Potápění na nádech je každému plavci dostupná sportovní aktivita nevyžadující žádné mimořádné technické vybavení. Ve své závodní podobě má potápění na nádech (také apnoické potápění či freediving) řadu disciplín, v nichž potápěči soutěží jednak v bazénu, jednak ve venkovních přírodních vodách. Nejzávažnějším rizikem je náhlá a nepozorovaná ztráta vědomí, tzv. potápěčský blackout. Ten může mít letální následky, pokud se potápěči nedostane okamžité pomoci. Zásadními preventivními opatřeními těchto příhod je nepotápět se nikdy bez dohledu druhé osoby, nehyperventilovat před ponořením pod vodní hladinu a případně absolvovat potápěčský kurz pod dohledem certifikovaného profesionálního instruktora.

Breath-hold diving is a sport activity available to every swimmer, not requiring any special technical equipment. In its competitive form, brath-hold diving (also apnea diving or freediving) has a number of disciplines in which divers compete both in the pool and in the outdoor natural waters. The most serious risk is a sudden and unobserved loss of consciousness, the so-called diving blackout. It can have lethal consequences if the diver does not get immediate help. The basic preventive measures of these events are never to dive without the supervision of another person, never to hyperventilate before immersion below the water surface and possibly complete a diving course under the supervision of a certified professional instructor.

• MeSH
• apnoe etiologie   mortalita   patofyziologie   MeSH
• hypoxie etiologie   mortalita   patologie   MeSH
• lidé MeSH
• poškození plic etiologie   patofyziologie   prevence a kontrola   MeSH
• potápění * škodlivé účinky   MeSH
• rizikové faktory MeSH
• zadržování dechu MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH
• přehledy MeSH

Pulmonary hypertension is a group of disorders characterized by elevated mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance. To test our hypothesis that combining two drugs useful in experimental pulmonary hypertension, statins and dehydroepiandrosterone sulfate (DHEA S), is more effective than either agent alone, we induced pulmonary hypertension in adult male rats by exposing them to hypoxia (10%O2) for 3 weeks. We treated them with simvastatin (60 mg/l) and DHEA S (100 mg/l) in drinking water, either alone or in combination. Both simvastatin and DHEA S reduced mPAP (froma mean±s.d. of 34.4±4.4 to 27.6±5.9 and 26.7±4.8 mmHg, respectively), yet their combination was not more effective (26.7±7.9 mmHg). Differences in the degree of oxidative stress (indicated by malondialdehydeplasma concentration),the rate of superoxide production (electron paramagnetic resonance), or blood nitric oxide levels (chemiluminescence) did not explain the lack of additivity of the effect of DHEA S and simvastatin on pulmonary hypertension. We propose that the main mechanism of both drugs on pulmonary hypertension could be their inhibitory effect on 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase, which could explain their lack of additivity.

• MeSH
• arteria pulmonalis MeSH
• dehydroepiandrosteron farmakologie   terapeutické užití   MeSH
• dehydroepiandrosteronsulfát MeSH
• hypoxie komplikace   farmakoterapie   patologie   MeSH
• krysa rodu rattus MeSH
• plicní hypertenze * farmakoterapie   MeSH
• simvastatin farmakologie   terapeutické užití   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Hypoxia is one of the major pathological factors affecting brain function. The aim of the present study was to describe the effect of neonatal hypobaric hypoxia on the behavior of rats and to analyze its effect on hippocampal neurodegeneration. Hypobaric hypoxia at a simulated altitude of 9000 m was induced for one hour in neonatal rat pups (PND7 and PND9) of both sexes. Subsequently, the rats underwent behavioral testing on PND25 and PND35 using a LABORAS apparatus to assess spontaneous behavior. Hypoxia did not cause any morphological damage in the hippocampus of rats. However, hypoxia on PND7 led to less horizontal locomotor activity both, in males (on PND25) and females (on PND35). Hypoxia on PND9 led to higher rearing in females on PND25. Hypoxic males exhibited higher grooming activity, while females lower grooming activity on PND35 following hypoxia induced on PND7. In females, hypoxia on PND9 resulted in higher grooming activity on PND25. Sex differences in the effect of hypoxia was observed on PND35, when hypoxic males compared to hypoxic females displayed more locomotor, rearing and grooming activity. Our data suggest that hypoxia on PND7 versus PND9 differentially affects locomotion and grooming later in adolescence and these effects are sex-dependent.

• MeSH
• hipokampus patologie   MeSH
• hypoxie patologie   psychologie   MeSH
• lokomoce * MeSH
• novorozená zvířata MeSH
• péče o zevnějšek u zvířat * MeSH
• pohlavní dimorfismus MeSH
• potkani Wistar MeSH
• věkové faktory MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

The reason why a few myeloma cells egress from the bone marrow (BM) into peripheral blood (PB) remains unknown. Here, we investigated molecular hallmarks of circulating tumor cells (CTCs) to identify the events leading to myeloma trafficking into the bloodstream. After using next-generation flow to isolate matched CTCs and BM tumor cells from 32 patients, we found high correlation in gene expression at single-cell and bulk levels (r ≥ 0.94, P = 10-16), with only 55 genes differentially expressed between CTCs and BM tumor cells. CTCs overexpressed genes involved in inflammation, hypoxia, or epithelial-mesenchymal transition, whereas genes related with proliferation were downregulated in CTCs. The cancer stem cell marker CD44 was overexpressed in CTCs, and its knockdown significantly reduced migration of MM cells towards SDF1-α and their adhesion to fibronectin. Approximately half (29/55) of genes differentially expressed in CTCs were prognostic in patients with newly-diagnosed myeloma (n = 553; CoMMpass). In a multivariate analysis including the R-ISS, overexpression of CENPF and LGALS1 was significantly associated with inferior survival. Altogether, these results help understanding the presence of CTCs in PB and suggest that hypoxic BM niches together with a pro-inflammatory microenvironment induce an arrest in proliferation, forcing tumor cells to circulate in PB and seek other BM niches to continue growing.

• MeSH
• epitelo-mezenchymální tranzice genetika   MeSH
• exprese genu genetika   MeSH
• genetická transkripce genetika   MeSH
• hypoxie genetika   patologie   MeSH
• kostní dřeň patologie   MeSH
• lidé MeSH
• mnohočetný myelom genetika   patologie   MeSH
• nádorové buněčné linie MeSH
• nádorové cirkulující buňky patologie   MeSH
• nádorové kmenové buňky patologie   MeSH
• nádorové mikroprostředí genetika   MeSH
• pohyb buněk genetika   MeSH
• prognóza MeSH
• proliferace buněk genetika   MeSH
• zánět genetika   patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Obstructive sleep apnea (OSA) has been demonstrated to be implicated in disorder of insulin secretion and diabetes mellitus. In this study, we aimed to evaluate the protective role of tempol, a powerful antioxidant, in chronic intermittent hypoxia (IH)-induced pancreatic injury. The rat model of OSA was established by IH exposure. The pathological changes, increased blood-glucose level, and raised proinsulin/insulin ratio in pancreatic tissues of rats received IH were effectively relieved by tempol delivery. In addition, the enhanced levels of pro-inflammatory cytokines, TNF-alpha, IL-1beta, IL-6, and inflammatory mediators, PGE2, cyclooxygenase-2 (COX-2), NO, and inducible nitric oxide synthase (iNOS) in pancreatic tissue were suppressed by tempol. Moreover, tempol inhibited IH-induced apoptosis in pancreatic tissue as evidenced by upregulated Bcl-2 level, and downregulated Bax and cleaved caspase-3 levels. Finally, the abnormal activation of mitogen-activated protein kinase (MAPK) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB) signaling pathways induced by IH was restrained by tempol administration. In summary, our study demonstrates that tempol relieves IH-induced pancreatic injury by inhibiting inflammatory response and apoptosis, which provides theoretical basis for tempol as an effective treatment for OSA-induced pancreatic injury.

• MeSH
• antioxidancia farmakologie   terapeutické užití   MeSH
• apoptóza účinky léků   fyziologie   MeSH
• cyklické N-oxidy farmakologie   terapeutické užití   MeSH
• hypoxie farmakoterapie   metabolismus   patologie   MeSH
• krysa rodu rattus MeSH
• mediátory zánětu antagonisté a inhibitory   metabolismus   MeSH
• obstrukční spánková apnoe farmakoterapie   metabolismus   patologie   MeSH
• pankreas účinky léků   metabolismus   patologie   MeSH
• potkani Wistar MeSH
• spinové značení MeSH
• zánět farmakoterapie   metabolismus   patologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Pulmonary arterial hypertension (PAH) remains a disease with limited therapeutic options and dismal prognosis. Despite its etiologic heterogeneity, the underlying unifying pathophysiology is characterized by increased vascular tone and adverse remodeling of the pulmonary circulation. Myeloperoxidase (MPO), an enzyme abundantly expressed in neutrophils, has potent vasoconstrictive and profibrotic properties, thus qualifying as a potential contributor to this disease. Here, we sought to investigate whether MPO is causally linked to the pathophysiology of PAH. Investigation of 2 independent clinical cohorts revealed that MPO plasma levels were elevated in subjects with PAH and predicted adverse outcome. Experimental analyses showed that, upon hypoxia, right ventricular pressure was less increased in Mpo-/- than in WT mice. The hypoxia-induced activation of the Rho-kinase pathway, a critical subcellular signaling pathway yielding vasoconstriction and structural vascular remodeling, was blunted in Mpo-/- mice. Mice subjected to i.v. infusion of MPO revealed activation of Rho-kinase and increased right ventricular pressure, which was prevented by coinfusion of the Rho-kinase inhibitor Y-27632. In the Sugen5416/hypoxia rat model, PAH was attenuated by the MPO inhibitor AZM198. The current data demonstrate a tight mechanistic link between MPO, the activation of Rho-kinase, and adverse pulmonary vascular function, thus pointing toward a potentially novel avenue of treatment.

• MeSH
• amidy aplikace a dávkování   MeSH
• arteria pulmonalis patologie   patofyziologie   MeSH
• dospělí MeSH
• hypoxie krev   etiologie   patologie   MeSH
• intravenózní infuze MeSH
• Kaplanův-Meierův odhad MeSH
• kinázy asociované s rho antagonisté a inhibitory   metabolismus   MeSH
• kohortové studie MeSH
• krysa rodu rattus MeSH
• lidé středního věku MeSH
• lidé MeSH
• modely nemocí na zvířatech MeSH
• myši inbrední C57BL MeSH
• myši knockoutované MeSH
• myši MeSH
• peroxidasa aplikace a dávkování   krev   metabolismus   MeSH
• plíce patologie   MeSH
• plicní hypertenze krev   mortalita   patologie   patofyziologie   MeSH
• potkani Sprague-Dawley MeSH
• pyridiny aplikace a dávkování   MeSH
• rekombinantní proteiny aplikace a dávkování   krev   metabolismus   MeSH
• remodelace cév účinky léků   fyziologie   MeSH
• vazokonstrikce účinky léků   fyziologie   MeSH
• zvířata MeSH
• Check Tag
• dospělí MeSH
• krysa rodu rattus MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

Obesity and insulin resistance are closely associated with chronic inflammation in adipose tissue, where macrophages play an important role. Adipose tissue macrophages can be divided into two main phenotypes: the classical M1 macrophages and alternatively activated macrophages M2. M1 macrophages produce pro-inflammatory cytokines (TNF-α, interleukin IL-6 and MCP-1) and thus contribute to the development of insulin resistance. On the other hand, M2 macrophages, anti-inflammatory, are involved in the maintenance of tissue homeostasis and are typical in the adipose tissue of slender individuals. Macrophages can also play a role in the pathogenesis of other serious illnesses such as cardiovascular diseases or cancer. This article reviews the latest data on macrophage polarization in adipose tissue.

• MeSH
• chemokin CCL2 metabolismus   MeSH
• fenotyp MeSH
• hypoxie metabolismus   patologie   MeSH
• interleukin-6 metabolismus   MeSH
• inzulinová rezistence fyziologie   MeSH
• lidé MeSH
• makrofágy patologie   MeSH
• obezita metabolismus   patologie   MeSH
• TNF-alfa metabolismus   MeSH
• tuková tkáň patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

• MeSH
• chemoreceptory fyziologie   MeSH
• hypoxie plodu patologie   MeSH
• hypoxie * etiologie   klasifikace   patologie   MeSH
• ischemická choroba srdeční MeSH
• lidé MeSH
• mozková hypoxie patofyziologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH

Pheochromocytomas (PHEOs) and paragangliomas (PGLs) are rare, neuroendocrine tumors derived from adrenal or extra-adrenal chromaffin cells, respectively. Metastases are discovered in 3-36% of patients at the time of diagnosis. Currently, only suboptimal treatment options exist. Therefore, new therapeutic compounds targeting metastatic PHEOs/PGLs are urgently needed. Here, we investigated if anthracyclines were able to suppress the progression of metastatic PHEO. We explored their effects on experimental mouse PHEO tumor cells using in vitro and in vivo models, and demonstrated that anthracyclines, particularly idarubicin (IDA), suppressed hypoxia signaling by preventing the binding of hypoxia-inducible factor 1 and 2 (HIF-1 and HIF-2) to the hypoxia response element (HRE) sites on DNA. This resulted in reduced transcriptional activation of HIF target genes, including erythropoietin (EPO), phosphoglycerate kinase 1 (PGK1), endothelin 1 (EDN1), glucose transporter 1 (GLUT1), lactate dehydrogenase A (LDHA), and vascular endothelial growth factor (VEGFA), which consequently inhibited the growth of metastatic PHEO. Additionally, IDA downregulated hypoxia signaling by interfering with the transcriptional activation of HIF1A and HIF2A. Furthermore, our animal model demonstrated the dose-dependent suppressive effect of IDA on metastatic PHEO growth in vivo. Our results indicate that anthracyclines are prospective candidates for inclusion in metastatic PHEO/PGL therapy, especially in patients with gene mutations involved in the hypoxia signaling pathway.

• MeSH
• antitumorózní látky terapeutické užití   MeSH
• buňky - růstové procesy účinky léků   MeSH
• endotelin-1 genetika   metabolismus   MeSH
• erythropoetin genetika   metabolismus   MeSH
• faktor 1 indukovatelný hypoxií - podjednotka alfa metabolismus   MeSH
• feochromocytom farmakoterapie   patologie   MeSH
• fosfoglycerátkinasa genetika   metabolismus   MeSH
• hypoxie farmakoterapie   patologie   MeSH
• idarubicin terapeutické užití   MeSH
• lidé MeSH
• metastázy nádorů MeSH
• myši nahé MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• nádory nadledvin farmakoterapie   patologie   MeSH
• signální transdukce účinky léků   MeSH
• transkripční faktory bHLH metabolismus   MeSH
• vazba proteinů MeSH
• xenogenní modely - testy antitumorózní aktivity MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Chronic hypoxia and exercise are natural stimuli that confer sustainable cardioprotection against ischemia-reperfusion (I/R) injury, but it is unknown whether they can act in synergy to enhance ischemic resistance. Inflammatory response mediated by tumor necrosis factor-α (TNF-α) plays a role in the infarct size limitation by continuous normobaric hypoxia (CNH), whereas exercise is associated with anti-inflammatory effects. This study was conducted to determine if exercise training performed under conditions of CNH (12% O2) affects myocardial ischemic resistance with respect to inflammatory and redox status. Adult male Wistar rats were assigned to one of the following groups: normoxic sedentary, normoxic trained, hypoxic sedentary, and hypoxic trained. ELISA and Western blot analysis, respectively, were used to quantify myocardial cytokines and the expression of TNF-α receptors, nuclear factor-κB (NF-κB), and selected components of related signaling pathways. Infarct size and arrhythmias were assessed in open-chest rats subjected to I/R. CNH increased TNF-α and interleukin-6 levels and the expression of TNF-α type 2 receptor, NF-κB, inducible nitric oxide synthase (iNOS), cytosolic phospholipase A2α, cyclooxygenase-2, manganese superoxide dismutase (MnSOD), and catalase. None of these effects occurred in the normoxic trained group, whereas exercise in hypoxia abolished or significantly attenuated CNH-induced responses, except for NF-κB, iNOS, and MnSOD. Both CNH and exercise reduced infarct size, but their combination provided the same degree of protection as CNH alone. In conclusion, exercise training does not amplify the cardioprotection conferred by CNH. High ischemic tolerance of the CNH hearts persists after exercise, possibly by maintaining the increased antioxidant capacity despite attenuating TNF-α-dependent protective signaling.NEW & NOTEWORTHYChronic hypoxia and regular exercise are natural stimuli that confer sustainable myocardial protection against acute ischemia-reperfusion injury. Signaling mediated by TNF-α via its type 2 receptor plays a role in the cardioprotective mechanism of chronic hypoxia. In the present study, we found that exercise training of rats during adaptation to hypoxia does not amplify the infarct size-limiting effect. Ischemia-resistant phenotype is maintained in the combined hypoxia-exercise setting despite exercise-induced attenuation of TNF-α-dependent protective signaling.

• MeSH
• cyklooxygenasa 2 metabolismus   MeSH
• fyzická vytrvalost fyziologie   MeSH
• fyziologická adaptace fyziologie   MeSH
• hypoxie metabolismus   patologie   MeSH
• interleukin-6 metabolismus   MeSH
• kondiční příprava zvířat fyziologie   MeSH
• krysa rodu rattus MeSH
• myokard metabolismus   patologie   MeSH
• NF-kappa B metabolismus   MeSH
• potkani Wistar MeSH
• receptory TNF - typ II metabolismus   MeSH
• reperfuzní poškození myokardu metabolismus   patofyziologie   MeSH
• superoxiddismutasa metabolismus   MeSH
• synthasa oxidu dusnatého, typ II metabolismus   MeSH
• TNF-alfa metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH