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ID PMID Title PublicationDate abstract
24717997 Visual problem and low back pain as initial manifestation of multiple myeloma complicating 2014 Mar Some connective tissue diseases are associated with an increased risk of developing neoplastic disorders. Association of rheumatoid arthritis and systemic lupus erythematosus with lymphoma, and of dermatomyositis with different malignancies including ovarian and lung cancer has been reported in the literature. Here, we describe a 58 years old man with systemic sclerosis (SSc) for 15 years who developed severe lumbar pain when he was admitted for intravenous infusion of prostaglandin E1 for his fingertip ulcers. He was found to have abnormal skeletal imaging. Laboratory tests including bone marrow aspiration and biopsy determined multiple myeloma causing extensive bony infiltration. The patient expired after two cycles of VAD and Bortezomide chemotherapy.
24593212 Amyloid A amyloidosis in a Japanese patient with familial Mediterranean fever associated w 2014 Mar Familial Mediterranean fever (FMF) is an autoinflammatory disease common in eastern Mediterranean populations. The most severe complication is the development of secondary amyloid A (AA) amyloidosis. A 51-year-old Japanese male who had been suffering from periodic fever since in his twenties was referred to our hospital for proteinuria. Histological findings from renal biopsy revealed the deposition of AA amyloid fibrils, suggesting that renal dysfunction was due to AA amyloidosis. Gene analysis of the patient and his mother showed that both were homozygous for the M694I mutation in the MEFV gene. His mother was also a carrier of the SAA1.3 allele, which is not only a univariate predictor of survival but also a risk factor for the association of AA amyloidosis with rheumatoid arthritis in Japanese patients, and the SAA1-13T allele in the 13T/C polymorphism on the 5'-flanking region of the SAA1 gene. The patient was also a carrier of the SAA-13T allele. Colchicine resulted in not only an amelioration of the acute febrile attacks of FMF inflammation, but also an improvement in kidney dysfunction due to AA amyloidosis.
24527209 Evaluation of a multiplex ELISA for autoantibody profiling in patients with autoimmune con 2014 The performance of immunoassays for the detection of autoantibodies is of critical importance in the diagnosis and assessment of patients with autoimmune connective tissue diseases (ACTD). Our objective was to compare the features of two multiplexed assays-INNO-LIA ANA and Gennova-PictArray ENA ELISA-for measurement of multiple autoantibodies and their utility as a clinical tool in ACTD diagnosis. The antigens included SS-A/Ro (60 and 52), SSB/La, Sm, Sm/RNP, CENP-B, Jo-1, and Scl-70. Stored sera from 85 ACTD patients and 80 controls consisting of patients with vasculitis, rheumatoid arthritis and infectious diseases, as well as healthy subjects were analyzed jointly with clinical and laboratory data. Agreement between the two methods varied between 58 and 99% (Cohen's kappa: 0.21-0.71) mostly for SSA and SSB. The frequency of specific autoantibodies measured using the two methods was more variable for SSA, SSB, and RNP/Sm. There were a higher number of ambiguous results when using INNO-LIA. The optimized cut-off values of the Gennova-PictArray resulted in over 99% specificities in samples obtained from the control group. Sensitivity patterns were more accurate in Gennova-PictArray than in INNO-LIA, as suggested in previously reported studies. A third method could be applied to determine which of the two methods is more accurate.
24489611 Advances and challenges in the diagnosis and treatment of polymyalgia rheumatica. 2014 Feb Polymyalgia rheumatica (PMR) is a common inflammatory condition that often affects people over the age of 50 years. Characteristic symptoms are shoulder and hip girdle pain and prolonged morning stiffness. Markers of inflammation are often elevated. Clinicians are often faced with the challenge of distinguishing PMR from other conditions, particularly rheumatoid arthritis and spondyloarthropathy that can mimic symptoms of PMR in older people. Additionally, there is an association between PMR and giant cell arteritis, a common large-vessel vasculitis which also affects people over the age of 50 years. Imaging of the large vessels in asymptomatic patients with PMR often reveals findings of subclinical vasculitis. Presently, there are no tests that are specific for the diagnosis of PMR and clinicians rely on a combination of history, physical examination, laboratory tests and imaging studies to make a diagnosis. A recent undertaking by the European League Against Rheumatism/American College of Rheumatology has led to the publication of provisional classification criteria of PMR. Ultrasonography, which is being increasingly used by rheumatologists, can greatly aid in the diagnosis of PMR and often shows changes of synovitis and tenosynovitis. Treatment consists of low doses of glucocorticoids which are associated with morbidity. Evaluation of newer biologic therapies targeting inflammatory cytokines is underway. Despite treatment, relapses are common.
24434759 Fasting therapy for treating and preventing disease - current state of evidence. 2013 Periods of deliberate fasting with restriction of solid food intake are practiced worldwide, mostly based on traditional, cultural or religious reasons. There is large empirical and observational evidence that medically supervised modified fasting (fasting cure, 200-500 kcal nutritional intake per day) with periods of 7-21 days is efficacious in the treatment of rheumatic diseases, chronic pain syndromes, hypertension, and metabolic syndrome. The beneficial effects of fasting followed by vegetarian diet in rheumatoid arthritis are confirmed by randomized controlled trials. Further beneficial effects of fasting are supported by observational data and abundant evidence from experimental research which found caloric restriction and intermittent fasting being associated with deceleration or prevention of most chronic degenerative and chronic inflammatory diseases. Intermittent fasting may also be useful as an accompanying treatment during chemotherapy of cancer. A further beneficial effect of fasting relates to improvements in sustainable lifestyle modification and adoption of a healthy diet, possibly mediated by fasting-induced mood enhancement. Various identified mechanisms of fasting point to its potential health-promoting effects, e.g., fasting-induced neuroendocrine activation and hormetic stress response, increased production of neurotrophic factors, reduced mitochondrial oxidative stress, general decrease of signals associated with aging, and promotion of autophagy. Fasting therapy might contribute to the prevention and treatment of chronic diseases and should be further evaluated in controlled clinical trials and observational studies.
27437459 Application of Hydrotropic Solubilization in Spectrophotometric Estimation of Lornoxicam f 2014 Lornoxicam is a selective cyclooxygenase-1 and cyclooxygenase-2 inhibitor that exhibits anti-inflammatory, analgesic, and antipyretic activities. It is used in osteoarthritis and rheumatoid arthritis; and in treatment of postoperative pain and primary dysmenorrhoea. Lornoxicam is completely insoluble in water but soluble in alkaline solutions. Hydrotropic solubilization is a technique used to increase the aqueous solubility of poorly water-soluble drugs and the present study was aimed at developing a hydrotropic technique to increase the solubility of lornoxicam, using 2 M sodium benzoate as the hydrotropic agent. Beer's law was obeyed in the concentration range of 4-24 μg/mL at 381 nm. The solubility of lornoxicam in distilled water considerably increased with the addition of a hydrotropic agent. The analysis of tablets indicated good correlation between the amounts estimated and label claim. The LOD and LOQ of lornoxicam were found to be 0.34 μg/mL and 1.038 μg/mL, respectively, indicating good sensitivity of the proposed method. The percentage recovery was found to be 99.99%-100.21%. Thus the proposed method is new, simple, environmentally friendly, accurate, and cost effective and can be successfully employed in routine analysis of lornoxicam in tablets.
24133494 MHC Class II Polymorphisms, Autoreactive T-Cells, and Autoimmunity. 2013 Oct 10 Major histocompatibility complex (MHC) genes, also known as human leukocyte antigen genes (HLA) in humans, are the prevailing contributors of genetic susceptibility to autoimmune diseases such as Type 1 Diabetes (T1D), multiple sclerosis, and rheumatoid arthritis, among others (1-3). Although the pathways through which MHC molecules afford autoimmune risk or resistance remain to be fully mapped out, it is generally accepted that they do so by shaping the central and peripheral T-cell repertoires of the host toward autoimmune proclivity or resistance, respectively. Disease-predisposing MHC alleles would both spare autoreactive thymocytes from central tolerance and bias their development toward a pathogenic phenotype. Protective MHC alleles, on the other hand, would promote central deletion of autoreactive thymocytes and skew their development toward non-pathogenic phenotypes. This interpretation of the data is at odds with two other observations: that in MHC-heterozygous individuals, resistance is dominant over susceptibility; and that it is difficult to understand how deletion of one or a few clonal autoreactive T-cell types would suffice to curb autoimmune responses driven by hundreds if not thousands of autoreactive T-cell specificities. This review provides an update on current advances in our understanding of the mechanisms underlying MHC class II-associated autoimmune disease susceptibility and/or resistance and attempts to reconcile these seemingly opposing concepts.
23943493 Purinergic signalling in the musculoskeletal system. 2013 Dec It is now widely recognised that extracellular nucleotides, signalling via purinergic receptors, participate in numerous biological processes in most tissues. It has become evident that extracellular nucleotides have significant regulatory effects in the musculoskeletal system. In early development, ATP released from motor nerves along with acetylcholine acts as a cotransmitter in neuromuscular transmission; in mature animals, ATP functions as a neuromodulator. Purinergic receptors expressed by skeletal muscle and satellite cells play important pathophysiological roles in their development or repair. In many cell types, expression of purinergic receptors is often dependent on differentiation. For example, sequential expression of P2X5, P2Y1 and P2X2 receptors occurs during muscle regeneration in the mdx model of muscular dystrophy. In bone and cartilage cells, the functional effects of purinergic signalling appear to be largely negative. ATP stimulates the formation and activation of osteoclasts, the bone-destroying cells. Another role appears to be as a potent local inhibitor of mineralisation. In osteoblasts, the bone-forming cells, ATP acts via P2 receptors to limit bone mineralisation by inhibiting alkaline phosphatase expression and activity. Extracellular ATP additionally exerts significant effects on mineralisation via its hydrolysis product, pyrophosphate. Evidence now suggests that purinergic signalling is potentially important in several bone and joint disorders including osteoporosis, rheumatoid arthritis and cancers. Strategies for future musculoskeletal therapies might involve modulation of purinergic receptor function or of the ecto-nucleotidases responsible for ATP breakdown or ATP transport inhibitors.
23762114 α -Synuclein Modification in an ALS Animal Model. 2013 Amyotrophic lateral sclerosis (ALS) is a progressively paralytic neurodegenerative disease that can be caused by mutations in Cu/Zn-superoxide dismutase 1 (SOD1). Transgenic mice that overexpress mutant SOD1 develop paralysis and accumulate aggregates of mutant protein in the brainstem and spinal cord. Bee venom (BV), which is also known as apitoxin, is extracted from honeybees and is commonly used in oriental medicine for the treatment of chronic rheumatoid arthritis and osteoarthritis. The purpose of the present study was to determine whether BV affects misfolded protein aggregates such as alpha-synuclein, which is a known pathological marker in Parkinson disease, and ubiquitin-proteasomal activity in hSOD1(G93A) mutant mice. BV was bilaterally administered into a 98-day-old hSOD1(G93A) animal model. We found that BV-treated hSOD1(G93A) transgenic mice showed reduced detergent-insoluble polymerization and phosphorylation of α -synuclein. Furthermore, phosphorylated or nitrated α -synuclein was significantly reduced in the spinal cords and brainstems of BV-treated hSOD1(G93A) mice and reduced proteasomal activity was revealed in the brainstems of BV-treated symptomatic hSOD1(G93A). From these findings, we suggest that BV treatment attenuates the dysfunction of the ubiquitin-proteasomal system in a symptomatic hSOD1(G93A) ALS model and may help to slow motor neuron loss caused by misfolded protein aggregates in ALS models.
23707259 The discovery of BMS-457, a potent and selective CCR1 antagonist. 2013 Jul 1 A series of compounds which exhibited good human CCR1 binding and functional potency was modified resulting in the discovery of a novel series of high affinity, functionally potent antagonists of the CCR1 receptor. Issues of PXR activity, ion-channel potency, and poor metabolic stability were addressed by the addition of a hydroxyl group to an otherwise lipophilic area in the molecule resulting in the discovery of preclinical candidate BMS-457 for the treatment of rheumatoid arthritis.
23514443 Subconjunctival dexamethasone implant for non-necrotizing scleritis. 2013 Jan 7 BACKGROUND: The purpose of this study is to report the management of non-necrotizing anterior scleritis with a single-dose subconjunctival 0.7 mg dexamethasone implant (Ozurdex®, Allergan, Inc., CA, USA). Six patients with clinical diagnosis of non-necrotizing anterior scleritis (diffuse, sectorial, and nodular) were submitted to subconjunctival injection of dexamethasone implant. The injection was performed under topical anesthesia at the slit lamp. All patients reported only mild discomfort related to the procedure. Five patients had subconjunctival hemorrhage. Follow-up was performed 1, 7, 15, 30, and 45 days, and 2, 3, 4, 5, and 6 months after the procedure. Visual acuity, intraocular pressure, anterior and posterior biomicroscopy, and fundus exams were performed in each visit. RESULTS: In all patients, symptoms disappeared before day 7, and most of them were symptoms-free on day 2. The implant was visible at least up to day 45. One recurrence was noted in the 6-month follow-up in a patient with rheumatoid arthritis and non-necrotizing diffuse scleritis and was treated with oral steroids. No patient developed ocular hypertension or any kind of complications during the follow-up period, except for subconjunctival hemorrhage. CONCLUSION: Dexamethasone implant was safely and effectively used as a local therapy for non-necrotizing scleritis.
23474800 Presence of interleukin-17C in the tissue around aseptic loosened implants. 2013 May PURPOSE: The most common long-term complication of joint arthroplasty is aseptic loosening. The proinflammatory cytokines secreted by macrophages are involved in aseptic loosening. Recently, a novel proinflammatory cytokine IL-17C was reported to participate in inflammatory diseases by synergising with proinflammatory cytokines. However, the relationship between IL-17C and the aseptic loosening is unclear. METHODS: The tissues around aseptic loosened implants were collected during revision surgery and handled by formalin fixation and embedded in paraffin. The presence of IL-17C in the tissues around the aseptic loosened implants was investigated in 12 aseptic loosening patients using immunofluorescence. RESULTS: The presence of IL-17C protein in the tissues around aseptic loosened implants was detected by immunofluorescence. There are no statistical differences between optical density of IL-17C in aseptic loosening samples and in rheumatoid arthritis samples (positive control). CONCLUSIONS: These results suggest the presence of IL-17C in aseptic loosening. Interleukin-17C was related to the inflammation of aseptic loosening, possibly by contributing to the inflammation and osteolysis in the tissues surrounding aseptic loosened implants.
26237061 Recurrent Fever of Unknown Origin (FUO) Due to Periodic Fever, Aphthous Stomatititis, Phar 2013 Aug 19 FAPA syndrome (periodic fever, aphthous stomatititis, pharyngitis and adenitis) is a relatively new entity described in pediatric patients. In adults, reports of FAPA are limited to rare case reports. The differential diagnosis of FAPA in adults includes Behcet's syndrome, familial Mediterranean fever (FMF), Hyper IgD syndrome and juvenile rheumatoid arthritis (JRA), i.e., adult Still's disease. With FAPA syndrome, between episodes patients are completely asymptomatic and serologic inflammatory markers such as erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and white blood cell (WBC) count are normal. The etiology of FAFA is unknown, but lack of secondary cases or clustering in close contacts, lack of seasonality, and the lack of progression for years argue against an infectious etiology. We describe an extremely rare case of an adult with a recurrent FUO with profuse night sweats and prominent chills due to FAPA syndrome.
23246567 Detection and isolation of human serum autoantibodies that recognize oxidatively modified 2013 Apr The breakdown of human immune tolerance to self-proteins occurs by a number of mechanisms, including posttranslational modifications of host molecules by reactive oxygen, nitrogen, or chlorine species. This has led to great interest in detecting serum autoantibodies raised against small quantities of oxidatively modified host proteins in patients with autoimmune inflammatory diseases, such as rheumatoid arthritis. Here, we provide protocols for the preparation and chemical characterization of oxidatively modified protein antigens and procedures for their use in immunoblotting and ELISAs that detect autoantibodies against these antigens in clinical samples. These gel electrophoresis- and plate reader-based immunochemical methods sometimes suffer from low analytical specificity and/or sensitivity when used for serum autoantibody detection. This is often because a single solid-phase protein (antigen) is exposed to a complex mixture of serum proteins that undergo nonspecific binding. Therefore more sensitive/specific techniques are required to detect autoantibodies specifically directed against oxidatively modified proteins. To address this, we describe novel affinity chromatography protocols by which purified autoantibodies are isolated from small volumes (<1 ml) of serum. We have also developed strategies to conjugate submilligram amounts of isolated immunoglobulins and other proteins to fluorophores. This set of methods will help facilitate the discovery of novel diagnostic autoantibodies in patients.
22826078 Atherosclerotic factors in PR3 pulmonary vasculitis. 2013 Autoimmune disease such as systemic lupus erythematosus or rheumatoid arthritis are connected with higher risk of atherosclerosis and cardiovascular complications and mortality. This results from inflammatory damage to the vessel wall by vasculitis. The aim of the present study was to evaluate whether patients with Wegener's granulomatosis (WG) and pulmonary involvement have an increased prevalence of atherosclerotic disease as characterized traditional risk factors. Twenty one patients with WG in remission and 15 control subject were entered to the study. Traditional risk factor for cardiovascular disease such as hyperglycemia, hypertension, smoking, obesity, and dyslipidemia were assessed. Both systolic and diastolic blood pressure were higher in WG patients (p<0.025). Total cholesterol, LDL and TG levels were markedly elevated in 18 of the 21 in pulmonary WG patients. Compared with controls, plasma levels of hsCRP were raised in WG patients; 3.68 (0.79-9.75) mg/l vs. 0.14 (0.12-0.59) mg/l (p<0.01). We conclude that non-pharmacological and pharmacological treatments of traditional risk factors are crucial to prevent cardiovascular disease in WG patients and thus should be part of therapy to control WG activity and damage caused by it.
24638890 Matricellular protein CCN1/CYR61: a new player in inflammation and leukocyte trafficking. 2014 Mar Cystein-rich protein 61 (CYR61/CCN1) is a component of the extracellular matrix, which is produced and secreted by several cell types including endothelial cells, fibroblasts and smooth muscle cells. CCN1 has been implicated in leukocyte migration and the inflammatory process, but it is also involved in cardiovascular development and carcinogenesis. It exerts its functions through binding to multiple integrins present in many different cell types. This multiplicity in function is now known to contribute to the diverse array of cellular processes it can regulate. The expression of CCN1 is tightly regulated by cytokines and growth factors. However, CCN1 can directly modulate cell adhesion and migratory processes whilst simultaneously regulating the production of other cytokines and chemokines through paracrine and autocrine feedback loops. This complex functionality of CCN1 has highlighted the pivotal role this molecule can play in regulating the immunosurveillance process. Furthermore, CCN1 has now emerged as an important partner when targeting components of the infectious or chronic inflammatory disease processes such as atherosclerosis or rheumatoid arthritis. This review will focus on CYR61/CCN1 and its ability to control the migration of leukocytes, the production of cytokines and cell proliferation or senescence at the site of inflammation.
25512892 Rituximab for troublesome cases of childhood nephrotic syndrome. 2014 Nov 8 Nephrotic syndrome (NS) is the most common glomerular disease of childhood. Steroid-dependent and steroid-resistant nephrotic syndrome present challenges in their pharmaceutical management; patients may need several immunosuppressive medication for optimum control, each of which medication has its own safety profile. Rituximab (RTX) is a monoclonal antibody that targets B cells and has been used successfully for management of lymphoma and rheumatoid arthritis. Recent clinical studies showed that rituximab may be an efficacious and safe alternative for the treatment of complicated nephrotic syndrome. In this review article, we aim to review the efficacy and safety of RTX therapy in nephrotic syndrome. We reviewed the literature pertaining to this topic by searching for relevant studies on PubMed and Medline using specific keywords. The initial search yielded 452 articles. These articles were then examined to ensure their relevance to the topic of research. We focused on multicenter randomized controlled trials with relatively large numbers of patients. A total of 29 articles were finally identified and will be summarized in this review. The majority of clinical studies of RTX in complicated pediatric NS showed that rituximab is effective in approximately 80% of patients with steroid-dependent NS, as it decreases the number of relapses and steroid dosage. However, RTX is less effective at achieving remission in steroid-resistant NS. RTX use was generally safe, and most side effects were transient and infusion-related. More randomized, double-blinded clinical studies are needed to assess the role of RTX in children with nephrotic syndrome.
25384990 Prevalence, incidence and clinical impact of cachexia: facts and numbers-update 2014. 2014 Dec Cachexia is a serious but underrecognised consequence of many chronic diseases. Its prevalence ranges from 5-15 % in end-stage chronic heart failure to 50-80 % in advanced cancer. Cachexia is also part of the terminal course of many patients with chronic kidney disease, chronic obstructive pulmonary disease (COPD) and rheumatoid arthritis. Mortality rates of patients with cachexia range from 10-15 % per year in COPD through 20-30 % per year in chronic heart failure and chronic kidney disease to 80 % in cancer. The condition is also associated with poor quality of life. In the industrialised world, the overall prevalence of cachexia (due to any disease and not necessarily associated with hospital admission) is growing and it currently affects around 1 % of the patient population, i.e. around 9 million people. It is also a significant health problem in other parts of the globe. Recently there have been advances in our understanding of the multifactorial nature of the condition, and particularly of the role of inflammatory mediators and the imbalance of anabolism and catabolism. Several promising approaches to treatment have failed to live up to the challenge of phase III clinical trials, but the ghrelin receptor agonist anamorelin seems to have fulfilled at least some early promise. Further advances are urgently needed.
24506890 Looking in the Porphyromonas gingivalis cabinet of curiosities: the microbium, the host an 2014 Apr The past decades of biomedical research have yielded massive evidence for the contribution of the microbiome in the development of a variety of chronic human diseases. There is emerging evidence that Porphyromonas gingivalis, a well-adapted opportunistic pathogen of the oral mucosa and prominent constituent of oral biofilms, best known for its involvement in periodontitis, may be an important mediator in the development of a number of multifactorial and seemingly unrelated chronic diseases, such as rheumatoid arthritis and orodigestive cancers. Orodigestive cancers represent a large proportion of the total malignancies worldwide, and include cancers of the oral cavity, gastrointestinal tract and pancreas. For prevention and/or enhanced prognosis of these diseases, a good understanding of the pathophysiological mechanisms and the interaction between P. gingivalis and host is much needed. With this review, we introduce the currently accumulated knowledge on P. gingivalis's plausible association with cancer as a risk modifier, and present the putative cancer-promoting cellular and molecular mechanisms that this organism may influence in the oral mucosa.
24468053 Increased circulating obestatin in patients with chronic obstructive pulmonary disease. 2014 Jan 28 BACKGROUND: Some peptides, which regulate the metabolic balance, are thought to play important roles in nutritional disorders and systemic inflammation in COPD. Treatment of rats with obestatin decreased body-weight gain. Obestatin was also found to be correlated with inflammation in rheumatoid arthritis. The aims of this study were to investigate the level of circulating obestatin in COPD and to analyze the relationship among obestatin and nutritional status, and systemic inflammation. METHODS: 32 COPD patients with BMI less than 20 kg/m2 and 22 normal controls were included. Body composition was estimated using "foot-to-foot" BIA technology. Circulating obestatin was determined with enzyme-linked immunosorbent assay. Pulmonary function, TNF-α and C reactive protein were also measured. RESULTS: The level of circulating obestatin was higher in COPD with underweight than that in normal control (5562.75 ± 3435.43 pg/ml in COPD, 3663.90 ± 2313.95 pg/ml in controls, p = 0.028). BMI, Waist circumference, hip circumference, bodyFAT and FAT% in COPD group were lower than those in normal control. Positive correlation was found among circulating C reactive protein, TNF-α and obestatin. There was no significant correlation among BMI, pulmonary function and obestatin. CONCLUSIONS: This study shows that circulating obestatin is higher in underweight COPD patients, and positively correlated to systemic inflammation, but not to nutritional status.