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

Is diet partly responsible for differences in COVID-19 death rates between and within countries?

Correction: Volume: 10 Issue: 1 Article Number: 44 DOI: 10.1186/s13601-020-00351-w Published: OCT 26 2020Reported COVID-19 deaths in Germany are relatively low as compared to many European countries. Among the several explanations proposed, an early and large testing of the population was put forward. Most current debates on COVID-19 focus on the differences among countries, but little attention has been given to regional differences and diet. The low-death rate European countries (e.g. Austria, Baltic States, Czech Republic, Finland, Norway, Poland, Slovakia) have used different quarantine and/or confinement times and methods and none have performed as many early tests as Germany. Among other factors that may be significant are the dietary habits. It seems that some foods largely used in these countries may reduce angiotensin-converting enzyme activity or are anti-oxidants. Among the many possible areas of research, it might be important to understand diet and angiotensin-converting enzyme-2 (ACE2) levels in populations with different COVID-19 death rates since dietary interventions may be of great benefit.Peer reviewe

Cabbage and fermented vegetables : From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT(1)R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT(1)R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.Peer reviewe

Nrf2-interacting nutrients and COVID-19 : time for research to develop adaptation strategies

There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPAR gamma:Peroxisome proliferator-activated receptor, NF kappa B: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2 alpha:Elongation initiation factor 2 alpha). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT(1)R axis (AT(1)R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity

Determination of risk factors for the development of metabolic syndrome in adult life in fetuses and neonates in intrauterine growth restriction

This thesis consists of two parts, the GENERAL and the SPECIFIC. The General Part includes the following chapters: I. Intrauterine growth restriction (IUGR). This part refers to the history, definition, epidemiology of IUGR and the clinical importance of distinguishing IUGR from SGA (small for gestational age) neonates, the stages of intrauterine growth and the types of IUGR. Special emphasis is given to the etiology of IUGR from the mother, fetus, placenta, genetic and endocrine factors. The diagnostic methods used to detect IUGR by defining gestational age, by clinical (abdominal palpation, symphysis-fundal height) or imaging procedures (ultrasonographically estimated fetal weight and amniotic fluid volume, three dimensional ultrasonography, Doppler velocimetry, increased ratio HC/AC, assessment of placenta) are analyzed. The importance of customized fetal growth charts and the distinction of symmetric vs. asymmetric IUGR for future prognosis, is highlighted. Finally, this part refers to the prevention of IUGR depending on time and mode of delivery, to the treatment and postnatal management, while morbidity, short and long term consequences, as well as the relation to adult’s diseases and mortality rates are also discussed. ΙΙ. IUGR and the Metabolic Syndrome In this chapter the history of previous definitions of the metabolic syndrome and the existing definition are reported (WHO, European Group for the Study of Insulin Resistance, ATPIII, IDF ). Also the history of the correlation between IUGR and metabolic syndrome, based on some important studies, the pathophysiology and the metabolic mechanisms of IUGR which explain this correlation as well as the existing hypotheses (thrifty phenotype hypothesis, thrifty genotype hypothesis, fetal insulin hypothesis, fetal salvage hypothesis, catch-up growth hypothesis, fetal programming, fetal origins of adult disease theory, developmental origins of adult disease, Developmental Origins of Health and Disease (DOHaD) concept ) concerning this correlation are analyzed. Finally, this part refers to the metabolic mechanisms of IUGR and the role of catch-up growth and glucocorticoids. ΙΙΙ. Leptin, Adiponectin, Ghrelin and their role in Intrauterine Growth Restriction. In this chapter are analyzed the structure, the synthesis, the functions, the clinical significance of leptin, adiponectin and ghrelin. Finally their role in pregnancy as well as in IUGR are reported. [...]Η διατριβή αποτελείται από το ΓΕΝΙΚΟ και το ΕΙΔΙΚΟ ΜΕΡΟΣ. Το Γενικό μέρος περιλαμβάνει τα κεφάλαια: Ι. Eνδομήτρια Υπολειπόμενη Αύξηση (ΕΥΑ)-Intrauterine growth restriction. (IUGR). Γίνεται ιστορική αναδρομή και δίνεται ο ορισμός της ΕΥΑ (και η σημασία της διάκρισης του ΕΥΑ από το small for gestational age-SGA νεογνό), καθώς και επιδημιολογικά δεδομένα. Αναφέρονται τα στάδια της ενδομήτριας αύξησης και οι τύποι της ΕΥΑ. Αναλύεται εκτενώς η αιτιολογία της ΕΥΑ από τη μητέρα, το έμβρυο, τον πλακούντα, τους γενετικούς και ενδοκρινικούς παράγοντες. Δίνεται ιδιαίτερη έμφαση στη διάγνωση της ΕΥΑ, με τον προσδιορισμό της ηλικίας κύησης, με κλινικές μεθόδους [ψηλάφηση των κοιλιακών τοιχωμάτων-χειρισμοί Λεοπόλδου, μέτρηση της απόστασης από τον πυθμένα της μήτρας ως την ηβική σύμφυση (symphysis-fundal height, S-F height)], με απεικονιστικές μεθόδους (υπερηχογραφικός προσδιορισμός του εμβρυϊκού βάρους και του όγκου του αμνιακού υγρού, τρισδιάστατη υπερηχογραφία-3D, Doppler υπερηχογραφία, βαθμολόγηση του πλακούντα, αυξημένος λόγος HC/AC), και τονίζεται η σημασία των καμπυλών εμβρυικής αύξησης και της διάκρισης της συμμετρικής από την ασύμμετρη ΕΥΑ για την πρόγνωση του εμβρύου. Αναφέρονται τρόποι πρόληψης ανάλογα με την επιλογή του χρόνου και του είδους του τοκετού. Αναλύεται η αντιμετώπιση της κύησης με ΕΥΑ και στη συνέχεια αναφέρονται διάφορες θεραπευτικές μέθοδοι που έχουν κατά καιρούς προταθεί για την αντιμετώπιση της ΕΥΑ, η αντιμετώπιση του νεογνού μετά τη γέννηση και τα άμεσα προβλήματα νεογνών με ΕΥΑ. Αναφέρεται η έκβαση μετά τη νεογνική περίοδο σε παιδιά με ΕΥΑ, όπου δίνονται στοιχεία για τη νοσηρότητα και τις επιπλοκές της ΕΥΑ (βραχυ- και μακροπρόθεσμες σχέση με νόσους ενηλίκων) και τη σχετιζόμενη με ΕΥΑ θνησιμότητα. ΙΙ. EYA και Μεταβολικό Σύνδρομο. Γίνεται ιστορική αναδρομή της έννοιας του μεταβολικού συνδρόμου και δίνονται οι ορισμοί που έχουν προταθεί μέχρι αυτόν που ισχύει σήμερα (WHO, European Group for the Study of Insulin Resistance, ATPIII, IDF ). Γίνεται ιστορική αναδρομή της συσχέτισης μεταξύ ΕΥΑ και μεταβολικού συνδρόμου, αναφέρονται οι βασικές μελέτες πάνω στις οποίες βασίστηκε αυτή η συσχέτιση καθώς και η παθοφυσιολογία της ΕΥΑ που οδηγεί στη συσχέτιση αυτή. Αναλύονται οι υποθέσεις για τη διερεύνηση του υποκείμενου παθογενετικού μηχανισμού της συσχέτισης ΕΥΑ και μεταβολικού συνδρόμου (υπόθεση του λιτού φαινοτύπου, υπόθεση του λιτού γονότυπου, υπόθεση της εμβρυϊκής ινσουλίνης, υπόθεση της «σωτηρίας» του εμβρύου, υπόθεση της αναπληρωματικής αύξησης, υπόθεση του εμβρυϊκού προγραμματισμού, υπόθεση της εμβρυϊκής προέλευσης των νοσημάτων των ενηλίκων). Ακολούθως, γίνεται αναφορά στους μεταβολικούς μηχανισμούς που συνδέουν την ΕΥΑ με νόσους ενηλίκων. Τέλος, αναφέρονται ο ρόλος της αναπληρωματικής αύξησης και των γλυκοκορτικοειδών. ΙΙΙ. Λεπτίνη, Αντιπονεκτίνη, Γκρελίνη και o ρόλος τους στην ΕΥΑ. Στο κεφάλαιο αυτό αναλύονται η δομή, η σύνθεση, οι λειτουργίες, η κλινική σημασία της λεπτίνης, της αντιπονεκτίνης και της γκρελίνης. Αναφέρεται ο ρόλος τους στην κύηση καθώς και στην ΕΥΑ. [...

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 S100Bprobably reflecting brain and adipose tissue inflammationin 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/neonatesdespite the lower birth weight, reflecting reduced fat mass in the formermight 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. Copyright © 2010 Theodora Boutsikou et al

Detection of local allergic rhinitis in children with chronic, difficult-to-treat, non-allergic rhinitis using multiple nasal provocation tests

Background: There is little evidence on the incidence and characteristics of local allergic rhinitis (LAR) in children. Most studies have included subjects with perennial rhinitis only, and results are based on the investigation of no more than three allergens per study. Our aim was to determine the proportion of children with LAR amongst children with chronic, difficult-to-treat, perennial or seasonal, rhinitis but no evidence of sensitization to aeroallergens, or other alternative diagnosis. Methods: We performed multiple nasal provocation tests (M-NPTs) with four locally relevant aeroallergens (Phleum pratense, Olea europea, Alternaria alternata, and Dermatophagoides pteronyssinus) in children with absence of aeroallergen sensitization, seen during a calendar year in a specialized rhinitis clinic. We additionally performed single NPT to children with allergic rhinitis (AR; positive control group). The result of the NPT was based on symptoms and acoustic rhinometry. Identification of nasal hyper-reactivity (NHR) triggers was through a questionnaire. Results: Local allergic rhinitis was confirmed in 29.2% (7/24) of the negative SPT/blood testing population. All but one of the children reacted to one allergen and one to two. All AR children had positive single NPT with results similar to the LAR. There were no differences in age at examination and rhinitis onset, gender distribution, family atopy, and past or current environment of residency, while the prevalence of reported NHR triggers was comparable amongst the three groups. Conclusion: This is the first pediatric study where the seasonal or perennial rhinitis population was thoroughly tested for LAR against four aeroallergens. LAR is present in a considerable proportion of children with chronic, difficult-to-treat rhinitis and no sensitization to aeroallergens, and therefore, the performance of NPT should be strongly considered in these cases. There were no distinct clinical characteristics between LAR, AR, and non-allergic rhinitis in children. © 2019 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd