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Biomedical subjects

W C Orr

Publications and source records attributed to W C Orr.

At least 37 records · Page 2Linked to original sources

Heart rate variability during waking and sleep in healthy males and females.

STUDY OBJECTIVES: The study goal was to investigate autonomic activity with heart rate variability analysis during different sleep stages in males and females. DESIGN: The study utilized a 2 Groups (males, females) x 4 States (waking, stage 2 sleep, stage 4 sleep, rapid-eye movement sleep) mixed design with one repeated, within-subjects factor (i.e., state). SETTING: The study was carried out in the sleep laboratory of the Thomas N. Lynn Institute for Healthcare Research. PARTICIPANTS: Twenty-four healthy adults (fourteen females and ten males). INTERVENTIONS: NA. MEASUREMENTS AND RESULTS: All participants underwent polysomnographic monitoring and electrocardiogram recordings during pre-sleep waking and one night of sleep. Fifteen-minute segments of beat-to-beat heart rate intervals during waking, stage 2 sleep, stage 4 sleep, and REM sleep were subjected to spectral analysis. Compared to NREM sleep, REM sleep was associated with decreased high frequency (HF) band power, and significantly increased low frequency (LF) to (HF) ratio. Compared to females, males showed significantly elevated LF/HF ratio during REM sleep. Males also demonstrated significantly decreased HF band power during waking when compared to females. No significant sleep- or gender-related changes in LF band power were found. CONCLUSIONS: The results confirmed changes in autonomic activity from waking to sleep, with marked differences between NREM and REM sleep. These changes were primarily due to stage-related alterations in vagal tone. REM sleep was characterized by increased sympathetic dominance, secondary to vagal withdrawal. The data also suggested gender differences in autonomic functioning during waking and sleep, with decreased vagal tone during waking and increased sympathetic dominance during REM sleep in the males.

Adult↗

Overexpression of Mn-containing superoxide dismutase in transgenic Drosophila melanogaster.

The general objective of this study was to examine the role of mitochondria in the aging process. Two alternative hypotheses were tested: (i) that overexpression of Mn superoxide dismutase (Mn SOD) in the mitochondria of Drosophila melanogaster would slow the accrual of oxidative damage and prolong survival or (ii) that there is an evolved optimum level of superoxide anion radical, such that overexpression of Mn SOD would have deleterious or neutral effects. Microinjection and mobilization of a transgene, which contained a 9-kb genomic sequence encoding Mn SOD, produced 15 experimental lines overexpressing Mn SOD by 5-116% relative to the parental y w strain. Comparisons between these lines and control lines containing inserted vector sequences alone indicated that the mean longevity of the experimental lines was decreased by 4-5% relative to controls. There were no compensatory changes in the metabolic rate, level of physical activity, or the levels of other antioxidants, namely Cu-Zn SOD, catalase, and glutathione. There were no differences between groups in rates of mitochondrial hydrogen peroxide release, protein oxidative damage, or resistance to 100% oxygen or starvation conditions. The experimental lines had a marginally increased resistance to moderate heat stress. These results are consistent with the existence of an optimum level of Mn SOD activity which minimizes oxidative stress. The naturally evolved level of Mn SOD activity in Drosophila appears to be near the optimum required under normal conditions, although the optimum may be shifted to a higher level under more stressful conditions.

Aging↗

Disruption of normal gastric myoelectric functioning by sleep.

STUDY OBJECTIVES: The aim of this study was to assess the effects of sleep on gastric myoelectric activity as measured by electrogastrography in healthy individuals. The goal was to elucidate the role of central influences in the regulation of normal gastric functioning. DESIGN: Electrograstrogram (EGG) was recorded during polysomnographically monitored waking and sleep. SETTING: Sleep laboratory. PARTICIPANTS: 17 healthy volunteers. MEASUREMENTS AND RESULTS: EGG parameters were computed for 20-minute segments of pre-sleep waking, stage 2 sleep, stage 4 sleep, and REM sleep using both overall and running spectral analysis of EGG data. The dominant power decreased significantly from waking (31.4 +/- 1.4 dB) to all sleep stages (23.1 +/- 1.5 dB during stage 2; 24.7 +/- 1.4 dB during stage 4; 24.3 +/- 1.3 dB during REM sleep). The percentage of 2-4cpm activity decreased significantly during NREM sleep (64.6 +/- 7.6% during stage 2 sleep; 57.5 +/- 5.5% during stage 4 sleep) compared to its waking value (90.8 +/- 3.2%), but not compared to REM sleep (74.1 +/- 5.4%). The instability coefficient of the dominant frequency increased significantly from waking (0.19 +/- 0.03) to all sleep stages (0.36 +/- 0.05 during stage 2 sleep; 0.47 +/- 0.05 during stage 4; 0.34 +/- 0.05 during REM sleep). No significant differences between the sleep stages were found for any measure. CONCLUSIONS: Sleep is associated with increases in gastric dysrhythmia and instability of the gastric slow wave frequency when compared to waking. These findings suggest that the intrinsic electrical activity of the stomach is significantly influenced by central nervous system mechanisms, and support the notion of a brain-gut axis.

Adult↗

Postprandial changes of sympathovagal balance measured by heart rate variability.

The aim of this study was to investigate the sympathovagal balance after meals by measuring the spectral analysis of heart rate variability (HRV). Nine healthy volunteers were enrolled in this study. The electrocardiogram (ECG) was recorded for 30 min in a fasting state and 60 min after a 500-kcal test meal. The HRV was derived from the ECG and was measured by power spectral analysis using fast-Fourier transform algorithm. It reveals two dominant spectral components. The low-frequency (LF) band reflects primarily sympathetic activity with some parasympathetic input. The high-frequency (HF) band is a reflection of parasympathetic (vagal) activity. The LF-to-HF ratio is considered a marker of sympathovagal balance. It was found that the postprandial LF-to-HF ratio, compared with the fasting state, was significantly increased at both the first 30 min (2.50 +/- 0.49 vs 1.78 +/- 0.33, P < 0.05) and the second 30 min (2.68 +/- 0.55 vs 1.78 +/- 0.33, P < 0.05). The postprandial HF diminished significantly at both the first (16.0 +/- 0.5 vs 21.8 +/- 4.2, P < 0.05) and the second (13.8 +/- 9.5 vs 21.8 +/- 4.2, P < 0.05) 30-min period. In conclusion, the postprandial sympathovagal ratio shows a sustained elevation lasting 1 hr, mainly attributed to diminished vagal activity.

Adult↗

Overexpression of glutathione reductase extends survival in transgenic Drosophila melanogaster under hyperoxia but not normoxia.

The purpose of this study was to test the hypothesis that overexpression of glutathione reductase in transgenic Drosophila melanogaster increases resistance to oxidative stress and retards the aging process. Transgenic flies were generated by microinjection and subsequent mobilization of a P element construct containing the genomic glutathione reductase gene of Drosophila, with 4 kb upstream and 1.5 kb downstream of the coding region. Transgenic animals stably overexpressed glutathione reductase by up to 100% throughout adult life and under continuous exposure to 100% oxygen or air. Under hyperoxic conditions, overexpressors had increased longevity, decreased accrual of protein carbonyls, and dramatically increased survival rates after recovery from a semi-lethal dose of 100% oxygen. Under normoxic conditions, overexpression of glutathione reductase had no effect on longevity, protein carbonyl content, reduced glutathione, or glutathione disulfide content, although the total consumption of oxygen was slightly decreased. Glutathione reductase activity does not appear to be a rate-limiting factor in anti-aging defenses under normoxic conditions, but it may become a limiting factor when the level of oxidative stress is elevated.

Animals↗

Subjective and objective sleep quality in irritable bowel syndrome.

OBJECTIVE: The aim of this study was to compare subjective and objective measures of sleep quality in patients with irritable bowel syndrome (IBS) and controls. METHODS: The Pittsburgh Sleep Quality Index (PSQI) was used to measure subjective sleep quality, and polysomnography was performed during one night to obtain objective measures of sleep quality, including sleep efficiency, sleep latency, number of arousals, and percentage of slow-wave sleep. Participants were 15 IBS patients and 15 healthy controls. RESULTS: The results showed a significantly increased global PSQI score in patients, as well as significantly higher scores on several subcomponents of the PSQI (i.e., sleep quality, sleep latency, habitual sleep efficiency, and daytime dysfunction). Analysis of polysomnographic parameters revealed no significant group differences on any measure. CONCLUSIONS: Complaints of poor sleep quality in the absence of objective sleep abnormalities suggest altered sleep perception, and support that IBS involves exaggerated responses to normal internal or external stimuli.

Adult↗

Identification of oxidized proteins based on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, immunochemical detection, isoelectric focusing, and microsequencing.

It has been demonstrated that an age-associated increase in protein oxidation is a highly selective rather than random phenomenon. Addition of carbonyl groups is a widely used marker for the detection of oxidative damage to the proteins. Carbonyls can be detected immunochemically using antibodies against dinitrophenylhydrazine (DNPH), a reagent that specifically reacts with protein carbonyl groups. In this paper, a procedure for the identification of oxidized proteins during aging or under pathological conditions is described. Protein samples were treated with DNPH and then separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), followed by immunochemical detection. Proteins exhibiting positive immunostain were then purified by SDS-PAGE followed by isoelectric focusing. The focused protein band was further concentrated by another run of SDS-PAGE and transferred onto Immobilon-P membrane. The identity of the protein was revealed by automated Edman microsequencing and a computer database search. This method is successfully demonstrated for the identification of housefly arginine kinase, a cytosolic protein that is involved in the energy metabolism of insect muscle cells.

Amino Acid Sequence↗

A comparison of feeding to cephalic stimulation on postprandial sleepiness.

This study investigated the effects of ingestion of a meal compared to a sham feeding on objectively measured sleepiness. It was hypothesized that the ingestion of a solid meal would produce significantly greater postprandial sleepiness evidenced by shorter sleep onset latencies (SOL) when compared to a sham feeding. Eleven men and eight women without evidence of gastrointestinal disease or sleep disorders participated in the 2-day study. Subjects underwent a premeal baseline nap at 1600 hours and were given a standardized meal at 1700 hours. On one study day, subjects consumed the entire meal, whereas on another study day, they were asked to chew and then expectorate the meal. Naps with polysomnographic monitoring followed at 1730, 1800, and 1900 hours. Sleep onset latencies were determined by standard polysomnographic measures. Statistical analyses revealed the sleep onset latencies for the two meal conditions differed significantly at the 1800 hours postprandial nap only. Individuals demonstrated a transient decrease in sleep latency after consuming a meal compared to a sham feeding. These results lend support to the existence of a gastrointestinal effect on postprandial sleepiness.

Cross-Over Studies↗

Responses to different levels of esophageal acidification during waking and sleep.

The purpose of this study was to assess the effect of hydrogen ion concentration of intraesophageal infusions during sleep on acid clearance time and latency to swallow and arousal responses from sleep. We studied 10 normal volunteers during sleep via polysomnography and concomitant esophageal pH monitoring. Sleep prolonged the acid clearance time of both pH 3.0 and 1.2. Swallow and arousal latencies were both progressively decreased with decreasing pH of the infusate (P < 0.05, 0.07, respectively). We concluded that intraluminal hydrogen ion concentration creates an afferent warning stimulus that produces prompt airway-protective responses.

Adult↗

Gastric myoelectrical activity in healthy children and children with functional dyspepsia.

The aim of this study was to investigate abnormalities in pediatric patients with functional dyspepsia. Fifteen symptomatic pediatric patients diagnosed with functional dyspepsia and 17 aged-matched healthy controls were studied. Gastric myoelectrical activity was recorded using surface electrogastrography for 1 hr in the fasting state and 1 hr after a test meal. It was found that, in comparison with the controls, the children with functional dyspepsia had a lower percentage of 2- to 4-cpm slow waves in both fasting state (66.0+/-4.7% vs 79.7+/-3.1%, P < 0.07) and fed state (72.4+/-5.4% vs 85.0+/-2.9%, P < 0.04), and a significantly higher instability of the dominant frequency in both fasting state (0.50+/-0.05 vs 0.31+/-0.04, P < 0.01) and fed state (0.39+/-0.05 vs 0.25+/-0.03, P < 0.05). It was also found the postprandial increase in EGG dominant power in the patients was inversely correlated with the total symptom score (r = 0.63, P = 0.03). It was concluded that abnormal gastric myoelectrical activity may play a role in the pathogenesis of pediatric functional dyspepsia.

Adolescent↗

Sleep-related gastro-oesophageal reflux: provocation with a late evening meal and treatment with acid suppression.

BACKGROUND: Two studies were carried out in order to investigate the issue of meal-provoked nocturnal gastrooesophageal reflux. METHODS: In Experiment 1, 20 symptomatic reflux patients underwent both pH and polysomnographic monitoring on two nights. On one night, patients ate a non-provocative meal prior to 19.00 hours, while on the other night patients consumed a late evening meal (21.00 hours). In Experiment 2.17 symptomatic reflux patients were studied using pH and polysomnographic monitoring on two nights subsequent to a late evening provocative meal. On one night, patients received 75 mg of the H2-antagonist ranitidine, while on another night they received a placebo. The data from 12 of the 17 patients studied were used in the analysis. RESULTS: For Experiment 1, no significant differences in the number or duration of reflux events, acid exposure (total %), or polysomnographic measures of per cent of sleep stages between the two nights were observed. The results of the second experiment demonstrated that when given ranitidine, patients experienced significant decrease in acid contact time (total %), and mean duration of reflux events. Subjective reports of discomfort and sleep disturbance were also significantly improved on the drug night. However, significant differences in polysomnographic measures were not observed. CONCLUSIONS: Based on these results, we conclude that in some symptomatic reflux patients a late-night non-provocative meal may not increase the incidence of gastro-oesophageal reflux, and that a low dose of an H2-antagonist is effective in decreasing oesophageal acid contact time following a late evening provocative meal.

Adult↗

Gastric myoelectrical activity in patients with cervical spinal cord injury.

OBJECTIVE: Dyspeptic symptoms are common in patients with cervical spinal cord injury (SCI). The supraspinal control of sympathetic innervation to the stomach is interrupted in these patients. Gastric emptying has been reported to be delayed in some patients with cervical SCI. Gastric myoelectrical activity is known to regulate gastric motility and is correlated with gastric emptying. The change in gastric myoelectrical activity after cervical SCI is unknown; our aim was to investigate it. METHODS: The study was performed in 12 cervical SCI patients and 14 healthy controls. Gastric myoelectrical activity was recorded using surface electrogastrography for 30 min in the fasting state and 1 h after a standard test meal. Spectral analysis was performed to compute the following parameters from the electrogastrogram; investigated were the percentage of 2-4 cycles/min (cpm) slow waves, the instability coefficient (IC) of the dominant frequency, the postprandial increment of dominant frequency (deltaF), and its power (deltaP). RESULTS: In both fasting and fed states, regular and stable gastric slow waves were observed in both the control group and patients with cervical SCI. The percentage of normal 2-4 cpm slow waves (preprandial, 80.7+/-3.6% vs 91.5+/-3.7%, p > 0.05; postprandial, 82.0+/-4.4% vs 87.2+/-4.2%, p > 0.05) and IC (preprandial, 0.19+/-0.04% vs 0.28+/-0.05%; postprandial, 0.24+/-0.04% vs 0.27+/-0.02%, p > 0.05) were not significantly different between the two groups. The dominant frequency and its power were also similar between the two groups, no matter whether in the fast (frequency, 2.92+/-0.3 vs 2.93+/-0.06 cpm; power, 30.05+/-1.29 vs 29.08+/-1.23 dB, p > 0.05) or fed (frequency, 3.17+/-0.07 vs 3.02+/-0.06 cpm; power, 32.55+/-0.90 vs 32.07+/-1.18 dB,p > 0.05) state. The postprandial response measured by deltaF (0.25+/-0.09 vs 0.09+/-0.07 cpm, p > 0.05) and deltaP (2.52+/-1.10 vs 2.24+/-1.20 dB, p > 0.05) were also similar between the two groups. CONCLUSION: Gastric myoelectrical activity was not altered after cervical SCI.

Adult↗

Effects of meal volume and composition on gastric myoelectrical activity.

The absence of a standard meal in electrogastrography may limit its clinical significance. Different meals may fail to produce the expected postprandial motility pattern. The aim of this study was to investigate the effect of meal volume and composition on postprandial myoelectrical activity. Fourteen healthy subjects were given four meals that differed from a "reference meal" in one single parameter (volume, calorie, or fiber content). Gastric myoelectrical activity was measured using surface electrogastrography. Spectral and statistical analyses were performed to investigate the effect of food properties on electrogastrogram (EGG) parameters. It was found that the reference meal produced a postprandial increase in the dominant frequency (P < 0.007), dominant power (P < 0.04), and percentage of normal 2-4 cycle/min gastric slow waves (P > 0.05). Similar changes were observed with the low-volume and high-fiber meals but not with the reduced-calorie meal. Fasting EGG parameters in all four sessions showed no significant difference. It was concluded that low-calorie meals do not result in expected postprandial physiological responses and thus are not appropriate for EGG tests. A volume reduction of down to one-half the volume of a regular meal does not affect postprandial changes of the EGG; thus a condensed test meal may be recommended for symptomatic patients.

Adult↗

Molecular organization of the glutathione reductase gene in Drosophila melanogaster.

Glutathione reductase catalyzes the conversion of the oxidized form of glutathione to regenerate reduced glutathione, which acts as a versatile intracellular reductant. The present study provides initial characterization of the glutathione reductase gene in Drosophila melanogaster and its response to experimentally induced oxidative stress. Drosophila cDNA clones were isolated, based on cross-hybridization to the Musca domestica glutathione reductase cDNA. Genomic clones were isolated by cross-hybridization with the Drosophila cDNA as hybridization probe. Northern analysis of adult Drosophila poly(A)+ RNA, utilizing the Drosophila cDNA probe, revealed a hybridization signal in the 2-kb range. The entire sequence of one cDNA was determined. In addition to a coding domain of 1431 bases, the sequence included 206 bases upstream of a putative start codon and 355 bases downstream of a putative stop codon. Based on the cDNA sequence, the 476 amino acid sequence of the Drosophila glutathione reductase gene was deduced and was found to have extensive similarities with the glutathione reductase gene from other species. Gene mapping of a 13-kb genomic fragment revealed that the glutathione reductase gene consists of at least two exons spanning approximately 5 kb. A first exon contains sequence for only the first 5 amino acids and the first base of the sixth and appears to be separated by a ca. 2.5-kb intron from the remainder of the coding region, which is confined to <2 kb. The Drosophila glutathione reductase is single copy and its cytogenetic position, as determined by in situ hybridization, is 7D-E on the X chromosome. mRNA levels of glutathione reductase, measured by RT-PCR, increased in response to exposure to 100% ambient oxygen by almost twofold and administration of paraquat by greater than threefold. Exposure of flies to hyperoxia also induced a 60% increase in the activity of glutathione reductase and augmented the concentration of total glutathione by ca. 40% following an initial drop. The present study, besides providing an initial molecular characterization of the glutathione reductase gene in Drosophila, demonstrates its dynamic involvement in response to experimentally induced oxidative stress.

Amino Acid Sequence↗

Meal composition and its effect on postprandial sleepiness.

Drowsiness is a commonly experienced phenomenon following food ingestion. The present two experiments were designed to assess separately the effects of a solid meal compared to a liquid meal and to an equal volume of water, and the effects of meal constituents (high-fat, high-carbohydrate, or mixed meal) on objective postprandial sleep latencies. Ten normal male subjects participated in each study. Both studies used identical protocols, differing only in the meals the subjects were fed. All subjects underwent a pre-meal baseline nap at 1600 hours. At 1700 hours, subjects consumed a test meal. Naps followed at 1730, 1800, 1900, and 2000 hours. Sleep onset latency was determined by standard polysomnographic measures. In both studies, a one-way repeated-measures ANOVA procedure revealed no significant difference in sleep latencies among the meal conditions for the nap at 1600 hours. However, for the postprandial naps at 1730, 1800, and 2000 hours, the solid meal demonstrated a significant decrease in postprandial sleep latency compared with an equivalent volume of water (control). No significant differences in sleep latency were found between the food constituents. Results indicate that in contrast to a liquid meal, a solid meal produces a decrease in sleep onset latency when compared to an equivalent volume of water. Further, it was demonstrated that meal constituents have no effect on postprandial sleepiness.

Adolescent↗

Sleep and gastric function in irritable bowel syndrome: derailing the brain-gut axis.

BACKGROUND: Recently, several studies have shown an alteration in bowel function during sleep in patients with irritable bowel syndrome (IBS), and a recent study also suggests a remarkable increase in rapid eye movement (REM) sleep. These studies have suggested that an alteration in CNS function may play an important role in the pathogenesis of IBS. AIMS: To confirm the presence of an alteration in REM sleep in patients with IBS and to assess the relation between sleep and a non-invasive measure of gastric functioning, the electrogastrogram (EGG). PATIENTS: Ten patients with IBS and 10 age and sex matched normal volunteers. METHODS: All subjects slept one night in the sleep laboratory and underwent polysomnographic monitoring to determine sleep patterns, and recording of the EGG from surface electrodes. RESULTS: The IBS group had a notable and significant increase in the percentage and duration of REM sleep (p < 0.05). The control group had a decrease in the amplitude of the dominant EGG frequency from waking to non-REM sleep (p < 0.05), and a subsequent increase in the amplitude from non-REM to REM sleep (p < 0.05). No such changes were noted in the patients with IBS. CONCLUSIONS: Results confirmed the enhancement of REM sleep in patients with IBS and suggested an intrinsic alteration in autonomic and CNS functioning in patients with IBS.

Adult↗