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Annual International Conference of the... Jul 2019Sleep is characterized by dynamic coupling between central (CNS) and peripheral autonomic (ANS) nervous systems. However, further research is needed to better understand...
Sleep is characterized by dynamic coupling between central (CNS) and peripheral autonomic (ANS) nervous systems. However, further research is needed to better understand the multiple interactions occurring among electroencephalographic (EEG) features and respiratory and cardiovascular (CV) outputs modulated by the ANS during sleep. Here, we developed new methods to study EEG slow-wave activity (SWA) during non-rapid eye movement (NREM) sleep with respect to the phases of peripheral oscillations. EEG, respiration, and continuous blood pressure signals recorded from 20 participants were analyzed. Digital filters, designed to decompose the signals into different frequency bands, and the Hilbert transform were applied to estimate the instantaneous phases and frequencies of the peripheral oscillations. The peripheral oscillations were categorized into four phases representing up and down states. EEG delta power (synchronized SWA) was computed and compared across these phases during NREM sleep. Results show that EEG delta power is higher during down phases of slow and respiratory frequency components of blood pressure and during up phases of respiration, suggestive of CNS-ANS coupling during NREM sleep. The developed techniques provide the preliminary framework to further analyze and interpret complex interactions between cortical and cardiac oscillations and their synchrony.
Topics: Autonomic Nervous System; Blood Pressure; Central Nervous System; Electroencephalography; Humans; Oscillometry; Respiration; Sleep Stages
PubMed: 31946420
DOI: 10.1109/EMBC.2019.8857490 -
Journal of Nuclear Medicine : Official... Jun 2008Hypoxia, a condition of insufficient O2 to support metabolism, occurs when the vascular supply is interrupted, as in stroke or myocardial infarction, or when a tumor... (Review)
Review
Hypoxia, a condition of insufficient O2 to support metabolism, occurs when the vascular supply is interrupted, as in stroke or myocardial infarction, or when a tumor outgrows its vascular supply. When otherwise healthy tissues lose their O2 supply acutely, the cells usually die, whereas when cells gradually become hypoxic, they adapt by up-regulating the production of numerous proteins that promote their survival. These proteins slow the rate of growth, switch the mitochondria to glycolysis, stimulate growth of new vasculature, inhibit apoptosis, and promote metastatic spread. The consequence of these changes is that patients with hypoxic tumors invariably experience poor outcome to treatment. This has led the molecular imaging community to develop assays for hypoxia in patients, including regional measurements from O2 electrodes placed under CT guidance, several nuclear medicine approaches with imaging agents that accumulate with an inverse relationship to O2, MRI methods that measure either oxygenation directly or lactate production as a consequence of hypoxia, and optical methods with NIR and bioluminescence. The advantages and disadvantages of these approaches are reviewed, along with the individual strategies for validating different imaging methods. Ultimately the proof of value is in the clinical performance to predict outcome, select an appropriate cohort of patients to benefit from a hypoxia-directed treatment, or plan radiation fields that result in better local control. Hypoxia imaging in support of molecular medicine has become an important success story over the last decade and provides a model and some important lessons for development of new molecular imaging probes or techniques.
Topics: Animals; Cell Hypoxia; Coordination Complexes; Electron Spin Resonance Spectroscopy; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Neoplasms; Neovascularization, Pathologic; Nitroimidazoles; Organometallic Compounds; Oximetry; Oxygen; Positron-Emission Tomography; Radiopharmaceuticals; Thiosemicarbazones
PubMed: 18523070
DOI: 10.2967/jnumed.107.045914 -
Pediatrics and Neonatology Mar 2023Neuromuscular disease (NMDs) encompass a heterogeneous group of genetic disorders, with respiratory problems of variable intensity and progression described at any... (Review)
Review
Neuromuscular disease (NMDs) encompass a heterogeneous group of genetic disorders, with respiratory problems of variable intensity and progression described at any pediatric age, from infancy to adolescence, and they are largely associated with significant lifelong morbidity and high mortality. Restriction of breathing, impaired gas exchange, decline of lung function and sleep disordered breathing progressively develop because of muscular weakness and culminate in respiratory failure. Depending on the disease progression, airways manifestations can take weeks to months or even years to evolve, thus depicting two major respiratory phenotypes, characterized by rapid or slow progression to respiratory failure. Assessing type and age at onset of airways problems and their evolution over time can support pediatricians in the diagnostic assessment of NMD. In addition, knowing the characteristics of patients' respiratory phenotype can increase the level of awareness among neonatologists, geneticists, neurologists, pulmonologists, nutritionists, and chest therapists, supporting them in the challenging task of the multidisciplinary medical care of patients. In this review we examine the issues related to the pediatric respiratory phenotypes of NMD and present a novel algorithm that can act as a guide for the diagnostic agenda and the key preventive or therapeutic interventions of airways manifestations. With prolonged survival of children with NMD, the advent of neuromuscular respiratory medicine, including accurate assessment of the respiratory phenotype, will help physicians to determine patients' prognoses and to design studies for the evaluation of new therapies.
Topics: Humans; Neuromuscular Diseases; Respiratory Insufficiency; Respiratory Rate; Pediatricians
PubMed: 36682912
DOI: 10.1016/j.pedneo.2022.09.016 -
International Journal of Molecular... Aug 2023Cellular respiration is associated with at least six distinct but intertwined biological functions. (1) biosynthesis of ATP from ADP and inorganic phosphate, (2)... (Review)
Review
Cellular respiration is associated with at least six distinct but intertwined biological functions. (1) biosynthesis of ATP from ADP and inorganic phosphate, (2) consumption of respiratory substrates, (3) support of membrane transport, (4) conversion of respiratory energy to heat, (5) removal of oxygen to prevent oxidative damage, and (6) generation of reactive oxygen species (ROS) as signaling molecules. Here we focus on function #6, which helps the organism control its mitochondria. The ROS bursts typically occur when the mitochondrial membrane potential (MMP) becomes too high, e.g., due to mitochondrial malfunction, leading to cardiolipin (CL) oxidation. Depending on the intensity of CL damage, specific programs for the elimination of damaged mitochondria (mitophagy), whole cells (apoptosis), or organisms (phenoptosis) can be activated. In particular, we consider those mechanisms that suppress ROS generation by enabling ATP synthesis at low MMP levels. We discuss evidence that the mild depolarization mechanism of direct ATP/ADP exchange across mammalian inner and outer mitochondrial membranes weakens with age. We review recent data showing that by protecting CL from oxidation, mitochondria-targeted antioxidants decrease lethality in response to many potentially deadly shock insults. Thus, targeting ROS- and CL-dependent pathways may prevent acute mortality and, hopefully, slow aging.
Topics: Animals; Reactive Oxygen Species; Respiration; Mitochondria; Aging; Cardiolipins; Adenosine Triphosphate; Mammals
PubMed: 37628720
DOI: 10.3390/ijms241612540 -
PloS One 2012A slow respiration-related rhythm strongly shapes the activity of the olfactory bulb. This rhythm appears as a slow oscillation that is detectable in the membrane...
BACKGROUND
A slow respiration-related rhythm strongly shapes the activity of the olfactory bulb. This rhythm appears as a slow oscillation that is detectable in the membrane potential, the respiration-related spike discharge of the mitral/tufted cells and the bulbar local field potential. Here, we investigated the rules that govern the manifestation of membrane potential slow oscillations (MPSOs) and respiration-related discharge activities under various afferent input conditions and cellular excitability states.
METHODOLOGY AND PRINCIPAL FINDINGS
We recorded the intracellular membrane potential signals in the mitral/tufted cells of freely breathing anesthetized rats. We first demonstrated the existence of multiple types of MPSOs, which were influenced by odor stimulation and discharge activity patterns. Complementary studies using changes in the intracellular excitability state and a computational model of the mitral cell demonstrated that slow oscillations in the mitral/tufted cell membrane potential were also modulated by the intracellular excitability state, whereas the respiration-related spike activity primarily reflected the afferent input. Based on our data regarding MPSOs and spike patterns, we found that cells exhibiting an unsynchronized discharge pattern never exhibited an MPSO. In contrast, cells with a respiration-synchronized discharge pattern always exhibited an MPSO. In addition, we demonstrated that the association between spike patterns and MPSO types appeared complex.
CONCLUSION
We propose that both the intracellular excitability state and input strength underlie specific MPSOs, which, in turn, constrain the types of spike patterns exhibited.
Topics: Animals; Intracellular Space; Kinetics; Male; Membrane Potentials; Odorants; Olfactory Bulb; Periodicity; Rats; Rats, Wistar; Respiration
PubMed: 22952828
DOI: 10.1371/journal.pone.0043964 -
PloS One 2022Busana et al. (doi.org/10.1152/japplphysiol.00871.2020) published 5 patients with COVID-19 in whom the fraction of non-aerated lung tissue had been quantified by...
Busana et al. (doi.org/10.1152/japplphysiol.00871.2020) published 5 patients with COVID-19 in whom the fraction of non-aerated lung tissue had been quantified by computed tomography. They assumed that shunt flow fraction was proportional to the non-aerated lung fraction, and, by randomly generating 106 different bimodal distributions for the ventilation-perfusion ([Formula: see text]) ratios in the lung, specified as sets of paired values {[Formula: see text]}, sought to identify as solutions those that generated the observed arterial partial pressures of CO2 and O2 (PaCO2 and PaO2). Our study sought to develop a direct method of calculation to replace the approach of randomly generating different distributions, and so provide more accurate solutions that were within the measurement error of the blood-gas data. For the one patient in whom Busana et al. did not find solutions, we demonstrated that the assumed shunt flow fraction led to a non-shunt blood flow that was too low to support the required gas exchange. For the other four patients, we found precise solutions (prediction error < 1x10-3 mmHg for both PaCO2 and PaO2), with distributions qualitatively similar to those of Busana et al. These distributions were extremely wide and unlikely to be physically realisable, because they predict the maintenance of very large concentration gradients in regions of the lung where convection is slow. We consider that these wide distributions arise because the assumed value for shunt flow is too low in these patients, and we discuss possible reasons why the assumption relating to shunt flow fraction may break down in COVID-19 pneumonia.
Topics: COVID-19; Humans; Lung; Oxygen; Perfusion; Pulmonary Gas Exchange; Ventilation-Perfusion Ratio
PubMed: 36040974
DOI: 10.1371/journal.pone.0273214 -
Scientific Reports Mar 2021Tumors experience temporal and spatial fluctuations in oxygenation. Hypoxia inducible transcription factors (HIF-α) respond to low levels of oxygen and induce re-supply...
Tumors experience temporal and spatial fluctuations in oxygenation. Hypoxia inducible transcription factors (HIF-α) respond to low levels of oxygen and induce re-supply oxygen. HIF-α stabilization is typically facultative, induced by hypoxia and reduced by normoxia. In some cancers, HIF-α stabilization becomes constitutive under normoxia. We develop a mathematical model that predicts how fluctuating oxygenation affects HIF-α stabilization and impacts net cell proliferation by balancing the base growth rate, the proliferative cost of HIF-α expression, and the mortality from not expressing HIF-α during hypoxia. We compare optimal net cell proliferation rate between facultative and constitutive HIF-α regulation in environments with different oxygen profiles. We find that that facultative HIF-α regulation promotes greater net cell proliferation than constitutive regulation with stochastic or slow periodicity in oxygenation. However, cell fitness is nearly identical for both HIF-α regulation strategies under rapid periodic oxygenation fluctuations. The model thus indicates that cells constitutively expressing HIF-α may be at a selective advantage when the cost of expression is low. In cancer, this condition is known as pseudohypoxia or the "Warburg Effect". We conclude that rapid and regular cycling of oxygenation levels selects for pseudohypoxia, and that this is consistent with the ecological theory of optimal defense.
Topics: Cell Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Models, Biological; Oxygen; Protein Stability; Stochastic Processes; Tumor Microenvironment
PubMed: 33707510
DOI: 10.1038/s41598-021-85184-8 -
Pulmonary Medicine 2017Portable inhalers are divisible into those that deliver medication by patient triggering (pMDIs: a gentle slow inhalation) and those that use the patient's inspiratory... (Review)
Review
Portable inhalers are divisible into those that deliver medication by patient triggering (pMDIs: a gentle slow inhalation) and those that use the patient's inspiratory effort as the force for deaggregation and delivery (DPIs: a stronger deeper inspiratory effort). Patient confusion and poor technique are commonplace. The use of training tools has become standard practice, and unique amongst these is an inspiratory flow meter (In-Check) which is able to simulate the resistance characteristics of different inhalers and, thereby, guide the patient to the correct effort. In-Check's origins lie in the 1960s peak flow meters, the development of the Mini-Wright peak flow meter, and inspiratory flow assessment via the nose during the 1970s-1980s. The current device (In-Check DIAL G16) is the third iteration of the original 1998 training tool, with detailed and ongoing assessments of all common inhaler resistances (including combination and breath-actuated inhaler types) summarised into resistance ranges that are preset within the device. The device works by interpolating one of six ranges with the inspiratory effort. Use of the tool has been shown to be contributory to significant improvements in asthma care and control, and it is being advocated for assessment and training in irreversible lung disease.
Topics: Administration, Inhalation; Dry Powder Inhalers; Equipment Design; Humans; Inhalation; Metered Dose Inhalers; Patient Education as Topic; Respiratory Therapy
PubMed: 29348936
DOI: 10.1155/2017/1495867 -
The Journal of Neuroscience : the... Jan 2016We have recently described a slow oscillation in the hippocampus of urethane-anesthetized mice, which couples to nasal respiration and is clearly distinct from... (Comparative Study)
Comparative Study
UNLABELLED
We have recently described a slow oscillation in the hippocampus of urethane-anesthetized mice, which couples to nasal respiration and is clearly distinct from co-occurring theta oscillations. Here we set out to investigate whether such type of patterned network activity, which we named "hippocampal respiration rhythm" (HRR), also occurs in awake mice. In freely moving mice, instantaneous respiration rate is extremely variable, and respiration is superimposed by bouts of sniffing. To reduce this variability, we clamped the behavior of the animal to either awake immobility or treadmill running by using a head-fixed setup while simultaneously recording respiration and field potentials from the olfactory bulb (OB) and hippocampus. Head-fixed animals often exhibited long periods of steady respiration rate during either immobility or running, which allowed for spectral and coherence analyses with a sufficient frequency resolution to sort apart respiration and theta activities. We could thus demonstrate the existence of HRR in awake animals, namely, a respiration-entrained slow rhythm with highest amplitude at the dentate gyrus. HRR was most prominent during immobility and running with respiration rates slower than theta oscillations. Nevertheless, HRR could also be faster than theta. Discharges of juxtacellularly recorded cells in CA1 and dentate gyrus were modulated by HRR and theta oscillations. Granger directionality analysis revealed that HRR is caused by the OB and that theta oscillations in OB are caused by the hippocampus. Our results suggest that respiration-coupled oscillations aid the exchange of information between olfactory and memory networks.
SIGNIFICANCE STATEMENT
Olfaction is a major sense in rodents. In consequence, the olfactory bulb (OB) should be able to transmit information to downstream regions. Here we report potential mechanisms underlying such information transfer. We demonstrate the existence of a respiration-entrained rhythm in the hippocampus of awake mice. Frequencies of the hippocampal respiration rhythm (HRR) overlap with classical theta oscillations, but both rhythms are clearly distinct. HRR is most prominent in the dentate gyrus, especially when respiration is slower than theta frequency. Discharges of neurons in CA1 and dentate gyrus are modulated by both HRR and theta. Directionality analysis shows that HRR is caused by the OB. Our results suggest that respiration-coupled oscillations aid the exchange of information between olfactory and memory networks.
Topics: Animals; Biological Clocks; Female; Hippocampus; Male; Mice; Mice, Inbred C57BL; Respiratory Center; Respiratory Rate; Theta Rhythm; Wakefulness
PubMed: 26740658
DOI: 10.1523/JNEUROSCI.2848-15.2016 -
Plant Physiology Nov 2010Malate dehydrogenase (MDH) catalyzes a reversible NAD(+)-dependent-dehydrogenase reaction involved in central metabolism and redox homeostasis between organelle...
Malate dehydrogenase (MDH) catalyzes a reversible NAD(+)-dependent-dehydrogenase reaction involved in central metabolism and redox homeostasis between organelle compartments. To explore the role of mitochondrial MDH (mMDH) in Arabidopsis (Arabidopsis thaliana), knockout single and double mutants for the highly expressed mMDH1 and lower expressed mMDH2 isoforms were constructed and analyzed. A mmdh1mmdh2 mutant has no detectable mMDH activity but is viable, albeit small and slow growing. Quantitative proteome analysis of mitochondria shows changes in other mitochondrial NAD-linked dehydrogenases, indicating a reorganization of such enzymes in the mitochondrial matrix. The slow-growing mmdh1mmdh2 mutant has elevated leaf respiration rate in the dark and light, without loss of photosynthetic capacity, suggesting that mMDH normally uses NADH to reduce oxaloacetate to malate, which is then exported to the cytosol, rather than to drive mitochondrial respiration. Increased respiratory rate in leaves can account in part for the low net CO(2) assimilation and slow growth rate of mmdh1mmdh2. Loss of mMDH also affects photorespiration, as evidenced by a lower postillumination burst, alterations in CO(2) assimilation/intercellular CO(2) curves at low CO(2), and the light-dependent elevated concentration of photorespiratory metabolites. Complementation of mmdh1mmdh2 with an mMDH cDNA recovered mMDH activity, suppressed respiratory rate, ameliorated changes to photorespiration, and increased plant growth. A previously established inverse correlation between mMDH and ascorbate content in tomato (Solanum lycopersicum) has been consolidated in Arabidopsis and may potentially be linked to decreased galactonolactone dehydrogenase content in mitochondria in the mutant. Overall, a central yet complex role for mMDH emerges in the partitioning of carbon and energy in leaves, providing new directions for bioengineering of plant growth rate and a new insight into the molecular mechanisms linking respiration and photosynthesis in plants.
Topics: Arabidopsis; Arabidopsis Proteins; Carbon Dioxide; Cell Respiration; Gene Knockout Techniques; Genetic Complementation Test; Malate Dehydrogenase; Mitochondrial Proteins; Mutagenesis, Insertional; Mutation; Photosynthesis; Plant Leaves
PubMed: 20876337
DOI: 10.1104/pp.110.161612