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ID PMID Title PublicationDate abstract
23117570 Can manual ability be measured with a generic ABILHAND scale? A cross-sectional study cond 2012 OBJECTIVES: Several ABILHAND Rasch-built manual ability scales were previously developed for chronic stroke (CS), cerebral palsy (CP), rheumatoid arthritis (RA), systemic sclerosis (SSc) and neuromuscular disorders (NMD). The present study aimed to explore the applicability of a generic manual ability scale unbiased by diagnosis and to study the nature of manual ability across diagnoses. DESIGN: Cross-sectional study. SETTING: Outpatient clinic homes (CS, CP, RA), specialised centres (CP), reference centres (CP, NMD) and university hospitals (SSc). PARTICIPANTS: 762 patients from six diagnostic groups: 103 CS adults, 113 CP children, 112 RA adults, 156 SSc adults, 124 NMD children and 124 NMD adults. PRIMARY AND SECONDARY OUTCOME MEASURES: Manual ability as measured by the ABILHAND disease-specific questionnaires, diagnosis and nature (ie, uni-manual or bi-manual involvement and proximal or distal joints involvement) of the ABILHAND manual activities. RESULTS: The difficulties of most manual activities were diagnosis dependent. A principal component analysis highlighted that 57% of the variance in the item difficulty between diagnoses was explained by the symmetric or asymmetric nature of the disorders. A generic scale was constructed, from a metric point of view, with 11 items sharing a common difficulty among diagnoses and 41 items displaying a category-specific location (asymmetric: CS, CP; and symmetric: RA, SSc, NMD). This generic scale showed that CP and NMD children had significantly less manual ability than RA patients, who had significantly less manual ability than CS, SSc and NMD adults. However, the generic scale was less discriminative and responsive to small deficits than disease-specific instruments. CONCLUSIONS: Our finding that most of the manual item difficulties were disease-dependent emphasises the danger of using generic scales without prior investigation of item invariance across diagnostic groups. Nevertheless, a generic manual ability scale could be developed by adjusting and accounting for activities perceived differently in various disorders.
23023676 Targeting IL-17 and TH17 cells in chronic inflammation. 2012 Oct The key role of interleukin-17 (IL-17) and T helper 17 (T(H)17) cells in tissue inflammation, autoimmunity and host defence led to the experimental targeting of these molecules in mouse models of diseases as well as in clinical settings. Moreover, the demonstration that IL-17 and T(H)17 cells contribute to local and systemic aspects of disease pathogenesis, as well as the finding that the IL-17-T(H)17 cell pathway is regulated by IL-23, prompted the identification of inhibitors. These inhibitors include biotechnology products that target IL-23 as well as the leading member of the IL-17 family, IL-17A, and one of its receptors, IL-17 receptor A. Several clinical trials of these inhibitors are underway, and positive results have been obtained in psoriasis, rheumatoid arthritis and ankylosing spondylitis. This Review focuses on the current knowledge of the IL-17-T(H)17 cell pathway to better understand the positive as well as potential negative consequences of targeting them.
23022892 Peptidylarginine deiminase and protein citrullination in prion diseases: strong evidence o 2013 Jan The post-translational citrullination (deimination) process is mediated by peptidylarginine deiminases (PADs), which convert peptidylarginine into peptidylcitrulline in the presence of high calcium concentrations. Over the past decade, PADs and protein citrullination have been commonly implicated as abnormal pathological features in neurodegeneration and inflammatory responses associated with diseases such as multiple sclerosis, Alzheimer disease and rheumatoid arthritis. Based on this evidence, we investigated the roles of PADs and citrullination in the pathogenesis of prion diseases. Prion diseases (also known as transmissible spongiform encephalopathies) are fatal neurodegenerative diseases that are pathologically well characterized as the accumulation of disease-associated misfolded prion proteins, spongiform changes, glial cell activation and neuronal loss. We previously demonstrated that the upregulation of PAD2, mainly found in reactive astrocytes of infected brains, leads to excessive citrullination, which is correlated with disease progression. Further, we demonstrated that various cytoskeletal and energy metabolism-associated proteins are particularly vulnerable to citrullination. Our recent in vivo and in vitro studies elicited altered functions of enolase as the result of citrullination; these altered functions included reduced enzyme activity, increased protease sensitivity and enhanced plasminogen-binding affinity. These findings suggest that PAD2 and citrullinated proteins may play a key role in the brain pathology of prion diseases. By extension, we believe that abnormal increases in protein citrullination may be strong evidence of neurodegeneration.
22982753 Prostaglandin E2 inhibits IL-23 and IL-12 production by human monocytes through down-regul 2013 Mar The heterodimeric cytokine IL-23 is important for the maintenance of Th17 cells, which are pivotal mediators of autoimmune diseases like rheumatoid arthritis, colitis, and multiple sclerosis. Prostaglandin E2 (PGE2) is a soluble regulator of inflammation that has both pro- and anti-inflammatory properties. PGE2 has been shown to elevate the IL-23 production by dendritic cells (DC). Monocytes are also producers of IL-23 but the effect of PGE2 on IL-23 production by human monocytes has hardly been investigated. We show here that PGE2 blocks the production of IL-23 by LPS-stimulated monocytes in an IL-10 and IL-1β independent manner. This effect was due to the down-regulation of the p40 subunit of IL-23 on mRNA and protein level. The p40 subunit is shared by IL-12 and, consistently, PGE2 also lowered the IL-12 production by monocytes. These effects of PGE2 were cAMP-dependent since the cAMP enhancer forskolin strongly reduced IL-23 and IL-12 production by monocytes. Taken together, PGE2 acts in an anti-inflammatory manner by lowering IL-23 production by monocytes while it has the opposite effect in DC. Our data may help to reconcile controversial point of views on the pro- and anti-inflammatory nature of PGE2 by making a strong case for a cell type-dependent function.
22956345 Use of vitamin D in various disorders. 2013 Mar Approximately 1 billion people worldwide have been identified as vitamin D deficient in the 21st century, and the number is on the rise; non-classical actions of vitamin D were initially recognized around 30 y ago when receptors for vitamin D were detected in neoplastic cells lines. The aim of this review is to provide a brief overview of the non-classical actions of vitamin D. Reports describing the associations of non skeletal actions of vitamin D, especially pertaining to the immune system, inflammatory disorders, cancers and cardiovascular disease have been summarized in this paper. Reports support a role for the active form of vitamin D in mediating normal function of both the innate and adaptive immune systems. Studies also suggest a link between vitamin D deficiency and autoimmune diseases, such as rheumatoid arthritis, systemic sclerosis, systemic lupus erythematosus and type 1 diabetes. There is believed to be an inverse association between serum 25-hydroxyvitamin D concentrations and the incidence of colorectal cancer, sporadic colorectal adenoma and breast cancer. Vitamin D deficiency has been linked with various cardiovascular diseases such as hypertension, myocardial infarction, and stroke. Several epidemiological and genetic studies suggest a strong association between vitamin D and non skeletal acute and chronic disorders. However, currently, robust clinical data are still lacking to support raising intake requirements and target vitamin D plasma levels. Nonetheless, the high prevalence of vitamin D deficiency is alarming and requires implementation of clear supplementation guidelines.
22950481 Good function after shoulder arthroplasty. 2012 Oct BACKGROUND AND PURPOSE: Different results after shoulder arthroplasty have been found for different diagnostic groups. We evaluated function, pain, and quality of life after shoulder arthroplasty in 4 diagnostic groups. PATIENTS AND METHODS: Patients with shoulder arthroplasties registered in the Norwegian Arthroplasty Register from 1994 through 2008 were posted a questionnaire in 2010. 1,107 patients with rheumatoid arthritis (RA), osteoarthritis (OA), acute fracture (AF), or fracture sequela (FS) returned completed forms (65% response rate). The primary outcome measure was the Oxford shoulder score (OSS), which assesses symptoms and function experienced by the patient on a scale from 0 to 48. A secondary outcome measure was the EQ-5D, which assesses life quality. The patients completed a questionnaire concerning symptoms 1 month before surgery, and another concerning the month before they received the questionnaire. RESULTS: Patients with RA and OA had the best results with a mean improvement in OSS of 16 units, as opposed to 11 for FS patients. Both shoulder pain and function had improved substantially. The change in OSS for patients with AF was negative (-11), but similar end results were obtained for AF patients as for RA and OA patients. Quality of life had improved in patients with RA, OA, and FS. INTERPRETATION: Good results in terms of pain relief and improved level of function were obtained after shoulder arthroplasty for patients with RA, OA, and-to a lesser degree-FS. A shoulder arthropathy had a major effect on quality of life, and treatment with shoulder replacement substantially improved it.
22905729 Incorporating gold into nanocrystalline silver dressings reduces grain boundary size and m 2013 Dec Nanocrystalline silver dressings are widely known to be potent antimicrobial and anti-inflammatory agents and have long been used to treat topical wounds. Gold is known to be a strong anti-inflammatory agent and has been used in the treatment of rheumatoid arthritis for >70 years. The purpose of this work was to study the effect of incorporating gold into nanocrystalline silver dressings from antimicrobial and anti-inflammatory perspectives. Gold and silver dressing alloys were created by direct current magnetron sputtering and compared with pure silver nanocrystalline dressings using conventional biological (log reduction and corrected zone of inhibition) and physical (X-ray diffraction, X-ray photoelectron spectroscopy, energy-dispersive X-ray spectroscopy, atomic absorption spectroscopy, atomic force microscopy and scanning electron microscopy) characterisation techniques. While the gold/silver dressings were slightly weaker antimicrobials than the pure silver nanocrystalline structures, the addition of gold to the nanostructure reduces the minimum crystallite size from 17 to 4 nm. This difference increases the number of grain boundary atoms from 12% to 40% which could augment the anti-inflammatory properties of the dressings. The formation of gold oxide (Au2O3) was thought to be responsible for the observed decrease in crystallite size.
22747766 Lay Person Slit Lamp Detection of Iritis in Absence of an Eye MD: Test of a Portable Model 2012 BACKGROUND: Asymptomatic - or minimally so, eye conditions like uveitis, iritis, and glaucoma are silent stealthily blinding diseases, especially when present in children. The iritis that accompanies Juvenile Idiopathic or Rheumatoid Arthritis (JIA or JRA) is characteristically asymptomatic. Children with these must be examined regularly and routinely(see Reference 1 and Table) on an opthalmologic biomicroscopic slit lamp for the microscopic cells (and aqueous flare) which occurr in the anterior chamber of the eye, signaling the presence of iritis, and an immediate need for anti-inflammatory agents. Such an exam is also indicated when the so afflicted develop most any symptoms of a new or recurrent eye problem. Slit lamp iritis determination remains challenging. It virtually requires a major, not portable, table mounted and expensive biomicroscope. And the examiner designated in schedules (1) is a trained ophthalmolgist,, an "Eye M.D.". Both. There are times and places throughout the world where and when a slit lamp may be available but there is no Eye MD (or qualified ophthalmic technician or assistant) available in a timely manner to timely examine for iritis when such is needed as noted. However, there are theoretical advantages if a parent could detect iritis in their J I A child if a slit lamp were available, if they had been trained to use it and recognize iritis cells and flare. METHODS: A portable model of varying iritis severity was developed. Parents of JIA patients were instructed on slit lamp use and then attempted to match unknown models of iritis severity with known training models of varying concentrations of cells and flare. RESULTS: Twelve parents ranked the 5 unknowns with an average summed deviation from expected of 2.2 +/-2 grade levels (out of 12). This was a good and useful degree of training. CONCLUSION: We were able to teach lay adults to match a model of iritis severity on a slit lamp. We would suggest that where needed, they could provide urgent and more convenient and faster diagnosis and treatment of recurrent iritis and also augment recommended scheduled Eye MD screening for iritis in JIA patients providing an effectively higher level of care, quality of life, and reduction in loss of vision for JIA victims at lower cost and greater facility for the patients, their caregivers and society as a whole.
22684508 A miR-19 regulon that controls NF-κB signaling. 2012 Sep Fine-tuning of inflammatory responses by microRNAs (miRNAs) is complex, as they can both enhance and repress expression of pro-inflammatory mediators. In this study, we investigate inflammatory responses following global miRNA depletion, to better define the overall contribution of miRNAs to inflammation. We demonstrate that miRNAs positively regulate Toll-like receptor signaling using inducible Dicer1 deletion and global miRNA depletion. We establish an important contribution of miR-19b in this effect, which potentiates nuclear factor-κB (NF-κB) activity in human and mouse cells. Positive regulation of NF-κB signaling by miR-19b involves the coordinated suppression of a regulon of negative regulators of NF-κB signaling (including A20/Tnfaip3, Rnf11, Fbxl11/Kdm2a and Zbtb16). Transfection of miR-19b mimics exacerbated the inflammatory activation of rheumatoid arthritis primary fibroblast-like synoviocytes, demonstrating its physiological importance in the pathology of this disease. This study constitutes, to our knowledge, the first description of a miR-19 regulon that controls NF-κB signaling, and suggests that targeting this miRNA and linked family members could regulate the activity of NF-κB signaling in inflammation.
22514678 Acquisition of complement inhibitor serine protease factor I and its cofactors C4b-binding 2012 Infection with the Gram-negative pathogen Prevotella intermedia gives rise to periodontitis and a growing number of studies implies an association of P. intermedia with rheumatoid arthritis. The serine protease Factor I (FI) is the central inhibitor of complement degrading complement components C3b and C4b in the presence of cofactors such as C4b-binding protein (C4BP) and Factor H (FH). Yet, the significance of complement inhibitor acquisition in P. intermedia infection and FI binding by Gram-negative pathogens has not been addressed. Here we show that P. intermedia isolates bound purified FI as well as FI directly from heat-inactivated human serum. FI bound to bacteria retained its serine protease activity as shown in degradation experiments with (125)I-labeled C4b. Since FI requires cofactors for its activity we also investigated the binding of purified cofactors C4BP and FH and found acquisition of both proteins, which retained their activity in FI mediated degradation of C3b and C4b. We propose that FI binding by P. intermedia represents a new mechanism contributing to complement evasion by a Gram-negative bacterial pathogen associated with chronic diseases.
22463930 Implementing changes in clinical practice to improve the management of Crohn's disease. 2012 Feb The introduction of anti-tumour necrosis factor therapies has provided highly effective treatments for Crohn's disease, making it possible to significantly improve the prognosis of patients. However, neither conventional non-biological therapies nor anti-tumour necrosis factor therapies are routinely used to optimum effect. There are several reasons for this, including a lack of specific evidence to guide common clinical questions and a lack of clearly defined treatment targets. This paper suggests some simple changes to the management of Crohn's disease that have the potential to significantly improve patient outcomes. A new treatment target, 'deep remission', which includes mucosal healing as well as clinical remission, may be the first step in defining the successful treatment of Crohn's disease; early clinical studies have demonstrated that this is a readily achievable target. Initiating appropriate treatment early can increase clinical remission rates, improve steroid sparing, induce mucosal healing and prevent structural bowel damage, whereby reducing the need for hospitalization and surgery. There are also clear indications that modifying treatment based on regular objective assessments of disease activity to provide tight disease control can improve patient outcomes in a similar way to that observed in rheumatoid arthritis. These simple changes to management strategy appear to allow the full potential of available treatments to be realized. Clinical studies to further define optimized treatment strategies for Crohn's disease are underway and will provide future direction.
22432804 B cells as effectors and regulators of autoimmunity. 2012 Aug A classic understanding of the interplay between B and T cell components of the immune system that drive autoimmunity, where B cells provide an effector function, is represented by systemic lupus erythematosus (SLE), an autoimmune condition characterised by the production of auto-antibodies. In SLE, CD4+T cells provide cognate help to self-reactive B cells, which in turn produce pathogenic auto-antibodies (1). Thus, B cells act as effectors by producing auto-antibody aided by T cell help such that B and T cell interactions are unidirectional. However, this paradigm of B and T cell interactions is challenged by new clinical data demonstrating that B cell depletion is effective for T cell mediated autoimmune diseases including type I diabetes mellitus (T1D) (2), rheumatoid arthritis (3), and multiple sclerosis (4). These clinical data indicate a model whereby B cells can influence the developing autoimmune T cell response, and therefore act as effectors, in ways that extend beyond the production of autoantibody (5). In this review by largely focusing on type I diabetes we will develop a hypothesis that bi-directional B and T interactions control the course of autoimmunity.
22374720 Toxicity of non-steroidal anti-inflammatory drugs: a review of melatonin and diclofenac so 2012 Apr Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for the purpose of anti-inflammation, antipyretic, and analgesia. For this aim, they are used for the alleviation of pain, fever, and inflammation associated with rheumatoid arthritis, sports injuries, and temporary pain. However, treatment with NSAIDs may be accompanied by adverse effects such as gastrointestinal damage and platelet dysfunction. As with the other NSAIDs, diclofenac sodium (sodium-(o-((2,6-dichlorophenyl)-amino)-phenyl)-acetate) (DS), an NSAID, has potent anti-inflammatory, analgesic, and antipyretic effects. However, treatment with DS may cause some adverse cerebral and cerebellar effects such as convulsions, disorientation, hallucination, and loss of consciousness. Melatonin (MLT) is a free-radical scavenger and possesses antioxidant properties. It has been reported to easily cross the blood-brain barrier, and is found in high concentrations in the brain after exogenous administration. It is also a neuroprotector in a wide range of conditions affecting the central nervous system CNS due to its free-radical scavenging activities and lipophilic-hydrophilic properties. Neuroprotective actions of MLT have been discovered in both in vitro and in vivo, and are a powerful scavenger of oxygen and nitrogen free radicals. Thus, MLT can protect the cell membrane, organelles, and core against free-radical damage. Therefore, it has been postulated that exogenous MLT acts as a neuroprotector contrary to DS neurotoxicity. In this review, we aimed to discuss the possible neuroprotective effects of MLT on DS toxicity.
22318811 Role of inflammation in the pathogenesis of arterial stiffness. 2012 Mar Increased arterial stiffness is an independent predictor of cardiovascular disease independent from blood pressure. Recent studies have shed new light on the importance of inflammation on the pathogenesis of arterial stiffness. Arterial stiffness is associated with the increased activity of angiotensin II, which results in increased NADPH oxidase activity, reduced NO bioavailability and increased production of reactive oxygen species. Angiotensin II signaling activates matrix metalloproteinases (MMPs) which degrade TGFβ precursors to produce active TGFβ, which then results in increased arterial fibrosis. Angiotensin II signaling also activates cytokines, including monocyte chemoattractant protein-1, TNF-α, interleukin-1, interleukin-17 and interleukin- 6. There is also ample clinical evidence that demonstrates the association of inflammation with increased arterial stiffness. Recent studies have shown that reductions in inflammation can reduce arterial stiffness. In patients with rheumatoid arthritis, increased aortic pulse wave velocity in patients was significantly reduced by anti tumor necrosis factor-α therapy. Among the major classes of anti hypertensive drugs, drugs that block the activation of the RAS system may be more effective in reducing the progression of arterial stiffness. Thus, there is rationale for targeting specific inflammatory pathways involved in arterial stiffness in the development of future drugs. Understanding the role of inflammation in the pathogenesis of arterial stiffness is important to understanding the complex puzzle that is the pathophysiology of arterial stiffening and may be important for future development of novel treatments.
22313365 Characterization of and functional evidence for Ste27 of Streptomyces sp. 139 as a novel s 2012 May 1 Ebosin, a novel exopolysaccharide produced by Streptomyces sp. 139, has remarkable anti-rheumatoid arthritis activity in vivo and its biosynthesis gene cluster (ste) consists of 27 ORFs (open reading frames). The present paper reports our study of the protein product encoded by ste27. Database searching reveals the homology of Ste27 with some spermidine/spermine acetyltransferases. To confirm the prediction, the ste27 gene was cloned and expressed in Escherichia coli BL21(DE3) cells and recombinant Ste27 was purified. The following enzymatic analysis revealed its ability of transferring the acetyl group from acetyl-CoA to spermidine and spermine, with spermidine being the preferred substrate. Ste27 can acetylate the N1, N4 and N8 positions on spermidine. The Km values of Ste27 were determined for spermidine and spermine, as well as for acetyl-CoA, poly-L-lysine and glucosamine 6-phosphate. Upon gene knockout, the exopolysaccharide-27m produced by the mutant strain Streptomyces sp. 139 (ste27-), compared with Ebosin, exhibited a significantly reduced binding activity to the interleukin-1 receptor. After gene complementation, the binding activity was partially restored. This demonstrated that the ste27 gene is involved in the biosynthesis of Ebosin. Molecular modelling was also carried out to predict the binding mode of Ste27 with acetyl-CoA, spermidine or spermine.
22250650 Adenosine deaminase in the modulation of immune system and its potential as a novel target 2012 Jun The adenosine pathway is a powerful evolutionarily selected mechanism aimed at a fine modulation of inflammatory responses and protection of tissues from injuries. Adenosine exerts its modulatory effects via interaction with G protein-coupled receptors, designated as A(1), A(2A), A(2B) and A(3). In this regard, extracellular adenosine concentrations are critical in determining its ability of regulating several biological functions. The levels achieved by adenosine in close proximity of its receptors are strictly regulated by a variety of dynamic mechanisms, including intracellular and extracellular biosynthesis, transport and metabolism, based on tissue energy status. In this context, the catabolic enzyme adenosine deaminase (ADA) represents a critical checkpoint in the regulation of extracellular adenosine levels and, consequently, in the control of receptor stimulation, thus playing a pivotal role in the modulation of purinergic responses to several pathophysiological events, such as chronic pulmonary diseases, rheumatoid arthritis, inflammatory bowel diseases and sepsis. This article reviews current data on the role played by ADA in the regulation of immune system activity through its modulation of adenosine pathways. Particular attention has been paid to the involvement of ADA in the pathophysiology of relevant inflammatory diseases. In addition, the interest in designing and developing novel ADA inhibitors, as new tools potentially useful for the therapeutic management of inflammatory disorders, has been discussed.
22024437 Increased levels of anti-glycan antibodies in patients with cystic fibrosis. 2011 Sep 12 BACKGROUND: The prevalence of Crohn's disease (CD) is increased in patients with cystic fibrosis (CF). Anti-Saccharomyces cerevisiae antibodies (ASCA) have been suggested as a screening tool to detect CD in CF. Recently, several new anti-glycan antibodies have been reported in CD. - MATERIALS AND METHODS: The sera of 119 CF patients of various age groups were prospectively screened for ASCA type IgG (gASCA), anti-laminaribioside carbohydrate IgG antibodies (ALCA), anti-chitobioside carbohydrate IgA antibodies (ACCA), and anti-mannobioside carbohydrate IgG antibodies (AMCA). The frequency of these anti-glycan antibodies was then compared in patients with CD, ulcerative colitis, rheumatoid arthritis and healthy volunteers. - RESULTS: A significant number of CF patients were positive for gASCA (51.3% (41.6-60.6)) and up to three other anti-glycan antibodies concurrently. Serum levels of anti-glycan antibodies in CF and CD were not related to parameters of inflammation. Despite the well-documented difference in clinical course between male and female CF patients no gender difference of anti-glycan antibodies was found. In contrast, there was a significant positive correlation between anti-glycan markers and age in CF patients. - CONCLUSIONS: Our findings demonstrate for the first time the increased frequency of a panel of anti-glycan antibodies in CF and provide a link between the presence of these serological biomarkers and patient's age. Anti-glycan antibody profiling may therefore become a valuable tool in the care of patients with CF.
21808653 Anti-Inflammatory Potential of Ethanolic Leaf Extract of Eupatorium adenophorum Spreng. Th 2011 Search for a novel anti-inflammatory agent from a herbal source, such as Eupatorium adenophorum Spreng., a plant from the Eastern Himalayas, is of prime interest in the present investigation. Inflammation causes tissue destruction and development of diseases such as asthma, rheumatoid arthritis, and so forth. The ethanolic leaf extract of E. adenophorum (EEA) was administered intravenously and in other cases topically at the site of delayed type hypersensitivity (DTH) reaction in mouse foot paw induced with dinitrofluorobenzene. EEA can effectively inhibit DTH reaction and bring back normalcy to the paw much earlier than the controls. Efficacy of EEA on regulatory mechanisms for inflammation has also been considered. Intravenous administration of EEA increased the number of CD4(+) T cells in spleen and tumor necrosis factor (TNF)-α in serum of DTH mice. Initially it was difficult to reconcile with the anti-inflammatory role of EEA and simultaneous induction of TNF-α, an established pro-inflammatory cytokine. EEA induces higher expression of TNF-α gene and amount of the cytokine in serum. We discussed the other role of TNF-α, its involvement in repairing tissue damage incurred in course of inflammatory reaction. EEA also induces TGF-β encoding a cytokine involved in tissue repair mechanism. EEA inhibits expression of another pro-inflammatory cytokine gene IL-1β and downregulates cycloxygenase 2 (COX2) gene responsible for metabolism of inflammatory mediators like prostaglandins. Furthermore, anti-inflammatory role of EEA is also revealed through its inhibition of hydroxyl radical generation. Notably EEA does not necessarily affect the expression of other inflammation-related genes such as IL-6, IL-10 and IKK. The present study reports and analyzes for the first time the anti-inflammatory property of the leaf extract of E. adenophorum.
21733728 Misleading abstract conclusions in randomized controlled trials in rheumatology: compariso 2012 May INTRODUCTION: Readers of scientific articles often read only the abstract and its conclusions because of lack of time or of access to the full-length articles. OBJECTIVES: To assess the prevalence of misleading conclusions in abstracts of randomized controlled trials (RCTs) in rheumatology, determine whether trials are registered and whether abstract conclusions are based on the primary outcome (PO), and identify the predictors of misleading abstract conclusions. METHODS: We searched Medline, Embase and the Cochrane Collaboration for reports of RCTs assessing rheumatoid arthritis, osteoarthritis or spondylarthropathies published between January 2006 and April 2008. Abstract conclusions were misleading if: the PO was not reported in the conclusion; the conclusions were based on only a secondary outcome or subgroup results; the results and conclusions were in disagreement; negative results were suggested as equivalent, or if there was no discussion of benefits and risks in cases of serious adverse events. RESULTS: Of the 144 reports selected, we focused on the 105 articles containing a clear PO. Twenty-four reports (23%) contained misleading conclusions. Lack of PO reporting (n=10) and conclusions disagreeing with article results (n=7) were the most frequent reasons. Nineteen out of 144 (13.2%) declared study registration with clear and similar registered and published POs and no misleading abstract conclusions. Reports of negative results showed a higher frequency of misleading conclusions as did those assessing osteoarthritis. On multivariable analysis, only negative results predicted misleading abstract conclusions (OR=9.58 [3.20-28.70]). CONCLUSIONS: Almost one-quarter of these RCT in rheumatology had misleading conclusions in the abstract, especially those with negative results.
21565278 Vascular-derived reactive oxygen species for homeostasis and diseases. 2011 Aug 1 Numerous basic and clinical studies have clearly identified that reactive oxygen species (ROS, i.e., H(2)O(2), O(2)(-), and ()OH) has a major role in the development of cardiovascular diseases. However, we still have no strong therapeutic strategy for clinical benefits of antioxidant administration. One potential reason for those could be a crucial role of ROS for intracellular signaling pathways that is important for vascular functions in a very low concentration. ROS contributes to the physiology and pathology of vasculature, but precise molecular regulations remain elusive. The mechanism how excessive ROS (oxidative stress) deteriorate vascular function and promote vascular diseases has not been clearly elucidated. Cyclophilin A (CyPA) has been studied as a multifunctional protein that is upregulated in a variety of inflammatory conditions, such as rheumatoid arthritis, autoimmune disease, and cancer. CyPA has been classified as an immunophilins and has a variety of intracellular functions including intracellular signaling, protein trafficking, and the regulating other proteins. Besides intracellular functions, we revealed that CyPA is a secreted molecule that has a pathological role in the cardiovascular system. CyPA has emerged as a potential biomarker and mediator of cardiovascular disease.