Increased oxidative stress in the brain during the course of Alzheimer's disease (AD) leads to an imbalance of antioxidants and formation of free radical reaction end-products which may be detected in blood as fluorescent lipofuscin-like pigments (LFPs). The aim of this study was to evaluate and compare LFPs with plasma selenium concentrations representing an integral part of the antioxidant system. Plasma samples from subjects with AD dementia (ADD; n=11), mild cognitive impairment (MCI; n=17) and controls (n=12), were collected. The concentration of selenium was measured using atomic absorption spectroscopy. LFPs were analyzed by fluorescence spectroscopy and quantified for different fluorescent maxima and then correlated with plasma selenium. Lower levels of selenium were detected in MCI and ADD patients than in controls (P=0.003 and P=0.049, respectively). Additionally, higher fluorescence intensities of LFPs were observed in MCI patients than in controls in four fluorescence maxima and higher fluorescence intensities were also observed in MCI patients than in ADD patients in three fluorescence maxima, respectively. A negative correlation between selenium concentrations and LFPs fluorescence was observed in the three fluorescence maxima. This is the first study focused on correlation of plasma selenium with specific lipofuscin-like products of oxidative stress in plasma of patients with Alzheimer´s disease and mild cognitive impairment.

• MeSH
• Alzheimerova nemoc krev   diagnóza   patofyziologie   psychologie   MeSH
• biologické markery krev   MeSH
• fluorescenční spektrometrie MeSH
• kognitivní dysfunkce krev   diagnóza   patofyziologie   psychologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lipofuscin krev   MeSH
• mozek metabolismus   patofyziologie   MeSH
• oxidační stres * MeSH
• peroxidace lipidů * MeSH
• selen krev   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• spektrofotometrie atomová MeSH
• studie případů a kontrol MeSH
• testy pro posouzení mentálních funkcí a demence MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH

Alzheimerova choroba je závažné neurodegenerativní one­mocnění a nejčastější příčina demence v populaci nad 60 let. Ukládání betaamyloidu a tvorba neurofibrilárních klubek v mozku předchází vznik demence o mnoho let. Neúspěch léčby omezující ukládání betaamyloidu vede k přehodnocování teorií o patofyziologii tohoto onemocnění. V této souvislosti se výzkum zaměřuje na roli zánětu jako spouštěcího momentu i doprovodného procesu neurodegenerace. V našem článku shrneme některé poznatky týkající se imunitních funkcí jednotlivých buněk mozku a jejich vztahu ke vzniku a rozvoji Alzheimerovy choroby ve světle hypotézy imunitní reakce.

Alzheimer's disease is a severe neurodegenerative disorder and the most common cause of dementia in the population above 60 years of age. Beta-amyloid accumulation and neurofibrillary tangles formation in the brain precedes the development of Alzheimer's dementia by many years. As beta-amyloid accumulation inhibition failed as a treatment option, the theories on the Alzheimer's disease pathophysio­lo­gy are being revised. In this context, research targets the role of inflammation as the possible trigger mechanism and accompanying process of neurodegeneration. This article summarizes some knowledge of the immune function of brain cells and its potential relation to Alzheimer's disease progression in the light of the immune reaction hypothesis.

• Klíčová slova
• imunitní odpověď,
• MeSH
• aktivace komplementu imunologie   MeSH
• Alzheimerova nemoc * etiologie   imunologie   patofyziologie   MeSH
• astrocyty fyziologie   imunologie   MeSH
• centrální nervový systém imunologie   MeSH
• imunitní systém - jevy * MeSH
• lidé MeSH
• membranolytický komplex MeSH
• mikroglie fyziologie   imunologie   MeSH
• neurony MeSH
• oligodendroglie fyziologie   MeSH
• zánět * imunologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

Alzheimer's disease (AD) is a severe neurodegenerative disorder characterized by cognitive decline. Prodromal stage of AD, also called mild cognitive impairment (MCI), especially its amnestic type (aMCI), precedes dementia stage of AD. There are currently no reliable diagnostic biomarkers of AD in the blood. Alzheimer's disease is accompanied by increased oxidative stress in brain, which leads to oxidative damage and accumulation of free radical reaction end-products. In our study, specific products of lipid peroxidation in the blood of AD patients were studied. Lipophilic extracts of erythrocytes (AD dementia = 19, aMCI = 27, controls = 16) and plasma (AD dementia = 11, aMCI = 17, controls = 16) were analysed by fluorescence spectroscopy. The level of these products is significantly increased in erythrocytes and plasma of AD dementia and aMCI patients versus controls. We concluded that oxidative stress end-products are promising new biomarkers of AD, but further detailed characterisation of these products is needed.

• MeSH
• Alzheimerova nemoc krev   MeSH
• erytrocyty metabolismus   MeSH
• fluorescenční spektrometrie MeSH
• lidé středního věku MeSH
• lidé MeSH
• lipidy krev   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Isolated beef heart mitochondria have been exposed to tert-butyl hydroperoxide (tBHP) and peroxynitrite (PeN) in order to model the effects of reactive oxygen and nitrogen species on mitochondria in vivo. The formation of malondialdehyde (MDA), protein carbonyls, lipofuscin-like pigments (LFP), and nitrotyrosine was studied during incubations with various concentrations of oxidants for up to 24 h. The oxidants differed in their ability to oxidize particular substrates. Fatty acids were more sensitive to the low concentrations of tBHP, whereas higher concentrations of PeN consumed MDA. Oxidation of proteins producing carbonyls had different kinetics and also a probable mechanism with tBHP or PeN. Diverse proteins were affected by tBHP or PeN. In both cases, prolonged incubation led to the appearance of proteins with molecular weights lower than 29 kDa bearing carbonyl groups that might have been caused by protein fragmentation. PeN induced nitration of protein tyrosines that was more intensive in the soluble proteins than in the insoluble ones. LFP, the end products of lipid peroxidation, were formed more readily by PeN. On the other hand, fluorometric and chromatographic techniques have confirmed destruction of LFP by higher PeN concentrations. This is a unique feature that has not been described so far for any oxidant.

• MeSH
• kyselina peroxydusitá MeSH
• reaktivní formy dusíku metabolismus   MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• skot MeSH
• srdeční mitochondrie metabolismus   MeSH
• terc-butylhydroperoxid MeSH
• zvířata MeSH
• Check Tag
• skot MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH

Oxidační stres je do určité míry fyziologickým důsledkem řady biochemických a bioenergetických pochodů a doprovází aerobní organizmy po celý jejich život. Podílí se na přirozeném stárnutí organizmu a významnou úlohu zastává v imunologické odpovědi. Každý organizmus má vyvinutý komplexní antioxidační systém, který ho chrání před radikálovým poškozením. Selhání tohoto vysoce specializovaného systému může vést k nevratnému poškození biomolekul a závažně tím poškodit jejich fyziologické funkce. Radikálové poškození a ztráta funkcí mozkových buněk je charakteristická pro neurodegenerativní onemocnění jako Alzheimerova choroba (ACH). To je důvod, proč se zvýšený oxidační stres považuje za iniciální impulz vzniku tohoto závažného progredientního onemocnění. Článek podává přehled patobiochemických mechanizmů oxidačního stresu v mozkové tkáni doprovázejících rozvoj Alzheimerovy choroby.

Oxidative stress is to some extent a physiological consequence of biochemical and bioenergetic processes and accompanies aerobic organisms throughout their lives. Oxidative stress contributes to the natural aging and plays an important role in the immune response. Each organism has developed a complex system of antioxidant defense which protects it against the free radical damage. The failure of this highly specialized system can lead to irreversible damage to biomolecules and thereby seriously damage their physiological functions. Radical damage and loss of functions of brain cells is characteristic of neurodegenerative diseases such as Alzheimer’s disease. This is the reason why the increased oxidative stress is thought to be the initial impetus for developing this progressive disease. This article brings an overview of pathobiochemical mechanisms of oxidative stress in the brain tissue that accompany progression of Alzheimer´s disease.

• MeSH
• Alzheimerova nemoc * patofyziologie   MeSH
• biochemické jevy MeSH
• imunitní systém - jevy fyziologie   MeSH
• lidé MeSH
• lipidy chemie   MeSH
• neurodegenerativní nemoci patofyziologie   MeSH
• oxidační stres * MeSH
• patologie MeSH
• poškození DNA MeSH
• přechodné kovy chemie   MeSH
• proteiny chemie   MeSH
• reaktivní formy kyslíku MeSH
• sacharidy chemie   MeSH
• štěpení RNA MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH

Alzheimer's disease (AD) is accompanied by oxidative stress in the brain. Because the brain tissue is rich in polyunsaturated fatty acids, it is prone to the free radical attack resulting in lipid peroxidation. Intermediates of lipid peroxidation may diffuse from the primary site, cross the blood-brain barrier and modify erythrocyte membranes in the bloodstream. We exposed isolated erythrocyte membranes from patients with AD and the control group to in vitro free radical damage and monitored the accumulation of the end products of lipid peroxidation, lipofuscin-like pigments (LFPs), by fluorescence spectroscopy. LFPs were analyzed by means of tridimensional and synchronous fluorescence spectroscopy. The levels of LFP formed during in vitro peroxidation were significantly higher in erythrocyte membranes from patients with AD compared with the control group. Furthermore, the chemical composition of LFP in AD was different from the control group. The analysis of the specific modifications of erythrocyte membranes in AD is of great medical importance regarding the need of a diagnostic blood biomarker.

• MeSH
• Alzheimerova nemoc metabolismus   MeSH
• erytrocytární membrána metabolismus   MeSH
• lidé MeSH
• lipofuscin metabolismus   MeSH
• oxidační stres MeSH
• peroxidace lipidů MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Alzheimerova choroba (ACH) je charakterizována ukládáním amyloidu β (Aβ) v senilních placích a tvorbou neurofibrilárních tanglů v mozkové tkáni, což je následováno zánikem neuronů. Příčina vzniku a rozvoje ACH je stále nejasná, nicméně existují faktory, které k patogenezi této choroby přispívají. Bylo zjištěno, že lipidové složení mozkové tkáně, především zastoupení polynenasycených mastných kyselin (PUFA), významně ovlivňuje patologický proces. Například přítomnost kyseliny dokosahexaenové (DHA) působí ochranně proti rozvoji ACH. U pacientů s ACH je v mozku snížené množství DHA v důsledku oxidačního stresu. Vzhledem k oboustranné výměně mastných kyselin mezi mozkovou tkání a krví, ovlivňuje složení PUFA v mozkové tkáni a oxidační stres i zastoupení jednotlivých mastných kyselin v erytrocytech, což se dá potenciálně využít k diagnostickým účelům.

Alzheimer‘s disease (AD) is characterized by accumulation of amyloid β (Aβ) in senile plaques and formation of neurofibrillary tangles followed by neuronal damage. The primary cause of AD is still unclear. However, there are factors that contribute to its pathogenesis. It has been found that the brain lipid composition, mainly polyunsaturated fatty acids (PUFA), affects the pathological process in the brain. For example, docosahexaenoic acid (DHA) has protective effect against AD. Reduced amount of DHA as a result of oxidative stress has been documented in AD patients. The changes in the composition of brain PUFA are reflected in erythrocytes due to the exchange of fatty acids between brain and blood, which can be used for diagnostic purposes.

• MeSH
• Alzheimerova nemoc diagnóza   MeSH
• erytrocyty MeSH
• financování organizované MeSH
• kyseliny dokosahexaenové MeSH
• lidé MeSH
• mastné kyseliny MeSH
• mozková amyloidní angiopatie diagnóza   MeSH
• nenasycené mastné kyseliny MeSH
• peroxidace lipidů MeSH
• Check Tag
• lidé MeSH

The effect of three-day fasting on cardiac ischemic tolerance was investigated in adult male Wistar rats. Anesthetized open-chest animals (pentobarbitone 60 mg/kg, i.p.) were subjected to 20-min left anterior descending coronary artery occlusion and 3-h reperfusion for infarct size determination. Ventricular arrhythmias were monitored during ischemia and at the beginning (3 min) of reperfusion. Myocardial concentrations of beta-hydroxybutyrate and acetoacetate were measured to assess mitochondrial redox state. Short-term fasting limited the infarct size (48.5+/-3.3 % of the area at risk) compared to controls (74.3+/-2.2 %) and reduced the total number of premature ventricular complexes (12.5+/-5.8) compared to controls (194.9+/-21.9) as well as the duration of ventricular tachycardia (0.6+/-0.4 s vs. 18.8+/-2.5 s) occurring at early reperfusion. Additionally, fasting increased the concentration of beta-hydroxybutyrate and beta-hydroxybutyrate/acetoacetate ratio (87.8+/-27.0) compared to controls (7.9+/-1.7), reflecting altered mitochondrial redox state. It is concluded that three-day fasting effectively protected rat hearts against major endpoints of acute I/R injury. Further studies are needed to find out whether these beneficial effects can be linked to altered mitochondrial redox state resulting from increased ketogenesis.

• MeSH
• acetoacetáty metabolismus   farmakologie   MeSH
• infarkt myokardu metabolismus   veterinární   MeSH
• komorová tachykardie komplikace   MeSH
• krysa rodu rattus MeSH
• kyselina 3-hydroxymáselná metabolismus   farmakologie   MeSH
• mitochondrie metabolismus   MeSH
• oxidace-redukce MeSH
• potkani Wistar MeSH
• reperfuzní poškození myokardu metabolismus   veterinární   MeSH
• srdeční arytmie patofyziologie   veterinární   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Pulmonary hypertension resulting from chronic hypoxia is at least partly caused by the increased production of reactive oxygen species (ROS). The goal of the presented study was to investigate the dynamics and the site of production of ROS during chronic hypoxia. In our study Wistar rats were kept for 1, 4 and 21 days in an isobaric hypoxic chamber (FiO2=0.1), while controls stayed in normoxia. We compared NO production in expired air, plasma and perfusate drained from isolated rat lungs and measured superoxide concentration in the perfusate. We also detected the presence of superoxide products (hydrogen peroxide and peroxynitrite) and the level of ROS-induced damage expressed as the concentration of lipid peroxydation end products. We found that the production and release of ROS and NO during early phase of chronic hypoxia has specific timing and differs in various compartments, suggesting the crucial role of ROS interaction for development of hypoxic pulmonary hypertension.

• MeSH
• arteria pulmonalis metabolismus   MeSH
• hypoxie komplikace   metabolismus   MeSH
• krysa rodu rattus MeSH
• kyselina peroxydusitá metabolismus   MeSH
• oxid dusnatý biosyntéza   krev   MeSH
• peroxid vodíku metabolismus   MeSH
• plicní hypertenze etiologie   MeSH
• potkani Wistar MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• práce podpořená grantem MeSH

Alzheimer's disease (AD) represents a highly common form of dementia, but can be diagnosed in the earlier stages before dementia onset. Early diagnosis is crucial for successful therapeutic intervention. The introduction of new diagnostic biomarkers for AD is aimed at detecting underlying brain pathology. These biomarkers reflect structural or biochemical changes related to AD. Examination of cerebrospinal fluid has many drawbacks; therefore, the search for sensitive and specific blood markers is ongoing. Investigation is mainly focused on upstream processes, among which oxidative stress in the brain is of particular interest. Products of oxidative stress may diffuse into the blood and evaluating them can contribute to diagnosis of AD. However, results of blood oxidative stress markers are not consistent among various studies, as documented in this review. To find a specific biochemical marker for AD, we should concentrate on specific metabolic products formed in the brain. Specific fluorescent intermediates of brain lipid peroxidation may represent such candidates as the composition of brain phospholipids is unique. They are small lipophilic molecules and can diffuse into the blood stream, where they can then be detected. We propose that these fluorescent products are potential candidates for blood biomarkers of AD.

• MeSH
• Alzheimerova nemoc krev   diagnóza   patofyziologie   MeSH
• antioxidancia analýza   MeSH
• biologické markery krev   MeSH
• lidé MeSH
• mozek metabolismus   patofyziologie   MeSH
• nukleové kyseliny metabolismus   MeSH
• oxidační stres * MeSH
• peroxidace lipidů MeSH
• proteiny metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH