Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
ID | PMID | Title | PublicationDate | abstract |
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26037655 | Association of Antibodies to Interferon-Inducible Protein-16 With Markers of More Severe D | 2016 Feb | OBJECTIVE: Interferon-inducible protein-16 (IFI16) is an intracellular DNA receptor involved in innate immunity. We evaluated the frequency, phenotypic characteristics, and clinical associations of anti-IFI16 antibodies in patients with primary Sjögren's syndrome (SS), and quantitated expression levels of IFI16 in SS and control salivary gland lysates. METHODS: Anti-IFI16 antibodies were assayed by enzyme-linked immunosorbent assay using sera from patients with primary SS (n = 133) and from healthy controls (n = 47). Sera from systemic lupus erythematosus (SLE) patients (n = 132) were included as disease controls. Immunoprecipitation of in vitro transcription-translated IFI16 was used to determine which portion of IFI16 the antibodies recognized. Expression of IFI16 in salivary gland lysates was quantitated by immunoblotting. RESULTS: Anti-IFI16 antibodies were present in the sera of 38 of 133 SS patients (29%) compared to 1 of 47 healthy controls (2.1%) (SS versus controls; P < 0.0002) and in 31 of 132 SLE controls (24%). In SS, anti-IFI16 antibodies were associated with an abnormal Schirmer's test (P = 0.003), hyperglobulinemia (P = 0.02), antinuclear antibody ≥1:320 (P = 0.01), germinal center-like structures in labial salivary gland lymphoid infiltrates (P = 0.01), and higher focus scores (3.4 versus 2.4; P = 0.005). High-titer IFI16 antibodies were directed against an epitope outside the N-terminus in 9 of 13 SS patients (69%). IFI16 was expressed in 4 of 5 (80%) of SS and 1 of 6 (17%) of control labial salivary glands. CONCLUSION: Anti-IFI16 antibodies are a prominent specificity in primary SS and are associated with markers of severe disease. IFI16 is expressed at higher levels in SS salivary glands compared to controls. These high levels in disease target tissue may contribute to the ongoing anti-IFI16 immune response. | |
25675069 | The continuance time of pressure effect in the rat model of complete Freund's adjuvant ind | 2015 Jan | BACKGROUND: We previously published on the pressure effect using a rheumatoid animal model (Pain Physician in 2013 and 2014). However, we do not know how long the pressure effect lasts after exposure to high pressure. OBJECTIVE: We evaluated the duration of the pressure effect in a day for a given study period. STUDY DESIGN: Laboratory animal study. METHODS: Following injection of Complete Freund's Adjuvant (CFA) into one side of the knee joint, 8 rats were assigned to 1.5 atmospheres absolute (ATA) hyperbaric chamber 3 hours per day for one or 2 weeks (1WPG or 2WPG). Pain levels were assessed daily for 2 weeks according to weight bearing force (WBF) of the affected limb. In addition, the levels of gelatinase, MMP-2, and MMP-9 expression in synovial fluids of the knees were analyzed. RESULTS: The reduction of WBF was high at one day after injection and then increased spontaneously up to 2 weeks in 1WPG and 2WPG. The pressure effects lasted for a given day and did not exceed the pressure effects of the next day in all study periods. Improvement of WBF in 2WPG was significantly greater than that of 1WPG during 8-14 days. The gelatinase expression ratio was significantly reduced in 1WPG and 2WPG, and 2WPG showed the lowest gelatinase ratio at 2 weeks. LIMITATION: Although enough samples were used for the study, more samples will be needed to raise the reliability. CONCLUSION: The 3 hours of 1.5 ATA pressure effect lasted for more than a day. Longer pressure exposure time appears to yield a greater therapeutic effect in an RA animal model up to a given study period. Continuous application of high pressure might be beneficial for achievement of a better therapeutic effect in clinical application. | |
28487867 | Non-ischemic cardiomyopathy after rituximab treatment for membranous nephropathy. | 2017 | Rituximab is an anti-CD20 monoclonal antibody frequently used for the treatment of non-Hodgkin's lymphoma, chronic lymphocytic leukemia (CLL), rheumatoid arthritis (RA), and anti-neutrophilic cytoplasmic antibody (ANCA)-associated vasculitis. In addition, rituximab has recently been increasingly used as an off-label treatment in a number of inflammatory and systemic autoimmune diseases. It is advised that rituximab infusion may cause infusion reactions and adverse cardiac effects including arrhythmia and angina, especially in patients with prior history of cardiovascular diseases. However, its detailed cardiotoxicity profile and effects on cardiac function were not well described. We report a 51-year-old man who developed non-ischemic cardiomyopathy after rituximab treatment for membranous nephropathy. The patient experienced reduced cardiac functions within 48 hours after the initial infusion, which remained markedly reduced at 9-month follow-up. As the utility of rituximab expands, physicians must be aware of this serious cardiovascular adverse effect. | |
26904130 | Stem Cell-Derived Exosomes: A Potential Alternative Therapeutic Agent in Orthopaedics. | 2016 | Within the field of regenerative medicine, many have sought to use stem cells as a promising way to heal human tissue; however, in the past few years, exosomes (packaged vesicles released from cells) have shown more exciting promise. Specifically, stem cell-derived exosomes have demonstrated great ability to provide therapeutical benefits. Exosomal products can include miRNA, other genetic products, proteins, and various factors. They are released from cells in a paracrine fashion in order to combat local cellular stress. Because of this, there are vast benefits that medicine can obtain from stem cell-derived exosomes. If exosomes could be extracted from stem cells in an efficient manner and packaged with particular regenerative products, then diseases such as rheumatoid arthritis, osteoarthritis, bone fractures, and other maladies could be treated with cell-free regenerative medicine via exosomes. Many advances must be made to get to this point, and the following review highlights the current advances of stem cell-derived exosomes with particular attention to regenerative medicine in orthopaedics. | |
26645022 | A short review on structure and role of cyclic-3',5'-adenosine monophosphate-specific phos | 2015 Oct | Cyclic nucleotide phosphodiesterases (PDEs) are known as a super-family of enzymes which catalyze the metabolism of the intracellular cyclic nucleotides, cyclic-3',5'-adenosine monophosphate (cAMP), and cyclic-3',5'-guanosine monophosphate that are expressed in a variety of cell types that can exert various functions based on their cells distribution. The PDE4 family has been the focus of vast research efforts over recent years because this family is considered as a prime target for therapeutic intervention in a number of inflammatory diseases such as asthma, chronic obstructive pulmonary disease, and rheumatoid arthritis, and it should be used and researched by pharmacists. This is because the major isoform of PDE that regulates inflammatory cell activity is the cAMP-specific PDE, PDE4. This review discusses the relationship between PDE4 and its inhibitor drugs based on structures, cells distribution, and pharmacological properties of PDE4 which can be informative for all pharmacy specialists. | |
26422561 | Sarcoidosis and risk of venous thromboembolism: A systematic review and meta-analysis. | 2015 Sep 14 | BACKGROUND: Several chronic inflammatory disorders, such as rheumatoid arthritis, inflammatory myositis and systemic lupus erythematosus, have been linked to an increased risk of venous thromboembolism (VTE). However, the data on sarcoidosis is unclear. OBJECTIVES: To evaluate the risk of VTE among patients with sarcoidosis. METHODS: We conducted a systematic review and meta-analysis of observational studies that reported odds ratio, relative risk, hazard ratio or standardized incidence ratio comparing risk of VTE in patients with sarcoidosis versus non-sarcoidosis participants. Estimated effects were extracted from each study and were pooled together using the random-effect, generic inverse variance method of DerSimonian and Laird. RESULT: Out of 772 potentially relevant articles, three eligible studies were identified and included in the data analysis. The pooled risk ratio of VTE in patients with sarcoidosis was 1.42 (95% CI, 1.12-1.79). The statistical heterogeneity of this study was moderate with an I2 of 72%. CONCLUSION: Our study demonstrated a statistically significant increased VTE risk among patients with sarcoidosis. | |
25907699 | Genetic architectures of seropositive and seronegative rheumatic diseases. | 2015 Jul | Rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis and some other rheumatic diseases are genetically complex, with evidence of familial clustering, but not of Mendelian inheritance. These diseases are thought to result from contributions and interactions of multiple genetic and nongenetic risk factors, which have small effects individually. Genome-wide association studies (GWAS) of large collections of data from cases and controls have revealed many genetic factors that contribute to non-Mendelian rheumatic diseases, thus providing insights into associated molecular mechanisms. This Review summarizes methods for the identification of gene variants that influence genetically complex diseases and focuses on what we have learned about the rheumatic diseases for which GWAS have been reported. Our review of the disease-associated loci identified to date reveals greater sharing of risk loci among the groups of seropositive (diseases in which specific autoantibodies are often present) or seronegative diseases than between these two groups. The nature of the shared and discordant loci suggests important similarities and differences among these diseases. | |
25854155 | [Biologics therapy for systemic lupus erythematosus. Current situation]. | 2015 Apr | BACKGROUND: Improved understanding of the immunopathogenesis of systemic lupus erythematosus (SLE) has paved the way for new specific immune interventions for this inflammatory disease similar to those for rheumatoid arthritis and spondylarthritides. METHODS: New biologics were developed on this basis or are in the process of clinical development and open up new therapy options for patients. In this context belimumab is of particular importance. As an innovative biologic the monoclonal antibody against the cytokine BAFF/BLyS (belimumab) has been approved for the treatment of serologically active SLE. A number of other biologics against other cytokines are in the clinical development phase and appear to be promising for further improvement of the current therapeutic possibilities in SLE. This article addresses the current aspects of immune interventions with biologics for SLE and the specific challenges of this disease. | |
25182149 | Intra-articular glucocorticoid injections and their effect on hypothalamic-pituitary-adren | 2015 Mar | The use of intra-articular (IA) glucocorticoids for reducing pain and inflammation in patients with osteoarthritis, rheumatoid arthritis, and other inflammatory arthropathies is widespread among primary care physicians, specialists, and non-specialists in the United States. Injectable glucocorticoids have anti-inflammatory and analgesic properties which can be effective in improving clinical parameters such as pain, range of motion, and quality of life. After injection into the IA space, glucocorticoids may be systemically absorbed; the degree of absorption can depend on the size of the joint injected, the injectable glucocorticoid preparation used, the dosage, and the frequency of the injection. The adverse effects of intra-articular glucocorticoid injections (IAGC) can often be overlooked by both the patient and physicians who administer them, in particular the potential deleterious effect on the hypothalamic-pituitary-adrenal (HPA)-axis which can result in adrenal suppression and/or iatrogenic Cushing syndrome. In this paper we provide an overview on the often under-recognized effects of IAGC on HPA-axis function. | |
28399787 | Diagnostic modalities for distal radioulnar joint. | 2017 May | The first imaging modality in patients suspected of distal radioulnar joint pathology should be conventional radiography to exclude or diagnose wrist pathology including osteoarthritis, rheumatoid arthritis, calcium pyrophosphate deposition disease, (healed) fractures, or impaction syndromes. When conventional radiography is inconclusive, high resolution 3 Tesla magnetic resonance imaging is advised. We provide a broad overview of the literature regarding the use of intra-articular contrast both with computed tomography (CTA) or magnetic resonance imaging (MRA). Conventional arthrography and unenhanced computed tomography are not indicated. This article discusses the most useful imaging techniques in terms of clinical indications, patient positioning, technical imaging requirements, and diagnostic performance in patients with suspected distal radioulnar joint pathology. Furthermore, the most prevalent pathologies are discussed, with the focus on imaging characteristics in both stable and unstable distal radioulnar joints. | |
27604956 | Fragment Pharmacophore-Based Screening: An Efficient Approach for Discovery of New Inhibit | 2016 | AIM AND OBJECTIVE: Rheumatoid Arthritis (RA) is a progressing autoimmune inflammatory disease of joint, hallmarked by inflammation, pain and atrophy of bones. Toll-like receptor 5 (TLR5) is a novel inflammatory mediator in RA, and TLR5 inhibitors are speculated to have a therapeutic potential for the treatment of RA. MATERIAL AND METHOD: Here we applied fragment pharmacophore-based virtual screening to identify novel TLR5 ligands. RESULTS: Among compounds collected from Otava peptidomimetic compounds, Maybridge fragment and ZINC libraries, 3355 compounds were selected for docking into the flagellin-binding site of TLR5. 16 compounds with the required interaction, critical amino acid residues and the binding free energies <-7 kcal/mol were identified as potential TLR5 inhibitors, one of which was followed up by molecular dynamics simulation. CONCLUSION: These compounds open a possibility to discover novel TLR5 inhibitors for the treatment of RA. | |
27593387 | Phytochemistry and Phytotherapeutic Aspects of Elaeagnus angustifolia L. | 2016 | Persian or Russian olive (Elaeagnus angustifolia L.), from the family Elaeagnaceae, is a nitrogen-fixing thorny shrub extensively used in traditional medicine to alleviate pain and treat rheumatoid arthritis, osteoarthritis, gastrointestinal problems, fever, and asthma. The current review has tried to give a concise overview of the phytochemistry and pharmacological properties of the plant from published data. Accordingly, published English literatures on Elaeagnus angustifolia were gathered from popular databases such as PubMed, Scopus, Web of Science, and ScienceDirect up to 31 December 2015. In accordance with traditional and ethnopharmacological uses, different extracts of E. angustifolia have been known for their antioxidant, anti-inflammatory, anti-nociceptive, antimicrobial, muscle relaxant, anti-ulcer and wound-healing capabilities. Additionally, cardioprotective, antitumor and anti-mutagenic effects of the herb have been demonstrated by current assessments. Despite numerous experimental studies, there is a notable lack of profound and comprehensive clinical trials as well as critical research on E. angustifolia toxicity and teratogenicity. With reference to various pharmacological effects based on experimental and animal investigation, it is worthy to mention a frame for respective clinical studies in further studies. | |
27501498 | Oral inflammation and infection, and chronic medical diseases: implications for the elderl | 2016 Oct | Oral diseases, such as caries and periodontitis, not only have local effects on the dentition and on tooth-supporting tissues but also may impact a number of systemic conditions. Emerging evidence suggests that poor oral health influences the initiation and/or progression of diseases such as atherosclerosis (with sequelae including myocardial infarction and stoke), diabetes mellitus and neurodegenerative diseases (such as Alzheimer's disease, rheumatoid arthritis and others). Aspiration of oropharyngeal (including periodontal) bacteria causes pneumonia, especially in hospitalized patients and the elderly, and may influence the course of chronic obstructive pulmonary disease. This article addresses several pertinent aspects related to the medical implications of periodontal disease in the elderly. There is moderate evidence that improved oral hygiene may help prevent aspiration pneumonia in high-risk patients. For other medical conditions, because of the absence of well-designed randomized clinical trials in elderly patients, no specific guidance can be provided regarding oral hygiene or periodontal interventions that enhance the medical management of older adults. | |
27313425 | Anticancer activity of Arkeshwara Rasa - A herbo-metallic preparation. | 2015 Jul | INTRODUCTION: Though metal based drugs have been prescribed in Ayurveda for centuries to treat various diseases, such as rheumatoid arthritis and cancer, toxicity of these drugs containing heavy metal is a great drawback for practical application. So, proper scientific validation of herbo-metallic drugs like Arkeshwara Rasa (AR) have become one of the focused research arena of new drugs against cancers. AIM: To investigate the in vitro anticancer effects of AR. MATERIALS AND METHODS: Anticancer activity of AR was investigated on two human cancer cell lines, which represent two different tissues (pancreas and skin). Lactate dehydrogenase (LDH) assay for enzyme activity and trypan blue assay for cell morphology were performed for further confirmation. RESULTS: AR showed potent activity against pancreatic cancer cells (MIA-PaCa-2). LDH activity confirmed that AR was active against pancreatic cancer cells. Finally, it was observed that AR exhibited significant effects on cancer cells due to synergistic effects of different compounds of AR. CONCLUSION: The study strongly suggests that AR has the potential to be an anticancer drug against pancreatic cancer. | |
27104043 | Amarkand: A comprehensive review on its ethnopharmacology, nutritional aspects, and taxono | 2016 Mar | In India, the term "Amarkand" is commonly used for around 30 different plant species belonging to genus Eulophia (Orchidaceae). This single local name Amarkand to different taxonomical species creates uncertainty about its ethnomedical and nutritional claims. In the present article, we have reviewed available literature regarding ethnopharmacology, phytochemistry, taxonomy, nutritional, and pharmacological studies of different Amarkand species. The literature was searched using Google Scholar, PubMed, Scopus, and Web of Science databases. Some textbooks and reference books were also used to collect information about traditional and ethnopharmacological records. Amarkand species have been used as a remedy for the treatment of various diseases such as diarrhea, stomach pain, rheumatoid arthritis, cancer, asthma, bronchitis, sexual impotency, tuberculosis, and so on. Nutritionally, Amarkand is considered as an excellent food for children and convalescents. Recent studies confirm antioxidant, anti-inflammatory, anti-diarrheal, and so forth activities to Amarkand species. These species are reported to possess various phytoconstituents such as flavonoids, terpenoids, and phenanthrene derivatives. The present review will help to understand overall ethnopharmacology, nutritional aspects, and taxonomy of Amarkand species. | |
26634137 | Case of acquired or pseudo-Pelger-Huët anomaly. | 2015 Apr | Pelger-Huët anomaly (PHA) is a rare benign autosomal-dominant anomaly with an incidence of ∼1 in 6000. It does not cause neutrophilia, but it can cause a false increase in band forms. It should be differentiated from acquired or pseudo-Pelger-Huët anomaly (PPHA), which has similar morphology, however; it is associated with different pathological states like Myelodysplastic syndrome, as well as with certain infections and drugs. We report a case of a 67-year-old Caucasian gentleman with past medical history of rheumatoid arthritis, type II diabetes mellitus and hypothyroidism, who presented with 1 day history of fever (101°F) and night sweats. Medications include ibuprofen, methotrexate, hydroxychloroquine and levothyroxine. Patient denied any other symptoms. His work-up showed normal WBC count (8.6) and increase in bands (24%). The patient was admitted for further evaluation. During the next 2 days, the patient did not have any fever or any new symptoms. Peripheral blood smear was done as part of his work-up for bandemia, showed findings suggestive of PHA. Ibuprofen was discontinued. Follow-up few weeks later showed normal blood smear. Diagnosis of PPHA was made. The presented case showed that we should think of PHAPPHA in any case with normal total WBC count and significant shift to the lift with no apparent explanation. Looking at smears directly under the microscopes is crucial to make diagnosis. | |
26153223 | Colon: a gateway for chronotherapeutic drug delivery systems. | 2015 | Colon-specific delivery systems have attracted considerable attention from the scientific community. One of the distinctions of this site-specific delivery system is its effectiveness in carrying a variety of medicinal agents (required for both localized diseases and systemic therapy). It has been proposed that the biological rhythm of the body may affect the normal physiological as well as biological functions. Diseases such as nocturnal asthma, angina pectoris, inflammation, rheumatoid arthritis, hypertension or cardiac arrhythmia, has been found to follow biological rhythm of the body. For the treatment of these diseases, development of a chronotherapeutic drug delivery system (CrDDS), which delivers a defined dose, at a selected time and chosen rate, and to a targeted site is required. Several CrDDSs have been developed by using various strategies (pH-, time-, microflora-triggered and pressure-controlled systems) with the aim of achieving colon-specific drug delivery. This Editorial article aims to highlight some of the recent advancements that have emerged in the field of colon-targeted drug delivery systems pertaining to the chronotherapy of certain disease conditions. | |
25788762 | Role of genetic alterations in the NLRP3 and CARD8 genes in health and disease. | 2015 | The complexity of a common inflammatory disease is influenced by multiple genetic and environmental factors contributing to the susceptibility of disease. Studies have reported that these exogenous and endogenous components may perturb the balance of innate immune response by activating the NLRP3 inflammasome. The multimeric NLRP3 complex results in the caspase-1 activation and the release of potent inflammatory cytokines, like IL-1β. Several studies have been performed on the association of the genetic alterations in genes encoding NLRP3 and CARD8 with the complex diseases with inflammatory background, like inflammatory bowel disease, cardiovascular diseases, rheumatoid arthritis, and type 1 diabetes. The aim of the present review is therefore to summarize the literature regarding genetic alterations in these genes and their association with health and disease. | |
25766275 | Modulation of autoimmunity and atherosclerosis - common targets and promising translationa | 2015 | Atherosclerosis is a chronic inflammatory disease of the arterial wall that is influenced by several risk factors, including hyperlipidemia and hypertension. Autoimmune diseases substantially increase the risk for cardiovascular disease (CVD). Although atherosclerotic CVD, such as myocardial and stroke, is much more prevalent than classical autoimmune conditions such as rheumatoid arthritis, psoriasis, and systemic lupus erythematosus, these types of pathology have many similarities, raising the possibility that therapies against autoimmune disease can have beneficial effects on CVD. Substantial clinical and experimental data support the potential for immunomodulatory approaches to combating both autoimmune and cardiovascular diseases, including classical immunosuppressants, anticytokine therapy, the targeting of T and B cells and their responses, and vaccination. In this review, we discuss experimental and clinical studies that have used immunomodulatory approaches to mitigate autoimmune reactions and examine their potential to prevent and treat atherosclerotic CVD. | |
24785099 | Multifocal Necrotizing Chorioretinitis Following Phacoemulsification Surgery. | 2015 Jun | INTRODUCTION: Toxoplasma chorioretinitis is a leading cause of infectious posterior uveitis worldwide. METHODS: We report an atypical presentation of Toxoplasma chorioretinitis presenting after uneventful cataract surgery in an 81-year-old male, with known hypernephroma and rheumatoid arthritis, treated with prednisolone and methotrexate. RESULTS: He was treated for acute retinal necrosis and cytomegalovirus retinitis before Toxoplasma chorioretinitis was confirmed by vitreous biopsy 11 months after presentation. He developed a secondary rhegmatogenous retinal detachment, treated successfully with pars plana vitrectomy, silicone oil and endolaser. Visual acuity at discharge was 6/12 following silicone oil removal. DISCUSSION: Necrotising chorioretinitis in immunosuppressed or elderly patients may present with an atypical phenotype. Clinical diagnosis in this context remains challenging. We discuss the clinical reasoning behind investigation and management of this patient group in whom viral and Toxoplasma retinitis may be clinically indistinguishable. The significance of vitreous PCR results in clinical decision making in the context of infectious posterior uveitis is discussed. |