Insulin-Like Growth Factor (IGF)-I and Insulin in Normal and Growth-Restricted Mother/Infant Pairs

Insulin-like growth factor (IGF)-I and insulin are essential for fetal growth. We investigated perinatal changes of both factors in 40 mothers and their 20 appropriate-for-gestational-age (AGA) and 20 intrauterine-growth-restricted (IUGR) fetuses and neonates on day 1 (N1) and day 4 (N4) postpartum. Fetal and N1, but not N4, IGF-I levels were increased in AGA (P < .001 and P = .037, resp.). N1 insulin levels were lower in IUGR (P = .048). Maternal, fetal, and N1 IGF-I, and fetal insulin levels positively correlated with customized centiles (r = .374, P = .035, r = .608, P < .001, r = .485, P = .006, and r = .654, P = .021, resp.). Female infants presented elevated fetal and N4 IGF-I levels (P = .023 and P = .016, resp.). Positive correlations of maternal, fetal, and neonatal IGF-I levels, and fetal insulin levels with customized centiles underline implication of both hormones in fetal growth. IUGR infants present gradually increasing IGF-I levels. Higher IGF-I levels are documented in females

Genomic investigations of unexplained acute hepatitis in children

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children

Determination of urinary leukotriene levels in atopic and non-atopic preschool children after infection (virus induced asthma phenotype)

The purpose of the proposed study is to identify the role of U-LTE4 in preschool children with recurrent episodes of wheezing after upper respiratory tract infections (infectious asthma phenotype) with or without atopic predisposition.Primary outcome of the study is the evaluation of the behavior of U-LTE4 in infectious asthma phenotype with or without atopy.Secondary benefits include the assessment of the role of atopy (IgE-mediated mechanisms) and the evaluation of U-LTE4 as an inflammatory marker in the early diagnosis of impending outbreaks and in predicting response to various anti-inflammatory drugs.The study showed that:During exacerbation, U-LTE4 was significantly higher in all children, atopic and non-atopic, with virus-induced asthma in comparison to A. Remission: 642.20±268 vs. 399.45±204, P value <0.001 and B. Controls: 642.20±268 vs 271.39±83 P value <0.001. Atopic patients demonstrated significantly higher levels of U-LTE4 in relation to non atopic, both during exacerbation (872.13±246 vs 613.15±150 P value=0.0013) and in the remission phase (507.59±182 vs 283.59±160 P value <0.001). During remission, a highly significant difference of U-LTE4 was found to persist when controls were compared to atopic patients: 271.39±83 vs 507.59±182 P value=0.002 but not when compared to non atopic ones: 271.39±83 vs 283.59±160 P value=0.432.The results suggest that U-LTE4 is a strong indicator of virus induced asthma exacerbation in preschool children, more so in atopics. Increased basal levels of urinary LTE4 occur only in atopics. This suggests a potential role of urinary LTE4 as a marker of atopic, virus induced asthma in preschool children.This knowledge helps to improve the predictive ability and form a better therapeutic strategy in the treatment of asthma.A very important part of the study was the kinetic measurement of U-LTE4 which can serve as a predictor ofexacerbation. It was found that the greatest change in the levels (drop) of U-LTE4 was within the first 50 days of the outbreak.Atopic patients never reached the baseline of the controls. Such results can make the U-LTE4 a potential marker of atopy or assist in locating prolonged inflammation and thus prolonged treatment with anti-inflammatory agents. The measurements of total IgE also confirmed their non-specific increase in the different viral respiratory infections, and also the presence of atopy during recession in the samples used.Σκοπός της προτεινόμενης μελέτης είναι ο προσδιορισμός των κυστεϊνιλικών λευκοτριενίων (LTE4) στα ούρα σε παιδιά προσχολικής ηλικίας με υποτροπιάζοντα επεισόδια συρίττουσας αναπνοής μετά από λοιμώξεις του ανώτερου αναπνευστικού (φαινότυπος λοιμώδους άσθματος) με η χωρίς ατοπική προδιάθεση.Πρωτεύον αποτέλεσμα αποτελεί η αξιολόγηση της συμπεριφοράς του κυστεϊνιλικού λευκοτριενίου Ε4 (LTE4) στο φαινότυπο του λοιμώδους άσθματος με ή χωρίς ατοπία.Τα δευτερογενή οφέλη που προκύπτουν είναι η εκτίμηση του ρόλου της ατοπίας (IgE-μεσολαβούμενοι μηχανισμοί) και η αξιολόγηση του U-LTE4 ως φλεγμονώδης δείκτης στην έγκαιρη διάγνωση επικείμενης έξαρσης και στην πρόβλεψη απάντησης στα διάφορα αντιφλεγμονώδη φάρμακα.Η μελέτη αυτή έδειξε ότι: Κατά τη διάρκεια της έξαρσης τα επίπεδα του U-LTE4 είναι σημαντικά υψηλότερα σε όλα τα παιδιά με ιογενές άσθμα, ατοπικά και μη-ατοπικά σε σύγκριση με Α. Τα παιδιά που ήταν σε ύφεση: 642,20 ± 399,45 έναντι 268 ± 204, P <0,001 και Β τους μάρτυρες.: 642,20 ± 268 έναντι 271,39 ± 83 P <0,001. Επιπρόσθετα, οι ατοπικοί ασθενείς είχαν σημαντικά υψηλότερα επίπεδα του U-LTE4 σε σχέση με τους μη ατοπικούς, τόσο κατά τη διάρκεια της έξαρσης (872,13 ± 613,15 έναντι 246 ± 150 P = 0.0013) όσο και στη φάση της ύφεσης (507,59 ± 283,59 έναντι 182 ± 160 P value <0,001) . Βρέθηκε επίσης ότι κατά τη διάρκεια της ύφεσης υπάρχει στατιστικώς σημαντική διαφορά των επιπέδων της U-LTE4 μεταξύ των ατοπικών ασθενών και τον μαρτύρων 271.39±83 vs 507.59±182 P=0.002 ενώ δεν παρατηρείται καμία διαφορά μεταξύ των μη-ατοπικών και των μαρτύρων 271.39±83 vs 283.59±160 P=0.432.Τα παραπάνω αποτελέσματα υποδεικνύουν ότι τα υψηλά επίπεδα των λευκοτριενίων Ε4 στα ούρα (U-LTE4) αποτελούν μια ισχυρή ένδειξη της επιδείνωσης του ιογενούς άσθματος στα παιδιά προσχολικής ηλικίας, πολύ περισσότερο στα ατοπικά, τα οποία είναι τα μόνα που παρουσιάζουν αυξημένα βασικά επίπεδα U-LTE4. Το γεγονός αυτό υποδηλώνει έναν πιθανό ρόλο των U-LTE4 ως δείκτη του ατοπικού ιογενούς άσθματος σε παιδιά προσχολικής ηλικίας.Η γνώση αυτή συμβάλλει στη βελτίωση της προγνωστικής δυνατότητας και στη μορφοποίηση θεραπευτικής στρατηγικής στην αντιμετώπιση του άσθματος. Ένα πολύ σημαντικό τμήμα της μελέτης ήταν η κινητική των επιπέδων των U-LTE4 η οποία μπορεί να χρησιμεύσει ως προγνωστικός δείκτης έξαρσης. Στη μελέτη μας βρέθηκε ότι η μεγαλύτερη μεταβολή στα επίπεδα (πτώση) των U-LTE4 έγινε μέσα στις πρώτες 50 μέρες από την έξαρση χωρίς να φτάνει στους ατοπικούς ασθενείς τα επίπεδα των μαρτύρων στο διάστημα αυτό. Κάτι τέτοιο μπορεί να καθιστά τα U-LTE4 πιθανούς δείκτες ατοπίας ή να βοηθά στην εντόπιση παρατεταμένης φλεγμονής, άρα και παρατεταμένης θεραπείας με αντιφλεγμονώδεις παράγοντες. Επίσης οι μετρήσεις της ολικής IgE επιβεβαίωσαν την μη ειδική αύξηση της σε ιογενείς λοιμώξεις του αναπνευστικού, και την παρουσία ατοπίας στην διάρκεια της ύφεσης στα δείγματα που χρησιμοποιήθηκαν

Bcl-2 and caspase-9 serum levels in children and adolescents with idiopathic epilepsy and active seizures.

BACKGROUND: In the present study we investigated the levels of proapoptotic caspase-9 and antiapoptotic Bcl-2 proteins in the sera of children and adolescents with idiopathic epilepsy and tried to relate the findings to the patients&apos; clinical parameters. METHODS: This retrospective study consisted of 118 children and adolescents with idiopathic epilepsy, categorized according to type and number of seizures, duration of the disease and the control of seizures and 30 age- and sex-matched controls. The relapse of seizures was taken into consideration. RESULTS: Mean serum level between Bcl-2 and caspase-9 was significantly higher only in Bcl-2 patients, compared to controls (P≤0.0001) and (P=0.987) respectively. Significant difference in Bcl-2 level was found among the different types of focal seizures. Caspase-9 level was statistically different in patients with two or more seizures per month compared to those with one seizure per month (P=0.048). No correlation was found between Bcl-2 and caspase-9 levels and age, gender, seizure frequency, total number of seizures and the duration of epilepsy. No significant difference was found in patients with and without drug treatment. CONCLUSIONS: Bcl-2 displays an association with apoptosis and highlights the potential of being a surrogate biomarker for active seizures and epilepsy. There is a significant difference in Bcl-2 serum level among the different types of focal seizures. Proapoptotic caspase-9 cannot act as a marker of active seizures and epilepsy. Caspase-9 serum level is increased acutely in controlled cases after a single relapse

Implication of the myokine irisin in maternal energy homeostasis in pregnancies with abnormal fetal growth

Objective: To prospectively investigate maternal concentrations of the myokine irisin in large for gestational age (LGA) and intrauterine growth restricted (IUGR) versus appropriate for gestational age (AGA) normal pregnancies and associate them with various perinatal parameters.Methods: Plasma irisin and insulin concentrations were measured by enzyme-linked immunosorbent assay (ELISA) and immunoradiometric assay (IRMA), respectively, in a cohort of 80 mothers delivering LGA (n=30), IUGR (n=30) and AGA (n=20) singleton full-term infants.Results: Maternal irisin concentrations were similar among LGA, IUGR and AGA groups and did not correlate with respective insulin ones or maternal body mass index. In a combined group, maternal irisin concentrations decreased with advancing gestational age (p&lt;0.001) and were lower in multi-, compared to nulliparous women (p=0.004). In the IUGR group, maternal irisin concentrations were higher in cases of smoking (p=0.006).Conclusions: Irisin may not be differentially regulated in insulin resistance-associated pregnancy disorders resulting in fetal macrosomia and IUGR. Maternal irisin down-regulation with advancing gestation could possibly contribute to the observed maternal fat accumulation and progressive insulin resistance towards term. Similarly, lower maternal irisin concentrations in multiparous women may reflect the documented positive association between parity and fat deposition. Irisin up-regulation in cases of smoking may indicate the need for enhanced oxygen consumption to maintain energy production under conditions of hypoxia

Cystatin-C levels in healthy children and adolescents: Influence of age, gender, body mass index and blood pressure

Objectives: Cystatin-C is considered a more sensitive and specific marker of kidney function than creatinine since it can diagnose patients with earlier-stage of renal dysfunction. The aim of this study is to determine the levels of Cystatin-C in healthy children and adolescents as well as any correlations to age, gender, body-mass index (BMI) and blood pressure (BP). Design and methods: Cystatin-C was measured in 536 healthy Greek children and adolescents (295 males and 241 females) using a nephelometric immunoassay. Additionally, the age, body mass index and blood pressure was recorded for each subject. Results: Overall, the mean serum Cystatin-C level was 0.79 +/- 0.10 mg/L. Cystatin-C was found to be statistically significantly lower in females than in males (p &lt; 0.001) as well as in prepubertal children compared to adolescents (p &lt; 0.001). Higher values of Cystatin-C were observed in subjects with increased BMI (p &lt; 0.001). Neither systolic nor diastolic blood pressure was found to significantly affect Cystatin-C levels. Conclusions: The levels of Cystatin-C were statistically significantly higher in males, compared to age matched females and also positively correlated with age and BMI. (C) 2015 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved

Cardiovascular Risk Factors and Subclinical Atherosclerosis in Greek Adolescents with Polycystic Ovary Syndrome: Its Relationship with Body Mass Index

Polycystic ovary syndrome (PCOS) is the most common endocrine condition affecting 6&ndash;18% of adolescents and is strongly associated with obesity and cardiovascular risk factors, enhancing the risk of atherosclerosis. Thirty-two adolescents with newly diagnosed PCOS were evaluated for lipid profile disorders, insulin resistance, inflammation, non-alcoholic fatty liver disease (NAFLD), and subclinical atherosclerosis through measurements of carotid intima&ndash;media thickness (cIMT). The relationships of the above markers with increased body mass index and abdominal obesity were investigated. Twenty-three adolescents (72%) were overweight (OW) or obese (OB). The OW/OB group had significantly higher insulin, HOMA-IR, high-sensitive C-reactive protein (hsCRP), visceral adiposity index (VAI), and lipid accumulation product (LAP) levels; and lower glucose-per-insulin ratios and HDL-C levels compared to the healthy weight group. The cIMT and small dense low-density lipoprotein cholesterol (sdLDL-C) levels did not differ between the two groups. Similarly, cIMT and sdLDL-C levels did not differ between PCOS-adolescents and healthy controls. CIMT was positively correlated with systolic blood pressure and waist circumference per height ratio. In conclusion, OW/OB PCOS-adolescents have a cluster of adverse factors predisposing them to atherosclerotic cardiovascular disease. Therefore, early cardiovascular risk assessment, as well as timely and targeted interventions, are necessary for prevention