Carbohydrate and Glutamine Supplementation Attenuates the Increase in Rating of Perceived Exertion during Intense Exercise in Hypoxia Similar to 4200 m.

The rating of perceived exertion (RPE) indicates the feeling of fatigue. However, hypoxia worsens the condition and can worsen RPE. We evaluated whether carbohydrate and glutamine supplementation alters RPE and physiological markers in running at 70% peak oxygen uptake until exhaustion in a simulated altitude of 4500 m. Nine volunteers underwent three running tests at 70% peak oxygen uptake until exhaustion: (1) hypoxia and placebo, (2) hypoxia and 8% maltodextrin, and (3) hypoxia after six days of glutamine supplementation (20 g/day) and 8% maltodextrin. The exercise and supplementation were randomized and double-blinded. Lactate, heart rate, haemoglobin O2 saturation (SpO2%), and RPE (6-20 scale) were analyzed at the 15th and 30th min. The level of significance was set at p ≤ 0.05. SpO2% decreased at the 15th and 30th minutes compared to resting in placebo, carbohydrate, and glutamine supplementation. RPE increased at the 30th minute compared to the 15th minute in placebo and carbohydrate supplementation; however, there was no difference in the glutamine supplementation condition. Heart rate and lactate increased after the 15th and 30th minutes compared to resting, similar to the three conditions studied. We conclude that previous supplementation with glutamine and carbohydrate during intense exercise in hypoxia similar to 4500 m can attenuate the increase in RPE by the increase in glycemia and can be a useful strategy for people who exercise in these conditions.

Spoken words are processed during dexmedetomidine-induced unresponsiveness.

BACKGROUND: Studying the effects of anaesthetic drugs on the processing of semantic stimuli could yield insights into how brain functions change in the transition from wakefulness to unresponsiveness. Here, we explored the N400 event-related potential during dexmedetomidine- and propofol-induced unresponsiveness. METHODS: Forty-seven healthy subjects were randomised to receive either dexmedetomidine (n=23) or propofol (n=24) in this open-label parallel-group study. Loss of responsiveness was achieved by stepwise increments of pseudo-steady-state plasma concentrations, and presumed loss of consciousness was induced using 1.5 times the concentration required for loss of responsiveness. Pre-recorded spoken sentences ending either with an expected (congruous) or an unexpected (incongruous) word were presented during unresponsiveness. The resulting electroencephalogram data were analysed for the presence of the N400 component, and for the N400 effect defined as the difference between the N400 components elicited by congruous and incongruous stimuli, in the time window 300-600 ms post-stimulus. Recognition of the presented stimuli was tested after recovery of responsiveness. RESULTS: The N400 effect was not observed during dexmedetomidine- or propofol-induced unresponsiveness. The N400 component, however, persisted during dexmedetomidine administration. The N400 component elicited by congruous stimuli during unresponsiveness in the dexmedetomidine group resembled the large component evoked by incongruous stimuli at the awake baseline. After recovery, no recognition of the stimuli heard during unresponsiveness occurred. CONCLUSIONS: Dexmedetomidine and propofol disrupt the discrimination of congruous and incongruous spoken sentences, and recognition memory at loss of responsiveness. However, the processing of words is partially preserved during dexmedetomidine-induced unresponsiveness. CLINICAL TRIAL REGISTRATION: NCT01889004.

Consumption of a Double-Fortified Salt Affects Perceptual, Attentional, and Mnemonic Functioning in Women in a Randomized Controlled Trial in India.

Background: Iron deficiency and iron deficiency anemia have been shown to have negative effects on aspects of perception, attention, and memory.Objective: The purpose of this investigation was to assess the extent to which increases in dietary iron consumption are related to improvements in behavioral measures of perceptual, attentional, and mnemonic function.Methods: Women were selected from a randomized, double-blind, controlled food-fortification trial involving ad libitum consumption of either a double-fortified salt (DFS) containing 47 mg potassium iodate/kg and 3.3 mg microencapsulated ferrous fumarate/g (1.1 mg elemental Fe/g) or a control iodized salt. Participants' blood iron status (primary outcomes) and cognitive functioning (secondary outcomes) were assessed at baseline and after 10 mo at endline. The study was performed on a tea plantation in the Darjeeling district of India. Participants (n = 126; 66% iron deficient and 49% anemic at baseline) were otherwise healthy women of reproductive age, 18-55 y.Results: Significant improvements were documented for iron status and for perceptual, attentional, and mnemonic function in the DFS group (percentage of variance accounted for: 16.5%) compared with the control group. In addition, the amount of change in perceptual and cognitive performance was significantly (P < 0.05) related to the amount of change in blood iron markers (mean percentage of variance accounted for: 16.0%) and baseline concentrations of blood iron markers (mean percentage of variance accounted for: 25.0%). Overall, there was evidence that the strongest effects of change in iron status were obtained for perceptual and low-level attentional function.Conclusion: DFS produced measurable and significant improvements in the perceptual, attentional, and mnemonic performance of Indian female tea pickers of reproductive age. This trial was registered at clinicaltrials.gov as NCT01032005.

The Effects of Caffeine Supplementation on Physiological Responses to Submaximal Exercise in Endurance-Trained Men.

OBJECTIVES: The aim of this study was to evaluate the effects of caffeine on physiological responses to submaximal exercise, with a focus on blood lactate concentration ([BLa]). METHODS: Using a randomised, single-blind, crossover design; 16 endurance-trained, male cyclists (age: 38 ± 8 years; height: 1.80 ± 0.05 m; body mass: 76.6 ± 7.8 kg; [Formula: see text]: 4.3 ± 0.6 L∙min-1) completed four trials on an electromagnetically-braked cycle ergometer. Each trial consisted of a six-stage incremental test (3 minute stages) followed by 30 minutes of passive recovery. One hour before trials 2-4, participants ingested a capsule containing 5 mg∙kg-1 of either caffeine or placebo (maltodextrin). Trials 2 and 3 were designed to evaluate the effects of caffeine on various physiological responses during exercise and recovery. In contrast, Trial 4 was designed to evaluate the effects of caffeine on [BLa] during passive recovery from an end-exercise concentration of 4 mmol∙L-1. RESULTS: Relative to placebo, caffeine increased [BLa] during exercise, independent of exercise intensity (mean difference: 0.33 ± 0.41 mmol∙L-1; 95% likely range: 0.11 to 0.55 mmol∙L-1), but did not affect the time-course of [BLa] during recovery (p = 0.604). Caffeine reduced ratings of perceived exertion (mean difference: 0.5 ± 0.7; 95% likely range: 0.1 to 0.9) and heart rate (mean difference: 3.6 ± 4.2 b∙min-1; 95% likely range: 1.3 to 5.8 b∙min-1) during exercise, with the effect on the latter dissipating as exercise intensity increased. Supplement × exercise intensity interactions were observed for respiratory exchange ratio (p = 0.004) and minute ventilation (p = 0.034). CONCLUSIONS: The results of the present study illustrate the clear, though often subtle, effects of caffeine on physiological responses to submaximal exercise. Researchers should be aware of these responses, particularly when evaluating the physiological effects of various experimental interventions.

Sensory transduction of weak electromagnetic fields: role of glutamate neurotransmission mediated by NMDA receptors.

Subliminal electromagnetic fields (EMFs) triggered nonlinear evoked potentials in awake but not anesthetized animals, and increased glucose metabolism in the hindbrain. Field detection occurred somewhere in the head and possibly was an unrecognized function of sensory neurons in facial skin, which synapse in the trigeminal nucleus and project to the thalamus via glutamate-dependent pathways. If so, anesthetic agents that antagonize glutamate neurotransmission would be expected to degrade EMF-evoked potentials (EEPs) to a greater extent than agents having different pharmacological effects. We tested the hypothesis using ketamine which blocks N-methyl-d-aspartate (NMDA) receptors (NMDARs), and xylazine which is an α2-adrenoreceptor agonist. Electroencephalograms (EEGs) of rats were examined using recurrence analysis to observe EEPs in the presence and absence of ketamine and/or xylazine anesthesia. Auditory evoked potentials (AEPs) served as positive controls. The frequency of observation of evoked potentials in a given condition (wake or anesthesia) was compared with that due to chance using the Fisher's exact test. EEPs were observed in awake rats but not while they were under anesthesia produced using a cocktail of xylazine and ketamine. In another experiment each rat was measured while awake and while under anesthesia produced using either xylazine or ketamine. EEPs and AEPs were detected during wake and under xylazine (P<0.05 in each of the four measurements). In contrast, neither EEPs nor AEPs were observed when anesthesia was produced partly or wholly using ketamine. The duration and latency of the EEPs was unaltered by xylazine anesthesia. The afferent signal triggered by the transduction of weak EMFs was likely mediated by NMDAR-mediated glutamate neurotransmission.

Effect of carbohydrate supplementation on the physiological and perceptual responses to prolonged tennis match play.

Carbohydrate supplementation is a popular nutritional practice used in tennis to enhance physical capacities, motor-skill performance, and delay fatigue. However, the effects of carbohydrate supplementation on physiological and perceptual responses during tennis match play are not established. This double blind, randomized, placebo (PLA)-controlled crossover study was designed to determine the influence of carbohydrate supplementation (0.5 g·kg·h) on glycemia, salivary hormones (cortisol and testosterone) concentration, salivary immunoglobulin A (IgA) concentration, and rating of perceived exertion (RPE) during 3 hours of tennis match play in 12 well-trained tennis players. The only significant difference between the 2 conditions was a lower salivary cortisol concentration postmatch in the carbohydrate trial (p < 0.05); however, there was a trend for higher glucose concentration (p = 0.06) and lower session-RPE (p = 0.08) after tennis match play in the carbohydrate condition, which may have some practical implications. There was no change in salivary testosterone, salivary IgA, and RPE responses during tennis match play between conditions (p > 0.05). These data indicate that carbohydrate ingestion during 3 hours of competitive tennis match play helps to maintain glycemia and attenuates the increase in salivary cortisol concentration compared with PLA.

Acute effects of Sceletium tortuosum (Zembrin), a dual 5-HT reuptake and PDE4 inhibitor, in the human amygdala and its connection to the hypothalamus.

The South African endemic plant Sceletium tortuosum has a long history of traditional use as a masticatory and medicine by San and Khoikhoi people and subsequently by European colonial farmers as a psychotropic in tincture form. Over the past decade, the plant has attracted increasing attention for its possible applications in promoting a sense of wellbeing and relieving stress in healthy individuals and for treating clinical anxiety and depression. The pharmacological actions of a standardized extract of the plant (Zembrin) have been reported to be dual PDE4 inhibition and 5-HT reuptake inhibition, a combination that has been argued to offer potential therapeutic advantages. Here we tested the acute effects of Zembrin administration in a pharmaco-fMRI study focused on anxiety-related activity in the amygdala and its connected neurocircuitry. In a double-blind, placebo-controlled, cross-over design, 16 healthy participants were scanned during performance in a perceptual-load and an emotion-matching task. Amygdala reactivity to fearful faces under low perceptual load conditions was attenuated after a single 25 mg dose of Zembrin. Follow-up connectivity analysis on the emotion-matching task showed that amygdala-hypothalamus coupling was also reduced. These results demonstrate, for the first time, the attenuating effects of S. tortuosum on the threat circuitry of the human brain and provide supporting evidence that the dual 5-HT reuptake inhibition and PDE4 inhibition of this extract might have anxiolytic potential by attenuating subcortical threat responsivity.

Free energy, precision and learning: the role of cholinergic neuromodulation.

Acetylcholine (ACh) is a neuromodulatory transmitter implicated in perception and learning under uncertainty. This study combined computational simulations and pharmaco-electroencephalography in humans, to test a formulation of perceptual inference based upon the free energy principle. This formulation suggests that ACh enhances the precision of bottom-up synaptic transmission in cortical hierarchies by optimizing the gain of supragranular pyramidal cells. Simulations of a mismatch negativity paradigm predicted a rapid trial-by-trial suppression of evoked sensory prediction error (PE) responses that is attenuated by cholinergic neuromodulation. We confirmed this prediction empirically with a placebo-controlled study of cholinesterase inhibition. Furthermore, using dynamic causal modeling, we found that drug-induced differences in PE responses could be explained by gain modulation in supragranular pyramidal cells in primary sensory cortex. This suggests that ACh adaptively enhances sensory precision by boosting bottom-up signaling when stimuli are predictable, enabling the brain to respond optimally under different levels of environmental uncertainty.

[Study on scientific connotation of four herbal properties on basis of cold and hot perceptions].

The theory of herbal properties of traditional Chinese medicine (TCM) is an indispensable part of theoretical system of TCM and plays an important role in the clinical prescription and application of TCM. In this theoretical system, the theory of four herbal properties takes a core and dominant position and becomes an indispensable part of TCM natures and actions. In combination of studies and experience, this essay proposes the latest discovery in modern biology-modern scientific connotation of cold and hot herbal properties on the basis of cold and hot perceptions of organism on the basis of analysis and summary of TRP channel protein and correlation of cold and hot perceptions of organism and thermoregulation, which is an effective approach to make breakthroughs in studies on modernization drive of the theory of four herbal properties of TCM.

The effect of lutein supplementation on visual fatigue: a psychophysiological analysis.

We used psychophysiological technology to examine the effect of an oral supplement, a combination of lutein, zeaxanthin and blackcurrant extract (LUT), on visual fatigue, within the context of a randomized, double-blind, placebo-controlled cross-over trial. The LUT supplement and placebo samples were randomly assigned to thirteen participants, who took the samples for two LUT (and vice versa) for another 2 week. Each participant completed visual proof reading tasks for 2h during each of four testing sessions. Saccade tests were administered before and after the proof reading task, during which the participants moved their eyes back and forth between two targets positioned in the center of two checkerboards. We recorded EEG, EOG, heart rate, and facial muscle potential/performance during the saccade tests. Blood pressure was measured and subjective fatigue and stress scores were collected before and after the proof reading task. We averaged EEG starting at saccade offset in order to analyze eye fixation related potentials (EFRP). Our results suggested that the proof reading task induced visual fatigue. An analysis of EFRP and other psychophysiological data revealed significant differences between the LUT and placebo conditions. These results suggest that supplementation with LUT could help to reduce symptoms of visual fatigue.

Glyconutrients and perception, cognition, and memory.

Neuropsychological tests were administered to 62 college students to assess the influence of glyconutrients on perception, cognition and memory in two randomized, double-blind, placebo-controlled, counterbalanced studies. Participants were given both a glyconutritional supplement and a control substance prior to testing. In Exp. 1. a Same-Different visual discrimination task, Raven's Standard Progressive Matrices, and the Stroop test were administered. In Exp. 2, simple and complex working-memory capacity were measured. Participants receiving the supplement performed significantly more accurately on the visual discrimination task and the first session of the simple working-memory test.

Women's perception of the efficacy of a soy extract with probiotic: the M3 study.

OBJECTIVES: To determine women's perception of soy extracts containing a probiotic on climacteric-related symptoms. DESIGN: A prospective multi-center survey. SUBJECTS AND METHODS: A total of 2044 women aged 40-65 years, who were recruited at random by a group of 198 Spanish gynecologists. The women completed a self-report survey at baseline and after 6 months' use of the soy extract (30 mg genistein and 30 mg daidzein) with probiotic (500 million spores of Lactobacillus sporogenes), calcium (141 mg) and vitamin D (5 microg). The questionnaire included 15 items on menopause and health and four about sexuality from the Cervantes scale. Patients and gynecologists completed an assessment about the clinical state. RESULTS: After 6 months, the studied soy extract improved climacteric symptoms and sexuality. Both patients and gynecologists were satisfied with the results. CONCLUSION: Peri- and postmenopausal patients usually experience common menopausal symptoms and many believe that soy extract improves their menopause symptoms. Physicians should be aware of patients' positive attitude to such products.

Nicotine withdrawal disrupts both foreground and background contextual fear conditioning but not pre-pulse inhibition of the acoustic startle response in C57BL/6 mice.

Nicotine withdrawal is associated with multiple symptoms such as anxiety, increased appetite, and disrupted cognition in humans. Although animal models have provided insights into the somatic and affective symptoms of nicotine withdrawal, less research has focused on the effects of nicotine withdrawal on cognition. Therefore, in this study, C57BL/6J mice were used to test the effects of withdrawal from chronic nicotine on foreground and background contextual fear conditioning, which present the context as a primary or secondary stimulus, respectively. Mice withdrawn from 12 days of chronic nicotine (6.3mg/kg/day) or saline were trained and tested in either foreground or background contextual fear conditioning; nicotine withdrawal-associated deficits in contextual fear conditioning were observed in both conditions. Mice were also tested for the effects of withdrawal on pre-pulse inhibition of the acoustic startle reflex (PPI), a measure of sensory gating, and on the acoustic startle reflex. Mice withdrawn from 12 days of chronic nicotine (6.3 or 12.6 mg/kg/day) or saline underwent one 30-min PPI and startle session; no effect of withdrawal from chronic nicotine on PPI or startle was observed for either dose at 24h after nicotine removal. Therefore, mice were tested at different time points following withdrawal from 12.6 mg/kg/day chronic nicotine (8, 24, and 48 h after nicotine removal). No effect of withdrawal from chronic nicotine was observed at any time point for PPI. Overall, these results demonstrate that nicotine withdrawal disrupts two methods of contextual learning but not sensory gating in C57BL/6J mice.

Effect of coffee ingestion on physiological responses and ratings of perceived exertion during submaximal endurance exercise.

This study examined the effect of coffee ingestion on physiological responses and ratings of perceived exertion (RPE) during submaximal endurance exercises by 10 healthy young adults. Participants performed a submaximal endurance cycling exercise corresponding to 60% of maximum oxygen uptake capacity for 60 min. They drank either caffeinated coffee with a caffeine content of 6 mg/kg body-mass of each participant (Caf) or a decaffeinated coffee (Dec) 60 min. before starting exercise. Participants participated in the blind design experiment under both conditions at a one-week interval. Oxygen uptake, respiratory exchange ratio, heart rate, RPE, and plasma lactate concentration were measured during the endurance exercise. The RPE under the Caffeinated coffee condition during the last 60 min. of endurance exercise was significantly lower than that in the Decaffeinated coffee condition. However, no significant differences in any physiological response were observed between conditions. Thus, caffeine ingestion 60 min. before starting exercise had an insignificant effect on the physiological responses, except for RPE during submaximal endurance exercises for 60 min. Caffeine ingestion before endurance exercise of relatively low intensity may have a beneficial effect on psychological responses.

Pattern of use and subjective effects of Salvia divinorum among recreational users.

BACKGROUND: Salvia divinorum is a member of the Lamiaceae family and contains the psychotropic diterpene and kappa-opioid receptor agonist salvinorin-A. Originally a shamanic inebriant used by the Mexican Mazatec Indians, the plant and its preparations are becoming increasingly popular among non-traditional users. METHODS: Demographic data and information on pattern of use and subjective effects were obtained by means of self-report questionnaires from a sample of 32 recreational users of salvia and other psychedelics. RESULTS: Involvement with salvia appeared to be a recent phenomenon. Smoking the extract was the preferred form of administration. Subjective effects were described as intense but short-lived, appearing in less than 1 min and lasting 15 min or less. They included psychedelic-like changes in visual perception, mood and somatic sensations, and importantly, a highly modified perception of external reality and the self, leading to a decreased ability to interact with oneself or with one's surroundings. CONCLUSIONS: Although some aspects of the subjective effects reported were similar to high doses of classical psychedelics with serotonin-2A receptor agonist activity, the intense derealization and impairment reported appear to be a characteristic of salvia. The observed simultaneous high scores on the LSD and PCAG subscales of the Addiction Research Center Inventory (ARCI) have been previously reported for other kappa-opioid agonists, and support kappa receptor activation as the probable pharmacologic mechanism underlying the modified state of awareness induced by salvia.

Distorted perception of smell by volatile agents facilitated inhalational induction of anesthesia.

BACKGROUND: Unpleasant smell of halogenated volatile agents is one of the frustrating factors for inhalational induction. We developed a new modification that might enable children to enjoy the smell itself while incrementally elevating sevoflurane concentration. Troposmia is usually a pathological quality change of smell perception and an olfactory stimulus is distortedly perceived in this state, which we applied to inhalational induction. METHODS: At the preoperative visit an anesthetist told the children that the smell of a facemask could be magically changed from strawberry into anything and promised to change the smell as they requested. In the operating room, a strawberry scented facemask was fitted to the face and the anesthetist announced to them that the magical change of the smell would begin when sevoflurane was added. Whether children perceived the change of the smell as they requested was investigated in the troposmia group, and resistance to fit a facemask was compared between the troposmia group and a control group. RESULTS: Significantly fewer children resisted the facemask in the troposmia group (1 of 32 vs 9 of 32; P = 0.0059). In the troposmia group 18, 22 and 25 of the 32 children said the smell of the facemask changed as they requested before they fell asleep, at the postoperative visit or both, respectively. CONCLUSIONS: Troposmia can be intentionally induced to perceive the smell of sevoflurane on request. Troposmia might contribute to promote children's participation in anesthesia induction and facilitate inhalational induction.

Subjective effects of antidepressants: a pilot study of the varieties of antidepressant-induced experiences in meditators.

The use of antidepressants continues to increase, yet relatively little is known about their precise subjective effects, and there is growing concern about subtle psychological side effects. One novel investigative approach to these problems may be to use introspectively trained subjects such as meditators. Experienced meditators recently taking antidepressants rated antidepressant effects on multiple dimensions of experience and reported significant emotional, motivational, and cognitive effects and benefits. This study suggests that a) meditators may benefit both clinically and meditatively from antidepressants, b) meditators may provide significant novel information on antidepressant effects, c) meditators may prove valuable for phenomenological investigations of psychopathology, drug effects, and therapies, d) meditation may prove a helpful maintenance therapy for depression, and e) enhanced equanimity may contribute to the broad therapeutic efficacy of antidepressants.

Effect of potassium phosphate supplementation on perceptual and physiological responses to maximal graded exercise.

This investigation evaluated the effect of oral potassium phosphate supplementation on ratings of perceived exertion (RPE) and physiological responses during maximal graded exercise tests (GXT). Eight highly trained endurance runners completed a GXT to anchor the Borg 15-point RPE scale and two double-blind counterbalanced GXTs. Subjects ingested either 4,000 mg x day(-1) of phosphate (PHOS) or a placebo (PLA) for 2 days. Two weeks separated GXTs. Phosphate levels obtained immediately prior to the GXTs were greater in PHOS than PLA. No differences between PHOS and PLA were noted for the submaximal and maximal physiological responses. RPE for the overall body were lower during PHOS than PLA at intensities corresponding to 70-80% of VO2max. This suggests that oral potassium phosphate supplementation mediates perceived exertion during moderately intense exercise.

Olfactory cues from an oxytocin-injected male rat can reduce energy loss in its cagemates.

Rats can recognize the odor of a stressed conspecific and react with stress themselves. Stress mobilizes energy, causing increased core temperatures and energy loss by radiation from the naked tail. Oxytocin administered in high doses (1 mg/kg, s.c.) reduces a rat's tail skin temperature and thereby the radiated energy loss. While administration of this high dose of oxytocin induces sedation low doses induce anxiolysis. This study demonstrates that the cagemates of an oxytocin-treated (1 mg/kg s.c.) rat, which themselves have not received any oxytocin-treatment, show energy conservation, apparent as reduced tail skin temperature. This effect was blocked by olfactory impairment. The temperature reduction in the cagemates probably reflects an oxytocin-mediated olfactorily activated stress inhibitory mechanism.

The effects of electrical stimulation at different frequencies on perception and pain in human volunteers: epidural versus intravenous administration of fentanyl.

The study was performed to determine whether epidural fentanyl produced segmental sensory changes to electrical stimulation at different frequencies. Eight healthy volunteers received fentanyl 1 microgram/kg both intravenously and epidurally in a randomized, double-blind, cross-over fashion. Perception thresholds and amount of current required to elicit a predetermined level of moderate pain (Cmp) at 5,250, and 2000 Hz stimulation were measured at ipsilateral dermatomes C2 and L2 at 0, 5, 15, 30, 45, and 60 min after injection. Perceptions to 5,250, and 2000 Hz stimulation were unaffected by either intravenous or epidural fentanyl (P > 0.08). Intravenous fentanyl increased Cmp at both 5 and 250 Hz at both dermatomes (P < 0.004) and thus did not produce segmental analgesia. In contrast, epidural fentanyl increased Cmp only at the L2 dermatome and only at 5 Hz (P = 0.005). We conclude that an epidural bolus of fentanyl results in segmental spinal analgesia to transcutaneous electrical stimulation only at specific frequencies. Furthermore, pain produced by stimulation at 5 Hz may have a different pharmacology than pain produced by 250 Hz stimulation.