthetic management. In this era of nuclear family and independent survival, physical mobility is of paramount importance. In recent years, with an increase in life expectancy, advances in geriatric medicine and better insurance coverage, the scenario of joint replacement surgery has changed significantly. Increasing number of young patients are undergoing joint replacement for pathologies like rheumatoid arthritis and ankylosing spondylitis. The diverse pathologies and wide range of patient population brings unique challenges for the anesthesiologist. This article deals with anesthetic issues in joint replacement surgery in patients with comorbidities.
21814030 [Denosumab as the potent therapeutic agent against Paget's disease of bone]. 2011 Aug Denosumab directly targets osteoclastgenesis by its specific action on the RANKL pathway, while bisphosphonate acts as antiresorptive agents mainly by their suppression on function of osteoclasts. The previous clinical trials showed that denosumab resulted in a quicker decrease in markers of bone resorption than bisphosphonate, that denosumab has beneficial effect against the prevention of fracture in postmenopausal women and bone erosion in patients with rheumatoid arthritis and that recombinant osteoprotegerin provided the therapeutic efficacy in two adult siblings with juvenile Paget's disease. Taken together, it is strongly expected that denosumab would be developed to be one of potent therapeutic agents for Paget's disease of bone which is characterized with the accerelated bone resorpton by osteoclasts as the primitive pathological condition.
21676609 Polymer therapeutics as nanomedicines: new perspectives. 2011 Aug A growing number of polymer therapeutics have entered routine clinical use as nano-sized medicines. Early products were developed as anticancer agents, but treatments for a range of diseases and different routes of administration have followed--recently the PEGylated-anti-TNF Fab Cimzia® for rheumatoid arthritis and the PEG-aptamer Macugen® for age related macular degeneration. New polymer therapeutic concepts continue to emerge with a growing number of conjugates entering clinical development, for example PEGylated-aptamers and a polymer-based siRNA delivery system. 'Hot' topics of the past 2 years include; emerging issues relating to polymer safety, the increasing use of biodegradable polymers, design of technologies for combination therapy, potential biomarkers for patient individualisation of treatment and Regulatory challenges for 'follow-on/generic' polymer therapeutics.
21410760 The 'psoriatic march': a concept of how severe psoriasis may drive cardiovascular comorbid 2011 Apr There is increasing awareness that psoriasis is more than 'skin deep'. Several recent reviews focussed on biomarkers indicating the systemic dimension of psoriasis and the aspect of comorbidity psoriasis shares with other chronic inflammatory diseases, such as Crohn's disease and rheumatoid arthritis. Of emerging significance is the relationship to cardiovascular disease, as this contributes substantially to the patients' increased mortality. In this viewpoint, we examine currently available evidence favouring the concept of a causal link between psoriasis and cardiovascular disease: systemic inflammation may cause insulin resistance, which in turn triggers endothelial cell dysfunction, leading to atherosclerosis and finally myocardial infarction or stroke. While this 'psoriatic march' is not yet formally proven, it raises clinically and academically relevant questions, and gains support by recent observations of numerous investigators.
24179724 Case report of long-term results of biaxial and volz total wrist arthroplasty. 2012 Nov The purpose of this case report was to look at the long-term (average 17.8 years) results of total wrist arthroplasty. Of the 12 wrists (9 patients) available for evaluation, 7 wrists still had the arthroplasty in place whereas 5 wrists had been revised to an arthrodesis. The average age at time of arthroplasty for those requiring an arthrodesis was 17 years less than those not requiring an arthrodesis. This suggests that there is a higher incidence of loosening when total wrist arthroplasty is performed in younger patients, perhaps due to these younger patients having higher demands or having more severe rheumatoid arthritis. In this younger population, the implant metacarpal stem cut out in three wrists and ulnar drift occurred in two wrists. All patients said that if given the chance, they would have a total wrist arthroplasty again, despite their long-term results being poor and many of them being revised to a wrist arthrodesis.
21909287 Health effects of omega-3,6,9 fatty acids: Perilla frutescens is a good example of plant o 2011 Mar Perilla frutescens seeds are a good source of polyunsaturated fatty acids (PUFAs). The seeds of perilla are small end globular weight about 4 g/1000, contained approximately 35-45% oil. However the leaves are a very poor source of oil, since they contain only 0.2%. In addition, only the seed oil contains the omega 3 fatty acid alpha-linolenic acid (ALA). In comparing to other plant oils, perilla seed oil consistently contains the one of the highest proportion of omega-3 (ALA) fatty acids, at 54-64%. The omega-6 (linoleic acid) component is usually around 14% and omega-9 (Oleic acid) is also present in perilla oil. These polyunsaturated fatty acids are most beneficial to human health and in prevention of different diseases like cardiovascular disorders, cancer, inflammatory, rheumatoid arthritis etc.
21619946 Autoimmune diseases and rehabilitation. 2012 Jan This review gives an overview of the rehabilitation of autoimmune diseases. After general remarks on rehabilitation, the effects of acute and chronic exercises on inflammatory markers are summarized. Most of the available literature deals with rheumatoid arthritis (RA) and multiple sclerosis (MS), and therefore, rehabilitation of these diseases is described in more detail. Exercise is the main component in the rehabilitation of patients with RA and aims at increasing physical capacity, muscle strength, aerobic endurance, cardiovascular fitness and functional abilities, and helps to prevent secondary deconditioning due to reduced activity levels. Since MS causes a wide range of symptoms, the rehabilitation of these patients requires a multidisciplinary approach and encompasses physiotherapy, exercise therapy, hippotherapy, cognitive rehabilitation, psychological therapy, strategies to improve fatigue and coping programs. The ultimate goal of rehabilitation is to enable patients with chronic conditions to reach and maintain their optimal physical, sensory, intellectual, psychological and social functional levels, and to attain independence and self-determination as far as possible.
21584186 Deciphering the key molecular and cellular events in neutrophil transmigration during acut 2011 Apr 22 Recruitment of leukocytes circulating in our blood to the sites of infection or tissue damage is the key phenomenon in the acute inflammatory response(s). Among the leukocytes, neutrophils are primarily recruited into the areas of acute inflammation. When neutrophils interact with activated endothelium of the blood vessels, they become migratory and cross the endothelial layer of the blood vessel wall in a process called as leukocyte extravasation. Identifying and understanding the gene regulation of this extravasation phenomenon is one of the key objective of biomedical research aimed at ameliorating or alleviating the symptoms of various diseases, such as rheumatoid arthritis, asthma, anaphylaxis, atherosclerosis, ulcerative colitis etc., that are exacerbated by inappropriate inflammatory stimuli. Here, we decipher and discuss the key genes implicated in the leukocyte transmigration using the acute inflammation model called as the Dextran Sulphate Sodium (DSS) induced Colitis in mice as a classic paradigm.
21548159 Spontaneous ulnar dislocation of the index, long, ring and small finger extensor tendons a 2011 Finger extensor tendon dislocation at the metacarpophalangeal joint is caused by various etiologies, such as trauma, congenital anomaly, or rheumatoid arthritis. When the dislocation occurs with no etiology, this is called spontaneous dislocation. Although spontaneous extensor tendon dislocation in one, two or three fingers has been described, to our knowledge, simultaneous dislocation in four fingers has not been reported. In this paper, we report a spontaneous ulnar dislocation of all the extensor tendons in the index, long, ring, and small fingers. Repair of the radial sagittal bands of the extensor digitorum communis of the middle and ring fingers reduced dislocation of all the extensor tendons in four fingers.
22400031 JAK2 Inhibition: Reviewing a New Therapeutical Option in Myeloproliferative Neoplasms. 2012 JAK2 is a tyrosine kinase gene that plays an essential role in the development of normal haematopoiesis. Hyperactivation of JAK2 occurs in myeloproliferative neoplasms by different mechanisms. As a consequence, JAK2 inhibitors have been designed to suppress the cytokine signalling cascade caused by the constitutive activation of JAK2. In clinical trials, JAK2 inhibitors are efficient in decreasing spleen size, controlling clinical symptoms, and improving quality of life in patients with myeloproliferative neoplasms. However, JAK2 inhibitors are unable to target uncommitted hematopoietic progenitors responsible of the initiation of the myeloproliferative disease. It is expected that, in order to cure the myeloproliferative disease, JAK2 inhibitors should be combined with other drugs to target simultaneously different pathways and to target the initiator hematopoietic cell population in myeloproliferative disorders. Taking advantage of the inhibition of the cytokine cascade of JAK2 inhibitors, these compounds are going to be used not only to treat patients with hematological neoplasms but may also be beneficial to treat patients with rheumatoid arthritis or other inflammatory diseases.