Hyperleptinemia accompanying obesity affects endothelial nitric oxide (NO) and is a serious factor for vascular disorders. NO, superoxide (O2−), and peroxynitrite (ONOO−) nanosensors were placed near the surface (5 ± 2 μm) of a single human umbilical vein endothelial cell (HUVEC) exposed to leptin or aortic endothelium of obese C57BL/6J mice, and concentrations of calcium ionophore (CaI)-stimulated NO, O2−, ONOO− were recorded. Endothelial NO synthase (eNOS) expression and l-arginine concentrations in HUVEC and aortic endothelium were measured. Leptin did not directly stimulate NO, O2−, or ONOO− release from HUVEC. However, a 12-h exposure of HUVEC to leptin increased eNOS expression and CaI-stimulated NO (625 ± 30 vs. 500 ± 24 nmol/l control) and dramatically increased cytotoxic O2− and ONOO− levels. The [NO]-to-[ONOO−] ratio ([NO]/[ONOO−]) decreased from 2.0 ± 0.1 in normal to 1.30 ± 0.1 in leptin-induced dysfunctional endothelium. In obese mice, a 2.5-fold increase in leptin concentration coincided with 100% increase in eNOS and about 30% decrease in intracellular l-arginine. The increased eNOS expression and a reduced l-arginine content led to eNOS uncoupling, a reduction in bioavailable NO (250 ± 10 vs. 420 ± 12 nmol/l control), and an elevated concentration of O2− (240%) and ONOO− (70%). l-Arginine and sepiapterin supplementation reversed eNOS uncoupling and partially restored [NO]/[ONOO−] balance in obese mice. In obesity, leptin increases eNOS expression and decreases intracellular l-arginine, resulting in eNOS an uncoupling and depletion of endothelial NO and an increase of cytotoxic ONOO−. Hyperleptinemia triggers an endothelial NO/ONOO− imbalance characteristic of dysfunctional endothelium observed in other vascular disorders, i.e., atherosclerosis and diabetes.
Coronavirus disease (COVID-19) and its outcomes remain one of the most challenging problems today. COVID-19 in children could be asymptomatic, but can result in a fatal outcome; therefore, predictions of the disease severity are important. The goal was to investigate the human genetic factors that could be associated with COVID-19 severity in children. Single-nucleotide polymorphisms of the following genes were studied: ACE2 (rs2074192), IFNAR2 (rs2236757), TYK2 (rs2304256), OAS1 (rs10774671), OAS3 (rs10735079), CD40 (rs4813003), FCGR2A (rs1801274) and CASP3 (rs113420705). In the case–control study were 30 children with mild or moderate course of the disease; 30 with severe COVID-19 symptoms and multisystem inflammatory syndrome in children (MIS-C) and 15 who were healthy, and who did not have SARS-CoV-2 (PCR negative, Ig G negative). The study revealed that ACE2 rs2074192 (allele T), IFNAR2 rs2236757 (allele A), OAS1 rs10774671 (allele A), CD40 rs4813003 (allele C), CASP3 rs113420705 (allele C) and male sex contribute to severe COVID-19 course and MIS-C in 85.6% of cases. The World Health Organization reported that new SARS-CoV-2 variants may cause previously unseen symptoms in children. Although the study has limitations due to cohort size, the findings can help provide a better understanding of SARS-CoV-2 infection and proactive pediatric patient management.
1 February 2008 in Journal of Cardiovascular Pharmacology
Biological aging is an independent risk factor for many cardiovascular diseases; some are treated with β-blockers that may protect dysfunctional endothelium during aging by increasing NO, decreasing ONOO-, and restoring NO/ONOO- balance. A nanotechnological approach was used to simultaneously monitor NO and ONOO- produced by a single aortic endothelial cell from Wistar-Kyoto rats of different ages. β-blockers (metoprolol and atenolol) were administered 2 weeks before the animals were sacrificed. Nanosensors were placed near the endothelium, and calcium ionophore- stimulated NO and ONOO- release was measured. Endothelial nitric oxide synthase (eNOS) undergoes uncoupling with aging, manifested by a decrease in NO (from 503 ± 12 to 163 ± 5 nmol/L) and a 3-fold increase in ONOO- for 16-week-old and 110- week- old rats, respectively. Metoprolol reversed eNOS uncoupling, increased the production rate and concentration of NO, and increased an overall ratio of NO]/ONOO-]. This effect was not observed with atenolol, but L-arginine, sepiapterin, and superoxide dismutase were beneficial.
21 November 2022 in Journal of Education, Health and Sport
Background. Earlier we showed that the Ukrainian phytocomposition “Balm Truskavets’” exerts immediate modulating effects on parameters of EEG and HRV as well as biophotonics. In a pilot study on 10 volunteers, we found that the use of the phytocomposition for 11 days causes changes in EEGs parameters accompanied by a sympatho(adreno)mimetic effect. The modulating effects on the EEG&HRV parameters are combined with the changes in biophotonics parameters. This study was conducted on a four times larger cohort and with a wider range of methods. Materials and Methods. The object of observation were 16 women 46±15 ys and 24 men 50±11 ys. The volunteers were practically healthy, but the initial testing revealed deviations from the norm in a number of parameters of the neuro-endocrine-immune complex as a manifestation of maladaptation. The adaptation hormones levels, Popovych’s leukocytary adaptation and strain indices, parameters of phagocytosis, biophotonics, acupuncture points, EEG and HRV, before and after a 9-day course of use of phytocomposition registered.Results. A noticeable effect of the phytocomposition on 38 parameters was revealed, grouped into 6 clusters, of which 4 are enhancing and 2 are reducing. In particular, the reduced levels of the adaptation index and phagocytosis parameters increase significantly, instead, the increased levels of the strain index, testosterone, triiodothyronine, LF band HRV as well as two biophotonics parameters decrease, that is, there is a normalizing/beneficial effect. At the same time, normal levels of HRV-markers of vagal tone decrease, and cortisol and circulating catecholamines as well as the activity of β- and α-rhythm generating neurons increase, but within the normal range. Finally, there is a further increase in the upper limit levels of activity of δ-rhythm generating neurons. Conclusion. Ukrainian phytocomposition “Balm Truskavets’” exerts classical adaptogenic effects on parameters of neuro-endocrine-immune complex as well as biophotonics and acupuncture in humans with maladaptation.
26 October 2017 in Health Problems of Civilization
Borelioza z Lyme (LB) jest najczęstszą chorobą przenoszoną przez kleszcze w Europie, a liczba zachorowań stale rośnie. Celem pracy było przedstawienie sytuacji epidemiologicznej oraz standardów diagnostycznych LB w dwóch sąsiadujących krajach Europy Środkowo-Wschodniej: Polsce i Ukrainie. Borelioza z Lyme uważana jest za endemiczną zarówno w Polsce jak i Ukrainie. W Polsce system nadzoru dla LB rozpoczęto w 1996 roku, a liczba rejestrowanych przypadków zachorowań systematycznie rośnie. Borelioza z Lyme zajmuje czołowe miejsce wśród rozpoznawanych w Polsce chorób zawodowych. Na Ukrainie rejestracja LB rozpoczęła się w 2000 roku, a częstość występowania tej choroby rośnie z każdym rokiem. Brakuje jednocześnie oficjalnego uznania LB jako choroby zawodowej z odpowiednimi gwarancjami socjalnymi. W Polsce dostępne są rekomendacje Polskiego Towarzystwa Epidemiologii i Chorób Zakaźnych dotyczące diagnostyki i leczenia LB. Zalecenia dotyczące metod diagnozowania i leczenia LB na Ukrainie są na dzień dzisiejszy nieobecne. W związku z brakiem rekomendacji dotyczących diagnostyki laboratoryjnej LB na Ukrainie, należy podjąć starania zmierzające do harmonizacji standardów w diagnostyce boreliozy z Lyme w tym kraju na podstawie wytycznych obowiązujących w krajach europejskich.