Voice Reactivity as a Response to Acute Hypobaric Hypoxia at High Altitude

BACKGROUND: Although the understanding of hypobaric hypoxia is increasing, it remains a hazard in aviation medicine. This study examined the feasibility of detecting voice markers sensitive to acute hypobaric hypoxia in an early presymptomatic (PRE-SYMP) stage.METHOD: Eight subjects qualified with hypobaric training completed a series of standardized speech tests in a hypobaric chamber at 20,000 ft and 25,000 ft (6096 and 7620 m) of altitude. Voice response patterns were analyzed in terms of fundamental frequency (F0), F0 range, and voice onset time (VOT). We hypothesized a PRE-SYMP compensatory stage in voice reactivity.RESULTS: There was a different dose-response reactivity course at 20,000 ft vs. 25,000 ft, nonlinear to altitude. At 20,000 ft, our hypothesis was confirmed. In comparison to sea level, a PRE-SYMP compensatory stage could be distinguished, characterized by a decreased F0 range, decreased VOT, and increased F0. During a transitional (TRANS) stage, in comparison with sea level, the F0-range reset, VOT decreased, and F0 increased. During a symptomatic (SYMP) stage, F0 increased, F0 range increased, and VOT decreased. At 25,000 ft, in comparison to sea level, voice reactivity showed increased F0 and F0 range and decreased VOT in a PRE-SYMP stage and increased F0 and F0 range in the SYMP stage.DISCUSSION: The compensatory PRE-SYMP stage is suggested to be the expression of ongoing bottom-up and top-down regulatory mechanisms, whereas the 25,000-ft results are interpreted as a combination of tonic and phasic voice reactivity. This tonic component needs to be foreseen in sea level baseline measures.Van Puyvelde M, Neyt X, Vanderlinden W, Van den Bossche M, Bucovaz T, De Winne T, Pattyn N. Voice reactivity as a response to acute hypobaric hypoxia at high altitude. Aerosp Med Hum Perform. 2020; 91(6):471–478.

Phytochemical Profile and Investigation of the Spasmolytic Activity of Hydroalcoholic Extract of Syzygium cumini (L.) Skeels Seeds

Aims: Perform the phytochemical analysis and investigate the spasmolytic activity of the hydroalcoholic extract obtained from S. cumini seeds (EHS-SC). Study Design: Qualitative phytochemical analysis and test of the EHS-SC on isolated smooth muscles (aorta, trachea, jejunum and uterus) of rat, to value effect relaxant and/or inhibitor. Place and Duration of Study: Pharmacognosy Laboratory II (Pharmacy course) and Pharmacology Research and Post-Graduate Laboratory (Department of Physiological Sciences) of the Federal University of Maranhão, between January 2017 and July 2018. Methodology: EHS-SC was submitted to phytochemical analysis and changes in color, fluorescence and absence or presence of precipitate were observed. The smooth muscle segments were suspended (tension of 1 g) in glass vats containing specific saline solution, at an appropriate temperature and after stabilization period, was stimulated by a suitable contractile agent to observe the effect of EHS-SC in the phasic and/or tonic component. Results: EHS-SC showed the majority presence of phenols, steroids, alkaloids and flavonoids (flavones, xanthones, flavonols) and was more potent in inhibiting phasic contractions induced by 10-6 M carbachol (CCh) in isolated rat jejunum (Emax: 83.5 ± 6.7%; n = 3). In addition, the EHS-SC (81.0; 243.0 and 729 µg/mL) antagonized the CCh effect (n = 4), increasing the EC50 (6.5 ± 1.3 x 10-7 M) of the CCh to 8.5 ± 1.1; 18.5 ± 3.4 and 40.5 ± 7.4 x 10-7 M and reducing the Emax (100%) of the CCh to 82.9 ± 10.5; 67.6 ± 6.0 and 10.1 ± 8.3%. Conclusion: Spasmolytic activity may be combined with antimicrobial and antidiarrheal activity according to literature data, where they show that the seeds have the same secondary metabolites, signaling the therapeutic potential for the treatment of colic and/or diarrhea.

Innovations in Electrodermal Activity Data Collection and Signal Processing: A Systematic Review

The electrodermal activity (EDA) signal is an electrical manifestation of the sympathetic innervation of the sweat glands. EDA has a history in psychophysiological (including emotional or cognitive stress) research since 1879, but it was not until recent years that researchers began using EDA for pathophysiological applications like the assessment of fatigue, pain, sleepiness, exercise recovery, diagnosis of epilepsy, neuropathies, depression, and so forth. The advent of new devices and applications for EDA has increased the development of novel signal processing techniques, creating a growing pool of measures derived mathematically from the EDA. For many years, simply computing the mean of EDA values over a period was used to assess arousal. Much later, researchers found that EDA contains information not only in the slow changes (tonic component) that the mean value represents, but also in the rapid or phasic changes of the signal. The techniques that have ensued have intended to provide a more sophisticated analysis of EDA, beyond the traditional tonic/phasic decomposition of the signal. With many researchers from the social sciences, engineering, medicine, and other areas recently working with EDA, it is timely to summarize and review the recent developments and provide an updated and synthesized framework for all researchers interested in incorporating EDA into their research.

Activation of the hypothalamic paraventricular nucleus by forebrain hypertonicity selectively increases tonic vasomotor sympathetic nerve activity

We recently reported that mean arterial pressure (MAP) is maintained in water-deprived rats by an irregular tonic component of vasomotor sympathetic nerve activity (SNA) that is driven by neuronal activity in the hypothalamic paraventricular nucleus (PVN). To establish whether generation of tonic SNA requires time-dependent (i.e., hours or days of dehydration) neuroadaptive responses or can be abruptly generated by even acute circuit activation, forebrain sympathoexcitatory osmosensory inputs to PVN were stimulated by infusion (0.1 ml/min, 10 min) of hypertonic saline (HTS; 1.5 M NaCl) through an internal carotid artery (ICA). Whereas isotonic saline (ITS; 0.15 M NaCl) had no effect ( n = 5), HTS increased ( P < 0.001; n = 6) splanchnic SNA (sSNA), phrenic nerve activity (PNA), and MAP. Bilateral PVN injections of muscimol ( n = 6) prevented HTS-evoked increases of integrated sSNA and PNA ( P < 0.001) and attenuated the accompanying pressor response ( P < 0.01). Blockade of PVN NMDA receptors with d-(2 R)-amino-5-phosphonovaleric acid (AP5; n = 6) had similar effects. Analysis of respiratory rhythmic bursting of sSNA revealed that ICA HTS increased mean voltage ( P < 0.001) without affecting the amplitude of inspiratory or expiratory bursts. Analysis of cardiac rhythmic sSNA likewise revealed that ICA HTS increased mean voltage. Cardiac rhythmic sSNA oscillation amplitude was also increased, which is consistent with activation of arterial baroreceptor during the accompanying pressor response. Increased mean sSNA voltage by HTS was blocked by prior PVN inhibition (muscimol) and blockade of PVN NMDA receptors (AP5). We conclude that even acute glutamatergic activation of PVN (i.e., by hypertonicity) is sufficient to selectively increase a tonic component of vasomotor SNA.

Synthetic Lapachol Derivatives Relax Guinea-Pig Ileum by Blockade of the Voltage-Gated Calcium Channels

The present study was designed to further evaluate a possible spasmolytic activity of synthetic lapachol derivatives, norlapachol, α-norlapachone, β-norlapachone and hydro-hydroxy- norlapachol (HH-norlapachol), on guinea-pig ileum. In guinea-pig ileum, except for norlapachol, all naphthoquinones inhibited the phasic contractions induced by carbachol or histamine. Even when the ileum was pre-contracted with KCl, carbachol or histamine, all naphthoquinones induced relaxation, suggesting that these naphthoquinones could be acting on the voltage-gated calcium channels (CaV). As the tonic component this contraction is maintained mainly by the opening of the CaV, we hypothesized that these naphthoquinones might be acting on these channels. This hypothesis was confirmed by the observation that norlapachol (pD’2 = 4.99), α-norlapachone (pD’2 = 4.49), β-norlapachone (pD’2 = 6.33), and HH-norlapachol (pD’2 = 4.53) antagonized the contractions induced by CaCl2 in depolarizing medium nominally without Ca2+. As β-norlapachone was the most potent we decided to continue the study of its action mechanism. The fact that this naphthoquinone has inhibited the tonic contractions induced by S-(-)-Bay K8644 [EC50 = (1.6 ± 0.30) · 10-5 M] suggests that the Ca2+ channel involved belongs to the type L (CaV1.2). In addition, in the functional level, the spasmolytic effect of β-norlapachone does not involve participation of free radicals, since its curve of relaxation was unchanged in the presence of glutathione, an antioxidant agent.

Accelerated Ca2+ entry by membrane hyperpolarization due to Ca2+-activated K+ channel activation in response to histamine in chondrocytes

In articular cartilage inflammation, histamine release from mast cells is a key event. It can enhance cytokine production and matrix synthesis and also promote cell proliferation by stimulating chondrocytes. In this study, the functional impact of Ca2+-activated K+ (KCa) channels in the regulation of intracellular Ca2+ concentration ([Ca2+]i) in chondrocytes in response to histamine was examined using OUMS-27 cells, as a model of chondrocytes derived from human chondrosarcoma. Application of histamine induced a significant [Ca2+]i rise and also membrane hyperpolarization, and both effects were mediated by the stimulation of H1 receptors. The histamine-induced membrane hyperpolarization was attenuated to ∼50% by large-conductance KCa (BK) channel blockers, and further reduced by intermediate (IK) and small conductance KCa (SK) channel blockers. The tonic component of histamine-induced [Ca2+]i rise strongly depended on the presence of extracellular Ca2+ ([Ca2+]o) and was markedly reduced by La3+ or Gd3+ but not by nifedipine. It was significantly attenuated by BK channel blockers, and further blocked by the cocktail of BK, IK, and SK channel blockers. The KCa blocker cocktail also significantly reduced the store-operated Ca2+ entry (SOCE), which was induced by Ca2+ addition after store-depletion by thapsigargin in [Ca2+]o free solution. Our results demonstrate that the histamine-induced membrane hyperpolarization in chondrocytes due to KCa channel activation contributes to sustained Ca2+ entry mainly through SOCE channels in OUMS-27 cells. Thus, KCa channels appear to play an important role in the positive feedback mechanism of [Ca2+]i regulation in chondrocytes in the presence of articular cartilage inflammation.

Tonically Discharging Genioglossus Motor Units Show No Evidence of Rate Coding With Hypercapnia

The genioglossus (GG) is considered the principle protrudor muscle of the human tongue. Unlike most skeletal muscles, GG electromyographic (EMG) activities are robustly preserved in sleep and thus may fulfill a critical role in preserving airway patency. Previous studies in human subjects also confirm that the GG EMG increases in response to chemoreceptor and mechanoreceptor stimulation. This increase occurs secondary to the recruitment of previously inactive motor units (MUs) and/or an increase in firing rate of already active MUs. Which strategy the nervous system uses when the synaptic drive onto GG motoneurons increases is not known. Here we report on GG whole muscle and tonic MU activities under conditions that mimic sleep, i.e., mild-moderate elevations in CO2 (3% inspired CO2 or the addition of a 1.0 l dead space) and elevated airway resistance. Based on previous work in rat, we hypothesized that mild hypercapnia would increase the firing rates of tonic MUs and that these effects would be further potentiated by a modest increase in airway resistance. Fine wire and tungsten microelectrodes were inserted into the GG to record whole muscle and single MU activities in 21 subjects (13 women, 8 men; 20–55 yr). Either 3% inspired CO2 or added dead space resulted in a 200–300% increase in the amplitude of both tonic and phasic components of the whole muscle GG EMG and a doubling of minute ventilation. Despite these changes, recordings obtained from a total of 84 tonically discharging GG single MUs provide no evidence of a change in firing rate under any of the conditions. On this basis we conclude that in healthy adults, the increase in the tonic component of the whole muscle GG EMG secondary to mild hypercapnia is due almost exclusively to the recruitment of previously inactive MUs.

Emerging principles and neural substrates underlying tonic sleep-state-dependent influences on respiratory motor activity

Respiratory muscles with dual respiratory and non-respiratory functions (e.g. the pharyngeal and intercostal muscles) show greater suppression of activity in sleep than the diaphragm, a muscle almost entirely devoted to respiratory function. This sleep-related suppression of activity is most apparent in the tonic component of motor activity, which has functional implications of a more collapsible upper airspace in the case of pharyngeal muscles, and decreased functional residual capacity in the case of intercostal muscles. A major source of tonic drive to respiratory motoneurons originates from neurons intimately involved in states of brain arousal, i.e. neurons not classically involved in generating respiratory rhythm and pattern per se . The tonic drive to hypoglossal motoneurons, a respiratory motor pool with both respiratory and non-respiratory functions, is mediated principally by noradrenergic and glutamatergic inputs, these constituting the essential components of the wakefulness stimulus . These tonic excitatory drives are opposed by tonic inhibitory glycinergic and γ-amino butyric acid (GABA) inputs that constrain the level of respiratory-related motor activity, with the balance determining net motor tone. In sleep, the excitatory inputs are withdrawn and GABA release into the brainstem is increased, thus decreasing respiratory motor tone and predisposing susceptible individuals to hypoventilation and obstructive sleep apnoea.

Coding of Luminance and Color Differences on Neurons in the Rabbit's Visual System

The neuronal activity in the rabbit's visual cortex, lateral geniculate nucleus and superior colliculus was investigated in responses to 8 color stimuli changes in pairs. This activity consisted of phasic responses (50-90 and 130-300 Ms after stimuli changes) and tonic response (after 300 Ms). The phasic responses used as a basis for the matrices (8 × 8) constructed for each neuron included the average of spikes/sec in responses to all stimuli changes. All matrices were treated by factor analysis and the basic axes of sensory spaces were revealed. Sensory spaces reconstructed from neuronal spike discharges had a two-dimensional (with brightness and darkness axes) or four-dimensional (with two color and two achromatic axes) structure. Thus it allowed us to split neurons into groups measuring only brightness differences and the measuring of color and brightness differences between stimuli. The tonic component of most of the neurons in the lateral geniculate nucleus showed linear correlation with changes in intensities; therefore, these neurons could be characterized as pre-detectors for cortical selective detectors. The neuronal spaces demonstrated a coincidence with spaces revealed by other methods. This fact may reflect the general principle of vector coding (Sokolov, 2000) of sensory information in the visual system.