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

ID PMID Title PublicationDate abstract
28710538 [Manifestations of autoimmune disorders in otorhinolaryngology : Classical symptoms and di 2017 Aug Manifestations of autoimmune disorders represent a diagnostic challenge. Many autoimmune disorders show typical manifestations in the ear, nose and throat and should be taken into account in the differential diagnosis. Sjogren's syndrome, various vasculitides and sarcoidosis represent the most common autoimmune disorders in otorhinolaryngology, but IgG4-related diseases, relapsing polychondritis and autoimmune disorders of the mucosa are also observed. Autoimmune diseases can lead to sensorineural deficits. Both hypo- and hyperthyroidism can be caused by autoimmune disorders. The diagnosis is usually based on the corresponding classification criteria, whose correct application can facilitate the clarification of these diseases.
29326703 Both Systemic and Intra-articular Immunization with Citrullinated Peptides Are Needed to I 2017 OBJECTIVES: Anti-citrullinated peptides antibodies (ACPAs) have high specificity for the diagnosis of rheumatoid arthritis (RA), but their role in the pathophysiology is not fully established. The main genetic risk factor for RA, the shared epitope in major histocompatibility complex class II, is associated with ACPAs. Among certain non-human primates, 8% carry the shared epitope called H6 haplotype, and being similar to humans, are ideal candidates to study the role of ACPAs in RA. The goal of this study was to develop a macaque model of RA based on immunization against citrullinated peptides to generate an ACPA-mediated model of arthritis. METHODS: Cynomolgus macaques were immunized with four citrullinated peptides from vimentin, fibrinogen, and aggrecan, known to induce T-cell response in RA patients, and received an intra-articular (IA) boost with the same four citrullinated peptides pooled. RESULTS: In the macaque, the T-cell response was specific to citrullinated peptides. Antibodies generated in response to immunization were cross-reactive between the citrulline and arginine peptides. The presence of the H6 haplotype did not affect the magnitude of the immune response. Since no clinical response was observed, macaques received an IA boost with the same four peptides pooled and incomplete Freund's adjuvant, which led to a prolonged neutrophil-rich mono-arthritis, preferentially in H6-positive animals. Conversely, animals boosted with incomplete Freund's adjuvant alone presented only transient mono-arthritis. CONCLUSION: This two-hit model of prolonged mono-arthritis mimics what could happen in RA. Despite the limited number of joints with disease in the macaque model, the model appears unique to study the events occurring during the preclinical phase of RA, from immunization against citrullinated peptides to the clinical appearance of disease.
29124434 Effect of prednisone treatment for 30 and 90 days on bone metabolism in collagen-induced 2018 Nov Glucocorticoids (GCs) are often prescribed to treat rheumatoid arthritis (RA) in the long term, but there is still controversy in the administration of GCs, mainly because of the adverse reactions such as osteoporosis. Numerous studies have demonstrated that osteoporosis could be induced by GCs in normal rats. However, few experiments have focused on whether osteoporosis could be induced or aggravated by GCs in collagen induced arthritis (CIA) rats. We have investigated bone changes in CIA rats treated with prednisone at 4.5 mg/kg/day for 30 and 90 days by bone histomorphometry, bone mineral density (BMD), micro-CT, biomechanical test, and enzyme-linked immunosorbant assay. We found that high bone turnover osteoporosis was shown in CIA rats. Prednisone treatment for 30 and 90 days improved articular structure and decelerated the degeneration of the femur in CIA rats, but did not improve BMD and bone biomechanics. We conclude that osteoporosis was not aggravated in CIA rats treated with prednisone for 30 and 90 days. On the contrary, prednisone treatment for 30 and 90 days could prevent bone loss of the femur in CIA rats. There was a negative effect on bone metabolism in CIA rats treated with prednisone for 90 days.
28181179 Clinical Examination, Ultrasound and MRI Imaging of The Painful Elbow in Psoriatic Arthrit 2017 Jun INTRODUCTION: The purpose of the current study was to examine the painful elbow, and in particular enthesitis, in psoriatic arthritis (PsA) and rheumatoid arthritis (RA) using clinical examination, ultrasonography (US) and magnetic resonance imaging (MRI). METHODS: Patients with elbow pain (11 with PsA and 9 with RA) were recruited. Clinical examination, US and MRI studies were performed on the same day. For enthesitis, the common extensor and flexor insertions and the triceps insertion were imaged (20 patients, giving a total of 60 sites with comparative data). Imaging was performed with the radiologists blinded to the diagnosis and clinical findings. US was used to assess 'inflammatory activity' (Power Doppler signal, oedema, tendon thickening and bursal swelling) and 'damage' (erosions, cortical roughening and enthesophytes). MRI was used to assess 'inflammation' (fluid in paratenon, peri-entheseal soft-tissue oedema, entheseal enhancement with gadolinium, entheseal oedema and bone oedema) and 'damage' (erosion, cortical roughening and enthesophyte). RESULTS: Complete scan data were not available for all patients as one patient could not tolerate the MRI examination. No significant differences in imaging scores were found between PsA and RA. Analysis of damage scores revealed complete agreement between US and MRI data in 43/55 (78%) comparisons; in 10/55 (18%) cases the US data were abnormal but the MRI data normal; in 2/55 (4%) cases, the MRI data were abnormal and the US data normal. Analysis of the inflammation scores revealed complete agreement between US and MRI data in 33/55 (60%) comparisons; in 3/55 (5%) cases US data were abnormal but MRI data normal; in 19/55 (35%) cases the MRI data were abnormal and the US data normal. There was a poor relationship between assessments based on clinical examination and imaging studies. Readers could not accurately identify the disease from imaging findings. CONCLUSION: Based on our results, at the elbow, US and MR have different roles in assessing enthesitis, with US apparently the better diagnostic tool for assessing damage and MR the better tool for assessing inflammation. In this study enthesitis and synovitis in the painful elbow were found equally in cases of established RA and PsA.
30775513 Compliance and discontinuation of denosumab treatment in postmenopausal Japanese women wit 2017 Jun OBJECTIVES: The aim of this study was to examine the discontinuation and occurrence of fracture during denosumab treatment in Japanese women with primary osteoporosis or rheumatoid arthritis (RA) with osteoporosis. METHODS: This retrospective study included 143 patients with primary osteoporosis and 96 patients with RA and osteoporosis who were treated with denosumab. Treatment discontinuation, fracture occurrence, lumbar spine (L1-4) bone mineral density (LS-BMD), and bilateral total hip BMD (TH-BMD) were examined before and at 1 and 2 years after treatment commencement. RESULTS: In the primary osteoporosis group, 32 cases dropped out and no fractures occurred from 0 to 1 year. Eighteen cases were lost to follow-up and no fractures were noted from 1 to 2 years. In the RA with osteoporosis group, 7 cases dropped out and no fracture occurred from 0 to 1 year. Twenty-one cases were lost to follow-up and 2 nonvertebral fractures were noted from 1 to 2 years. In this group, 13 cases dropped out from 1 to 2 years and 16 cases dropped out during the 2-year study period due to economic reasons. LS-BMD and TH-BMD values increased continuously for 2 years of treatment in both primary osteoporosis and RA with osteoporosis groups. CONCLUSIONS: These results suggest that during denosumab therapy, the discontinuation rate is expected to remain low during 2 years of treatment in primary osteoporotic patients. In RA patients with osteoporosis, however, the discontinuation rate may increase due to economic reasons from 1 to 2 years of therapy.
30207562 Tofacitinib Versus Non-Tumor Necrosis Factor Biologics for Patients With Active Rheumatoid 2018 Jun OBJECTIVES: This study aims to compare the disease status of patients with active rheumatoid arthritis (RA) after treatment with tofacitinib or non- tumor necrosis factor (TNF) biologics. PATIENTS AND METHODS: The study included a total of 50 RA patients (18 males, 32 females; mean age 68.3±1.3 years; range 42 to 92 years). We prospectively and randomly enrolled 25 patients for treatment with tofacitinib (Tofa group: 10 males, 15 females; mean age 68.3±2.0 years; range, 42 to 92 years) and 25 for treatment with non-TNF biologics (non-TNF group: 8 males, 17 females; mean age 68.3±1.7 years; range 51 to 92 years). Mean disease activity score 28 (DAS28), C-reactive protein (CRP), clinical disease activity index (CDAI), health assessment questionnaire (HAQ)-disability index (DI), and matrix metalloproteinase-3 values were recorded at baseline and at 4, 8, and 12 months. RESULTS: There was a significant difference in the percent changes of DAS28, CRP and CDAI at every time point versus baseline in both treatment groups. HAQ-DI was also significantly different at every time point in both groups except for at four months in the non-TNF group. CONCLUSION: Tofacitinib was well tolerated in active RA patients and exerted effects comparable to those of non-TNF biologics.
29445673 Periodontitis in rheumatoid arthritis patients, abundance and association with disease act 2017 Background: There are some discrepancy in association between activity of rheumatoid arthritis (RA) and periodontitis. The aim of this study was to evaluate the periodontal status of outpatients with RA. Methods: The study was conducted in 2013-14 in a rheumatology clinic in Sari, north of Iran on 74 patients with RA. Evaluation of RA disease activity was according to disease activity score 28 (DAS28). Periodontitis was evaluated by probing depth (PD), gingival index (GI), clinical attachment level (CAL index), plaque index (PI), and panoramic X-ray. Statistical analysis included independent ttest and Mann-Whitney U test for quantitative, and chi square and OR for qualitative variables and evaluation of RA activity and periodontitis severity. Results: The mean±SD of age and disease duration were 47.01±8.1 and 8.93±8.6 years, respectively and the mean±SD number of teeth was 20.70±6.8. Twenty-seven (36.5%) patients had moderate to severe disease. Forty-seven cases (63.5%) were found with periodontitis and 14 (12.2%) were identified to have moderate to severe periodontitis, unrelated to disease activity (p=0.22). For active/inactive periodontitis OR =1.33 (95% CI: 0.46 - 3.87) was computed. There was no association between RA disease activity and number of teeth, CAL, PI, PD, and GI, (p>0.05). Conclusion: About 60% of RA patients suffered from periodontitis, but there was not any significant relation between RA disease activity and severity of periodontitis. Periodontitis may interfere with management and follow up of RA, so periodic periodontal examination is suggested in these patients.
28883856 Interleukin-21 gene polymorphism rs2221903 is associated with disease activity in patients 2017 Aug INTRODUCTION: Interleukin-21 (IL-21) is a cytokine which plays a significant role in the pathogenesis and disease activity of rheumatoid arthritis (RA). Genetic polymorphisms in the IL-21 gene may alter the synthesis of IL-21. The aim of this study was to examine IL-21 and IL-21R polymorphisms in patients with RA. MATERIAL AND METHODS: We examined 422 patients with RA and 338 healthy controls. Single nucleotide polymorphisms (SNPs) within the IL-21 (rs6822844 G>T, rs6840978 C>T, rs2221903 T>C) and IL-21R (rs2285452 G>A) genes were genotyped using TaqMan genotyping assays. RESULTS: There were no statistically significant differences in the distribution of studied genotypes and alleles between RA patients and the control group. To examine whether IL-21 polymorphisms affect disease activity in RA patients, we compared the distribution of IL-21 genotypes between patients with DAS28 ≤ 2.5 (patients with remission of disease symptoms) and patients with DAS28 > 2.5 (patients with active RA). Among patients with DAS28 > 2.5, increased prevalence of rs2221903 CT and CC genotypes was observed (OR = 1.54; 95% CI: 1.04-2.28; p = 0.035). CONCLUSIONS: The results of this study suggest that IL-21 and IL-21R gene polymorphisms are not risk loci for RA susceptibility, whereas the IL-21 rs2221903 polymorphism is associated with disease activity.
28638694 Giant cell arteritis, polymyalgia rheumatica, and late-onset rheumatoid arthritis: Can the 2017 Jun OBJECTIVE: To report two patients with giant cell arteritis (GCA) who developed rheumatoid arthritis (RA) and to review the literature in terms of coexistence of RA, GCA, and polymyalgia rheumatica (PMR). METHODS: We conducted a comprehensive review of the English literature from 1980 to 2015 to analyze data on the coexistence of GCA and RA. The PubMed, Web of Science, Proquest, and Ovid databases were searched for articles using the term RA combined with temporal arteritis, GCA, and PMR. RESULTS: We identified 17 other cases of coexistent GCA and RA reported in the English literature, together with our 2 cases (19 cases). They included 14 females and 5 males, with a mean age of 74.3 years (range: 57-84) at the time of GCA. The mean age at the time of RA diagnosis was 69.6 years (range 24-83). The average time elapsed between the onset of GCA and the development of RA was 6.7 years (range: 3 month-34 years). RA and GCA were reported as the first disease in 10 cases and 4 cases, respectively. The development of these 2 diseases in a narrow period of time appeared in 4 cases (3 months-19 months). PMR was the first disease in 1 case. CONCLUSION: RA, GCA, and PMR may appear simultaneously or consecutively; therefore, we suggest that physicians should be alert about such a fact so that a proper diagnosis and treatment could be tailored accordingly.
28451396 Association between interleukin-1 receptor associated kinase 1 rs3027898 A/C gene polymorp 2017 Mar Rheumatoid arthritis (RA) is a systemic autoimmune disease predominantly involving the synovial joints and affects up to 1% of adults worldwide. The aim of the present study was to determine whether the interleukin-1 receptor (IL1R)-associated kinase (IRAK1) rs3027898 gene polymorphism confers susceptibility to RA in a sample of patients from Iran. This gene encodes IRAK1, one of two putative serine/threonine kinases that associates with IL1R upon stimulation. IRAK1 is partially responsible for IL-1-induced upregulation of the transcription factor, nuclear factor-κB. The present case-control study was performed on 120 patients with RA and 120 healthy individuals. Genomic DNA was extracted from whole blood, and the gene polymorphism was evaluated using a tetra-primer amplification refractory mutation system-polymerase chain reaction method. The results demonstrated that there was no association between IRAK1 rs3027898 CA genotype and the risk of RA in women (odds ratio=0.72, 95% confidence interval=0.41-1.49; P=0.446). Further studies with larger sample sizes and different ethnicities are required to validate the present findings.
28638686 Rheumatoid Arthritis: Are psychological factors effective in disease flare? 2017 Jun OBJECTIVE: Rheumatoid arthritis (RA) is clinically an undulant disease, and reasons for flare or remission vary. We aimed to identify factors potentially associated with disease flare and remission. MATERIAL AND METHODS: Two hundred and seventy-four patients with RA who were admitted to our center between January 2010 and January 2016 were included. Disease activity was evaluated using disease activity score 28 (DAS 28); functional status was evaluated using the modified Health Assessment Questionnaire (m-HAQ), a questionnaire that comprises flare or remission domains such as psychological stress and mood status, physical trauma, nutrition regimen, infection, antibiotic use, and seasonal weather changes. Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI) were used to identify if patients had a mood disorder. Four subscales of Arthritis Impact Measurement Scale-2 (AIMS-2) (level of tension, mood, general perception of health, and satisfaction with health) were used to determine patient quality of life. RESULTS: Of the 274 patients, 261 were female (95.3%) and 13 were male (4.7%); the mean age was 52.10±9.41 years. According to patients' perception, the most frequent reasons for joint symptoms were psychological stress/mood disorder (86.1%), followed by infection (49.6%) and trauma (46.4%). The most frequent factors for remission of symptoms were antibiotic use (42.7%), cold weather (34.3%), and hot weather (19%). CONCLUSION: Psychological stress and mood status are independent factors for relapse periods in patients with RA. These should be considered particularly in patients who are resistant to different treatment regimens and in whom any other reason for disease flare is not obvious.
31473721 Scrutinising the Link between Periodontal Disease and Systemic Conditions: Does Recent Evi 2017 Apr 1 During the 9th European Workshop in Periodontology, the evidence base for the link between periodontal disease and systemic conditions was scrutinised. In response, the European Federation of Periodontology (EFP) issued a manifesto that summarised these findings. This article has critically evaluated the research published after the 9th European Workshop in Periodontology in November 2012 to ascertain whether recent research has affected the merit of the manifesto. It was found that recent research supports the manifesto regarding diabetes mellitus, cardiovascular disease and adverse pregnancy outcomes, although further high-quality randomised controlled trials are required to support the manifesto statement that "certain populations of pregnant women may benefit from periodontal therapy." Furthermore, there is now good evidence from systematic reviews for an association between periodontal disease and chronic obstructive pulmonary disease, rheumatoid arthritis, chronic kidney disease and metabolic syndrome. This may be sufficient to warrant an update to the manifesto. Causal relationships remain debatable. There is also recent emerging evidence for an association with obstructive sleep apnoea. The recent evidence investigating obesity and periodontal disease is mixed, and no new systematic studies or randomised controlled trials were found relating to cognitive impairment.
28879055 Working in cold environment and risk of developing rheumatoid arthritis: results from the 2017 OBJECTIVES: To investigate (1) whether working in cold environment (WCE) is associated with an increased risk of developing rheumatoid arthritis (RA) (overall), anticitrullinated protein antibody (ACPA)-positive RA and ACPA-negative RA and (2) whether WCE interacts with occupational physical workload in conferring RA risk. METHODS: Data from the Swedish population-based case-control study Epidemiological Investigation of Rheumatoid Arthritis involving 3659 incident cases and 5925 controls were analysed. Study participants were asked whether they had ever worked in cold/outdoor environment along with their exposure duration and frequency. Occurrence of RA among exposed and unexposed subjects were compared by calculating ORs with 95% CI using logistic regression. Additive interactions between WCE and six types of physical workload were assessed using the principle of departure from additivity by calculating attributable proportion due to interaction (AP). RESULTS: The OR associated with having ever worked in cold environment was 1.5 (95% CI 1.4 to 1.7) for RA (overall), 1.6 (95% CI 1.4 to 1.8) for ACPA-positive RA and 1.4 (95% CI 1.2 to 1.6) for ACPA-negative RA. The risk of developing RA increased with increasing cumulative dose of working in cold indoor environment (p value <0.001), but not working in cold outdoor environment. Positive additive interaction was observed between WCE and repetitive hand/finger movements (AP 0.3 (95% CI 0.1 to 0.5)). CONCLUSIONS: WCE is associated with increased risk of developing both ACPA-positive and ACPA-negative RA. A dose-response relationship was found between working in cold indoor environment and risk of developing RA. Moderate additive interaction was observed between exposure to cold environment and exposure to repetitive hand/finger movements.
28337386 Long-term clinical outcomes of patients with rheumatoid arthritis and concomitant coronary 2017 BACKGROUND: Rheumatoid arthritis (RA) is associated with high morbidity and mortality predominately due to increased cardiovascular risk. Few reports are available regarding the management of coronary artery disease (CAD) in RA patients and the long-term clinical outcomes after coronary revascularization. METHODS AND RESULTS: All consecutive patients with RA were identified by retrospective review at a rheumatology tertiary center in Milan, Italy between 2001 and 2013. RA patients affected by significant CAD (RA-CAD+) were prospectively followed for major adverse cardiovascular and cerebrovascular events (MACCE) after percutaneous coronary revascularization (RA-PCI), coronary artery bypass grafting (RA-CABG) or medical therapy (RA-MT). Among 936 patients with RA, the presence of clinically significant CAD was found in 5.6% (53 patients, RA-CAD+). Of these, 32 patients (60%) underwent PCI (RA-PCI), 10 patients (19%) underwent CABG (RA-CABG) and 11 patients (21%) treated with MT (RA-MT). After a mean follow-up of 9±7 years, the rate of MACCE was 56% in RA-PCI patients, 50% in RA-CABG and 27% in RA-MT patients (P=0.184). The high MACCE rate was mainly driven by repeat coronary revascularization (47%) in the RA-PCI group and high rate of strokes (30%) in RA-CABG patients. CONCLUSION: In patients with rheumatoid arthritis and concomitant coronary artery disease (RA-CAD+), we observed at long-term follow-up a high MACCE rate, predominantly in those who underwent coronary revascularization.
29089788 Adalimumab impact on fatigue measured by FACIT-F: a study of rheumatoid arthritis patients 2017 OBJECTIVE: The objective of the study was to assess the effectiveness of adalimumab as a treatment for fatigue in patients with rheumatoid arthritis (RA). METHODS: Fatigue was monitored in patients with RA who were already on an adalimumab treatment regimen. Fatigue, general well-being, comorbidities, and disease activity were measured at baseline and ~8, 16, and 24 weeks, thereafter. RESULTS: Significant reductions in fatigue scores and disease activity were observed from baseline to 6 months after. A predictive regression model of fatigue severity was proposed and was found to be significant, with RA disease activity as the most significant predictor of fatigue severity. CONCLUSION: This quasi-experimental study is a good starting point for research on the efficacy of adalimumab in treating fatigue in RA patients. The results here suggest that a randomized controlled trial assessing adalimumab as a treatment option for RA patients suffering from fatigue is warranted.
28560193 Comparative Evaluation of Heavy Metals in Patients with Rheumatoid Arthritis and Healthy C 2017 May BACKGROUND: Exposure to heavy metals in development of many diseases has been investigated previously, specially created by oxidative stress. The etiology of Rheumatoid arthritis (RA) is still not fully understood but oxidative stress created by heavy metals may have role in development of RA. The aim of present study was to compare serum level of heavy metals in RA and healthy control individuals. METHODS: Blood samples of 100 RA patients were collected from different hospitals in district Sargodha, Punjab, Pakistan and 100 control individuals from Dec 2013 to May 2014.The serum samples were analyzed for determination of Pb, Cd, Cr and Ni through Atomic absorption spectrophotometer (AA 6600 Shimadzu). RESULTS: Statistically highly significant difference was observed between RA patients and healthy control individuals for Pb, Cd, Cr, and Ni level (P<0.01). The difference between the means of both sexes was not significant for Pb and Cd concentrations (P>0.01). For Cr the difference between the means of both sexes was statistically not significant in RA +ve patients and highly significant difference was observed between both sexes in healthy control group (P<0.01). The difference between the means of both sexes for Ni was statistically non-significant in healthy control group while significant difference was observed between both sexes in RA +ve group (P<0.05). Statistically non-significant difference for Pb, Cd, Cr and Ni level was found among the all three age groups of RA and healthy control individuals (P>0.01). CONCLUSION: Concentration of heavy metals in serum samples of RA patients and healthy control individuals differ significantly, which shows that heavy metals may contributes towards development of RA.
27391167 John Cunningham (JC) virus genotypes in kidney transplant recipients, rheumatoid arthritis 2017 Feb In healthy individuals John Cunningham virus is latent without any clinical signs, but in the cases of the use of immunosuppressive drugs in graft recipients, autoimmune diseases and also increasing of age, that the immune system is suppressed it may cause disease in reactivation. Progressive multifocal leukoencephalopathy (PML) is the well-known disease caused by the virus. It has also been associated with nephropathy and tumorogensis. At present, based on vp1 capsid gene 7 genotypes have been detected. Genetic variations of JC virus in different geographical areas and the presence of different subtypes is a useful tool for reconstructing of the genetic information of JC virus and understanding of its evolution. The aim of this study was to investigate different genotypes of the JC virus in the urine of 100 kidney transplant recipients, 43 rheumatoid arthritis patients, and 100 healthy individuals as control group in Isfahan. DNA was extracted by phenol-chloroform method and subjected to a nested PCR using specific primer for vp1 capsid gene designed by Oligo 7 software. Fisher's exact test was used for statistical analyses. Using MEGA 6 software the sequences were aligned using Clustal W tool and phylogenetic trees were constructed by neighbor joining method. Thirty-one positive samples were sequenced. Genotypes 1, 3, and 4 of the virus were detected for the first time in Iran. For the first time genotype 3 was reported as the dominant genotype in Iran. For the first time in the world, genotype 4 was detected in rheumatoid arthritis patients. J. Med. Virol. 89:337-344, 2017. © 2016 Wiley Periodicals, Inc.
29068268 Structural insights into the binding mode of flavonols with the active site of matrix meta 2018 Nov Cartilage degradation in rheumatoid arthritis is mediated principally by the collagenases and gelatinases. Gelatinase B (also called matrix metalloproteinase 9 - MMP-9), is a valid target molecule which is known to participate in cartilage degradation as well as angiogenesis associated with the disease and inhibition of its activity shall prevent cartilage damage and angiogenesis. The focus of this study is to investigate the possibilities of MMP-9 inhibition by flavonol class of bioflavonoids by studying their crucial binding interactions at the active site of MMP 9 using molecular docking (Glide XP and QPLD) and further improvisation by post-docking MM-GBSA and molecular dynamic (MD) simulations. The results show that flavonols can convincingly bind to active site of MMP-9 as demonstrated by their stable interactions at the S1' specificity pocket and favourable binding energies. Gossypin has emerged as a promising candidate with a docking score of -14.618 kcal/mol, binding energy of -79.97 kcal/mol and a stable MD pattern over 15 ns. In addition, interaction mechanisms with respect to catalytic site zinc are also discussed. Further, the drug-like characters of the ligands were also analysed using ADME analysis.
29122658 Endothelium-derived contraction in a model of rheumatoid arthritis is mediated via angiote 2018 Jan A role for endothelium-derived constricting factors (EDCF), and the angiotensin II type 1 receptor (AT1R) pathway, in the vascular impairment found in the rat Freund's complete adjuvant (FCA)-model of rheumatoid arthritis (RA) was examined. FCA arthritis was induced in rats±losartan. Vehicle-treated rats served as controls. Knee-joint swelling and red blood cell (RBC) aggregation were measured as indicators of inflammation and endothelium reactivity assessed by response to acetylcholine (ACh) on aortic rings. Results show that knee-joint swelling and RBC aggregation were elevated in the FCA+vehicle group and restored to control levels in the FCA+losartan-treated animals. ACh-induced relaxation of aortic rings taken from FCA+vehicle animals was significantly impaired compared to vehicle-controls and this vasoreactivity was restored to control levels in the FCA+losartan-treated group. Further examination of aorta from the FCA+vehicle animals revealed an EDCF that was reliant on cyclooxygenase-2 (but not cyclooxygenase-1), generation of superoxide anion generation (but not hydrogen peroxide) and activation of thromboxane-prostanoid receptor. Losartan administration in vivo or ex vivo (to aortic rings) prevented the generation of the EDCF. In summary, this is the first evidence of an EDCF in a model of RA and identifies this mechanism as potentially significant in the cardiovascular disorder associated with the disease.
29056772 The role of ultrasonography in monitoring long-standing rheumatoid arthritis: a pilot stud 2017 OBJECTIVE: Rheumatoid arthritis (RA) is a condition that poses many diagnostic problems. As a result, it is often diagnosed too late, which makes effective treatment more difficult. The course of the disease is chronic, and it causes irreversible changes in the musculoskeletal system, as well as bone destruction, and this in turn impairs the proper monitoring of the treatment. Therefore, in order to assess the treatment's efficacy, as well as a clinical examination of the patient and laboratory tests, diagnostic imaging is being used more frequently in routine practice. The aim of this paper is to assess the usefulness of power Doppler ultrasonography in the assessment of MCP joints in patients with chronic RA (LSRA), in comparison with DAS28, X-ray, and MRI. MATERIAL AND METHODS: The study involved 26 patients with LSRA, treated with biologics. It lasted for a year. At the moment of enrolment, the condition had lasted for a minimum of 5 years, and DAS28 was > 5.1. The patients had visits every three months. During every visit, a PDUS test was performed and the DAS28 was determined. In the first and last month of the study the patients underwent X-ray and MRI tests. RESULTS: At the end of the study, the DAS28 of 26 (100%) patients was lower or equal to 3.2. Based on PDUS and MRI tests, no synovitis was found in 21 (81%) and 18 (69%) patients, respectively. According to the MRI results, radiological changes progressed in 5 (19%) of them. All patients who showed progress of radiological changes also had visible synovitis during their PDUS test. CONCLUSIONS: PDUS in patients with LSRA can be helpful in selecting patients, who are likely to develop a progression of radiological changes.