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 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.

scholarly journals A Case of Rheumatoid Arthritis Associated with Microcytic Anemia

2021 ◽  
pp. 114-117
Author(s):  
Jaya Khandar ◽  
Achita Sawarkar ◽  
Madhuri Shambharkar ◽  
Pooja Kasturkar
Keyword(s):  
Rheumatoid Arthritis ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Microcytic Anemia ◽  
The Body ◽  
High Dose ◽  
Laboratory Findings ◽  
Packed Red Blood Cells ◽  
Hematological Disorders ◽  
Immune Hemolytic Anemia

Rheumatoid arthritis (RA) is one of the most common inflammatory arthritides. It is associated with multiple systemic features, including hematological manifestations such as anemia, neutropenia and thrombocytopenia. However, immune hemolytic anemia is extremely rare with only 3 reports indexed in medline, and one of them being due to methotrexate toxicity. Microcytic anemia is a condition in which the body's tissues and organs do not get enough oxygen. This lack of oxygen can happen because the body does not have enough red blood cells, or because the red blood cells do not contain enough hemoglobin, which is a protein that transports oxygen in the blood. Case Presentation: A 60 year old female a known case of rhematoid arthritis and hypothyrodisam in 2013 for last past 3 years. Who presented to us with history of recurrent anemia . In march 2021, she was admitted to hospital because of palpitations and shortness of breath due to severe anemia. Results of laboratory studies were hemoglobin, 6.9 gm/dl and haptoglobin, less than 29.8mg/dl. A diagnosis of anemia was made on the basis of the laboratory findings She was transfused with 1units packed red blood cells (pRBCs) over less than 6 hours. High-dose PSL (50 mg/day) was started, and the anemia improved. The hemoglobin level increased to 7.0 gm/dl within the 1st week. Conclusion: The differential diagnosis of various hematological disorders should include rheumatic autoimmune diseases among other causes of blood cell and hemostasis abnormalities. It is crucial that hematologists be aware of Treatment should be administered promptly, with rheumatological consultation.

Clock gene-independent daily regulation of haemoglobin oxidation in red blood cells

2021 ◽  
Author(s):  
Andrew D. Beale ◽  
Priya Crosby ◽  
Utham K. Valekunja ◽  
Rachel S. Edgar ◽  
Johanna E. Chesham ◽  
...  
Keyword(s):  
Circadian Rhythms ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Human Subjects ◽  
Developmental Regulation ◽  
Physiological Role ◽  
Cell Types ◽  
The Body

AbstractCellular circadian rhythms confer daily temporal organisation upon behaviour and physiology that is fundamental to human health and disease. Rhythms are present in red blood cells (RBCs), the most abundant cell type in the body. Being naturally anucleate, RBC circadian rhythms share key elements of post-translational, but not transcriptional, regulation with other cell types. The physiological function and developmental regulation of RBC circadian rhythms is poorly understood, however, partly due to the small number of appropriate techniques available. Here, we extend the RBC circadian toolkit with a novel biochemical assay for haemoglobin oxidation status, termed “Bloody Blotting”. Our approach relies on a redox-sensitive covalent haem-haemoglobin linkage that forms during cell lysis. Formation of this linkage exhibits daily rhythms in vitro, which are unaffected by mutations that affect the timing of circadian rhythms in nucleated cells. In vivo, haemoglobin oxidation rhythms demonstrate daily variation in the oxygen-carrying and nitrite reductase capacity of the blood, and are seen in human subjects under controlled laboratory conditions as well as in freely-behaving humans. These results extend our molecular understanding of RBC circadian rhythms and suggest they serve an important physiological role in gas transport.

EFEKTIVITAS PEMBERIAN INFUSED WATER KURMA TERHADAP PENINGKATAN KADAR HEMOGLOBIN REMAJA PUTRI KEBIDANAN POLTEKKES MEDAN TAHUN 2020

2021 ◽  
Vol 2 (1) ◽  
pp. 64-69
Author(s):  
HIJRA HIDAYANA ◽  
Suswati Suswati
Keyword(s):  
Red Blood Cells ◽  
Adolescent Girls ◽  
Blood Cells ◽  
The Body ◽  
Rank Test ◽  
Plain Water ◽  
P Value ◽  
Signed Rank ◽  
Wilcoxon Signed Rank Test ◽  
Signed Rank Test

Hemoglobin is the red pigment-protein contained in red blood cells. The function of hemoglobin is to transport oxygen from the lungs and in the bloodstream to be carried to the tissues. Hemoglobin can increase by increasing the intake of iron in the body. One way to increase hemoglobin can be done by giving method Infused Water Dates. Infused water is a drink consisting of plain water with fresh fruit added and soaking or settling together for a certain time. The making of infused water is carried out by soaking for a period of 0 to 12 hours, so that the infused water becomes a liquid medium that carries more nutrients than ordinary water and will be more easily absorbed by cells and distributed throughout the body (Sidauruk, 2018 ). In several studies, it is stated that dates can increase hemoglobin levels in the blood. Where dates contain iron, vitamin A, vitamin C, protein to form red blood cells. With the method, Infused Water the date palm water becomes alkaline so that it can accelerate the absorption process in the body. The purpose of this study was to determine the effectiveness of dates infused water provision to increase hemoglobin levels of midwifery adolescent girls at Medan Health Polytechnic in 2020. This research was quasi-experimental study using the One Group Pretest-Posttest Without Control Design approach. The sample in this study were 20 respondents of midwifery adolescent girls from Medan Health Polytechnic, using the technique of purposive sampling. The statistical test used wa the Wilcoxon Signed Rank Test because the data was not normal. The results of the Wilcoxon Signed Rank Test obtained the value of P-Value = 0.001. So it can be concluded that the date infused water  is effective in increasing hemoglobin levels of midwifery adolescent girls at Medan Health Polytechnic in 2020.   Keywords: Dates Infused Water, Increased Hemoglobin Levels, Girls Adolescent

scholarly journals BIOLOGICAL EFFECTS OF SILICON OXIDE NANOPARTICLES ON BROILER CHICKEN

2020 ◽  
Vol 5 (2) ◽  
pp. 63-71
Author(s):  
Vladimir Nikulin ◽  
Aleksandra Mustafina
Keyword(s):  
Red Blood Cells ◽  
Total Protein ◽  
Blood Cells ◽  
Broiler Chickens ◽  
Broiler Chicken ◽  
Silicon Oxide ◽  
The Body ◽  
Control Group ◽  
The Third ◽  
Experimental Group

The aim of the study is to increase the productive qualities of broiler chickens by including ultrafine silicon oxide into main diet. During the experiment, the biological effect of ultrafine silicon oxide on broiler chickens was estab-lished. Use of ultrafine SiO2 particles for poultry feeding contributed to an increase in the number of red blood cells and content of total protein and albumins. By the end of the experiment, the number of red blood cells in birds in-creased by 17.43% (P≤0.001) – in the blood of birds of the first experimental group, 16.51% (P≤0.01) – the second one, 20.80% (P≤0.001) – the third experimental and 21.71% (P≤0.001) – the fourth experimental group, compared with the indicator of the control group. The amount of total protein in blood serum of chickens of the first and the second experimental groups increased by 1.36-1.39 %, in the third and fourth ones there was a significant (P≤0.05) increase by 5.45 and 3.05%, respectively. The blood glucose content of chickens in the experimental groups is higher by 8.04-23.65% compared to this indicator with ones in the control group. During the experiment feed con-sumption per 1 kg gain of live weight decreased: in the first experimental group by 3.00 % in the second by – 0.50 %, the third – 6.00 % the fourth– by 4.50 %, compared to this with the control group. The chicken’s vibrancy of the first the experimental group was higher by 4.77 %, the second – by 6.20 %, the third – by 19.25 % and the fourth– by 11.59% than in the control one. Consequently, when converting the feed energy into the body energy of a broiler chicken, the energy conversion coefficient of the experimental group of poultry is higher than that of the control one by 7.16-21.76 %. Thus, the most optimal dose for further research was determined.

scholarly journals Voltage dependence of DIDS-insensitive chloride conductance in human red blood cells treated with valinomycin or gramicidin.

1994 ◽  
Vol 104 (5) ◽  
pp. 961-983 ◽  
Author(s):  
J C Freedman ◽  
T S Novak ◽  
J D Bisognano ◽  
P R Pratap
Keyword(s):  
Red Blood Cells ◽  
Blood Cells ◽  
Disulfonic Acid ◽  
Mean Cell Volume ◽  
Partial Inhibition ◽  
Human Red Blood Cells ◽  
Specific Effects ◽  
Voltage Curve ◽  
Current Voltage Curve ◽  
Cl Conductance

Net K and Cl effluxes induced by valinomycin or by gramicidin have been determined directly at varied external K, denoted by [K]o, in the presence and absence of the anion transport inhibitors DIDS (4,4'-diiso-thiocyano-2,2'-disulfonic acid stilbene), and its less potent analogue SITS (4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid). The results confirm that pretreatment with 10 microM DIDS, or 100 microM SITS, for 30 min at 23 degrees C inhibits conductive Cl efflux, measured in the continued presence of the inhibitors at 1 mM [K]o, by only 59-67%. This partial inhibition by 10 microM DIDS at 1 mM [K]o remains constant when the concentration of DIDS, or when the temperature or pH during pretreatment with DIDS, are increased. Observations of such partial inhibition previously prompted the postulation of two Cl conductance pathways in human red blood cells: a DIDS-sensitive pathway mediated by capnophorin (band 3 protein), and a DIDS-insensitive pathway. The present experiments demonstrate that at [K]o corresponding to values of EK between -35 and 0 mV the DIDS-insensitive component of net Cl efflux is negligible, being &lt; or = 0.1 muMol/g Hb/min, both with valinomycin (1 microM) and with gramicidin (0.06 microgram/ml). At lower [K]o, where EK is below approximately -35 mV, the DIDS-insensitive fraction of net Cl efflux increases to 2.6 muMol/g Hb/min with valinomycin (1 microM), and to 4.8 muMol/g Hb/min with gramicidin (0.06 microgram/ml). With net fluxes determined from changes in mean cell volume, and with membrane potentials measured from changes in the external pH of unbuffered red cell suspensions, a current-voltage curve for DIDS-insensitive Cl conductance has been deduced. While specific effects of varied [K]o on net Cl efflux are unlikely but cannot strictly be ruled out, the results are consistent with the hypothesis that DIDS-insensitive Cl conductance turns on at an Em of approximately -40 mV.

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.

Establishment of a murine model of cerebral malaria in KunMing mice infected with Plasmodium berghei ANKA

Parasitology ◽  
2016 ◽  
Vol 143 (12) ◽  
pp. 1672-1680 ◽  
Author(s):  
YAN DING ◽  
WENYUE XU ◽  
TAOLI ZHOU ◽  
TAIPING LIU ◽  
HONG ZHENG ◽  
...  
Keyword(s):  
Red Blood Cells ◽  
Cerebral Malaria ◽  
Plasmodium Berghei ◽  
Blood Cells ◽  
Mononuclear Cells ◽  
Clinical Signs ◽  
Necrosis Factor Alpha ◽  
Experimental Cerebral Malaria ◽  
Km Mice

SUMMARYMalaria remains one of the most devastating diseases. Cerebral malaria (CM) is a severe complication of Plasmodium falciparum infection resulting in high mortality and morbidity worldwide. Analysis of precise mechanisms of CM in humans is difficult for ethical reasons and animal models of CM have been employed to study malaria pathogenesis. Here, we describe a new experimental cerebral malaria (ECM) model with Plasmodium berghei ANKA infection in KunMing (KM) mice. KM mice developed ECM after blood-stage or sporozoites infection, and the development of ECM in KM mice has a dose-dependent relationship with sporozoites inoculums. Histopathological findings revealed important features associated with ECM, including accumulation of mononuclear cells and red blood cells in brain microvascular, and brain parenchymal haemorrhages. Blood–brain barrier (BBB) examination showed that BBB disruption was present in infected KM mice when displaying clinical signs of CM. In vivo bioluminescent imaging experiment indicated that parasitized red blood cells accumulated in most vital organs including heart, lung, spleen, kidney, liver and brain. The levels of inflammatory cytokines interferon-gamma, tumour necrosis factor-alpha, interleukin (IL)-17, IL-12, IL-6 and IL-10 were all remarkably increased in KM mice infected with P. berghei ANKA. This study indicates that P. berghei ANKA infection in KM mice can be used as ECM model to extend further research on genetic, pharmacological and vaccine studies of CM.

Sign in / Sign up

Export Citation Format

Share Document