Oxidized nitrogen
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OBJECTIVES: To evaluate the effect of short-term inhalational exposure to nanoparticles released during dental composite grinding on oxidative stress and antioxidant capacity markers. MATERIALS AND METHODS: Twenty-four healthy volunteers were examined before and after exposure in dental workshop. They spent 76.8 ± 0.7 min in the testing room during grinding of dental nanocomposites. The individual exposure to aerosol particles in each participant ́s breathing zones was monitored using a personal nanoparticle sampler (PENS). Exhaled breath condensate (EBC), blood, and urine samples were collected pre- and post-exposure to measure one oxidative stress marker, i.e., thiobarbituric acid reactive substances (TBARS), and two biomarkers of antioxidant capacity, i.e., ferric-reducing antioxidant power (FRAP) and reduced glutathione (GSH) by spectrophotometry. Spirometry and fractional exhaled nitric oxide (FeNO) were used to evaluate the effect of acute inhalational exposure. RESULTS: Mean mass of dental nanocomposite ground away was 0.88 ± 0.32 g. Average individual doses of respirable particles and nanoparticles measured by PENS were 380 ± 150 and 3.3 ± 1.3 μg, respectively. No significant increase of the post-exposure oxidative stress marker TBARS in EBC and plasma was seen. No decrease in antioxidant capacity biomarkers FRAP and GSH in EBC post-exposure was seen, either. Post-exposure, conjunctival hyperemia was seen in 62.5% volunteers; however, no impairment in spirometry or FeNO results was observed. No correlation of any biomarker measured with individual exposure was found, however, several correlations with interfering factors (age, body mass index, hypertension, dyslipidemia, and environmental pollution parameters) were seen. CONCLUSIONS: This study, using oxidative stress biomarker and antioxidant capacity biomarkers in biological fluids of volunteers during the grinding of dental nanocomposites did not prove a negative effect of this intense short-term exposure. However, further studies are needed to evaluate oxidative stress in long-term exposure of both stomatologists and patients and diverse populations with varying health statuses.
- MeSH
- antioxidancia analýza MeSH
- biologické markery * analýza MeSH
- dechové testy MeSH
- dospělí MeSH
- glutathion analýza MeSH
- inhalační expozice * škodlivé účinky analýza MeSH
- látky reagující s kyselinou thiobarbiturovou analýza MeSH
- lidé MeSH
- nanokompozity * chemie MeSH
- oxid dusnatý analýza metabolismus MeSH
- oxidační stres * MeSH
- pracovní expozice * analýza škodlivé účinky MeSH
- zubní lékaři MeSH
- zubní materiály MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Telomere length is a biomarker of cellular aging, influenced by various environmental and lifestyle factors. Air pollution is a known environmental stressor that may impact telomere dynamics. This study aimed to investigate the effect of age, lifetime exposure to air pollution, inflammatory parameters and selected lifestyle factors on telomere length. METHODS: The study included 356 participants aged 35-65 living in two regions with varying pollution. Telomere length was measured using qPCR. Individual lifetime exposures to PM10, PM2.5, NO2, benzo(a)pyrene and benzene were calculated based on historical air quality data. Statistical analysis of age, pollution exposure, inflammatory parameters, and lifestyle factors on telomere length was performed using logistic regression and generalized linear models, with odds ratios calculated. RESULTS: Unexpectedly, higher air pollutants lifetime exposures were associated with longer telomeres, particularly for PM10 51-55 μg/m3 (OR = 5.67, p < 0.001), PM2.5 42-45 μg/m3 (OR = 6.56, p < 0.001), B(a)P 6.9-8.3 ng/m3 (OR = 5.25, p = 0.002), NO2 26-27 μg/m3 (OR = 5.22, p = 0.001) and benzene 2.45-2.75 μg/m3 (OR = 6.13, p < 0.001). Age significantly affected telomere length, with older individuals having shorter telomeres. Socioeconomic factors such as college education were positively associated with longer telomeres, while lifestyle factors did not show significant associations. IL-8 was identified as a significant inflammatory marker negatively associated with very long telomeres. CONCLUSION: These baseline findings bring new perspective to the relationship between air pollution and telomere length. Contrary to traditional views, the results suggest potential adaptive responses, highlighting the need for further longitudinal research to explore telomere dynamics over time in conjunction with other factors.
- MeSH
- benzen analýza škodlivé účinky MeSH
- benzopyren analýza MeSH
- dospělí MeSH
- homeostáza telomer * MeSH
- kohortové studie MeSH
- látky znečišťující vzduch * analýza škodlivé účinky MeSH
- lidé středního věku MeSH
- lidé MeSH
- oxid dusičitý analýza MeSH
- pevné částice analýza škodlivé účinky MeSH
- senioři MeSH
- telomery * účinky léků MeSH
- vystavení vlivu životního prostředí * analýza škodlivé účinky MeSH
- životní styl MeSH
- znečištění ovzduší * škodlivé účinky analýza MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Accumulating evidence suggests that manganese oxide nanoparticles (NPs) show multiple enzyme-mimicking antioxidant activities, which supports their potential in redox-targeting therapeutic strategies for diseases with impaired redox signaling. However, the systemic administration of any NP requires thorough hemocompatibility testing. In this study, we assessed the hemocompatibility of synthesized Mn3O4 NPs, identifying their ability to induce spontaneous hemolysis and eryptosis or impair osmotic fragility. Concentrations of up to 20 mg/L were found to be safe for erythrocytes. Eryptosis assays were shown to be more sensitive than hemolysis and osmotic fragility as markers of hemocompatibility for Mn3O4 NP testing. Flow cytometry- and confocal microscopy-based studies revealed that eryptosis induced by Mn3O4 NPs was accompanied by Ca2+ overload, altered redox homeostasis verified by enhanced intracellular reactive oxygen species (ROS) and reactive nitrogen species (RNS), and a decrease in the lipid order of cell membranes. Furthermore, Mn3O4 NP-induced eryptosis was calpain- and caspase-dependent.
- MeSH
- buněčná membrána * metabolismus účinky léků MeSH
- eryptóza * účinky léků MeSH
- erytrocyty účinky léků metabolismus MeSH
- hemolýza účinky léků MeSH
- kalpain * metabolismus MeSH
- kaspasy * metabolismus MeSH
- lidé MeSH
- nanočástice * chemie MeSH
- oxidy * farmakologie chemie MeSH
- reaktivní formy dusíku * metabolismus MeSH
- reaktivní formy kyslíku * metabolismus MeSH
- sloučeniny manganu * farmakologie chemie MeSH
- vápník * metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Nitric oxide (NO)-stimulated cyclic guanosine monophosphate (cGMP) is a key regulator of cardiovascular health, as NO-cGMP signalling is impaired in diseases like pulmonary hypertension, heart failure and chronic kidney disease. The development of NO-independent sGC stimulators and activators provide a novel therapeutic option to restore altered NO signalling. sGC stimulators have been already approved for the treatment of pulmonary arterial hypertension (PAH), chronic thromboembolic pulmonary hypertension (CTEPH), and chronic heart failure (HFrEF), while sGC activators are currently in phase-2 clinical trials for CKD. The best characterized effect of increased cGMP via the NO-sGC-cGMP pathway is vasodilation. However, to date, none of the sGC agonists are in development for hypertension (HTN). According to WHO, the global prevalence of uncontrolled HTN continues to rise, contributing significantly to cardiovascular mortality. While there are effective antihypertensive treatments, many patients require multiple drugs, and some remain resistant to all therapies. Thus, in addition to improved diagnosis and lifestyle changes, new pharmacological strategies remain in high demand. In this review we explore the potential of sGC stimulators and activators as novel antihypertensive agents, starting with the overview of NO-sGC-cGMP signalling, followed by potential mechanisms by which the increase in cGMP may regulate vascular tone and BP. These effects may encompass not only acute vasodilation, but also mid-term and chronic effects, such as the regulation of salt and water balance, as well as mitigation of vascular ageing and remodelling. The main section summarizes the preclinical and clinical evidence supporting the BP-lowering efficacy of sGC agonists.
- MeSH
- agonisté guanylátcyklasy terapeutické užití farmakologie MeSH
- aktivátory enzymů terapeutické užití farmakologie MeSH
- antihypertenziva * terapeutické užití farmakologie MeSH
- guanosinmonofosfát cyklický * metabolismus MeSH
- hypertenze * farmakoterapie patofyziologie MeSH
- lidé MeSH
- oxid dusnatý metabolismus MeSH
- rozpustná guanylátcyklasa * metabolismus MeSH
- signální transdukce účinky léků MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Adverse events during the perinatal period are associated with an increased risk to develop cardiometabolic diseases later in life. We established a murine model to study long-term effects of perinatal hypoxia (PH) on the pulmonary circulation. We previously demonstrated that PH led to an impaired regulation of pulmonary vascular tone in adulthood, linked to alterations in K+ channels in males and in the nitric oxide (NO)/cyclic guanosine monophosphate pathway in females. Moreover, simultaneous administration of inhaled NO (iNO) during PH exposure prevented adverse effects of PH on adult pulmonary vasculature in females. The present study showed that PH induced a significant increase in right ventricular pressure in males and females, and an enhanced sensitivity to acute hypoxia in females. PH significantly reduced acetylcholine-induced relaxation in pulmonary artery, to a greater extent in females than in males. PH led to right ventricular hypertrophy in adulthood, appearing earlier in males than in females. Morphometric measurements showed a significant increase in the number of 25-75-μm pulmonary vessels in male lungs following PH, probably resulting in increased pulmonary vascular resistance. The effects of prolonged hypoxia in adulthood differed between males and females. Perinatal iNO during PH prevented PH-induced alterations in the cardiopulmonary system, whereas perinatal iNO alone could have some adverse effects. Therefore, PH led to long-lasting alterations in the regulation of adult pulmonary circulation, which vary between males and females. In males, the increased pulmonary vascular resistance was associated with morphological changes besides functional alterations, whereas females showed an important pulmonary vascular dysfunction. Keywords: Perinatal hypoxia, Pulmonary circulation, Endothelium-dependent relaxation, Phosphodiesterases, Sex differences.
- MeSH
- arteria pulmonalis metabolismus patofyziologie účinky léků MeSH
- cévní rezistence fyziologie MeSH
- hypoxie * patofyziologie metabolismus MeSH
- modely nemocí na zvířatech MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- novorozená zvířata MeSH
- oxid dusnatý metabolismus MeSH
- plicní oběh * fyziologie MeSH
- pohlavní dimorfismus MeSH
- sexuální faktory MeSH
- těhotenství MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Trimethylamine N-oxide (TMAO), a bioactive metabolite of gut microbes, plays a pivotal role in the pathogenesis of kidney diseases by activating programmed cell death (PCD) pathways. However, whether trimethylamine (TMA) contributes to chronic kidney injury and which kind of PCD is involved in TMA-induced chronic kidney injury has not been previously evaluated. To observe the effect of TMA, male C57BL/6J mice were randomly divided into two groups: the Control group and the TMA group. The mice in the TMA group were intraperitoneally injected with 100 micromol/kg/day TMA for three months, whereas the mice in the Control group were injected with normal saline for the same period. After three months, plasma creatinine and blood urea nitrogen levels, indicators of kidney function, increased significantly in the TMA group as compared with those in the Control group. Furthermore, Masson staining assay showed that TMA treatment led to a larger area of fibrosis than the Control group. TMA treatment did not change the Bax/Bcl-2 ratio, RIP1, RIP3 and MLKL phosphorylation, or iron and malondialdehyde levels in kidney tissues, indicating that apoptosis, ferroptosis and necroptosis were not involved in TMA-induced chronic kidney injury. However, compared with the Control group, TMA treatment significantly upregulated NLRP3, Caspase-1, IL-1beta, cleaved-Caspase 8, Caspase-8, and ZBP1 protein expression in kidney tissues. These results indicated that the ZBP1-NLRP3 inflammasome pathway was involved in TMA-induced chronic kidney injury. In conclusion, our studies revealed that the ZBP1-NLRP3 inflammasome may take part in the progression of TMA induced chronic kidney injury.
- MeSH
- chronická renální insuficience * metabolismus chemicky indukované patologie MeSH
- inflamasomy * metabolismus MeSH
- ledviny metabolismus účinky léků patologie MeSH
- methylaminy * metabolismus MeSH
- myši inbrední C57BL * MeSH
- myši MeSH
- protein NLRP3 * metabolismus MeSH
- signální transdukce * MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
The cardioprotective effect of ischemic preconditioning (IPC) and ischemic postconditioning (IPoC) in adult hearts is mediated by nitric oxide (NO). During the early developmental period, rat hearts exhibit higher resistance to ischemia-reperfusion (I/R) injury, contain higher levels of serum nitrates, and their resistance cannot be further increased by IPC or IPoC. NOS blocker (L-NAME) lowers their high resistance. Wistar rat hearts (postnatal Days 1 and 10) were perfused according to Langendorff and exposed to 40 min of global ischemia followed by reperfusion with or without IPoC. NO and reactive oxygen species donors (DEA-NONO, SIN-1) and L-NAME were administered. Tolerance to ischemia decreased between Days 1 and 10. DEA-NONO (low concentrations) significantly increased tolerance to I/R injury on both Days 1 and 10. SIN-1 increased tolerance to I/R injury on Day 10, but not on Day 1. L-NAME significantly reduced resistance to I/R injury on Day 1, but actually increased resistance to I/R injury on Day 10. Cardioprotection by IPoC on Day 10 was not affected by either NO donors or L-NAME. It can be concluded that resistance of the neonatal heart to I/R injury is NO dependent, but unlike in adult hearts, cardioprotective interventions, such as IPoC, are most likely NO independent.
- MeSH
- donory oxidu dusnatého farmakologie MeSH
- ischemické přivykání metody MeSH
- ischemický postconditioning * metody MeSH
- krysa rodu rattus MeSH
- molsidomin farmakologie analogy a deriváty MeSH
- myokard metabolismus MeSH
- NG-nitroargininmethylester * farmakologie MeSH
- novorozená zvířata * MeSH
- oxid dusnatý * metabolismus MeSH
- potkani Wistar * MeSH
- reperfuzní poškození myokardu * prevence a kontrola metabolismus MeSH
- srdce účinky léků MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
INTRODUCTION: Patients who have sustained extensive burns frequently exhibit substantial damage to skeletal muscle and associated complications. The rehabilitation of these patients can be challenging due to the nature of the injury and the subsequent complications. Nevertheless, there is a possibility that functional proprioceptive stimulation (illusory movements) may facilitate effective rehabilitation in patients with limited physiotherapy options. Nevertheless, this approach has yet to be tested in patients with burn injuries. MATERIAL AND METHODOLOGY: A prospective, randomised, crossover trial was conducted at a burn centre in a tertiary teaching hospital. The objective was to assess the effects of illusory movements on energy metabolism, insulin sensitivity, and skeletal muscle biology in adult critically ill patients with deep burns covering 30 % or more of the total body surface area. Two 30-minute daily sessions of functional proprioceptive stimulation were administered in addition to the standard physical therapy or physical activity regimen. Subsequently, the patients proceeded to the next stage of the trial, which involved a two-week crossover period. MEASUREMENTS AND MAIN RESULTS: Daily indirect calorimetry and calculation of nitrogen balance. Skeletal muscle biopsies from vastus lateralis for high resolution respirometry and euglycemic clamps to assess whole body glucose disposal were performed three times: at baseline and then fortnightly after each intervention period. The intervention was feasible and well tolerated in both early and late stages of burn disease. It did not change energy expenditure (mean change -33 [95 % CI: -292;+227] kcal .24 h-1, p = 0.79), nitrogen balance (+2.0 [95 % CI: -3.1;+7.1] g N .1.73 m-2 BSA .24 h-1), or insulin sensitivity (mean change of insulin-mediated glucose disposal -0.33 [95 % CI: -1.18;+0.53] mmol.h-1). At the cellular level, the intervention increased the capacity of mitochondria to synthesize ATP by aerobic phosphorylation and tended to increase mitochondrial coupling. Functional capacities of fatty acid oxidation and electron transfer chain complexes I, II, and IV were unaffected. CONCLUSIONS: Compared to physical therapy alone, two daily sessions of functional proprioceptive stimulation in addition to usual physical therapy in patients with extensive burns did not change energy expenditure, insulin sensitivity, nitrogen balance, or energy substrate oxidation. At cellular level, the intervention improved the capacity of aerobic phosphorylation in skeletal muscle mitochondria. Clinical effects remain to be demonstrated in adequately powered trials.
- MeSH
- dospělí MeSH
- energetický metabolismus * fyziologie MeSH
- inzulinová rezistence fyziologie MeSH
- klinické křížové studie * MeSH
- kosterní svaly * metabolismus patofyziologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- nepřímá kalorimetrie MeSH
- popálení * metabolismus terapie rehabilitace patofyziologie komplikace MeSH
- povrch těla MeSH
- propriocepce fyziologie MeSH
- prospektivní studie MeSH
- techniky fyzikální terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- randomizované kontrolované studie MeSH
Persons living in industrial environments are exposed to levels of air pollution that can affect their health and fertility. The Czech capital city, Prague, and the Ostrava industrial agglomeration differ in their major sources of air pollution. In Prague, heavy traffic produces high levels of nitrogen oxides throughout the year. In the Ostrava region, an iron industry and local heating are sources of particulate matter (PM) and benzo[a]pyrene (B[a]P), especially in the winter. We evaluated the effects of air pollution on human sperm mitochondrial DNA (mtDNA). Using real-time PCR, we analysed sperm mtDNA copy number and deletion rate in Prague city policemen in two seasons (spring and autumn) and compared the results with those from Ostrava. In Prague, the sperm mtDNA deletion rate was significantly higher in autumn than in spring, which is the opposite of the results from Ostrava. The sperm mtDNA copy number did not show any seasonal differences in either of the cities; it was correlated negatively with sperm concentration, motility, and viability, and with sperm chromatin integrity (assessed with the Sperm Chromatin Structure Assay). The comparison between the two cities showed that the sperm mtDNA deletion rate in spring and the sperm mtDNA copy number in autumn were significantly lower in Prague vs. Ostrava. Our study supports the hypothesis that sperm mtDNA deletion rate is affected by the composition of air pollution. Sperm mtDNA abundance is closely associated with chromatin damage and standard semen characteristics.
- MeSH
- dospělí MeSH
- látky znečišťující vzduch toxicita škodlivé účinky MeSH
- lidé MeSH
- mitochondriální DNA * genetika MeSH
- motilita spermií účinky léků MeSH
- pevné částice toxicita škodlivé účinky MeSH
- policie MeSH
- roční období MeSH
- spermie * účinky léků MeSH
- variabilita počtu kopií segmentů DNA * MeSH
- znečištění ovzduší * škodlivé účinky MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
- Geografické názvy
- Česká republika MeSH
The paper reports a low-cost handheld source of a cold air plasma intended for biomedical applications that can be made by anyone (detailed technical information and a step-by-step guide for creating the NTP source are provided). The plasma source employs a 1.4 W corona discharge in the needle-to-cone electrode configuration and is an extremely simple device, consisting basically of two electrodes and a cheap power supply. To achieve the best bactericidal effect, the plasma source has been optimized on Escherichia coli. The bactericidal ability of the plasma source was further tested on a wide range of microorganisms: Staphylococcus aureus as a representative of gram-positive bacteria, Pseudomonas aeruginosa as gram-negative bacteria, Candida albicans as yeasts, Trichophyton interdigitale as microfungi, and Deinococcus radiodurans as a representative of extremophilic bacteria resistant to many DNA-damaging agents, including ultraviolet and ionizing radiation. The testing showed that the plasma source inactivates all the microorganisms tested in several minutes (up to 105-107 CFU depending on a microorganism), proving its effectiveness against a wide spectrum of pathogens, in particular microfungi, yeasts, gram-positive and gram-negative bacteria. Studies of long-lived reactive species such as ozone, nitrogen oxides, hydrogen peroxide, nitrite, and nitrate revealed a strong correlation between ozone and the bactericidal effect, indicating that the bactericidal effect should generally be attributed to reactive oxygen species. This is the first comprehensive study of the bactericidal effect of a corona discharge in air and the formation of long-lived reactive species by the discharge, depending on both the interelectrode distance and the discharge current.