Hypoxia Research Papers - Academia.edu (original) (raw)

Background. The interests in mesenchymal stem cells (MSCs) and their application in cell therapy have resulted in a better understanding of the basic biology of these cells. Recently hypoxia has been indicated as crucial for complete... more

Background. The interests in mesenchymal stem cells (MSCs) and their application in cell therapy have resulted in a better understanding of the basic biology of these cells. Recently hypoxia has been indicated as crucial for complete chondrogenesis. We aimed at analyzing bone marrow MSCs (BM-MSCs) differentiation capacity under normoxic and severe hypoxic culture conditions.Methods. MSCs were characterized by flow cytometry and differentiated towards adipocytes, osteoblasts, and chondrocytes under normoxic or severe hypoxic conditions. The differentiations were confirmed comparing each treated point with a control point made of cells grown in DMEM and fetal bovine serum (FBS).Results. BM-MSCs from the donors displayed only few phenotypical differences in surface antigens expressions. Analyzing marker genes expression levels of the treated cells compared to their control point for each lineage showed a good differentiation in normoxic conditions and the absence of this differentiatio...

The cell membrane of rat locus coeruleus (LC) neurons is sensitive to both extra-and intracellular ATP. Extracellular ATP or its enzymatically stable analogues activate membrane receptors of the P2 type. These receptors inhibit a... more

The cell membrane of rat locus coeruleus (LC) neurons is sensitive to both extra-and intracellular ATP. Extracellular ATP or its enzymatically stable analogues activate membrane receptors of the P2 type. These receptors inhibit a persistent potassium current and simultaneously activate a nonselective cationic conductance. The resulting depolarization increases the spontaneous firing rate. A decrease in the concentration of intracellular ATP during hypoxia or hypoglycemia opens ATP-sensitive K+ (KATP) channels of LC neurons. The resulting hyperpolarization depresses the discharge of action potentials and conserves energy. The hypoxia-induced hyperpolarization is additionally due to the release of adenosine from neighboring neurons or glial cells. A certain class of compounds, termed potassium channel openers, also decrease the firing, while sulphonylurea antidiabetics known to block KATp channels increase it. Sulphonylurea antidiabetics antagonize the excitability decrease induced both by potassium channel openers and metabolic damage.

The main purposes of the present study were to substantiate the existence of the four types of performance categories (i.e., optimal-automatic, optimal-controlled, suboptimal-controlled, and suboptimal-automatic) as hypothesised in the... more

The main purposes of the present study were to substantiate the existence of the four types of performance categories (i.e., optimal-automatic, optimal-controlled, suboptimal-controlled, and suboptimal-automatic) as hypothesised in the multi-action plan (MAP) model, and to investigate whether some specific affective, behavioural, psychophysiological, and postural trends may typify each type of performance. A 20-year-old athlete of the Italian shooting team, and a 46-year-old athlete of the Italian dart-throwing team participated in the study. Athletes were asked to identify the core components of the action and then to execute a large number of shots/flights. A 2 × 2 (optimal/suboptimal × automated/controlled) within subjects multivariate analysis of variance was performed to test the differences among the four types of performance. Findings provided preliminary evidence of psychophysiological and postural differences among four performance categories as conceptualized within the MA...

The possible effects of blue light during acute hypoxia and the circadian rhythm on several physiological and cognitive parameters were studied. Fifty-seven volunteers were randomly assigned to 2 groups: nocturnal (2200-0230 hours) or... more

The possible effects of blue light during acute hypoxia and the circadian rhythm on several physiological and cognitive parameters were studied. Fifty-seven volunteers were randomly assigned to 2 groups: nocturnal (2200-0230 hours) or diurnal (0900-1330 hours) and exposed to acute hypoxia (4000 m simulated altitude) in a hypobaric chamber. The participants were illuminated by blue LEDs or common artificial light on 2 different days. During each session, arterial oxygen saturation (Spo2), blood pressure, heart rate variability, and cognitive parameters were measured at sea level, after reaching the simulated altitude of 4000 m, and after 3 hours at this altitude. The circadian rhythm caused significant differences in blood pressure and heart rate variability. A 4% to 9% decrease in waking nocturnal Spo2 under acute hypoxia was observed. Acute hypoxia also induced a significant reduction (4%-8%) in systolic pressure, slightly more marked (up to 13%) under blue lighting. Women had significantly increased systolic (4%) and diastolic (12%) pressures under acute hypoxia at night compared with daytime pressure; this was not observed in men. Some tendencies toward better cognitive performance (d2 attention test) were seen under blue illumination, although when considered together with physiological parameters and reaction time, there was no conclusive favorable effect of blue light on cognitive fatigue suppression after 3 hours of acute hypobaric hypoxia. It remains to be seen whether longer exposure to blue light under hypobaric hypoxic conditions would induce favorable effects against fatigue.

Changes in contractility of newborn and adult hearts with different substrates were studied under oxygenation and hypoxia. Under oxygenation, insulin (50 mU/l) and low doses of fatty acids (sodium palmitate 0.12 mM) increased the... more

Changes in contractility of newborn and adult hearts with different substrates were studied under oxygenation and hypoxia. Under oxygenation, insulin (50 mU/l) and low doses of fatty acids (sodium palmitate 0.12 mM) increased the differential ventricular pressure (DVP), while higher doses of fatty acids (from 0.3 to 1.5 mM) decreased it. However, when both low doses of fatty acids and insulin were added simultaneously, tension development decreased. Hypoxia reduced DVP, and low doses of fatty acids restored cardiac force. The contractile response to extracellular glucose concentrations changed during development, and sensitivity to high doses of fatty acids increased with age. In adult cardiomyocytes, glucose uptake was also inhibited by sodium palmitate under oxygenation when cardiac metabolism is fatty acid dependent, but not under hypoxia, when it consumes carbohydrates. Newborn cardiomyocytes consumed more glucose than adult cells, they did not respond to insulin, and palmitate did not completely inhibit glucose uptake neither under oxygenation nor under hypoxia. Substrate availability modified glucose uptake and contractility by independent mechanisms.

Acute exposure to moderate (552Torr, 73.6kPa) and high (428Torr, 57.1 kPa) altitude resulted in a decrease in the thermosensitivity of arm, chest and thigh sweating during light and moderate exercise. This effect was not accompanied by... more

Acute exposure to moderate (552Torr, 73.6kPa) and high (428Torr, 57.1 kPa) altitude resulted in a decrease in the thermosensitivity of arm, chest and thigh sweating during light and moderate exercise. This effect was not accompanied by any change in the esophageal temperature threshold for sweating onset at any of the three sites. 2. Whole body wettedness was decreased an average of 23% at high altitude during light (40°/. ~O 2 peak) and moderate (60% ~O2 peak) exercise. There was no change in mean weighted skin temperature at either moderate or high altitude.

Towards the end of the first trimester, blood flow and oxygenation rise within the placenta, supporting an increased capacity for mitochondrial oxidative metabolism in both the placenta and developing fetus. In this regard, the placenta... more

Towards the end of the first trimester, blood flow and oxygenation rise within the placenta, supporting an increased capacity for mitochondrial oxidative metabolism in both the placenta and developing fetus. In this regard, the placenta acts uniquely as both a conduit of oxygen to the fetal circulation and a significant consumer of oxygen in order to support its own energy demands for the processes of nutrient transport and protein synthesis for hormone production and growth. When the supply of oxygen becomes restricted, for example during chronic exposure to hypobaric hypoxia at high altitude, placental and fetal tissues respond in order to optimise the allocation of oxygen between competing demands. In this case, the placenta appears to remodel its metabolism to decrease oxygen consumption, probably by increasing ATP production via glycolysis. This process can maintain oxygen supply to the fetus but is still associated with growth restriction. Oxidative stress, a feature of pre-eclampsia, might elicit similar metabolic changes in the absence of hypoxia. This review considers what is known about the metabolic response of the placenta and fetal tissues to hypoxia and oxidative stress, and suggests possible mechanisms that might underlie such metabolic remodelling using lessons from other tissues and organ systems. Aspects of the hypoxia response that remain to be addressed are highlighted and future studies suggested. Much remains unknown about the coordinated metabolic response of the fetalplacental unit to chronic hypoxia and oxidative stress, but it would appear to be more than a simple question of supply and demand.

Non-arteritic anterior ischemic optic neuropathy is caused by a transient optic nerve ischemia and results in permanent vision loss. Currently, there is no effective treatment for this ischemic optic nerve injury. This study characterized... more

Non-arteritic anterior ischemic optic neuropathy is caused by a transient optic nerve ischemia and results in permanent vision loss. Currently, there is no effective treatment for this ischemic optic nerve injury. This study characterized the duration and extent of ischemia induced after a coagulopathy injury to the optic nerve of adult rats. Acute ischemia was induced in adult rats by intravenous injection of Rose Bengal dye, followed by argon green laser treatment of the vessels at the optic disc. Rats were assessed in the short-term for hypoxyprobe-1 binding and expression of hypoxia inducible factor-1α (HIF-1 α) and fractin, markers of neuronal injury. Five months after injury, optic axon number was quantified. The coagulopathy injury resulted in short-term hypoxia in the optic nerve and retina. Tissues were hypoxic within 15 min of the coagulopathy injury, but normoxic by 24 h as measured by hypoxyprobe-1 staining. Both HIF-1α and fractin were upregulated in ganglion cells variably across the retina. Five months after the ischemic injury, there was a 71% reduction in optic axon number compared to controls. It is critical to have a reproducible and relevant method for producing transient hypoxia in order to test therapeutic strategies for rescuing injured neurons. The coagulopathy induced in this study resulted in a reproducible and transient ischemic optic nerve injury and long-term axonal loss. This ischemia shows similar, although not identical, morphological and physiological changes to those seen in the human eye after optic nerve ischemia. We are currently testing therapeutic strategies to protect ganglion cells from degeneration after this ischemic injury.

During waterlogging conditions plants switch from aerobic respiration to anaerobic fermentation to cope with the lack of available oxygen. Plants have two main fermentation pathways: ethanol and lactic acid fermentation. In this paper we... more

During waterlogging conditions plants switch from aerobic respiration to anaerobic fermentation to cope with the lack of available oxygen. Plants have two main fermentation pathways: ethanol and lactic acid fermentation. In this paper we carry out a functional analysis of the Arabidopsis lactate dehydrogenase gene, LDH1. Our results indicate that LDH1, like some other anaerobic genes, is expressed in a root-specific manner and is affected by a variety of abiotic stresses (hypoxia, drought, cold) and mechanical wounding. Functional analysis of LDH1 was carried out using transgenic Arabidopsis overexpressing the gene (35S promoter) and a T-DNA knockout line. Overexpression of LDH1 resulted in improved survival of low oxygen stress conditions in roots but not in shoots. Increased lactic acid fermentation also resulted in significantly higher activities of pyruvate decarboxylase (PDC). Knockout mutants of LDH1 showed reduced survival under low oxygen conditions and PDC activity levels w...

Micropaleontological and geochemical analyses were carried out on two sediment box cores (AH00-2220 and CR02-23) recovered in the Lower St. Lawrence Estuary (LSLE) in order to document recent temporal variations of primary productivity... more

Micropaleontological and geochemical analyses were carried out on two sediment box cores (AH00-2220 and CR02-23) recovered in the Lower St. Lawrence Estuary (LSLE) in order to document recent temporal variations of primary productivity and carbon fluxes to the bottom waters. These reveal a tenfold increase in the accumulation rate of dinoflagellate cysts and benthic foraminifera in the sediment over the last four decades which can be interpreted as a recent increase in pelagic and benthic production. Furthermore, the appearance of the benthic foraminiferal species Brizalina subaenariensis and Bulimina exilis, which are tolerant of low oxygen concentrations and high organic fluxes, in the upper 20 cm of the cores, may reflect significant changes in bottom water conditions over the last 40 yrs. Variations in the microfossil abundances in core AH00-2220 are strongly correlated with an increase in organic carbon (OC) content (from 1.1 to 1.6%) and to a shift in the isotopic signature of the latter (δ 13 C ORG from −24.8 to − 24.0‰). Similarly, a concomitant decrease in the C ORG :N ratio (from 15 to 12), an increase in organic carbon content (from 1.3 to 1.9%) and an increase in δ 13 C ORG (from − 24.5 to − 23.5‰) were observed in core CR02-23, all of which suggest an enhanced accumulation of marine over terrestrial OC in the LSLE. Our results imply that a significant increase in marine productivity in the LSLE occurred since the 1960's.

Exposure to hypobaric hypoxia, a condition involving decreased availability of oxygen is known to be associated with oxidative stress, neurodegeneration and memory impairment. The multifactorial response of the brain and the complex... more

Exposure to hypobaric hypoxia, a condition involving decreased availability of oxygen is known to be associated with oxidative stress, neurodegeneration and memory impairment. The multifactorial response of the brain and the complex signaling pathways involved therewith limits the therapeutic efficacy of several antioxidants in ameliorating hypobaric hypoxia-induced memory impairment. The present study was therefore aimed at investigating the potential of acetyl-L-carnitine (ALCAR), a known antioxidant that has been reported to augment neurotrophin-mediated survival mechanisms, in ameliorating hypoxia-induced neurodegeneration and memory impairment. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key transcription factor involved in the cellular defense mechanism against oxidative stress related to brain injury and neurological disorders. The study was designed to understand the mechanisms involving Nrf2 stabilization following exposure to hypobaric hypoxia. The results displayed reference memory impairment in Sprague-Dawley rats exposed to hypobaric hypoxia (7620 m) for 14 consecutive days which however improved on administration of ALCAR during hypoxic exposure. The study also revealed Nrf2 regulated augmented antioxidant response on administration of ALCAR which was through a novel tyrosine kinase A (TrkA) receptor-mediated mechanism. A decrease in free radical generation, lipid peroxidation and protein oxidation was also observed along with a concomitant increase in thioredoxin and reduced glutathione levels on administration of ALCAR during exposure to hypobaric hypoxia. The present study therefore reveals the therapeutic potential of ALCAR under conditions of hypobaric hypoxia and elucidates a novel mechanism of action of the drug.

The South American lungfish Lepidosiren paradoxa is an obligatory air-breathing fish possessing well-developed bilateral lungs, and undergoing seasonal changes in its habitat, including temperature changes. In the present study we aimed... more

The South American lungfish Lepidosiren paradoxa is an obligatory air-breathing fish possessing well-developed bilateral lungs, and undergoing seasonal changes in its habitat, including temperature changes. In the present study we aimed to evaluate gas exchange and pulmonary breathing pattern in L. paradoxa at different temperatures (25 and 30°C) and different inspired O2 levels (21, 12, 10, and 7%). Normoxic breathing pattern consisted of isolated ventilatory cycles composed of an expiration followed by 2.4±0.2 buccal inspirations. Both expiratory and inspiratory tidal volumes reached a maximum of about 35ml.kg(-1), indicating that L. paradoxa is able to exchange nearly all of its lung air in a single ventilatory cycle. At both temperatures, hypoxia caused a significant increase in pulmonary ventilation (V̇E), mainly due to an increase in respiratory frequency. Durations of the ventilatory cycle and expiratory and inspiratory tidal volumes were not significantly affected by hypoxia...

Peptidylarginine deiminases (PADs) and extracellular vesicles (EVs) may be indicative biomarkers of physiological and pathological status and adaptive responses, including to diseases and disorders of the central nervous system (CNS) and... more

Peptidylarginine deiminases (PADs) and extracellular vesicles (EVs) may be indicative biomarkers of physiological and pathological status and adaptive responses, including to diseases and disorders of the central nervous system (CNS) and related to hypoxia. While these markers have been studied in hypoxia-intolerant mammals, in vivo investigations in hypoxia-tolerant species are lacking. Naked mole-rats (NMR) are among the most hypoxia-tolerant mammals and are thus a good model organism for understanding natural and beneficial adaptations to hypoxia. Thus, we aimed to reveal CNS related roles for PADs in hypoxia tolerance and identify whether circulating EV signatures may reveal a fingerprint for adaptive whole-body hypoxia responses in this species. We found that following in vivo acute hypoxia, NMR: (1) plasma-EVs were remodelled, (2) whole proteome EV cargo contained more protein hits (including citrullinated proteins) and a higher number of associated KEGG pathways relating to the total proteome of plasma-EVs Also, (3) brains had a trend for elevation in PAD1, PAD3 and PAD6 protein expression, while PAD2 and PAD4 were reduced, while (4) the brain citrullinome had a considerable increase in deiminated protein hits with hypoxia (1222 vs. 852 hits in normoxia). Our findings indicate that circulating EV signatures are modified and proteomic content is reduced in hypoxic conditions in naked mole-rats, including the circulating EV citrullinome, while the brain citrullinome is elevated and modulated in response to hypoxia. This was further reflected in elevation of some PADs in the brain tissue following acute hypoxia treatment. These findings indicate a possible selective role for PAD-isozymes in hypoxia response and tolerance.

Bottom hypoxia has reemerged as a prominent feature of Lake Erie's central basin during late summer. Similar to coastal and marine systems, the influence of hypoxia on pelagic organisms remains largely enigmatic in Lake Erie. During 2005,... more

Bottom hypoxia has reemerged as a prominent feature of Lake Erie's central basin during late summer. Similar to coastal and marine systems, the influence of hypoxia on pelagic organisms remains largely enigmatic in Lake Erie. During 2005, we used a plankton survey system (a sensor package consisting of an optical plankton counter, fluorometer, dissolved oxygen sensor, light sensor, and conductivity-temperaturedepth sensor), coupled with a fish hydroacoustics system, to explore how the distribution of phytoplankton (chlorophyll), mesozooplankton, and fish varied vertically and horizontally in relation to oxygen concentrations. To do so, we conducted surveys of the entire water column on a continuous basis during mild (August) and severe (September) hypoxia. Our surveys included two sampling designs: 1) basin-wide transects sampled during day and night to define broad-scale patterns of spatial overlap among pelagic organisms; and 2) shorter (5 km) transects sampled every 4 h over a 24-h period to explore how diel vertical migration and hypoxia interact to affect time-specific spatial overlap among fishes, mesozooplankton, and phytoplankton. Our findings indicated that fish avoided regions of the hypolimnion with dissolved oxygen concentrations b3 mg l − 1 by 1) moving horizontally into areas with higher oxygen or 2) moving vertically into the metalimnion, where a sharp thermocline and oxycline existed. A portion of the mesozooplankton continued to use the hypoxic hypolimnion as a refuge from fish predation during daytime at oxygen concentrations between 1 and 3 mg l − 1 ; however, there was usually a mesozooplankton maximum in the metalimnion, even when fish were compressed into this region. Prior to development of hypoxia, the metalimnion in some areas may have served as thermal refuge from predation from the epilimnetic planktivore, the emerald shiner, and the hypolimnetic planktivore-benthivore, the rainbow smelt. Overall, the horizontal compression of fish into lesshypoxic regions in the deep area of the central basin followed by vertical compression into the metalimnion as hypoxia developed further may have led to local reduction of mesozooplankton prey in these regions. Herein, we discuss the potential implications of these hypoxia-induced impacts for understanding food web interactions and fisheries management.

Purpose: Intermittent altitude exposure leads to improvements in aerobic performance and blood parameters of athletes. The variety of hypoxic devices and simulated altitude training models requires a detailed study of their effects to... more

Purpose: Intermittent altitude exposure leads to improvements in aerobic performance and blood parameters of athletes. The variety of hypoxic devices and simulated altitude training models requires a detailed study of their effects to achieve the best results. The aim of this study was to investigate the effect of a four-week training camp at sea level conditions, combined with normobaric hypoxia, provided by hypoxicators during the night's sleep of the athletes. Material: Sixteen rowers of the Bulgarian national team (17.13±0.83 years old) were divided into a control group (n=8) and an experimental group (n=8) subjected to hypoxia for a period of four weeks. At the beginning and end of the training camp, anthropometric and hematological data were measured. A submaximal test on the Concept II rowing ergometer was performed, and the physical work capacity and anaerobic threshold were determined. Results: The results showed: 1) a lack of significant changes in the aerobic performance after training camp, both within and between groups; 2) at the end of the training camp in the experimental group a statistically significant increase in hemoglobin concentration (156.25±4.11 vs 162.75±4.11 g/L, p<0.01) and erythrocyte count (5.26±0.13 vs 5.49±0.10 g/L, p<0.01) was observed. Conclusions: The encouraging results regarding the higher increase in blood oxygen-carrying capacity in the experimental group did not lead to an increased working capacity. Further research should be provided in the search for optimal hypoxic training parameters, allowing not only a rise in hemoglobin concentration, but also the preservation of blood rheological properties.

The avian egg has been proven to be an excellent model for the study of the physical principles and the physiological characteristics of embryonic gas exchange. In recent years, it has become a model for the studies of the prenatal... more

The avian egg has been proven to be an excellent model for the study of the physical principles and the physiological characteristics of embryonic gas exchange. In recent years, it has become a model for the studies of the prenatal development of pulmonary ventilation, its chemical control and its interaction with extra-pulmonary gas exchange. Differently from mammals, in birds the initiation of pulmonary ventilation and the transition from diffusive to convective gas exchange are gradual and slow-occurring events amenable to detailed investigations. The absence of the placenta and of the mother permits the study of the mechanisms of embryonic adaptation to prenatal perturbations in a way that would be impossible with mammalian preparations. First, this review summarises the general aspects of the natural history of the avian egg that are pertinent to embryonic metabolism, growth and gas exchange and the characteristics of the structures participating in gas exchange. Then, the review focuses on the embryonic development of pulmonary ventilation, its regulation in relation to the embryo's environment and metabolic state, the effects that acute or sustained changes in embryonic temperature or oxygenation can have on growth, metabolism and ventilatory control.

Ascent to high altitude is associated with a fall in the partial pressure of inspired oxygen (hypobaric hypoxia). For oxidative tissues such as skeletal muscle, resultant cellular hypoxia necessitates acclimatization to optimize energy... more

Ascent to high altitude is associated with a fall in the partial pressure of inspired oxygen (hypobaric hypoxia). For oxidative tissues such as skeletal muscle, resultant cellular hypoxia necessitates acclimatization to optimize energy metabolism and restrict oxidative stress, with changes in gene and protein expression that alter mitochondrial function. It is known that lowlanders returning from high altitude have decreased muscle mitochondrial densities, yet the underlying transcriptional mechanisms and time course are poorly understood. To explore these, we measured gene and protein expression plus ultrastructure in muscle biopsies of lowlanders at sea level and following exposure to hypobaric hypoxia. Subacute exposure (19 d after initiating ascent to Everest base camp, 5300 m) was not associated with mitochondrial loss. After 66 d at altitude and ascent beyond 6400 m, mitochondrial densities fell by 21%, with loss of 73% of subsarcolemmal mitochondria. Correspondingly, levels of the transcriptional coactivator PGC-1␣ fell by 35%, suggesting down-regulation of mitochondrial biogenesis. Sustained hypoxia also decreased expression of electron transport chain complexes I and IV and UCP3 levels. We suggest that during subacute hypoxia, mitochondria might be protected from oxidative stress. However, following sustained exposure, mitochondrial biogenesis is deactivated and uncoupling down-regulated, perhaps to improve the efficiency of ATP productionAcclimatization of skeletal muscle mitochondria to high-altitude hypoxia during an ascent of Everest. FASEB J. 26, 000-000 (2012). www.fasebj.org

ABSTRACT Salmon fish farmers are seeking methods to reduce infestations of salmon lice. The highest concentrations of salmon lice copepodites are typically found in the upper meters of the water column and preventing this water from... more

ABSTRACT Salmon fish farmers are seeking methods to reduce infestations of salmon lice. The highest concentrations of salmon lice copepodites are typically found in the upper meters of the water column and preventing this water from passing through the salmon cages has been proposed as a way to reduce salmon lice infestation. One simple implementation proposed by the industry is to place a permanent tarpaulin skirt around the upper part of the sea cages. Currently, there is little evidence that a skirt will block the entrance of surface water to the cages and thereby reduce infestation. However, this pilot study shows that putting a tarpaulin skirt around a full scale commercial sea cage may seriously decrease the oxygen saturation levels available for the fish inside the skirt. Further investigations into the effectiveness of skirts as a means of reducing the exposure of farmed salmon to sea lice must therefore take precautional measures.

The expression of neuroglobin (Ngb) and cytoglobin (Cygb), two recently discovered globins with a potential neuroprotective activity against hypoxia and oxidative stress, was investigated in the cerebellum of young rats (postnatal day 20)... more

The expression of neuroglobin (Ngb) and cytoglobin (Cygb), two recently discovered globins with a potential neuroprotective activity against hypoxia and oxidative stress, was investigated in the cerebellum of young rats (postnatal day 20) after being exposed to chronic mild carbon monoxide (CO) at 25 ppm during prenatal (group A), prenatal and postnatal (group B), the postnatal period only (group C), and air (group D). The expression of genes associated with hypoxia signaling pathways was also investigated in the rat cerebella by real-time RT-PCR after CO exposure. Ngb and Cygb mRNAs did not change in any CO-exposed group. Quantitative immunohistochemistry showed no significant change in Ngb protein; however, there was a significant increase of Cygb protein in rats from groups A, B, and C when compared with group D. In group B, genes related to the generation of reactive oxygen species (Nos2) and lipid metabolism (Apat2) were upregulated. In contrast, no changes were found in the expression of 8 genes typically upregulated by hypoxic conditions (Angptl4, Arnt2, Casp1, Crebbp, Hif1a, Hif3a, Mt3, or Vegfa) in any CO-exposed group, suggesting that hypoxia-related gene expression is not altered by this mild CO exposure. Cygb but not Ngb may protect cerebellar cells from the chronic presence of CO exposure during prenatal and postnatal development.

This article examines the neurocognitive sequelae of repeated exposure to hypoxemia in apnea (breath-hold) divers. A brief review of the literature on the physiological and neurological adaptations involved in the ''human diving reflex''... more

This article examines the neurocognitive sequelae of repeated exposure to hypoxemia in apnea (breath-hold) divers. A brief review of the literature on the physiological and neurological adaptations involved in the ''human diving reflex'' is presented. The results from a neuropsychological investigation of N ¼ 21 elite apnea divers are evaluated. Standard neuropsychological tests, with known sensitivity to mild brain insults, included speed of visuo-motor responding, speed of language comprehension, response inhibition, and visual and verbal attention and recall tasks. Results indicated that the breath-hold divers performed tasks within the average range compared to norms on all tests, suggesting that 1-20 years of repeated exposure to hypoxemia including multiple adverse neurological events did not impact on performance on standard neuropsychological tasks. The results are discussed in relation to implications for clinical conditions such as sleep apnea, respiratory disorders, altitude sickness, and recreational apnea activities.

Global climate change is expected to intensify hypoxic conditions during coastal upwelling events along the west coast of North America, but the potential effects on nearshore fishes are not well understood. Viviparous rockfishes (genus... more

Global climate change is expected to intensify hypoxic conditions during coastal upwelling events along the west coast of North America, but the potential effects on nearshore fishes are not well understood. Viviparous rockfishes (genus Sebastes) that gestate and give birth during the upwelling season, such as gopher rockfish (S. carnatus), may be among the most affected. We tested the transgenerational effects of future hypoxic conditions on the metabolic status of gopher rockfish larvae. Four pregnant females were held during gestation in either ambient conditions (DO~8 mg/L) or a hypoxic treatment (DO~4 mg/L). A subset of larvae was sampled immediately post-parturition and remaining larvae were then split into two groups and placed in either control or hypoxic conditions for five days and sampled again. Citrate synthase (CS) and lactate dehydrogenase (LDH), proxies for aerobic and anaerobic metabolism, respectively, were assayed in pooled larval samples from all treatments. We expected that larvae would exhibit relatively greater reliance on aerobic metabolism (e.g., higher CS/LDH ratios) if exposure to hypoxia during pregnancy enhances larval performance to hypoxia post-parturition, compared with larvae from control mothers. We also expected that larvae from control mothers would exhibit relatively greater reliance on anaerobic metabolism if exposed to hypoxic post-parturition. Lastly, we hypothesized that larvae from hypoxic mothers would rely more on anaerobic metabolism immediately post-parturition. At birth, we found larvae from hypoxic mothers were more anaerobic compared to those from control mothers, but after five days we found trends that larvae from hypoxic mothers that continued developing in hypoxic conditions were more aerobic compared to those from control mothers. Our findings suggest the potential for larval gopher rockfish to exhibit a more aerobic phenotype when gestated during hypoxic conditions and placed in similar conditions post-parturition.

Abstrakt Fragestellung Auf dem Markt befinden sich mehrere Heimmonitore, deren Zuverl~issigkeit bei der Detektion yon Apnoen, Desaturationen, Bradykardien und Tachykardien nicht gegen den Goldstandard einer kompletten Polysomnographie... more

Abstrakt Fragestellung Auf dem Markt befinden sich mehrere Heimmonitore, deren Zuverl~issigkeit bei der Detektion yon Apnoen, Desaturationen, Bradykardien und Tachykardien nicht gegen den Goldstandard einer kompletten Polysomnographie iiberprtift wurde. In dieser Studie wurde die Zuverl~,issigkeit des Heimmonitorings am Beispiel des Ger~ites Nellcor Puritan Bennett Assurance A4000 kombiniert mit dem Pulsoximeter NPB 290 tiberprtift. Patienten und Methodik 21 S~iuglinge (12 Knaben, 9 M~idchen) wurden im Alter von 15,2+ 12,0 Wochen (median 13,0; Bereich 3-51 Wochen; Gestationsalter 37,6 _+ 4,2 Wochen, median 39,0, Bereich 25 +41 Wochen) zum Ausschluss schlafbezogener kardiorespiratorischer Atemregulationsst6rungen polysomnographisch untersucht (Alice 3, manuelle Evaluierung). Ergebnisse WiJ.hrend dieser Untersuchung erfolgte eine simultane Ableitung mit dem Monitor Nellcor Puritan Bennett Assurance A4000 gemeinsam mit dem Pulsoximeter NPB 290 (Fa. Mallinckrodt). Mit beiden Systemen wurden bei 7/21 Patienten keinerlei Ereignisse registriert (patientenbezogene Spezifit~it 100%). 16 Apnoen mit Desaturationen wurden bei 4 Patienten durch den Monitor nicht erkannt. Von 26 weiteren Apnoen mit Bradykardien wurden lediglich 10 detektiert. Zus~itzliche 42 Bradykardien bei 2 Patienten wuro den nut 27-mal bei 1 Patienten erkannt. 116 isolierte Desaturationen bei 3 Patienten wurden in keinem Fall erfasst. Beztiglich der Erkennung von Apnoen ergab sich eine ereignisbezogene Sensitivit~it von 64,3 % (bei 5/21 Patienten mit Apnoen wurden diese nicht detektiert). Die Apnoe-, Bradykardie-und Hypox~imiedetektion des Monitorsystems erwies sich als unzureichend. Schlussfolgerung Vor der Markteinftihrung von 0berwachungsger~iten ist generell eine polysomnographische Prtifung zu fordern.

Current cancer research is being increasingly focused on the study of distinctive characters of tumour metabolism, resulting in a switch from oxidative phosphorylation to glycolysis (Warburg effect). Isoform 5 of human lactate... more

Current cancer research is being increasingly focused on the study of distinctive characters of tumour metabolism, resulting in a switch from oxidative phosphorylation to glycolysis (Warburg effect). Isoform 5 of human lactate dehydrogenase (hLDH5), which catalyzes the final step in the glycolytic cascade (pyruvate to lactate), constitutes a relatively new and untapped anti-cancer target. In this study, careful design and synthesis of a selected series of aryl-substituted N-hydroxyindole-2-carboxylates (NHIs) has led to several hLDH5-inhibitors, showing "first-in-class" potency and isoform selectivity. Enzyme kinetics studies indicated that these inhibitors exhibit a competitive mode of inhibition. Some representative examples were tested against two human pancreatic carcinoma cell lines, and displayed a good antiproliferative activity, which was even more evident under hypoxic conditions.

Poor angiogenesis within tissue-engineered grafts has been identified as a main challenge limiting the clinical introduction of bone tissue-engineering (BTE) approaches for the repair of large bone defects. Thick BTE grafts often exhibit... more

Poor angiogenesis within tissue-engineered grafts has been identified as a main challenge limiting the clinical introduction of bone tissue-engineering (BTE) approaches for the repair of large bone defects. Thick BTE grafts often exhibit poor cellular viability particularly at the core, leading to graft failure and lack of integration with host tissues. Various BTE approaches have been explored for improving vascularisation in tissue-engineered constructs and are briefly discussed in this review. Recent investigations relating to co-culture systems of endothelial and osteoblast-like cells have shown evidence of BTE efficacy in increasing vascularization in thick constructs. This review provides an overview of key concepts related to bone formation and then focuses on the current state of engineered vascularized co-culture systems using bone repair as a model. It will also address key questions regarding the generation of clinically relevant vascularized bone constructs as well as potential directions and considerations for research with the objective of pursuing engineered co-culture systems in other disciplines of vascularized regenerative medicine. The final objective is to generate serious and functional long-lasting vessels for sustainable angiogenesis that will enable enhanced cellular survival within thick voluminous bone grafts, thereby aiding in bone formation and remodelling in the long term. However, more evidence about the quality of blood vessels formed and its associated functional improvement in bone formation as well as a mechanistic understanding of their interactions are necessary for designing better therapeutic strategies for translation to clinical settings. Figure 1. (A) Hierarchical structure of bone from a sub-nanostructure of collagen molecules to a nanostructure of cylindrically arranged microfibrils to lamellar layers forming the macrostructure of cortical bone (adapted from Rho et al. (1998). (B) Vascularised bone anatomy and microenvironmental influences such as biomechanical, microarchitectural and low oxygen tension factors Y. Liu et al.

The relationship between induced limbal hyperaemia and lens oxygen transmissibility was investigated in a series of clinical studies in which subjects wore a range of soft contact lenses for eight hours each. Data representing the degree... more

The relationship between induced limbal hyperaemia and lens oxygen transmissibility was investigated in a series of clinical studies in which subjects wore a range of soft contact lenses for eight hours each. Data representing the degree of limbal hyperaemia induced in each case was extracted and subjected to non linear regression analysis with hyperaemia as dependent, and oxygen transmissibility as independent variables. Strong, statistically significant associations were found, particularly when oxygen transmissibility in a 12 mm diameter annular zone at the lens periphery was considered. Best fitting functions were of an inverse form for nasal (r# l 0n86, P l 0n008) and temporal (r# l 0n81, P l 0n014) quadrants and a logarithmic form for superior (r# l 0n87, P l 0n007) and inferior (r# l 0n97, P 0n005) quadrants. These findings provide support for an hypoxic theory of soft contact lens induced limbal hyperaemia. Estimates based on the logarithmic model suggest a 95 % confidence interval for the peripheral oxygen transmissibility required to avoid limbal hyperaemia of 56-274i10 −* (cm s −" ) (mlO # ml −" imm Hg).

There are many factors in mucosal secretions that contribute to innate immunity and the 'first line of defence' at mucosal surfaces. Few studies, however, have investigated the effects of exercise on many of these 'defence' factors. The... more

There are many factors in mucosal secretions that contribute to innate immunity and the 'first line of defence' at mucosal surfaces. Few studies, however, have investigated the effects of exercise on many of these 'defence' factors. The aim of the present study was to determine the acute effects of prolonged exercise on salivary levels of selected antimicrobial peptides (AMP) that have not yet been studied in response to exercise (HNP1-3 and LL-37) in addition to immunoglobulin A (IgA). A secondary objective was to assess the effects of exercise on saliva antibacterial capacity. Twelve active men exercised on a cycle ergometer for 2.5 h at approximately 60% of maximal oxygen uptake. Unstimulated whole saliva samples were obtained before and after exercise. There was a significant decrease (P < 0.05) in salivary IgA:osmolality ratio, following exercise, but IgA concentration and secretion rate were unaltered. Salivary HNP1-3 and LL-37 concentrations (P < 0.01 and P < 0.05, respectively), concentration:osmolality ratios (P < 0.01) and secretion rates (P < 0.01) all increased following exercise. Salivary antibacterial capacity (against E. coli) did not change. The increased concentration of AMPs in saliva may confer some benefit to the 'first line of defence' and could result from synergistic compensation within the mucosal immune system and/or airway inflammation and epithelial damage. Further study is required to determine the significance of such changes on the overall 'defence' capacity of saliva and how this influences the overall risk for infection.

Insects exhibit a remarkable array of adaptations that allow them to handle more or less severe hypoxia associated with numerous aquatic and terrestrial habitats. We consider these habitats and then discuss physiological, behavioral and... more

Insects exhibit a remarkable array of adaptations that allow them to handle more or less severe hypoxia associated with numerous aquatic and terrestrial habitats. We consider these habitats and then discuss physiological, behavioral and morphological mechanisms that facilitate insect life under oxygen deprivation. Actually or potentially hypoxic habitats include aquatic systems, flood-prone soils and burrows, intertidal zones, ice encasement and high altitudes. Some microhabitats, including dung, carrion, mammalian alimentary canals, grain and wood, also are subject to hypoxia. Adaptations to hypoxia include the ability to switch from aerobic to anaerobic metabolic pathways (with attendant generation of end products), the ability to drastically attenuate basal metabolic rates, altered behaviors and enlarged tracheal system volumes. Research into the biology of hypoxia seems to be progressing from early observations of the abilities of some insects to withstand exposure to hypoxia or anoxia through studies of organismal mechanisms operating in hypoxia to detailed investigations of cellular and intracellular signaling processes. Our hope is this essay will help crystallize the emergent picture of this area for those interested in contributing to future research.

Il ruolo fisiopatologico dell'aumentata sensibilità chemocettiva all'ipossia e/o all'ipercapnia è stato sottolineato in diverse patologie cardiovascolari, tra cui lo scompenso cardiaco, dove il chemoriflesso inizialmente ha una azione... more

Il ruolo fisiopatologico dell'aumentata sensibilità chemocettiva all'ipossia e/o all'ipercapnia è stato sottolineato in diverse patologie cardiovascolari, tra cui lo scompenso cardiaco, dove il chemoriflesso inizialmente ha una azione compensatoria; nelle fasi avanzate della malattia, sostiene attraverso un circolo vizioso l'attivazione simpatica con ripercussione negative della funzione ventricolare sinistra e sulla prognosi dei pazienti.

Objective: To assess the Groningen Sleep Quality Scale (GSQS) for evaluation of high-altitude sleep (HAS) disturbance and employ GSQ questionnaire to describe HAS. Methods: After the first night's stay at the altitude of 3500 m, quality... more

Objective: To assess the Groningen Sleep Quality Scale (GSQS) for evaluation of high-altitude sleep (HAS) disturbance and employ GSQ questionnaire to describe HAS. Methods: After the first night's stay at the altitude of 3500 m, quality of sleep for 100 participants (age: 29.13 ± 11.01 years; 36 females/64 males) was assessed using the self-administered 15-item GSQS translated into Farsi. Results: Mean GSQS score was 5.36 ± 4.32; 38 (38%) participants had a score equal to or less than 2, and 46 (46%) participants had a score equal to or more than 6. A Cronbach's alpha of 0.90 was calculated for internal consistency. Waking up several times during the night was the most prevalent complaint during the first night of sleep, and absolute inability to sleep was the most uncommon problem. Conclusions: HAS disturbance, which involved many of newcomers to a high altitude, had various harmful effects. For HAS research, GSQS was confirmed to be valid and reliable.

M, CASAS H, PAGES T, RAMA R, RICART Ar VENTURA JL, IBANEZ J, RODRiGUEZ FA, VISCOR G. Intermittent hypobaric hypoxia induces altitude acclimation and improves the lactate threshold. Aviat Space Environ Med 2000; 71:125-30.

Hypoxia-ischemia (HI) brain injury is a major cause of neuronal cell death especially apoptosis in the perinatal period. This study was designated to examine the effect of hydrogen therapy on apoptosis in an established neonatal HI rat... more

Hypoxia-ischemia (HI) brain injury is a major cause of neuronal cell death especially apoptosis in the perinatal period. This study was designated to examine the effect of hydrogen therapy on apoptosis in an established neonatal HI rat pup model. Seven-day-old rat pups were subjected to left common carotid artery ligation and then 90 min hypoxia (8% oxygen at 37 • C). Immediately after HI insult, pups were placed into a chamber filled with 2% H 2 for 30 min, 60 min, or 120 min, respectively. 24 h after 2% H 2 therapy, the pups were decapitated and brain injury was assessed by 2,3,5-triphenyltetrazoliumchloride (TTC), Nissl, and TUNEL staining, as well as caspase-3, caspase-12 activities in the cortex and hippocampus. H 2 treatment in a duration-dependent manner significantly reduced the number of positive TUNEL cells and suppressed caspase-3 and -12 activities. These results indicated H 2 administration after HI appeared to provide brain protection via inhibition of neuronal apoptosis.

Extremes of climate and hypobaric hypoxia cause poor growth performance in broiler chickens at high altitude and the present study investigates the effect of aqueous extract of Salix alba leaves on growth performance, antioxidant level... more

Extremes of climate and hypobaric hypoxia cause poor growth performance in broiler chickens at high altitude and the present study investigates the effect of aqueous extract of Salix alba leaves on growth performance, antioxidant level and immune status of broiler chickens reared at high altitude cold desert (3500 m). High performance liquid chromatography (HPLC) analysis of the extract revealed the presence of salicin and caffeic acid. In vitro efficacy evaluation revealed that the extract had a significant cytoprotective effect on lymphocytes. For in-vivo study, a total of 105 one d old RIR cross-bred broiler chickens were randomly assigned to seven groups: 1) Control fed basal diet and 2) Six treatments fed basal diet + S. alba extract @100, 150, 200, 300, 400, and 800 mg kg−1 body weight of chicken, respectively. Chickens in the Salix 300 group had greater body weight (p < 0.05) and improved feed conversion ratio (FCR) compared to other treatments. Furthermore, chickens had greater (p < 0.05) total antioxidant capacity (TAC), free radical scavenging activity, interleukin-2, and lower malondialdehyde (MDA), interleukin-1, and interleukin-6 concentration as compared to the control group. Net profit was also increased in all the treatments that were fed diet with S. alba extract due to less mortality in chickens. These findings indicated that inclusion S. alba extract at dose concentration of 300 mg kg−1 body weight of chicken, exhibited a beneficial effect on growth performance through immunomodulation and up-regulation of antioxidants, and therefore, it has a potential to be used as a phytogenic feed additive for improving broiler performance at high altitude.

Candidate number: EXTENDED ESSAY in BIOLOGY The effect of Chios Mastic Gum Oil (Pistacia lentiscus var. chia) on neuronal survival under nonphysiological conditions Word Count: 3697 MAY 2015 Figure 1 : Cells in Normal (left) and Hypoxia... more

Candidate number: EXTENDED ESSAY in BIOLOGY The effect of Chios Mastic Gum Oil (Pistacia lentiscus var. chia) on neuronal survival under nonphysiological conditions Word Count: 3697 MAY 2015 Figure 1 : Cells in Normal (left) and Hypoxia Condition (right) Live Photomicrograph power ×20 depicting cultures under normal and hypoxic conditions Photo provided by Dr. Vekrellis

Herein we present results from one of the first extensive bay-wide oceanographic surveys of Manila Bay, wherein 31 stations were sampled during the northeast monsoon (cold and dry season). A band of hypoxic bottom water (dissolved oxygen... more

Herein we present results from one of the first extensive bay-wide oceanographic surveys of Manila Bay, wherein 31 stations were sampled during the northeast monsoon (cold and dry season). A band of hypoxic bottom water (dissolved oxygen <2.8 mg/L) spanned the midsection of the bay from east to west.

Repeated sprint ability (RSA) is a critical success factor for intermittent sport performance. Repeated sprint training has been shown to improve RSA, we hypothesised that hypoxia would augment these training adaptations. Thirty male... more

Repeated sprint ability (RSA) is a critical success factor for intermittent sport performance. Repeated sprint training has been shown to improve RSA, we hypothesised that hypoxia would augment these training adaptations. Thirty male well-trained academy rugby union and rugby league players (18.4±1.5 years, 1.83±0.07 m, 88.1±8.9 kg) participated in this singleblind repeated sprint training study. Participants completed 12 sessions of repeated sprint training (10×6 s, 30 s recovery) over 4 weeks in either hypoxia (13% F i O 2 ) or normoxia (21% F i O 2 ). Pretraining and post-training, participants completed sports specific endurance and sprint field tests and a 10×6 s RSA test on a non-motorised treadmill while measuring speed, heart rate, capillary blood lactate, muscle and cerebral deoxygenation and respiratory measures. Yo-Yo Intermittent Recovery Level 1 test performance improved after RS training in both groups, but gains were significantly greater in the hypoxic (33±12%) than the normoxic group (14±10%, p<0.05). During the 10×6 s RS test there was a tendency for greater increases in oxygen consumption in the hypoxic group (hypoxic 6.9±9%, normoxic (−0.3±8.8%, p=0.06) and reductions in cerebral deoxygenation (% changes for both groups, p=0.09) after hypoxic than normoxic training. Twelve RS training sessions in hypoxia resulted in twofold greater improvements in capacity to perform repeated aerobic high intensity workout than an equivalent normoxic training. Performance gains are evident in the short term (4 weeks), a period similar to a preseason training block.

An 80-year-old woman from Iran presented to our institution for evaluation of insidious onset of dyspnea and progressive hypoxemia. She had a history of hypertension, COPD attributed to secondhand smoke, and an unprovoked pulmonary... more

An 80-year-old woman from Iran presented to our institution for evaluation of insidious onset of dyspnea and progressive hypoxemia. She had a history of hypertension, COPD attributed to secondhand smoke, and an unprovoked pulmonary embolus that was treated with lifelong anticoagulation. In addition, she had a history of latent TB status posttreatment with isoniazid 10 years prior. One year ago, home oxygen therapy was started at 4 L/min via nasal cannula, and because of her decline, her son had brought her to the United States 3 months earlier for medical help. After a contrast-enhanced thoracic CT scan followed by a nondiagnostic thoracentesis, another hospital informed her that she likely had inoperable lung cancer. She presented to our institution for a second opinion.

A broad pattern of correlations between mechanisms of brain function impairment and self-transcendence is shown. The pattern includes such mechanisms as cerebral hypoxia, physiological stress, transcranial magnetic stimulation,... more

A broad pattern of correlations between mechanisms of brain function impairment and self-transcendence is shown. The pattern includes such mechanisms as cerebral hypoxia, physiological stress, transcranial magnetic stimulation, trance-induced physiological effects, the action of psychoactive substances and even physical trauma to the brain. In all these cases, subjects report self-transcending experiences o en described as ‘mystical’ and ‘awareness-expanding,’ as well as self-transcending skills o en described as ‘savant.’ The idea that these correlations could be rather trivially accounted for on the basis of disruptions to inhibitory neural processes is reviewed and shown to be implausible. Instead, this paper suggests that an as-of-yet unrecognized causal principle underlying the entire pattern might be at work, whose further elucidation through systematic research could hold great promise.

Noninvasive ventilation [NIV] is used extensively in acute and chronic settings, at home, and in hospitals. It plays a pivotal role in managing respiratory failure during the COVID-19 pandemic with robust use in hospitals to avert the... more

Noninvasive ventilation [NIV] is used extensively in acute and chronic settings, at home, and in hospitals. It plays a pivotal role in managing respiratory failure during the COVID-19 pandemic with robust use in hospitals to avert the need for intubation as well as re-intubation. However, its use is associated with aerosol generation, which poses an immediate threat to all who work around it, like healthcare workers. Besides, domiciliary use is also associated with the same risk to the household and caregivers. Therefore, we need to plan the therapy and forge guidelines and recommendations to keep NIV safe during infections. Here we have reviewed the available literature and applied our experience to formulate guidelines and recommendations. However, updates and appraisals are evolving rapidly, and we need to keep our eyes open to tailor our approach.

Hypoxia is a global phenomenon affecting recruitment as well as the embryonic development of aquatic fauna. The present study depicts hypoxia induced disruption of the intrinsic pathway of programmed cell death (PCD), leading to embryonic... more

Hypoxia is a global phenomenon affecting recruitment as well as the embryonic development of aquatic fauna. The present study depicts hypoxia induced disruption of the intrinsic pathway of programmed cell death (PCD), leading to embryonic malformation in the goldfish, Carrasius auratus. Constant hypoxia induced the early expression of pro-apoptotic/tumor suppressor p53 and concomitant expression of the cell death molecule, caspase-3, leading to high level of DNA damage and cell death in hypoxic embryos, as compared to normoxic ones. As a result, the former showed delayed 4 and 64 celled stages and a delay in appearance of epiboly stage. Expression of p53 efficiently switched off expression of the antiapoptotic Bcl-2 during the initial 12 hours post fertilization (hpf) and caused embryonic cell death. However, after 12 hours, simultaneous downregulation of p53 and Caspase-3 and exponential increase of Bcl-2, caused uncontrolled cell proliferation and prevented essential programmed cell death (PCD), ultimately resulting in significant (p,0.05) embryonic malformation up to 144 hpf. Evidences suggest that uncontrolled cell proliferation after 12 hpf may have been due to downregulation of p53 abundance, which in turn has an influence on upregulation of anti-apoptotic Bcl-2. Therefore, we have been able to show for the first time and propose that hypoxia induced downregulation of p53 beyond 12 hpf, disrupts PCD and leads to failure in normal differentiation, causing malformation in gold fish embryos.