Naltrexón sa používa v liečbe závislosti od alkoholu v dávkach 50 mg naltrexóniumchloridu denne (v USA aj v liečbe závislosti od opioidov, orálne aj injekčne), v kombinácii s bupropiónom pri liečbe obezity. V nízkych dávkach (1-5 mg denne) sa špecificky viaže na TLR-4 receptory, kde pôsobí antagonisticky. Pôsobí protizápalovo prostredníctvom buniek mikroglie. Jeho nízke dávky redukujú syntézu faktoru nekrózy nádoru (TNF)-α a interferónu-β. Nízkodávkový naltrexón (LDN) je modulačným nástrojom neuroimunitnej osi, tá interferuje s neuroendokrinnou osou. Prechodne sa zvyšuje signalizácia opioidového rastového faktoru (OGFr). LDN pôsobí stereoselektívne. Podaním (+)-naltrexónu nie je zasiahnutá opioidná signalizácia, ale iba TLR-4 signalizácia. Je prínosom pri liečbe fibromyalgie, Crohnovej choroby, sklerózy multiplex, tumorov, pri chronickom benígnom pemphigu (Hailey-Hailey disease) aj Gulf War Illness. Ultranízke dávky naltrexónu (ULDN) sú nižšie ako 1 μg. Analgetický efekt sprostredkováva druhý posol filamín A Využíva sa hlavne v postoperačnej kontrole analgézie. Dávky medzi 1 μg a 1 mg sú veľmi nízke dávky naltrexónu (VLDN). Sú efektívne ako „add on“ pri metadónovej udržiavacej liečbe.
- MeSH
- hormeze účinky léků MeSH
- lidé MeSH
- naltrexon * aplikace a dávkování MeSH
- Check Tag
- lidé MeSH
The exposure of living organisms to environmental stress triggers defensive responses resulting in the activation of protective processes. Whenever the exposure occurs at low doses, defensive effects overwhelm the adverse effects of the exposure; this adaptive situation is referred to as "hormesis". Environmental, physical, and nutritional hormetins lead to the stimulation and strengthening of the maintenance and repair systems in cells and tissues. Exercise, heat, and irradiation are examples of physical hormetins, which activate heat shock-, DNA repair-, and anti-oxidative-stress responses. The health promoting effect of many bio-actives in fruits and vegetables can be seen as the effect of mildly toxic compounds triggering this adaptive stimulus. Numerous studies indicate that living organisms possess the ability to adapt to adverse environmental conditions, as exemplified by the fact that DNA damage and gene expression profiling in populations living in the environment with high levels of air pollution do not correspond to the concentrations of pollutants. The molecular mechanisms of the hormetic response include modulation of (a) transcription factor Nrf2 activating the synthesis of glutathione and the subsequent protection of the cell; (b) DNA methylation; and (c) microRNA. These findings provide evidence that hormesis is a toxicological event, occurring at low exposure doses to environmental stressors, having the benefit for the maintenance of a healthy status.
In our experiment, we deal with the phenomenon of radiation hormesis and improvements based on this phenomenon to different growing characteristics of the fast-growing, very feed-efficient, and with a high-yielding carcass hybrid of the Peking duck (Cherry Valley SM3 medium). In the first phase of the project, we exposed hatching duck eggs to low and middle doses of gamma radiation 60Co (0.06-2.00 Gy) before placing them into a setter in the hatchery. We then followed the standards of artificial incubation. The treatment of our chosen doses of gamma radiation has no significant influence on the history and results of hatching (from 85.5% to 92.6%); it was influenced only by the basic management and husbandry of the parent stock. From our observations we confirm that the Peking duck, despite genetic progress, retained its vitality and robustness. Its embryos are not damaged even with a dose of 2 Gy, which is over the deterministic effect of ionizing radiation for vertebrates. At the end of the fatting period a significant drop in plasma phosphorus levels was measured in the ducks; however, it was dependent on the radiation dose to which the hatching eggs were exposed (r = -0.965). A positive effect of radiation hormesis may be expected in the case of 1 Gy dose where the highest values of mean corpuscular hemoglobin, mean corpuscular hemoglobin, combined hemoglobin, and drake weight were measured. Lower and higher doses of ionizing radiation used did not display these effects.
- MeSH
- hormeze MeSH
- kachny fyziologie MeSH
- náhodné rozdělení MeSH
- ovum fyziologie účinky záření MeSH
- radioizotopy kobaltu aplikace a dávkování MeSH
- rozmnožování účinky záření MeSH
- vztah dávky záření a odpovědi MeSH
- záření gama * MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
It has been proposed that oxidative stress, elicited by high levels of reactive oxygen species, accelerates telomere shortening by erosion of telomeric DNA repeats. While most eukaryotes counteract telomere shortening by telomerase-driven addition of these repeats, telomeric loss in Drosophila is compensated by retrotransposition of the telomeric retroelements HeT-A, TART and TAHRE to chromosome ends. In this study we tested the effect of chronic exposure of flies to non-/sub-lethal doses of paraquat, which is a redox cycling compound widely used to induce oxidative stress in various experimental paradigms including telomere length analyses. Indeed, chronic paraquat exposure for five generations resulted in elevated transcriptional activity of both telomeric and non-telomeric transposable elements, and extended telomeric length in the tested fly lines. We propose that low oxidative stress leads to increased telomere length within Drosophila populations. For a mechanistic understanding of the observed phenomenon we discuss two scenarios: adaption, acting through a direct stimulation of telomere extension, or positive selection favoring individuals with longer telomeres within the population.
- MeSH
- Drosophila melanogaster účinky léků genetika MeSH
- genetická transkripce účinky léků MeSH
- homeostáza telomer účinky léků MeSH
- hormeze * MeSH
- paraquat farmakologie MeSH
- reaktivní formy kyslíku farmakologie MeSH
- retroelementy účinky léků MeSH
- telomery účinky léků fyziologie MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zkracování telomer účinky léků MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
The hallmarks of tumor tissue are not only genetic aberrations but also the presence of metabolic and oxidative stress as a result of hypoxia and lactic acidosis. The stress activates several prosurvival pathways including metabolic remodeling, autophagy, antioxidant response, mitohormesis, and glutaminolysis, whose upregulation in tumors is associated with a poor survival of patients, while their activation in healthy tissue with statins, metformin, physical activity, and natural compounds prevents carcinogenesis. This review emphasizes the dual role of stress response pathways in cancer and suggests the integrative understanding as a basis for the development of rational therapy targeting the stress response.
- MeSH
- antioxidancia metabolismus MeSH
- autofagie MeSH
- cvičení MeSH
- fyziologický stres fyziologie MeSH
- hormeze MeSH
- kalorická restrikce MeSH
- lidé MeSH
- mutageneze MeSH
- nádory etiologie prevence a kontrola terapie MeSH
- oxidační stres MeSH
- polyfenoly farmakologie MeSH
- zánět komplikace metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Klíčová slova
- dimethylrtuť, arzenik (utrejch),
- MeSH
- antitumorózní látky MeSH
- arsenikové přípravky * dějiny škodlivé účinky terapeutické užití MeSH
- dějiny lékařství MeSH
- hormeze * MeSH
- lidé MeSH
- methylortuťné sloučeniny škodlivé účinky terapeutické užití MeSH
- otrava arsenem MeSH
- otrava oxidem uhelnatým MeSH
- otrava rtutí MeSH
- oxid uhelnatý * škodlivé účinky terapeutické užití MeSH
- oxidy dějiny škodlivé účinky terapeutické užití MeSH
- rtuť * dějiny škodlivé účinky terapeutické užití MeSH
- toxikologie trendy MeSH
- tradiční lékařství MeSH
- xenobiotika škodlivé účinky terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- historické články MeSH
