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British Journal of Hospital Medicine... Jan 2023Optimisation of oxygenation strategies in patients with hypoxaemic respiratory failure is a top priority for acute care physicians, as hypoxaemic respiratory failure is... (Review)
Review
Optimisation of oxygenation strategies in patients with hypoxaemic respiratory failure is a top priority for acute care physicians, as hypoxaemic respiratory failure is one of the leading causes of admission. Various oxygenation methods range from non-invasive face masks to high flow nasal cannulae, which have advantages and disadvantages for this heterogeneous patient group. Focus has turned toward examining the benefits of non-invasive ventilation, as this was heavily researched in resource-limited settings during the COVID-19 pandemic. The oxygenation strategy should be determined on an individualised basis for patients, and with new evidence from the COVID-19 pandemic, providers may now consider placing further emphasis on non-invasive approaches. As non-invasive ventilation continues to be used in increasing frequency, new methods of monitoring patient response, including when to escalate ventilation strategy, will need to be validated.
Topics: Humans; Pandemics; COVID-19; Hypoxia; Respiratory Insufficiency; Noninvasive Ventilation; Oxygen Inhalation Therapy
PubMed: 36708347
DOI: 10.12968/hmed.2022.0420 -
Journal of Controlled Release :... Dec 2015One of the most challenging and clinically important goals in nanomedicine is to deliver imaging and therapeutic agents to solid tumors. Here we discuss the recent... (Review)
Review
One of the most challenging and clinically important goals in nanomedicine is to deliver imaging and therapeutic agents to solid tumors. Here we discuss the recent design and development of stimuli-responsive smart nanoparticles for targeting the common attributes of solid tumors such as their acidic and hypoxic microenvironments. This class of stimuli-responsive nanoparticles is inactive during blood circulation and under normal physiological conditions, but is activated by acidic pH, enzymatic up-regulation, or hypoxia once they extravasate into the tumor microenvironment. The nanoparticles are often designed to first "navigate" the body's vascular system, "dock" at the tumor sites, and then "activate" for action inside the tumor interstitial space. They combine the favorable biodistribution and pharmacokinetic properties of nanodelivery vehicles and the rapid diffusion and penetration properties of smaller drug cargos. By targeting the broad tumor habitats rather than tumor-specific receptors, this strategy has the potential to overcome the tumor heterogeneity problem and could be used to design diagnostic and therapeutic nanoparticles for a broad range of solid tumors.
Topics: Animals; Enzyme Activation; Humans; Hydrogen-Ion Concentration; Hypoxia; Nanoparticles; Neoplasms; Tumor Microenvironment
PubMed: 26341694
DOI: 10.1016/j.jconrel.2015.08.050 -
Biological Reviews of the Cambridge... Feb 2023Non-indigenous species (NIS) and hypoxia (<2 mg O l ) can disturb and restructure aquatic communities. Both are heavily influenced by human activities and are... (Review)
Review
Non-indigenous species (NIS) and hypoxia (<2 mg O l ) can disturb and restructure aquatic communities. Both are heavily influenced by human activities and are intensifying with global change. As these disturbances increase, understanding how they interact to affect native species and systems is essential. To expose patterns, outcomes, and generalizations, we thoroughly reviewed the biological invasion literature and compiled 100 studies that examine the interaction of hypoxia and NIS. We found that 64% of studies showed that NIS are tolerant of hypoxia, and 62% showed that NIS perform better than native species under hypoxia. Only one-quarter of studies examined NIS as creators of hypoxia; thus, NIS are more often considered passengers associated with hypoxia, rather than drivers of it. Paradoxically, the NIS that most commonly create hypoxia are primary producers. Taxa like molluscs are typically more hypoxia tolerant than mobile taxa like fish and crustaceans. Most studies examine individual-level or localized responses to hypoxia; however, the most extensive impacts occur when hypoxia associated with NIS affects communities and ecosystems. We discuss how these influences of hypoxia at higher levels of organization better inform net outcomes of the biological invasion process, i.e. establishment, spread, and impact, and are thus most useful to management. Our review identifies wide variation in the way in which the interaction between hypoxia and NIS is studied in the literature, and suggests ways to address the number of variables that affect their interaction and refine insight gleaned from future studies. We also identify a clear need for resource management to consider the interactive effects of these two global stressors which are almost exclusively managed independently.
Topics: Animals; Humans; Introduced Species; Ecosystem; Fishes; Hypoxia
PubMed: 36097368
DOI: 10.1111/brv.12900 -
International Journal of Molecular... Jul 2019Eukaryotes are often subjected to different kinds of stress. In order to adjust to such circumstances, eukaryotes activate stress-response pathways and regulate gene... (Review)
Review
Eukaryotes are often subjected to different kinds of stress. In order to adjust to such circumstances, eukaryotes activate stress-response pathways and regulate gene expression. Eukaryotic gene expression consists of many different steps, including transcription, RNA processing, RNA transport, and translation. In this review article, we focus on both transcriptional and post-transcriptional regulations of gene expression under hypoxic conditions. In the first part of the review, transcriptional regulations mediated by various transcription factors including Hypoxia-Inducible Factors (HIFs) are described. In the second part, we present RNA splicing regulations under hypoxic conditions, which are mediated by splicing factors and their kinases. This work summarizes and discusses the emerging studies of those two gene expression machineries under hypoxic conditions.
Topics: Animals; Gene Expression Regulation; Humans; Hypoxia; RNA Splicing; Transcription Factors; Transcription, Genetic
PubMed: 31277312
DOI: 10.3390/ijms20133278 -
Journal of Applied Physiology... Dec 2015The human pulmonary vasculature vasoconstricts in response to a reduction in alveolar oxygen tension, a phenomenon termed hypoxic pulmonary vasoconstriction (HPV). This... (Review)
Review
The human pulmonary vasculature vasoconstricts in response to a reduction in alveolar oxygen tension, a phenomenon termed hypoxic pulmonary vasoconstriction (HPV). This review describes the time course of this behavior, which occurs in distinct phases, and then explores the importance for HPV of the hypoxia-inducible factor (HIF) pathway. Next, the HIF-hydroxylase enzymes that act as molecular oxygen sensors within the HIF pathway are discussed. These enzymes are particularly sensitive to intracellular iron availability, which confers iron-sensing properties on the HIF pathway. Human studies of iron chelation and supplementation are then reviewed. These demonstrate that the iron sensitivity of the HIF pathway evident from in vitro experiments is relevant to human pulmonary vascular physiology. Next, the importance of iron status in high-altitude illness and chronic cardiopulmonary disease is explored, and the therapeutic potential of intravenous iron discussed. The review concludes by highlighting some further complexities that arise from interactions between the HIF pathway and other intracellular iron-sensing mechanisms.
Topics: Altitude Sickness; Animals; Humans; Hypoxia; Iron; Oxygen Consumption; Pulmonary Circulation; Vasoconstriction
PubMed: 26066825
DOI: 10.1152/japplphysiol.00179.2015 -
Acta Physiologica (Oxford, England) Jul 2022Hypoxic environments pose a severe challenge to vertebrates and even short periods of oxygen deprivation are often lethal as they constrain aerobic ATP production.... (Review)
Review
Hypoxic environments pose a severe challenge to vertebrates and even short periods of oxygen deprivation are often lethal as they constrain aerobic ATP production. However, a few ectotherm vertebrates are capable of surviving long-term hypoxia or even anoxia with little or no damage. Among these, freshwater turtles and crucian carp are the recognized champions of anoxia tolerance, capable of overwintering in complete oxygen deprivation for months at freezing temperatures by entering a stable hypometabolic state. While all steps of the oxygen cascade are adjusted in response to oxygen deprivation, this review draws from knowledge of freshwater turtles and crucian carp to highlight mechanisms regulating two of these steps, namely oxygen transport in the blood and oxygen utilization in mitochondria during three sequential phases: before anoxia, when hypoxia develops, during anoxia, and after anoxia at reoxygenation. In cold hypoxia, reduced red blood cell concentration of ATP plays a crucial role in increasing blood oxygen affinity and/or reducing oxygen unloading to tissues, to adjust aerobic metabolism to decrease ambient oxygen. In anoxia, metabolic rewiring of oxygen utilization keeps largely unaltered NADH/NAD ratios and limits ADP degradation and succinate buildup. These critical adjustments make it possible to restart mitochondrial respiration and energy production with little generation of reactive oxygen species at reoxygenation when oxygen is again available. Inhibition of key metabolic enzymes seems to play crucial roles in these responses, in particular mitochondrial complex V, although identifying the nature of such inhibition(s) in vivo remains a challenge for future studies.
Topics: Adenosine Triphosphate; Animals; Carps; Hypoxia; Oxygen; Turtles; Vertebrates
PubMed: 35548887
DOI: 10.1111/apha.13841 -
Physiology (Bethesda, Md.) Mar 2020
Topics: History, 21st Century; Humans; Hypoxia; Hypoxia-Inducible Factor 1; Medicine; Nobel Prize; Physiology; Vascular Endothelial Growth Factor A; Von Hippel-Lindau Tumor Suppressor Protein
PubMed: 32024429
DOI: 10.1152/physiol.00001.2020 -
Global Change Biology Aug 2022Oxygen availability is decreasing in many lakes and reservoirs worldwide, raising the urgency for understanding how anoxia (low oxygen) affects coupled biogeochemical...
Oxygen availability is decreasing in many lakes and reservoirs worldwide, raising the urgency for understanding how anoxia (low oxygen) affects coupled biogeochemical cycling, which has major implications for water quality, food webs, and ecosystem functioning. Although the increasing magnitude and prevalence of anoxia has been documented in freshwaters globally, the challenges of disentangling oxygen and temperature responses have hindered assessment of the effects of anoxia on carbon, nitrogen, and phosphorus concentrations, stoichiometry (chemical ratios), and retention in freshwaters. The consequences of anoxia are likely severe and may be irreversible, necessitating ecosystem-scale experimental investigation of decreasing freshwater oxygen availability. To address this gap, we devised and conducted REDOX (the Reservoir Ecosystem Dynamic Oxygenation eXperiment), an unprecedented, 7-year experiment in which we manipulated and modeled bottom-water (hypolimnetic) oxygen availability at the whole-ecosystem scale in a eutrophic reservoir. Seven years of data reveal that anoxia significantly increased hypolimnetic carbon, nitrogen, and phosphorus concentrations and altered elemental stoichiometry by factors of 2-5× relative to oxic periods. Importantly, prolonged summer anoxia increased nitrogen export from the reservoir by six-fold and changed the reservoir from a net sink to a net source of phosphorus and organic carbon downstream. While low oxygen in freshwaters is thought of as a response to land use and climate change, results from REDOX demonstrate that low oxygen can also be a driver of major changes to freshwater biogeochemical cycling, which may serve as an intensifying feedback that increases anoxia in downstream waterbodies. Consequently, as climate and land use change continue to increase the prevalence of anoxia in lakes and reservoirs globally, it is likely that anoxia will have major effects on freshwater carbon, nitrogen, and phosphorus budgets as well as water quality and ecosystem functioning.
Topics: Carbon; Ecosystem; Humans; Hypoxia; Lakes; Nitrogen; Oxygen; Phosphorus
PubMed: 35611634
DOI: 10.1111/gcb.16228 -
British Journal of Anaesthesia Oct 2022Peri-intubation oxygen administration to the pregnant patient during induction of general anaesthesia is critical to avoiding hypoxaemia and harm to the mother and...
Peri-intubation oxygen administration to the pregnant patient during induction of general anaesthesia is critical to avoiding hypoxaemia and harm to the mother and fetus. Recent modelling comparing low-flow with high-flow nasal oxygen in simulated term pregnant women of varying body habitus, taken together with previous work, suggests that face mask preoxygenation with the use of low-flow or high-flow nasal oxygen during the period of apnoea prolongs the safe apnoea period, with the benefit varying by body habitus. Low-flow compared with high-flow nasal oxygen may be easier to combine with face mask preoxygenation and is readily available in all operating theatres, although future improvements in high-flow nasal oxygen delivery systems may improve ease of use for this indication.
Topics: Apnea; Cesarean Section; Female; Humans; Hypoxia; Intubation, Intratracheal; Oxygen; Oxygen Inhalation Therapy; Pregnancy
PubMed: 35985842
DOI: 10.1016/j.bja.2022.07.014 -
Frontiers in Neural Circuits 2023Severe hypoxia induces seizures, which reduces ventilation and worsens the ictal state. It is a health threat to patients, particularly those with underlying hypoxic...
Severe hypoxia induces seizures, which reduces ventilation and worsens the ictal state. It is a health threat to patients, particularly those with underlying hypoxic respiratory pathologies, which may be conducive to a sudden unexpected death in epilepsy (SUDEP). Recent studies provide evidence that brain microglia are involved with both respiratory and ictal processes. Here, we investigated the hypothesis that microglia could interact with hypoxia-induced seizures. To this end, we recorded electroencephalogram (EEG) and acute ventilatory responses to hypoxia (5% O in N) in conscious, spontaneously breathing adult mice. We compared control vehicle pre-treated animals with those pre-treated with minocycline, an inhibitory modulator of microglial activation. First, we histologically confirmed that hypoxia activates microglia and that pre-treatment with minocycline blocks hypoxia-induced microglial activation. Then, we analyzed the effects of minocycline pre-treatment on ventilatory responses to hypoxia by plethysmography. Minocycline alone failed to affect respiratory variables in room air or the initial respiratory augmentation in hypoxia. The comparative results showed that hypoxia caused seizures, which were accompanied by the late phase ventilatory suppression in all but one minocycline pre-treated mouse. Compared to the vehicle pre-treated, the minocycline pre-treated mice showed a delayed occurrence of seizures. Further, minocycline pre-treated mice tended to resist post-ictal respiratory arrest. These results suggest that microglia are conducive to seizure activity in severe hypoxia. Thus, inhibition of microglial activation may help suppress or prevent hypoxia-induced ictal episodes.
Topics: Mice; Animals; Minocycline; Seizures; Microglia; Brain; Hypoxia
PubMed: 37035503
DOI: 10.3389/fncir.2023.1006424