Effect of orexin-A (hypocretin-1) on hyperalgesic and cachectic manifestations of experimentally induced rheumatoid arthritis in rats

2014 ◽  
Vol 92 (10) ◽  
pp. 813-820 ◽  
Author(s):  
Adham R. Mohamed ◽  
Wessam F. El-Hadidy
Keyword(s):  
Rheumatoid Arthritis ◽  
Body Mass ◽  
Joint Destruction ◽  
Serum Levels ◽  
Intradermal Injection ◽  
Pain Sensation ◽  
Orexin A ◽  
Male Wistar Rats ◽  
Normal Controls ◽  
Inflammatory Effect

Orexin-A has been shown to modulate pain sensation and increase appetite. Rheumatoid arthritis (RA) is characterized by joint destruction, deformity, hyperalgesia, and weight reduction. Aim: Evaluate the possible effect of orexin-A on hyperalgesic and cachectic manifestations in an adjuvant-induced arthritis (AIA) rat model. Methods: Forty adult male Wistar rats were distributed among 4 groups; I, normal controls; II, rats with AIA induced by intradermal injection of Mycobacterium butyricum, but with no other treatment; III, AIA rats treated daily with an intravenous injection of orexin-A for 8 days; and IV, AIA rats treated orally with dexamethasone for 8 days. The parameters we assessed were pain-associated behavior, body mass, hind paw volume, serum levels of nerve growth factor (NGF) and neuropeptide Y (NPY). Results: Orexin-A caused a significant reduction in pain sensation and NGF levels, and increased body mass and the levels of NPY, whereas treatment with dexamethasone led to significant reductions in paw swelling and pain sensation. Conclusion: Orexin-A has hypoalgesic properties and increases body mass, whereas dexamethasone has a potent anti-inflammatory effect. Therefore, the combination of orexin-A and dexamethasone should have a greater effect with respect to attenuating the manifestations and complications associated with RA.

scholarly journals SAT0007 BLOCKING HISTAMINE-RELEASING FACTOR/TRANSLATIONALLY CONTROLLED TUMOR PROTEIN (HRF/TCTP) ATTENUATES AGGRESSIVENESS OF FIBROBLAST-LIKE SYNOVIOCYTES AND AMELIORATES COLLAGEN-INDUCED ARTHRITIS IN RHEUMATOID ARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 934.3-934
Author(s):  
M. Kim ◽  
Y. Choe ◽  
H. Lee ◽  
Y. H. Cheon ◽  
S. I. Lee
Keyword(s):  
Rheumatoid Arthritis ◽  
Cancer Progression ◽  
Inflammatory Responses ◽  
Joint Destruction ◽  
Serum Levels ◽  
Therapeutic Effects ◽  
Collagen Induced Arthritis ◽  
Translationally Controlled Tumor Protein ◽  
Biochemical Analyses ◽  
Fibroblast Like Synoviocytes

Background:Histamine-releasing factor/translationally controlled tumor protein (HRF/TCTP) stimulates cancer progression and allergic responses. Increased expression of HRF/TCTP occurs in joints of rheumatoid arthritis (RA) patients, but the role of HRF/TCTP in RA remains undefinedObjectives:In this study, we explored the pathogenic significance of HRF/TCTP and evaluated therapeutic effects of HRF/TCTP blockade in RA.Methods:HRF/TCTP transgenic (TG) and knockdown (KD) mice with collagen-induced arthritis (CIA) were used to determine experimental phenotypes of RA. HRF/TCTP levels were measured in sera and joint fluids in patients with RA and compared to those with osteoarthritis, ankylosing spondylitis, Behcet disease, and healthy controls. HRF/TCTP expression was also assessed in synovium and fibroblast-like synoviocytes (FLS) obtained from RA or OA patients. Finally, we assessed effects of HRF/TCTP and dimerized HRF/TCTP binding peptide-2 (dTBP2), an inhibitor of HRF/TCTP, in RA-FLS and CIA mice.Results:Our clinical, radiological, histological, and biochemical analyses indicate that inflammatory responses and joint destruction were increased in HRF/TCTP TG mice, and decreased in KD mice compared to wild-type littermates. HRF/TCTP levels were higher in sera, synovial fluid, synovium, and FLS of patients with RA than in control groups. Serum levels of HRF/TCTP correlated well with disease activity in RA. Tumor-like aggressiveness of RA-FLS was exacerbated by HRF/TCTP stimulation and ameliorated by dTBP2 treatment. dTBP2 exerted protective and therapeutic effects in CIA mice, and had no detrimental effect in a murine tuberculosis model.Conclusion:Our results indicate that HRF/TCTP represents a novel biomarker and therapeutic target for diagnosis and treatment of RA.References:N/AAcknowledgments :National Research Foundation of KoreaKorea Health Industry Development InstituteDisclosure of Interests:None declared

IgG Glycosylation Changes and MBL2 Polymorphisms: Associations with Markers of Systemic Inflammation and Joint Destruction in Rheumatoid Arthritis

2012 ◽  
Vol 39 (3) ◽  
pp. 463-469 ◽  
Author(s):  
LONE N. TROELSEN ◽  
SØREN JACOBSEN ◽  
JODIE L. ABRAHAMS ◽  
LOUISE ROYLE ◽  
PAULINE M. RUDD ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Systemic Inflammation ◽  
Joint Destruction ◽  
Serum Levels ◽  
High Expression ◽  
Markers Of Inflammation ◽  
Spearman's Rho ◽  
Spearman’S Rho ◽  
Factor Α ◽  
Igg Glycosylation

Objective.To examine whether IgG glycosylation changes and MBL2 genotypes are associated with systemic inflammation and joint destruction in rheumatoid arthritis (RA).Methods.IgG N-glycan content was determined from serum in 118 patients with RA by high-throughput glycan analysis using normal-phase high-pressure liquid chromatography. MBL2 extended genotypes (YA/YA, YA/XA, XA/XA, YA/YO, XA/YO, YO/YO) were determined. Systemic inflammation was assessed by serum levels of C-reactive protein (CRP), interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α). Joint destruction was assessed by total Sharp score (TSS) and alloplastic surgery records.Results.IgG hypogalactosylation was significantly correlated to IL-6 (Spearman’s rho = 0.32, p < 0.001), CRP (Spearman’s rho = 0.31, p < 0.001), TSS (Spearman’s rho = 0.25, p = 0.01), and alloplastic replacement of joints (Spearman’s rho = 0.18, p = 0.05). In multivariate analysis including age, CRP, anticitrullinated protein antibodies (ACPA), and other confounders, IgG hypogalactosylation was significantly associated with TSS (p = 0.014) and alloplastic joint replacement (OR 76.5, p = 0.041) in patients homozygous for the high expression MBL2 genotype YA/YA, but not in carriers of lower expression genotypes.Conclusion.Decreased galactosylation of IgG correlated to markers of inflammation, i.e., IL-6 and CRP. Only in patients homozygous for high expression of the MBL2 genotype YA/YA was IgG hypogalactosylation associated with markers of joint destruction. Our results suggest that inflammation-associated decreased galactosylation of IgG combined with high expression MBL2 genotypes are involved in the pathophysiology of RA.

scholarly journals AB0837 SERUM YKL-40 LEVELS IN PATIENTS WITH EARLY RHEUMATOID ARTHRITIS: RELATION TO DISEASE ACTIVITY AND JOINT DESTRUCTION

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1442.2-1443
Author(s):  
E. Aleksandrova ◽  
A. Novikov ◽  
E. Luchikhina ◽  
D. Karateev ◽  
G. Lukina
Keyword(s):  
Rheumatoid Arthritis ◽  
Serum Level ◽  
Disease Activity ◽  
Joint Destruction ◽  
Elevated Serum ◽  
Serum Levels ◽  
Control Group ◽  
Human Cartilage ◽  
Amyloid A ◽  
Early Ra

Background:YKL-40 (chitinase-3-like 1 protein, human cartilage glycoprotein 39) is one of the major proteins secreted locally in the arthritic joint by activated macrophages, chondrocytes, synoviocytes and neutrophils, YKL-40 an important marker for inflammation, cartilage remodelling and synovial hyperplasia is recognized as a possible auto-antigen in rheumatoid arthritis (RA).Objectives:The aims of the study were to determine the serum level of YKL-40 in early RA and investigate his relationship with biomarkers of disease activity and joint destruction.Methods:We studied 22 patients with early RA (ACR/EULAR 2010 classification criteria); 4 males, 18 females; median and interquartile range (25th—75th percentile) of age 55,0 (43,0-64,0) years, disease duration 7,0 (5,0-11,0) months, DAS28 4,9 (4,3-5,8); 86% IgM rheumatoid factor (IgM RF) +; 91% anti-cyclic citrullinated peptide antibody (anti-CCP) +. All patients were treated with methotrexate (MTX). Three (14 %) patients received low oral doses of steroids and intra-articular injections. The control group included 22 healthy donors (HC). Radiographs were scored according to the van der Heijde-modified Sharp score. YKL-40, matrix metalloproteinase-3 (MMP-3), anti-CCP were detected using commercially available enzyme-linked immunosorbent assays (ELISA). The serum levels of IgM RF, C-reactive protein (CRP), serum amyloid A (SAA) were measured by immunonephelometry.Results:RA patients had significantly higher serum level of YKL-40 than HC (92,1; 68,5-153,1 pg/ml vs 54,0; 41,7-83,2 pg/ml, p<0.01). Serum YKL-40 concentration was positively correlated with DAS 28 (r=0,5; p<0,05), erythrocyte sedimentation rate (ESR) (r=0,5; p<0,05), CRP (r=0,8; p<0,05), SAA (r=0,6; p<0,05) and MMP-3 (r = 0,6; p<0,05). We found no relationship between the level of YKL-40 and articular radiographic changes.Conclusion:Elevated serum concentration of YKL-40 in early RA is associated with clinical and laboratory indicators of disease inflammatory activity and increased level of MMP-3 - an immunological marker of joint destruction.Disclosure of Interests:Elena Aleksandrova: None declared, Alexander Novikov: None declared, Elena Luchikhina Speakers bureau: Abbvie, Roche, Pfizer, Biocad, MSD, Sanofi, Johnson & Johnson, Glaxo, UCB, Celgene, Novartis, Consultant of: Abbvie, Biocad, Sanofi, Celgene, Dmitriy Karateev Speakers bureau: Abbvie, Roche, Pfizer, Biocad, MSD, Sanofi, Johnson & Johnson, Glaxo, UCB, Celgene, Novartis, Lilly, Bayer, Paid instructor for: Abbvie, Pfizer, Biocad, Sanofi, Novartis, Lilly, Galina Lukina Speakers bureau: Abbvie, Roche, Pfizer, Biocad, MSD, Sanofi, Johnson & Johnson, Glaxo, UCB, Celgene, Novartis, Paid instructor for: Abbvie, Biocad, Sanofi, Celgene

Effect of Manual Therapy on Pain Sensation and Hand Dexterity and Grip Strength in a Patient with RA. Didactic Case Study

2018 ◽  
Vol 20 (2) ◽  
pp. 157-163
Author(s):  
Mateusz Wojciech Romanowski ◽  
Maciej Majchrzak ◽  
Anna Kostiukow ◽  
Roksana Malak ◽  
Włodzimierz Samborski
Keyword(s):  
Rheumatoid Arthritis ◽  
Manual Therapy ◽  
Joint Destruction ◽  
Joint Mobility ◽  
Pain Sensation ◽  
Limited Joint Mobility ◽  
Joint Mobilization ◽  
Hand Dexterity ◽  
Organ Complications

Rheumatoid arthritis (RA) is an inflammatory immune-dependent systemic connective tissue disease leading to joint destruction and organ complications. Recent years have seen a strong interest in manual therapy and its possible use in patients with pain and limited joint mobility. This prompted us to evaluate the effectiveness of joint mobilization in a patient with RA. The present paper assesses the effects of a joint mobilization technique on pain and functionality of the hand and wrist in a patient with rheumatoid arthritis.

Serum Pyridinoline Levels and Prediction of Severity of Joint Destruction in Rheumatoid Arthritis

2013 ◽  
Vol 40 (8) ◽  
pp. 1303-1306 ◽  
Author(s):  
Annemarie Krabben ◽  
Rachel Knevel ◽  
Tom W.J. Huizinga ◽  
Guy Cavet ◽  
Annette H.M. van der Helm-van Mil
Keyword(s):  
Rheumatoid Arthritis ◽  
Predictive Accuracy ◽  
Characteristic Curve ◽  
Linear Regression Analysis ◽  
Joint Destruction ◽  
Serum Levels ◽  
Disease Course ◽  
Normal Regression ◽  
Multivariable Linear Regression Analysis ◽  
Near Term

Objective.Previous studies indicated that pyridinoline, a collagen crosslink in cartilage and bone, might be a good marker to predict joint destruction in patients with rheumatoid arthritis (RA), although large prospective studies are lacking. We evaluated the predictive value of serum pyridinoline levels for joint destruction, both at baseline for longterm prediction and during the disease course for near-term prediction.Methods.Patients with early RA from the Leiden Early Arthritis Clinic were studied. Radiographs at baseline and yearly during 7 years of followup were scored according to the Sharp-van der Heijde Scoring (SHS) method. Pyridinoline serum levels at baseline and during followup were measured by ELISA. The association between baseline pyridinoline levels and difference in SHS over 7 years was tested, with a multivariate normal regression model. Second, the association between pyridinoline levels determined during the disease course and progression of SHS over the next year was tested with a multivariable linear regression analysis.Results.Studying baseline pyridinoline serum levels in 437 patients revealed that the mean SHS over 7 years was 6% higher for every higher pyridinoline level (nmol/l) at baseline (p = 0.001). Subsequently, during followup (n = 184 patients) the progression in SHS in the upcoming year was 17% higher for every higher nmol/l pyridinoline level (p = 0.001). The area under the receiver-operation characteristic curve for rapid radiological progression was 0.59.Conclusion.Increased pyridinoline serum levels, both at baseline and during the disease course, are associated with more severe joint destruction during the coming year(s), although the predictive accuracy as a sole predictor was moderate.

Serum keratan sulphate levels rise in rheumatoid arthritis patients, but fall in ankylosing spondylitis patients compared with normal controls

1990 ◽  
Vol 18 (5) ◽  
pp. 964-965 ◽  
Author(s):  
ROB WILL ◽  
JUDITH ELSWOOD ◽  
LAUREL EDMUNDS ◽  
ANDREI CALIN
Keyword(s):  
Rheumatoid Arthritis ◽  
Ankylosing Spondylitis ◽  
Serum Levels ◽  
Control Population ◽  
Joint Activity ◽  
Keratan Sulphate ◽  
Normal Controls

Summary Serum levels of keratan sulphate (KS) were found to be significantly elevated in patients with destructive and predominantly seronegative rheumatoid arthritis (RA) compared with a control population. Levels in RA did not correlate with clinical or laboratory indices of joint activity or damage. Conversely levels were depressed in ankylosing spondylitis (AS) compared with controls.

FRI0169 Influence of Body Mass Index (BMI) on Serum Levels of Infliximab in Patients with Rheumatoid Arthritis (RA):

2016 ◽  
Vol 75 (Suppl 2) ◽  
pp. 490.3-491
Author(s):  
A. Villalba Yllan ◽  
M.V. Navarro Compan ◽  
C. Plasencia Rodriguez ◽  
D. Peiteado Lopez ◽  
G. Bonilla Hernan ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Body Mass Index ◽  
Body Mass ◽  
Serum Levels

scholarly journals Formoterol decreases muscle wasting as well as inflammation in the rat model of rheumatoid arthritis

2016 ◽  
Vol 310 (11) ◽  
pp. E925-E937 ◽  
Author(s):  
Ana Belén Gómez-SanMiguel ◽  
Carolina Gomez-Moreira ◽  
María Paz Nieto-Bona ◽  
Carmen Fernández-Galaz ◽  
Maria Ángeles Villanúa ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Body Weight ◽  
Muscle Wasting ◽  
Body Weight Loss ◽  
Intradermal Injection ◽  
Cross Sectional ◽  
Akt Phosphorylation ◽  
Male Wistar Rats ◽  
And Control ◽  
Igfbp 3

Adjuvant-induced arthritis is an experimental model of rheumatoid arthritis that is associated with body weight loss and muscle wasting. β2-adrenergic receptor agonists are powerful anabolic agents that trigger skeletal muscle hypertrophy and have been proposed as a promising treatment for muscle wasting in human patients. The aim of this work was to determine whether formoterol, a selective β2-adrenoreceptor agonist, is able to ameliorate muscle wasting in arthritic rats. Arthritis was induced in male Wistar rats by intradermal injection of Freund's adjuvant. Control and arthritic rats were injected daily with 50 μg/kg sc formoterol or saline for 12 days. Body weight change, food intake, and arthritis index were analyzed. After euthanasia, in the gastrocnemius mRNA was analyzed by PCR, and proteins were analyzed by Western blotting. Arthritis decreased gastrocnemius weight, cross-sectional area, and myofiber size, whereas formoterol increased those variables in both arthritic and control rats. Formoterol decreased the external signs of arthritis as well as NF-κB(p65) activation, TNFα, and COX-2 levels in the gastrocnemius of arthritic and control rats. Those effects of formoterol were associated with a decreased expression of myostatin, atrogin-1, and MuRF1 and in LC3b lipidation. Arthritis increased the expression of MyoD, myogenin, IGF-I, and IGFBP-3 and -5 in the gastrocnemius. In control and in arthritic rats, treatment with formoterol increased Akt phosphorylation and myogenin levels, whereas it decreased IGFBP-3 expression in the gastrocnemius. These data suggest that formoterol has an anti-inflammatory effect and decreases muscle wasting in arthritic rats through increasing Akt activity and myogenin and decreasing myostatin, the p-NF-κB(p65)/TNF pathway, and IGFBP-3.

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