Circulating Levels of Inflammatory Markers in Intrauterine Growth Restriction

We aimed to investigate possible alterations in circulating levels of the perinatal stress markers high sensitivity (hs)-CRP, PAI-1, and S100B—probably reflecting brain and adipose tissue inflammation—in intrauterine growth-restricted-(IUGR) and appropriate-for-gestational-age-(AGA) pregnancies, given that these groups differ in fat mass and metabolic mechanisms involving aseptic inflammation. Serum hs-CRP, PAI-1, and S100B levels were measured in 40 mothers, and their 20 AGA and 20 IUGR full-term fetuses and neonates on postnatal days 1 and 4. hs-CRP, PAI-1, and S100B levels did not differ at all time points between AGA and IUGR groups. We conclude that the lack of difference in hs-CRP, PAI-1 and S100B levels, between IUGR and AGA fetuses/neonates—despite the lower birth weight, reflecting reduced fat mass in the former—might indicate more intense adipose tissue and nervous system inflammation in IUGRs. However, implication of other inflammation-related mechanisms, common in the IUGR state (e.g. preeclampsia), cannot be excluded

Evidence of a Redox-Dependent Regulation of Immune Responses to Exercise-Induced Inflammation

We used thiol-based antioxidant supplementation (n-acetylcysteine, NAC) to determine whether immune mobilisation following skeletal muscle microtrauma induced by exercise is redox-sensitive in healthy humans. According to a two-trial, double-blind, crossover, repeated measures design, 10 young men received either placebo or NAC (20 mg/kg/day) immediately after a muscle-damaging exercise protocol (300 eccentric contractions) and for eight consecutive days. Blood sampling and performance assessments were performed before exercise, after exercise, and daily throughout recovery. NAC reduced the decline of reduced glutathione in erythrocytes and the increase of plasma protein carbonyls, serum TAC and erythrocyte oxidized glutathione, and TBARS and catalase activity during recovery thereby altering postexercise redox status. The rise of muscle damage and inflammatory markers (muscle strength, creatine kinase activity, CRP, proinflammatory cytokines, and adhesion molecules) was less pronounced in NAC during the first phase of recovery. The rise of leukocyte and neutrophil count was decreased by NAC after exercise. Results on immune cell subpopulations obtained by flow cytometry indicated that NAC ingestion reduced the exercise-induced rise of total macrophages, HLA+ macrophages, and 11B+ macrophages and abolished the exercise-induced upregulation of B lymphocytes. Natural killer cells declined only in PLA immediately after exercise. These results indicate that thiol-based antioxidant supplementation blunts immune cell mobilisation in response to exercise-induced inflammation suggesting that leukocyte mobilization may be under redox-dependent regulation

Maternal chronic stress correlates with serum levels of cortisol, glucose and C-peptide in the fetus, and maternal non chronic stress with fetal growth

Introduction: During pregnancy, maternal stressors cause changes in both maternal and fetal HPA axes. We therefore investigated the impact of maternal non chronic and chronic stress on fetal glucose metabolism and growth, and serum levels of cortisol in the fetus. Materials and methods: Normal weight pregnant women (n = 192; mean ± SD 27.9 ± 4.2 years old, and; 26.9 ± 2.4 kg/m²) were assessed during the 2nd and 3rd trimester with anthropometry, fetal ultrasound, blood samples for serum CRH, cortisol and IL6, and STAI trait and state stress questionnaires. We measured serum cortisol, insulin and c-peptide, and plasma glucose from cord blood. Neonates underwent anthropometry at the 3rd post-delivery day. Results: In both 2nd and 3rd trimesters, women with STAI trait scores ≥40 had significantly greater levels of fasting serum CRH and cortisol than those with STAI trait scores<40. 2nd trimester: STAI trait scores correlated positively with cord blood glucose and c-peptide. Maternal serum CRH correlated negatively with U/S fetal biparietal head diameter, while serum cortisol correlated positively with abdominal circumference. Maternal serum IL6, CRH and cortisol all correlated positively with birth waist circumference. 3rd trimester: Women with STAI state scores ≥40 had fetuses with larger U/S abdominal and smaller head circumferences compared to those of women with STAI scores <40. Women with STAI trait scores ≥40 had greater levels of cord blood cortisol, glucose, and c-peptide compared to women with STAI scores <40. STAI state scores ≥40 correlated positively with maternal CRH and U/S fetal abdominal circumference, and negatively with fetal head circumference and biparietal diameter. STAI trait scores correlated positively with cord blood c-peptide, glucose, insulin and cortisol. Maternal serum levels of CRH correlated positively with U/S fetal abdominal circumference and cord blood cortisol, and negatively with fetal head circumference and biparietal head diameter. Maternal serum levels of both CRH and cortisol correlated positively with cord blood c-peptide, glucose, and insulin. STAI trait was the best positive predictor of cord blood cortisol, glucose and c-peptide, whilst STAI state was the best positive and negative predictor, respectively of fetal abdominal circumference and fetal head circumference or biparietal diameter. Conclusions: Increased maternal chronic stress (reflected by the STAI trait score) associates with increased fetal cortisol, glucose, c-peptide secretion and thus, insulin resistance. Maternal non chronic stress (STAI state) in the 3rd trimester associates with changes in fetal growth pattern, including increased and decreased measurements of fetal abdominal and head growth respectively

Άμεση επίδραση πλειομετρικών αλμάτων στα κινητικά και κινηματικά χαρακτηριστικά

Ως μεταδιεγερτική ενεργοποίηση ορίζεται το φαινόμενο κατά το οποίο ο μυς εμφανίζει αύξηση της ικανότητας παραγωγής δύναμης λόγω της προηγηθείσας δραστηριότητας του. Οι πλειομετρικές ασκήσεις αποτελούν ένα πολλά υποσχόμενο είδος ασκήσεων ενεργοποίησης, λόγω της εύκολης εφαρμογής τους στο πεδίο. Ωστόσο, δεν έχει μελετηθεί η επίδραση αμιγώς μονοποδικής πλειομετρικής άσκησης στην πρόκληση ΜΔΕ μέχρι σήμερα. Σκοπός της παρούσας έρευνας ήταν να μελετήσει την άμεση επίδραση οριζόντιων μονοποδικών αλμάτων στην ισχύ και στην σκληρότητα των κάτω άκρων. Η ισχύς αξιολογήθηκε σύμφωνα με τη μέθοδο των Samozino και συνεργατών (2008), ενώ η σκληρότητα μέσω της μεθόδου των Morin και συνεργατών (2005). Στην μελέτη συμμετείχαν 15 άρρενες αθλητές, οι οποίοι εκτέλεσαν 3 συνθήκες. Η μια συνθήκη αποτελούσε την συνθήκη ελέγχου και οι άλλες δύο τις πειραματικές συνθήκες. Στη μία πειραματική συνθήκη εκτελέσθηκαν 30 οριζόντια μονοποδικά άλματα (15 για κάθε πόδι) χωρίς βάρος, ενώ στην άλλη πειραματική συνθήκη εκτελέσθηκε ο ίδιος αριθμός πλειομετρικών αλμάτων αλλά με πρόσθετο βάρος, ίσο με το 10% του σωματικού βάρους. Στην συνθήκη ελέγχου, αντί για εκτέλεση πλειομετρικών αλμάτων, οι δοκιμαζόμενοι παρέμειναν καθιστοί. Πριν και μετά από κάθε συνθήκη εκτελέσθηκαν δυο κάθετα άλματα και 15 sec τρεξίματος στο δαπεδοεργόμετρο για την εκτίμηση της ισχύος και των κινητικών και κινηματικών χαρακτηριστικών, αντίστοιχα. Η ανάλυση των δεδομένων περιλάμβανε παραγοντική ανάλυση διασποράς. Τα αποτελέσματα έδειξαν σημαντική αύξηση του άλματος και της ισχύος μετά τα πλειομετρικά άλματα, τόσο με βάρος (9.03%; 9.38%) όσο και χωρίς (8.75%; 9.29%), (p&lt;0.05). Αντιθέτως, τα κινητικά και κινηματικά χαρακτηριστικά δεν παρουσίασαν σημαντική μεταβολή (p&gt;0.05). Συμπερασματικά, το πρωτόκολλο μονοποδικών αλμάτων που χρησιμοποιήθηκε, φαίνεται να αυξάνει σημαντικά την παραγόμενη ισχύ των κάτω άκρων αλλά και το ύψος άλματος, χωρίς όμως να μεταβάλλει τα κινητικά και κινηματικά χαρακτηριστικά κατά το τρέξιμο.Post-activation potentiation (PAP) is the phenomenon where the muscle displays an increased ability for force production due to its previous activity. Plyometric exercises are very promising as conditioning exercises, due to their convenience application in the field. However, the effect of unilateral plyometric exercises on PAP has not been studied yet. The aim of the present study was to investigate the acute effect of horizontal unilateral jumps on leg power and stiffness. Power was assessed according to Samozino’s et al. (2008) method, while stiffness was estimated using Morin’s et al. (2005) method. Fifteen male athletes participated in this study and performed 3 conditions. One condition was the control, while the other two were the experimental conditions. During one experimental condition 30 horizontal unilateral jumps were executed (15 for each leg) without weight, while during the other condition the same number of plyometric jumps were performed with additional weight, equal to 10% of body weight. In the control group, instead of performing plyometric jumps, participants stayed seated. Before and after each condition, 2 vertical jumps and 15 sec of treadmill running was performed for the evaluation of power and kinetic and kinematic characteristics, respectively. Data analysis included factorial ANOVA. Results revealed significant increases in jump height and power after the plyometric jumps, with (9.03%; 9.38%) or without additional weight (8.75%; 9.29%), (p&lt;0.05). Contrariwise, the assessed kinetic and kinematic characteristics were not changed (p&gt;0.05). In conclusion, the used protocol of unilateral horizontal jumps increased significantly the power output of legs and jump height; however, did not change any kinetic or kinematic characteristic during running

Η σχέση των διατροφικών προτύπων και του τρόπου ζωής με καρδιομεταβολικούς δείκτες υγείας σε ηλικιωμένα άτομα

Εισαγωγή: Τα καρδιαγγειακά νοσήματα αποτελούν μία από τις κύριες αιτίες νοσηρότητας και θνησιμότητας παγκοσμίως. Οι συνήθειες του τρόπου ζωής, μεταξύ αυτών και η διατροφή, αποτελούν σημαντικούς τροποποιήσιμους παράγοντες που μπορούν να μειώσουν σημαντικά την επίπτωση των καρδιαγγειακών νοσημάτων. Στόχος: Η διερεύνηση της σχέσης μεταξύ των διατροφικών προτύπων καθώς και ενός συνθετικού δείκτη συμπεριφορών υγείας με επιλεγμένους καρδιομεταβολικούς βιοχημικούς δείκτες. Υλικό και Μέθοδος: Ο πληθυσμός της μελέτης αποτελείται από 3.461 άνδρες και γυναίκες ηλικίας &gt;50 ετών συμμετέχοντες στην Health and Retirement Study, μία διαχρονική μελέτη που διενεργείται στις ΗΠΑ. Η συλλογή των διατροφικών δεδομένων έγινε με ένα ημιποσοτικοποιημένο ερωτηματολόγιο συχνότητας τροφίμων, ενώ για τον προσδιορισμό των διατροφικών προτύπων έγινε ανάλυση κυρίων συνιστωσών και χρήση του Mediterranean Diet Score (MDS), για να προσδιορισθεί η προσήλωση στη μεσογειακή διατροφή (ΜΔ). Για τον συνθετικό δείκτη συμπεριφορών υγείας χρησιμοποιήθηκε ο δείκτης μάζας σώματος (ΔΜΣ), η σωματική δραστηριότητα, το κάπνισμα και η προσήλωση στη μεσογειακή διατροφή. Οι καρδιαγγειακοί βιοδείκτες που αξιολογήθηκαν ήταν τα επίπεδα της γλυκοζυλιωμένης αιμοσφαιρίνης, της HDL και της ολικής χοληστερόλης, της C-αντιδρώσας πρωτεΐνης (CRP) και της κυστατίνης C του αίματος. Η τρέχουσα μελέτη αποτελεί μια συγχρονική ανάλυση. Αποτελέσματα: Βρέθηκαν τέσσερα διατροφικά πρότυπα, με τα δύο κυριότερα να περιγράφουν ένα υγιεινό διατροφικό πρότυπο και ένα πρότυπο δυτικής διατροφής. Η υψηλή προσήλωση στη ΜΔ συσχετίστηκε αρνητικά με την CRP [b = -9.3 (-13.5 – -4.9)] και την κυστατίνη C [b = -3.1 (-4.3 – -1.9)]. Ο συνθετικός δείκτης υγιεινών συμπεριφορών εμφάνισε θετική συσχέτιση με την HDL-χοληστερόλη [b = 0.5 (0.1 – 0.9)] και αρνητική συσχέτιση με τον λόγο ολικής/HDL-χοληστερόλης [b = -0.7 (-0.3 – -1.1)], την CRP [b = -9.0 (-10.6 – -7.3)] και την κυστατίνη C [b = -1.0 (-1.5 – -0.6)]. Συμπεράσματα: Η παρούσα μελέτη επιβεβαιώνει τη σχέση μεταξύ της διατροφής με βιοχημικούς δείκτες που αποτελούν προγνωστικούς παράγοντες της καρδιαγγειακής υγείας, αλλά και τη σημασία να εξετάζονται αθροιστικά οι παράγοντες του τρόπου ζωής.Introduction: Cardiovascular diseases are the leading causes of morbidity and mortality worldwide. Lifestyle habits, including diet, are important factors that can significantly reduce the incidence of cardiovascular disease. Objective: To investigate the relationship between dietary patterns as well as a cumulative index of health behaviors with selected cardiometabolic biochemical indicators. Materials and Methods: The study population consisted of 3,461 men and women aged&gt; 50 years participating in the Health and Retirement Study conducted in the USA. Nutritional data were collected using a semi-quantitative food frequency questionnaire, while Principal Component Analysis was used to determine dietary patterns, and the Mediterranean Diet Score (MDS) was used to determine adherence to Mediterranean diet (MD). Body mass index (BMI), physical activity, smoking, and adherence to the Mediterranean diet were used for the construction of a cumulative health behavior index. Cardiovascular biomarkers assessed included blood levels of glycosylated hemoglobin, HDL-cholesterol, total cholesterol, C-reactive protein (CRP) and cystatin C. Results: Four dietary patterns, with the two main ones describing a healthy dietary pattern and a Western dietary pattern were found. The MDS index showed that high adherence to MD was negatively correlated with CRP [b = -9.3 (-13.5 – -4.9)] and cystatin C [b = -3.1 (-4.3 – -1.9)]. The cumulative index of healthy behaviors showed a positive correlation with HDL-cholesterol [b = 0.5 (0.1 – 0.9)] and a negative correlation with the ratio of total to HDL-cholesterol [b = -0.7 (-0.3 – -1.1)], CRP [b = -9.0 (-10.6 – -7.3)] and cystatin C [b = -1.0 (-1.5 – -0.6)]. Conclusions: The present study confirms the relationship between diet and specific biochemical indicators that are prognostic factors of cardiovascular health, but also the importance of cumulatively examining lifestyle factors

Growth differentiation factor 15 (GDF-15) as potential cardiovascular risk biomarker in antiphospholipid syndrome

Objective An interplay between thrombo-inflammatory and atherogenic mechanisms is recognized in cardiovascular disease (CVD) pathogenesis in APS. Herein, we examine associations of growth differentiation factor-15 (GDF-15), a pro-inflammatory cytokine identified as a potent CVD risk biomarker in the general population, with subclinical atherosclerosis in APS. Methods We measured plasma GDF-15 levels by an electrochemiluminescence immunoassay (cut-off 1200 pg/ml) and we examined carotid intima-media thickness (IMT) and the presence of carotid and femoral plaques using vascular ultrasound in 80 patients with APS (44 primary, 36 SLE/APS) and 40 healthy controls. We calculated the adjusted Global APS Score for cardiovascular disease (aGAPSSCVD), a revised adjusted Global APS Score (aGAPSS) for predicting CVD, including lupus anticoagulant, anticardiolipin and anti-beta2glycoprotein-I antibodies, and hypertension, dyslipidaemia, obesity, diabetes and smoking. Results GDF-15 levels were higher in APS patients vs controls, after adjusting for age and gender [absolute difference: 281 (95% CI: 141, 421) pg/ml, P &lt; 0.001]. GDF-15 levels &gt;= 1200 pg/ml were associated with higher mean IMT of the right and left carotid arteries [beta coefficient 0.068 (95% CI: 0.020, 0.116), P = 0.006] compared with GDF-15 levels &lt;1200 pg/ml. GDF-15 was independently associated with mean IMT, after adjusting for gender and aGAPSSCVD [beta coefficient 0.059 (95% CI: 0.008, 0.110), P = 0.024], and additionally for statin (P = 0.025) and HCQ use (P = 0.011). GDF-15 levels &gt;= 1200 pg/ml were associated with 2.4 times higher odds for atherosclerotic plaques (odds ratios = 2.438, 95% CI: 0.906, 6.556, P = 0.078), while this effect was reduced by including more covariates in the model. Conclusion GDF-15 is independently associated with subclinical atherosclerosis in APS patients, suggesting its potential role in CVD risk stratification in APS

Novel Therapeutic Advances in β-Thalassemia

The main characteristic of the pathophysiology of β-thalassemia is reduced β-globin chain production. The inevitable imbalance in the α/β-globin ratio and α-globin accumulation lead to oxidative stress in the erythroid lineage, apoptosis, and ineffective erythropoiesis. The result is compensatory hematopoietic expansion and impaired hepcidin production that causes increased intestinal iron absorption and progressive iron overload. Chronic hemolysis and red blood cell transfusions also contribute to iron tissue deposition. A better understanding of the underlying mechanisms led to the detection of new curative or “disease-modifying” therapeutic options. Substantial evolvement has been made in allogeneic hematopoietic stem cell transplantation with current clinical trials investigating new condition regimens as well as different donors and stem cell source options. Gene therapy has also moved forward, and phase 2 clinical trials with the use of β-globin insertion techniques have recently been successfully completed leading to approval for use in transfusion-dependent patients. Genetic and epigenetic manipulation of the γ- or β-globin gene have entered the clinical trial setting. Agents such as TGF-β ligand traps and pyruvate kinase activators, which reduce the ineffective erythropoiesis, have been tested in clinical trials with favorable results. One TGF-β ligand trap, luspatercept, has been approved for use in adults with transfusion-dependent β-thalassemia. The induction of HbF with the phosphodiesterase 9 inhibitor IMR-687, which increase cyclic guanosine monophosphate, is currently being tested. Another therapeutic approach is to target the dysregulation of iron homeostasis, using, for example, hepcidin agonists (inhibitors of TMPRSS6 and minihepcidins) or ferroportin inhibitors (VIT-2763). This review provides an update on the novel therapeutic options that are presently in development at the clinical level in β-thalassemia