Correlation between inflammation markers and micronutrients (trace elements and vitamin C), in children with infections

Trace elements and vitamins play important role in the function of the immune system. Alterations in the serum concentrations of micronutrients and inflammation markers have been observed as a result of inflammation response. In this study we determined simultaneously the serum levels of trace elements (Se, Zn, Cu), vitamin C and inflammation markers (CRP, PCT, SAA, WBC, Ceruloplasmin), in 80 children (45 males-35 females, ages- 3 months up to 13 years) with viral and bacterial infections, which divided in two groups. The samples of the patient groups were collected in three different periods: a) in the acute phase (admission) b) during the inflammatory process (fourth day of hospitalization) and c) after recovery. The patients didn’t intake nutrient supplements. The purpose of this study was to investigate the behavior of trace elements (Se, Zn, Cu) and vitamin C, in children with viral and bacterial infections. The above mentioned biochemical and serological parameters were determined in the Biochemical laboratory of the Children’s Hospital “Aghia Sophia”, except the measurements of WBC and CRP which performed in the Hematological and Microbiological laboratory, respectively. We used the program SPSS 13.0 for the statistic analysis of our results. The interpretation of results and the correlation between micronutrients and inflammation markers in both patient groups during the three periods, indicate the following conclusions. The serum alterations of the essential micronutrients (Se, Zn, Cu and vitamin C), which were observed as part of an inflammatory response are transient and resolved without any dietary intervention. Selenium and zinc act as antioxidants and considered as negative acute phase reactants. The magnitude of their changes correlates with the intensity of the inflammatory stimulus. The alterations in serum copper levels in viral and bacterial infections are mainly due to the increased hepatic synthesis of ceruloplasmin. In bacterial infections, organism may utilize the trace element in order to boost the immune system, and as a result its concentration didn’t associate with the severity of infection. The significant decline of vitamin C in bacterial infections reflects to the effort of organism to improve its antioxidant defense, in order to scavenge the free radicals generated in the process of active phagocytosis. Finally, the determination of micronutrients (Se, Zn, Cu and vitamin C) and the monitoring of their alterations in the acute phase stage and at remission, taking under consideration other parameters such as clinical profile and inflammation markers, provide important information to the clinicians, in order to assess the severity of infection.Τα ιχνοστοιχεία και οι βιταμίνες συμβάλλουν στην εύρυθμη λειτουργία του ανοσοποιητικού συστήματος. Κατά την εξέλιξη της φλεγμονώδους διεργασίας παρατηρούνται μεταβολές στις συγκεντρώσεις τόσο των μικροθρεπτικών συστατικών (ιχνοστοιχείων και βιταμινών), όσο και των δεικτών λοίμωξης. Στην παρούσα μελέτη πραγματοποιήθηκε προσδιορισμός των επιπέδων των ιχνοστοιχείων (Se, Zn,Cu), της βιταμίνης C, καθώς και των αντίστοιχων δεικτών φλεγμονής (CRP, PCT, SAA, WBC, σερουλοπλασμίνης), σε 80 παιδιά (45 αγόρια και 35 κορίτσια, ηλικίας 3 μηνών έως 13 ετών) με ιογενείς και μικροβιακές λοιμώξεις, στα οποία δεν έγινε χορήγηση διατροφικών συμπληρωμάτων. Η παραπάνω διαδικασία έλαβε χώρα και για τις δύο ομάδες ασθενών σε τρείς διαφορετικές χρονικές περιόδους: α) στην οξεία φάση (εισαγωγή στο νοσοκομείο), β) κατά την εξέλιξη της λοίμωξης (τέταρτη ημέρα νοσηλείας) και γ) μετά την ανάρρωση. Σκοπός της παρούσης διατριβής ήταν η διερεύνηση της συμπεριφοράς των ιχνοστοιχείων (Cu, Zn, Se) και της βιταμίνης C, κατά τη διάρκεια και μετά την αποκατάσταση των ιογενών και των μικροβιακών λοιμώξεων. Οι προσδιορισμοί των προαναφερόμενων παραμέτρων πραγματοποιήθηκαν στο Βιοχημικό Εργαστήριο του Νοσοκομείου Παίδων «Αγία Σοφία», με εξαίρεση τις μετρήσεις των WBC και της CRP που διενεργήθηκαν στο Αιματολογικό και το Μικροβιολογικό Εργαστήριο, αντίστοιχα. Η επεξεργασία των αποτελεσμάτων έγινε με το στατιστικό πρόγραμμα SPSS 13.0. Η ερμηνεία και η αξιολόγηση τόσο των συσχετίσεων, όσο και των διακυμάνσεων των μικροθρεπτικών συστατικών και των δεικτών φλεγμονής που προέκυψαν από τη μελέτη και των δύο ομάδων ασθενών σε όλες τις χρονικές περιόδους, στοιχειοθετούν τα παρακάτω συμπεράσματα. Οι παρατηρούμενες μεταβολές των ιχνοστοιχείων (Se, Zn, Cu) και της βιταμίνης C κατά τη διάρκεια των λοιμώξεων είναι παροδικές και για την αποκατάσταση τους δεν απαιτείται διαιτητική παρέμβαση. Το Se και ο Zn εμφανίζουν ισχυρή αντιοξειδωτική δράση και αποτελούν αρνητικούς δείκτες οξείας φάσης. Το μέγεθος της μεταβολής τους σχετίζεται με την ένταση του φλεγμονώδους ερεθίσματος. Οι διακυμάνσεις των επιπέδων του Cu κατά τη διάρκεια των μικροβιακών και των ιογενών λοιμώξεων, οφείλονται κατά κύριο λόγο στην αυξημένη ηπατική σύνθεση της σερουλοπλασμίνης. Η αντιοξειδωτική χρησιμοποίηση του ιχνοστοιχείου από τον οργανισμό στις βακτηριακές λοιμώξεις, έχει σαν συνέπεια τη μη συσχέτιση των συγκεντρώσεων του με τη σοβαρότητα της λοίμωξης. Η σημαντική μείωση της βιταμίνης C στις μικροβιακές λοιμώξεις αποτελεί μέρος της διαδικασίας ενίσχυσης της αντιοξειδωτικής άμυνας του οργανισμού, με σκοπό την επιτυχή αντιμετώπιση των παραγόμενων ελευθέρων ριζών. Οι προσδιορισμοί των ιχνοστοιχείων (Se, Zn, Cu) και της βιταμίνης C και η παρακολούθηση των μεταβολών τους κατά τη διάρκεια της οξείας φάσης, μπορούν να συνεκτιμηθούν με άλλους παράγοντες (κλινική εικόνα, δείκτες φλεγμονής) και να αποτελέσουν χρήσιμο εργαλείο στα χέρια των κλινικών παρέχοντας τους πληροφορίες για την πορεία της λοίμωξης

Thermodynamic transitions on metabolism and proliferation of glucocorticoid-treated acute leukemia cells

<p>Glucocorticoids play an essential part in anti-leukemic therapies. Resistance is considered crucial for disease prognosis. Glucocorticoids influence the metabolic properties of the cell and consequently the leukemic cells. We have previously outlined the differences that emerge from glucocorticoid treatment used in various concentrations, and lower concentrations manifested a mitogenic effect. A critical established glucocorticoid action is the apoptotic effect they exert on leukemic cells. However, little is known about the molecular response of malignant cells following glucocorticoid exposure. Even less is known about the cell proliferation dynamics governing leukemic cells under glucocorticoid influence. Growth and metabolic features are assumed to be of nonlinear nature. A model based prediction of glucocorticoid effects is derived by applying a non-linear fitting approximation to the measured parameters. Additionally, borrowing principles from the metabolic engineering and thermodynamics disciplines, we calculated the required energetics for cell proliferation under prednisolone treatment. Finally, we utilized a previously reported microarray dataset, to examine whether the predicted and measured parameters of the metabolism and proliferation under glucocorticoids are reflected in gene expression. Hence, making such an approach more pragmatic since those genes could shed light into the mechanisms of glucocorticoid-induced apoptotic resistance action, and subsequently identify novel targets for more efficient glucocorticoid treatments. We have eventually attempted to answer the basic question of what the thermodynamic mechanisms in the transition of the cell population from one state to the next are.</p

Oxidant/Antioxidant Status Is Impaired in Sepsis and Is Related to Anti-Apoptotic, Inflammatory, and Innate Immunity Alterations

Oxidative stress is considered pivotal in the pathophysiology of sepsis. Oxidants modulate heat shock proteins (Hsp), interleukins (IL), and cell death pathways, including apoptosis. This multicenter prospective observational study was designed to ascertain whether an oxidant/antioxidant imbalance is an independent sepsis discriminator and mortality predictor in intensive care unit (ICU) patients with sepsis (n = 145), compared to non-infectious critically ill patients (n = 112) and healthy individuals (n = 89). Serum total oxidative status (TOS) and total antioxidant capacity (TAC) were measured by photometric testing. IL-6, -8, -10, -27, Hsp72/90 (ELISA), and selected antioxidant biomolecules (Ζn, glutathione) were correlated with apoptotic mediators (caspase-3, capsase-9) and the central anti-apoptotic survivin protein (ELISA, real-time PCR). A wide scattering of TOS, TAC, and TOS/TAC in all three groups was demonstrated. Septic patients had an elevated TOS/TAC, compared to non-infectious critically ill patients and healthy individuals (p = 0.001). TOS/TAC was associated with severity scores, procalcitonin, IL-6, -10, -27, IFN-γ, Hsp72, Hsp90, survivin protein, and survivin isoforms -2B, -ΔΕx3, -WT (p p TOS/TAC (0.96 (95% CI = 0.93–0.99)) was higher than AUCTAC (z = 20, p TOS (z = 3.1, p = 0.002) in distinguishing sepsis. TOS/TAC, TOS, survivin isoforms -WT and -2B, Hsp90, IL-6, survivin protein, and repressed TAC were strong predictors of mortality (p < 0.01). Oxidant/antioxidant status is impaired in septic compared to critically ill patients with trauma or surgery and is related to anti-apoptotic, inflammatory, and innate immunity alterations. The unpredicted TOS/TAC imbalance might be related to undefined phenotypes in patients and healthy individuals

Oxidant/Antioxidant Status Is Impaired in Sepsis and Is Related to Anti-Apoptotic, Inflammatory, and Innate Immunity Alterations

Oxidative stress is considered pivotal in the pathophysiology of sepsis. Oxidants modulate heat shock proteins (Hsp), interleukins (IL), and cell death pathways, including apoptosis. This multicenter prospective observational study was designed to ascertain whether an oxidant/antioxidant imbalance is an independent sepsis discriminator and mortality predictor in intensive care unit (ICU) patients with sepsis (n = 145), compared to non-infectious critically ill patients (n = 112) and healthy individuals (n = 89). Serum total oxidative status (TOS) and total antioxidant capacity (TAC) were measured by photometric testing. IL-6, -8, -10, -27, Hsp72/90 (ELISA), and selected antioxidant biomolecules (Zeta n, glutathione) were correlated with apoptotic mediators (caspase-3, capsase-9) and the central anti-apoptotic survivin protein (ELISA, real-time PCR). A wide scattering of TOS, TAC, and TOS/TAC in all three groups was demonstrated. Septic patients had an elevated TOS/TAC, compared to non-infectious critically ill patients and healthy individuals (p = 0.001). TOS/TAC was associated with severity scores, procalcitonin, IL-6, -10, -27, IFN-gamma, Hsp72, Hsp90, survivin protein, and survivin isoforms -2B, -Delta Epsilon x3, -WT (p &lt; 0.001). In a propensity probability (age-sex-adjusted) logistic regression model, only sepsis was independently associated with TOS/TAC (Exp(B) 25.4, p &lt; 0.001). The AUC(TOS/TAC) (0.96 (95% CI = 0.93-0.99)) was higher than AUC(TAC) (z = 20, p &lt; 0.001) or AUC(TOS) (z = 3.1, p = 0.002) in distinguishing sepsis. TOS/TAC, TOS, survivin isoforms -WT and -2B, Hsp90, IL-6, survivin protein, and repressed TAC were strong predictors of mortality (p &lt; 0.01). Oxidant/antioxidant status is impaired in septic compared to critically ill patients with trauma or surgery and is related to anti-apoptotic, inflammatory, and innate immunity alterations. The unpredicted TOS/TAC imbalance might be related to undefined phenotypes in patients and healthy individuals