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ID PMID Title PublicationDate abstract
24783157 Primary Extranodal Lymphomas of Lip - A Rare Manifestation in Sjogren's Syndrome. 2014 Mar Sjogren's syndrome (SS) is a chronic autoimmune disorder which is characterized by lymphocyte-mediated destruction of exocrine glands, which produces the classical symptoms of dry eyes and dry mouth, which is referred to as primary SS or the Sicca complex. When it is associated with another autoimmune disease such as rheumatoid arthritis or lupus erythematosus, the condition is termed as secondary SS. One of the known major complications in patients with Sjogren's syndrome is the occurrence of Non-Hodgkin's lymphoma of B cell type. It is not uncommon for malignant lymphomas to occur in head and neck region at nodal and sometimes, extranodal sites. However, only rarely may they involve the oral cavity primarily. This case report describes a rare occurrence of isolated extranodal lymphomas in the upper and lower lips of a patient, which clinically resembled a mucocele, and eventually was diagnosed as lymphoma which was associated with Sjogren's syndrome, thereby stressing the importance which was played by an oral diagnostician.
24748221 Historical and biochemical aspects of a seventeenth century gold-based aurum vitae recipe. 2014 Aug The medicinal chemistry and biomedical applications of gold complexes have been intensively studied over the last decades. Some complexes have been used for the treatment of rheumatoid arthritis, and a considerable number of new metallodrug candidates have been developed as new anticancer drugs and anti-infectives. However, the therapeutic use of gold and its complexes goes back to ancient times and was also of great importance for alchemists until the modern age. In this report, we give an overview of the alchemic medicine between the sixteenth and the early eighteenth century and describe the cytotoxicity and thioredoxin reductase (TrxR) inhibition of a typical "aurum vitae" medicine, which was prepared according to a recipe by Bartholomäus Kretschmar from the seventeenth century. "Aurum vitae" consists of a mixture of gold, mercury and antimony complexes and shows the expected cytotoxic and TrxR inhibitory properties providing some rationale for therapeutic effects of this kind of historical medicinal preparation.
24685838 A review of analytical methods for eicosanoids in brain tissue. 2014 Aug 1 Eicosanoids are potent lipid mediators of inflammation and are known to play an important role in numerous pathophysiological processes. Furthermore, inflammation has been proven to be a mediator of diseases such as hypertension, atherosclerosis, Alzheimer's disease, cancer and rheumatoid arthritis. Hence, these lipid mediators have gained significant attention in recent years. This review focuses on chromatographic and mass spectrometric methods that have been used to analyze arachidonic acid and its metabolites in brain tissue. Recently published analytical methods such as LC-MS/MS and GC-MS/MS are discussed and compared in terms of limit of quantitation and sample preparation procedures, including solid phase extraction and derivatization. Analytical challenges are also highlighted.
24512550 Uncovering the pathogenesis of large granular lymphocytic leukemia-novel STAT3 and STAT5b 2014 May Large granular lymphocytic (LGL) leukemia is an incurable chronic disease, characterized by clonal expansion of cytotoxic T- or NK-cells in blood and bone marrow. Cytopenias (anemia, neutropenia) and autoimmune disorders such as rheumatoid arthritis are the most common clinical manifestations of LGL leukemia. Recently, somatic activating STAT3 gene mutations were shown to be specific for LGL leukemia with a prevalence of up to 70%. Analogous mutations in the STAT5b gene were seen in a smaller proportion of patients. These gain-of-function mutations are located in the SH2 domain of STAT3 and affect the phosphotyrosine-SH2 interaction required for dimerization of STAT3. The mutations increase the phosphorylation of STAT3 and STAT5b and enhance the transcriptional activity of the mutated proteins. STAT3 and STAT5b mutations can be used as molecular markers for LGL leukemia diagnostics, and they present novel therapeutic targets for STAT3 and STAT5b inhibitors, which currently are in development for treatment of cancer and autoimmune disorders.
24404337 Inhibitory Effects of Eucommia ulmoides Oliv. Bark on Scopolamine-Induced Learning and Mem 2013 Nov Eucommia ulmoides Oliv. Bark (EUE) is commonly used for the treatment of hypertension, rheumatoid arthritis, lumbago, and ischialgia as well as to promote longevity. In this study, we tested the effects of EUE aqueous extract in graded doses to protect and enhance cognition in scopolamine-induced learning and memory impairments in mice. EUE significantly improved the impairment of short-term or working memory induced by scopolamine in the Y-maze and significantly reversed learning and memory deficits in mice as measured by the passive avoidance and Morris water maze tests. One day after the last trial session of the Morris water maze test (probe trial session), EUE dramatically increased the latency time in the target quadrant in a dose-dependent manner. Furthermore, EUE significantly inhibited acetylcholinesterase (AChE) and thiobarbituric acid reactive substance (TBARS) activities in the hippocampus and frontal cortex in a dose-dependent manner. EUE also markedly increased brain-derived neurotrophic factor (BDNF) and phosphorylation of cAMP element binding protein (CREB) in the hippocampus of scopolamine-induced mice. Based on these findings, we suggest that EUE may be useful for the treatment of cognitive deficits, and that the beneficial effects of EUE are mediated, in part, by cholinergic signaling enhancement and/or protection.
24156176 The elusive diagnosis: recurrent benign lymphocytic meningitis. 2013 Sep BACKGROUND: Recurrent benign lymphocytic meningitis (RBLM) or Mollaretmeningitis is a rare disease with a prevalence of 1-2.2/100,000 population. It is characterized by recurrent episodes of aseptic meningitis. The diagnosis is made via history fitting Bruyn's criteria, and confirmatory detection of HSV-2 in cerebrospinal fluid (CSF) via polymerase chain reaction (PCR). CASE: A 59-year-old female with a past medical history (PMH) of rheumatoid arthritis in remission and 11 prior episodes of aseptic meningitis presented with sudden and severe headache, photophobia, nausea, vomiting, and meningismus without focal findings. CSF analysis revealed aseptic meningitis with Herpes simplex 2 virus (HSV-2) present by PCR. CONCLUSION: RBLM remains a rare and elusive diagnosis but PCR technology has made it easier to diagnose. We present a 59-year-old female with classic features of RBLM, now suffering a 12th episode of aseptic meningitis. Heightened awareness of RBLM among clinicians may allow for an earlier diagnosis, reduced use of unnecessary antibiotics, shortened hospitalizations, and lower costs.
24001811 Bioactive compounds from marine mussels and their effects on human health. 2014 Jan 1 The consumption of marine mussels as popular seafood has increased steadily over the past decades. Awareness of mussel derived molecules, that promote health, has contributed to extensive research efforts in that field. This review highlights the bioactive potential of mussel components from species of the genus Mytilus (e.g. M. edulis) and Perna (e.g. P. canaliculus). In particular, the bioactivity related to three major chemical classes of mussel primary metabolites, i.e. proteins, lipids, and carbohydrates, is evaluated. Within the group of proteins the focus is mainly on mussel peptides e.g. those obtained by bio-transformation processes, such as fermentation. In addition, mussel lipids, comprising polyunsaturated fatty acids (PUFAs), are discussed as compounds that are well known for prevention and treatment of rheumatoid arthritis (RA). Within the third group of carbohydrates, mussel polysaccharides are investigated. Furthermore, the importance of monitoring the mussel as food material in respect to contaminations with natural toxins produced by microalgae is discussed.
23992328 Autoimmune (auto-inflammatory) syndrome induced by adjuvants (ASIA)--animal models as a pr 2013 ASIA syndrome, "Autoimmune (Auto-inflammatory) Syndromes Induced by Adjuvants" includes at least four conditions which share a similar complex of signs and symptoms and have been defined by hyperactive immune responses: siliconosis, macrophagic myofasciitis syndrome, Gulf war syndrome and post-vaccination phenomena. Exposure to adjuvants has been documented in these four medical conditions, suggesting that the common denominator to these syndromes is a trigger entailing adjuvant activity. An important role of animal models in proving the ASIA concept has been established. Experimentally animal models of autoimmune diseases induced by adjuvants are currently widely used to understand the mechanisms and etiology and pathogenesis of these diseases and might thus promote the development of new diagnostic, predictive and therapeutic methods. In the current review we wish to unveil the variety of ASIA animal models associated with systemic and organ specific autoimmune diseases induced by adjuvants. We included in this review animal models for rheumatoid arthritis-like disease, for systemic lupus erythematosus-like disease, autoimmune thyroid disease-like disease, antiphospholipid syndrome, myocarditis and others. All these models support the concept of ASIA, as the Autoimmune (Auto-inflammatory) Syndrome Induced by Adjuvants.
23904866 Latest advances in connective tissue disorders. 2013 Aug The connective tissue disorders comprise a number of related conditions that include systemic lupus erythematosus (SLE) and the antiphospholipid (Hughes) syndrome, scleroderma, myositis and Sjögren's syndrome. They are characterized by autoantibody production and other immune-mediated dysfunction. There are common clinical and serological features with some patients having multiple overlapping connective tissue disorders. The latest advances include new approaches to therapy, including more focused utilization of existing therapies and the introduction of biological therapies in SLE, more precise protocols for assessment of severe disease manifestations such as in interstitial lung disease and pulmonary artery hypertension in scleroderma, new antibodies for disease characterization in myositis and new approaches to patient assessment in Sjögren's syndrome. B cells have a critical role in most, if not all of these disorders such that B-cell depletion or suppression of B-cell activating cytokines improves disease in many patients. In particular, the introduction of rituximab, a monoclonal antibody targeting the CD20 molecule on B cells, into clinical practice for rheumatoid arthritis and B-cell lymphoma has been a key driver of experimental approaches to therapy in connective tissue disorders. Genetic studies also suggest a role for the innate immune system in disease pathogenesis, suggesting further future targets for biological therapies over the next few years.
23884028 Temporomandibular joint dysfunction in various rheumatic diseases. 2013 Jul 24 Temporomandibular disorder (TMD) is an inclusive term in which those conditions disturbing the masticatory function are embraced. It has been estimated that 33% of the population have signs of TMD, but less than 5% of the population will require treatment. The objective of this study was to measure the frequency of TMD in rheumatoid arthritis (RA), osteoarthrosis (OA), ankylosing spondylitis (AS) and systemic lupus erythematosus, and to define the limitations in everyday's life that patients perceive when present. A six-month survey of consecutive outpatients in a rheumatology clinic in a teaching hospital in Mexico was carried out. We defined TMD as: 1) the presence of pain; 2) difficulty on mouth opening, chewing or speaking; 3) the presence of non-harmonic movements of the temporomaxilar joints. All three characteristics had to be present. Z test was used to define differences between proportions. We present the results of 171 patients. Overall, 50 patients had TMD according to our operational definition (29.24%). Up to 76% of the sample had symptoms associated with the condition. TMD is more frequent in OA and in AS (29.24% vs 38% OA, P=0.009; 39% AS; P=0.005). We found no association between the severity of TMD and the request for specific attention for the discomfort produced by the condition. Only 8 of 50 (16%) patients with TMD had requested medical help for their symptoms, and they were not the most severe cases. TMD is more frequent in RA and OA. Although it may produce severe impairment, patients seem to adapt easily.
23812074 [Development and pharmacological effects of anti-RANKL monoclonal antibody drug denosumab] 2013 Denosumab (called RANMARK(®) in Japan), an anti-bone resorptive drug, is a complete human type monoclonal antibody that targets the osteoclast differentiation factor receptor activator of NF-κB ligand (RANKL). Using advanced gene-engineering techniques, Amgen Inc. (USA) has developed the drug, and it is now utilized in Japan for treatment of cancerous bone lesions associated with multiple myeloma and bone metastasis. On the other hand, denosumab has also shown inhibitory effects on bone resorption seen in patients with osteoporosis, rheumatoid arthritis, and Paget's disease, thus its range of use for medical treatment is expected to widen. Because of its long half-life in the body, subcutaneous denosumab administrations every 6 months are sufficient to obtain inhibitory effects on bone resorption, suggesting that this agent is more efficacious than bisphosphonates, which are presently used as anti-bone resorptive drugs. However, hypocalcemia might develop in patients with massive renal dysfunction. Denosumab binds to a specific loop structure of the RANKL molecule and inhibits its interaction with its receptor RANK. When labeled with radioactivity, denosumab was detected in lymph nodes and the spleen after subcutaneous administration, indicating its binding to RANKL expressed in those tissues. Thus, many medical doctors and investigators are interested in the inhibitory effects of denosumab on bone resorption as well as its mode of action.
23798274 Risk factors predicting fractures in early postmenopausal women. 2013 May Abstract Few studies exist evaluating fracture prediction in women aged 50-59. Clinical risk factors are important determinants for fracture prediction in younger postmenopausal women since most fractures occur outside the range of an osteoporotic bone mineral density. Although fracture incidence rates in this age group are about one-half of those aged 60-69, considerable costs and loss of quality-adjusted life years are still incurred in this age group. We sought to determine what clinical risk factors would predict subsequent fractures. Questionnaires were mailed out to 546 rural women who underwent osteoporosis screening 8.3 years previously by bone densitometry and a 24-item clinical risk factor assessment. Our survey had a 55% response rate and found that 11.9% of respondents had subsequent fractures. A prior fracture history, self-reported rheumatoid arthritis, and menopause age <40 were significantly associated with subsequent fractures. A logistic regression analyses showed only a prior fracture history and menopause age
23757294 Subsequent brain tumors in patients with autoimmune disease. 2013 Sep BACKGROUND: Previous studies have reported increased risk of brain tumors after allergic conditions, but no systematic analyses of these tumors in patients with autoimmune disease (AId) have been performed. No data are available on survival among patients with AId from brain tumors. We analyzed systematically risks and survival in histological types of brain tumors among patients who received a diagnosis of 33 different AIds. PATIENTS AND METHODS: Standardized incidence ratios (SIRs) for brain tumors or hazard ratios (HRs) of deaths after brain tumors were calculated up to 2008 in 402 462 patients hospitalized for AId after 1964 and were compared with data on the population not hospitalized for AIds. RESULTS: Brain tumors were diagnosed in 880 patients with AId. No increased or decreased risks (SIRs) were noted for glioma, whereas the increased SIRs for meningioma after many AIds were likely to be attributable to surveillance bias. The data on survival showed overall decreases for glioma (HR, 1.15) and meningioma (HR, 1.26). The survival in both was decreased in patients with chronic rheumatic heart disease, multiple sclerosis, and rheumatoid arthritis. Overall, HRs were increased for glioma after 6 AIds and for meningioma after 7 AIds. CONCLUSIONS: The present data showed that none of the 33 AIds influenced the risk of glioma. However, many AIds negatively influence survival in glioma and meningioma, probably through added physical burden or therapeutic limitations. Information of an existing AId in patients with newly diagnosed brain tumors should help the prognostic assessment and the design of treatment.
23580906 The risk of herpes zoster in the anti-TNF-α era: a case report and review of the literatu 2013 Mar 30 BACKGROUND: Tumor necrosis factor-α (TNF-α) inhibitors represent efficacious therapeutic agents in many chronic inflammatory diseases such as psoriasis and rheumatoid arthritis. However they have been connected with increased risk of infection and reactivation of a variety of infectious agents, such as viruses. The reactivation of varicella zoster virus infection causes herpes zoster (HZ), a self-limiting, dermatomally localized, vesicular rash that can be accompanied by postherpetic neuralgia and severe neurological complications. MAIN OBSERVATIONS: Limited information has been published regarding HZ during therapy with TNF-α inhibitors especially for the occurrence of HZ during adalimumab treatment. We report the case of a 58-year-old immunocompetent man with a 18-year history of plaque psoriasis who develops ophthalmic HZ during treatment with adalimumab. CONCLUSION: We report this case to enrich the literature and to highlight the increased risk of HZ infections in patient on anti-TNF-α therapy (incidence of HZ is about 3-fold increased respect to general population). Clinically, these infections often have atypical presentations that may hamper prompt diagnosis. Therefore, it is very important to identify early signs and symptoms of herpes zoster in patients on biologic therapy in order to start prompt efficient antiviral treatment to prevent the development of severe complications.
23523202 Targeting kinases: a new approach to treating inflammatory rheumatic diseases. 2013 Jun After two decades of research and development activity focussed on orally active kinase inhibitors, the first such drug (the JAK inhibitor Xeljanz, tofacitinib) was approved by the FDA in November 2012 for the treatment of rheumatoid arthritis (RA). There is an intense activity in many companies both on expanding the utility of JAK inhibitors in other auto-immune indications and in discovering inhibitors of the JAK family with different and more selective profiles. Progress is also being made with orally active Syk inhibitors. One such inhibitor (fostamatinib) is currently in large-scale phase 3 trials, and there are others in clinical development. The last two to three years have been transformative for kinase inhibitors in auto-immune diseases, as several inhibitors have finally progressed beyond phase 2 trials after so many failures on other targets. Thus, there are new treatment options for RA patients beyond existing oral DMARDs and parenteral biologics.
23378145 The role of the microbiome in rheumatic diseases. 2013 Mar There is a growing understanding of the mechanisms by which the influence of the microbiota projects beyond sites of primary mucosal occupation to other human body systems. Bacteria present in the intestinal tract exert a profound effect on the host immune system, both locally and at distant sites. The oral cavity has its own characteristic microbiota, which concentrates in periodontal tissues and is in close association with a permeable epithelium. In this review we examine evidence which supports a role for the microbiome in the aetiology of rheumatic disease. We also discuss how changes in the composition of the microbiota, particularly within the gastrointestinal tract, may be affected by genetics, diet, and use of antimicrobial agents. Evidence is presented to support the theory that an altered microbiota is a factor in the initiation and perpetuation of inflammatory diseases, including rheumatoid arthritis (RA), spondyloarthritis (SpA), and inflammatory bowel disease (IBD). Mechanisms through which the microbiota may be involved in the pathogenesis of these diseases include altered epithelial and mucosal permeability, loss of immune tolerance to components of the indigenous microbiota, and trafficking of both activated immune cells and antigenic material to the joints. The potential to manipulate the microbiome, by application of probiotics and faecal microbial transplant (FMT), is now being investigated. Both approaches are in their infancy with regard to management of rheumatic disease but their potential is worthy of consideration, given the need for novel therapeutic approaches, and the emerging recognition of the importance of microbial interactions with human hosts.
23373967 Association between polymorphisms in PDCD1 gene and aplastic anemia in Chinese Han populat 2013 Oct Single nucleotide polymorphism (SNP) of programmed cell death 1 (PD-1, encoded by PDCD1) has been reported to be associated with several autoimmune diseases including rheumatoid arthritis (RA), Graves' disease and multiple sclerosis (MS). In order to study the correlation between PD-1 gene polymorphism and aplastic anemia in a Chinese Han population, two SNPs, PD-1.1 G/A (rs36084323) and PD-1.6 G/A (rs10204525), were genotyped in 166 patients with aplastic anemia and 144 healthy controls by direct sequencing. All genotype distributions in both patients and controls were in Hardy-Weinberg equilibrium. Associations of genotypes and alleles with aplastic anemia were analyzed. The results suggested that the G allele of PD-1.1 was associated with an increased risk for aplastic anemia, while SNP of PD-1.6 was not associated with aplastic anemia in a Chinese Han population.
23256814 Small-molecule inhibitors of the interaction between TNF and TNFR. 2013 Jan The overexpression of TNF has been implicated in a variety of disease conditions including rheumatoid arthritis, Crohn's disease, HIV and cancer. It is presently a therapeutic target for inflammatory diseases. Many of the therapeutics currently used are biologics designed to sequester TNF, preventing it from binding with its receptors. Recent research has been focused on finding small molecules that alter the production of TNF, modulate its signal transduction pathways, or directly inhibit the binding to its receptors. Modulation of a protein-protein interaction with small molecules is an interesting and nontrivial approach. The various strategies used in obtaining small-molecule, nonpeptide, inhibitors of the TNF-TNF receptor interaction through disruption of the TNF trimer or direct inhibition of the TNF-TNF receptor interaction are presented here.
22743033 Overlap connective tissue disease syndromes. 2013 Jan Overlap Syndromes (OSs) have been defined as entities satisfying classification criteria of at least two connective tissue diseases (CTDs) occurring at the same or at different times in the same patient. CTDs include systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), systemic sclerosis (SSc), polymyositis/dermatomyositis (PDM), and Sjögren syndrome (SS). Every combination between these disorders has been reported. In some OS a specific autoantibody has been indentified, supporting the hypothesis that these syndromes are not a mere association of two or more CTD in the same patient, but a well defined clinical entity with specific clinical characteristics. As an example, anti-t-RNA synthetase syndrome is characterized by the presence of anti-t-RNA synthetase antibodies. Notably, clinical manifestations observed in OS may be different from those observed in the single CTD. The treatment of OS is mainly based on the use of corticosteroids and immunosuppressants. Biologic drugs, i.e. anti-TNFα or anti-CD20 monoclonal antibodies, have been recently introduced as alternative treatments in refractory cases. Moreover, there are some concerns with the use of anti-TNF agents in patients with systemic autoimmune diseases due to the risk of triggering disease exacerbations. In this paper the most frequent OS are described with a special focus on the specific immunologic and clinical aspects. Furthermore, some personal data on anti-t-RNA synthetase syndrome and rhupus syndrome are reported.
22743032 Autoimmune diseases in the intensive care unit. An update. 2013 Jan Autoimmune diseases (ADs) are a challenge at the intensive care unit. The management of patients with these diseases in the critical care setting has improved over time since there are new and more aggressive alternatives to treat and diagnose them. We aimed to review the current causes of admission, clinical features, outcomes and variables associated with mortality of patients with ADs admitted to the intensive care unit (ICU). International classification criteria for ADs were used to include patients. Search was done through PubMed, SCOPUS, SciELO, and LILACS databases up to December of 2011.Twenty-nine case series and forty-one case reports were analyzed after quality assessment. Respiratory involvement was the leading cause of admission. Systemic lupus erythematosus (SLE) (33.5% of reported patients), rheumatoid arthritis (25%) and systemic vasculitis (15%) were the most frequent ADs in patients admitted to the ICU in the last decade. Mortality ranged from 17% to 55% in case series including all ADs, but in the ones that only included patients with a specific AD, such as SLE, it reached up to 79%. High APACHE score, multi-organ dysfunction, older age and cytopenia were the most reported variables associated with mortality. In conclusion, ADs should always be considered in patients with life threatening conditions that warrant critical care. Variables influencing mortality should be promptly identified in order to improve the patients' outcomes.