ΕΠΙΔΡΑΣΗ ΔΙΑΦΟΡΩΝ ΠΡΟΣΘΕΤΙΚΩΝ ΤΡΟΦΙΜΩΝ ΣΤΟ ΑΝΟΣΟΠΟΙΗΤΙΚΟ ΣΥΣΤΗΜΑ ΤΟΥ ΑΝΘΡΩΠΟΥ (IN VITRO ΜΕΛΕΤΗ)

THIS STUDY DESCRIBES S SENSITIVE AND REPRODUCIBLE MICROASSAY MODEL USING HUMAN PERIPHERAL BLOOD LYMPHOCYTES FOR THE DISCRIMINATION BETWEEN THE CYTOTOXIC AND IMMUNOSUPPRESIVE EFFECTS OF SOME FOOD ADDITIVES,SUCH AS,SODIUM BENROATE,BHT,HEXAMINE,SODIUM NITRATE AMARANTH AND TARFRARINE.THE CYTOTOXIC EFFECTS OF A WIDE RANGE OF CONCETRATIONS OF THESE SUBSTANCES WERE STUDIED ON HUMAN PERIPHERALS BLOOD LYMPHOCYTES(PBL)BY TWO COLORIMETRIC IN VITRO ASSAYS,NAMELY THE NEUTRAL RED UPTAKE(NR) AND THE THIAROLYL BLUE TETRAROLIUM BLOMIDE(MTT)ASSAY.FURTHERMORE,THE IMMUNOTOXIC PROPERTIES OF THESE SUBSTANCES WERE DETERMINED BY A [3H] THYMIDINE INCORPORATION ASSAY ON PHYTOHAEMAGGLERTINIU (PHA) STIMULATED OR NON-STIMULATED LYMPHOCYTES,AS WELL AS BY ^51CR RELEASE NU ASSAY.THE RESULTS SHOWED A CLEAR IMMUNOSUPPRESIVE EFFECT OF ALL THE SUBSTANCES TESTED ALTHOUGH THE CONCETRATIONS WHICH WERE CHOSEN FOR THIS STUDY WERE PROVED TO BE NON CYTOTOXIC BY THE NR AND MTT ASSAY.Η ΜΕΛΕΤΗ ΑΥΤΗ ΠΕΡΙΓΡΑΦΕΙ ΕΝΑ ΕΥΑΙΣΘΗΤΟ ΚΑΙ ΑΝΑΠΑΡΑΓΩΜΕΝΟ ΜΟΝΤΕΛΟ ΠΟΥ ΧΡΗΣΙΜΟΠΟΙΕΙ ΑΝΘΡΩΠΙΝΑ ΠΕΡΙΦΕΡΙΚΑ ΛΕΜΦΟΚΥΤΤΑΡΑ ΓΙΑ ΤΗΝ ΔΙΑΚΡΙΣΗ ΜΕΤΑΞΥ ΤΩΝ ΚΥΤΤΑΡΟΤΟΞΙΚΩΝ ΚΑΙ ΑΝΟΣΟΚΑΤΑΣΤΑΛΤΙΚΩΝ ΙΔΙΟΤΗΤΩΝ ΔΙΑΦΟΡΩΝ ΠΡΟΣΘΕΤΙΚΩΝ ΤΡΟΦΙΜΩΝ ΟΠΩΣ ΕΙΝΑΙΤΟ ΒΕΝΖΟΙΚΟ ΝΑΤΡΙΟ,ΤΟ ΝΙΤΡΙΚΟ ΝΑΤΡΙΟ,Η ΕΞΑΜΙΝΗ,ΤΟ ΒΗΤ,Η ΑΜΑΡΑΝΘΗ ΚΑΙ Η ΤΑΡΤΑΖΙΝΗ.Η ΚΥΤΤΑΡΟΤΟΞΙΚΟΤΗΤΑ ΕΝΟΣ ΕΥΡΕΟΣ ΦΑΣΜΑΤΟΣ ΣΥΓΚΕΝΤΡΩΣΕΩΝ ΤΩΝ ΥΠΟ ΜΕΛΕΤΗ ΟΥΣΙΩΝ ΜΕΛΕΤΗΘΗΚΕ ΜΕ ΤΗ ΒΟΗΘΕΙΑ ΔΥΟ ΧΡΩΜΑΤΟΜΕΤΡΙΚΩΝ IN VITRO ΔΟΚΙΜΑΣΙΩΝ ΚΥΤΤΑΡΟΤΟΞΙΚΟΤΗΤΑΣ,ΤΗΝ ΔΟΚΙΜΑΣΙΑ ΠΡΟΣΛΗΨΗΣ ΤΗΣ ΧΡΩΣΤΙΚΗΣ ΜΤΤ ΚΑΙ ΤΗΣ ΧΡΩΣΤΙΚΗΣ NEUTRAL FED.OI ΑΝΟΣΟΤΡΟΠΟΠΟΙΗΤΙΚΕΣ ΙΔΙΟΤΗΤΕΣ ΤΩΝ ΠΑΡΑΠΑΝΩ ΟΥΣΙΩΝ ΚΑΘΟΡΙΣΤΗΚΑΝ ΜΕ ΤΗΝ ΔΟΚΙΑΜΑΣΙΑ ΠΡΟΣΛΗΨΗΣ ΤΡΙΤΙΩΜΕΝΗΣ ΘΥΜΙΔΙΝΗΣ ΑΠΟ ΔΙΕΓΕΡΜΕΝΑ(ΜΕ ΡΗΑ) ΚΑΙ ΜΗ ΔΙΕΓΕΡΜΕΝΑ ΛΕΜΦΟΚΥΤΤΑΡΑ ΟΠΩΣ ΚΑΙ ΜΕ ΤΗΝ ΔΟΚΙΜΑΣΙΑ ΑΠΕΛΕΥΘΕΡΩΣΗΣ CR 51 ΑΠΟΚΑΡΚΙΝΙΚΑ ΚΥΤΤΑΡΑ U562 ΜΕΤΑ ΤΗΝ ΕΠΙΔΡΑΣΗ ΤΩΝ ΦΥΣΙΚΩΝ ΦΟΝΙΚΩΝ ΚΥΤΤΑΡΩΝ Τ'ΑΠΟΤΕΛΕΣΜΑΤΑ ΕΔΕΙΞΑΝ ΜΙΑ ΑΝΟΣΟΚΑΤΑΣΤΑΛΤΙΚΗ ΔΡΑΣΗ ΤΩΝ ΥΠΟ ΜΕΛΕΤΗ ΟΥΣΙΩΝ ΠΑΡ ~ΛΟΠΟΥΟΙ ΣΥΓΚΕΚΡΙΜΕΝΕΣ ΠΟΥ ΕΠΙΛΕΧΘΗΚΑΝ ΗΤΑΝ ΜΗ ΚΥΤΤΑΡΟΤΟΞΙΚΕΣ

The Double-Edged Sword of T1-Mapping in Systemic Sclerosis—A Comparison with Infectious Myocarditis Using Cardiovascular Magnetic Resonance

Aims: T1-mapping is considered a surrogate marker of acute myocardial inflammation. However, in diffuse cutaneous systemic sclerosis (dcSSc) this might be confounded by coexisting myocardial fibrosis. We hypothesized that T1-based indices should not by themselves be considered as indicators of myocardial inflammation in dcSSc patients. Methods/Results: A cohort of 59 dcSSc and 34 infectious myocarditis patients was prospectively evaluated using a 1.5-Tesla system for an indication of suspected myocardial inflammation and was compared with 31 healthy controls. Collectively, 33 (97%) and 57 (98%) of myocarditis and dcSSc patients respectively had ≥1 pathologic T2-based index. However, 33 (97%) and 45 (76%) of myocarditis and dcSSc patients respectively had ≥1 pathologic T2-based index. T2-signal ratio was significantly higher in myocarditis patients compared with dcSSc patients (2.5 (0.6) vs. 2.1 (0.4), p < 0.001). Early gadolinium enhancement, late gadolinium enhancement and T2-mapping did not differ significantly between groups. However, both native T1-mapping and extracellular volume fraction were significantly lower in myocarditis compared with dcSSc patients (1051.0 (1027.0, 1099.0) vs. 1120.0 (1065.0, 1170.0), p < 0.001 and 28.0 (26.0, 30.0) vs. 31.5 (30.0, 33.0), p < 0.001, respectively). The original Lake Louise criteria (LLc) were positive in 34 (100%) myocarditis and 40 (69%) dcSSc patients, while the updated LLc were positive in 32 (94%) and 44 (76%) patients, respectively. Both criteria had good agreement with greater but nonsignificant discordance in dcSSc patients. Conclusions: ~25% of dcSSc patients with suspected myocardial inflammation had no CMR evidence of acute inflammatory processes. T1-based indices should not be used by themselves as surrogates of acute myocardial inflammation in dcSSc patients

Can cardiovascular magnetic resonance prompt early cardiovascular/rheumatic treatment in autoimmune rheumatic diseases? Current practice and future perspectives

Life expectancy in autoimmune rheumatic diseases (ARDs) remains lower compared to the general population, due to various comoborbidities. Cardiovascular disease (CVD) represents the main contributor to premature mortality. Conventional and biologic disease-modifying antirheumatic drugs (DMARDs) have considerably improved long-term outcomes in ARDs not only by suppressing systemic inflammation but also by lowering CVD burden. Regarding atherosclerotic disease prevention, EULAR has recommended tight disease control accompanied by regular assessment of traditional CVD risk factors and lifestyle changes. However, this approach, although rational and evidence-based, does not account for important issues such as myocardial inflammation and the long asymptomatic period that usually proceeds clinical manifestations of CVD disease in ARDs before or after the diagnosis of systemic disease. Cardiovascular magnetic resonance (CMR) can offer reliable, reproducible and operator independent information regarding myocardial inflammation, ischemia and fibrosis. Some studies suggest a role for CMR in the risk stratification of ARDs and demonstrate that oedema/fibrosis visualisation with CMR may have the potential to inform cardiac and rheumatic treatment modification in ARDs with or without abnormal routine cardiac evaluation. In this review, we discuss how CMR findings could influence anti-rheumatic treatment decisions targeting optimal control of both systemic and myocardial inflammation irrespective of clinical manifestations of cardiac disease. CMR can provide a different approach that is very promising for risk stratification and treatment modification; however, further studies are needed before the inclusion of CMR in the routine evaluation and treatment of patients with ARDs

Combined Brain/Heart Magnetic Resonance Imaging in Systemic Lupus Erythematosus

Cardiovascular Disease (CVD) in Systemic Lupus Erythematosus (SLE) and Neuropsychiatric SLE (NPSLE) has an estimated prevalence of 50% and 40%, respectively and both constitute major causes of death among SLE patients. In this review, we proposea combined brain/heart Magnetic Resonance Imaging (MRI) for SLE risk stratification has been proposed. The pathophysiologic background of NPSLE includes microangiopathy, macroscopic infarcts and accelerated atherosclerosis. Classic brain MRI findings demonstrate lesions suggestive of NPSLE in 50% of the NPSLE cases, while advanced MRI indices can detect pre-clinical lesions in the majority of them, but their clinical impact still remains unknown. Cardiac involvement in SLE includes myo-pericarditis, valvular disease/endocarditis, Heart Failure (HF), coronary macro-microvascular disease, vasculitis and pulmonary hypertension. Classic and advanced Cardiovascular Magnetic Resonance (CMR) indices allow function and tissue characterization for early diagnosis and treatment follow-up of CVD in SLE. Although currently, there are no clinical data supporting the combined use of brain/heart MRI in asymptomatic SLE, it may have a place in cases with clinical suspicion of brain/heart involvement, especially in patients at high risk for CVD/stroke such as SLE with antiphospholipid syndrome (SLE/APS), in whom concurrent cardiac and brain lesions have been identified. Furthermore, it may be of value in SLE with multi-organ involvement, NPSLE with concurrent cardiac involvement, and recent onset of arrhythmia and/or heart failure

Myocardial Involvement in Rheumatic Disorders

Purpose of review: Autoimmune rheumatic diseases (ARDs) affect 8% of the population and approximately 78% of patients are women. Myocardial disease in ARDs is the endpoint of various pathophysiologic mechanisms including atherosclerosis, valvular disease, systemic, myocardial, and/or vascular inflammation, as well as myocardial ischemia and replacement/diffuse fibrosis. Recent findings: The increased risk of CVD in ARDs leads to excess comorbidity not fully explained by traditional cardiovascular risk factors. It seems that the chronic inflammatory status typically seen in ARDs, promotes both the development of myocardial inflammation/fibrosis and the acceleration of atherosclerosis. CMR (cardio-vascular magnetic resonance) is the ideal imaging modality for the evaluation of cardiac involvement in patients with ARDs, as it can simultaneously assess cardiac function and characterize myocardial tissues with regard to oedema and fibrosis. Due to its high spatial resolution, CMR is capable of identifying various disease entities such as myocardial oedema /inflammation, subendocardial vasculitis and myocardial fibrosis, that are often missed by other imaging modalities, notably at an early stage of development. Although generally accepted guidelines about the application of CMR in ARDs have not yet been formulated, according to our experience and the available published literature, we recommend CMR in ARD patientS with new-onset heart failure (HF), arrhythmia, for treatment evaluation/change or if there is any mismatch between patient symptoms and routine non-invasive evaluation

CMR feature tracking in cardiac asymptomatic systemic sclerosis : Clinical implications

BACKGROUND: Impaired myocardial deformation has been sporadically described in cardiac asymptomatic systemic sclerosis (SSc). We aimed to study myocardial deformation indices in cardiac asymptomatic SSc patients using cardiac magnetic resonance feature tracking (CMR-FT) and correlate these findings to the phenotypic and autoimmune background.METHODS: Fifty-four cardiac asymptomatic SSc patients (44 females, 56±13 years), with normal routine cardiac assessment and CMR evaluation, including cine and late gadolinium enhancement (LGE) images, were included. SSc patients were compared to 21 sex- and age- matched healthy controls (17 females; 54±19 years). For CMR-FT analysis, a mid-ventricular slice for LV peak systolic radial and circumferential strain and a 4-chamber view for LV/RV peak systolic longitudinal strain were used.RESULTS: Twenty-four patients had diffuse cutaneous SSc and 30 limited cutaneous SSc. Thirteen patients had digital ulcers. Median disease duration was 3.6 years. LV ejection fraction was higher in SSc patients compared to controls (62±6% vs. 59±5%, p = 0.01). Four patients had no LGE examination; in the remaining patients LGE was absent in 74%, while 18% had RV insertion fibrosis and 8% evidence of subendocardial infarction. LV longitudinal strain differed in those with insertion fibrosis (-18.0%) and infarction (-16.7%) compared to no fibrosis (-20.3%, p = 0.04). Patients with SSc had lower RV longitudinal strain and strain rate compared to controls (p<0.001 and p = 0.01, respectively). All other strain and strain rate measurements were non-significant between patients and controls.CONCLUSIONS: In cardiac asymptomatic SSc patients with normal routine functional indices, CMR-FT identifies subclinical presence of insertion fibrosis and/or myocardial infarction by impaired LV longitudinal strain. RV derived longitudinal indices were impaired in the patient group. CMR FT indices did not correlate to the patients' phenotypic and autoimmune features

CMR feature tracking in cardiac asymptomatic systemic sclerosis: Clinical implications

Background Impaired myocardial deformation has been sporadically described in cardiac asymptomatic systemic sclerosis (SSc). We aimed to study myocardial deformation indices in cardiac asymptomatic SSc patients using cardiac magnetic resonance feature tracking (CMR-FT) and correlate these findings to the phenotypic and autoimmune background. Methods Fifty-four cardiac asymptomatic SSc patients (44 females, 56 +/- 13 years), with normal routine cardiac assessment and CMR evaluation, including cine and late gadolinium enhancement (LGE) images, were included. SSc patients were compared to 21 sex- and age-matched healthy controls (17 females; 54 +/- 19 years). For CMR-FT analysis, a mid-ventricular slice for LV peak systolic radial and circumferential strain and a 4-chamber view for LV/RV peak systolic longitudinal strain were used. Results Twenty-four patients had diffuse cutaneous SSc and 30 limited cutaneous SSc. Thirteen patients had digital ulcers. Median disease duration was 3.6 years. LV ejection fraction was higher in SSc patients compared to controls (62 +/- 6% vs. 59 +/- 5%, p = 0.01). Four patients had no LGE examination; in the remaining patients LGE was absent in 74%, while 18% had RV insertion fibrosis and 8% evidence of subendocardial infarction. LV longitudinal strain differed in those with insertion fibrosis (-18.0%) and infarction (-16.7%) compared to no fibrosis (-20.3%, p = 0.04). Patients with SSc had lower RV longitudinal strain and strain rate compared to controls (p&lt;0.001 and p = 0.01, respectively). All other strain and strain rate measurements were non-significant between patients and controls. Conclusions In cardiac asymptomatic SSc patients with normal routine functional indices, CMR-FT identifies subclinical presence of insertion fibrosis and/or myocardial infarction by impaired LV longitudinal strain. RV derived longitudinal indices were impaired in the patient group. CMR FT indices did not correlate to the patients’ phenotypic and autoimmune features

Pseudo-infarction pattern in diffuse systemic sclerosis. Evaluation using cardiovascular magnetic resonance

Background: Diffuse systemic sclerosis (dSSc) is characterized by vascular lesions and fibrosis. Cardiac involvement, although silent, accounts for 36% of deaths. We hypothesized that cardiovascular magnetic resonance (CMR) can clarify the pathophysiology of Q waves in dSSc patients. Patients-methods: 105 dSSc, aged 48 +/- 2 years, with atypical symptoms and normal routine assessment, were evaluated by ECG and CMR using a 1.5 T system. Biventricular function was assessed by steady-state free-precession sequence (SSFP). To identify fibrosis, late gadolinium enhanced areas (LGE) were evaluated 15 min after injection of 0.2 mmol/kg gadolinium-DTPA and expressed as % of LV mass. Results: Q waves in V1-V5 (Group A), II, III, AVF (Group B) and I, AVL, II, III, AVF, V1-V5 (Group C) were found in 25/105, 8/105 and 5/105 dSSc, respectively. In 25 dSSc with Q in V1-V6, patchy intramyocardial LGE was detected in 24/25 and involved 8 +/- 2% of LV mass. LGE involved the intraventricular septum (IVS) in 11/24 and the lateral wall (LAT) in 5/24 dSSc. Only in 1/25 dSSc, an anterior, transmural LGE, due to LAD occlusion, was identified. In 8 dSSc with Q in II, III, AVF, patchy intramyocardial LGE was detected in the inferior wall and involved 5 +/- 2% of LV mass. In 5 dSSc with Q in V1-V5, II, III, AVF, patchy intramyocardial LGE was detected in anterior and inferolateral wall and involved 9 +/- 2% of LV mass. Conclusion: CMR unveiled that the pattern of myocardial fibrosis in dSSc with Q waves is due to the systemic disease and not to CAD. (C) 2016 Elsevier Ireland Ltd. All rights reserved

Cardiac magnetic resonance predicts ventricular arrhythmias in scleroderma: the Scleroderma Arrhythmia Clinical Utility Study (SAnCtUS)

Objectives: Cardiac rhythm disturbances constitute the most frequent cardiovascular cause of death in SSc. However, electrocardiographic findings are not a part of risk stratification in SSc. We aimed to translate 24 h Holter findings into a tangible risk prediction score using cardiovascular magnetic resonance.Methods: The Scleroderma Arrhythmia Clinical Utility Study (SAnCtUS) was a prospective multicentre study including 150 consecutive SSc patients from eight European centres, assessed with 24 h Holter and cardiovascular magnetic resonance, including ventricular function, oedema (T2 ratio) and late gadolinium enhancement (%LGE). Laboratory/clinical parameters were included in multivariable corrections. A combined endpoint of sustained ventricular tachycardia requiring hospitalization and sudden cardiac death at a median (interquartile range) follow-up of 1 (1.0-1.4) year was generated.Results: Only T2 ratio and %LGE were significant predictors of ventricular rhythm disturbances, but not of supraventricular rhythm disturbances, after multivariable correction and adjustment for multiple comparisons. Using decision-tree analysis, we created the SAnCtUS score, a four-category scoring system based on T2 ratio and %LGE, for identifying SSc patients at high risk of experiencing ventricular rhythm disturbance at baseline. Increasing SAnCtUS scores were associated with a greater disease and arrhythmic burden. All cases of non-sustained ventricular tachycardia (n = 7) occurred in patients with the highest SAnCtUS score (=4). Having a score of 4 conveyed a higher risk of reaching the combined endpoint in multivariable Cox regression compared with scores 1/2/3 [hazard ratio (95% CI): 3.86 (1.14, 13.04), P = 0.029] independently of left ventricular ejection fraction and baseline ventricular tachycardia occurrence.Conclusion: T2 ratio and %LGE had the greatest utility as independent predictors of rhythm disturbances in SSc patients