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Biomedical subjects

M G Hughes

Publications and source records attributed to M G Hughes.

At least 19 recordsLinked to original sources
PubMed2006

Reliability of repeated sprint exercise in non-motorised treadmill ergometry.

Although repeated sprint tests are relatively common, there have been few investigations of repeated sprint exercise using non-motorised treadmill ergometry. The purpose of this study was to determine the reliability of a repeated sprint procedure using this apparatus. Ten healthy, active males, performed three repeated sprint tests (six repetitions of 6 s sprints with 30 s recovery) on three separate occasions. Performance as determined by maximal speed, average force production, and fatigue were compared across the three trials. Maximal speed and average force were not significantly different between visits (p < 0.05) and a variety of reliability measures suggested good agreement (e.g., coefficient of variations no more than 5 %). The fatigue indices for maximal speed and for average force were generally less reliable (coefficients of variation around 30 % in both cases). In conclusion, measures of performance (maximal speed and average force) can provide reliable results in a repeated sprint protocol but the reliability of fatigue measures appears to be low.

Adult↗
PubMed2004

Evidence that infiltrating neutrophils do not release reactive oxygen species in the site of spinal cord injury.

The release of reactive oxygen species (ROS) by neutrophils, which infiltrate the region of damage following spinal cord injury (SCI), was investigated to determine if such release is significant following spinal cord injury. The relationship of extracellular levels of hydroxyl radicals and hydrogen peroxide obtained by microdialysis sampling and oxidized protein levels in tissue to neutrophil infiltration following spinal cord injury was examined. Neither of the reactive oxygen species were elevated in the site of spinal cord injury relative to their concentrations in normal tissue at a time (24 h) when the numbers of neutrophils were maximum in the site of injury. Surprisingly, ablation with a neutrophil antiserum actually increased the level of oxidized proteins in Western blots. Thus, our findings are (1) that neutrophils, which infiltrate the site of damage following a spinal cord injury, do not release detectable quantities of reactive oxygen species; and (2) that the presence of neutrophils reduces the concentrations of oxidized proteins in the site of spinal cord injury. Therefore, release of reactive oxygen species by neutrophils does not contribute significantly to secondary damage following spinal cord injury. Reduced levels of oxidized proteins in the presence of neutrophils may reflect removal of damaged tissue by neutrophils.

Animals↗
PubMed2001

Hyaluronan enhances contraction of collagen by smooth muscle cells and adventitial fibroblasts: Role of CD44 and implications for constrictive remodeling.

Remodeling contributes to restenosis when cells shrink the artery wall at sites of injury. This may be analogous to wound healing, where tissue remodeling achieves wound contraction. Hyaluronan (HA) is prominent in wound matrix and inhibits fetal scarring. HA is also produced in the artery wall after angioplasty, where it may inhibit constrictive remodeling. This hypothesis was tested in vitro using a model of matrix contraction. Primate aortic smooth muscle cells and adventitial fibroblasts were seeded into collagen I gels containing increasing amounts of HA (0% to 50%, wt/wt). Both cell types reduced the diameter of collagen alone approximately 65% at 18 hours. HA significantly increased gel contraction (diameter in mm: 0% HA, 7. 7+/-0.9; 2%, 7.1+/-0.7; 10%, 6.7+/-0.5; 50%, 5.6+/-0.9; P<0.05 for >/=10%), cell spreading and telopodia, and pericellular accumulation of collagen fibrils. These effects were mediated in part by cellular HA binding, because an antibody against CD44 receptors blocked pericellular collagen accumulation and enhanced gel contraction without altering cell shape. The role of CD44 was specific, because inhibiting receptor for hyaluronic acid-mediated motility (RHAMM) had no effect. Blocking ss(1)-integrins completely inhibited contraction of collagen, but gels containing HA required CD44 and ss(1)-integrin blockade for complete inhibition. Enhanced collagen reorganization and contraction were not attributable to increased collagenase activity, because the metalloproteinase inhibitor batimastat had no effect. In summary, HA enhanced collagen reorganization by the cell types most likely to mediate constrictive remodeling after angioplasty. These effects were CD44-dependent, thus providing a potential target for therapies to prevent constrictive remodeling and restenosis.

Animals↗
PubMed2001

Rating of perceived exertion during high-intensity treadmill running.

PURPOSE: The purpose of this investigation was 1) to evaluate the time course of the rating of perceived exertion (RPE; 6-20 Borg scale) during short-term, high-intensity, constant-load running (ST); and 2) to determine the reproducibility of RPE during ST. METHODS: Fifteen well-trained males (VO2max = 58.0 +/- 4.6 mL x kg(-1) x min(-1), mean +/- SD) performed treadmill running (i.e., between 3 and 4 m.s-1 at 10.5% incline) to volitional exhaustion (Tlim) at an exercise intensity equivalent to 125% VO2max. A total of four RPE measurements were taken during each test, one every 30 s during the first 120 s of the exercise. The tests were repeated at the same time of day on three occasions within a 3-wk period. RESULTS: Tlim for the three tests was 197.6 +/- 34.8 s. RPE was linearly related with exercise time (mean +/- SD for the three tests: RPE at 30 s = 10.8 +/- 2.2; RPE at 60 s = 12.6 +/- 1.8; RPE at 90 s = 14.5 +/- 1.7; RPE at 120 s = 16.0 +/- 1.9; RPE = 9.06 + (0.06 x time (s)); r = 0.71, SEE = 2.0, P < 0.01). Repeated ANOVA revealed no systematic bias between the three tests for RPE, and other measures of reliability were also favorable. These included intraclass correlation coefficients ranging from 0.78 to 0.87 and sample coefficients of variation of between 4.4% and 6.0%. The 95% limits of agreement ranged between 0.0 +/- 2.3 and 0.0 +/- 2.5. CONCLUSION: ST RPE displays a positive linear response during the first 2 min. The measurement of ST RPE appears to be reliable and could thus add a new dimension to ST investigations.

Adult↗
PubMed2000

Evidence that reversed glutamate uptake contributes significantly to glutamate release following experimental injury to the rat spinal cord.

Released excitatory amino acids contribute significantly to secondary damage following spinal cord injury. Reversal of normal transport due to cell membrane depolarization may contribute to this release. We tested this by administering dihydrokainic acid (DHK), a non-transported glutamate uptake blocker, into the rat spinal cord by microdialysis in association with contusion spinal cord injury. Glutamate release in response to injury was reduced by 34% (P<0.05) when 3 mM DHK was administered within the microdialysis fiber, suggesting that reversed transport is an important contributor to glutamate release upon spinal cord injury.

Animals↗
PubMed2000

Adenosine release upon spinal cord injury.

The hypothesis that release of adenosine following spinal cord injury (SCI) may provide neuroprotective feedback is explored. Consistent with this hypothesis, substantial release of adenosine, estimated to reach 100 microM in the extracellular space, was detected by microdialysis sampling immediately following contusion SCI. There is also considerable release of excitatory amino acids following SCI. The latter was not affected by administration of the general adenosine receptor antagonist theophylline and the A1 antagonist 8-cyclopentyl-1,3-dipropylxanthine, implying that the adenosine released following SCI does not significantly influence the release of neurotoxic amino acids. Administration of the concentration of glutamate released upon SCI into the spinal cord caused only about 1% as much release of adenosine as did injury, evidence that elevated excitatory amino acids do not elicit an appreciable fraction of the release of adenosine that follows SCI. Results obtained suggest that release of endogenous adenosine is not neuroprotective by blocking release of excitatory amino acids following SCI.

Adenosine↗
PubMed1999

Changes in amino acid concentrations over time and space around an impact injury and their diffusion through the rat spinal cord.

Release of amino acids, particularly the neurotoxin glutamate, in and around the site of an experimental spinal cord injury was characterized over time by microdialysis. Increases in amino acid concentrations caused by injury decline steeply and then slowly over distance from the impact area, becoming undetectable beyond about 5 mm from the injury epicenter. Diffusion profiles determined in the cord by administering amino acids through one microdialysis fiber and sampling them in a parallel fiber declined steeply with distance. Distant increases coincided temporally with those in the injury epicenter. We conclude that elevated amino acids more than about 1 mm into the periimpact zone are predominantly released in that region rather than diffusing into it from the trauma epicenter. In the outer areas of lesion development, glutamate does not appear to reach concentrations ordinarily toxic, and elevated concentrations do not persist nearly as long as the therapeutic window of NBQX in any part of the lesion. Therefore, the mechanisms whereby excitatory amino acid antagonists reduce the dimensions of injury lesions are unclear. However, sensitization of neurons following impact injury could be important in amino acid neurotoxicity.

Amino Acids↗
PubMed1998

Considerations in the determination by microdialysis of resting extracellular amino acid concentrations and release upon spinal cord injury.

The following issues are further addressed: (1) Is there considerable leakage of amino acids from the circulation into the space around microdialysis probes, or are amino acid concentrations naturally much higher in the interstitial space than is generally thought? (2) Do observed high interstitial concentrations or depletion of substances in the intracellular space by microdialysis affect release measurements upon spinal cord injury? Amino acid concentrations around microdialysis fibres in the spinal cord of rats were found to approach those in the circulation and to be much higher than interstitial concentrations previously estimated in the CNS. However, much lower concentrations of amino acids were derived in the hippocampus by analogous experiments. Considerable Evans Blue/albumin leaked from the circulation into the interstitial space in the spinal cord immediately after fibre insertion. However, this movement diminished considerably by 4 h later, demonstrating substantial resealing of the blood-brain barrier, at least to large molecules. There is either substantial damage-induced movement of amino acids from the circulation into the dialysis zone after insertion of a microdialysis probe, or there is much less impediment to movement of amino acids across the blood-brain barrier in the spinal cord than in the brain. At low flow rates through the fibre, adding concentrations of amino acids to the inside of the fibre equal to the concentrations around the fibre to prevent their depletion by removal through the microdialysis fibre did not affect increases in concentrations of amino acids in microdialysates following injury. Thus the high concentrations of amino acids present around microdialysis fibres following their insertion do not seem to disturb measurements of amino acid release upon spinal cord injury.

Amino Acids↗
PubMed1997

Plasma leptin concentrations and OB gene expression in subcutaneous adipose tissue are not regulated acutely by physiological hyperinsulinaemia in lean and obese humans.

OBJECTIVES: To determine the effects of obesity on fasting plasma leptin levels and assess the effects of feeding on plasma leptin and OB gene expression in subcutaneous adipose tissue in non-diabetic subjects. DESIGN: Blood and subcutaneous adipose tissue needle biopsy samples were obtained after an overnight fast and 1, 2 and 3 h following a mixed meal (606 kcal). SUBJECTS: Eighteen female subjects: eight lean with a mean age of 40.1 yr (range 20-65) and mean body mass index of 22.24 kg/m2 (range 18.6-26.6) and ten obese subjects with a mean age of 48.6 yr (range 29-71) and body mass index of 33.53 kg/m2 (range 28.7-41.7). RESULTS: Apart from obesity the only significant difference between groups was a 2.6 fold higher fasting plasma leptin concentration in obese subjects compared to leans (26.9 +/- 2.9 vs 10.2 +/- 2.22 (P < 0.05) respectively). Adipose tissue OB mRNA levels were not significantly higher in the obese group. Plasma leptin correlated with BMI and visceral fat weight in lean subjects only. No significant association between plasma leptin and adiposity was evident in obese patients. In addition, there was no association between plasma leptin and the insulin: glucose ratio (an index of insulin sensitivity). Following a mixed meal, post-prandial plasma insulin levels were significantly increased, with a concomitant significant reduction in plasma NEFA levels in both groups. Despite the large increase in plasma insulin, there were no post-prandial changes in either plasma leptin concentrations or subcutaneous adipose tissue OB mRNA levels in either lean or obese subjects. CONCLUSIONS: The data indicate that plasma leptin levels are correlated with the degree of adiposity, especially in lean subjects, and confirm that circulating leptin levels are greater in obese subjects than lean subjects. The present study also failed to show a significant association between plasma leptin and insulin sensitivity in lean and obese women. Furthermore, plasma leptin and subcutaneous adipose tissue OB gene expression are not under short term regulation following feeding in fasted lean or obese female subjects.

Adipose Tissue↗
PubMed1997

Microdialysis studies of the role of chemical agents in secondary damage upon spinal cord injury.

Assorted microdialysis studies of the roles endogenous chemical agents may play in secondary damage upon spinal cord injury (SCI) are described. Issues addressed include the concentrations reached upon injury, mechanisms of release upon injury, and effects of drugs on injury-elicited increases in glutamate concentrations. An important question in identifying an agent of secondary damage upon central nervous system (CNS) trauma is not simply whether the substance is released upon injury, but whether it reaches harmful levels. To resolve this requires establishing the concentration attained and then determining whether administering that level damages neurons. To make microdialysis measurements of amino acids in the CNS more quantitative, we characterized the effects of insertion of a microdialysis fiber on leakage of glutamate from the circulation and explored the effects of depletion by microdialysis on release caused by SCI. Very high glutamate concentrations were found around the fiber for several hours after fiber insertion and 2 days later, and there was substantial leakage of alpha-aminoisobutyric acid from the circulation into the dialysis zone for several hours after fiber insertion. Glutamate concentrations reached upon SCI under nondepleting conditions were similar to those estimated earlier under depleting conditions. Mg2+ release was detectable when microdialysis probes were perfused with Mg2+-free fluid, but not when the concentrations in the perfusing fluid approximated those in the interstitial space. It is concluded (1) that insertion of microdialysis probes into CNS tissue can cause long-lasting leakage of amino acids from the circulation into the space around the fiber, (2) that this leakage can obscure concentration changes that otherwise occur, and (3) that depletion of substances in the fluid around the fiber may cause increases in concentration to be observed that do not normally happen. We also describe demonstrations that administration of methylprednisolone and dihydrokainic acid diminish increases in glutamate concentrations caused by SCI, showing that microdialysis can be used to explore effects of drugs on actions of damaging substances.

Animals↗
PubMed1997

Antidiabetic efficacy of BRL 49653, a potent orally active insulin sensitizing agent, assessed in the C57BL/KsJ db/db diabetic mouse by non-invasive 1H NMR studies of urine.

High resolution 1H nuclear magnetic resonance (NMR) spectroscopic analysis of biofluids is a recently established tool for evaluating inherited and acquired errors in metabolic control. In the present study 1H NMR analysis of urine was used to monitor efficacy of BRL 49653, a potent and selective antihyperglycaemic agent, following oral administration for up to 36 weeks to the genetically diabetic C57BL/KsJ db/db mouse. The effects of BRL 49653 on carbohydrate and fatty acid metabolism were monitored by determination of changes in concentrations of low molecular weight urinary metabolites. A qualitative comparison of the NMR spectra of urine from untreated diabetic mice with those of lean littermates and literature examples revealed several abnormalities, the majority of which could be explained in terms of the non-insulin dependent diabetes syndrome exhibited by these animals. Quantitatively the most prominent was the extreme glycosuria of both young (8-12 weeks; 0.9 g glucose kg-1 h-1) and older (42 weeks; 2 g glucose kg-1 h-1) diabetic mice. This was accompanied by the excretion of a number of unassigned sugar derivatives and by ketone bodies. Administration of BRL 49653 (3 mumol kg-1) to db/db mice for 24 days reduced blood glucose concentrations to values comparable with non-diabetic lean littermates and reduced glycosuria by > 90%. BRL 49653 significantly reduced excretion of unassigned sugars, acetate, lactate, and the ketone bodies, acetoacetate, 3-D-hydroxybutyrate and acetone. The anti-diabetic efficacy of BRL 49653, assessed from the pattern of urinary metabolites, was maintained over a 36-week treatment period. These results demonstrate the value of 1H NMR to evaluate non-invasively the efficacy of novel therapeutic agents.

Administration, Oral↗
PubMed1996

Effects of aging and obesity on respiratory muscle phenotype in Zucker rats.

Because obesity results in an increased work of breathing, we tested the hypothesis that the oxidative properties and myosin heavy chain (MHC) isoform profiles in respiratory muscles would differ between lean and obese animals. Furthermore, we postulated that obesity-related changes in respiratory muscles would be independent of age. To test these hypothesis, samples of the costal diaphragm, crural diaphragm, and parasternal intercostal muscles were removed from three age groups (young, adult, and old) of obese and lean Zucker rats. Citrate synthase (CS) activity was measured as a marker of oxidative capacity, and MHC isoforms were identified with gel electrophoresis. Analysis revealed that CS activity was significantly higher in the crural and costal diaphragms and parasternal intercostal of obese animals compared with lean animals (P < 0.05); this obesity-related increased in CS activity was related independent of age. Furthermore, respiratory muscle percent type IIb MHC was lower and percent type I MHC isoforms were higher in obese animals compared with lean animals. These data support the notion that obesity results in a fast-to-slow shift in MHC phenotype and an increase in oxidative capacity in major inspiratory muscles. The shift in MHC isoforms in obese animals is also age related, whereas the obesity-mediated increase in oxidative capacity is relatively independent of age.

Aging↗
PubMed1991

Release and metabolism of 5-hydroxytryptamine in the cat spinal cord examined with microdialysis.

The primary objective of this work was to investigate how in vivo administration of depolarizing agents increases extracellular concentrations of 5-hydroxytryptamine (5-HT) and simultaneously decreases levels of its chief metabolite 5-hydroxyindole-3-acetic acid (5-HIAA). To this end the effects of a number of agents on extracellular levels of 5-HT and 5-HIAA in cat spinal cord were determined by microdialysis and high-pressure liquid chromatography with electrochemical detection. The semipermeable portion of the dialysis probe was centered in the dorsal horn. Artificial cerebrospinal fluid containing elevated K+ or drugs was introduced into the dorsal horn via the dialysis probe. Increases in recovered 5-HT were assumed to reflect increased levels in the extracellular fluid due to release, reduced reuptake and/or reduced metabolism. Depolarizing agents (K+, veratridine and aconitine) increased 5-HT, but dramatically decreased 5-HIAA levels. Extracellular 5-HT returned to near base-line levels with removal of the depolarizing agents. The reduction in 5-HIAA was transient after potassium infusion, but outlasted the infusion of veratridine or aconitine by several hours. Reduction of 5-HIAA could be blocked or reversed with the Na+ channel blockers, lidocaine and tetrodotoxin. Evidently, the decrease in 5-HT metabolism followed activation of sodium channels. Parachloroamphetamine caused an increase in 5-HT levels, presumably reflecting increased 5-HT release, but did not change 5-HIAA levels. Although fluoxetine increased 5-HT, it reduced 5-HIAA, presumably through blockade of 5-HT reuptake leading to a secondary reduction in metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)

Aconitine↗
PubMed1991

Study of the management of chlamydial cervicitis in general practice.

The role of the general practitioner in the detection and management of Chlamydia trachomatis infections of the cervix is uncertain. The management by the primary care team of women presenting with lower genital tract symptoms has therefore been studied in one suburban practice. Of 386 women presenting with lower genital tract symptoms over the two year study period 25 (6%) had a positive cervical MicroTrak (Syva) test for Chlamydia trachomatis. Twenty four of these chlamydia positive patients were given their results and treatment by the practice. Twenty two women returned for a follow-up MicroTrak test after treatment and two of these patients (9%) had a positive test following treatment. A review of the patients' notes indicated that contact tracing had been discussed with 22 of the 25 chlamydia positive patients. The results of the management of chlamydial cervicitis by this primary health care team are acceptable when compared with studies from hospital clinics. Provided the primary care team has access to facilities for the diagnosis of C trachomatis and can follow up non-attenders to ensure they receive their results, provide information about contact tracing and follow up positive patients then chlamydial cervicitis can be managed in general practice.

Adolescent↗
PubMed1989

Amino acid uptake and incorporation not cell-specific peptides and evidence for intracellular peptide pools in Aplysia neurons R3-R14.

1. Relationships between intracellular amino acid concentrations and uptake rates and their utilization in synthesis of cell-specific peptides in neurons R3-R14 in the Aplysia parietovisceral ganglion are explored. 2. The uptake rates and intracellular concentrations of most amino acids are positively correlated and inversely related to their degree of incorporation into the peptides. 3. The bulk cellular pool of arginine is probably utilized in the synthesis of R3-R14 peptides, but much of the glycine taken up appears not to be readily available for protein synthesis. 4. There are rapidly and slowly turning over pools of the peptides, and portions of the peptides stay in the cell bodies for days.

Amino Acids↗
PubMed1988

Microdialysis recovery of serotonin released in spinal cord dorsal horn.

Methods for making and using hollow microdialysis fibers suitable for recovering extracellular substances from discrete regions of the spinal cord are described. After placement of the fiber, artificial cerebrospinal fluid was pushed through it at a low (4-5 microliters/min) rate. The perfusate was collected and samples analyzed on a high performance liquid chromatograph with an electrochemical detector. Serotonin, 5-hydroxyindole acetic acid and norepinephrine were recovered and identified. Single unit extracellular recordings were made during the perfusion and collection; thus simultaneous observation of neurotransmitter release and modulation of single cell activity is now possible.

Animals↗
PubMed1983

The distribution of serotonin in the CNS of an elasmobranch fish: immunocytochemical and biochemical studies in the Atlantic stingray, Dasyatis sabina.

The distribution of serotonin (5HT) in the brain of the Atlantic stingray was studied with peroxidase-antiperoxidase immunocytochemistry and high-pressure liquid chromatography. The regional concentrations of 5HT determined for this stingray fell within the range of values previously reported for fishes. A consistent trend in vertebrates for the hypothalamus and midbrain to have the highest concentrations and the cerebellum the lowest was confirmed in stingrays. Neuronal cell bodies and processes exhibiting 5HT-like immunoreactivity were distributed in variable densities throughout the neuraxis. Ten groups of 5HT cells were described: (I) spinal cord, (II-IV) rhombencephalon, (V, VI) mesencephalon, (VII, VIII) prosencephalon, (IX) pituitary, and (X) retina. There were three noteworthy features of the 5HT system in the Atlantic stingray: (1) 5HT cells were demonstrated in virtually every location in which 5HT-containing cells have been described or alluded to in the previous literature. The demonstration of immunopositive cells in the spinal cord, the retina, and the pars distalis of the pituitary suggests that 5HT may be an intrinsic neurotransmitter (or hormone) in these regions. (2) The distribution of 5HT cells in the brainstem shared many similarities with that in other vertebrates. However, there were many 5HT cells outside of the raphe nuclei, in the lateral tegmentum. It appears that the hypothesis that "lateralization" of the 5HT system is an advanced evolutionary trend cannot be supported. (3) 5HT fibers and terminals were more widely distributed in the Atlantic stingray brain than has been reported for other nonmammalian vertebrates on the basis of histofluorescence. It appears that this feature of the 5HT system arose early in phylogeny, and that the use of immunohistochemistry might reveal a more general occurrence of widespread 5HT fibers and terminals.

Animals↗