Exercise limb blood flow response to acute and chronic hypoxia in Danish lowlanders and Aymara natives

Aim: The femoral artery blood flow response to submaximal, one‐legged, dynamic, knee‐extensor exercise was determined in acute and chronic hypoxia to investigate the hypotheses that with adaptation to chronic hypoxia blood haemoglobin increases, allowing preservation of blood flow as in normoxia. Methods: Sixteen Danish lowlanders participated, in groups of six to eight, in the experiments at sea level normoxia (FiO₂ ? 0.21) and acute hypoxia (FiO₂ ? 0.11), and chronic hypoxia after ～7 and 9–10 weeks at ～5260 m altitude breathing ambient air (FiO₂ ? 0.21) or a hyperoxic gas (FiO₂ ? 0.55). The response was compared with that in six Aymara natives. Results: The haemoglobin and haematocrit increased (P < 0.003) in the lowlanders at altitude vs. at sea level by ～39 and 27% respectively; i.e. to a similar (P = ns) level as in the natives. At rest, blood flow was the same (P = ns) in the lowlanders at sea level and altitude, as in the natives at altitude. During the onset of and incremental exercise, blood flow was the same (P = ns) in the lowlanders at sea level and altitude, as in the natives at altitude. Acute hypoxia increased (P < 0.05) blood flow by ～55% during exercise in the lowlanders at sea level. Acute hyperoxia decreased (P < 0.05) blood flow by ～22–29% during exercise in the lowlanders and natives at altitude. Conclusion: In chronic hypoxia, blood haemoglobin increases, allowing normalization of the elevated exercise blood flow response in acute hypoxia, and preservation of the kinetics and steady‐state exercise blood flow as in normoxia, being similar as in the natives at altitude.     

Engineered erythrocytes: influence of P50 rightward shift and oxemia on oxygen transport to tissues

The red blood cell (RBC) membrane may be reversibly opened using a lysis-resealing continuous flow method. The technology was adapted to the internalisation of an allosteric effector of haemoglobin, Inostiol-Hexaphosphate (IHP). This molecule, occupying the allosteric site of 2,3 Bis-Phosphoglycerate with a very large affinity, induces a rightward shift of the oxyhaemoglobin dissociation curve (ODC). From ODC parameters in human volunteers, the potential effect of P₅₀ (oxygen pressure at 50% haemoglobin saturation) on oxygen exchangeable fraction (OEF%), for various oxygen partial pressures (oxemia) was evaluated. For hyperoxic or normoxic arterial oxygen pressure (paO₂), rightward shift greatly improved OEF%. In optimised conditions, engineered erythrocytes were potentially able to deliver two to three times more oxygen than normal cells. For patients with decreased paO₂, as observed in chronic obstructive pulmonary deficiency (COPD), the reduction in arterial oxygen saturation (saO₂%) reduces the benefit of the treatment for paO₂ values between 60 and 80 mmHg. Below 60 mmHg, the saO₂% reduction cannot be compensated by a corresponding reduction in svO₂%, particularly for organs with physiologically low svO₂%. In these organs, deleterious effects could be observed for a very large rightward shift of the ODC. Such engineered cells have unique properties for oxygen transport improvement and may be used for the treatment of patients suffering from diseases associated with hypoxia and ischemia.     

Antioxidant and redox status after maximal aerobic exercise at high altitude in acclimatized lowlanders and native highlanders

Exercise-induced increase in oxygen consumption leads to oxidative stress. On the contrary, hypoxia triggers oxidative stress despite decreased oxygen flux. Therefore, exercise under hypoxia may aggravate oxidative damage. Highlanders are expected to have better antioxidant capacity than lowlanders as a result of adaptation to hypoxia. The present study was undertaken to investigate the effect of exercise on antioxidant system in lowlanders and highlanders at high altitudes (HA). This study was conducted on active male volunteers, randomly selected and categorized into three groups, i.e., lowlanders tested at sea level (LL-SL, n = 35), lowlanders tested at altitude of 4560 m (LL-HA, n = 35) and native highlanders tested (HAN, n = 20) at the same height. Volunteers performed maximal exercise until exhaustion. Blood samples were collected before and after exercise. Both LL-SL and HAN had shown similar VO_2max, which was significantly higher than LL-HA. GSH/GSSG ratio significantly increased in LL-SL and decreased in HAN after exercise. With exercise there were a decrease in superoxide dismutase and increase in glutathione peroxidase and catalase activities in HAN. Therefore, the results have suggested that HAN are more susceptible to oxidative stress when subjected to high-intensity exercise than lowlanders. The cumulative effect of higher VO_2max and longer duration of exercise in hypoxia may be the reason of higher level of oxidative insult among HAN. Comparatively better management of antioxidant system observed in lowlanders at HA may be explained by the lower VO_2max and shorter duration of exercise in hypoxia.     

Protein nitration,lipid peroxidation and DNA damage at high altitude in acclimatized lowlanders and native highlanders: Relation with oxygen consumption

Reactive oxygen and nitrogen species have been reported to be increased due to hypobaric hypoxia. It was hypothesized that lowlanders are more susceptible to protein nitration, lipid peroxidation and DNA damage at high altitude than highlanders and formation of these biomarkers may have strong correlation with oxygen consumption. Male volunteers were randomly selected and categorized into 3 groups, i.e. lowlanders at sea level (LL-SL, n = 10), lowlanders at an altitude of 4560 m (LL-HA, n = 10) and highlanders (HAN, n = 10). Volunteers performed maximal aerobic exercise. Resting and post-exercise blood samples were taken at sea level and high altitude. Both resting and maximum oxygen consumption showed positive correlation with stress markers. LL-HA showed increased 3-nitrotyrosine and lipid hydroperoxide than LL-SL at rest. 3-Nitrotyrosine and lipid hydroperoxide increased after exercise in 3 groups, but percentage increase was higher in HAN than LL-SL and LL-HA. LL-SL and HAN showed significant DNA damage after exercise. Results indicate that resting oxygen consumption is positively correlated with nitrosative and oxidative stress markers irrespective of environmental condition and adaptation levels. Lowlanders have shown higher susceptibility to hypoxic insult than highlanders at rest, but when subjected to exercise test, they showed better tolerance to hypoxia than highlanders.     

Oxygen transport in guinea pigs native to high altitude (Junin,Peru, 4,105 m)

In guinea pigs native to high altitude in the Andes (Peru) the arterial and mixed-venousP _{O 2},P _{CO 2}, pH, and O₂ content were measured at high altitude during breathing ambient air.Identical measurements were done in Nijmegen, The Netherlands, on sea-level natives and on guinea pigs exposed for 4–5 weeks to simulated altitude in a low pressure chamber, while breathing ambient air (normoxia) or an hypoxic mixture of O₂ in N₂ with aP _{I O 2} similar to that of the ambient air at high altitude. A standard blood O₂ dissociation curve (ODC) was estimated in vitro (at pH=7.4 and 37.5°C), and a standard in vivo ODC was derived from measuredP _{O 2},S _{O 2} and pH in all three groups.Both guinea pigs native to natural or simulated high altitude had a higher hematocrit and blood O₂ capacity than sea-level controls. These increased altitude values were, however, almost the same as the sea-level values of man or rat. No difference in the ideal alveolararterialP _{O 2} difference or lung diffusing capacity for O₂ was found between (natural or simulated) high altitude animals and their corresponding controls, when measured at hypoxia. Mixed-venousP _{O 2} was higher in guinea pigs from the natural high altitude (but not in those from the low pressure chamber) when compared with control sea-level natives studied at hypoxia. No difference among groups in cardiac output was found, while breathing the same inspiratory mixture. In the guinea pigs native to high altitude a higher P₅₀ and a lower Hill numbern for the in vitro ODC were found when compared with the controls or with the guinea pigs exposed to simulated high altitude. This was not observed when the ODC's were estimated in vivo.The rather modest polycythemic response to high altitude in guinea pigs coincides with a low value of P₅₀, when related to body weight. In this respect the guinea pig seems to be more closely related to the typical high altitude mammals like Andean camelids and rodents than to man or rat that respond to high altitude with a pronounced polycythemia and possess a rather high P₅₀ with respect to body weight.All data obtained in Peru are part of the scientific material acquired during the Italian Lake Mountain Scientific Expedition to Peru, march and April 1978, under the direction of Prof. Dr. P. G. Data from the University of Chieti, Italy.Part of the results were presented at the 12. Atmungsphysiologische Arbeitstagung, Göttingen, FRG, January 26–27, 1979     

Human erythropoietin response to hypocapnic hypoxia,normocapnic hypoxia,and hypocapnic normoxia

This study investigated the human erythropoietin (EPO) response to short-term hypocapnic hypoxia, its relationship to a normoxic or hypoxic increase of the haemoglobin oxygen affinity, and its suppression by the addition of CO₂ to the hypoxic gas. On separate days, eight healthy male subjects were exposed to 2 h each of hypocapnic hypoxia, normocapnic hypoxia, hypocapnic normoxia, and normal breathing of room air (control experiment). During the control experiment, serum-EPO showed significant variations (ANOVAP = 0.047) with a 15% increase in mean values. The serum-EPO measured in the other experiments were corrected for these spontaneous variations in each individual. At 2 h after ending hypocapnic hypoxia (10% O₂ in nitrogen), mean serum-EPO increased by 28% [baseline 8.00 (SEM 0.84) U · 1⁻¹, post-hypoxia 10.24 (SEM 0.95) U · 1⁻¹, P = 0.005]. Normocapnic hypoxia was produced by the addition of CO₂ (10% Co₂ with 10% O₂) to the hypoxic gas mixture. This elicited an increased ventilation, unaltered arterial pH and haemoglobin oxygen affinity, a lower degree of hypoxia than during hypocapnic hypoxia, and no significant changes in serum-EPO (ANOVAP > 0.05). Hypocapnic normoxia, produced by hyperventilation of room air, elicited a normoxic increase in the haemoglobin oxygen affinity without changing serum-EPO. Among the measured blood gas and acid-base parameters, only the partial pressures of oxygen in arterial blood during hypocapnic hypoxia were related to the peak values of serum-EPO (r = −0.81,P = 0.01). The present human EPO responses to hypoxia were lower than those which have previously been reported in rodents and humans. In contrast with the earlier rodent studies, it was found that human EPO production could not be triggered by short-term increases in pH and haemoglobin oxygen affinity per se, and the human EPO response to hypoxia could be suppressed by concomitant normocapnia without acidosis.     

Effects of breathing control on cardiocirculatory modulation in Caucasian lowlanders and Himalayan Sherpas

This study was performed to investigate the influence of breathing control on the autonomic cardiac regulation at high altitude in adapted and non-adapted awake subjects. We recorded electrocardiogram and pulse oximetry in 14 short-term acclimatized lowlanders and 14 Himalayan Sherpas during resting conditions at an altitude of 5,050 m. Spectrum analysis was performed on synchronized 15 min periods of R-R intervals and the oxygen saturation of arterial blood (S_aO₂). Despite mean S_aO₂ being similar in lowlanders and Himalayan Sherpas [78.5 (SD 7.0)% compared to 79.4 (SD5.8)%, respectively], fluctuations in S_aO₂ were significantly increased in lowlanders compared to Sherpas, thus indicating an unstable regulation of respiration control in lowlanders. Regression analysis demonstrated a significant relationship between spectrum power of S_aO₂ and the relative power of R-R intervals in the frequency band between 0.01 and 0.08 Hz in lowlanders, but not in Sherpas. Our results demonstrate differences in respiratory and autonomic cardiac control between non-adapted lowlanders and Himalayan high-altitude residents and indicate that unstable breathing control during chronic hypobaric hypoxia is significantly correlated with the autonomic cardiocirculatory regulation. Accepted: 11 September 2000     

Central-peripheral respiratory chemoreflex interaction in humans

We investigated the interaction between the central and peripheral chemoreflexes in humans using a temporal separation technique in three tests. In two tests hyperventilation was used to reduce central PCO₂. In these tests the difference in the responses to the same step increases in PCO₂ to 45 mmHg at normoxic and hypoxic O₂ tensions provided a measure of the response to isocapnic hypoxia at a low central PCO₂. In a third test the response to a hypoxic step during sustained isocapnia at 45 mmHg provided a measure of the response to isocapnic hypoxia at a high central PCO₂. The responses to isocapnic hypoxia at high and low central PCO₂ were not significantly different, confirming the conclusion of previous studies that central and peripheral chemoreflex signals interact additively. This finding contrasts with those from recent animal experiments and emphasizes the need for caution when using animal experiments to make conclusions about the physiology of the respiratory chemoreflexes in humans.     

Indium-111 labeled gold nanoparticles for in-vivo molecular targeting

The present report describes the synthesis and biological evaluation of a molecular imaging platform based on gold nanoparticles directly labeled with indium-111. The direct labeling approach facilitated radiolabeling with high activities while maintaining excellent stability within the biological environment. The resulting imaging platform exhibited low interference of the radiolabel with targeting molecules, which is highly desirable for in-vivo probe tracking and molecular targeted tumor imaging. The indium-111 labeled gold nanoparticles were synthesized using a simple procedure that allowed stable labeling of the nanoparticle core with various indium-111 activities. Subsequent surface modification of the particle cores with RGD-based ligands at various densities allowed for molecular targeting of the α_vß₃ integrin in-vitro and for molecular targeted imaging in human melanoma and glioblastoma models in-vivo. The results demonstrate the vast potential of direct labeling with radioisotopes for tracking gold nanoparticles within biological systems.     

The effects of intermittent exposure to hypoxia during endurance exercise training on the ventilatory responses to hypoxia and hypercapnia in humans

The present study was performed to investigate the effects of a combination of intermittent exposure to hypoxia during exercise training for short periods on ventilatory responses to hypoxia and hypercapnia (HVR and HCVR respectively) in humans. In a hypobaric chamber at a simulated altitude of 4,500?m (barometric pressure 432?mmHg), seven subjects (training group) performed exercise training for 6 consecutive days (30 min?·?day^?1), while six subjects (control group) were inactive during the same period. The HVR, HCVR and maximal oxygen uptake (V˙O_{2 max}) for each subject were measured at sea level before (pre) and after exposure to intermittent hypoxia. The post exposure test was carried out twice, i.e. on the 1st day and 1 week post exposure. It was found that HVR, as an index of peripheral chemosensitivity to hypoxia, was increased significantly (P?V˙O_{2 max} increased significantly in the training group. These results would suggest that endurance training during intermittent exposure to hypoxia depresses the increment of chemosensitivity to hypoxia, and that intermittent exposure to hypoxia in the presence or absence of exercise training does not induce an increase in the chemosensitivity to hypercapnia in humans.     

Exhaled nitric oxide is associated with acute mountain sickness susceptibility during exposure to normobaric hypoxia

Nitric oxide is a gaseous signaling molecule that participates in a large variety of physiological functions and may have a role in the pathology of altitude illnesses, such as acute mountain sickness (AMS). The effect of normobaric hypoxia on the fraction of exhaled NO (FENO) is a controversial area of high altitude physiology, with the effect varying widely across studies. We exposed 19 male subjects to normobaric hypoxia for 6 h and measured FENO and AMS (via Lake Louise Score) each hour. For data analysis, subjects were divided into AMS-positive and AMS-negative groups based on their Lake Louise Scores during exposure. Eighteen subjects completed the study, and the incidence of AMS was 50%. Mean FENO was unchanged at hour 1 but was significantly elevated above baseline for the remainder of the normobaric hypoxia exposure (p < 0.001). Subjects who developed AMS had a significantly lower mean FENO at baseline compared to resistant subjects (p = 0.013). Further investigations are warranted to confirm our results and to understand the physiological basis of this association.     

Cardiac output,arterial and mixed-venous O2 saturation,and blood O2 dissociation curve in growing rats adapted to a simulated altitude of 3500 m

Summary In rats adapted to a simulated altitude of 3500 m cardiac output measured at hypoxia by the direct Fick principle was significantly lower than in the control animals (mean values 54.3 ml/min and 69.8 ml/min, resp.). The decrease of cardiac output was accompanied by an increase of arterio-venous O₂ difference and a decrease of stroke volume in the adapted rats. It is suggested that the decrease of cardiac output might be related to the increase of hematocrit. The adapted rats also showed higher arterial and mixed-venous O₂ content (both at hypoxia) and increased O₂ capacity. Arterial O₂ saturation of the animals previously exposed to simulated high altitude hypoxia was significantly higher (67.3% as against 61.2% in the controls). The standard O₂ dissociation curve showed lower oxygen affinity in the blood of the adapted animals but no physiological advantage concerning the transport of O₂ to the tissues was found. In another group of animals the Bohr factor was estimated and no difference was found between rat and human blood.     

Chronic hypoxia increases blood pressure and noradrenaline spillover in healthy humans

Chronic hypoxia is associated with elevated sympathetic activity and hypertension in patients with chronic pulmonary obstructive disease. However, the effect of chronic hypoxia on systemic and regional sympathetic activity in healthy humans remains unknown. To determine if chronic hypoxia in healthy humans is associated with hyperactivity of the sympathetic system, we measured intra-arterial blood pressure, arterial blood gases, systemic and skeletal muscle noradrenaline (norepinephrine) spillover and vascular conductances in nine Danish lowlanders at sea level and after 9 weeks of exposure at 5260 m. Mean blood pressure was 28% higher at altitude ( P < 0.01) due to increases in both systolic (18% higher, P < 0.05) and diastolic (41% higher, P < 0.001) blood pressures. Cardiac output and leg blood flow were not altered by chronic hypoxia, but systemic vascular conductance was reduced by 30 % ( P < 0.05). Plasma arterial noradrenaline (NA) and adrenaline concentrations were 3.7- and 2.4-fold higher at altitude, respectively ( P < 0.05). The elevation of plasma arterial NA concentration was caused by a 3.8-fold higher whole-body NA release ( P < 0.001) since whole-body noradrenaline clearance was similar in both conditions. Leg NA spillover was increased similarly (× 3.2, P < 0.05). These changes occurred despite the fact that systemic O₂ delivery was greater after altitude acclimatisation than at sea level, due to 37 % higher blood haemoglobin concentration. In summary, this study shows that chronic hypoxia causes marked activation of the sympathetic nervous system in healthy humans and increased systemic arterial pressure, despite normalisation of the arterial O₂ content with acclimatisation.     

The effects of acute altitude exposure in swiss highlanders and lowlanders

Summary The functional characteristics at rest in responding to stepwise acute exposure to simulated altitude (6000 m) were compared in 10 acclimatized mountaineers (highlanders), residents of Zermatt (1616 m) working at an altitude up to about 4000 m, and in 11 nonacclimatized control subjects (lowlanders) living and working in Zurich (450 m). In comparison with the lowlanders, the highlanders showed at altitude significantly greater hyperventilation, lower heart rate and systolic blood pressure, smaller haemoconcentration, lower urodilatin secretion and natriuresis, and a preserved neuropsychological ability (attentiveness) and vasomotor tone (diastolic blood pressure); the critical altitude at which hypoxic short-term adaptation became insufficient was 6000 m. The lowlanders, however, manifested reduced tolerance of hypoxia, i.e. insufficient short-term adjustment with subjective and objective distress coinciding with the first signs of hypoxia of the central nervous system, already apparent at and above 4000 m. It was concluded that the functional differences between highlanders and lowlanders in responding to acute gradual hypoxia indicated factors contributing to altitude acclimatization.Dedicated to Prof. F. J. Wagenhäuser on the occasion of his retirement.     

Lactate during exercise at high altitude

In acclimatized humans at high altitude the reduction, compared to acute hypoxia, of the blood lactate concentration (1a) at any absolute oxygen uptake ( ), as well as the reduction of maximum la (la_max) after exhaustive exercise, compared to both acute hypoxia or normoxia, have been considered paradoxical, and these phenomena have therefore become known as the lactate paradox. Since, at any given power output and , mass oxygen transport to the contracting locomotor muscles is not altered by the process of acclimatization to high altitude, the gradual reduction in [la^–]_max in lowlanders exposed to chronic hypoxia seems not to be due to changes in oxygen availability at the tissue level. At present, it appears that the acclimatization-induced changes in [la^–] during exercise are the result of at least two mechanisms: (1) a decrease in maximum substrate flux through aerobic glycolysis due to the reduced in hypoxia; and (2) alterations in the metabolic control of glycogenolysis and glycolysis at the cellular level, largely because of the changes in adrenergic drive of glycogenolysis that ensue during acclimatization, although effects of changes in peripheral oxygen transfer and the cellular redox state cannot be ruled out. With regard to the differences in lactate accumulation during exercise that have been reported to occur between lowlanders and highlanders, both groups either being acclimatized or not, these do not seem to be based upon fundamentally different metabolic features. Instead, they seem merely to reflect points along the same continuum of phenotypic adaptation of which the location depends on the time spent at high altitude.     

Enhanced chemosensitivity after intermittent hypoxic exposure does not affect exercise ventilation at sea level

The purpose of the present study was to test the hypothesis that the ventilatory response to exercise at sea level may increase after intermittent hypoxic exposure for 1 week, accompanied by an increase in hypoxic or hypercapnic ventilatory chemosensitivity. One group of eight subjects (hypoxic group) were decompressed in a chamber to 432 torr (where 1 torr=1.0 mmHg, simulating an altitude of 4,500 m) over a period of 30 min and maintained at that pressure for 1 h daily for 7 days. Oxygen uptake and pulmonary ventilation (V_E) were determined at 40%, 70%, and 100% of maximal oxygen uptake at sea level before (Pre) and after (Post) 1 week of daily exposures to hypoxia. The hypoxic ventilatory response (HVR) was determined using the isocapnic progressive hypoxic method as an index of ventilatory chemosensitivity to hypoxia, and the hypercapnic ventilatory response (HCVRSB) was measured by means of the single-breath carbon dioxide method as an index of peripheral ventilatory chemosensitivity to hypercapnia. The same parameters were measured in another group of six subjects (control group). In the hypoxic group, resting HVR increased significantly (P<0.05) after intermittent hypoxia and HCVRSB increased at Post, but the change was not statistically significant (P=0.07). In contrast, no changes in HVR and HCVRSB were found in the control group. There were no changes in either V_E or the ventilatory equivalent for oxygen during maximal and submaximal exercise at sea level throughout the experimental period in either group. These results suggest that the changes in resting hypoxic and peripheral hypercapnic chemosensitivities following short-term intermittent hypoxia have little effect on exercise ventilation at sea level. Electronic Publication     

Modelling study of the acute cardiovascular response to hypocapnic hypoxia in healthy and anaemic subjects

The present study analyses the cardiovascular response to acute hypocapnic hypoxia (simulating the effect of respiration at high altitude) both in healthy, unacclimatised subjects and in subjects with moderate anaemia, by means of a mathematical model of short-term cardiovascular regulation. During severe hypoxia, cardiac output and heart rate (HR) exhibit a significant increase compared with the basal level (cardiac output: +90%; HR: +64%). Systemic arterial pressure remains quite constant or shows a mild increase. Coronary blood flow increases dramatically (+200%), thus maintaining a constant oxygen delivery to the heart. However, blood oxygen utilisation in the heart augments, to fulfil the increased power of the cardiac pump during hypoxia. Cerebral blood flow rises only at very severe hypoxia but, owing to the vasoconstrictory effect of hypocapnia, its increase (+80%) is insufficient to maintain oxygen delivery to the brain. The model suggests that a critical level for the aerobic metabolism in these organs (heart and brain) is reached at an oxygen partial pressure in arterial blood (PaO₂) of approximately 25 mmHg. Moderate anaemia during normoxia is compensated by an increase in cardiac output (+22%), a decrease in total peripheral resistance (−30%) and an increase in O₂ extraction from blood (+40%). As cardiovascular regulation mechanisms are already recruited in anaemic subjects at rest, their action soon becomes exhausted during hypocapnic hypoxia. Critical levels for vital functions are already reached at a PaO₂ of approximately 45 mmHg.     

Development of a biological scaffold engineered using the extracellular matrix secreted by skeletal muscle cells

The performance of implantable biomaterials derived from decellularized tissue, including encouraging results with skeletal muscle, suggests that the extracellular matrix (ECM) derived from native tissue has promising regenerative potential. Yet, the supply of biomaterials derived from donated tissue will always be limited, which is why the in-vitro fabrication of ECM biomaterials that mimic the properties of tissue is an attractive alternative. Towards this end, our group has utilized a novel method to collect the ECM that skeletal muscle myoblasts secrete and form it into implantable scaffolds. The cell derived ECM contained several matrix constituents, including collagen and fibronectin that were also identified within skeletal muscle samples. The ECM was organized into a porous network that could be formed with the elongated and aligned architecture observed within muscle samples. The ECM material supported the attachment and in-vitro proliferation of cells, suggesting effectiveness for cell transplantation, and was well tolerated by the host when examined in-vivo. The results suggest that the ECM collection approach can be used to produce biomaterials with compositions and structures that are similar to muscle samples, and while the physical properties may not yet match muscle values, the in-vitro and in-vivo results indicate it may be a suitable first generation alternative to tissue derived biomaterials.     

Hypoxia and brain aging: Neurodegeneration or neuroprotection?

The absolute reliance of the mammalian brain on oxygen to generate ATP renders it acutely vulnerable to hypoxia, whether at high altitude or in clinical settings of anemia or pulmonary disease. Hypoxia is pivotal to the pathogeneses of myriad neurological disorders, including Alzheimer’s, Parkinson’s and other age-related neurodegenerative diseases. Conversely, reduced environmental oxygen, e.g. sojourns or residing at high altitudes, may impart favorable effects on aging and mortality. Moreover, controlled hypoxia exposure may represent a treatment strategy for age-related neurological disorders. This review discusses evidence of hypoxia’s beneficial vs. detrimental impacts on the aging brain and the molecular mechanisms that mediate these divergent effects. It draws upon an extensive literature search on the effects of hypoxia/altitude on brain aging, and detailed analysis of all identified studies directly comparing brain responses to hypoxia in young vs. aged humans or rodents. Special attention is directed toward the risks vs. benefits of hypoxia exposure to the elderly, and potential therapeutic applications of hypoxia for neurodegenerative diseases. Finally, important questions for future research are discussed.     

A systematic in-vivo toxicity evaluation of nanophosphor particles via zebrafish models

Lanthanide ion-doped nanophosphors are an emerging group of nanomaterials with excellent optical properties, and have been suggested as alternatives to quantum dots. In this letter, we determine the in-vitro and in-vivo toxicity of β-NaYF₄:Ce,Tb nanophosphors using Capan-1 cells and embryonic zebrafish, respectively. In particular, we are the first to report on the in-vivo toxicity of β-phase nanophosphors and examine phenotypic developmental abnormalities (growth retardation, heart deformity, and bent tail), apoptotic cell death, and changes in heart function due to the nanophosphors. This study suggests the use of β-NaYF₄:Ce,Tb nanophosphors as alternatives for QDs in a wide variety of biomedical imaging applications.