- Intracellular pH Regulation in iPSCs-derived Astrocytes from Subjects with Chronic Mountain Sickness. [Journal Article]
- NNeuroscience 2018 Feb 10
- Chronic Mountain Sickness (CMS) occurs in high-altitude residents with major neurological symptoms such as migraine headaches, dizziness and cognitive deficits. Recent work demonstrated that highland...
Chronic Mountain Sickness (CMS) occurs in high-altitude residents with major neurological symptoms such as migraine headaches, dizziness and cognitive deficits. Recent work demonstrated that highlanders have increased intracellular pH (pHi) in their brain cells, perhaps for the sake of adaptation to hypoxemia and help to facilitate glycolysis, DNA synthesis, and cell cycle progression. Since there are well adapted (non-CMS) and maladapted (CMS) high-altitude dwellers, it is not clear whether pHiis differently regulated in these two high-altitude populations. In this work, we obtained induced pluripotent stem cell (iPSC)-derived astrocytes from both CMS and non-CMS highlanders who live in the Peruvian Andes (>14,000 ft) and studied pHiregulation in these astrocytes using pH-sensitive dye BCECF. Our results show that the steady-state pHi(ss pHi) is lower in CMS astrocytes compared with non-CMS astrocytes. In addition, the acid extrusion following an acid loading is faster and the pHidependence of H+flux rate becomes steeper in CMS astrocytes. Furthermore, the Na+dependency of ss pHiis stronger in CMS astrocytes and the Na+/H+exchanger (NHE) inhibitors blunted the acid extrusion in both CMS and non-CMS astrocytes. We conclude that (a) NHE contributes to the ss pHistabilization and mediates active acid extrusion during the cytosolic acidosis in highlanders; (b) acid extrusion becomes less pHisensitive in non-CMS (versus CMS) astrocytes which may prevent NHE from over-activated in the hypoxia-induced intracellular acidosis and render the non-CMS astrocytes more resistant to hypoxemia challenges.
- Ganglioside GM1 protects against high altitude cerebral edema in rats by suppressing the oxidative stress and inflammatory response via the PI3K/AKT-Nrf2 pathway. [Journal Article]
- MIMol Immunol 2018 Feb 08; 95:91-98
- High altitude cerebral edema (HACE) is a severe type of acute mountain sickness (AMS) that occurs in response to a high altitude hypobaric hypoxic (HH) environment. GM1 monosialoganglioside can allev...
High altitude cerebral edema (HACE) is a severe type of acute mountain sickness (AMS) that occurs in response to a high altitude hypobaric hypoxic (HH) environment. GM1 monosialoganglioside can alleviate brain injury under adverse conditions including amyloid-β-peptide, ischemia and trauma. However, its role in HACE-induced brain damage remains poorly elucidated. In this study, GM1 supplementation dose-dependently attenuated increase in rat brain water content (BWC) induced by hypobaric chamber (7600 m) exposurefor 24 h. Compared with the HH-treated group, rats injected with GM1 exhibited less brain vascular leakage, lower aquaporin-4 and higher occludin expression, but they also showed increase in Na+/K+-ATPase pump activities. Importantly, HH-incurred consciousness impairment and coordination loss also were ameliorated following GM1 administration. Furthermore, the increased oxidative stress and decrease in anti-oxidant stress system under the HH condition were also reversely abrogated by GM1 treatment via suppressing accumulation of ROS, MDA and elevating the levels of SOD and GSH. Simultaneously, GM1 administration also counteracted the enhanced inflammation in HH-exposed rats by muting pro-inflammatory cytokines IL-1β, TNF-α, and IL-6 levels in serum and brain tissues. Subsequently, GM1 potentiated the activation of the PI3K/AKT-Nrf2 pathway. Cessation of this pathway by LY294002 reversed GM1-mediated inhibitory effects on oxidative stress and inflammation, and ultimately abrogated the protective role of GM1 in abating brain edema, cognitive and motor dysfunction. Overall, GM1 may afford a protective intervention in HACE by suppressing oxidative stress and inflammatory response via activating the PI3K/AKT-Nrf2 pathway, implying a promising agent for the treatment of HACE.
- Antihypoxic activities of constituents from Arenaria kansuensis. [Journal Article]
- PPhytomedicine 2018 Jan 01; 38:175-182
- CONCLUSIONS: This study demonstrated that pyrocatechol and tricin 7-O-β-d-glucopyranoside could be therapeutic candidates for treatment of AS. It is the first time to find the major active constituents of AKE for anti-hypoxia. Meanwhile, a RSC96 cell model of hypoxia was established to screen anti-hypoxic activity of compounds for the first time.
- Acetazolamide reduces exercise capacity following a 5-day ascent to 4559 m in a randomised study. [Journal Article]
- BOBMJ Open Sport Exerc Med 2018; 4(1):e000302
- CONCLUSIONS: Maximum exercise performance at altitude was reduced more in subjects taking Az compared with placebo, particularly in older individuals. The age-related effect may reflect higher tissue concentrations of Az due to reduced renal excretion. Future studies should explore the effectiveness of smaller Az doses (eg, 250 mg daily or less) in older individuals to optimise the altitude-Az-exercise relationships.
- Bioactive fraction of Rhodiola algida against chronic hypoxia-induced pulmonary arterial hypertension and its anti-proliferation mechanism in rats. [Journal Article]
- JEJ Ethnopharmacol 2018 Jan 08; 216:175-183
- CONCLUSIONS: Our results suggest that ACRT could alleviate chronic hypoxia-induced pulmonary arterial hypertension. And its anti-proliferation mechanism in rats based on decreasing PCNA, cyclin D1, CDK4 expression level and inhibiting p27Kip1 degradation.
- "The Great Silk Road" and the First Description of Hypoxia. [Historical Article]
- VVesalius 2016; 22(2 Suppl):53-8
- The first written reports about the effect of high-altitude air on the human organism in Ancient China (the 30s BC) and in South America during the conquest (late XVI century) are discussed in this p...
The first written reports about the effect of high-altitude air on the human organism in Ancient China (the 30s BC) and in South America during the conquest (late XVI century) are discussed in this paper.
- Barometric pressure change and heart rate response during sleeping at ~ 3000 m altitude. [Journal Article]
- IJInt J Biometeorol 2017 Dec 27
- We investigated effects of change in barometric pressure (PB) with climate change on heart rate (HR) during sleep at 3000 m altitude. Nineteen healthy adults (15 males and four females; mean age 32 y...
We investigated effects of change in barometric pressure (PB) with climate change on heart rate (HR) during sleep at 3000 m altitude. Nineteen healthy adults (15 males and four females; mean age 32 years) participated in this study. We measured PB(barometry) and HR (electrocardiography) every minute during their overnight stay in a mountain lodge at ~ 3000 m. We also measured resting arterial oxygen saturation (SpO2) and evaluated symptoms of acute mountain sickness (AMS) by using the Lake Louise Questionnaire at 2305 and 3000 m, respectively. PBgradually decreased during the night at the speed of approximately - 0.5 hPa/h. We found that HR during sleep decreased linearly as PBdecreased in all subjects, with significance (r = 0.492-0.893; all, P < 0.001). Moreover, cross correlation analysis revealed that HR started to decrease after ~ 15 min following the decrease in PB,on average. SpO2was 93.8 ± 1.7% at 2305 m before climbing, then decreased significantly to 90.2 ± 2.2% at the lodge before going to bed, and further decreased to 87.5 ± 2.7% after waking (all, P < 0.05). Four of the 19 subjects showed a symptom of AMS after waking (21%). Further, the decrease in HR in response to a given decrease in PB(ΔHR/ΔPB) was negatively related with a decrease in SpO2from before going to bed to after waking at 3000 m (r = - 0.579, P = 0.009) and with total AMS scores after waking (r = 0.489, P = 0.033).
- Relationship between Smoking and Acute Mountain Sickness: A Meta-Analysis of Observational Studies. [Review]
- BRBiomed Res Int 2017; 2017:1409656
- CONCLUSIONS: The meta-analysis indicates that no difference was found in AMS risk with regard to smoking status.
- Diseases potentially related to Flammer syndrome. [Review]
- EJEPMA J 2017; 8(4):327-332
- Flammer syndrome (FS) is a prevalent and mostly benign condition. Subjects with FS seem to have a good life expectancy. Nevertheless, FS subjects are at increased risk for certain diseases, mainly wh...
Flammer syndrome (FS) is a prevalent and mostly benign condition. Subjects with FS seem to have a good life expectancy. Nevertheless, FS subjects are at increased risk for certain diseases, mainly when they are challenged by psychological stress or other stimuli such as coldness. FS is related to ocular diseases, such as normal-tension glaucoma, retinitis pigmentosa, central serous chorioretinopathy, optic nerve compartment syndrome, Leber's hereditary optic neuropathy, arterial or venous occlusions in the retina, and choroid and optic nerve head, despite the absence of classical vascular risk factors. FS is also related to some non-ocular diseases, such as multiple sclerosis, breast cancer, and altitude sickness. The role of FS in other diseases such as tinnitus, sudden hearing loss, Ménière's disease, anorexia nervosa, and thyroid dysfunction is currently under investigation. The exact relationship of FS to related diseases however still needs to be established. This may hopefully lead to more targeted diagnostics and personalized treatments.
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- Isolated psychosis during exposure to very high and extreme altitude - characterisation of a new medical entity. [Journal Article]
- PMPsychol Med 2017 Dec 05; :1-8
- CONCLUSIONS: Episodes of psychosis during exposure to high altitude are frequently reported, but have not been specifically examined or assigned to medical diagnoses. In addition to the risk of suffering from somatic mountain illnesses, climbers and workers at high altitude should be aware of the potential occurrence of psychotic episodes, the associated risks and respective coping strategies.