The expression of heat shock protein in human skeletal muscle: effects of muscle fibre phenotype and training background.

AIM: Exercise-induced adaptations of skeletal muscle are related to training mode and can be muscle fibre type specific. This study aimed to investigate heat shock protein expression in type I and type II muscle fibres in resting skeletal muscle of subjects with different training backgrounds. METHODS: Three groups of subjects were included: healthy active not engaged in any training programme (ACT, n = 12), resistance trained (RES, n = 6) and endurance trained (END, n = 8). Biopsies were obtained from vastus lateralis, and immunohistochemistry was performed using monoclonal antibodies against myosin heavy chain I and IIA, αB-crystallin, HSP27, HSP60 and HSP70. RESULTS: In ACT and RES, but not in END, a fibre type-specific expression with higher staining intensity in type I than type II fibres was seen for αB-crystallin. The opposite (II > I) was found for HSP27 in subjects from ACT (6 of 12 subjects) and RES (3 of 6), whereas all subjects from END displayed uniform staining. HSP60 showed no fibre-specific expression. HSP70 displayed a fibre-specific expression pattern (I > II) in ACT (4 of 12), but not in END or RES. CONCLUSION: This study shows that the level of expression of the different HSPs in human skeletal muscle is influenced by muscle fibre phenotype. The fibre type-specific expression of HSP70 is influenced by resistance and endurance training, whereas those of αB-crystallin and HSP27 is influenced only by endurance training, suggesting the existence of a training-modality-specific action on the adaptive processes including heat shock proteins in human skeletal muscle.

Physical performance and muscular characteristics in different stages of COPD.

This study has examined exercise capacity and muscle morphology in patients with different severities of chronic obstructive pulmonary disease (COPD). Twenty-three patients and 12 healthy matched controls were recruited. Based on the severity of airflow obstruction, patients were divided into two subgroups. Exercise capacity was determined using a 6-min walk test. Muscle fiber composition, fiber area and number of satellite cells/muscle fiber were determined in muscle biopsies using immunohistochemistry. A progressive decline in exercise capacity was noted with ascending disease severity. Furthermore, a correlation between reduction in exercise capacity and changes in muscle fiber composition was observed in COPD. The group with severe and very severe COPD had a lower proportion of type I and a higher proportion of type IIa fibers compared with the other groups. In severe and very severe COPD, a reduction in fiber area of type IIa fibers was also seen. The number of satellite cells/muscle fiber did not differ between the groups. In conclusion, a decline in exercise capacity occurs already in mild and moderate COPD, indicating that the 6-min walk test is a reliable indicator of disease severity. Furthermore, changes in skeletal muscle morphology are associated with disease severity while muscle regenerative capacity is not altered.

Improved intramuscular blood flow and normalized metabolism in lateral epicondylitis after botulinum toxin treatment.

Lateral epicondylitis is a common cause of elbow pain, and decreased microcirculation in extensor carpi radialis brevis (ECRB) has recently been suggested to contribute to the symptoms. The purpose of this pilot study was to investigate the treatment response after injection of botulinum toxin type A. Ten patients with unilateral epicondylitis and decreased intramuscular blood flow in ECRB participated. Handgrip, 2-pinch grip and muscle strength during radial deviation and dorsal extension of the wrist were recorded. Perceived pain during contraction was evaluated with the Visual Analogue Scale (VAS) and function in daily activities was assessed using the Disability of Arm, Shoulder and Hand instrument (DASH) and the Canadian Occupational Performance Measure instrument (COPM). Intramuscular blood flow was recorded by laser Doppler flowmetry, and microdialysis was used to analyze muscle metabolism. The difference in intramuscular blood flow between the control and the affected side had decreased 3 and 12 months after treatment (P=0.03). Lactate concentration at the 12-month follow-up had decreased (P=0.02); perceived pain was reduced and function in daily activities had improved. Injection of botulinum toxin is an alternative treatment for epicondylitis. Symptom relief may be due to enhanced microcirculation causing an aerobic metabolism.

Overexpression of von Hippel-Lindau protein in skeletal muscles of patients with chronic obstructive pulmonary disease.

BACKGROUND: A significant number of patients with chronic obstructive pulmonary disease (COPD) exhibit skeletal muscle wasting and decreased capillary area formation, which correlate with increased mortality. AIM: To determine the molecular mechanisms mediating decreased capillary formation in COPD. METHODS: 24 patients with COPD and 12 matching controls were recruited. Patients with COPD were classified into mild, moderate and severe groups according to GOLD (global initiative for chronic obstructive lung disease) criteria. Biopsy specimens were obtained from the tibialis anterior muscle. Fibre typing and capillary formation, together with messenger RNA (mRNA) expression of hypoxia-inducible factors (HIF1alpha and HIF3alpha), vascular endothelial growth factors (VEGF-A, VEGF-B and VEGF-C isoforms) and von Hippel-Lindau (VHL) protein, were determined. VHL expression and localisation were further studied by immunohistochemistry. RESULTS: Skeletal muscle capillary formation decreased significantly with increasing disease severity. Compared with controls, a tendency to mRNA overexpression of HIF1alpha, HIF3alpha and VEGF isoforms was observed in mild and moderate COPD, which decreased at the severe stage. In contrast, skeletal muscle biopsy samples from patients with COPD exhibited significant overexpression of VHL at both the mRNA and protein level by immunohistochemistry. VHL protein was further determined to be localised to satellite cells. CONCLUSIONS: Overexpression of VHL was identified in the skeletal muscle of patients with COPD. Increased VHL activity may have a negative effect on transduction of the hypoxic signal and may contribute to decreased capillarisation in skeletal muscles of patients with COPD.

Muscle strength correlates with total body bone mineral density in young women but not in men.

BACKGROUND: Osteoporosis is a growing health problem. One of the proposed reasons for this is a more sedentary lifestyle. The aim of this study was to investigate the associations between muscle strength and total body bone mineral density (TBMD) in young adults at expected peak bone mass. METHODS: Sixty-four women and 61 men (total 125) 21 years of age were included. Handgrip strength, isokinetic knee-flexion and -extension muscle strength, TBMD, and body composition were measured. RESULTS: Univariate regression analyses showed that knee flexion and extension explained almost 30% of the variation in TBMD in women, whereas handgrip strength was not associated with TBMD. In men, no correlation between any measures of muscle strength and TBMD was evident. Stepwise regression analysis showed that knee-flexion and -extension muscle strength in women were associated with TBMD, R2=0.27. In men, lean body mass, fat mass, weight, and height were predictors for TBMD, R2=0.43, whereas muscle strength did not affect the prediction of TBMD. CONCLUSIONS: Muscle strength at weight-bearing sites is related to TBMD in women, whereas body composition is related to TBMD in men. The association of lower limb strength on TBMD only in young women indicates a gender difference.

Muscle glycogen resynthesis rate in humans after supplementation of drinks containing carbohydrates with low and high molecular masses.

The rate of muscle glycogen synthesis during 2 and 4 h of recovery after depletion by exercise was studied using two energy equivalent carbohydrate drinks, one containing a polyglucoside with a mean molecular mass of 500 000-700 000 (C drink), and one containing monomers and oligomers of glucose with a mean molecular mass of approximately 500 (G drink). The osmolality was 84 and 350 mosmol. l(-1), respectively. A group of 13 healthy well-trained men ingested the drinks after glycogen depleting exercise, one drink at each test occasion. The total amount of carbohydrates consumed was 300 g (4.2 g. kg(-1)) body mass given as 75 g in 500 ml water immediately after exercise and again 30, 60 ad 90-min post exercise. Blood glucose and insulin concentrations were recorded at rest and every 30 min throughout the 4-h recovery period. Muscle biopsies were obtained at the end of exercise and after 2 and 4 h of recovery. Mean muscle glycogen contents after exercise were 52.9 (SD 27.4) mmol glycosyl units. kg(-1) (dry mass) in the C group and 58.3 (SD 35.4) mmol glycosyl units. kg(-1) (dry mass) in the G group. Mean glycogen synthesis rate was significantly higher during the initial 2 h for the C drink compared to the G drink: 50.2 (SD 13.7) mmol. kg(-1) (dry mass). h(-1) in the C group and 29.9 (SD 12.5) mmol. kg(-1) (dry mass). h(-1) in the G group. During the last 2 h the mean synthesis rate was 18.8 (SD 33.3) and 23.3 (SD 22.4) mmol. kg(-1) (dry mass). h(-1) in the C and G group, respectively (n.s.). Mean blood glucose and insulin concentrations did not differ between the two drinks. Our data indicted that the osmolality of the carbohydrate drink may influence the rate of resynthesis of glycogen in muscle after its depletion by exercise.

[Osteoporosis is prevented by physical activity, calcium and hormone supplementation]. / Benskörhet förebyggs med fysisk aktivitet, kalcium och hormoner.

As the incidence of osteoporosis-related fractures is increasing and constitutes a major health problem in the Western world, their prevention is of great importance. Physical activity, combined with adequate calcium intake and hormone levels, is necessary for the formation and maintenance of bone tissue. The effects of physical exercise on bone tissue variables are most beneficial when it is intensive, regular, and of weight-bearing character. Physical exercise may also be of value in the future treatment of osteoporosis. In addition to its skeletal effects, such exercise improves physical fitness, muscle strength and co-ordination, resulting in a reduced risk of fractures and improved quality of life.

Short-term intermittent normobaric hypoxia--haematological, physiological and mental effects.

Effects on erythropoiesis and blood pressure as well as physical performance and mental effects were studied in 15 healthy subjects during intermittent exposure to normobaric hypoxia corresponding to either 2000 m (6 persons) or 2700 m (9 persons) above sea level; another group (5 persons) also served as controls at normoxia. The concept "live high-train low" was used for 10 d consecutively and the exposure to hypoxia was 12 h/d. Blood pO2 and oxygen saturation were significantly decreased during the 10 d at hypoxia. [Hb] and Hct decreased significantly after 2 d in hypoxia and then returned to pre-study levels. Erythropoietin was significantly elevated in both hypoxia groups during the initial 3-5 d. Reticulocytes were significantly increased during 7 d of hypoxia. Submaximal and maximal oxygen uptake, blood pressure at rest and during exercise and the profile of mood states (POMS test) did not change during the study. In conclusion, intermittent normobaric hypoxia for 10 d resulted in a significant stimulation of erythropoiesis. Staying at normobaric hypoxia may serve as a complement to an ordinary altitude level sojourn.

Increased left ventricular muscle mass after long-term altitude training in athletes.

The effects of long-term altitude training on altitude and sea-level physiological characteristics in elite endurance athletes were investigated. Seven Swedish elite cross-country skiers (five men, two women; mean age 27 years) spent 1 month training at 1900 m above sea level in Italy. Rollerski treadmill tests were performed before and 5 and 11 days after the altitude sojourn; three tests were also performed at altitude. Before and 1, 11 and 35 days after the altitude camp, echocardiographic and blood volume measurements were performed. The heart rates at both maximal (P < 0.05) and submaximal (P < 0.01) work loads were decreased by 5-9 beats min-1 at altitude. The haemoglobin concentration and haematocrit increased quickly at altitude with a corresponding decrease on return to sea level. The blood volume (7%) and total haemoglobin (3%) tended to be higher day 11 post-altitude (NS). There were no significant changes in diastolic internal diameter or wall thickness of the left ventricle, but the calculated cardiac left ventricular muscle mass was increased post-altitude (9-10%, P < 0.01). The maximal oxygen uptake increased in six of the seven skiers after the altitude training (day 11, mean 3%, NS). In conclusion, training at moderate altitude may cause a reduction in heart rates during exercise. Moreover, after long-term training at altitude, there may be an increase in the cardiac left ventricular muscle mass.

Bone metabolism during exercise and recovery: the influence of plasma volume and physical fitness.

Understanding the reaction of bone to physical exercise is important for the development of strategies to increase and maintain bone mass. In this study the aim was to investigate the relationship among exercise intensity, physical capacity, and the biochemical responses, estimated by measuring biochemical markers of bone metabolism in serum. As a complement to the circulating concentrations we also accounted for the plasma volume shifts during and after exercise. The study included 10 men and 10 women, mean age 29 years, with a wide range of physical capacity, who performed a standardized running exercise test on a motor-driven treadmill with loads corresponding to 47 and 76% of VO2 max (maximal oxygen uptake) followed by a maximal effort until exhaustion. Total work time was about 35 minutes. Venous blood samples were drawn at rest, after each load, and after 30 minutes and 24 hours of recovery. The reductions in plasma volume during exercise were 4.3% (P < 0.05) and 15.1% (P < 0.001) whereas after 24 hours in recovery there was an expansion of 7.5% (P < 0.001). There were marked, intensity-related, increases of PICP and tALP concentrations (P < 0.001) during exercise. Since these were of the order of plasma volume reduction they did not correspond to a change in the calculated circulating amount (content). However, as the concentrations returned to basal during recovery, the total circulating amounts were increased at this point (P < 0.05). Osteocalcin was also increased during recovery (P < 0.01), although concentrations were unchanged during the entire study. The amount (P < 0.001) and concentration (P < 0. 05) of ICTP were also increased during follow-up. Serum PTH concentrations rose (P < 0.05) in proportion to the intensity of exercise and remained elevated during recovery. The subjects' VO2 max demonstrated positive relationships to the biochemical responses to exercise in bone and BMD of the legs, and a negative relationship to basal PTH levels. Bone turnover and PTH secretion was stimulated by exercise, and low basal levels of PTH and high BMD were induced by a high level of physical fitness. These observations correlate well with the favorable effects of exercise and training on bone mass.

Net fluxes over working thigh of hormones, growth factors and biomarkers of bone metabolism during short lasting dynamic exercise.

The purpose of this study was to evaluate the responses of hormones, growth factors, and biomarkers involved in bone and muscle metabolism during exercise and in recovery. One leg knee-extension exercise and concomitant sampling from the artery and vein were performed. In 12 healthy individuals (6 men and 6 women; age 21-36 years) blood was drawn from the femoral artery and vein at rest, after 10 minutes warm-up, after 15 minutes work at 61% of peak one leg VO2, and after 5 minutes work at peak one leg VO2, as well as 5, 30, and 60 minutes in recovery. Blood flow in the femoral vein was measured using the thermodilution technique. Arteriovenous differences were measured over working thigh for growth hormone (GH), insulin-like growth factor I (IGF-I), insulin-like growth factor binding protein 3 (IGF BP3), parathyroid hormone (PTH) and bone biomarkers, i.e., the carboxyterminal propeptide of type I procollagen (PICP), the carboxyterminal cross-linked telopeptide of type I collagen (ICTP), osteocalcin, and bone-specific alkaline phosphatase (b-ALP). There was an uptake of GH (3.1 +/- 1.2 mU x min(-1), P < 0.001; mean +/- SE) over thigh during exercise and a release of IGF-I at the end of exercise (60 +/- 36 microg x min(-1); P < 0.01). PICP was also released after the maximal exercise (23 +/- 12 microg x min(-1); P < 0.01) as well as ICTP (0.5 +/- 0.3 microg x min(-1); P < 0.05) and b-ALP (0.2 +/- 0.1 microkat x min(-1); P < 0.05). Osteocalcin, IGF BP3, and PTH revealed no clearcut pattern. In the present study, exercise induces endocrine changes which point to anabolic effects on muscle and bone tissue.

Bone metabolism in endurance trained athletes: a comparison to population-based controls based on DXA, SXA, quantitative ultrasound, and biochemical markers.

In general, physical exercise appears to have favorable effects on the skeleton. However, a few recent reports have described negative effects, including reduced bone density (BMD) and high bone turnover in runners. The aim of our study was to compare endurance runners to controls with respect to BMD at different sites and ultrasound transmission through the peripheral skeleton, and to use PTH, total serum calcium, and biochemical markers of bone metabolism as a complement in evaluating the effects of endurance running on bone. Thirty runners (mean age 32 years, range 19-54 years) participated in the study. Their main form of training consisted of endurance running at moderate intensity for about 7 hours (range 2-12 hours) per week, and they had been active in their sport for about 12 years (range 1-21 years). For a comparison, 30 age- and sex-matched population based controls were investigated. BMD values, measured by dual energy X-ray absorptiometry (DXA), were higher in runners than in controls for the total body (3.6%; P = 0.03), legs (9.6%; P = 0. 001), femoral neck (10.0%; P = 0.01), trochanter (9.9%; P = 0.01), and Wards triangle (11.8%; P = 0.02), but not in the lumbar spine or in the forearm measured by single energy X-ray absorptiometry (SXA). The quantitative ultrasound measurement of the calcaneus also revealed higher values in runners than in controls for both broadband ultrasound attenuation (9.2%; P = 0.002) and speed of sound (3.1%; P = 0.0001). At all sites, BMD was related to ultrasound measurements in controls, but no such relationship was evident in runners. Concentrations of parathyroid hormone (PTH) were lower (23.2%; P = 0.02) in runners than in controls, whereas total serum calcium concentrations were slightly higher (3.0%; P = 0.003). The levels of PICP (bone formation) and ICTP (bone resorption) in serum were lower (18.0%; P = 0.03 and 22.2%; P = 0.004, respectively) in runners than in controls, but no differences were seen for osteocalcin or bone specific alkaline phosphatase (b-ALP). In conclusion, BMD at the focus of strain for running, that is, the legs, is higher in endurance runners when compared to matched controls. Low bone turnover in runners, indicated by lower levels of PTH and biochemical markers of bone metabolism, point to an influence of endurance running at the cellular level.

Biochemical markers of bone metabolism during distance running in healthy, regularly exercising men and women.

The purpose of the present study was to evaluate the effects of long distance running on bone metabolism, using the biochemical markers ICTP (the carboxyterminal cross-linked telopeptide of type I collagen), PICP (the carboxyterminal propeptide of type I procollagen), osteocalcin and bALP (bone specific alkaline phosphatase) as well as parathyroid hormone (PTH) and serum calcium. Twenty healthy, regularly exercising individuals, 10 women and 10 men, participated in a running competition. The mean age was 38 (range 22-55) and 39 (range 22-53) years respectively, the performed distance 15 (range 5-30) and 28 (range 15-30) km respectively, with a speed of 5:30, 5:02 per kilometer respectively. Fasting blood samples were drawn in the morning the day before the race, and also the day after and two days after. A decrease of PICP concentrations among women was evident the day after the competition (from 170 +/- 17 micrograms/l to 158 +/- 17 micrograms/l) which returned to pre-exercise levels two days after the race (167 +/- 19 micrograms/l). Furthermore, a decrease of osteocalcin could be seen in the men one day after the exercise (from 12.1 +/- 1.1 micrograms/l to 10.3 +/- 1.1 micrograms/l). In the men, there was also an increase of ICTP concentrations two days after (3.98 +/- 0.35 micrograms/l) this long-term and demanding exercise, when compared with pre-exercise levels (3.67 +/- 0.28). One single bout of long-term, exhaustive running exercise in well-trained men and women seems to induce a temporary inhibition of bone formation as well as a stimulation of bone resorption.

Intact serum parathyroid hormone levels increase during running exercise in well-trained men.

The purpose of this study was to examine the influence of exercise on the serum concentrations of intact parathyroid hormone (PTH). Serum PTH and plasma lactate were measured in 15 well-trained men, 9 long-distance runners and 6 fire-fighters, during two running exercises. Test one consisted of 40-minute treadmill running with a step-wise increased load and test two consisted of 50-minute treadmill running with a constant velocity. When the load was step-wise increased, the PTH concentrations increased moderately at the slower running paces but reached a final value that was about 50% higher than the starting value. This rise occurred despite a concomitant increase of total serum calcium from 2.38 +/- 0.06 to 2.49 +/- 0.05 mmol/liter (P < 0.01). During the constant running exercise, the long-distance runners, but not the fire-fighters, displayed a significant increase in PTH concentrations although the rise in total serum calcium was similar in both groups. There was a weak correlation between the changes in PTH and lactate in both exercises. The findings demonstrate that both high and low intensity exercise enhance release of PTH in long-distance runners through a mechanism that does not involve serum calcium. This relationship might be of importance for bone mass in men performing long-distance training.

Hyaluronan in human skeletal muscle of lower extremity: concentration, distribution, and effect of exercise.

The concentration and localization of hyaluronan (HYA) were determined in biopsy specimens from resting human quadriceps femoris and anterior tibial muscles. The influence of physical exercise on HYA concentrations in the quadriceps femoris muscle and in blood was also evaluated. A sensitive radioassay was used for the quantification of HYA. The distribution of the glycosaminoglycan was demonstrated using a histochemical method that involved microwave-aided fixation and an HYA-binding protein. At rest, the muscle HYA concentration was 34.9 +/- 23.6 (SD) micrograms/g muscle wet wt with a large interindividual variation. Exercise had no significant effect on the muscle HYA concentration. The serum HYA concentration increased from 35.9 +/- 22.7 to 53.4 +/- 57.1 micrograms/l during exercise, but 30 min after the exercise the HYA concentration was significantly lower (19.1 +/- 6.3 micrograms/l) than the initial preexercise value. In resting skeletal muscles of the lower extremity, HYA was heterogeneously distributed in the perimysium and endomysium. Perivascular and perineural connective tissues were distinctly HYA positive.