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ID PMID Title PublicationDate abstract
25368445 Anti-inflammatory activities of light emitting diode irradiation on collagen-induced arthr 2014 Sep 30 BACKGROUND AND AIMS: Rheumatoid arthritis (RA) is an auto-immune disease afflicting multiple joints of the body, where as a result of the increase in inflammatory cytokines and tissue destructive factors such as matrix metalloproteinase (MMP)-3, deterioration of the bones and cartilages of the joints occurs. The present investigation was carried out to study the anti-inflammatory activities of light emitting diode (LED) irradiation on hind paw inflammation in collagen-induced arthritis (CIA) mice models. MATERIALS AND METHOD: RA in the CIA mouse model was induced by immunization of DBA/1J mice with intradermal injections of an emulsion of bovine type II collagen and complete Freund's adjuvant. A total of 20 CIA mice were subdivided into the following groups: control group, CIA group and 2 groups of LED irradiated CIA mice (LED groups) (n=5 per group). The mouse knee joint area in the LED groups (the 570 nm and 940 nm groups) was irradiated with LED energy, three times a week for 500 s per session over 8 weeks at a dose of 5 J/cm(2). The hind paw swelling was assessed by the increase in hind paw thickness. The serum levels of the inflammatory cytokines and arthritic factor MMP-3 were determined with an enzyme-linked immunosorbent assay (ELISA). RESULTS: In the LED-570 and LED-940 groups at 4 weeks after arthritis induction, the swelling inhibition index was 18.1±4.9 and 29.3±4.0 respectively. Interleukin (IL)-1β, IL-6 and MMP-3 serum levels were significantly lower in the LED-940 group. CONCLUSIONS: LED irradiation, particularly in the near-infrared was effective for inhibition of the inflammatory reactions caused by RA.
25398489 IL-17 and IL-17R: an auspicious therapeutic target for psoriatic disease. 2014 Oct The continuous discovery of new T cell subpopulations in human autoimmune diseases is making the immunopathological network more complex. Th17 cells are one such newly identified subset of T cells, characterized by the production of signature cytokine IL-17. In last few years, several studies have strongly established the regulatory role of Th17 cells and its signature cytokine IL-17 in autoimmune diseases including psoriasis, psoriatic arthritis, rheumatoid arthritis, inflammatory bowel disease, systemic lupus erythematosus and multiple sclerosis. Psoriasis and PsA are immune mediated hyperproliferative diseases, affecting skin and joint respectively. Before the discovery of Th17 cells, psoriasis and psoriatic diseases were thought to be chiefly Th1 mediated diseases; later on IL-17 knockout animal studies as well as human experimental data indicate the crucial role of Th17 cells and its signature cytokine IL-17 in the pathogenesis of these diseases. In vitro human studies have shown the abundance of Th17 cells in the psoriatic plaques. Subsequently our research group has extended this observation in psoriatic arthritis and found the abundance of CD4+IL-17+ T cells in the synovial fluid and majority of these T cells are of memory phenotype (CD4RO+CD45RA-CD11a+). In addition, we showed the significant presence of functional IL-17 receptor in synovial fibroblast of psoriatic arthritis patients. Considering the strong association of IL-17 and psoriatic disease, IL-17 targeted therapy have shown promises in preclinical and clinical trials. In this review article, we have discussed the pathogenic role of IL-17 in psoriatic disease and summarized the therapeutic efficacy and safety profile of different anti IL-17 therapy as an anti-psoriatic agent.
23364870 Latent viral infections in young patients with inflammatory diseases treated with biologic 2013 Apr Treatment with biological drugs is associated with increased susceptibility to viral infections. Reactivation of JC virus (JCV) and human cytomegalovirus (HCMV) in adults after therapy has been documented. The long-term effects of biological and conventional therapy on human herpesviruses and polyomaviruses infections in young patients were assessed. One hundred eighty-six samples [urine, serum, and blood cells (PBMCs)] from 62 patients (15.8 ± 6.2 years old) with Crohn's disease, ulcerative rectocolitis or juvenile rheumatoid arthritis treated with immunotherapy or conventional therapy for over 12 months were tested by real time PCR. One hundred twenty-four samples (urine and blood) from 62 matched healthy volunteers (13.8 ± 8.6 years old) were included as controls. Sequencing of the JCV viral protein 1 (VP1) and transcriptional control region (TCR) was performed. Herpes simplex virus 1/2 and varicella zoster virus genomes were not detected in any patients, whereas Epstein-Barr virus, HCMV, and human herpesvirus-6 genomes were detected in 4.8%, 3.2%, and 1.6% of the patients, respectively. JCV was detected in 22.6% (14/62) of urine samples from patients and in 8% (5/62) from controls, in 50% (7/14) of sera from patients shedding JCV, and in 71.4% (5/7) of matched PBMCs. There was a significant association between infliximab treatment and excretion of JCV genotype 2. Subclinical infection/reactivation of JCV genotype 2 in young patients during infliximab therapy was demonstrated. Conversely, increased susceptibility to herpesviruses infection was not shown. Future studies are warranted to investigate the effects of JCV reactivation on the health of young patients treated with infliximab.
24005567 Results of a specific smoking cessation program for patients with arthritis in a rheumatol 2014 Jan The purpose of this study is to evaluate an intervention program in smoker patients. We selected consecutive active smoker patients with rheumatoid arthritis, spondyloarthritis, or connective tissue diseases. The intervention consisted of the following: (1) a baseline visit, which included verbal and written advice by the rheumatologist, emphasizing the practical benefits of smoking cessation. Patients completed a questionnaire that included smoking dependence tests and previous attempts to quit. (2) A follow-up visit to the nurse in the 3rd month for reinforcement and the receiving of pharmacological treatment to help patients quit smoking. The primary outcome was total abstinence in the last 7 days of a phone interview at 3, 6, and 12 months. The secondary outcome was a reduction in cigarette consumption by at least 50%. A total of 945 patients were screened. About 185 (19.5%) were current smokers, and 152 were included for intervention. In the previous 5 years, the mean annual withdrawal rate was 4.6%. The smoking cessation rate was 11.8, 14.4, and 15.7% at 3, 6, and 12 months (OR compared with previous cessation rate 3.8 (CI 95% 1.8-8.1)). Twenty-nine patients (19%) reduced ≥50% of the cigarette consumption at 12 months. The linear regression analysis showed that a score of less dependence (p = 0.03) and previous attempts to quit smoking (p = 0.04) were significantly associated with definitive smoking cessation at 12 months. One out of six patients quit smoking with the aid of an educational program which included verbal and written advice by the rheumatologist and the nurse. As far as we know, this is the first interventional study in smoker patients with arthritis.
25543266 Bitter correlationship between autoimmune hepatitis and smoking. 2015 Feb Cigarette smoke contains numerous toxic, carcinogenic and mutagenic chemicals, stable and unstable free radicals and reactive oxygen species (ROS) which cause biological oxidative damage. Continuous exposure to those chemicals leads to immense amount of damage to the human health either directly or indirectly. A hypothesis is advanced here that a possible explanation for developing autoimmune hepatitis (AIH) is due to regular smoking for long years of time. To examine this hypothesis, I relied on an experience of a case of a patient, as well as critical reading of the literature on smoking and different autoimmune disorders. Among the autoimmune diseases, rheumatoid arthritis (RA), multiple sclerosis (MS), thyroid disease, primary biliary cirrhosis (PBC) are reported mostly among tobacco-exposed animals. The observational and theoretical knowledge strengthen the hypothesis that smoking can be one of the causes of generating autoimmune hepatitis. This hypothesis could lead to a new diagnostic category, as well as therapeutic approaches for changing the regular smoking behavior.
25343123 Pulmonary nocardiosis in patients with connective tissue disease: A report of two cases. 2014 Feb Reported here are 2 patients with connective tissue disease who developed pulmonary nocardiosis. Case 1 involved a 73-year-old man with malignant rheumatoid arthritis treated with prednisolone 25 mg/day. Chest X-rays revealed a pulmonary cavity and bronchoscopy detected Nocardia species. The patient was successfully treated with trimethoprim/sulfamethoxazole. Case 2 involved a 41-year-old woman with systemic lupus erythematosus. The patient received remission induction therapy with 50 mg/day of prednisolone and tacrolimus. Six weeks later, a chest CT scan revealed a pulmonary cavity; bronchoscopy resulted in a diagnosis of pulmonary nocardiosis. The patient had difficulty tolerating trimethoprim/sulfamethoxazole, so she was switched to and successfully treated with imipenem/cilastatin and amikacin.
24946285 Proteomics of citrullination in cardiovascular disease. 2014 Aug Citrullination is an enzymatic posttranslational modification (PTM), which has become a topic of recent research due to its involvement in various physiologic and pathologic processes. This review will focus primarily on the cardiovascular pathology associated to date with citrullination, including myocardial citrullination as well as the potential role of citrullination in atherosclerosis as a driver inflammation, especially in patients with rheumatoid arthritis (RA). There is extensive citrullination within normal and RA myocardium as well as the atherosclerotic plaque; and increased levels of antibodies to citrullinated proteins have been associated with increased cardiovascular burden in patients with RA. Given robust citrullination in both RA as well as non-RA patients, there also exists the potential for protein citrullination to contribute to cardiovascular pathology in the general population. However, to investigate this possibility will require development of improved biochemical and proteomic tools for the study of protein citrullination. The remainder of this review will discuss current and developing methodologies to study protein citrullination and discuss their applicability for the analysis of complex samples. The ability to identify and quantify citrullinated protein is a key to understanding the role of this PTM. Methodologies and limitations of current technology for the identification of citrullination are discussed.
24786784 Synovitis with pitting edema as the presenting manifestation of systemic lupus erythematos 2014 Sep Rheumatologists are increasingly aware of the entity synovitis with pitting edema. The remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome has been reported with an array of conditions that include polymyalgia rheumatica, rheumatoid arthritis, Sjögren's syndrome and psoriatic arthropathy. Synovitis with pitting edema is now being increasingly recognized with systemic lupus erythematosus (SLE). We report a patient who presented with edema of hands and feet and was diagnosed eventually with definite SLE. With magnetic resonance imaging, joint effusions and tenosynovitis were confirmed to be associated with the otherwise-unexplained extremity edema.
24639111 Targeting IL-10 in auto-immune diseases. 2014 Sep IL-10 is a multifunctional cytokine secreted by a variety of cells. It not only inhibits activation of monocyte/macrophage system and synthesis of monocyte cytokine and inflammatory cytokine but also promotes the proliferation and maturation of non-monocyte-dependent T cell, stimulating proliferation of antigen-specific B cell. Increasing evidence indicates that IL-10 plays an important role in both the onset and development of auto-immune diseases, such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), Sjogren's syndrome (SS), multiple sclerosis (MS), Crohn's disease (CD), and psoriasis. However, the exact mechanisms of IL-10 in auto-immune diseases remain unclear. In the present review, we will summarize the biological effects of IL-10, as well as its role and therapeutic potential in auto-immune diseases.
24429047 Acute blue finger: a diagnostic challenge. 2014 Jan 15 The management of the acute blue finger is controversial with many regarding it as a benign condition. However, we would argue that it should always be considered as an emergency. We present a challenging case of a 43-year-old woman who presented with a 1-week history of sudden onset blue discolouration of the left fifth digit, and a 6-week history of episodic joint problems. Examination showed bilateral normal radial and ulnar pulses. Following blood investigations, an initial working diagnosis of early rheumatoid arthritis with associated Raynaud's phenomenon was made. Also, infective endocarditis was considered due to temporary misleading physical signs. Later, CT angiography of the left upper limb arteries showed a significant proximal left subclavian stenosis. Subsequently, a diagnosis of the left subclavian arteritis associated with digit ischaemia from embolic debris was made and the patient underwent a left subclavian angioplasty. However, delayed management resulted in a necrotic digit, which was left to autoamputate.
24375944 Immune response to chemically modified proteome. 2014 Feb Both enzymatic and nonenzymatic PTMs of proteins involve chemical modifications. Some of these modifications are prerequisite for the normal functioning of cell, while other chemical modifications render the proteins as "neo-self" antigens, which are recognized as "non-self" leading to aberrant cellular and humoral immune responses. However, these modifications could be a secondary effect of autoimmune diseases, as in the case of type I diabetes, hyperglycemia leads to protein glycation. The enigma of chemical modifications and immune response is akin to the "chick-and-egg" paradox. Nevertheless, chemical modifications regulate immune response. In some of the well-known autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis, chemically modified proteins act as autoantigens forming immune complexes. In some instances, chemical modifications are also involved in regulating immune response during pathogen infection. Further, the usefulness of proteomic analysis of immune complexes is briefly discussed.
24229038 Trigger finger release with stepwise preservation of the A1 pulley: a functional pulley-pr 2013 Oct The first annular (A1) pulley is an important structure of the hand, providing a biomechanical support to the metacarpophalangeal joint and maintaining joint stability and flexor tendon alignment. Albeit uncommon, disruption of this pulley can result in dislocation or ulnar drift of the digit, particularly pronounced in patients with rheumatoid arthritis. Despite this, the A1 pulley is commonly divided without reconstruction in trigger finger. Several annular pulley reconstructive techniques have been developed to preserve its function. However, development of recurrent triggering has been observed due to fibrosis, largely due to inadequate release of the pulley. We have developed a technique to increase the volume within the flexor sheath while preserving the A1 pulley by way of stepwise lengthening. This has enabled an increase in the diameter of the pulley to 4 times its original size. A prospective study was performed comprising 10 trigger finger releases with stepwise lengthening of the A1 pulley. In all patients, there were no complications, and good hand function was achieved with no recurrence of triggering at 6 weeks of follow-up. This technique can thus safely achieve trigger release without sacrifice of the function of the A1 pulley.
23968576 Novel Kv1.3 blockers for immunosuppression: WO2012155199. 2013 Nov A recent patent application from Bionomics/Merck Serono describes novel compounds as blockers of the voltage-gated Kv1.3 ion channel. The blockade of this channel shows great promise as a new therapeutic target for the treatment of autoimmune disorders such as multiple sclerosis, psoriasis, diabetes and rheumatoid arthritis. The generic claim of this patent refers to a new chemotype of Kv1.3 blockers based on an amide core with potent IC50's which are potentially within the nanomolar range. This article briefly reviews the chemistry and biology found in the patent and compares it with previous discoveries in the field.
23926723 Dupuytren disease: on our way to a cure? 2013 Jun Despite its high prevalence, the clinical presentation and severity of Dupuytren disease is extremely variable. The disease features a broad spectrum of symptoms, from simple nodules without the slightest clinical impact towards an extremely disabling form requiring multiple surgical procedures, sometimes even partial hand amputations. Recurrence after surgery is considered a failure for both patient and surgeon, but its definition is vague. The term 'recontracture' was coined by a patient and reflects the disappointment of recurrent disease. Wether or not a treatment option will insure a definite result, may depend more on the severity of the disease, which is patient specific, than on the treatment method itself. If a patient presents with Dupuytren disease, one should not merely evaluate his hands. Different clinical and personal history features may uncover a severe fibrosis diathesis and both correct information to the patient and an individualized treatment plan are needed. In the near future, a simple genetic test may help to identify patients at risk. Similar to the evolving knowledge and treatment modalities seen in rheumatoid arthritis, treatment of Dupuytren disease is likely to advance in the direction of disease control with pharmacotherapy and single shot minimal invasive enzymatic fasciotomy with collagenase to correct established contractures.
23102645 Pattern recognition receptors--molecular orchestrators of inflammation in inflammatory bow 2013 Apr Pattern recognition receptors (PRRs) are a family of germline encoded receptors responsible for the detection of "pathogen associated molecular patterns" (PAMPs) or host derived "damage associated molecular patterns" (DAMPs) which induce innate immune signalling to generate a pro-inflammatory profile within the host. Four main classes of PRRs are recognised, Toll-like receptors (TLRs), NOD-like receptors (NLRs), RIG-like receptors (RLRs) and C-type lectin receptors (CLRs). Abnormal activation of PRRs has been implicated in various autoimmune and inflammatory conditions including rheumatoid arthritis and asthma. Recent growing evidence has implicated these PRRs as contributory elements to the pathogenesis of inflammatory bowel disease (IBD) and colitis-associated cancer (CAC). Here, the current literature which implicates PRRs in IBD and CAC is comprehensively reviewed.
22441965 Increased levels of matrix metalloproteinase-3 in the sera and synovial fluids of patients 2013 Jul Pustulotic arthro-osteitis (PAO) is occasionally seen in patients with palmoplantar pustulosis (PPP); however, its pathogenesis is still obscure. Herein, two patients with PAO associated with PPP were described. Both patients developed hydrarthrosis on the knees, along with sternocostoclavicular pain. Detail examination revealed odontogenic infection in both cases. Matrix metalloproteinase-3 (MMP-3) is a useful marker reflecting the activity of rheumatoid arthritis. In this study, MMP-3 levels in the sera as well as joint fluids were examined. Serum MMP-3 levels were increased in both cases (274 ng/ml in Case 1 and 242 ng/ml in Case 2, normal; 17.3-59.7). Also, MMP-3 concentration in the joint fluids was markedly elevated (Case 1 > 80,000 ng/ml and 48,000 ng/ml in Case 2). Our studies suggest that MMP-3 may play a role in the pathogenesis of joint involvement of PPP.
25531357 Biosimilars: are they bioequivalent? 2014 Biologics have revolutionized several areas of medical therapeutics, and dozens of them are used by millions of patients. Monoclonal antibodies are only one type of biologics, but more than 900 are now in different phases of development. These drugs are complex to make and not cheap. The market is constantly increasing, and several biosimilars (copies of biologics) are being used, while many are still waiting to become available to the public. Biosimilars are more complex than generics, and regulatory agencies have very stringent criteria for approval. In the IBD field, the biosimilar infliximab (Inflectra®, Remsima®) has been recently approved by the EMA, but not by Canadian authorities. The EMA has considered that 'high similarity' in preclinical studies together with clinical data from two trials in ankylosing spondylitis and rheumatoid arthritis warrant the 'extrapolation' for all approved indications for original infliximab (Remicade®), specifically Crohn's disease and ulcerative colitis. Canadian authorities have not accepted extrapolation, based on differences in glycosylation (fucosylation) that could be related to properties important in Crohn's disease. Most scientific societies do support the idea of asking for specific clinical trials before approval, although they acknowledge that following EMA, FDA, and WHO guidelines warrant safe products. Practical issues such as interchangeability and substitution remain unsolved, and it is very likely that there will be different solutions at the national level. Pharmacovigilance plans will be key for obtaining reliable data. Biosimilars are not better drugs, but can be clearly cheaper and may facilitate access to new treatments in many populations.
25474159 Adopted orphans as regulators of inflammation, immunity and skeletal homeostasis. 2014 Adopted orphan nuclear receptors, such as peroxisome proliferator-activated receptors (PPARs) and liver X receptors (LXRs), have emerged as key regulators of inflammation and immunity and likewise control skeletal homeostasis. These properties render them attractive targets for the therapy of various inflammatory and autoimmune diseases affecting the musculoskeletal system. This review summarises the current knowledge on the role of these families of receptors during innate and adaptive immunity as well as during the control of bone turnover and discuss the potential use of targeting these molecules during the treatment of chronic diseases such as osteoarthritis, rheumatoid arthritis and osteoporosis.
25340431 The role of radiology in the evolution of the understanding of articular disease. 2014 Nov Both the clinical practice of radiology and the journal Radiology have had an enormous effect on our understanding of articular disease. Early descriptions of osteoarthritis (OA) appeared in Radiology. More recently, advanced physiologic magnetic resonance (MR) techniques have furthered our understanding of the early prestructural changes in patients with OA. Sodium imaging, delayed gadolinium-enhanced MR imaging of cartilage, and spin-lattice relaxation in the rotating frame (or T1ρ) sequences have advanced understanding of the pathophysiology and pathoanatomy of OA. Many pioneering articles on rheumatoid arthritis (RA) also have been published in Radiology. In the intervening decades, our understanding of the natural history of RA has been altered by these articles. Many of the first descriptions of crystalline arthropathies, including gout, calcium pyrophosphate deposition, and hydroxyapatite deposition disease, appeared in Radiology.
25326566 Atraumatic sternum fracture. 2014 Oct 17 The spine, pelvic bones and long bones of the lower extremities are common sites for insufficiency fractures. Cases of sternum insufficiency fractures have rarely been reported among elderly patients. Insufficiency fractures tend to occur in bones with decreased mechanical strength especially among elderly patients, in postmenopausal women and patients with underlying diseases. We describe a case of spontaneous sternum insufficiency fracture in a healthy man, with no known risk factors to fracture, or previous history of fractures. Sternum insufficiency fracture is a rare cause of chest pain. This case serves to remind the emergency physician to remain vigilant for other non-cardiac, non-pulmonary and non-traumatic causes of chest pain, especially among patients with known risk factors such as osteoporosis, chronic obstructive pulmonary disease, rheumatoid arthritis, systemic lupus erythematosus and patients on long-term steroid treatment. If diagnosed correctly, these patients can be discharged and treated as outpatients as this case emphasises.