Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are well recognized for playing a dual role, since they can be either deleterious or beneficial to biological systems. An imbalance between ROS production and elimination is termed oxidative stress, a critical factor and common denominator of many chronic diseases such as cancer, cardiovascular diseases, metabolic diseases, neurological disorders (Alzheimer's and Parkinson's diseases), and other disorders. To counteract the harmful effects of ROS, organisms have evolved a complex, three-line antioxidant defense system. The first-line defense mechanism is the most efficient and involves antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). This line of defense plays an irreplaceable role in the dismutation of superoxide radicals (O2•-) and hydrogen peroxide (H2O2). The removal of superoxide radicals by SOD prevents the formation of the much more damaging peroxynitrite ONOO- (O2•- + NO• → ONOO-) and maintains the physiologically relevant level of nitric oxide (NO•), an important molecule in neurotransmission, inflammation, and vasodilation. The second-line antioxidant defense pathway involves exogenous diet-derived small-molecule antioxidants. The third-line antioxidant defense is ensured by the repair or removal of oxidized proteins and other biomolecules by a variety of enzyme systems. This review briefly discusses the endogenous (mitochondria, NADPH, xanthine oxidase (XO), Fenton reaction) and exogenous (e.g., smoking, radiation, drugs, pollution) sources of ROS (superoxide radical, hydrogen peroxide, hydroxyl radical, peroxyl radical, hypochlorous acid, peroxynitrite). Attention has been given to the first-line antioxidant defense system provided by SOD, CAT, and GPx. The chemical and molecular mechanisms of antioxidant enzymes, enzyme-related diseases (cancer, cardiovascular, lung, metabolic, and neurological diseases), and the role of enzymes (e.g., GPx4) in cellular processes such as ferroptosis are discussed. Potential therapeutic applications of enzyme mimics and recent progress in metal-based (copper, iron, cobalt, molybdenum, cerium) and nonmetal (carbon)-based nanomaterials with enzyme-like activities (nanozymes) are also discussed. Moreover, attention has been given to the mechanisms of action of low-molecular-weight antioxidants (vitamin C (ascorbate), vitamin E (alpha-tocopherol), carotenoids (e.g., β-carotene, lycopene, lutein), flavonoids (e.g., quercetin, anthocyanins, epicatechin), and glutathione (GSH)), the activation of transcription factors such as Nrf2, and the protection against chronic diseases. Given that there is a discrepancy between preclinical and clinical studies, approaches that may result in greater pharmacological and clinical success of low-molecular-weight antioxidant therapies are also subject to discussion.
- MeSH
- anthokyaniny metabolismus farmakologie MeSH
- antioxidancia * farmakologie metabolismus MeSH
- chronická nemoc MeSH
- kyselina peroxydusitá farmakologie MeSH
- lidé MeSH
- nádory * MeSH
- oxid dusnatý MeSH
- oxidační stres MeSH
- peroxid vodíku MeSH
- reaktivní formy kyslíku metabolismus MeSH
- superoxiddismutasa metabolismus MeSH
- superoxidy MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
The unique potential of fullerene C60 for various biological applications has ignited significant interest. However, its inherent non-polarity poses a critical challenge for its effective integration within biological systems. This study delves into the intricate physicochemical characteristics of the innovative [C60 + NO] complex using density functional theory and time-dependent density functional theory. The computational analyses encompass molecular charge, surface electrostatic potential, and dipole moment evaluations. Impressively, the dipole moment of the [C60 + NO] complex significantly increases to 12.92 D. Meticulous surface analysis reveals a subtle interplay between molecular structures, indicating weak interactions. The analysis of the absorption spectrum unveils a noteworthy red-shift of 200 nm subsequent to complex formation. To elucidate the electron transfer mechanisms, we explore photo-induced electron transfer through CAM-B3LYP. This exploration elucidates intricate pathways governing electron transfer, with complementary insights gleaned from Marcus theory's outputs, especially the Gibbs free energy of electron transfer. Changes in the physicochemical properties of approaching C60 and NO molecules reveal interesting results compared to separate molecules. These findings resonate profoundly in the context of potential biological and pharmaceutical utilization. With implications for the biomedical area, the outcomes linked to the [C60 + NO] complex kindle optimism for pioneering biomedical applications.
Inducible NO synthase (NOS II) was proposed to play an important role in salt resistance of Dahl salt-resistant (SR/Jr) rats. Its chronic inhibition by specific inhibitors was accompanied by blood pressure (BP) elevation in animals subjected to high salt intake. The aim of our study was to evaluate 1) whether such inhibitors affect BP and/or its particular components (sympathetic tone and NO-dependent vasodilation) only under the conditions of high salt intake, and 2) whether similar BP effects are elicited after systemic or intracerebroventricular (icv) application of these inhibitors. Wistar rats fed Altromin diet (0.45 % NaCl) and SR/Jr rats fed either a low-salt (LS, 0.3 % NaCl) or a high-salt (HS, 4 % NaCl) diet were studied. Aminoguanidine (AMG) and 2-amino-5,6-dihydro-6-methyl-4H-1,3-thiazine (AMT) were used as NOS II inhibitors. BP and its responses to acute blockade of renin-angiotensin system (captopril), sympathetic nervous system (pentolinium) and NO synthase (L-NAME) were measured in conscious cannulated rats. There were no significant changes of BP or its components in either Wistar rats or SR/Jr rats subjected to chronic inhibition of NOS II by peroral aminoguanidine administration (50 mg/kg/day for 4 weeks). This was true for SR/Jr rats fed either LS or HS diets. Furthermore, we have studied BP effects of chronic icv administration of both NOS II inhibitors in SR/Jr rats fed HS diet, but we failed to find any BP changes elicited by such treatment. In conclusion, inducible NO synthase does not participate in the resistance of SR/Jr rats to hypertensive effects of excess salt intake.
- MeSH
- chlorid sodný MeSH
- hypertenze * chemicky indukované MeSH
- krevní tlak fyziologie MeSH
- krysa rodu rattus MeSH
- kuchyňská sůl * MeSH
- oxid dusnatý MeSH
- potkani inbrední Dahl MeSH
- potkani Wistar MeSH
- synthasa oxidu dusnatého, typ II MeSH
- synthasa oxidu dusnatého MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- antibakteriální látky terapeutické užití MeSH
- aplikace inhalační MeSH
- cilie patologie MeSH
- dechová cvičení metody MeSH
- diferenciální diagnóza MeSH
- elektronová mikroskopie metody MeSH
- genetické testování metody MeSH
- infekce dýchací soustavy etiologie MeSH
- infertilita etiologie MeSH
- lidé MeSH
- oxid dusnatý analýza MeSH
- poruchy ciliární motility * diagnóza patologie terapie MeSH
- situs inversus etiologie MeSH
- videomikroskopie metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Úvod: Práce hasičů patří mezi rizikové z hlediska možného ohrožení zdraví. Během zásahů jsou hasiči vystavováni nebezpečným zplodinám hoření, které mohou mít akutní i chronický účinek. Cílem tohoto projektu bylo zjistit, k jakým změnám ve ventilačních parametrech dochází u hasičů časně po zásahu u požáru. Metodika: Projektu se účastnilo 24 hasičů (průměrný věk 37,1 let), kteří byli v rámci výcviku exponováni zplodinám hoření při hašení v zařízení simulujícím reálné prostředí požáru (flashover kontejner). Před zásahem, ihned po něm a druhý den byla provedena spirometrie. Před expozicí bylo provedeno měření vydechovaného oxidu dusnatého (FeNO) k posouzení možného alergického zánětu v dýchacích cestách. Výsledky: Průměrná hodnota FeNO byla u sledovaných osob 18,8 ppb (rozmezí 5–59). Při měření klidové spirometrie před zásahem byla u jedné osoby snížená hodnota FEV1 (usilovně vydechnutý objem za 1. sekundu), snížené hodnoty obstrukce v periferních dýchacích cestách (MEF – maximální průtoky vydechnutého vzduchu v různých úrovních usilovné vitální kapacity) byly nalezeny u 18 osob, zvýšená hodnota odporů v dýchacích cestách (Rocc) u 12 osob. Vitální kapacita (VC) plic byla u všech osob v normě. Ihned po cvičném zásahu došlo ve skupině sledovaných osob ke zlepšení průměrné hodnoty všech sledovaných ventilačních parametrů. Změny byly významné v parametrech FEV1, MEF25 (maximální průtok vydechnutého vzduchu v 25 % usilovné vitální kapacity), AEX (plocha pod výdechovou částí křivky) (p ≤ 0,001), FVC (usilovná vitální kapacita) a Rocc (p < 0,01). Druhý den došlo naopak ke zhoršení sledovaných ventilačních parametrů, a to jak vzhledem k hodnotám ihned po zásahu, tak i ke vstupním hodnotám. Změny druhý den po zásahu v porovnání s hodnotami před zásahem byly významné pro parametr VC, Rocc (p < 0,001), FEV1 (p < 0,01). Závěr: Sledování ventilačních parametrů během simulovaného požárního zásahu ukázalo, že ke zhoršení došlo až s odstupem – druhý den, a to v dynamických i statických parametrech. Z hlediska regenerace organismu hasičů je tedy velmi důležitá rekonvalescence ve dnech následujících po zásahu.
Introduction: The work of firefighters is one of the most risk in terms of potential health hazards. Firefighters are exposed to hazardous combustion products, which can have both acute and chronic effects. The aim of this project was to investigate what changes in ventilation parameters occur in firefighters early after a fire exposure. Methodology: Twenty-four firefighters (mean age 37.1 years) participated in the project and were exposed to combustion products during training in a device simulating a real fire exposure (flashover container). Spirometry was performed before, immediately after and the next day. Before exposure, exhaled nitric oxide (FeNO) measurement was taken to assess possible allergic inflammation in the airways. Results: The mean FeNO value in the subjects was 18.8 ppb (range 5–59). When measuring resting spirometry before the intervention, one person had a reduced FEV1 value (forced expiratory volume in 1 second), reduced values of peripheral airway obstruction (MEF-maximal expiratory flow rates at different levels of forced vital capacity) were found in 18 persons, increased values of airway resistance (Rocc) in 12 persons. The vital capacity (VC) of the lungs was normal in all persons. Immediately after the training intervention, the mean value of all the monitored ventilatory parameters improved in the group of subjects. The changes were significant in the parameters FEV1, MEF25 (maximum expiratory flow rate at 25 % of the forced vital capacity), AEX (area under the expiratory part of the curve) (p ≤ 0.001), FVC (forced vital capacity) and Rocc (p < 0.01). On the second day, there was a deterioration of the monitored ventilatory parameters, both with respect to the values immediately after the exposure and to the initial values. Changes on the second day after the exposure compared to pre-exposure values were significant for the VC parameter, Rocc (p < 0.001), FEV1 (p < 0.01). Conclusion: The monitoring of ventilation parameters during the simulated fire incident showed that the deterioration occurred only after the second day, both in dynamic and static parameters. Thus, from the point of view of the recovery of the firefighters’ organism, recovery in the days following the intervention is very important.
- MeSH
- dospělí MeSH
- hasiči * MeSH
- inhalační expozice MeSH
- kouř škodlivé účinky MeSH
- lidé středního věku MeSH
- lidé MeSH
- měření vydechovaného oxidu dusnatého * MeSH
- oxid dusnatý MeSH
- spirometrie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- práce podpořená grantem MeSH
During phototherapy of jaundiced newborns, vasodilation occurs in the skin circulation compensated by vasoconstriction in the renal and mesenteric circulation. Furthermore, there is a slight decrease in cardiac systolic volume, and blood pressure, as well as an increase in heart rate and discrete changes in the heart rate variability (HRV). The primary change during phototherapy is the skin vasodilation mediated by multiple mechanisms: 1) Passive vasodilation induced by direct skin heating effect of the body surface and subcutaneous blood vessels, modified by myogenic autoregulation. 2) Active vasodilation mediated via the mechanism provided by axon reflexes through nerve C-fibers and humoral mechanism via nitric oxide (NO) and endothelin 1 (ET-1). During and after phototherapy is a rise in the NO:ET-1 ratio. 3) Regulation of the skin circulation through the sympathetic nerves is unique, but their role in skin vasodilation during phototherapy was not studied. 4) Special mechanism is a photorelaxation independent of the skin heating. Melanopsin (opsin 4) - is thought to play a major role in systemic vascular photorelaxation. Signalling cascade of the photorelaxation is specific, independent of endothelium and NO. The increased skin blood flow during phototherapy is enabled by the restriction of blood flow in the renal and mesenteric circulation. An increase in heart rate indicates activation of the sympathetic system as is seen in the measures of the HRV. High-pressure, as well as low-pressure baroreflexes, may play important role in these adaptation responses. The integrated complex and specific mechanism responsible for the hemodynamic changes during phototherapy confirm adequate and functioning regulation of the neonatal cardiovascular system, including baroreflexes.
- MeSH
- fototerapie MeSH
- hyperbilirubinemie * MeSH
- kůže krevní zásobení MeSH
- lidé MeSH
- novorozenec MeSH
- oxid dusnatý MeSH
- srdce * fyziologie MeSH
- vazodilatace fyziologie MeSH
- Check Tag
- lidé MeSH
- novorozenec MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Heart failure (HF) has been declared as global pandemic and current therapies are still ineffective, especially in patients that develop concurrent cardio-renal syndrome. Considerable attention has been focused on the nitric oxide (NO)/soluble guanylyl cyclase (sGC)/cyclic guanosine monophosphate (cGMP) pathway. In the current study, we aimed to investigate the effectiveness of sGC stimulator (BAY41-8543) with the same mode of action as vericiguat, for the treatment of heart failure (HF) with cardio-renal syndrome. As a model, we chose heterozygous Ren-2 transgenic rats (TGR), with high-output heart failure, induced by aorto-caval fistula (ACF). The rats were subjected into three experimental protocols to evaluate short-term effects of the treatment, impact on blood pressure, and finally the long-term survival lasting 210 days. As control groups, we used hypertensive sham TGR and normotensive sham HanSD rats. We have shown that the sGC stimulator effectively increased the survival of rats with HF in comparison to untreated animals. After 60 days of sGC stimulator treatment, the survival was still 50% compared to 8% in the untreated rats. One-week treatment with sGC stimulator increased the excretion of cGMP in ACF TGR (109 ± 28 nnmol/12 h), but the ACE inhibitor decreased it (-63 ± 21 nnmol/12 h). Moreover, sGC stimulator caused a decrease in SBP, but this effect was only temporary (day 0: 117 ± 3; day 2: 108 ± 1; day 14: 124 ± 2 mmHg). These results support the concept that sGC stimulators might represent a valuable class of drugs to battle heart failure especially with cardio-renal syndrome, but further studies are necessary.
- MeSH
- guanosinmonofosfát cyklický metabolismus MeSH
- guanylátcyklasa MeSH
- hypertenze * farmakoterapie MeSH
- kardiorenální syndrom * MeSH
- krysa rodu rattus MeSH
- lidé MeSH
- oxid dusnatý metabolismus MeSH
- píštěle * MeSH
- potkani transgenní MeSH
- rozpustná guanylátcyklasa metabolismus MeSH
- srdeční selhání * farmakoterapie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- analýza potravin MeSH
- arginin * chemie fyziologie nedostatek MeSH
- erektilní dysfunkce etiologie farmakoterapie MeSH
- lidé MeSH
- oxid dusnatý * dějiny fyziologie nedostatek MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- populární práce MeSH
Příspěvek reflektuje v modifikované formě evropská doporučení, která jsou na pracovišti standardizována písemně. I když mechanismy poškozování plic mechanickou ventilací mají univerzální účinky na plicní tkáň, u nezralých novorozenců mají specifické dopady vzhledem k fázi fetálního vývoje plic a často přítomné fetální zánětlivé odpovědi. Jedním ze základních principů protekce nezralých plic mechanickou ventilací je udržování plic v relativně homogenním stavu a bez adverzních účinků na oběh. Z tohoto úhlu pohledu lze používané parametry rozdělit na méně a více zraňující. Dynamické změny objemu plic jsou více zraňující než statické. V průběhu konvenčních módů mechanické ventilace respektujeme používání fyziologických dechových objemů a optimálním nastavením úrovně pozitivního tlaku na konci exspiria dosahujeme jejich rovnoměrné distribuce. Zároveň preferujeme konvenční módy, které umožňují co největší míru synchronizace s vlastním dechovým úsilím, či dokonce proporcionální podporu během celého dechového cyklu pacienta. U závažných forem respiračního selhání a u extrémně nezralých novorozenců (< 26. týdnu těhotenství) indikujeme elektivně vysokofrekvenční oscilační ventilaci s předpokladem snížení působení smykových sil v kanalikulárně-sakulárním vývojovém stadiu plic. V průběhu mechanické ventilace preferujeme pronační polohu, kterou považujeme za paraventilační faktor facilitující rovnoměrnou distribuci plynu v plicích. Příspěvek se rovněž zabývá využitím inhalace oxidu dusnatého u nezralých novorozenců s anamnézou závažného oligohydramnia různé etiologie a preeklampsie matky, kde lze očekávat v adaptační fázi po porodu snížení endogenního oxidu dusnatého. Využití postnatálních steroidů, jejich volba a dávkování je vztaženo k diagnóze a postnatálnímu stáří extrémně nezralých novorozenců, a to nejen na mechanické ventilaci.
The chapter reflects, in a modified form, European recommendations that are standardized in the workplace in writing. Although the mechanisms of lung injury due to mechanical ventilation have universal effects on lung tissue, in premature newborns, they have specific impacts due to the fetal stage of lung development and frequently present fetal inflammatory responses. One of the fundamental principles of protecting immature lungs during mechanical ventilation is to maintain the lungs in a relatively homogeneous state without adverse effects on circulation. From this perspective, the parameters used can be divided into less and more injurious ones. Dynamic changes in lung volume are more injurious than static ones. During conventional mechanical ventilation modes, we adhere to the use of physiological tidal volumes and achieve their even distribution by optimizing the positive end-expiratory pressure level. At the same time, we prefer conventional modes that allow for the highest degree of synchronization with the patient's own breathing effort or even proportional support throughout the patient's entire respiratory cycle. For severe forms of respiratory failure and extremely premature infants < 26 weeks of gestation, we electively indicate high frequency oscillatory ventilation with the assumption of reducing the impact of shear forces in the canalicular-saccular developmental stage of the lungs. During mechanical ventilation, we prefer the prone position, which we consider a protective factor facilitating the even distribution of gas in the lungs. The chapter also deals with the use of inhaled nitric oxide in premature newborns with a history of severe oligohydramnios of various etiologies and maternal preeclampsia, where a reduction in endogenous nitric oxid can be expected in the adaptation phase after birth. The use of postnatal steroids, their choice, and dosage are related to the diagnosis and postnatal age of extremely premature newborns, not only on mechanical ventilation.
- Klíčová slova
- homogenní ventilace, synchronizovaná proporcionální ventilace, inhalační oxid dusnatý, postnatální steroidy,
- MeSH
- lidé MeSH
- novorozenec nedonošený MeSH
- novorozenec MeSH
- oxid dusnatý terapeutické užití MeSH
- poškození plic mechanickou ventilací prevence a kontrola MeSH
- směrnice pro lékařskou praxi jako téma MeSH
- umělé dýchání * metody MeSH
- Check Tag
- lidé MeSH
- novorozenec MeSH
Spontaneously hypertensive rats (SHR) display deficiency of epoxyeicosatrienoic acids (EETs). Their possible interaction with renal sympathetic nerves remains unexplored; synthesis of EET-A [disodium (S)-2-(13-(3-pentyl)ureido)-tridec-8(Z)-enamido)succinate], a stable 14,15-EET analog, helps clarify the issue. In anesthetized SHR, untreated or pretreated with EET-A, we assessed early responses of blood pressure (MAP), renal hemodynamics and excretion, and indices of nitric oxide (NO) activity, to bilateral noninvasive renal denervation (DNX). DNX significantly decreased MAP, with or without EET-A pretreatment. Renal perfusion decreased in EET-A treated but not in control rats. After EET-A pretreatment DNX decreased renal excretion of sodium and total solutes, compared to increasing tendency in untreated rats. In EET-A treated but not in untreated SHR denervation reduced the excretion of NO metabolites. Antihypertensive action of EET-A in anesthetized SHR was not clearly dependent on renal nerve activity. On the other hand, DNX unmasked the unexpected effect of EET-A to lower renal perfusion. The mechanism of this novel finding is unclear, as is also the simultaneous post-denervation decrease in renal excretion, again, observed only under EET-A treatment. Possibly, the decrease was secondary to falling MAP and renal perfusion. Increased renal excretion of nitric oxide metabolites under EETs elevation strongly suggests facilitation of NO release; the effect that was observed only with intact renal nerve activity.
- MeSH
- antihypertenziva * farmakologie MeSH
- hemodynamika MeSH
- hypertenze * metabolismus MeSH
- ikosanoidy MeSH
- krevní tlak MeSH
- krysa rodu rattus MeSH
- ledviny metabolismus MeSH
- oxid dusnatý farmakologie MeSH
- potkani inbrední SHR MeSH
- potkani inbrední WKY MeSH
- sodík MeSH
- sukcináty farmakologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
