scholarly journals Estrogen Receptors, ERK 1/2 Phosphorylation and Reactive Oxidizing Species in Red Blood Cells From Patients With Rheumatoid Arthritis

2021 ◽  
Author(s):  
Manuela Di Franco ◽  
Lucrezia Gambardella ◽  
Camilla Cittadini ◽  
Martina Favretti ◽  
Chiara Gioia ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Estrogen Receptor Alpha ◽  
Redox Balance ◽  
Das 28 ◽  
Increased Risk ◽  
Total Antioxidant ◽  
Oxidant Status ◽  
Chronic Autoimmune Disease

Rheumatoid arthritis (RA) is a chronic autoimmune disease associated with a significantly increased risk of cardiovascular mortality, mainly attributed to accelerated atherosclerosis. Methods: Thirty-two women (aged more than 18 years) with RA, and 25 age-matched healthy women were included in this study. Biomarkers of inflammation, red blood cells (RBCs) redox balance, estrogen receptor alpha (ER-α) expression as well as ERK 1/2 phosphorylation content were evaluated in RA patients at baseline and six months after treatment with disease modifying anti‐rheumatic drugs (DMARDs). Results: For the first times we demonstrated that in RA patients: i) disease activity score (DAS-28) positively correlated with RBC ER-α expression, and negatively with total antioxidant capacity of plasma; ii) RBC ER-α expression positively correlated with systemic inflammatory biomarkers and oxidative stress parameters as well as ERK 1/2 phosphorylation; and iii) DMARDs treatments improved the clinical condition measured by DAS-28 score decrease, although the RBCs appeared to be more prone to pro-oxidant status associated to the expression of survival molecules. Conclusion: Our data strongly suggest that RBCs could also participate in vascular homeostasis through fine modulation of an intracellular signal linked to the ER-α.

scholarly journals Glucocorticoid-Responsive Cold Agglutinin Disease in a Patient with Rheumatoid Arthritis

2015 ◽  
Vol 2015 ◽  
pp. 1-4
Author(s):  
Kyoko Honne ◽  
Takao Nagashima ◽  
Masahiro Iwamoto ◽  
Toyomi Kamesaki ◽  
Seiji Minota
Keyword(s):  
Rheumatoid Arthritis ◽  
Bovine Serum Albumin ◽  
Serum Albumin ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Bovine Serum ◽  
Cold Agglutinin ◽  
Cold Agglutinin Disease ◽  
Cold Agglutinins ◽  
Thermal Amplitude

A 57-year-old man with rheumatoid arthritis developed severe anemia during treatment with adalimumab plus methotrexate. Cold agglutinin disease was diagnosed because haptoglobin was undetectable, cold agglutinin was positive (1 : 2048), and the direct Coombs test was positive (only to complement). Although the cold agglutinin titer was normalized (1 : 64) after treatment with prednisolone (0.7 mg/kg/day for two weeks), the patient’s hemoglobin did not increase above 8 g/dL. When cold agglutinins were reexamined using red blood cells suspended in bovine serum albumin, the titer was still positive at 1 : 1024. Furthermore, the cold agglutinin had a wide thermal amplitude, since the titer was 1 : 16 at 30°C and 1 : 1 at 37°C. This suggested that the cold agglutinin would show pathogenicity even at body temperature. After the dose of prednisolone was increased to 1 mg/kg/day, the patient’s hemoglobin rapidly returned to the normal range. The thermal amplitude test using red blood cells suspended in bovine serum albumin is more sensitive than the standard test for detecting pathogenic cold agglutinins.

scholarly journals Assessment of total (anti)oxidant status in goat kids

2021 ◽  
Vol 64 (1) ◽  
pp. 139-146
Author(s):  
Stefano Cecchini ◽  
Francesco Fazio
Keyword(s):  
Radical Scavenging Activity ◽  
Analytical Data ◽  
Radical Scavenging ◽  
Redox Balance ◽  
Reactive Oxygen Metabolites ◽  
Strongly Correlated ◽  
Antioxidant Assays ◽  
Reducing Ability ◽  
Total Antioxidant ◽  
Oxidant Status

Abstract. The redox potential of goat serum was assessed by different spectrophotometric assays. Among them, three methods are commonly applied for the evaluation of the oxidative (reactive oxygen metabolites, ROMs, and total oxidant status, TOS) and nitrosative (NO⚫ metabolites, NOx) stress, and four methods for the evaluation of the antioxidant status: the total antioxidant capacity (TAC) based on the ferric reducing ability of plasma (FRAP), the total antioxidant activity (TAA) based on the reduction of the coloured ABTS⚫+ radical cation, the free radical scavenging activity (FRSA) based on the reduction of the purple DPPH⚫, and the total thiol levels (TTLs) based on their interaction with DTNB to form a highly coloured anion. Besides, myeloperoxidase (MPO) and ceruloplasmin oxidase (CP) activities were also assessed. Except for TAA, analytical data showed a great inter-individual variation for both oxidant and antioxidant assays. ROMs were strongly correlated with CP, while TOS with MPO and TAC. Furthermore, a tendency between TOS and FRSA was shown. NOx was correlated with TAC and TAA, and a tendency with TOS was shown. No correlations appeared among the antioxidant assays, even if a tendency between TAC and TAA was evidenced, but TAC was correlated with MPO activity. The observed correlation between ROMs and CP is discussed as a possible analytical interference. The absence of correlation among the antioxidant biomarkers suggests the simultaneous use of a panel of tests to verify any changes in the redox balance, mainly in livestock in which reference values for each biomarker are lacking.

scholarly journals Concentration of methotrexate in red blood cells and its relevance for disease activity in patients with rheumatoid arthritis

2013 ◽  
Vol 5 ◽  
pp. 370-374
Author(s):  
Sylwia Elert-Kopeć ◽  
Małgorzata Tłustochowicz ◽  
Laura Załucka ◽  
Grzegorz Kopeć ◽  
Witold Tłustochowicz
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Red Blood Cells ◽  
Blood Cells

scholarly journals Transfusion of packed red blood cells at the end of shelf life is associated with increased risk of mortality – a pooled patient data analysis of 16 observational trials

Haematologica ◽  
2018 ◽  
Vol 103 (9) ◽  
pp. 1542-1548 ◽  
Author(s):  
Monica S.Y. Ng ◽  
Michael David ◽  
Rutger A. Middelburg ◽  
Angela S.Y. Ng ◽  
Jacky Y. Suen ◽  
...  
Keyword(s):  
Data Analysis ◽  
Red Blood Cells ◽  
Shelf Life ◽  
Blood Cells ◽  
Patient Data ◽  
Packed Red Blood Cells ◽  
Risk Of Mortality ◽  
Increased Risk

scholarly journals AB0277 ASSOCIATION BETWEEN INTRA-ERYTHROCYTE METHOTREXATE POLYGLUTAMATE CONCENTRATION AND CLINICAL RESPONSE IN RHEUMATOID ARTHRITIS IN PATIENTS TREATED WITH METHOTREXATE INJECTABLE SUBCUTANEOUSLY

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1164-1164
Author(s):  
M. Poudret ◽  
M. Norman ◽  
S. Hodin ◽  
A. S. Amouzougan ◽  
K. Boussoualim ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Liquid Chromatography ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Clinical Status ◽  
University Hospital ◽  
Chromatography Method ◽  
Cross Sectional ◽  
Active Disease

Background:Methotrexate (MTX) is the first-line treatment for rheumatoid arthritis (RA). Due to its short half-life, blood MTX dosage is not performed in current practice. Erythrocyte MTX-polyglutamate (MTX-PG), which penetrates into the red blood cells, would be correlated with the area under the MTX curve and would be more accessible for dosing. When treatment is initiated, its concentration correlates with efficacy and therapeutic adherence.Objectives:To determine the interest of erythrocyte MTX-PG dosage in case of failure of 1st line MTX treatment.Methods:In this single-centre cross-sectional study, RA patients presenting for consultation at the Saint-Etienne University Hospital, with a stable dose of MTX for more than 3 months at least 15 mg/week subcutaneously with either clinical remission (DAS28<2.6) or active disease (DAS28>3.2) were included between July 2nd 2018 and May 28th 2020. In order to assess therapeutic compliance, the patient completed the compliance questionnaire of Rheumatology (CQR) questionnaire. The determination of erythrocytic MTX-PG was performed on a 5 mL blood sample by liquid chromatography method for the determination of the different PG forms.Results:Sixty patients were included, 34 in the active RA group and 26 in the RA group in remission. One patient withdrew his consent. Only 16% of patients were observed with a CQR score > 80%. Patients in remission were leaner with a longer duration of disease and MTX treatment. The sex ratio, RA status, creatinine clearance and MTX dose was not different in both groups. The CQR was better in the remission group than in the active RA group. However, total MTX-PG was not different in the two groups. The same results were observed for the different forms of MTX-PG 1, 2, 3 or 4. In contrast, in the remission PR group, total MTX-PG or MTX-PG2, 3, 4 and 5 correlated inversely with BMI while MTX-PG3 correlated positively with BMI in the active PR group. In the active PR group, MTX-PG5 correlated with MTX dose.Conclusion:MTX-PG dosage is not a biomarker of good response to MTX in our study. However, compliance is a key factor to be considered in RA with active disease in adapting patient management.References:[1]Pasma A, Boer E den, Spijker A van ’t, Timman R, Bemt B van den, Busschbach JJV, et al. Nonadherence to disease modifying antirheumatic drugs in the first year after diagnosis: comparing three adherence measures in early arthritis patients. Rheumatology 2016;55:1812–1819.[2]Haandel L van, Becker ML, Leeder JS, Williams TD, Stobaugh JF. A novel high-performance liquid chromatography/mass spectrometry method for improved selective and sensitive measurement of methotrexate polyglutamation status in human red blood cells. Rapid Commun Mass Spectrom RCM 2009;23:3693–3702.[3]Dervieux T. Pharmacogenetic and metabolite measurements are associated with clinical status in patients with rheumatoid arthritis treated with methotrexate: results of a multicentred cross sectional observational study. Ann Rheum Dis 2005;64:1180–1185.Disclosure of Interests:Marion POUDRET: None declared, Myriam Norman: None declared, Sophie Hodin: None declared, Adamah Stanislas AMOUZOUGAN: None declared, Karima BOUSSOUALIM: None declared, Astrid Coassy: None declared, Tiphany Neel: None declared, THIERRY THOMAS: None declared, Xavier DELAVENNE: None declared, Hubert MAROTTE Speakers bureau: Pfizer, Nordic, Paid instructor for: Amgen, Consultant of: Novartis, Grant/research support from: Nordic

scholarly journals POS0467 STUDY OF METHOTREXATE METABOLITES CONCENTRATIONS IN RED BLOOD CELLS AND MONONUCLEAR CELLS IN RHEUMATOID ARTHRITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 465.2-465
Author(s):  
V. Sygyrta ◽  
G. Gridneva ◽  
A. Lila ◽  
E. Samarkina ◽  
N. Baymeeva ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Red Blood Cells ◽  
Correlation Coefficient ◽  
Blood Cells ◽  
Mononuclear Cells ◽  
Total Concentration ◽  
Pairwise Comparison ◽  
The Body ◽  
Inadequate Response ◽  
Mean Cell Volume

Background:Studying the dynamics of the methotrexate metabolites concentration in cells will help to predict the therapeutic effect and assess patient compliance. We suggest that studying the dynamics of changes in the concentration of methotrexate metabolites in mononuclear cells (MO) may be a more accurate method than measuring in red blood cells (RBC).Objectives:To study the dynamics of changes in the concentration of MTX and its metabolites in RBC and MO in methotrexate-naive patients with RA.Methods:33 patients (26 women, 7 men) aged 53.2 ± 11.7 years with a diagnosis of rheumatoid arthritis, according to the ACR / EULAR 2010 criteria, were included. All patients had GFR >60 ml/min. Patients were monitored after 4, 12, 24 and 36 weeks from the start of МТX. Mean Cell Volume (MCV) of RBC was measured by standard methods. Samples of RBC and MO were collected separately to determine the concentrations of MTX (basic monoglutamate form), total concentration of MTPG2, MTPG3 and MTPG4 (MTPG2-4), 7- hydroxymethotrexate (7-OH-MTX) by tandem mass spectrometry.Results:Table 1.Total concentration of MTPG2, MTPG3 and MTPG4 (MTPG2-4), nmol/lMe[25;75]MinMaxWeek 4RBC42.819.0;155.03987.7MO6.25.3;11.91.6147.2Week 12RBC48.117.1;89.00.1519.9MO10.93.9;31.00.9147.6Week 24RBC39.417.2;70.62.7191.8MO8.32.7;14.00.472.4A pairwise comparison of MTX, MTPG2-4 and 7-OH-MTX concentrations, according to the Wilcoxon method did not reveal statistically significant differences at weeks 4, 12 and 24. The concentration of the studied substances did not correlate with the value of the body mass index, taking statins, glucocorticoids, a cumulative dose of MTX, and the frequency of adverse reactions. At the week 4, of therapy, the level of MTPG4 in MO was inversely correlated with the duration of the disease (correlation coefficient - 0.58, p 0.05) The concentration of MTX and its metabolites in MO was lower in smokers (MTX 11.2 [2.6;21.9], 7-OH-MTX 2.1 [0.5; 10.4], MTPG2 0.5 [0.1;1.3]) than in non-smokers (MTX 46.5 [25.3;97.5], 7-OH-MTX 28.2 [7.1; 64.7], MTPG2 8.2 [4.1;32.9]), p = 0.02, 0.01 and 0.003, respectively. At week 24 of therapy, a negative correlation was found between age and MTPG4 level (correlation coefficient 0.51, p <0.05).Conclusion:The inadequate response to MT therapy in smokers, described in many previous studies, may be associated with a low concentration of the MTX metabolites in mononuclear cells.The level of MTPG4 in mononuclear cells increases more slowly in patients with a longer duration of the disease.Disclosure of Interests:None declared

scholarly journals Red Blood Cell Distribution Width-to-Platelet Ratio Inversely Correlates with Indicators of Disease Activity Status in Rheumatoid Arthritis Patients

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Amela Dervišević ◽  
Amila Muhić ◽  
Asija Začiragić ◽  
Almir Fajkić ◽  
Lejla Dervišević ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Blood Cell ◽  
Disease Activity ◽  
Red Blood Cells ◽  
Red Blood Cell ◽  
Blood Cells ◽  
Cell Distribution ◽  
Distribution Width ◽  
Low Disease Activity ◽  
Red Blood Cell Distribution

AbstractIntroduction: Present study was performed to verify red blood cell distribution width-to-platelet ratio (RPR) level in rheumatoid arthritis (RA) patients and to examine its correlation with clinical and biochemical indicators of disease activity status.Methods: In this cross-sectional analytical study, 67 patients with RA and 34 age- and gender-matched healthy control subjects were enrolled. Based on the disease activity score 28-ESR (DAS28-ESR), RA patients were divided into subgroups: low disease activity (n=20), moderate disease activity (n=22) and high disease activity (n=25). Laboratory tests included erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) concentration, platelet count (PLT), red blood cells count (RBC), red blood cells distribution width (RDW) and fibrinogen concentration. Statistical analyses were carried out using SPSS 13 software. Statistical significance was set at a p-value less than 0.05.Results: There was statistically significant difference (p=0.006) between RPR in RA patients with different stages of disease activity, with higher values in patients with low disease activity. The RPR showed statistically significant negative correlations with ESR (rho= -0.309; p=0.012), CRP (rho= -0.421; p=0.001), swollen joint count - SJC (rho = -0.368; p=0.002) and tender joint count - TJC (rho= -0.355; p=0.003), DAS28-ESR (rho= -0.409; p=0.001), DAS28-CRP (rho= -0.422; p<0.0005) and Visual analogue scale - VAS (rho= -0.260; p=0.033) in RA patients.Conclusion: The present study provided evidence that the lower RPR values in RA patients are significantly associated with the disease activity indicators.

scholarly journals Therapeutic drug monitoring of methotrexate and its metabolites in the red blood cells and mononuclear cells of patients with rheumatoid arthritis

2020 ◽  
Vol 14 (4) ◽  
pp. 60-64
Author(s):  
G. I. Gridneva ◽  
Yu. V. Muravyev ◽  
N. V. Baimeeva ◽  
V. S. Sygyrta ◽  
S. I. Glukhova ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Therapeutic Drug Monitoring ◽  
Red Blood Cells ◽  
Drug Monitoring ◽  
Blood Cells ◽  
Older Patients ◽  
Time Course ◽  
Mononuclear Cells ◽  
Individual Characteristics ◽  
Therapeutic Drug

Objective: to assess the time course of changes in the concentration of methotrexate (MTX) and its main metabolites in the red blood cells (RBC) and mononuclear cells (MNC) of patients with rheumatoid arthritis (RA), by taking into account individual characteristics (age, statin therapy, and smoking).Patients and methods. The investigation enrolled 33 MTX-treated patients (mean age 53.2±11.7 years) with RA, who underwent therapeutic drug monitoring to measure the RBC and MNC concentrations of free MTX and MTX polyglutamates (MTXPGs) with 2, 3, and 4 glutamate residues (MTXPG 2–4) in using tandem chromatomass spectrometry after 4, 12, and 24 weeks of therapy.Results and discussion. Following 12 weeks, the concentration of MTXPG4 in the MNC was higher in patients taking statins, while that of MTX and MTXPG2 in the RBC were significantly lower than in smokers. At 24 weeks, older patients were observed to have a higher MTX level and a lower MTXPG4 concentration in the RBC.Conclusion. After 24 weeks of therapy, the RBC concentration of MTPG4 was lower and that of MTX was higher in older patients than in others, which confirms data on a slower MTX metabolism in the elderly. The use of statins is likely to have a positive impact on the accumulation of MTXPG. There is a statistically significantly lower RBC concentration of MTXPG in at 12 weeks of therapy.

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