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Biomedical subjects

P M Clarkson

Publications and source records attributed to P M Clarkson.

At least 19 recordsLinked to original sources

Immobilization effects in young and older adults.

This experiment compared the effects of disuse on the adductor pollicis (AP) muscle in young (YM) and old (OM) men. The AP of the YM and OM was assessed for strength (MVC), compound muscle action potential (CMAP), and volume, and then immobilized for 2 weeks. MVC decreased approximately 22% in the YM, and OM (P<0.001). AP volume was 4.1% (not significant) and 9.5% (P<0.05) less in the YM and OM, respectively. CMAP increased in the OM 0, 24, and 48 h post-immobilization, and did not change in the YM. However, the YM showed a greater decrease in specific force as compared to the OM. YM and OM experienced similar losses in strength, yet muscle volume loss was only significant in OM. Although OM are more susceptible to immediate losses in muscle volume, muscle activation strategies appear to preserve strength during atrophy.

Adult↗

Large-scale disruption of microtubule pathways in morphologically normal human spastin muscle.

OBJECTIVE: To investigate the molecular pathways disrupted by dominant spastin mutations in apparently unaffected skeletal muscle from patients with motor neuron disease (SPG4). METHODS: The authors studied muscle of three individuals from two unrelated families affected by spastic paraplegia caused by spastin mutations. The authors compared RNA expression profiles to 7 normal and 13 pathologic muscle U95A profiles (Duchenne dystrophy, acute quadriplegic myopathy, and spinal muscular atrophy). Data were validated with U133A arrays with seven different control specimens. mRNA and protein confirmations were done for a subset of genes. RESULTS: Both nonsense and missense mutations in the spastin gene disrupted microtubule pathways in nonpathologic tissue, including microtubule dynamics, stability, exocytosis, and endocytosis. CONCLUSIONS: Normal muscle can be used to uncover biochemical perturbation in motor neuron disease. Altered microtubule metabolism in SPG4-linked hereditary spastic paraplegia patients leads to pathology of the long descending tracks of motor neurons that likely have a stringent need for efficient microtubular transport. As many inherited neurologic conditions show a systemic biochemical defect with disease limited to neurons, our data have broader implications for biochemical pathway studies of many neurologic disorders.

Adenosine Triphosphatases↗

The repeated bout effect and heat shock proteins: intramuscular HSP27 and HSP70 expression following two bouts of eccentric exercise in humans.

Exercise-induced damage significantly and predictably alters indirect indicators of muscle damage after one bout of damaging exercise but this response is dampened following a second bout of the same exercise performed 1-6 weeks later. Previously we have described a marked increase in the levels of heat shock proteins (HSPs) HSP27 and HSP70 in human biceps muscle following one bout of high-force eccentric exercise. The purpose of the present study was to examine the intramuscular HSP27 and HSP70 response following two identical bouts of exercise [bout 1 (B1) and bout 2 (B2), separated by 4 weeks] relative to indirect indices of muscle damage. Ten human subjects performed 50 high-force eccentric contractions with their non-dominant forearm flexors; muscle damage of the biceps brachii was evaluated 48 h post-exercise with indirect indices [serum creatine kinase (CK) activity, soreness, isometric maximal voluntary contraction (MVC) force and relaxed arm angle] and immunoblotting of high ionic strength muscle biopsy extracts for both HSPs. Not unexpectedly, the indirect indicators of damage changed dramatically and significantly (P < 0.01) after B1 but had a much smaller response after B2. The magnitude of the HSP response was the same after both bouts of exercise, though the control and exercised samples of B2 demonstrated a lower basal HSP expression. Thus, though both indirect and cellular indicators of exercise-induced muscle damage demonstrate an adaptation consequent to the first bout of exercise, these adaptations are quite different. It is possible that the lower basal HSP expression of the cellular response mediates the attenuation of damage associated with B2 as indicated by indirect indices.

Adaptation, Physiological↗

Differential response of muscle phosphocreatine to creatine supplementation in young and old subjects.

This study compared the effects of short-term creatine supplementation on muscle phosphocreatine, blood and urine creatine levels, and urine creatinine levels in elderly and young subjects. Eight young (24 +/- 1.4 years) and seven old (70 +/- 2.9 years) men ingested creatine (20 g day-1) for 5 days. Baseline muscle phosphocreatine measurements were taken pre- and post-supplementation using nuclear magnetic resonance spectroscopy (NMR). On the first day of supplementation subjects had blood samples taken immediately before and hourly for 5 h following ingestion of 5 g of creatine, and a pharmacokinetic analysis of plasma creatine levels was conducted. Twenty-four hour urine collections were conducted for 2 days prior to the supplementation period and for 5 days during supplementation. Old subjects had significantly higher baseline plasma creatine levels than young subjects (68.5 +/- 12.5 vs. 34.9 +/- 4.7 micromol L-1; P < 0.02). There were no significant differences between groups in plasma creatine pharmacokinetic parameters (i.e. area under the curve, elimination rate constant, absorption rate constant, time to maximum concentration, and maximum concentration) following the 5 g oral creatine bolus. Urine creatine, assessed pre and on 5 days of supplementation, increased (P < 0.001), with no difference between groups. Urine creatinine did not change as a result of creatine supplementation. Young subjects showed a significantly greater increase in muscle phosphocreatine compared with old subjects, and post-supplementation muscle phosphocreatine levels were greater in young subjects (young 27.6 +/- 0.5; old 25.7 +/- 0.8 mmol kg-1 ww) (P=0.02). There were no differences in blood or urine creatine between groups in response to supplementation, but old subjects had a relatively small increase (young 35% vs. old 7%) in muscle phosphocreatine after supplementation.

Adult↗

A single bout of eccentric exercise increases HSP27 and HSC/HSP70 in human skeletal muscle.

Changes in heat shock proteins (HSPs), HSP27 and HSC/HSP70 were characterized in human biceps brachii muscle following damaging high-force eccentric exercise. Male and female volunteers performed a maximal eccentric resistance exercise with the elbow flexor muscles of the non-dominant arm known to be sufficient to cause substantial muscle damage. Protein extracts of biopsy tissue samples taken 48 h post-exercise were immunoblotted for HSC/HSP70 and HSP27. Densitometric analysis demonstrated that these proteins increased significantly (P < 0.01) in the damaged biceps brachii relative to the control arm. The HSC/HSP70 increased 1064% in the exercised sample while HSP27 increased by 234%. Although the literature reports a muscular heat shock response following aerobic, oxidative exercise, this is the first documentation of increases in protein expression of both HSC/HSP70 and HSP27 in human skeletal muscle in response to a single bout of resistance exercise.

Actins↗

Effect of ketoprofen on muscle function and sEMG activity after eccentric exercise.

PURPOSE: This study examined whether ketoprofen, a nonsteroidal anti-inflammatory drug, attenuated muscle soreness (SOR), improved maximal isometric force (MIF) recovery, and/or altered myoelectric activity after high-force eccentric exercise. METHODS: 48 subjects were randomly assigned to one of four groups: CON: no exercise/no drug (N = 12); PLA: exercise + placebo (N = 12); TRT-100: exercise + 100 mg oral ketoprofen (N = 12); and TRT-25: exercise + 25 mg oral ketoprofen (N = 12). PLA, TRT-100, and TRT-25 were administered in a double-blind fashion. Baseline measurements of SOR, MIF, and surface electromyographic (EMG) amplitude were taken, and PLA, TRT-100, and TRT-25 performed 50 maximal eccentric contractions of the elbow flexors; 36 h later, subjects reporting moderate soreness were given ketoprofen or placebo and SOR measures were taken hourly for 8 h. EMG amplitude was assessed during MIF before dosing and again 8 h later and during submaximal contractions of 5%, 10%, and 20% of MIF before dosing and hourly for 8 h. RESULTS: Eccentric exercise increased myoelectric activity during submaximal force measurements in PLA, TRT-100, and TRT-25 in all conditions. Ketoprofen had no effect on reducing this increase in EMG activity. Ketoprofen attenuated perceived SOR (P < 0.05) and enhanced MIF recovery (P < 0.05) compared with placebo. TRT-100 and TRT-25 demonstrated 10% and 19% reductions in SOR, respectively, and 16% and 9% increases in MIF, respectively, whereas PLA demonstrated a 1% increase in SOR and 9% decrease in MIF over 8 h. CONCLUSION: Ketoprofen treatment after muscle damaging exercise reduces muscle soreness and improves force recovery.

Adult↗

Are women less susceptible to exercise-induced muscle damage?

Investigations using animal models show that estrogen is related to enzyme release, specifically creatine kinase, from exercised skeletal muscle. In humans, women have lower resting blood creatine kinase levels than men and have an attenuated blood creatine kinase response after prolonged endurance exercise. These results have led to the common belief that women may be protected from exercise-induced muscle damage due to circulating estrogen. Studies using laboratory models to examine gender differences in exercise-induced muscle damage, however, have not consistently documented that women have an attenuated response compared with men. Furthermore, research on exercise responses in women with different circulating levels of estrogen has not found estrogen to be related to indicators of muscle damage. Recent studies, in fact, have reported that women may experience more muscle damage, based on indirect measures, than men. Although some data exist that women may have a faster recovery from exercise-induced muscle damage, these results are tentative at this time.

Animals↗

The effects of creatine supplementation on exercise-induced muscle damage.

This investigation evaluated the effects of oral creatine (Cr) supplementation on markers of exercise-induced muscle damage following high-force eccentric exercise in subjects randomly administered Cr or placebo (P) in a double-blind fashion. When injected, exogenous phosphocreatine has been shown to stabilize the muscle membrane in cardiac tissue and enhance recovery of strength and power following injury. Twenty-three men aged 18-36 years ingested either 20 g of Cr or P for 5 days. Criterion measures were maximal isometric force of the elbow flexors (MIF), range of motion (ROM) about the elbow, mid and distal arm circumference (CIR; to assess swelling), soreness with movement and palpation (SOR), and blood levels of creatine kinase (CK) and lactate dehydrogenase (LDH). Following the supplementation period, subjects performed 50 maximal eccentric contractions of the elbow flexors. Criterion measures were assessed pre-exercise, immediately postexercise, and for 5 days after exercise. Both groups experienced a significant loss of MIF and ROM (time effect, p < 0.05). There was a significant increase in CIR of the mid and distal biceps, SOR with movement and palpation, CK, and LDH (time effect, p < 0.05), indicating that there was significant muscle damage. However, there were no significant differences in any of the criterion measures between groups (group x time interaction term, p > 0.05). The pattern of change over the 6 days, in response to the eccentric exercise, was nearly identical between groups. These data suggest that 5 days of Cr supplementation does not reduce indirect markers of muscle damage or enhance recovery from high-force eccentric exercise.

Adult↗

The effect of diet on vitamin E intake and oxidative stress in response to acute exercise in female athletes.

Vitamin E is the major lipid-soluble antioxidant found in foods, and its bioavailability is affected by the presence of dietary fats. Athletes often consume lowfat diets and may be more susceptible to the oxidative stress produced by exercise due to the low availability of vitamin E. In this study, the effects of a low-fat diet on vitamin E intake and oxidative stress markers were assessed in collegiate female rowers. All subjects habitually consumed either a low-fat (LF; <40 g fat x day(-1)) or a high-fat (HF; >60 g fat x day(-1) diet. Subjects ran downhill for 45 min at 75% of their age-predicted maximal heart rate. Blood samples were collected immediately pre- and post-exercise, and at 6, 24, and 48 h post-exercise. Subjects in the LF group consumed significantly less vitamin E (2.9 mg vitamin E x day(-1)) than advised by the Recommended Dietary Allowance (RDA; 8.0 mg vitamin E x day(-1)) and than those in the HF group (9.8 mg vitamin E x day(-1); P<0.05). Plasma concentrations of vitamin E, malondialdehyde, and conjugated dienes were not significantly different between LF and HF before or after exercise. Creatine kinase became significantly elevated above baseline at 6 h and 24 h post-exercise in both groups (P<0.05). We can conclude from these data that although the subjects in the LF group were not consuming the recommended amount of vitamin E in their diets, their vitamin E intake appears to be sufficient to protect against the oxidative stress produced by this moderate-intensity exercise.

Adolescent↗

Acute creatine supplementation in older men.

The hypothesis of this study was that short term creatine (Cr) ingestion in older individuals would increase body mass and exercise performance, as has been shown in younger subjects. Seventeen males 60-78 years old were randomly placed into two groups, Cr and placebo (P), and supplemented in double-blind fashion for 5 days. Subjects ingested either 5 g of Cr plus 1 g of sucrose 4x per day or 6 g of a sucrose placebo 4x per day. Isometric strength of the elbow flexors was assessed using a modified preacher bench attached to a strain gauge. Isokinetic exercise performance was assessed using an intermittent fatigue test of the knee extensors. Subjects performed 3 sets of 30 repetitions with 60 sec rest between sets. There was a small (0.5 kg) but statistically significant increase in body mass (p < 0.05) in the Cr group after supplementation. There was a significant overall interaction between groups in isokinetic performance from pre to post supplementation (group x time x set, p < 0.05). However, analysis of the groups separately revealed that the subjects in the Cr group demonstrated a small non-significant increase in isokinetic performance while subjects in the P group demonstrated a small non-significant performance decrement. There was no significant difference in isometric strength between groups from pre to post supplementation. These data suggest that acute oral Cr supplementation does not increase isometric strength and only produces small increases in isokinetic performance and body mass in men over the age of 60.

Aged↗

Response of males and females to high-force eccentric exercise.

It has previously been shown that females incur less muscle damage than males after strenuous exercise, but limited data are available for humans. To determine possible differences between the sexes in humans, the response to high-force eccentric exercise was examined in a large sample of women (n = 83) and men (n = 82). The participants performed a bout of eccentric exercise of the elbow flexors consisting of 70 maximal repetitions. Isometric strength, resting elbow angle and muscle soreness were measured before, immediately after (except soreness) and then daily for 7 days after exercise. There was a significant loss in strength among both groups (69% for women and 63% for men) (P < 0.01) immediately after exercise; at 168 h post-exercise, women still had a 27% strength loss and men had a 24% strength loss. No significant difference in strength loss or recovery rate was found between men and women. Soreness reached peak values 32-48 h post-exercise (P < 0.01), with no significant difference between men and women. Range of motion decreased significantly until 3 days after exercise (14.6 degrees or 0.255 rad loss for women; 12.2 degrees or 0.213 rad loss for men) (P < 0.01); at 168 h post-exercise, the women and men still showed a loss of 4.8 degrees (0.084 rad) and 4.0 degrees (0.07 rad), respectively. There was a significant interaction of sex x time (P < 0.01); a post-hoc test indicated that the women experienced a greater loss in range of motion at 72 h than men and this difference was maintained to 168 h post-exercise (P < 0.01). Thus, our results do not support the contention that women have a lower response to eccentric exercise than men.

Adult↗

Antioxidants: what role do they play in physical activity and health?

Exercise appears to increase reactive oxygen species, which can result in damage to cells. Exercise results in increased amounts of malondialdehyde in blood and pentane in breath; both serve as indirect indicators of lipid peroxidation. However, not all studies report increases; these equivocal results may be due to the large intersubject variability in response or the nonspecificity of the assays. Some studies have reported that supplementation with vitamins C and E, other antioxidants, or antioxidant mixtures can reduce symptoms or indicators of oxidative stress as a result of exercise. However, these supplements appear to have no beneficial effect on performance. Exercise training seems to reduce the oxidative stress of exercise, such that trained athletes show less evidence of lipid peroxidation for a given bout of exercise and an enhanced defense system in relation to untrained subjects. Whether the body's natural antioxidant defense system is sufficient to counteract the increase in reactive oxygen species with exercise or whether additional exogenous supplements are needed is not known, although trained athletes who received antioxidant supplements show evidence of reduced oxidative stress. Until research fully substantiates that the long-term use of antioxidants is safe and effective, the prudent recommendation for physically active individuals is to ingest a diet rich in antioxidants.

Antioxidants↗

Activity and immobilization after eccentric exercise: I. Recovery of muscle function.

PURPOSE: The purpose of the present study was to determine whether activity would affect the recovery of muscle function after high-force eccentric exercise of the elbow flexors. METHODS: Twenty-six male volunteers were randomly assigned to one of three groups for a 4-d treatment period: immobilization (N = 9), control (N = 8), and light exercise (N = 9). Relaxed arm angle (RANG), flexed arm angle (FANG), maximal isometric force (MIF), and perceived muscle soreness (SOR) were obtained for 3 consecutive days pre-exercise (baseline), immediately post-exercise, and for 8 consecutive days after the 4-d treatment period (recovery). During the treatment period, the immobilization group had their arm placed in a cast and supported in a sling at 90 degrees. The control group had no restriction of their arm activity. The light exercise group performed a daily exercise regimen of 50 biceps curls with a 5-lb dumbbell. RESULTS: All subjects showed a prolonged decrease in RANG, increase in FANG, loss in MIF, and increase in SOR in the days after eccentric exercise. During recovery, there was no significant interaction observed among groups over time in RANG (P > 0.05) or FANG (P > 0.05), but there was a significant interaction observed among groups over time in both MIF (P < 0.01) and SOR (P < 0.01). Recovery of MIF was facilitated by light exercise and immobilization, whereas recovery from SOR was facilitated by light exercise and delayed by immobilization. CONCLUSIONS: The recovery of MIF in both the light exercise and immobilization groups suggests that more than one mechanism may be involved in the recovery of isometric force after eccentric exercise.

Adult↗

Activity and immobilization after eccentric exercise: II. Serum CK.

PURPOSE: The purpose of the present study was to examine the effect of muscle activity level on serum creatine kinase (CK) activity after high-force eccentric exercise of the elbow flexors. METHODS: Twenty-six male volunteers were randomly assigned to one of three groups for a 4-d treatment period after exercise: immobilization (N = 9), control (N = 8), and light exercise (N = 9). During the treatment period, the immobilization group had their arm casted and supported in a sling at 90 degrees. The control group had no restriction of their arm activity. The light exercise group performed a daily exercise regimen of 50 biceps curls with a 5-lb dumbbell. Serum CK activity was obtained by venipuncture for three consecutive days before eccentric exercise and during the 4-d treatment period. To quantify activity of the arm, CSA (Computer Science and Applications, Inc.) activity-monitoring devices were worn. RESULTS: Serum CK measurements revealed that there was a significant group by time interaction in the analysis of variance (P < 0.05). Peak serum CK activity of the immobilized group (668 IU) was lower than either the control (4230 IU) or light exercise (2740 IU) group. During the treatment period, activity level among the three groups was significantly different from each other (P < 0.001): 529 counts x min(-1) for the immobilization group, 944 counts x min(-1) for the control group, and 1334 counts x min(-1) for the light exercise group. CONCLUSIONS: These results suggest that immobilization of exercised damaged muscle during recovery significantly blunted serum CK activity, which may be due to attenuated removal of CK from the muscle and/or decrease lymphatic transport.

Adult↗

Effects of 30 days of creatine ingestion in older men.

In this investigation we evaluated the effects of oral creatine (Cr) supplementation on body composition, strength of the elbow flexors, and fatigue of the knee extensors in 20 males aged 60-82 years who were randomly administered Cr or placebo (P) in a double-blind fashion. Subjects ingested either 20 g of Cr or P for 10 days, followed by either 4 g of Cr or P, respectively, for 20 days. Tests were conducted pre-supplementation and following 10 and 30 days of supplementation. Leg fatigue was determined using an isokinetic dynamometer; subjects performed 5 sets of 30 maximal voluntary contractions at 180 degrees x s(-1), with 1 min of recovery between sets. The strength of the elbow flexors was assessed using a modified preacher bench attached to a strain gauge. There was a significant interaction (P < 0.05; group x time) in leg fatigue following supplementation. However, this interaction appears to have resulted from a combination of the improved fatigue score by the Cr-supplemented group and the decreased fatigue score by the P-supplemented group, because when the simple main effects were analyzed for the groups individually, there was no significant difference over time for either of the groups. There were no significant differences in body mass, body density, or fat-free mass as assessed by hydrostatic weighing, or strength between the Cr-supplemented or P-supplemented groups. These data suggest that 30 days of Cr-supplementation may have a beneficial effect on reducing muscle fatigue in men over the age of 60 years, but it does not affect body composition or strength.

Aged↗

Blood leukocyte and glutamine fluctuations after eccentric exercise.

Skeletal muscle, as a producer of glutamine, is important for lymphocytes, monocytes and macrophages. Exercise-induced muscle damage could burden the immune system by concurrently eliciting a local inflammatory response and decreasing glutamine availability. The aim of this study was to determine whether blood leukocyte and glutamine concentrations were affected in individuals with high serum creatine kinase (CK) activity (indirect indication of muscle damage) compared to those with no change in CK. Twelve females performed maximal eccentric resistance exercise using one arm and one leg. Blood leukocyte subsets and glutamine were measured at 24 and 0 h pre-exercise, and post-exercise at intervals up to 9 d post-exercise. Eleven subjects were placed in High (n = 6) and Low CK (n = 5) groups. Lymphocytes, (total, natural killer, and T), monocytes, and granulocytes did not change significantly in either group, at any time. Whole blood glutamine concentration decreased (p < 0.05) from 437 microM pre-exercise to 332 microM 3 d post-exercise in both groups. The decrease in glutamine suggests that the metabolism of the muscle may be affected by this exercise, however, the occurrence of this decrease in both groups suggests that this change was not a response to muscle damage.

Adult↗

Nutritional supplements to increase muscle mass.

Although nutritional supplements purported to increase muscle mass are widely available at health food stores, gyms, by mail order, and over the Internet, many of these supplements have little or no data to support their claims. This article reviews the theory and research behind popular nutritional supplements commonly marketed as muscle mass builders. Included are the minerals chromium, vanadyl sulfate, and boron, the steroid hormone dehydroepiandrosterone (DHEA), beta-methyl-hydroxy-beta-methylbutyrate (HMB), creatine, protein supplements, and amino acids. Research has shown that chromium vanadyl sulfate, and boron do not appear to be effective in increasing lean body mass. The few studies examining DHEA have not supported the claim of increased muscle gain. Preliminary work on HMB supports an anticatabolic effect, but only one human study is currently available. Many studies reported increased body mass and several have reported increased lean body mass following creatine ingestion. This weight gain is most likely water retention in muscle but could also be due to some new muscle protein. Although athletes have a greater protein requirement than sedentary individuals, this is easily obtained through the diet, negating the use of protein supplements. Studies on amino acids have not supported their claim to increase growth hormone or insulin secretion. Nutritional supplements can be marketed without FDA approval of safety or effectiveness. Athletes who choose to ingest these supplements should be concerned with unsubstantiated claims, questionable quality control, and safety of long-term use.

Adult↗

Adverse events associated with eccentric exercise protocols: six case studies.

PURPOSE: Rhabdomyolysis is a condition characterized by muscle damage and degeneration of muscle cells after strenuous, overexertion exercise. Although the incidence of severe rhabdomyolysis is rare, this condition can be dangerous and even fatal. Eccentric exercise protocols are currently being used to induce and study mild forms of muscle damage. However, serious adverse events can occur in these laboratory investigations. The purpose of this report was to expose some of the adverse events resulting from performance of eccentric exercise protocols to study muscle damage in humans. METHODS: The following case studies involved an eccentric exercise protocol where two sets of 25 maximal eccentric actions of the elbow flexors were performed, separated by a 5-min rest period. RESULTS: Case reports are presented that reveal prolonged losses in the ability of the muscle to generate force lasting 43-47 d, extreme swelling of the exercised arm lasting several weeks, and greatly elevated serum creatine kinase levels. CONCLUSIONS: Although adverse events resulting from eccentric exercise are rare, our laboratory has observed a 3% incidence rate during the past year. Investigators should be knowledgeable of the sequelae of events that are associated with muscle damage after high-force eccentric exercise and take appropriate precautions.

Arm↗