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

Ποσοτικός προσδιορισμός των επιπέδων ανασταλτικών αμινοξέων (GABA,γλυκίνη) στο ΕΝΥ και το πλάσμα ασθενών με νευρολογικά νοσήματα

The inhibitory neurotransmission is an important mechanism regarding thefunction of the central nervous system. Over the last two decades a number oftheories have been developed to explain the relationship of the inhibitory aminoacids, GABA and glycine, and their metabolism with the physiological role in thenervous system.In the current study we describe the biochemistry, the metabolism thephysiology and the neurotransmitional activities of the GABA and Glycineaminoaxids. Furthermore, the clinical aspects of amyotrophic lateral sclerosis(ALS) and Alzheimer’ s disease (AD) are presented as well as the possibleimplication of these amino acids in their pathogenesis. In the second part, we describe the material, method and results of thisstudy: the amino acids, GABA and glycine levels were studied in the plasmaand the CSF (erebro-Spinal fluid) of 39 controls,26 patients with ALS and 27patients with AD. The determination of the amino acids was performed by themethod of reverse phase High Performance Liquid Chromatography (HPLC)with pre-column derivatization and UV absorbency at 256 nm wavelength.Our results, in brief, are as it follows:1. ALS patients demonstrate statistically significant decrease GABA plasmaand CSF glycine levels, as compared to the controls.2. AD patients demonstrate statistically significant decrease GABA levels inCSF, as compared to the controls.We concluded that the inhibitory neurotransmitters evaluated may have arole in the pathogenesis of ALS & AD. Further studies are needed toconfirm and validate our findings.Η ανασταλτική νευρομεταβίβαση διαδραματίζει σημαντικό ρόλο στηλειτουργία του ΚΝΣ. και έχουν αναπτυχθεί αρκετές θεωρίες για τη συμμετοχήτων ανασταλτικών αμινοξέων στην αιτιοπαθογένεια διαφόρων νευρολογικώννοσημάτων.Στο πρώτο μέρος της παρούσας μελέτης συζητιέται ο ρόλος τωναμινοξέων ως νευρομεταβιβαστών και παρουσιάζεται η βιοχημεία τωνανασταλτικών αμινοξέων GABA και γλυκίνης, και ο φυσιολογικός ρόλος τουςστο νευρικό σύστημα. Στη συνέχεια γίνεται αναφορά στα κλινικά δεδομένα τηςπλάγιας μυατροφικής σκλήρυνσης (ΠΜΣ) και της νόσου του Alzheimer (ΝΑ)καθώς και της πιθανής αιτιοπαθογενετικής σχέσης τους με τα αμινοξέα. Το δεύτερο μέρος της μελέτης περιλαμβάνει το υλικό και τη μέθοδο, τααποτελέσματα, τη συζήτηση και τα συμπεράσματα. Μελετήθηκαν τα αμινοξέαGABA και γλυκίνη στο πλάσμα και το ΕΝΥ 39 μαρτύρων, 26 ασθενών με ΠΜΣκαι 27 ασθενών με ΝΑ. Ο ποσοτικός προσδιορισμός των αμινοξέων έγινε μευγρή χρωματογραφία αντιστρόφου φάσεως υψηλής απόδοσης (HPLC).Τα ευρήματα έχουν ως εξής:1. Στους ασθενείς με ΠΜΣ παρατηρήθηκε, σε σύγκριση με τους μάρτυρες,στατιστικά σημαντική ελάττωση των επιπέδων του GABA στο πλάσμα καιτης γλυκίνης στο ΕΝΥ.2. Στους ασθενείς με ΝΑ παρατηρήθηκε, σε σύγκριση με τους μάρτυρες,στατιστικά σημαντική ελάττωση των επιπέδων του GABA στο ΕΝΥ, ενώδεν παρατηρήθηκε στατιστικά σημαντική διαφορά των επιπέδων τηςγλυκίνης στο ΕΝΥ και στο πλάσμα

Newly diagnosed and growing subependymal giant cell astrocytoma in adults with tuberous sclerosis complex: Results from the international TOSCA study

International audienceThe onset and growth of subependymal giant cell astrocytoma (SEGA) in tuberous sclerosis complex (TSC) typically occurs in childhood. There is minimal information on SEGA evolution in adults with TSC. Of 2,211 patients enrolled in TOSCA, 220 of the 803 adults (27.4%) ever had a SEGA. Of 186 patients with SEGA still ongoing in adulthood, 153 (82.3%) remained asymptomatic, and 33 (17.7%) were reported to ever have developed symptoms related to SEGA growth. SEGA growth since the previous scan was reported in 39 of the 186 adults (21%) with ongoing SEGA. All but one patient with growing SEGA had mutations in TSC2. Fourteen adults (2.4%) were newly diagnosed with SEGA during follow-up, and majority had mutations in TSC2. Our findings suggest that surveillance for new or growing SEGA is warranted also in adulthood, particularly in patients with mutations in TSC2

Treatment patterns and use of resources in patients with tuberous sclerosis complex : insights from the TOSCA registry

Tuberous Sclerosis Complex (TSC) is a rare autosomal-dominant disorder caused by mutations in the TSC1 or TSC2 genes. Patients with TSC may suffer from a wide range of clinical manifestations; however, the burden of TSC and its impact on healthcare resources needed for its management remain unknown. Besides, the use of resources might vary across countries depending on the country-specific clinical practice. The aim of this paper is to describe the use of TSC-related resources and treatment patterns within the TOSCA registry. A total of 2,214 patients with TSC from 31 countries were enrolled and had a follow-up of up to 5 years. A search was conducted to identify the variables containing both medical and non-medical resource use information within TOSCA. This search was performed both at the level of the core project as well as at the level of the research projects on epilepsy, subependymal giant cell astrocytoma (SEGA), lymphangioleiomyomatosis (LAM), and renal angiomyolipoma (rAML) taking into account the timepoints of the study, age groups, and countries. Data from the quality of life (QoL) research project were analyzed by type of visit and age at enrollment. Treatments varied greatly depending on the clinical manifestation, timepoint in the study, and age groups. GAB Aergics were the most prescribed drugs for epilepsy, and mTOR inhibitors are dramatically replacing surgery in patients with SEGA, despite current recommendations proposing both treatment options. mTOR inhibitors are also becoming common treatments in rAML and LAM patients. Forty-two out of the 143 patients (29.4%) who participated in the QoL research project reported inpatient stays over the last year. Data from non-medical resource use showed the critical impact of TSC on job status and capacity. Disability allowances were more common in children than adults (51.1% vs 38.2%). Psychological counseling, social services and social worker services were needed by <15% of the patients, regardless of age. The long-term nature, together with the variability in its clinical manifestations, makes TSC a complex and resource-demanding disease. The present study shows a comprehensive picture of the resource use implications of TSC