scholarly journals Effect of Peroxisome Proliferator-Activated Receptor Gamma Agonist (Pioglitazone) and Methotrexate on Disease Activity in Rheumatoid Arthritis (Experimental and Clinical Study)

2011 ◽  
Vol 4 ◽  
pp. CMAMD.S5951 ◽  
Author(s):  
Dina Shahin ◽  
Ehab El Toraby ◽  
Hala Abdel-Malek ◽  
Vivian Boshra ◽  
Ayman Z. Elsamanoudy ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Treated Group ◽  
Control Group ◽  
Peroxisome Proliferator ◽  
Das28 Score ◽  
Peroxisome Proliferator Activated Receptor ◽  
Reactive Protein ◽  
Usual Treatment ◽  
Ppar Γ

Objective To investigate the combined effect of both pioglitazone and methotrexate on disease activity of rheumatoid arthritis in a biphasic study; experimental and clinical. Methods Experimentally: 50 rats were divided into 5 equal groups; controls, experimental arthritis, methorexate treated (0.1 mg/Kg daily), pioglitazone-treated (10 mg/kg daily), and methotrexate and pioglitazone treated. Clinically: forty-nine diabetic rheumatoid arthritis patients were included. Patients group consisted of 28 patients and they received pioglitazone 30 mg orally beside their usual treatment. Control group consisted of 21 patients and they continued their usual treatment plus placebo. Disease activity was assessed using DAS28 score. Patients were followed up for 3 months. Results Pioglitazone produced a significant improvement of serum oxidative stress parameters ( P < 0.05), and inflammatory cytokines in the treated arthritic group ( P < 0.05). Clinically, the pioglitazone treated group showed significant improvement in DAS28 ( P = 0.001) and C-reactive protein ( P < 0.0001) compared to placebo group. Conclusion The concomitant use of the PPAR γ agonist pioglitazone and methotrexate appears to be promising therapeutic strategy for rheumatoid arthritis patients.

scholarly journals Abdominal Fat SIRT6 Expression and Its Relationship with Inflammatory and Metabolic Pathways in Pre-Diabetic Overweight Patients

2019 ◽  
Vol 20 (5) ◽  
pp. 1153 ◽  
Author(s):  
Nunzia D’Onofrio ◽  
Gorizio Pieretti ◽  
Feliciano Ciccarelli ◽  
Antonio Gambardella ◽  
Nicola Passariello ◽  
...  
Keyword(s):  
Regulatory Element ◽  
Abdominal Fat ◽  
Control Group ◽  
Diabetic Patients ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Metformin Therapy ◽  
Ppar Γ ◽  
Visceral Abdominal Fat ◽  
Factor Α

: The role of sirtuin 6 (SIRT6) in adipose abdominal tissue of pre-diabetic (pre-DM) patients is poorly known. Here, we evaluated SIRT6 expression in visceral abdominal fat of obese pre-diabetic patients and the potential effects of metformin therapy. Results indicated that obese pre-DM subjects showed low SIRT6 protein expression and high expression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), peroxisome proliferator-activated receptor gamma (PPAR-γ), and sterol regulatory element-binding transcription factor 1 (SREBP-1). Obese pre-DM patients showed high values of glucose, insulin resistance (HOMA-IR), C reactive protein (CRP), nitrotyrosine, tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6), and low values of insulin (p < 0.05). Of note, abdominal fat tissue of obese pre-DM patients treated with metformin therapy presented higher SIRT6 expression and lower NF-κB, PPAR-γ, and SREBP-1 expression levels compared to pre-DM control group. Collectively, results show that SIRT6 is involved in the inflammatory pathway of subcutaneous abdominal fat of obese pre-DM patients and its expression responds to metformin therapy.

scholarly journals Effects of Antitumor Necrosis Factor Therapy on Osteoprotegerin, Neopterin, and sRANKL Concentrations in Patients with Rheumatoid Arthritis

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Katharina Kurz ◽  
Manfred Herold ◽  
Elisabeth Russe ◽  
Werner Klotz ◽  
Guenter Weiss ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Systemic Autoimmune Disease ◽  
Das28 Score ◽  
Reactive Protein ◽  
Adalimumab Therapy ◽  
Receptor Activator ◽  
Joint Erosions ◽  
Factor Therapy ◽  
Necrosis Factor

Background. Rheumatoid arthritis is a systemic autoimmune disease characterized by joint erosions, progressive focal bone loss, and chronic inflammation.Methods. 20 female patients with moderate-to-severe rheumatoid arthritis were treated with anti-TNF-antibody adalimumab in addition to concomitant antirheumatic therapies. Patients were assessed for overall disease activity using the DAS28 score, and neopterin, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) concentrations as well as osteoprotegerin (OPG) and soluble receptor activator of NF-κB ligand (sRANKL) concentrations were determined before therapy and at week 12. Neopterin as well as OPG and sRANKL were determined by commercial ELISAs.Results. Before anti-TNF therapy patients presented with high disease activity and elevated concentrations of circulating inflammatory markers. OPG concentrations correlated with neopterin (rs=0.494,p=0.027), but not with DAS28. OPG concentrations and disease activity scores declined during anti-TNF-treatment (bothp<0.02). Patients who achieved remission (n=7) or showed a good response according to EULAR criteria (n=13) presented with initially higher baseline OPG levels, which subsequently decreased significantly during treatment (p=0.018for remission,p=0.011for good response).Conclusions. Adalimumab therapy was effective in modifying disease activity and reducing proinflammatory and bone remodelling cascades.

scholarly journals The Effect of Diabetes Mellitus, Insulin, and Thiazolidinediones on Bone Histomorphometry in Streptozotocin-induced Diabetic Postmenopausal Wistar Rats

2021 ◽  
pp. 56-69
Author(s):  
Derya Köseoğlu ◽  
Gülnur Take ◽  
Banu Aktaş Yılmaz ◽  
Erdal Kan ◽  
Nuri Çakır
Keyword(s):  
Diabetes Mellitus ◽  
Bone Histomorphometry ◽  
Wistar Rats ◽  
Treated Group ◽  
Control Group ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Trabecular Thickness ◽  
Skeletal Disease ◽  
Negative Effect

Background: Osteoporosis is a metabolic skeletal disease with low bone mass and bone microarchitectural disorganization. Thiazolidinediones (TZD) increase insulin sensitivity through activation of peroxisome proliferator-activated receptor gamma (PPARγ). One of the most important side effects of this drugs is its effects on bone, especially in postmenopausal women. The purpose of this study was to evaluate the effect of diabetes mellitus (DM), insulin, and TZDs on bone in postmenopausal Wistar rats. Methods: Sixteen postmenopausal Wistar rats were divided into four groups: (i) control group, (ii) Streptozotocin-induced DM group without treatment, (iii) Streptozotocin-induced DM group with insulin therapy, and (iv) Streptozotocin-induced DM group receiving rosiglitazone. Pictures of the obtained samples were taken under computer-equipped photo-light microscope, and bone tissue ratios were calculated in an area of 1 mm2. In this area, trabecular thicknesses were measured from six randomly selected regions. In addition, femoral neck regions were determined by measuring the farthest distance. Results: Compared to the control group, trabecular thicknesses were decreased in the uncontrolled DM and rosiglitazone groups. In the rosiglitazone-treated group, trabecular thickness was decreased compared to the uncontrolled DM group. The histological examination of the bones showed that uncontrolled DM and rosiglitazone treatment negatively affected the osteoblast and osteocyte activity. Insulin-treated group had a similar histologic examination compared to the control group. Conclusion: Our study showed that DM had unfavorable effects on bones, and rosiglitazone further exerts this effect. However, the negative effect of DM may be neutralized with the use of insulin. Keywords: diabetes mellitus, bone, osteoporosis, bone histomorphometry, rosiglitazone, insulin, thiazolidinediones

scholarly journals Neuroprotective Effect and Mechanism of Thiazolidinedione on Dopaminergic Neurons In Vivo and In Vitro in Parkinson’s Disease

PPAR Research ◽  
2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Yanqin Wang ◽  
Weilin Zhao ◽  
Ge Li ◽  
Jinhu Chen ◽  
Xin Guan ◽  
...  
Keyword(s):  
Dopaminergic Neurons ◽  
Neuroprotective Effect ◽  
Oral Treatment ◽  
Treated Group ◽  
Control Group ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Nuclear Respiratory Factor

The aim of the present study was to gain insight into the neuroprotection effects and mechanism of thiazolidinedione pioglitazone in both in vitro and in vivo MPP+/MPTP induced PD models. In vivo experimental results showed that oral treatment of pioglitazone resulted in significant improvements in behavior symptoms damaged by MPTP and increase in the survival of TH positive neurons in the pioglitazone intervention groups. In addition, oral treatment of pioglitazone increased the expression of peroxisome proliferator-activated receptor-γ coactivator of 1α (PGC-1α) and increased the number of mitochondria, along with an observed improvement in mitochondrial ultrastructure. From in vitro studies, 2,4-thiazolidinedione resulted in increased levels of molecules regulated function of mitochondria, including PGC-1α, nuclear respiratory factor 1 (NRF1), NRF2, and mitochondria fusion 2 (Mfn2), and inhibited mitochondria fission 1 (Fis1). We show that protein levels of Bcl-2 and ERK were reduced in the MPP+-treated group compared with the control group. This effect was observed to be reversed upon treatment with 2,4-thiazolidinedione, as Bcl-2 and ERK expression levels were increased. We also observed that levels of the apoptotic protein Bax showed opposite changes compared to Bcl-2 and ERK levels. The results from this study confirm that pioglitazone/2,4-thiazolidinedione is able to activate PGC-1α and prevent damage of dopaminergic neurons and restore mitochondria ultrastructure through the regulation of mitochondria function.

scholarly journals Gene expressions of de novo hepatic lipogenesis in feline hepatic lipidosis

2019 ◽  
Vol 22 (6) ◽  
pp. 500-505
Author(s):  
Chiara Valtolina ◽  
Joris H Robben ◽  
Monique E van Wolferen ◽  
Hedwig S Kruitwagen ◽  
Ronald J Corbee ◽  
...  
Keyword(s):  
Gene Expression ◽  
Fatty Acid ◽  
Liver Tissue ◽  
Fatty Acid Synthase ◽  
De Novo ◽  
Control Group ◽  
Peroxisome Proliferator ◽  
Hepatic Lipidosis ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ

Objectives The aim of this study was to evaluate if de novo hepatic lipid synthesis contributes to fatty acid overload in the liver of cats with feline hepatic lipidosis (FHL). Methods Lipogenic gene expression of peroxisome proliferator-activated receptor-alpha ( PPAR-α), peroxisome proliferator-activated receptor-gamma ( PPAR-γ), fatty acid synthase ( FASN) and sterol regulatory element-binding factor ( SREBF1) were evaluated using quantitative RT-PCR in liver tissue of six cats with FHL and compared with the liver tissue of eight healthy cats. Results In liver tissue, PPAR-α, PPAR-γ and FASN mRNA expression levels were not significantly different ( P >0.12, P >0.89 and P >0.5, respectively) in the FHL group compared with the control group. SREBF1 gene expression was downregulated around 10-fold in the FHL group vs the control group ( P = 0.039). Conclusions and relevance The downregulation of SREBF1 in the liver tissue of cats with FHL does not support the hypothesis that de novo lipogenesis in the liver is an important pathway of fatty acid accumulation in FHL.

scholarly journals Investigation of the Association between Metabolic Syndrome and Disease Activity in Rheumatoid Arthritis

2011 ◽  
Vol 11 ◽  
pp. 1195-1205 ◽  
Author(s):  
Maryam Sahebari ◽  
Ladan Goshayeshi ◽  
Zahra Mirfeizi ◽  
Zahra Rezaieyazdi ◽  
Mohammad R. Hatef ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Metabolic Syndrome ◽  
Disease Activity ◽  
Multiple Logistic Regression Analysis ◽  
Considerable Proportion ◽  
Control Group ◽  
Das28 Score ◽  
Reduced Physical Activity ◽  
The Relationship ◽  
Apparently Healthy

Rheumatoid arthritis (RA) is the most common form of autoimmune arthritis. Increased prevalence of metabolic syndrome (MetS) in RA may occur secondary to specific drug treatment and reduced physical activity associated with this condition. However, some recent studies suggest contradictory theories about the association of RA with MetS. This study was designed to evaluate the frequency of MetS in RA patients and the relationship between MetS with RA disease activity and body mass index (BMI). The study was conducted on 120 RA patients and 431 age- and sex-matched apparently healthy controls. A considerable proportion of patients were being treated with prednisolone and/or methotrexate and/or hydroxychloroquine. Disease activity was measured by the 28 joint count of disease activity score-Cerythrocyte sedimentation rate (DAS28ESR). MetS was evaluated according to International Diabetic Federation (IDF) and Adult Treatment Panel III (ATP III) criteria. The prevalence of MetS was significantly higher in the control group (p= 0.005). We did not find any difference in the prevalence of MetS between the patients with DAS < 3.2 and DAS ≥ 3.2. There was no association between the DAS28 score and the presence of MetS components by either definition. Multiple logistic regression analysis showed that the odds of a DAS > 3.2 in patients with BMI between 25 and 30 kg/m2(OR = 0.1,p= 0.01) and BMI > 30 kg/m2(OR = 0.3,p= 0.1), in comparison to BMI < 25 kg/m2, was 1/5 and 1/3, respectively. RA was not found to increase the risk of MetS. In addition, disease activity in RA patients was not influenced by the presence of MetS.

scholarly journals Serum Adenosine Deaminase Level is High But Not Related with Disease Activity Parameters in Patients with Rheumatoid Arthritis

2014 ◽  
Vol 8 (1) ◽  
pp. 24-28 ◽  
Author(s):  
Gülseren Demir ◽  
Pınar Borman ◽  
Figen Ayhan ◽  
Tuba Özgün ◽  
Ferda Kaygısız ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Adenosine Deaminase ◽  
Disease Duration ◽  
Control Group ◽  
Mean Values ◽  
Reactive Protein ◽  
Control Subjects ◽  
Rheumatology Unit ◽  
The Mean

Serum adenosine deaminase (ADA) has been previously proposed to predict disease activity in patients with rheumatoid arthritis (RA). The aim of this study was to investigate the level of serum ADA, and the relationship between ADA and disease activity markers, in a group of patients with RA.A hundred and 10 patients with a diagnosis of RA were recruited from outpatient clinic of Rheumatology Unit. Demographic properties comprising age, gender, disease duration and drugs were recorded. Disease activity based on disease activity score (DAS)28-erythrocyte sedimentation rate (ESR) and DAS28- C reactive protein (CRP,) ESR, CRP levels, as well as pain by visual analog scale and rheumatoid factor (RF) were recorded. Serum ADA levels (IU/L) were determined in all RA patients and in 55 age and sex similar healthy control subjects.Ninety-six female and 14 male RA patients with a mean age of 54.32±11.51, and with a mean disease duration of 11.5±9.13 years were included to the study. The control group comprised of 48 female and 7 male healthy subjects. 35.5% of the patients were on methotrexate (MTX) and 64.5% of patients were on combined DMARDs or combined MTX and anti-TNF therapies. The mean serum ADA level was statistically higher in RA patients than in control subjects (27.01±10.6 IU/Lvs21.8 ±9.9 IU/L). The mean values of ESR (23.2±14.8 mm/h), CRP (1.71±1.11mg/dL), pain by VAS (37.2±27.1), DAS28-ESR (2.72±0.77), DAS28 CRP (1.37±0.5) were not correlated with ADA levels (p>0.05).Our results have shown that serum ADA levels are higher in RA patients than in controls but were not related with any of the disease activity markers. We conclude that ADA in the serum may not be a reliable biochemical marker to predict disease activity in patients with RA.

C-Reactive Protein-to-Albumin Ratio: A Novel Inflammatory Marker and Disease Activity Sign in Early Rheumatoid Arthritis

2021 ◽  
Author(s):  
Mustafa Erkut Onder ◽  
Nurdan Orucoglu ◽  
Firat Omar ◽  
Abdullah Canataroglu
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Early Rheumatoid Arthritis ◽  
Control Group ◽  
C Reactive Protein ◽  
Albumin Ratio ◽  
Reactive Protein ◽  
Early Ra ◽  
Inflammatory Status ◽  
Das 28

Abstract Objective A novel inflammation-based score, C-reactive protein (CRP)-to-albumin ratio (CAR), has been shown to have an association with the inflammatory status in several diseases. We aimed to analyse the association between CAR and disease activity in patients with early rheumatoid arthritis (RA) and to determine the cut-off value of CAR in early and established RA. Methods A total of 177 patients with RA and 111 age and gender-matched healthy controls were included in this study. Cases with a disease duration of less than 1 year were classified as early RA. Serum albumin, CRP, erythrocyte sedimentation rate (ESR), Disease Activity Score-28 (DAS-28-ESR), Clinical Disease Activity Index (CDAI) and Health Assessment Questionnaire (HAQ) scores were recorded. Results CAR was 2.44 (0.21–30.83) in the RA group and 0.45 (0.21–10.47) in the control group (p<0.001). Eighty-seven (49.15%) of the RA cases were classified as early RA. The analyses indicated that the ESR, CRP and CAR values were higher in patients with early RA than in those with established RA and controls. CAR was correlated with albumin, CRP, ESH, DAS-28 and HAQ scores in both early RA and established RA groups. The receiver operating characteristic curves revealed a CAR cut-off value of 2.67 (80% sensitivity and 85% specificity) and 1.63 (77% sensitivity and 72% specificity) for the prediction of early and established RA, respectively. Conclusion CAR, a formulated ratio, has been described as a predictor for disease activity in patients with early RA as well as in those with established RA. However, CAR has higher sensitivity and specificity for early RA than for established RA.

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