Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
25818493 Medium-term outcomes and complications after total replacement of the temporomandibular jo 2015 May In this prospective analysis, we assess the medium-term benefits, efficacy, and safety of the TMJ Concepts joint replacement system in the United Kingdom. Outcome measures of pain, maximum mouth opening, and diet were recorded preoperatively and at intervals up to 3 and 5 years. All patients who had replacement temporomandibular joints (TMJ) within a 6-year period were included. A total of 58 patients (84 joints) were followed up for 3 years (mean age 47, range 19-72) and 26 (42 joints) for 5 years (mean age 46, range 27-70). The female to male ratio was 52:6 at 3 years and 23:3 at 5 years. The most common diagnosis was degenerative disease, and the mean number of previous TMJ procedures was 2.4 (range 0-14). There were significant improvements in pain scores (7.4 reduced to 0.6 at 3 years and 0.8 at 5 years), maximum mouth opening (21.0-35.5mm at 3 years and 23.8-33.7mm at 5 years), and dietary scores (4.1-9.7 at 3 years and 3.7-9.6 at 5 years). Revision operations were required in 2 patients (not included in the outcome data) for biofilm infection of the prosthesis secondary to local infection in the head and neck. One patient had weakness of the temporal branch of the facial nerve that needed correction. TMJ replacement is an effective form of management for an irreparably damaged joint, particularly in cases of ankylosis. It lessens pain and improves function with minimal long-term morbidity.
27988789 Systematic review of rheumatic disease phenotypes and outcomes in the Indigenous populatio 2017 Apr We performed a systematic review designed to characterize clinical phenotypes and outcomes in Indigenous populations with rheumatic disease to enhance the understanding of how rheumatic disease presents in Indigenous populations and allow for better projection of the healthcare needs of the communities affected. A systematic search was performed in medical (Medline, EMBASE, CINAHL), Indigenous and conference abstract databases (to June 2015). Search terms for Indigenous populations were combined with terms for inflammatory arthritis conditions, connective tissue disorders, crystal arthritis and osteoarthritis. Studies were included if they reported on disease features, disease activity measures, or patient-reported outcomes in Canadian, American, Australian or New Zealand Indigenous populations. Data were extracted in duplicate, and a narrative summary was prepared. A total of 5269 titles and abstracts were reviewed, of which 504 underwent full-text review and 85 met inclusion criteria. Nearly all the studies described outcomes in the North American populations (n = 77), with only four studies from Australia and four studies from New Zealand. The majority of studies were in rheumatoid arthritis (n = 31) and systemic lupus erythematosus (n = 19). Indigenous patients with rheumatoid arthritis had higher disease activity and reported more significant impact on patient-reported outcomes and quality of life than non-Indigenous patients. Spondyloarthropathy features were described in North American populations, with most patients having advanced manifestations. In systemic lupus erythematosus, nephritis was more frequent in Indigenous populations. Gout and osteoarthritis were more severe in New Zealand Maori populations. The existing literature supports differences in disease phenotype and severity in Indigenous populations of Canada, America, Australia and New Zealand. We encourage investigators in this area of research to undertake contemporary studies that disentangle differences between phenotype and severity that are biologic in etiology or merely reflecting differences in access to care and that provide a longitudinal assessment of outcomes in more diverse populations.
27159398 Gene Therapy Induces Antigen-Specific Tolerance in Experimental Collagen-Induced Arthritis 2016 Here, we investigate induction of immunological tolerance by lentiviral based gene therapy in a mouse model of rheumatoid arthritis, collagen II-induced arthritis (CIA). Targeting the expression of the collagen type II (CII) to antigen presenting cells (APCs) induced antigen-specific tolerance, where only 5% of the mice developed arthritis as compared with 95% of the control mice. In the CII-tolerized mice, the proportion of Tregs as well as mRNA expression of SOCS1 (suppressors of cytokine signaling 1) increased at day 3 after CII immunization. Transfer of B cells or non-B cell APC, as well as T cells, from tolerized to naïve mice all mediated a certain degree of tolerance. Thus, sustainable tolerance is established very early during the course of arthritis and is mediated by both B and non-B cells as APCs. This novel approach for inducing tolerance to disease specific antigens can be used for studying tolerance mechanisms, not only in CIA but also in other autoimmune diseases.
26939782 Difficult-To-Treat Juvenile Idiopathic Arthritis: Current and Future Options. 2016 Apr Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in childhood and is usually treated with non-steroidal anti-inflammatory drugs or disease-modifying anti-rheumatic drugs (DMARDs) such as methotrexate or sulfasalazine. However, not all patients respond to these treatments, and toxicities may limit long-term use or diminish compliance. With advances in pharmacotherapy and the development of new therapeutic agents, there have been improvements in treatment of both systemic and non-systemic JIA, particularly with biologic agents such as anti-tumor necrosis factor (TNF)-α, anti-interleukin (IL)-1, and anti-IL6. Anti-cell therapies, such as co-stimulator blockers or anti-CD20, small molecules, and biosimilars represent new areas of interest, and, while many are not yet currently commercially available for use in children, preliminary studies appear to be promising. In the present article, the authors review therapeutic strategies for the different JIA subtypes, mainly according to guidelines and recommendations. Newer and possible future treatments for arthritis, already approved in adults but currently under study in children, are also discussed. Drugs currently in development plans for rheumatoid arthritis, which hopefully will also be useful for JIA patients in the future, are also mentioned in this paper.
25853428 Antioxidant and angiostatic effect of Spirulina platensis suspension in complete Freund's 2015 BACKGROUND: Currently, natural products have built a well-recognized role in the management of many degenerative diseases, mainly rheumatoid arthritis. Recent studies suggest that Spirulina, a unicellular blue-green alga, may have a variety of health benefits and curative properties and is also competent of acting as an anti-inflammatory, antioxidant and recently anti-angiogenic agent. In the present study, the antioxidant and the immunomodulatory effect of Spirulina platensis as well as its anti-angiogenic effect against complete Freund's adjuvant-induced arthritis (AIA) in rat model were tested. RESULTS: We found that the development of arthritis was concealed; moreover it successfully inhibited the development of macroscopic as well as microscopic and histopathological lesions in AIA rats when compared to control. Spirulina treated group showed a higher survival rate and moreover, it reduced the clinical score of RA in a dose dependent manner. Furthermore, Spirulina decreased serum levels of COX-2, TNF-α, IL-6, TBARS, VEGF and increased serum levels of GSH compared to the RA non-treated group. CONCLUSIONS: The present study concluded that Spirulina is able to restrain the changes produced through adjuvant-induced arthritis. The suppressing effect of Spirulina could be attributed, at least in part, to anti-inflammatory, antioxidant and anti-angiogenic properties.
27273006 Th2 and eosinophil responses suppress inflammatory arthritis. 2016 Jun 7 Th2-eosinophil immune responses are well known for mediating host defence against helminths. Herein we describe a function of Th2-eosinophil responses in counteracting the development of arthritis. In two independent models of arthritis, Nippostrongylus brasiliensis infection leads to Th2 and eosinophil accumulation in the joints associated with robust inhibition of arthritis and protection from bone loss. Mechanistically, this protective effect is dependent on IL-4/IL-13-induced STAT6 pathway. Furthermore, we show that eosinophils play a central role in the modulation of arthritis probably through the increase of anti-inflammatory macrophages into arthritic joints. The presence of these pathways in human disease is confirmed by detection of GATA3-positive cells and eosinophils in the joints of rheumatoid arthritis patients. Taken together, these results demonstrate that eosinophils and helminth-induced activation of the Th2 pathway axis effectively mitigate the course of inflammatory arthritis.
26472504 Anti-TNFα-therapy as an evidence-based treatment option for different clinical manifestat 2015 Sep The development programmes of different TNF-blocking agents in psoriatic arthritis (PsA) not only provided substantial evidence for the therapeutic benefits of the specific treatment options, but also enabled new insights into the differential treatment effects on distinct disease manifestations. For the first time, specific robust evidence for distinctive effects on different manifestations of PsA, as a distinct entity separate from rheumatoid arthritis (RA), has been generated in a standardized way. The clearest evidence was shown for an effect on peripheral arthritis (polyarticular) with ACR20 response rates from 45 up to 58% (vs. 9-24% for placebo), and an inhibition of radiographic progression demonstrated for the first time for a treatment principle in PsA. However, as PsA does not remain confined to the peripheral joints, it was necessary to address diverse patterns of PsA-subtypes in the outcome measurements of the anti-TNF trials. Accordingly, the results of the clinical studies on anti-TNF treatment also have demonstrated efficacy on enthesitis, dactylitis and skin psoriasis, either in sub analysis of results from phase III RCTs, or in additional prospective studies.
27611176 Autophagy and mitochondrial dysfunction in adjuvant-arthritis rats treatment with resverat 2016 Sep 9 Resveratrol is a polyphenol derivatives which exhibits a pro-apoptotic effect in a variety of human cancers by triggering mitochondria apoptosis pathway and autophagy. However, there are scarcely reports on its apoptosis-promoting effect in abnormal proliferation fibroblast-like synoviocytes (FLSs). In this study, we investigated the underlying mechanism and apoptosis-inducing effects of resveratrol on the abnormal proliferation of FLSs in adjuvant-arthritis (AA) rats. Since using resveratrol for 12 days resulted in a significant decreasing the swelling degree of the paw, reducing malondialdehyde (MDA) content and enhancing superoxide dismutase (SOD) activity, antioxidant capacity, glutathione peroxidase and glutathione reductase ratio in AA rats. Moreover, we found that 5 μMH2O2 could increase cells viability, Beclin1, LC3A/B, MnSOD, SIRT3 protein expression in FLSs. But, resveratrol could reverse these effects by changing mitochondrial membrane potential (Δψm) to promote mitochondrial reactive oxygen species (mtROS) generation in 5 μMH2O2-treatment FLSs. These results suggest that oxidative stress existed in AA rats. Resveratrol could suppress oxidative stress in AA rats and increase mtROS production by reducing autophagy protein Beclin1, LC3A/B and oxidative stress protein MnSOD to promoted the apoptosis of FLSs. Thus, targeting of mtROS may be a crucial mechanism of resveratrol confers patients with rheumatoid arthritis.
25917994 A 2-year-old with 4 weeks of daily fever. 2015 May A 2-year-old female presents for evaluation of 4 weeks of daily fevers. When the fevers began, she had mild upper respiratory tract symptoms, which quickly resolved. The fevers persisted, however, with a maximum of 40°C. The child's review of symptoms was significant for a 1-kg weight loss over the past month. Ten months before presentation, she had moved from Saudi Arabia with her family. One week before the onset of symptoms, she had visited a petting zoo. During episodes of fever, the patient was ill-appearing and had an elevated heart rate and respiratory rate. On examination, she was found to be thin, febrile, tachycardic, and with scattered lymphadenopathy. Results of laboratory tests were remarkable for an elevated white blood cell count of 16,100 cells per uL with a neutrophilic predominance. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were elevated at 99 mm/h and 27 mg/dL, respectively. A chest radiograph indicated a small amount of fluid in the interlobar fissures. Our expert panel examines her case, offers a definition of fever of unknown origin, and makes diagnostic considerations.
25746826 Septic arthritis due to methylcyllin-resistant Staphylococcus aureus in adults. 2015 Nov INTRODUCTION: Septic arthritis due to methylcyllin resistant Staphylococcus aureus (MRSA) is a serious infection that has increased in incidence in the past 10years. METHODS: We conducted a retrospective study (1984-2011) in which a description of the clinical and epidemiological characteristics of MRSA arthritis in adults was performed and then compared to native joint infections caused by MRSA vs. methylcyllin sensitive Staphylococcus aureus (MSSA). RESULTS: Fourteen MRSA infections were included (7 native joint, 5 prosthetic and 2 bursae). No case was polyarticular. There was significant comorbidity, although none was associated to rheumatoid arthritis. Seven patients had bacteremia. Four required surgical treatment. Six died. When comparing the 7 patients with native joint MRSA infection with the 17 cases caused by MSSA, no significant differences in risk factors were seen, except more malignancies in the MRSA group. The infection was polyarticular in 7 cases (41%) of the MSSA group. Bacteremia was more frequent in the MRSA group (71.4 vs 58.8%). Empirical antibiotic was useful in 28.6% of MRSA cases versus 100% of MSSA cases. There was a greater tendency to associated mortality in MRSA arthritis (57.1% vs 17.6%, P=.07). CONCLUSIONS: MRSA septic arthritis is a serious condition that occurs in the elderly and patients with high comorbidity. It is usually monoarticular, with positive blood cultures and higher mortality than MSSA arthritis. In patients at risk, vancomycin empiric antibiotic therapy is indicated.
25306263 An investigation into the interactions of gold nanoparticles and anti-arthritic drugs with 2015 Jan Gold(I) complexes are an important tool in the arsenal of established approaches for treating rheumatoid arthritis (RA), while some recent studies have suggested that gold nanoparticles (Au NPs) may also be therapeutically efficacious. These observations prompted the current biological studies involving gold(I) anti-RA agents and Au NPs, which are aimed towards improving our knowledge of how they work. The cytotoxicity of auranofin, aurothiomalate, aurothiosulfate and Au NPs towards RAW264.7 macrophages was evaluated using the MTT assay, with the former compound proving to be the most toxic. The extent of cellular uptake of the various gold agents was determined using graphite furnace atomic absorption spectrometry, while their distribution within macrophages was examined using microprobe synchrotron radiation X-ray fluorescence spectroscopy. The latter technique showed accumulation of gold in discrete regions of the cell, and co-localisation with sulfur in the case of cells treated with aurothiomalate or auranofin. Electrospray ionization mass spectrometry was used to characterize thioredoxin reductase (TrxR) in which the penultimate selenocysteine residue was replaced by cysteine. Mass spectra of solutions of TrxR and aurothiomalate, aurothiosulfate or auranofin showed complexes containing bare gold atoms bound to the protein, or protein adducts containing gold atoms retaining some of their initial ligands. These results support TrxR being an important target of gold(I) drugs used to treat RA, while the finding that Au NPs are incorporated into macrophages, but elicit little toxicity, indicates further exploration of their potential for treatment of RA is warranted.
27242784 Immune Complexes in Juvenile Idiopathic Arthritis. 2016 Juvenile idiopathic arthritis (JIA) reflects a group of clinically heterogeneous, autoimmune disorders in children characterized by chronic arthritis and hallmarked by elevated levels of circulating immune complexes (CICs) and associated complement activation by-products in their sera. Immune complexes (ICs) have been detected in patients' sera with JIA utilizing a variety of methods, including the anti-human IgM affinity column, C1q solid-phase assay, polyethylene glycol precipitation, Staphylococcal Protein A separation method, anti-C1q/C3 affinity columns, and FcγRIII affinity method. As many as 75% of JIA patients have had IC detected in their sera. The CIC proteome in JIA patients has been examined to elucidate disease-associated proteins that are expressed in active disease. Evaluation of these ICs has shown the presence of multiple peptide fragments by SDS-PAGE and 2-DE. Subsequently, all isotypes of rheumatoid factor (RF), isotypes of anti-cyclic citrullinated peptide (CCP) antibodies, IgG, C1q, C4, C3, and the membrane attack complex (MAC) were detected in these IC. Complement activation and levels of IC correlate with disease activity in JIA, indicating their role in the pathophysiology of the disease. This review will summarize the existing literature and discuss the role of possible protein modification that participates in the generation of the immune response. We will address the possible role of these events in the development of ectopic germinal centers that become the secondary site of plasma cell development in JIA. We will further address possible therapeutic modalities that could be instituted as a result of the information gathered by the presence of ICs in JIA.
27847735 Diseases having an influence on inhibition of angiogenesis as risk factors of osteonecrosi 2016 Oct OBJECTIVES: The objective of this study was to retrospectively investigate the association of diseases having an influence on inhibition of angiogenesis such as hypertension, diabetes mellitus type II, hypercholesterolemia, and rheumatoid arthritis (RA) with the development of osteonecrosis of the jaws. MATERIALS AND METHODS: The 135 patients were allocated into 4 groups of bisphosphonate-related osteonecrosis of the jaw (BRONJ) group (1A); non-BRONJ group (1B); osteonecrosis of the jaw (ONJ) group (2A); and control group (2B), according to histologic results and use of bisphosphonate. This retrospective study was conducted with patients who were treated in one institute from 2012 to 2013. Fisher's exact test and logistic regression analysis were used to analyze the odds ratios of diseases having an influence on inhibition of angiogenesis for development of ONJ. RESULTS: The effects of diabetes and hypertension were not statistically significant on development of ONJ. When not considering bisphosphonate use, RA exhibited a high odds ratio of 3.23 (P=0.094), while hyperlipidemia showed an odds ratio of 2.10 (P=0.144) for development of ONJ. More than one disease that had an influence on inhibition of angiogenesis showed a statistically significant odds ratio of 2.54 (P=0.012) for development of ONJ. CONCLUSION: Patients without diseases having an influence on inhibition of angiogenesis were at less risk for developing ONJ.
26408009 Liver cirrhosis in selected autoimmune diseases: a nationwide cohort study in Taiwan. 2016 Feb The association between autoimmune diseases and liver cirrhosis has rarely been explored in Asian populations, an endemic area of viral hepatitis. The aim of this study was to investigate the comparative risk of liver cirrhosis among a group of selective autoimmune diseases in Taiwanese patients and to identify groups of high risk. This retrospective study was a nationwide, population-based study and used Taiwan's National Health Insurance Research Database. A total of 29,856 patients with definite diagnosis of selected autoimmune diseases (Registry of Taiwan Catastrophic Illness Database, ACR classification) at the starting time point of January 1, 2005, were enrolled in this study. After tracked for a 5-year period, the endpoints were diagnosis of liver cirrhosis (in accordance with International Classification of Diseases, Ninth Revision, Clinical Modification, ICD-9-CM codes 571). The control group was composed of other patients in the same database and consisted of randomly selected 753,495 sex- and age-matched non-autoimmune disease patients. The Cox proportional hazard regression model was used to calculate the risk of liver cirrhosis after adjusting for certain variables such as comorbidity, living area, and socioeconomic status. Among the patients with selected autoimmune diseases, 1987 liver cirrhosis were observed. Patients with psoriasis had a significantly increased risk of liver cirrhosis (HR 1.87, 95 % CI 1.25-2.81) than control group without psoriasis. The risk of liver cirrhosis was significantly lower in patients with rheumatoid arthritis (HR 0.29, 95 % CI 0.19-0.44). There is a gradient of risk of liver cirrhosis among the autoimmune diseases; the specific risks need to be investigated on the basis of hypotheses. Conventional immunosuppressive drug administration should be carefully implemented by regular monitoring of liver condition in order to avoid causing an adverse effect of chronic liver fibrosis.
27672484 Pharmaceutical Innovation in the Treatment of Schizophrenia and Mental Disorders Compared 2016 Jul OBJECTIVES: The objectives of this study were to assess the level of private and public investment in research and development of treatments for schizophrenia and other mental disorders compared to other diseases in order to present data on the economic burden and pharmaceutical innovation by disease area, and to compare the level of investment relative to burden across different diseases. DESIGN: The levels of investment and pharmaceutical innovation relative to burden across different diseases were assessed. Disease burden and prevalence for mental disorders (schizophrenia, bipolar disorder, and major depressive disorder); cancer; rheumatoid arthritis; chronic obstructive pulmonary disorder; diabetes; cardiovascular disease; and neurological disorders (dementia and epilepsy) were estimated from literature sources. SETTING: Pharmaceutical treatment innovation was measured by the total number of drug launches and the number of drugs launched categorized by innovativeness. Research and development expenditures were estimated using published information on annual public and domestic private research and development expenditures by disease area. Lastly, investment relative to disease burden was measured among the set of disease classes for which all three measures were available: schizophrenia, bipolar disorder, major depressive disorder, cancer, rheumatoid arthritis, chronic obstructive pulmonary disease, diabetes, cardiovascular disease, and neurology (dementia and epilepsy combined). RESULTS: The level of investment and pharmaceutical innovation in mental disorders was comparatively low, especially relative to the burden of disease. For mental disorders, investment was $3.1 per $1,000 burden invested in research and development for schizophrenia, $1.8 for major depressive disorder, and $0.4 for bipolar disorder relative to cancer ($75.5), chronic obstructive pulmonary disease ($9.4), diabetes ($7.6), cardiovascular disease ($6.3), or rheumatoid arthritis ($5.3). Pharmaceutical innovation was also low for mental disorders. CONCLUSION: Despite the significant burden mental disorders impose on society, investment and pharmaceutical innovation in this disease area remains comparatively low. Policymakers should consider new strategies to stimulate public and private investment in the research and development of novel and effective therapies to treat schizophrenia and other mental disorders.
26309442 Ameliorating Role Exerted by Al-Hijamah in Autoimmune Diseases: Effect on Serum Autoantibo 2015 Apr Autoimmune diseases have common properties characterized by abnormal blood chemistry with high serum autoimmune antibodies, and inflammatory mediators. Those causative pathological substances (CPS) cannot be excreted by physiological mechanisms. Current treatments for autoimmune diseases involve steroids, cytotoxic drugs, plasmapheresis and monoclonal antibodies. Wet cupping therapy (WCT) of prophetic medicine is called Al-hijamah that treats numerous diseases having different etiology and pathogenesis via a pressure-dependent and size-dependent non-specific filtration then excretion of CPS causing clearance of blood and interstitial fluids. Al-hijamah clears blood passing through the fenestrated skin capillaries. Medical bases of Al-hijamah were reported in the evidence-based Taibah mechanism (Taibah theory). Al-hijamah was reported to be an excellent treatment for rheumatoid arthritis that improved patients' blood chemistry and induced significant clinical improvement and pharmacological potentiation. Al-hijamah improved the natural immunity and suppressed the pathological immunity through decreasing the serum level of autoantibodies, inflammatory mediators, and serum ferritin (a key player in autoimmunity). Al-hijamah reduced significantly pain severity, number of swollen joints and disease activity with no significant side effects. Main steps of Al-hijamah are skin suction (cupping), scarification (sharatmihjam in Arabic) and second suction (triple S technique) that is better therapeutically than the traditional WCT (double S technique). Whenever an excess noxious substance is to be removed from patients' blood and interstitial fluids, Al-hijamah is indicated. Shartatmihjam is a curative treatment in prophetic teachings according to the prophetic hadeeth: "Cure is in three: in shartatmihjam, oral honey and cauterization. I do not recommend my nation to cauterize". Al-hijamah may have better therapeutic benefits than plasmapheresis. Al-hijamah may be promising in treating autoimmune diseases as a sole treatment or adjuvant treatment.
25981510 Whole-Genome Sequencing and Integrative Genomic Analysis Approach on Two 22q11.2 Deletion 2015 Aug The 22q11.2 deletion syndrome (22q11DS) affects 1:4,000 live births and presents with highly variable phenotype expressivity. In this study, we developed an analytical approach utilizing whole-genome sequencing (WGS) and integrative analysis to discover genetic modifiers. Our pipeline combined available tools in order to prioritize rare, predicted deleterious, coding and noncoding single-nucleotide variants (SNVs), and insertion/deletions from WGS. We sequenced two unrelated probands with 22q11DS, with contrasting clinical findings, and their unaffected parents. Proband P1 had cognitive impairment, psychotic episodes, anxiety, and tetralogy of Fallot (TOF), whereas proband P2 had juvenile rheumatoid arthritis but no other major clinical findings. In P1, we identified common variants in COMT and PRODH on 22q11.2 as well as rare potentially deleterious DNA variants in other behavioral/neurocognitive genes. We also identified a de novo SNV in ADNP2 (NM_014913.3:c.2243G>C), encoding a neuroprotective protein that may be involved in behavioral disorders. In P2, we identified a novel nonsynonymous SNV in ZFPM2 (NM_012082.3:c.1576C>T), a known causative gene for TOF, which may act as a protective variant downstream of TBX1, haploinsufficiency of which is responsible for congenital heart disease in individuals with 22q11DS.
26866930 Effect of Angiotensin-(1-7) on Aortic Response, TNF-α, IL-1β and Receptor for Advanced G 2016 Altered vascular reactivity due to endothelial dysfunction, consequent to vascular damage, is observed in rheumatoid arthritis. We investigated the effect of angiotensin (Ang)-(1-7) on vasculature changes in arthritis induced by complete Freund's adjuvant in male Wistar rats. Arthritis decreased soluble receptor for advanced glycation end products (sRAGE) whereas elevated aortic RAGE expression, increased interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), systolic blood pressure and the contractility induced by phenylephrine and KCl. Moreover, arthritis decreased the relaxing effect of acetylcholine. Neither arthritis nor Ang-(1-7) altered sodium nitroprusside relaxation. Ang-(1-7) reversed the effect of arthritis on TNF-α, sRAGE and RAGE expression without any effect on the IL-1β. Ang-(1-7) decreased phenylephrine and KCl contractility, especially in the endothelial-denuded aorta, whereas increased acetylcholine relaxation in the endothelial-intact aorta. Ang-(1-7) could find its place in the treatment protocol of arthritis and vascular diseases.
26424019 Excessive Interleukin 18 Relate the Aggravation of Indomethacin-Induced Intestinal Ulcerog 2015 It is well known that rheumatoid arthritis patients taking nonsteroidal anti-inflammatory drugs (NSAIDs) are more susceptible to NSAIDs-induced gastroenteropathy in comparison with other patients. In this study we demonstrate that expression levels of interleukin (IL)-18 are related to aggravation of intestinal ulcerogenic lesions in adjuvant-induced arthritis (AA) rats following oral administration of indomethacin. AA rats were administered oral indomethacin (40 mg/kg) and killed under deep isoflurane anesthesia after 24 h. The small intestinal mucosa was then examined. Oral administration of indomethacin caused hemorrhagic lesions in the small intestinal mucosa of AA rats, and the lesion score of AA rats 24 h after indomethacin treatment was approximately 5.6-fold higher than for normal rats administered indomethacin. IL-18 expression in the small intestinal mucosa of AA rats administered indomethacin was also higher in comparison with normal rats receiving indomethacin. In addition, interferon-γ and nitric oxide levels in the small intestinal mucosa of AA rats were increased following oral administration of indomethacin. It is possible that IL-18 expression in AA rats renders the small intestinal mucosa more sensitive to indomethacin, and that IL-18 may play a role in aggravating intestinal ulcerogenic lesions in AA rats treated with this drug.
27294654 Palisaded neutrophilic and granulomatous dermatitis - cutaneous manifestation of Lyme dise 2016 Jun 2 INTRODUCTION: Palisaded neutrophilic and granulomatous dermatitis (PNGD) are terms which include such diseases as rheumatoid nodules, Churg-Strauss granuloma, and interstitial granulomatous dermatitis with arthritis. This heterogeneous group was first described in 1965. It is associated with immunological diseases. There are reported cases of coexistence with systemic lupus erythematosus, rheumatoid arthritis, Wegener's granuloma, inflammatory bowel disease, generalized vascular inflammation, and lymphoproliferative disorders. The etiology of the disease is unknown. It is probable that the deposition of immune complexes in blood vessels leads to cutaneus leukocytoclastic vasculitis, degeneration of collagen fibres and palisaded granulomatous inflammation. Ultimately, this leads to fibrosis of the skin. OBJECTIVE: The aim of the study is to present a patient with skin lesions and histopathological features of palisaded neutrophilic and granulomatous dermatitis during the course of infection Borrelia burgdorferi. Several cases of this disease have been reported worldwide (30 entries in the PubMed database). To-date, there have been no reports of PNGD in Polish literature. MATERIALS AND METHOD: The patient, aged 72, was admitted to hospital because of erythematous, indurated lesion of the skin on the side surface of the left thigh. Diagnosis of PNGD was made on the basis of typical histopathologic features due to clinical symptoms. CONCLUSIONS: Clinical diagnosis of PNGD is difficult, and is based mainly on the histopathological picture. Systemic therapy is incorporated mainly due to the systemic disease. The patient requires further observation in the direction of associated systemic disorders.