scholarly journals The Abnormal CD4+T Lymphocyte Subset Distribution and Vbeta Repertoire in New-onset Rheumatoid Arthritis Can Be Modulated by Methotrexate Treament

Cells ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 871 ◽  
Author(s):  
Jorge Monserrat ◽  
Cristina Bohórquez ◽  
Ana María Gómez Lahoz ◽  
Atusa Movasat ◽  
Ana Pérez ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Lymphocytes ◽  
Effector Memory ◽  
Disease Modifying Drugs ◽  
Tcr Repertoire ◽  
Before And After ◽  
Polychromatic Flow Cytometry ◽  
Pre Treatment ◽  
Vbeta Repertoire

Patients with long-term, treated, rheumatoid arthritis (RA) show abnormalities in their circulating CD4+ T-lymphocytes, but whether this occurs in recently diagnosed naïve patients to disease-modifying drugs (DMARDs) is under discussion. These patients show heterogeneous clinical response to methotrexate (MTX) treatment. We have examined the count of circulating CD4+ T-lymphocytes, and their naïve (TN), central memory (TCM), effector memory (TEM) and effector (TE) subsets, CD28 expression and Vβ TCR repertoire distribution by polychromatic flow cytometry in a population of 68 DMARD-naïve recently diagnosed RA patients, before and after 3 and 6 months of MTX treatment. At pre-treatment baseline, patients showed an expansion of the counts of CD4+ TN, TEM, TE and TCM lymphocyte subsets, and of total CD4+CD28− cells and of the TE subset with a different pattern of numbers in MTX responder and non-responders. The expansion of CD4+TEM lymphocytes showed a predictive value of MTX non-response. MTX treatment was associated to different modifications in the counts of the CD4+ subsets and of the Vβ TCR repertoire family distribution and in the level of CD28 expression in responders and non-responders. In conclusion, the disturbance of CD4+ lymphocytes is already found in DMARD-naïve RA patients with different patterns of alterations in MTX responders and non-responders.

scholarly journals SAT0028 PERIPHERAL BLOOD REGULATORY T-LYMPHOCYTES OF PATIENTS WITH RHEUMATOID ARTHRITIS BEFORE AND AFTER ALFACALCIDOL THERAPY

2019 ◽  
Author(s):  
Tatjana Radnic ◽  
Katarina Pasalic ◽  
Mirjana Sefik Bukilica ◽  
Ivanka Markovic ◽  
Nemanja Damjanov ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Lymphocytes ◽  
Peripheral Blood ◽  
Regulatory T Lymphocytes ◽  
Before And After

scholarly journals Does immunological remission, defined as disappearance of autoantibodies, occur with current treatment strategies? A long-term follow-up study in rheumatoid arthritis patients who achieved sustained DMARD-free status

2019 ◽  
Vol 78 (11) ◽  
pp. 1497-1504 ◽  
Author(s):  
Debbie M Boeters ◽  
Leonie E Burgers ◽  
René EM Toes ◽  
Annette van der Helm-van Mil
Keyword(s):  
Rheumatoid Arthritis ◽  
Treatment Strategies ◽  
Signs And Symptoms ◽  
Current Treatment ◽  
Dmard Therapy ◽  
Before And After ◽  
Long Term Follow Up ◽  
Free Status

ObjectivesSustained disease-modifying antirheumatic drug (DMARD)-free status, the sustained absence of synovitis after cessation of DMARD therapy, is infrequent in autoantibody-positive rheumatoid arthritis (RA), but approximates cure (ie, disappearance of signs and symptoms). It was recently suggested that immunological remission, defined as disappearance of anti-citrullinated protein antibodies (ACPA) and rheumatoid factor (RF), underlies this outcome. Therefore, this long-term observational study determined if autoantibodies disappear in RA patients who achieved sustained DMARD-free remission.MethodsWe studied 95 ACPA-positive and/or RF-positive RA patients who achieved DMARD-free remission after median 4.8 years and kept this status for the remaining follow-up (median 4.2 years). Additionally, 21 autoantibody-positive RA patients with a late flare, defined as recurrence of clinical synovitis after a DMARD-free status of ≥1 year, and 45 autoantibody-positive RA patients who were unable to stop DMARD therapy (during median 10 years) were studied. Anti-cyclic citrullinated peptide 2 (anti-CCP2) IgG, IgM and RF IgM levels were measured in 587 samples obtained at diagnosis, before and after achieving DMARD-free remission.Results13% of anti-CCP2 IgG-positive RA patients had seroreverted when achieving remission. In RA patients with a flare and persistent disease this was 8% and 6%, respectively (p=0.63). For anti-CCP2 IgM and RF IgM, similar results were observed. Evaluating the estimated slope of serially measured levels revealed that RF levels decreased more in patients with than without remission (p<0.001); the course of anti-CCP2 levels was not different (p=0.66).ConclusionsSustained DMARD-free status in autoantibody-positive RA was not paralleled by an increased frequency of reversion to autoantibody negativity. This form of immunological remission may therefore not be a treatment target in patients with classified RA.

Effects of open field testing and associated handling v. handling alone on the adrenocortical reactivity of piglets around weaning

2002 ◽  
Vol 74 (3) ◽  
pp. 485-491 ◽  
Author(s):  
M. S. Herskin ◽  
K. H. Jensen
Keyword(s):  
Blood Sample ◽  
Open Field ◽  
Field Testing ◽  
Blood Sampling ◽  
Cortisol Response ◽  
Temporal Development ◽  
Novel Object ◽  
Before And After ◽  
Pre Treatment

AbstractEffects of open field testing and associated handling (including blood sampling) v. handling (with blood sampling) alone on adrenocortical reactivity were investigated in piglets around weaning. After weaning at day 28, piglets were mixed to form eight replicates with three litter each and kept on slatted floors. Treatments were open field/novel object testing and associated handling (OFT + H) v. handling alone (H) (no. = 40). Testing took place on the following days (weaning day 0): -4, 0, 1, 4 and 8 (no. = 16). The open field/novel object test lasted 10 min and blood was sampled by venipuncture before and after the test and/or handling procedures. In the first blood sample, plasma concentration of cortisol did not differ between OFT + H and H piglets. In the second blood sample, however, OFT + H piglets had a higher concentration of cortisol and a larger increase in cortisol than H piglets (P < 0·01). In the first blood sample the concentration of cortisol was affected by day (P < 0·05), with concentration on day -4 being lower than those on day 0, 1, and 4 and the concentration on day 8 was lower than the concentration on day 0 as well. However, no differences were found between days for the second blood sample nor the adrenocortical reactivity. In conclusion, the increase in pre-treatment cortisol in the first 4 days after weaning as well as the lack of changes in the adrenocortical reactivity after weaning suggest that the temporal development of HPA activity and reactivity in piglets after weaning are comparable with other, more standardized long-term stressors. Exposure to an open field/novel object test and associated handling results in higher adrenocortical reactivity than handling alone but the latter (including blood sampling) in itself accounts for proportionately 0·74 of the cortisol response.

scholarly journals The Efficacy of a Virtual Reality Exposure Therapy Treatment for Fear of Flying: A Retrospective Study

2021 ◽  
Vol 12 ◽  
Author(s):  
Amihai Gottlieb ◽  
Glen M. Doniger ◽  
Yara Hussein ◽  
Shlomo Noy ◽  
Meir Plotnik
Keyword(s):  
Virtual Reality ◽  
Treatment Period ◽  
Outcome Measures ◽  
Large Scale ◽  
Exposure Therapy ◽  
Fear Of Flying ◽  
Efficacy Outcome ◽  
Before And After ◽  
Pre Treatment

Background: Fear of flying (FoF) is a phobia with 10–40% prevalence in the industrialized world. FoF is accompanied by severe economic, social, vocational, and emotional consequences. In recent years, virtual reality (VR)-based exposure therapy (VRET) for FoF has been introduced. Positive long-term efficacy of FoF-VRET has been reported by several studies, which, however, were limited by relatively small, non-representative samples and a lack of comparative pre/post functional efficacy outcome measures. Our objective was to evaluate the efficacy of a VRET treatment utilizing a large-scale VR system, experienced by a representative sample of self-referred individuals.Methods: We conducted a retrospective survey. Of 274 individuals who received the treatment (over a period of 3 years), 209 met inclusion/criteria, and 98 agreed to participate. We mainly collected information regarding flight activity before and after treatment relying on evidence such as boarding passes and flight tickets. The primary outcome measures were (1) number of flights per month (FpM) and (2) number of flight hours per month (FHpM). For each participant, these outcomes were computed for the post-treatment period (≥6 months after FoF-VRET) and the corresponding pre-treatment period.Results: FpM (mean ± SD) increased from 0.04 ± 0.06 to 0.16 ± 14 flights (p &lt; 0.0001). FHpM rose from 0.19 ± 0.35 to 0.79 ± 0.87 h per month (p &lt; 0.0001).Conclusion: These results are indicative of FoF-VRET treatment efficacy. Future studies should evaluate long-term maintenance of the treatment effect and thus identify the optimal frequency for delivery of periodic booster treatments.

scholarly journals Methrotexate Treatment Inmunomodulates Abnormal Cytokine Expression by T CD4 Lymphocytes Present in DMARD-Naïve Rheumatoid Arthritis Patients

2020 ◽  
Vol 21 (18) ◽  
pp. 6847
Author(s):  
Jorge Monserrat Sanz ◽  
Cristina Bohórquez ◽  
Ana Maria Gómez ◽  
Atusa Movasat ◽  
Ana Pérez ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Lymphocytes ◽  
T Lymphocyte ◽  
Lymphocyte Subsets ◽  
Cytokine Expression ◽  
Effector Memory ◽  
T Lymphocyte Subsets ◽  
Relevant Role ◽  
Circulating Levels ◽  
New Onset

CD4+T-lymphocytes are relevant in the pathogenesis of rheumatoid arthritis (RA), however, their potential involvement in early RA remains elusive. Methotrexate (MTX) is a commonly used disease-modifying antirheumatic drug (DMARD), but its mechanism has not been fully established. In 47 new-onset DMARD-naïve RA patients, we investigated the pattern of IFNγ, IL-4 and IL-17A expression by naïve (TN), central (TCM), effector memory (TEM) and effector (TE) CD4+ subsets; their STAT-1, STAT-6 and STAT-3 transcription factors phosphorylation, and the circulating levels of IFNγ, IL-4 and IL-17. We also studied the RA patients after 3 and 6 months of MTX treatment and according their clinical response. CD4+T-lymphocyte subsets and cytokine expression were measured using flow cytometry. New-onset DMARD-naïve RA patients showed a significant expansion of IL-17A+, IFNγ+ and IL-17A+IFNγ+ CD4+T-lymphocyte subsets and increased intracellular STAT-1 and STAT-3 phosphorylation. Under basal conditions, nonresponder patients showed increased numbers of circulating IL-17A producing TN and TMC CD4+T-lymphocytes and IFNγ producing TN, TCM, TEM CD4+T-lymphocytes with respect to responders. After 6 months, the numbers of CD4+IL-17A+TN remained significantly increased in nonresponders. In conclusion, CD4+T-lymphocytes in new-onset DMARD-naïve RA patients show IL-17A and IFNγ abnormalities in TN, indicating their relevant role in early disease pathogenesis. Different patterns of CD4+ modulation are identified in MTX responders and nonresponders.

scholarly journals Renal ischemia-reperfusion leads to long term infiltration of activated and effector-memory T lymphocytes

2009 ◽  
Vol 75 (5) ◽  
pp. 526-535 ◽  
Author(s):  
Miguel Ascon ◽  
Dolores B. Ascon ◽  
Manchang Liu ◽  
Chris Cheadle ◽  
Chaitali Sarkar ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Ischemia Reperfusion ◽  
Renal Ischemia ◽  
Effector Memory ◽  
Memory T Lymphocytes

Haemodynamic Responses to Exercise and Acute β-Receptor Blockade in Renin Sub-Types of Essential Hypertension

1976 ◽  
Vol 51 (s3) ◽  
pp. 493s-496s ◽  
Author(s):  
F. Burkart ◽  
F. R. Bühler ◽  
M. Pfisterer ◽  
B. E. Lütold ◽  
M. Küng
Keyword(s):  
Essential Hypertension ◽  
Plasma Renin ◽  
Receptor Blockade ◽  
Control Mechanisms ◽  
Exercise Tachycardia ◽  
Adrenergic Control ◽  
Before And After ◽  
Pre Treatment ◽  
Β Receptor

1. Haemodynamic and renin responses to dynamic exercise before and after intravenous β-adrenoreceptor blockade with propranolol were compared in twenty-one patients with essential hypertension and either high (n = 7), normal (n = 7) or low plasma renin activity (n = 7). 2. Renin and heart-rate responses to exercise and β-receptor blockade diminished from high-renin to normal and to low-renin patients, effects which were blunted with increasing age. 3. Among the renin groups cardiac output, stroke volume, diastolic pulmonary artery pressure, systemic pressure and peripheral vascular resistance as well as their changes produced by exercise and acute β-receptor blockade were not significantly different. 4. Long-term anti-hypertensive propranolol effects correlated with the pre-treatment renin status, renin stimulation and its suppression by acute β-receptor blockade as well as with the exercise tachycardia and the patient's age. 5. The results suggest different adrenergic control mechanisms in renin sub-types of essential hypertension, age being a modulating factor.

Influence of dopaminergic inhibition on serum levels of thyrotrophin and prolactin in patients with hypothyroidism before and after prolonged oral administration of TRH

1983 ◽  
Vol 104 (2) ◽  
pp. 183-188 ◽  
Author(s):  
Harald M. M. Frey ◽  
Egil Haug
Keyword(s):  
Oral Administration ◽  
Serum Levels ◽  
Primary Hypothyroidism ◽  
Dopamine Antagonist ◽  
Trh Stimulation ◽  
Before And After ◽  
The Mean ◽  
Pre Treatment ◽  
Serum Tsh

Abstract. Forty mg TRH/day given orally for 3 weeks to 8 patients with mild primary hypothyroidism decreased serum TSH from a mean of 4.0 ng/ml ± 1.2 (se) to 2.0 ng/ml ± 0.4 (49%), and their mean incremental TSH response to iv TRH was equally reduced from 8.6 ng/ml ± 2.5 to 4.0 ng/ml ± 1.9 (46%). In the same patients serum Prl was 8.2 ng/ml ± 2.2 before oral TRH treatment and 6.6 ng/ml ± 1.5 (81%) after treatment, and the mean incremetal Prl response to iv TRH was reduced from 43.5 ng/ml ± 5.0 to 35.9 ng/ml ± 7.5(83%). The oral administration of 10 mg of the dopamine antagonist metoclopramide increased mean serum TSH from 0.6 ng/ml ± 0.1 (se) to 0.7 ng/ml ± 0.1 (120%) in euthyroid subjects and from 4.0 ng/ml ±1.2 to 5.7 ng/ml ± 1.6 (145%) in patients with primary hypothyroidism, and mean serum Prl from 8.6 ng/ml ± 0.8 to 109.5 ng/ml ± 24.3 (1251%) and from 8.2 ng/ml ± 2.2 to 119.6 ng/ml ± 45.5(1460%), respectively. The incremental TSH responses to iv TRH increased 2.3-fold in euthyroid subjects pre-treated with metoclopramide, while no change was observed in the TSH responsiveness in patients with primary hypothyroidism following metoclopramide pre-treatment. In the euthyroid subjects metoclopramide treatment had no effect on the Prl response to iv TRH. In the primary hypothyroid group metoclopramide pre-treatment caused a reduced Prl response to iv TRH in more than 50% of the patients. It is concluded that long-term TRH treatment decreased the serum levels of TSH and Prl as well as the incremental increases in TSH and Prl to iv TRH stimulation in patients with primary hypothyroidism. Long-term TRH treatment did not change the TSH and Prl responses to the dopamine antagonist metoclopramide.

scholarly journals The efficacy of a virtual reality exposure therapy treatment for fear of flying: A retrospective study

2020 ◽  
Author(s):  
Amihai Gottlieb ◽  
Glen M. Doniger ◽  
Yara Hussein ◽  
Shlomo Noy ◽  
Meir Plotnik
Keyword(s):  
Virtual Reality ◽  
Treatment Period ◽  
Outcome Measures ◽  
Exposure Therapy ◽  
Medical Center ◽  
Fear Of Flying ◽  
Efficacy Outcome ◽  
Before And After ◽  
Pre Treatment

AbstractBackgroundFear of flying (FoF) is an anxiety disorder classified as a phobia. Its prevalence is estimated at 10–40% in the industrialized world, and it is accompanied by severe economic, social, vocational and emotional consequences. In recent years, virtual reality-based exposure therapy (VRET) for FoF has been introduced. One such FoF-VRET is offered as a paid clinical service at the Center of Advanced Technologies in Rehabilitation (CATR), Sheba Medical Center, Israel. Positive long-term efficacy of FoF-VRET has been found in several studies. However, these studies are limited by relatively small, non-representative samples and a lack of comparative pre/post functional efficacy outcome measures.MethodsTo address these limitations, we conducted a retrospective survey of self-referred individuals treated with FoF-VRET at CATR over the previous four years. The aim of the present study was to evaluate the efficacy of our FoF-VRET in this representative real-world sample. Of 274 individuals who received the treatment, 214 met inclusion/criteria, and 103 agreed to participate. The survey focused mainly on collecting information regarding flight activity before and after treatment. The primary outcome measures were: (1) number of flights per month (FpM); (2) number of flight hours per month (FHpM). For each participant, these outcomes were computed for the post-treatment period (≥6 months after FoF-VRET) and the corresponding pre-treatment period.ResultsFpM (mean±SD) increased from .05±.07 to .16±.07 flights (p<.0001). FHpM rose from.22±.41 to .80±.86 hours per month (p<.0001).ConclusionsThese results are indicative of FoF-VRET treatment efficacy. Future studies should evaluate long-term maintenance of the treatment effect and thus identify the optimal frequency for delivery of periodic booster treatments.

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