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ID PMID Title PublicationDate abstract
24717145 Cloud computing for detecting high-order genome-wide epistatic interaction via dynamic clu 2014 Apr 10 BACKGROUND: Taking the advantage of high-throughput single nucleotide polymorphism (SNP) genotyping technology, large genome-wide association studies (GWASs) have been considered to hold promise for unravelling complex relationships between genotype and phenotype. At present, traditional single-locus-based methods are insufficient to detect interactions consisting of multiple-locus, which are broadly existing in complex traits. In addition, statistic tests for high order epistatic interactions with more than 2 SNPs propose computational and analytical challenges because the computation increases exponentially as the cardinality of SNPs combinations gets larger. RESULTS: In this paper, we provide a simple, fast and powerful method using dynamic clustering and cloud computing to detect genome-wide multi-locus epistatic interactions. We have constructed systematic experiments to compare powers performance against some recently proposed algorithms, including TEAM, SNPRuler, EDCF and BOOST. Furthermore, we have applied our method on two real GWAS datasets, Age-related macular degeneration (AMD) and Rheumatoid arthritis (RA) datasets, where we find some novel potential disease-related genetic factors which are not shown up in detections of 2-loci epistatic interactions. CONCLUSIONS: Experimental results on simulated data demonstrate that our method is more powerful than some recently proposed methods on both two- and three-locus disease models. Our method has discovered many novel high-order associations that are significantly enriched in cases from two real GWAS datasets. Moreover, the running time of the cloud implementation for our method on AMD dataset and RA dataset are roughly 2 hours and 50 hours on a cluster with forty small virtual machines for detecting two-locus interactions, respectively. Therefore, we believe that our method is suitable and effective for the full-scale analysis of multiple-locus epistatic interactions in GWAS.
24292093 Fli1 deficiency contributes to the suppression of endothelial CXCL5 expression in systemic 2014 May CXCL5 is a member of CXC chemokines with neutrophilic chemoattractant and pro-angiogenic properties, which has been implicated in the pathological angiogenesis of rheumatoid arthritis and inflammatory bowel diseases. Since aberrant angiogenesis is also involved in the developmental process of systemic sclerosis (SSc), we herein measured serum CXCL5 levels in 63 SSc and 18 healthy subjects and investigated their clinical significance and the mechanism explaining altered expression of CXCL5 in SSc. Serum CXCL5 levels were significantly lower in SSc patients than in healthy subjects. In diffuse cutaneous SSc (dcSSc), serum CXCL5 levels were uniformly decreased in early stage (<1 year) and positively correlated with disease duration in patients with disease duration of <6 years. In non-early stage dcSSc (≥1 year), decreased serum CXCL5 levels were linked to the development of digital ulcers. Consistently, the expression levels of CXCL5 proteins were decreased in dermal blood vessels of early stage dcSSc. Importantly, Fli1 bound to the CXCL5 promoter and its gene silencing significantly suppressed the CXCL5 mRNA expression in human dermal microvascular endothelial cells. Furthermore, endothelial cell-specific Fli1 knockout mice, an animal model of SSc vasculopathy, exhibited decreased CXCL5 expression in dermal blood vessels. Collectively, these results indicate that CXCL5 is a member of angiogenesis-related genes, whose expression is suppressed at least partially due to Fli1 deficiency in SSc endothelial cells. Since Fli1 deficiency is deeply related to aberrant angiogenesis in SSc, it is plausible that serum CXCL5 levels inversely reflect the severity of SSc vasculopathy.
24278115 Non-invasive imaging of tumors by monitoring autotaxin activity using an enzyme-activated 2013 Autotaxin (ATX), an autocrine motility factor that is highly upregulated in metastatic cancer, is a lysophospholipase D enzyme that produces the lipid second messenger lysophosphatidic acid (LPA) from lysophosphatidylcholine (LPC). Dysregulation of the lysolipid signaling pathway is central to the pathophysiology of numerous cancers, idiopathic pulmonary fibrosis, rheumatoid arthritis, and other inflammatory diseases. Consequently, the ATX/LPA pathway has emerged as an important source of biomarkers and therapeutic targets. Herein we describe development and validation of a fluorogenic analog of LPC (AR-2) that enables visualization of ATX activity in vivo. AR-2 exhibits minimal fluorescence until it is activated by ATX, which substantially increases fluorescence in the near-infrared (NIR) region, the optimal spectral window for in vivo imaging. In mice with orthotopic ATX-expressing breast cancer tumors, ATX activated AR-2 fluorescence. Administration of AR-2 to tumor-bearing mice showed high fluorescence in the tumor and low fluorescence in most healthy tissues with tumor fluorescence correlated with ATX levels. Pretreatment of mice with an ATX inhibitor selectively decreased fluorescence in the tumor. Together these data suggest that fluorescence directly correlates with ATX activity and its tissue expression. The data show that AR-2 is a non-invasive and selective tool that enables visualization and quantitation of ATX-expressing tumors and monitoring ATX activity in vivo.
23962530 Factors predictive of the perceived osteoporosis-fracture link in fragility fracture patie 2013 Oct OBJECTIVE: Given the asymptomatic nature of osteoporosis, a fragility fracture provides an opportunity to make the issue of osteoporosis relevant to patients. Patients who link their fragility fracture with osteoporosis are more likely to initiate osteoporosis treatment, yet to date, we know little about who is likely to make this link. This study examined whether demographic, health, and osteoporosis belief factors predicted a perceived link between a fragility fracture and osteoporosis. STUDY DESIGN: This longitudinal cohort study analyzed baseline and follow up data collected as part of a provincial osteoporosis screening initiative targeting fragility fracture patients. Logistic regression analysis was used to examine the relationship between hypothesized predictors and the outcome. MAIN OUTCOME MEASURE: Patient perception of the osteoporosis-fracture link at follow up. RESULTS: At baseline, 93% (1615/1735) of patients did not believe their fracture could have been caused by osteoporosis. Of these, only 8.2% changed this perception at follow up. Adjusted analyses showed that baseline characteristics associated with making the osteoporosis-fracture link at follow up were: a previous fracture (odds ratio (OR) 1.7, confidence interval (CI) 1.2-2.6), perception of osteoporosis pharmacotherapy benefits OR 1.2 (CI 1.0-1.5), diagnosis of rheumatoid arthritis OR 2.6 (CI 1.4-4.9) and the perception of bones as "thin" OR 8.2 (CI 5.1-13.1). CONCLUSION: These results shed more light on patient-level barriers to osteoporosis management following an osteoporosis educational programme. They may be used to identify patients less likely to make the link between their fracture and osteoporosis and to inform interventions for this patient group.
23958959 Brain-reactive IgG correlates with autoimmunity in mothers of a child with an autism spect 2013 Nov It is believed that in utero environmental factors contribute to autism spectrum disorder (ASD). The goal of this study was to demonstrate, using the largest cohort reported so far, that mothers of an ASD child have an elevated frequency of anti-brain antibodies and to assess whether brain reactivity is associated with an autoimmune diathesis of the mother. We screened plasma of 2431 mothers of an ASD child from Simon Simplex Collection and plasma of 653 unselected women of child-bearing age for anti-brain antibodies using immunohistology on mouse brain. Positive and negative plasma from mothers with an ASD child were analyzed for anti-nuclear antibodies and for autoimmune disorders. Mothers of an ASD child were four times more likely to harbor anti-brain antibodies than unselected women of child-bearing age (10.5 vs 2.6%). A second cohort from The Autism Genetic Resource Exchange with multiplex families displayed an 8.8% prevalence of anti-brain antibodies in the mothers of these families. Fifty-three percent of these mothers with anti-brain antibodies also exhibited anti-nuclear autoantibodies compared with 13.4% of mothers of an ASD child without anti-brain antibodies and 15% of control women of child-bearing age. The analysis of ASD mothers with brain-reactive antibodies also revealed an increased prevalence of autoimmune diseases, especially rheumatoid arthritis and systemic lupus erythematosus. This study provides robust evidence that brain-reactive antibodies are increased in mothers of an ASD child and may be associated with autoimmunity. The current study serves as a benchmark and justification for studying the potential pathogenicity of these antibodies on the developing brain. The detailed characterization of the specificity of these antibodies will provide practical benefits for the management and prevention of this disorder.
23952468 Complex cases in primary care: report of a CME-certified series addressing patients with m 2013 Sep AIM: To assess whether participation in a series of continuing medical education-certified activities presenting complicated case scenarios resulted in evidence-based decision making for patients with chronic comorbid conditions. METHODS: A series of interactive live workshops and online case studies presented evidence-based, practical information addressing the care of patients with multiple chronic diseases to primary care physicians. Clinical case vignettes were used to assess workshop participant knowledge and competence. Results were compared with those of matched non-participant controls. Online participants were surveyed to evaluate immediate knowledge gains from the activity. RESULTS: Overall, physician workshop participants were 27% more knowledgeable of evidence-based treatment decisions. Participants were more likely to refer a patient with rheumatoid arthritis to a rheumatologist (57% vs. 36%; p = 0.035) and showed better recognition of medications that can contribute to overactive bladder symptoms (36% vs. 18%; p = 0.043) compared with non-participant controls. Non-significant differences in favour of participants included evidence-based decisions regarding the management of osteoporosis, attention deficit hyperactivity disorder in adults and type 2 diabetes mellitus in adolescents. Online participants demonstrated significant knowledge gains (p < 0.001) on 17 of 18 assessment questions across all therapeutic areas. DISCUSSION: Chronic comorbid conditions afflict a sizable minority of patients. However, specific recommendations and education surrounding patient management are often overlooked because of the inherent difficulty of treating this group. Highly interactive educational activities can improve participant knowledge and competency in treating these patients by providing an opportunity to interact with faculty experts, receive immediate feedback and practice new skills. CONCLUSION: Interactive educational activities that discuss complicated case scenarios can improve participant application of evidence-based medicine for patients with multiple chronic comorbidities.
23889005 Neurological and psychiatric adverse events with prucalopride: case report and possible me 2013 Dec WHAT IS KNOWN AND OBJECTIVE: Chronic constipation is very frequent in the general population. Although usually considered banal, this disorder has considerable personal, social and healthcare impact. Several studies have shown that the psychological impact exceeds that caused by rheumatoid arthritis or haemodialysis. Recently, prucalopride, a highly selective 5-HT4 receptor agonist has been shown to improve the symptoms of chronic constipation and to have a beneficial effect on social and healthcare impact. The drug was approved by the European Medicine Agency, in 2009 at a dose of 2 mg/day, 'for symptomatic treatment of chronic constipation in women in whom laxatives fail to provide adequate relief'. Neurological side effects or psychiatric disorders have not been reported previously with prucalopride. We present the case of a 61-year-old woman, who developed such adverse effects when given prucalopride for the treatment for chronic constipation. CASE SUMMARY: A few hours after oral administration of this drug at therapeutic dose (2 mg/day), the patient experienced life-threatening neurological effects that included visual hallucination, loss of balance and memory, disorientation, exhaustion and suicidal ideation. Analysis with the Naranjo algorithm indicated a 'possible' relationship between prucalopride and these disorders. WHAT IS NEW AND CONCLUSION: This is the first report of prucalopride-induced neurological side effects and psychiatric disorders with prucalopride. The absence of other similar reports suggests that prucalopride rarely causes these adverse effects.
23856277 Ultrasound in rheumatology: where are we and where are we going? 2014 Jan OBJECTIVE: To know rheumatologists' opinion on the usefulness of ultrasound in diagnostic and therapeutic decision making as applied to rheumatic diseases. MATERIAL AND METHODS: A National survey was sent to all rheumatology units in hospitals with at least 200 beds. The questionnaire included: a) general data, b) purpose and most common areas of ultrasound exploration and c) assessment of the usefulness of ultrasound in routine clinical practice in general and in some rheumatologic diseases. RESULTS: One-hundred-sixty-nine out of 234 rheumatology units contacted answered the questionnaire. The utility in routine clinical practice was scored at 7.8 (scale 0-10) and ultrasound was integrated in making diagnostic and therapeutic decisions. Half of the indications (50.9%) were ultrasound related to the process of diagnosis of diseases or treatment decision making (monitoring synovitis 14.6%, guided puncture 11.4%, early detection of joint erosion or synovitis 10.3%, early detection of enthesopathy 5.9%, carpal tunnel syndrome or other peripheral neuropathies 3.4%, detection of uric acid or pyrophosphate deposits 3%, vasculitis 1% and others 1.1%. On a 1-5 Likert, scale most of the answers support the use of ultrasound in clinical practice, especially in diagnostic and therapeutic decision making for detection of subclinical synovitis, erosions and treatment decisions in rheumatoid arthritis, enthesitis diagnosis, crystal diseases, polymyalgia rheumatica and giant cell arteritis. CONCLUSIONS: Ultrasound is becoming a useful tool integrated into clinical practice and is linked to the decision making processes in the areas of diagnosis, activity and treatment.
23652591 A 'toothache tree' alkylamide inhibits Aδ mechanonociceptors to alleviate mechanical pain 2013 Jul 1 In traditional medicine, the 'toothache tree' and other plants of the Zanthoxylum genus have been used to treat inflammatory pain conditions, such as toothache and rheumatoid arthritis. Here we examined the cellular and molecular mechanisms underlying the analgesic properties of hydroxy-α-sanshool, the active alkylamide produced by Zanthoxylum plants. Consistent with its analgesic effects in humans, sanshool treatment in mice caused a selective attenuation of mechanical sensitivity under naïve and inflammatory conditions, with no effect on thermal sensitivity. To elucidate the molecular mechanisms by which sanshool attenuates mechanical pain, we performed single fibre recordings, calcium imaging and whole-cell electrophysiology of cultured sensory neurons. We found that: (1) sanshool potently inhibits Aδ mechanonociceptors that mediate both sharp acute pain and inflammatory pain; (2) sanshool inhibits action potential firing by blocking voltage-gated sodium currents in a subset of somatosensory neurons, which express a unique combination of voltage-gated sodium channels; and (3) heterologously expressed Nav1.7 is most strongly inhibited by sanshool as compared to other sodium channels expressed in sensory neurons. These results suggest that sanshool targets voltage-gated sodium channels on Aδ mechanosensory nociceptors to dampen excitability and thus induce 'fast pain' analgesia.
23574996 Four cases of invasive anterior mediastinal tumors definitively diagnosed by the chamberla 2014 Percutaneous needle biopsy, commonly used for a definitive diagnosis of anterior mediastinal tumors, is sometimes inconclusive because of the small size of the biopsy specimens and the histologic heterogeneity of the tumors. We herein report 4 cases of invasive anterior mediastinal tumors, in which the definitive diagnosis was made using the Chamberlain procedure. [Case 1] A 33-year-old man was found to have an anterior mediastinal tumor on chest X-ray and computed tomography (CT). The tumor was histologically diagnosed as thymic carcinoma (squamous cell carcinoma) using the Chamberlain procedure. After 3 courses of preoperative chemotherapy, the patient underwent surgery and postoperative radiotherapy. He remains well, 35 months after the biopsy. [Case 2] A 17-year-old boy was found to have a tumor in the anterior mediastinum on chest CT. His serum alpha-fetoprotein level was elevated to 2,461 ng/mL. Histological diagnosis of yolk sac tumor was confirmed using the Chamberlain procedure. He was treated with one course of chemotherapy, followed by surgery; he remains well 57 months after the biopsy. [Case 3] A 72-year-old man was found, on chest X-ray and CT, to have a left upper anterior mediastinal tumor with invasion of the subclavian vessels. The tumor was confirmed histologically as thymic (sarcomatoid) carcinoma using the Chamberlain procedure. Despite 2 courses of chemotherapy, the tumor continued to enlarge and metastasized to the lung and bone. The patient died 7 months after the biopsy. [Case 4] A 62-year-old woman under treatment for rheumatoid arthritis (RA) was found, on a chest X-ray, to have a right anterior mediastinal tumor. Histological diagnosis using the Chamberlain procedure suggested lymphoproliferative disorder, and the RA medication was discontinued. This was followed by a decrease in the tumor size and avoidance of invasive surgery. The patient remains well, 15 months after the biopsy. [Conclusion] The Chamberlain procedure proved useful for definitive diagnosis in all 4 cases of invasive anterior mediastinal tumors. We recommend the Chamberlain procedure for biopsy since it enables safe, rapid, and successful collection of tissue samples.
23545925 Infections associated with the use of tumor necrosis factor-α inhibitors in psoriasis. 2013 Mar Tumor necrosis factor (TNF)-α inhibitors have been shown to increase the risks of overall infection and serious infection in rheumatoid arthritis. However, it is uncertain whether we can draw the same conclusion in the psoriatic population. This article focuses on the 3 most commonly used TNF-α inhibitors in psoriasis: adalimumab, etanercept, and infliximab. In order to assess the risks of overall infection and serious infection in patients with psoriasis, we reviewed the underlying mechanism of the potential infection risk, different types of serious infection associated with TNF-α inhibitors, and current evidence in the psoriatic population. Results from 11 randomized controlled trials and open-label extension studies showed that there was no apparent significant association between the use of TNF-α inhibitors and increasing risks of overall infection and serious infection. Because of the limitations of current evidence, large, long-term follow-up studies with appropriate control groups using real-life data, such as postmarket surveillance, are warranted.
23306537 Current concepts of elbow-joint disorders and their treatment. 2013 Jan BACKGROUND: Recently, many studies have emphasized the importance of the comprehension of detailed functional anatomy and biomechanics of the elbow and its significant contribution in facilitating good functional outcomes of conservative and surgical treatment in the field of elbow disorders. METHODS: The most common disease of elbow disorders and their treatment was reviewed. RESULTS: Lateral epicondylitis of the elbow, is defined as a microscopic tear of extensor carpi radialis brevis tendon, and microscopic findings show immature reparative tissue (angiofibroblastic hyperplasia). The patient needs coordinated rehabilitation, range-of motion-exercise, stretching, and bracing in the second phase. Ninety-five percent of patients with lateral epicondylitis heal spontaneously or conservatively. The medial collateral ligament injury of the elbow is most common in the overhead-throwing athlete. Jobe's procedure, the original reconstruction technique, and its modifications in bone-tunnel creation, allow a tendon graft to be wound in a figure-eight configuration through the tunnels. Further modification of Jobe's procedure in bone-tunnel configuration reduced the total number of tunnels and facilitates easier graft tensioning. Outcomes with these reconstruction techniques have proven effective in returning high-level throwing athletes back to their sport. Arthroscopic surgery for the elbow in the throwing athlete has evolved and has proven successful results. Arthroscopic treatment includes debridement of posteromedial synovitis, loose-body removal, and excision of the olecranon spur. Posteromedial elbow impingement is also a source of disability in the overhead-throwing athlete. Twenty-five percent of these patients require a medial collateral ligament reconstruction after removal of a posteromedial bony spur. Linked and unlinked total elbow arthroplasty are successful treatment procedures for patients with rheumatoid arthritis, posttraumatic osteoarthritis, and elderly patients with comminuted distal humeral fractures and the salvage of distal humeral nonunion. Proper selection and implantation of prostheses are also important to achieve good functional outcome and longevity. CONCLUSION: The success of treatment of elbow disorders depends greatly on surgical design and technique, both of which require comprehensive knowledge of detailed anatomy and biomechanics of the elbow.
23286253 Implication of antithrombotic agents on potential bleeding from endoscopically determined 2013 Jan BACKGROUND AND AIM: Little is known about the clinical significance of treatment for endoscopically determined peptic ulcers (EPU), incidentally detected as surrogate endpoints for non-steroidal anti-inflammatory drugs (NSAIDs)-associated ulcers complication, such as overt bleeding and perforation. Even uncomplicated-EPU without overt bleeding signs when antithrombotic agents (AT) were cotherapied may be of potential bleeding sites. The aim of the present study was to evaluate whether microcytic anemia, implying potential bleeding, is associated with NSAIDs-associated EPU or cotherapies with AT. METHODS: Two hundred and thirty-eight outpatients with rheumatoid arthritis under long-term NSAIDs therapies underwent upper endoscopy and were divided into the following four groups according to the pattern (presence: + or absence: -) of AT cotherapy/EPU, respectively: A, -/- (n = 165); B, -/+ (n = 44); C, +/- (n = 25); and D, +/+ (n = 4). RESULTS: EPU were found in 48 of the 238 studied patients (20.2%). After significant interactions among four groups hadstatistically been identified, hemoglobin (Hb) and mean corpuscular volume (MCV) as biomarkers for potential bleeding were compared between the groups.Hb and MCV were significantly lower in the D group than in the A,B, or C groups (Hb: P < 0.01, respectively; P < 0.05, MCV; P < 0.01 or P < 0.05, respectively). CONCLUSIONS: Patients with NSAIDs-associated EPU and AT cotherapy indicated significantly more severe microcytic anemia pattern than those without EPU or AT cotherapy, despite no evidence of overt bleeding. Even uncomplicated-EPU without overt bleeding when ATs were cotherapied may be of potential bleeding sites.
23173724 Analysis of altered microRNA expression profiles in peripheral blood mononuclear cells fro 2013 Mar BACKGROUND AND AIM: MicroRNA, as an important regulator of gene expression, has been found to be associated with several diseases. MicroRNA expression profiles have been identified in several autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis. However, the expression profile in peripheral blood mononuclear cells (PBMCs) from primary biliary cirrhosis (PBC) patients and the role of microRNA in PBC remained unclear. The present study aimed to explore abnormal microRNA regulation in PBC. METHODS: MicroRNA array was performed in PBMCs obtained from PBC patients versus healthy controls. Then, six of the 17 differentially expressed microRNAs were confirmed using quantitative real-time polymerase chain reaction. Based on bioinformatics analysis, we identified the potential biological processes and significant signaling pathways affected by these microRNAs, and generated the microRNA-gene network. RESULTS: According to microRNA array, a total of 17 microRNAs were found to be differentially expressed. Six microRNAs have been validated using quantitative real-time polymerase chain reaction, and the results were consistent with microRNA array analysis. The bioinformatics analysis showed that the potential target genes of these microRNAs were involved in cell proliferation, cell differentiation, apoptosis, and signal transduction. Similarly, these microRNAs also affected endocytosis, mitogen-activated protein kinase signaling pathway, transforming growth factor-β signaling pathway, Wnt signaling pathway, calcium signaling pathway, etc. CONCLUSION: In the present study, 17 microRNAs were identified to be differentially expressed in PBMCs from PBC patients. Functional bioinformatics analysis demonstrated that prediction genes targeted by these microRNAs were involved in multiple biological processes and signaling pathways. The present study offers intriguing new perspectives on the involvement of microRNA in PBC, but the precise mechanisms need to be validated further.
22229536 Lipid profiles in untreated patients with dermatomyositis. 2013 Feb BACKGROUND AND OBJECTIVE: Altered lipid levels may occur in autoimmune diseases, such as systemic lupus erythematosus and rheumatoid arthritis. However, serum lipid profiles in patients with dermatomyositis (DM) have not been investigated. Our aim was to identify lipid profiles in untreated DM patients, and to assess the relationship of the inflammatory condition of DM with lipid profiles. METHODS: This work was designed and conducted as a case-control study. Forty-one DM patients and 41 age- and gender-matched healthy controls were included. None of the patients had received corticosteroids or disease-modifying antirheumatic drugs prior to the study. Triglyceride (TG), total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C) and high-density lipoprotein-cholesterol (HDL-C), C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were assessed using standard techniques. RESULTS: Twenty-nine patients (70.7%) had an increase level of TG, and 41.5% had a decrease level of HDL-C. The levels of HDL-C in DM were significantly lower than in controls (P < 0.01). The levels of TG, Non- HDL-cholesterol and very LDL-cholesterol (VLDL-C) were significantly higher than in controls (P < 0.001, P < 0.001 and P < 0.05 respectively). The ratios of VLDL-C/LDL-C, TC/HDL-C and LDL-C/HDL-C were significantly higher than in controls (P < 0.001). Spearman's correlation test demonstrated that serum CRP levels correlated negatively with HDL-C in DM(r = -0.420, P = 0.006). CONCLUSION: Dyslipoproteinemia is a common feature in patients with DM that is characterized by an increase in TG and a decrease in HDL-C, suggesting a high risk of atherosclerosis. Inflammation might partly account for the changes of serum lipid profiles in DM.
25287433 Chronic kidney disease and premature ageing. 2014 Dec Chronic kidney disease (CKD) shares many phenotypic similarities with other chronic diseases, including heart failure, chronic obstructive pulmonary disease, HIV infection and rheumatoid arthritis. The most apparent similarity is premature ageing, involving accelerated vascular disease and muscle wasting. We propose that in addition to a sedentary lifestyle and psychosocial and socioeconomic determinants, four major disease-induced mechanisms underlie premature ageing in CKD: an increase in allostatic load, activation of the 'stress resistance response', activation of age-promoting mechanisms and impairment of anti-ageing pathways. The most effective current interventions to modulate premature ageing-treatment of the underlying disease, optimal nutrition, correction of the internal environment and exercise training-reduce systemic inflammation and oxidative stress and induce muscle anabolism. Deeper mechanistic insight into the phenomena of premature ageing as well as early diagnosis of CKD might improve the application and efficacy of these interventions and provide novel leads to combat muscle wasting and vascular impairment in chronic diseases.
25242798 Abatacept use in graft-versus-host disease after orthotopic liver transplantation: a case 2014 Sep BACKGROUND: Graft-versus-host disease (GVHD) is a rare, serious, fatal disease that occurs after orthotopic liver transplantation (OLT). CASE REPORT: We treated a 60-year-old man who underwent OLT owing to familial amyloidosis. The patient developed fever on postoperative day 16. The fever was persistent and did not respond to antibiotic therapy. Cultures and radiologic studies were done and excluded infection as a potential cause. On postoperative day 26, a skin rash appeared on his chest, accompanied by diarrhea and persistent fever. The rash spread all over the trunk, neck, and arms, but spared the palms of his hands and soles of his feet. In the meantime, his blood cell count revealed pancytopenia. Skin biopsy was done and showed interface lymphocytic infiltrate that are largely centered on the dermal-epidermal junction, is consistent with GVHD (this pattern of rash distribution is unique and different from the rash of GVHD after hematopoietic stem cell transplant, which is confined to palms of the hands and soles of the feet; Fig 1). The diagnosis was confirmed by colonoscopy and multiple forceps biopsies, which revealed extensive crypt loss. After hematology consultation, the patient was treated by withdrawal of all immunosuppressive therapy coupled with abatacept infusion. Abatacept is a chimeric protein that inhibits T-lymphocytes and is approved by the US Food and Drug Administration for the treatment of rheumatoid arthritis. Interestingly, after second dose of abatacept the patient showed marked clinical and laboratory improvement. The patient was discharged after 47 days in a stable condition. CONCLUSION: Because of the lack of a consensus for treatment of these patients, we report our experience with a male patient who had post-OLT GVHD and showed a marked improvement in response to abatacept.
25121969 iNitro-Tyr: prediction of nitrotyrosine sites in proteins with general pseudo amino acid c 2014 Nitrotyrosine is one of the post-translational modifications (PTMs) in proteins that occurs when their tyrosine residue is nitrated. Compared with healthy people, a remarkably increased level of nitrotyrosine is detected in those suffering from rheumatoid arthritis, septic shock, and coeliac disease. Given an uncharacterized protein sequence that contains many tyrosine residues, which one of them can be nitrated and which one cannot? This is a challenging problem, not only directly related to in-depth understanding the PTM's mechanism but also to the nitrotyrosine-based drug development. Particularly, with the avalanche of protein sequences generated in the postgenomic age, it is highly desired to develop a high throughput tool in this regard. Here, a new predictor called "iNitro-Tyr" was developed by incorporating the position-specific dipeptide propensity into the general pseudo amino acid composition for discriminating the nitrotyrosine sites from non-nitrotyrosine sites in proteins. It was demonstrated via the rigorous jackknife tests that the new predictor not only can yield higher success rate but also is much more stable and less noisy. A web-server for iNitro-Tyr is accessible to the public at http://app.aporc.org/iNitro-Tyr/. For the convenience of most experimental scientists, we have further provided a protocol of step-by-step guide, by which users can easily get their desired results without the need to follow the complicated mathematics that were presented in this paper just for the integrity of its development process. It has not escaped our notice that the approach presented here can be also used to deal with the other PTM sites in proteins.
25073722 Cardiovascular disease in psoriatic post-menopausal women. 2015 Jun BACKGROUND: It is generally accepted that the risk of cardiovascular disease (CVD) in women is significantly increased after the menopause. Hormonal changes associated with the menopausal transition may also alter the course of autoimmune diseases. It has been reported that menopause may exacerbate the symptoms of rheumatoid arthritis, systemic sclerosis and giant cell arteritis, but attenuate the course of systemic lupus erythemathosus. There is a growing body of literature indicating that the course of psoriasis may be altered by menopausal hormone changes. Considering the fact that both psoriasis and menopause are independent risk factors for CVD, and that menopause may exacerbate the course of psoriasis, a possible additive effect between these two conditions may be crucial for proper monitoring and treatment of peri- and post-menopausal psoriatic patients. OBJECTIVE: The aim of this study is to analyse potential relationship between psoriasis, menopausal status and risk of CVD. MATERIALS AND METHODS: A retrospective analysis of the Clalit Health Services database was performed in an attempt to provide new data and the available literature concerning these issues was reviewed. Data on cardiovascular events in 10 872 female psoriatic patients and 19 471 controls were extracted and compared. RESULTS: In both psoriatic and control patients the association of CVD increased with age. The association of CVD was significantly greater in psoriatic patients, but no significant differences were found between any of age groups. CONCLUSIONS: The association of psoriasis and CVD in women increases with age but there is insufficient evidence to confirm that menopause increases the risk of psoriasis. Further studies directly addressing this issue are needed.
25000305 Delphinidin suppresses PMA-induced MMP-9 expression by blocking the NF-κB activation thro 2014 Aug Matrix metalloproteinase-9 (MMP-9) plays an important role in the invasion and metastasis of cancer cells. The synthesis and secretion of MMP-9 can be stimulated by a variety of stimuli, including cytokines and phorbol 12-myristate 13-acetate (PMA), during various pathological processes, such as tumor invasion, atherosclerosis, inflammation, and rheumatoid arthritis, whereas MMP-2 is usually expressed constitutively. Delphinidin, an anthocyanidin present in pigmented fruits and vegetables, possesses potent antioxidant, anti-inflammatory, and antiangiogenic properties. In this study, we investigated the antiproliferative and antiinvasive effects of delphinidin on PMA-induced MMP-9 expression in MCF-7 human breast carcinoma cells using zymography, western blotting, reverse transcription-polymerase chain reaction, and Matrigel invasion assay. Delphinidin significantly suppressed PMA-induced MMP-9 protein expression in MCF-7 human breast carcinoma cells, and it also inhibited the MMP-9 gene transcriptional activity by blocking the activation of NFkappaB (NF-κB) through MAPK signaling pathways. Moreover, the Matrigel invasion assay showed that delphinidin reduces PMA-induced cancer cell invasion. These results suggest that delphinidin is a potential antimetastatic agent that suppresses PMA-induced cancer cell invasion through the specific inhibition of NF-κB-dependent MMP-9 gene expression.