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ID PMID Title PublicationDate abstract
25676516 Epidemiology of human pulmonary infection with nontuberculous mycobacteria: a review. 2015 Mar Population-based data have documented a worldwide increase in the prevalence of human nontuberculous mycobacterial (NTM) infections since 2000. Mycobacterium avium complex is predominant in North America and East Asia, whereas in regions within Europe, M kansasii, M xenopi, and M malmoense are more common. Host factors important to the current epidemiology of NTM pulmonary disease include thoracic skeletal abnormalities, rheumatoid arthritis, and use of immunomodulatory drugs. Clustering of disease within families suggests a heritable genetic predisposition to disease susceptibility. Warm, humid environments with high atmospheric vapor pressure contribute to population risk.
25525453 Effect of cervus and cucumis peptides on osteoblast activity and fracture healing in osteo 2014 Osteoporosis is associated with delayed and/or reduced fracture healing. As cervus and cucumis are the traditional Chinese treatments for rheumatoid arthritis, we investigated the effect of supplementation of these peptides (CCP) on bone fracture healing in ovariectomized (OVX) osteoporotic rats in vitro and in vivo. CCP enhanced osteoblast proliferation and increased alkaline phosphatase activity, matrix mineralization, and expression of runt-related transcription factor 2 (Runx2), bone morphogenetic protein 4 (BMP4), and osteopontin. In vivo, female Sprague-Dawley rats underwent ovariectomy and the right femora were fractured and fixed by intramedullary nailing 3 months later. Rats received intraperitoneal injections of either CCP (1.67 mg/kg) or physiological saline every day for 30 days. Fracture healing and callus formation were evaluated by radiography, micro-CT, biomechanical testing, and histology. At 12 weeks after fracture, calluses in CCP-treated bones showed significantly higher torsional strength and greater stiffness than control-treated bones. Bones in CCP-treated rats reunified and were thoroughly remodeled, while two saline-treated rats showed no bone union and incomplete remodeling. Taken together, these results indicate that use of CCP after fracture in osteoporotic rats accelerates mineralization and osteogenesis and improves fracture healing.
25440698 [Infliximab is effective in difficult-to-control peripheral ulcerative keratitis. A report 2015 May Peripheral ulcerative keratitis is caused by an inflammatory and destructive process of the perilimbal peripheral cornea. This inflammation is due to immune complex deposition in this region of the cornea and in adjacent vessels. It can be idiopathic, or a manifestation of systemic disease such as rheumatoid arthritis, vasculitis of small vessels associated with ANCA, relapsing polychondritis, systemic lupus erythematosus and Crohn's disease. Its treatment includes the use of high-dose corticosteroids and, in some cases, the concomitant use of immunosuppressants such as methotrexate, azathioprine, mycophenolate mofetil, cyclophosphamide or cyclosporine. The use of immunobiological agents can be a strategy in cases of difficult control. The authors describe the treatment of three patients who, after failure with the use of corticosteroids or immunosuppressants, showed good response after the use of infliximab.
25139725 Recent advances in the structure-based and ligand-based design of IKKβ inhibitors as anti 2014 NF-κB is a significant transcription factor that regulates the expression of various pro-survival genes. IKK is a crucial protein kinase that activates NF-κB translocating from cytoplasm to nucleus for DNA binding. It is composed of three subunits, IKKα, IKKβ, IKKγ (NEMO), where IKKα and IKKβ are catalytic subunits, and IKKγ is the regulatory subunit. Many diseases, such as Hodgkin's disease, Hepatitis-associated hepatocellular carcinoma, colorectal cancer, prostate cancer, rheumatoid arthritis and inflammatory bowel disease, are related to IKK and NF-κB. So far, various IKK inhibitors targeting the ATP binding site have been identified through high throughput screening, rational design or in silico methods, however, only three of them (CHS-828, EB-1627 and IMD-1041) have been under clinical studies, indicating the strategy for the design of IKK inhibitors need to be reinspected. Besides ATP-competitive inhibitors, several other inhibitors have also been disclosed recently, which provide novel concepts to the discovery of IKK inhibitors. In this review, we focus on two parts: 1) the chemotypes and binding patterns of the traditional ATP-competitive IKK inhibitors; 2) novel strategies for the identification of non-ATP-competitive IKK inhibitors as NF-κB modulators. Through these discussions we hope to present inspirations for the development of new IKK inhibitors.
25025716 Sleep disturbances and inflammatory bowel disease. 2014 Nov With an estimated 70 million Americans suffering, sleep disorders have become a global issue, and discovering their causes and consequences are the focus of many clinical research studies. Sleep is now also considered to be an important environmental and behavioral factor associated with the process of inflammation and the immune system. Increased sleepiness is considered part of the acute phase of response to tissue injury, and sleep loss activates inflammatory cytokines such as interleukin (IL)-1 and tumor necrosis factor (TNF)-α. Clinical studies in many immune-mediated diseases, such as systemic lupus erythematosus, rheumatoid arthritis, and ankylosing spondylitis, have revealed an association of sleep disturbances with disease activity. Recent research suggests that individuals with sleep abnormalities are also at greater risk of serious adverse health, economic consequences, and most importantly increased all-cause mortality. The importance of sleep in inflammatory bowel disease has recently gained attention with some published studies demonstrating the association of sleep disturbances with disease activity, subclinical inflammation, and risk of disease relapse. A comprehensive review of sleep physiology and its association with the immune system is provided here. Experimental and clinical studies exploring this relationship in inflammatory bowel disease are reviewed, and the clinical implications of this relationship and future directions for research are also discussed.
25022060 [Performance and clinical evaluation of antinuclear antibody test based on fluorescence en 2014 Apr BACKGROUND: The measurement of antinuclear antibodies (ANA) is used for screening of connective tissue diseases (CTD) in the laboratory. ANA detection is performed by indirect immunofluorescence (IF) assay on HEp-2 cells from human larynx carcinoma. However, it lacks specificity for the identification of specific diseases and antigen reactivity. The aim of the present study was to evaluate the EliA CTD Screen (EliA), a new enzyme fluoroimmunoassay (Phadia AB, Uppsala, Sweden) for detection of ANA in human serum. PATIENTS AND METHODS: The study involved a total of 732 serum samples, 200 from healthy donors, 297 from patients with CTD and 235 from patients with rheumatoid arthritis, vasculitis syndrome and relative disease of CTD. For all sera, ANA was measured by IF, commercial assay (MESACUP) and EliA. RESULT: The sensitivity and specificity of EliA were 73.7% and 78.7%, respectively, whereas those of MESACUP were 80.8% and 64.7%, respectively. Area under the receiver operating curves for EliA, MESACUP and IF were 0.821, 0.786 and 0.730, respectively. The concordance rate between EliA and MESACUP was 84.2%. These discrepancies between those 2 assays were found in 84 sera. Further investigation were done by each ANA antigen tests for the discrepant results of EliA in 83 sera. The discrepancies might be occurred by antigen difference or non-specific response. CONCLUSION: AUC results showed that the diagnostic performance of EliA was superior to MESACUP and IF. EliA had a good performance as method for screening of CTD.
24910558 A dangerous duo in adipose tissue: high-mobility group box 1 protein and macrophages. 2014 Jun High-mobility group box 1 (HMGB1) protein first made headlines 40 years ago as a non-histone nuclear protein that regulates gene expression. Not so long ago, it was also shown that HMGB1 has an additional surprising function. When released into the extracellular milieu, HMGB1 triggers an inflammatory response by serving as an endogenous danger signal. The pro-inflammatory role of HMGB1 is now well-established and has been associated with several diseases, including sepsis, rheumatoid arthritis, and atherosclerosis. Yet very little is known about its role in obesity, wherein adipose tissue is typified by a persistent, smoldering inflammatory response instigated by high macrophage infiltrate that potentiates the risk of obesity-associated comorbidities. This mini-review focuses on the putative causal relationship between HMGB1 and macrophage pro-inflammatory activation in pathologically altered adipose tissue associated with obesity.
24891252 [Role of orthopedic rheumatologist in the therapy of rheumatic diseases with biologics]. 2014 Jun The international strategies in the treatment of rheumatic diseases have changed dramatically in the last 10 years. In addition to the prescription of a basic medication as soon as possible, biologics are increasingly being used for drug treatment of rheumatic diseases in Germany. The domains of orthopedic surgeons and orthopedic rheumatologists are still the extended conservative and surgical treatment of inflammatory systemic diseases, which continue to play an important role despite the improved drug therapy options. Orthopedic surgeons should principally be familiar with the use of antirheumatic drugs, especially with respect to the perioperative management. However, there is also a role for the orthopedic surgeon in the early detection of inflammatory systemic diseases and in cooperation with rheumatologists in the medicinal treatment of selected diseases. Because patients with initial stages of joint pain, e.g. from rheumatoid arthritis (RA), spondyloarthritis (SpA) or psoriatic arthropathy often present first to an orthopedic surgeon, recognition of the early stages by the primary treating physician, including the necessary rapid induction of drug therapy is especially important. In addition there is a shortage of internist rheumatologists in Germany so that selective referral and close cooperation between the two physicians become of great importance.
24871974 Prediction of bacterial microRNAs and possible targets in human cell transcriptome. 2014 Jun Recent studies have examined gene transfer from bacteria to humans that would result in vertical inheritance. Bacterial DNA appears to integrate into the human somatic genome through an RNA intermediate, and such integrations are detected more frequently in tumors than normal samples and in RNA than DNA samples. Also, vertebrate viruses encode products that interfere with the RNA silencing machinery, suggesting that RNA silencing may indeed be important for antiviral responses in vertebrates. RNA silencing in response to virus infection could be due to microRNAs encoded by either the virus or the host. We hypothesized that bacterial expression of RNA molecules with secondary structures is potentially able to generate miRNA molecules that can interact with the human host mRNA during bacterial infection. To test this hypothesis, we developed a pipeline-based bioinformatics approach to identify putative micro-RNAs derived from bacterial RNAs that may have the potential to regulate gene expression of the human host cell. Our results suggest that 68 bacterial RNAs predicted from 37 different bacterial genomes have predicted secondary structures potentially able to generate putative microRNAs that may interact with messenger RNAs of genes involved in 47 different human diseases. As an example, we examined the effect of transfecting three putative microRNAs into human embryonic kidney 293 (HEK293) cells. The results show that the bacterially derived microRNA sequence can significantly regulate the expression of the respective target human gene. We suggest that the study of these predicted microRNAs may yield important clues as to how the human host cell processes involved in human diseases like cancer, diabetes, rheumatoid arthritis, and others may respond to a particular bacterial environment.
24864097 [The advanced oxidation protein products as potential diagnostic and prognostic factor in 2014 May 8 The possibility of diagnostic and/or prognostic use of measuring the concentration of advanced oxidation protein products (AOPPs) in chronic diseases with well-documented involvement of oxidative stress (OS) in their pathogenesis were the subject of numerous studies. In the present study discussed the pathological conditions and disorders, in which the role of OS and oxidative damage of proteins is also indicated as one of the factors in their etiopathogenesis. The presented data concerned clinical and diagnostic aspects of AOPPs as well as biochemical mechanisms of disturbances in the infection and autoimmune diseases, cancers, genetic and neurological diseases. Participation of AOPPs in disturbances connected with fertility, pregnancy delivery and prematurity are also shown. Moreover the single literature data concerning other pathological states, in which AOPPs are also becoming the object of intensive investigations are presented. The review and application possibilities of AOPPs measurement as useful marker for diagnosis, prognosis and monitoring the course of these diseases were performed. Diagnostic or prognostic utility of AOPPs are especially indicated in the course of rheumatoid arthritis, development of pregnancy complication both in mother and child, and dementia. However, AOPPs measurement seems to be most promising in plasma or urine in course of cancer diseases.
24609719 Anaplastic large cell lymphoma with paraneoplastic neutrophilia: an association between IL 2014 Jun We report a case of anaplastic large cell lymphoma (ALCL) with involvement of bone marrow, exhibiting extreme leukocytosis leading to death due to multi-organ failure within 1 week after admission. The patient had a history of rheumatoid arthritis, and had severe pneumonia at admission. To elucidate the basis for the observed extreme neutrophilia, we analysed the levels of several cytokines in serum samples taken from the patient at diagnosis. The patient exhibited an extreme increase in interleukin-17 (IL-17), one of the major regulatory cytokines for inflammation and neutrophil migration. Interestingly, a recent study revealed that anaplastic lymphoma kinase (ALK)-positive ALCL cells produce IL-17. IL-17 also contributes to treatment resistance in multiple types of cancer. Given these previous findings, our case may suggest a possible link between overproduction of IL-17 and an aggressive ALCL phenotype. Further studies will be required to determine whether serum IL-17 levels serve as a useful prognostic marker for ALCL.
24595859 SOCS signaling in autoimmune diseases: molecular mechanisms and therapeutic implications. 2014 May Suppressor of cytokine signaling (SOCS) proteins are mainly induced by various cytokines and have been described as classical inhibitors of cytokine signaling. SOCS signaling is involved in the regulation of immune cells, and recent findings suggest that SOCS proteins, especially SOCS1 and SOCS3, are often dysregulated in a wide variety of autoimmune diseases, including systemic lupus erythematosus, rheumatoid arthritis, type 1 diabetes, psoriasis, and multiple sclerosis. Recent studies suggest that SOCS signaling could be therapeutically targeted in various autoimmune diseases. In this review, we discuss recent studies on the role of SOCS proteins in the development and pathogenesis of autoimmune diseases, as well as their clinical implications.
24512514 A review of the current literature and a guide to the early diagnosis of autoimmune disord 2014 May Neuromyelitis optica (NMO) is an immune-mediated neurological disorder characterised by recurrent episodes of optic neuritis and longitudinally extensive transverse myelitis. A serum biomarker, aquaporin-4 IgG, the autoantibody against aquaporin-4 water channel, has been specifically associated with NMO and has assisted early recognition and prediction of relapses. Less commonly, a monophasic course, associated with antibodies to myelin oligodendrocyte glycoprotein has been reported. Specific diagnostic criteria have been defined; however, some cases that do not fulfil these criteria (but are nevertheless associated with aquaporin-4 IgG) are classified as NMO spectrum disorder and follow the same relapsing course. An ever-growing list of autoimmune disorders, both organ-specific and non-organ-specific, have been associated in up to 20-30% of patients with NMO. These disorders, which may become symptomatic before or after the development of NMO, are often diagnosed long after the diagnosis of NMO, as symptoms may be wrongly attributed to NMO, its residual effects or medication side effects. In addition, autoantibodies can be found in patients with NMO without coexisting disease (up to 40% in some series) and maybe suggestive of a heightened humoral immune response. We present a comprehensive review of the current literature on autoimmune disorders co-existing with NMO and identified 22 autoimmune conditions (myasthenia gravis, coeliac disease, ulcerative colitis, sclerosing cholangitis, systemic lupus erythematosus, rheumatoid arthritis, antiphospholipid antibody syndrome, Sjogren's syndrome, autoimmune hypothyroidism, immune thrombocytopenic purpura, pernicious anaemia, narcolepsy, pemphigus foliaceus, alopecia areata, psoriasis, scleroderma, dermatitis herpetiformis, polymyositis, chronic inflammatory demyelinating polyneuropathy, paraneoplastic disorders, insulin dependent diabetes mellitus and autoimmune encephalitis).
24454481 Th17 cells in immunity and autoimmunity. 2013 Th17 and IL-17 play important roles in the clearance of extracellular bacterial and fungal infections. However, strong evidence also implicates the Th17 lineage in several autoimmune disorders including multiple sclerosis, psoriasis, rheumatoid arthritis, inflammatory bowel disease, systemic lupus erythematosus, and asthma. The Th17 subset has also been connected with type I diabetes, although whether it plays a role in the pathogenicity of or protection from the disease remains a controversial issue. In this review we have provided a comprehensive overview of Th17 pathogenicity and function, including novel evidence for a protective role of Th17 cells in conjunction with the microbiota gut flora in T1D onset and progression.
24426249 Antioxidant status and oxidative stress in the circulation of younger and elderly human su 2013 Oct Extensive research has demonstrated the protective properties of antioxidants, which scavenge reactive oxygen species and their precursors, as well as up-regulate enzymes involved in the repair of cellular damage. Several case-control studies have showed higher blood levels of antioxidants and decreased oxidative stress in younger individuals when compared with older ones. Cell damage caused by free radicals appears to be a major contributor in aging and degenerative diseases of aging such as cancer, cardiovascular disease, cataracts, compromised immune system, rheumatoid arthritis and brain dysfunction. The objective of this study was to determine the variation of Circulating levels of selected antioxidants (enzymic and non enzymic) and oxidative stress marker in younger and older humans. The results showed that a majority of the younger age group participants showed a significant increase in enzymic and nonenzymic antioxidant status and a decrease in oxidative stress when compared with the older age group.
24418297 Cogan syndrome--pathogenesis, clinical variants and treatment approaches. 2014 Apr Non-syphilitic keratitis, coexisting with vestiboloauditory symptoms namely hearing loss and dizziness was first reported by Morgan and Baumgartner back in 1934. It was then ten years later when D.G. Cogan, an ophthalmologist (1908-1993) described 4 patients having the same symptoms but in addition, attacks of vertigo, tinnitus, hearing loss and ocular symptoms. This was published in Archives of Ophthalmology in 1945 and later named Cogan's syndrome (CS). Almost 20years later on, bilateral recurrent episcleritis associated with vestiboloauditory symptoms were defined to be the atypical form of CS occurring in association with rheumatoid arthritis (RA). During the coming two decades the division of CS into typical (classical) and atypical variants, based mainly on the clinical presentation of this syndrome was accepted. Typical CS manifests primarily with interstitial keratitis and hearing loss, whereas atypical CS is usually presented with scleritis, chroiditis and more frequently with systemic inflammation. Approximately, 70% of these patients have systemic manifestations, of which vasculitis is considered the pathogenic mechanism and therefore carries a less favorable prognosis than typical CS. Since then, CS was considered by many to be autoimmune or immune mediated in origin, supported mainly by the beneficial response to corticosteroids. It was only later, using well developed assays such as western blotting and immunofluorescence (IF) when antibodies to inner ear antigens, anti neutrophil cytoplasmic antibodies (ANCA) and anti-endothelial antibodies were found and described to be associated with CS.
24392446 Fish tank granuloma caused by Mycobacterium marinum in two aquarists: two case reports. 2013 Mycobacterium marinum, the cause of chronic systemic infections in fish, occasionally causes granulomatous skin and soft tissue lesions in humans. Cutaneous mycobacterial infection in two patients owing to unusual circumstances is presented in this report. The first patient was infected through improper hygienic behavior, while infection in the second patient was previously misdiagnosed as rheumatoid arthritis and treated with methylprednisolone for a period of three months, which resulted in a rare systemic spread of M. marinum into the bones of the hand, testis, and epididymis. Simultaneously, screening for possible sources of M. marinum infection in patients' aquaria revealed positive fish harboring VNTR profiles identical to those obtained for clinical isolates from patients.
24383985 The role of T cell immunoglobulin and mucin domain-3 in immune thrombocytopenia. 2014 Apr T cell immunoglobulin and mucin domain-3 (TIM-3), originally identified as a T helper (Th) 1-specific type I membrane protein, plays a vital role in Th1 immunity and tolerance induction through interaction with its ligand, galectin-9. The binding of TIM-3 by galectin-9 serves to downregulate Th1 responses. Moreover, the regulatory function of TIM-3 has been extended to other cells, such as Th17 cells, CD4(+) CD25(+) regulatory T cells (Tregs), CD8(+) T cells and certain innate immune cells. Previous studies have acknowledged that the TIM-3 pathway is involved in the pathogenesis of several human autoimmune diseases, such as systemic lupus erythematous, rheumatoid arthritis and aplastic anaemia. Moreover, genetic data suggest a role for TIM-3 in human autoimmune diseases. However, in immune thrombocytopenia (ITP), a common Th1- and possibly Th17-biased autoimmune disorder, the role of TIM-3 has not been explored. Recently, our data have demonstrated that TIM-3 expression is reduced in ITP patients, and we have found a potential link between ITP and the TIM-3 pathway. In this article, we discuss and speculate on the role of the TIM-3 pathway in ITP.
26113889 Neglected rupture of the quadriceps tendon in a patient with chronic renal failure (case r 2014 Spontaneous ruptures of the quadriceps tendon are infrequent injuries, it is seen primarily in patients with predisposing diseases such as gout, rheumatoid arthritis and chronic renal failure. A 32-year-old man had a history of end stage renal disease and received regular hemodialysis treatment for more than 5 years. He was admitted in our service for total functional impotence of the right lower limb with knee pain after a common fall two months ago. The radiogram showed a ''patella baja" with suprapatellar calcifications. The ultrasound and MRI showed an aspect of rupture of the quadriceps tendon in its proximal end with retraction of 3 cm. Quadriceps tendon repair was performed with a lengthening plasty, and the result was satisfactory after a serial rehabilitation program. The diagnosis of quadriceps tendon ruptures needs more attention in patients with predisposing diseases. They should not be unknown because the treatment of neglected lesions is more difficult. We insist on the early surgical repair associated with early rehabilitation that can guarantee recovery of good active extension.
24371251 Connective Tissue Disease-Associated Interstitial Lung Disease: A Focused Review. 2015 Oct The connective tissue diseases (CTDs) are a group of systemic disorders characterized by autoimmunity and autoimmune-mediated organ damage. The lung is a frequent target and all components of the respiratory system are at risk. Interstitial lung disease (ILD) represents a broad group of diffuse parenchymal lung injury patterns characterized by varying degrees of inflammation and fibrosis, is a common manifestation of CTD particularly common in systemic sclerosis, polymyositis/dermatomyositis, and rheumatoid arthritis, and is a leading cause of significant morbidity and mortality. The lung injury patterns of CTD-associated ILD (CTD-ILD) mirror those of idiopathic interstitial pneumonia and may arise at any time during the course of the CTD or may be the first manifestation of CTD. Patients with CTD that present with respiratory failure often present significant diagnostic dilemmas. Thorough and comprehensive assessments to exclude respiratory *infection, acute interstitial pneumonia, medication toxicity, pulmonary embolism, cardiac dysfunction, and diffuse alveolar hemorrhage are the fundamental components for the evaluation of such patients. Furthermore, patients with CTD are also at risk of acute exacerbations of underlying ILD. Acute exacerbations are manifested by subacute respiratory deterioration with worsening hypoxemia in the setting of new radiographic abnormalities. The prognosis of patients with CTD having respiratory failure is often quite poor, highlighting the need for prompt and thorough clinical assessments to determine the underlying etiology and implementation of appropriate therapeutic strategies.