Exploring nasopharyngeal microbiota profile in children affected by SARS-CoV-2 infection.

The relationship between COVID-19 and nasopharyngeal (NP) microbiota has been investigated mainly in the adult population. We explored the NP profile of children affected by COVID-19, compared to healthy controls (CTRLs). NP swabs of children with COVID-19, collected between March and September 2020, were investigated at the admission (T0), 72 h to 7 days (T1), and at the discharge (T2) of the patients. NP microbiota was analyzed by 16S rRNA targeted-metagenomics. Data from sequencing were investigated by QIIME 2.0 and PICRUSt 2. Multiple machine learning (ML) models were exploited to classify patients compared to CTRLs. The NP microbiota of COVID-19 patients (N = 71) was characterized by reduction of α-diversity compared to CTRLs (N = 59). The NP microbiota of COVID-19 cohort appeared significantly enriched in Streptococcus, Haemophilus, Staphylococcus, Veillonella, Enterococcus, Neisseria, Moraxella, Enterobacteriaceae, Gemella, Bacillus, and reduced in Faecalibacterium, Akkermansia, Blautia, Bifidobacterium, Ruminococcus, and Bacteroides, compared to CTRLs (FDR < 0.001). Exploiting ML models, Enterococcus, Pseudomonas, Streptococcus, Capnocytopagha, Tepidiphilus, Porphyromonas, Staphylococcus, and Veillonella resulted as NP microbiota biomarkers, in COVID-19 patients. No statistically significant differences were found comparing the NP microbiota profile of COVID-19 patients during the time-points or grouping patients on the basis of high, medium, and low viral load (VL). This evidence provides specific pathobiont signatures of the NP microbiota in pediatric COVID-19 patients, and the reduction of anaerobic protective commensals. Our data suggest that the NP microbiota may have a specific disease-related signature since infection onset without changes during disease progression, regardless of the SARS-CoV-2 VL. IMPORTANCE: Since the beginning of pandemic, we know that children are less susceptible to severe COVID-19 disease. A potential role of the nasopharyngeal (NP) microbiota has been hypothesized but to date, most of the studies have been focused on adults. We studied the NP microbiota modifications in children affected by SARS-CoV-2 infection showing a specific NP microbiome profile, mainly composed by pathobionts and almost missing protective anaerobic commensals. Moreover, in our study, specific microbial signatures appear since the first days of infection independently from SARS-CoV-2 viral load.

Effect of age on the vasodilatory action of elastin peptides.

We have recently shown, on young adult rat aorta rings, that elastin peptides induce a dose and endothelium-dependent vasodilation mediated by the 67 kDa subunit of the high affinity elastin-laminin receptor and, at least in part, by EDRF (NO). Here we have studied the effects of elastin peptides at circulating concentrations and below, on noradrenaline-contracted rat aortic rings, as a function of age. First, we have observed that, unlike 2-month-old (2M), 4-6-month-old (4M) and 12-month-old (12M) rat aorta rings, 30-month-old (30M) rat aorta rings were unable to maintain their contraction in long lasting experiments. Secondly, elastin peptides at physiological circulating concentrations (10(-6)-10(-3) mg/ml) induce a dose-dependent vasodilation on 4M rings. By contrast, only higher elastin peptide concentrations (10(-3) mg/ml) were effective on 12M rings, whereas rings from both younger (2M) and older animals (30M) did not respond to elastin peptides. Finally, using lactose and laminin as inhibitors, we have demonstrated that elastin peptide-induced vasodilation on 4M and 12M rings is mediated by the 67 kDa subunit of the elastin-laminin receptor. These experiments suggest that the functional availability of the 67 kDa subunit of the elastin-laminin receptor changes with age. It could be hypothesized that in young animals (0-2M) the reusable shuttle role recently demonstrated for the 67 kDa receptor subunit during elastic fiber formation leads to a major decrease in its availability for signal transduction. On the contrary, in adult animals. (4-12M), when developmental elastogenesis is completed, this subunit is essential for extracellular signal transduction. Inefficiency of this receptor in old animals (30M) can be attributed to its uncoupling from its transduction pathway, as previously shown on human cells. Finally, the age-dependent variations of circulating elastin peptide concentration and elastin-laminin receptor responsiveness to elastin peptides are two independent parameters which could influence the vascular tension regulation.

Effect of elastin peptides on vascular tone.

Elastin peptides are present in human blood. As elastin receptors exist on several cell types, especially endothelial cells, this investigation was carried out to study the effect of elastin peptides on vascular tone. For this purpose, rat aortic rings were mounted in an organ bath for isometric tension measurements. Elastin peptides (kappa-elastin) were added in the concentration range of 0.1 ng/ml to 1 microgram/ml, concentrations similar to those found in the circulating blood. In rat aortic rings, precontracted or not with noradrenaline (10(-6) M), elastin peptides induced an endothelium-dependent vasodilation. The pretreatment of aortic rings with N-omega-nitro-L-arginine methyl ester (10(-5) M), an inhibitor of nitric oxide (NO) production, or with indomethacin (10(-5) M), an inhibitor of cyclooxygenase, prevented elastin peptide-induced vasodilation. These findings suggest that elastin peptides act through the synthesis of prostanoids, leading to the production of NO. Moreover, this relaxant effect of elastin peptides was decreased or inhibited when aortic rings were treated with lactose (10(-5) to 10(-2) M) or laminin (10(-6) to 10(-4) mg/ml) whereas lactose or laminin was unable to inhibit acetylcholine-induced vasodilation. These findings suggest that the inhibitory effects of lactose and laminin are specific for elastin peptide receptors and are in agreement with previous studies on these receptors. As there is evidence of the degradation of elastin in several vascular diseases, the concept that elastin peptides may contribute to the control of vascular tone is discussed.

Effects of chronic angiotensin I-converting enzyme inhibition on the relations between ventricular action potential changes and myocardial hypertrophy in aging rats.

We studied the effect of aging on cardiac hypertrophy and action potential duration (APD) in normotensive male WAG/Rij rats and evaluated the role of the renin-angiotensin system (RAS) in these effects. Cardiac hypertrophy occurs in 30-month-old rats, as indicated by an increase in heart weight, and APD gradually increases with aging in the epicardial region of the right and the left ventricle. Short-term treatment (1 month) with the angiotensin-converting enzyme inhibitor (ACEI) perindopril prevented age-related increase in heart weight/body weight ratio independent of its antihypertensive effects, but did not prevent changes in APD in 30-month-old rats. Our results show a dissociation of changes in cardiac mass from changes in APD during aging. The effect of ACEI on hypertrophy may be due in part to a direct angiotensin effect on cellular growth. Changes in APD are not related to hypertrophy but rather to the process of aging.

[Role of the elastin-laminin receptor in the vasoregulation]. / Rôle du récepteur de l'élastine-laminine dans la vasorégulation.

The elastin-laminin receptor was shown to be present on several benign and malignant cell types and to mediate several important cell reactions such as chemotactic movements of fibroblasts and monocytes, release of lytic enzymes and oxygen free radicals from leucocytes, increased adhesion of mesenchymal cells to elastin fibers as well as modifications of ion fluxes-increase of calcium and sodium influxes and decrease of ouabain-dependent potassium influx. We now demonstrated that the addition of elastin peptides to rat aorta rings precontracted with noradrenaline produced an endothelium-dependent vasorelaxation. The inhibition of this effect by laminin and lactose is in favor of the mediation of this action of elastin peptides by the 67 kDa subunit of the elastin-laminin receptor which possesses a lectin site. As elastin peptides are present in the circulating blood and their concentration was shown to increase in some pathological conditions, this phenomenon may well have physiopathological significance.

Effects of taurine on rat aorta in vitro.

The effects of taurine on vascular tone of isolated thoracic aortic rings were investigated. We have observed that: 1) taurine is able to induce reduction of the basal contractile tone; 2) taurine exerts a relaxing action in artery segments preconstricted with high potassium medium noradrenaline; 3) the effect of taurine is either dependent on endothelium, nor mediated by adrenoceptors or muscarinic cholinoceptors; 4) in vessels with basal tone or in those preconstricted with noradrenaline, the presence of endothelium reduces the taurine-induced relaxation; 5) the actions of taurine are independent of extracellular calcium; 6) taurine increases the vasodilatation induced by a perfusion with a calcium-free medium. The physiological role of taurine in the maintenance of vascular tone in normal and pathological situations is discussed.

Plasma catecholamines in rainbow trout (Salmo gairdneri) during hypoxia.

Plasma catecholamines (CAs) were assayed radioenzymatically in normoxic and variably hypoxic rainbow trout (Salmo gairdneri). Results were grouped according to four levels of progressively deeper hypoxemia. Only in animals where PaO2 fell below 6.7 kPa, were both adrenaline (A) and noradrenaline (NA), slightly, but significantly, increased. In contrast, substantial increases of plasma CAs occurred when PaO2 was reduced below 3.99 kPa (increment factor: A = 3.8, NA = 3.4). Comparisons between dose/response data from the literature and the present results suggest that plasma CAs might have a functional role during deep hypoxia. The regulatory role during mild hypoxia remains uncertain due to the lack of data concerning plasma CA prebranchial concentrations and of more precise dose/response relationships.

Effects of experimental anemia on the ATP content and the oxygen affinity of the blood in the rainbow trout (Salmo gairdnerii).

Blood oxygenation properties have been investigated in rainbow trout, 1 and 48 hr after an approximately 25% loss of blood. In both cases the hematocrit was nearly halved. The ATP/Hb4 ratio was significantly increased by 35 and 46% after 1 and 48 hr, respectively. The P 1/2 value (at pH 7.7 and 20 degrees C) was significantly raised, by about 2 mmHg, in both cases. After 48 hr, this decrease in the blood-oxygen affinity and the increase in the red-cell ATP content were significantly positively correlated. The mean corpuscular hemoglobin concentration (MCHC) value was never significantly changed. The pH was decreased by about 0.1 unit after 1 hr but normal values were found after 48 hr. It is suggested that these variations might be of adaptative value for fish in conditions of normal environmental pO2.

Plasma catecholamines and glucose during moderate exercise in the trout: comparison with bursts of violent activity.

A sensitive radioenzymatic method was used to measure the plasma adrenaline and noradrenaline levels in Salmo gairdneri during and after long but moderate exercise (30 min, 2.2 body length s-1), and after brief but violent exercise (3 min chasing). No significant change occurred under the former experimental conditions whereas adrenaline increased significantly under the second. Plasma glucose increased only after violent exercise. These results suggest that plasma catecholamines do not participate in physiological regulations related to exercise when trout is swimming at velocities up to 2.2 body length s-1.

[Vascular perfusion of an intestinal segment in the catfish (Ictalurus melas, R): demonstration of the vasoactive effects of mammalian VIP and of gastrointestinal extracts from teleost fish]. / Perfusion vasculaire d'un segment intestinal chez le poissonchat (Ictalurus mélas, R.): démonstration des effets vasoactifs du VIP de mammifère et d'extraits de tractus gastro-intestinal de Poisson téléostéen.

Through the middle mesenteric artery and the hepatic portal vein it is possible to perfuse specifically a small part of the catfish midgut. Using a tested VIP extraction procedure it is shown that trout and catfish extracts of oesophagus, stomach, midgut and hindgut induce a vasodilation similar to that of porcine VIP. The importance of the vasodilatory response depends on the level of perfused VIP and extracted tissue.

[The effect of hypoxia on the branchial vascular system of the perfused trout head]. / Action de l'hypoxie sur le système vasculaire branchial de la tête perfusée de Truite.

Measurements of inflow (VE) and arterial (Vsa) and venous (VSv) outflow in trout perfused head preparations show significant decreases of VE and VSa during low PO2 saline perfusion (20 torr). Comparable results are gained during adenosine perfusion (1.10(-8) to (1.10(-6) M). Theophylline (10(-4) M) inhibits both hypoxia and adenosine effects.