Growth hormone induces muscle fibre type transformation in growth hormone-deficient rats

The effect of recombinant human growth hormone (rhGH) on growth and composition of muscle was studied in growth hormone-deficient rats (dw/dw) treated for 10 days with either rhGH (GH) or with placebo (PLA). Age-matched control rats (DW/dw) (AGE) were treated as PLA. Growth rate increased (P < 0.05) when rats were treated with rhGH and plasma insulin-like growth factor-1 concentration was higher (P < 0.05) in GH and AGE than in PLA. The wet weight of the soleus (SOL) and the extensor digitorum longus muscles (EDL) was less in PLA compared to GH and AGE (P < 0.05). In the SOL, the amount of myosin heavy chain (MHC) I was lower (69.1 ± 1.7%) (Mean ± SEM) in PLA compared to both GH (85.3 ± 2.3%) and AGE (76.4 ± 1.6%) (P < 0.05). At the same time the amount of MHC IIA/IIX was higher (30.9 ± 2.2%) in PLA compared to GH (14.7 ± 2.3%) and AGE (23.6 ± 1.6% (P < 0.05)). In EDL, treatment with rhGH did not significantly affect MHC-isoforms or the fibre type composition, but 11% more MHC IIB and 11% less MHC IIA/IIX was observed in PLA compared to AGE (P < 0.05) suggesting a long-term effect of growth hormone. MHC-isoform data were confirmed using histochemistry. In addition, in the SOL, the maximal activity of 3-hydroxyacyl-CoA dehydrogenase (HAD) in GH and AGE was higher (22 and 27%, respectively) than in PLA (P < 0.05). In the EDL, no differences were observed in maximal activity of HAD. In conclusion, the data support a role for growth hormone in muscle fibre growth and differentiation.     

Glomerular hypertrophy after subtotal nephrectomy: relationship to early glomerular injury

Structural adaptations in response to approx. 70% nephrectomy were studied in male Sprague-Dawley rats. Rats developed systemic hypertension as well as progressive albuminuria after nephrectomy. At 18–26 weeks after nephrectomy (n=6) or sham treatment (n=6) kidneys were perfusion-fixed and examined by light and electron microscopy. Glomerular tuft volume (+140%), capillary volume (+151%) and length (+77%), mesangial volume (+115%), podocyte volume (+96%), glomerular basement membrane surface area (+107%) and filtration slit length (+85%) were all significantly greater in nephrectomized rats. The incidence of segmental glomerular sclerosis was low and variable among these rats, but was significantly higher than in controls (P=0.037). Urinary albumin excretion was elevated in the nephrectomized rats (89±72 SD mg/day vs 11±11 mg/day in control rats, P=0.01) and correlated significantly with the incidence of sclerosis (r=+0.8311, P<0.05). The relationships of the level of albuminuria and the sclerosis rate to various morphometric parameters were examined by regression analysis for the nephrectomy group. A significant negative correlation was found between albuminuria and average tuft volume (r=–0.8136) and glomerular basement membrane surface area (r=–0.8168). Both sclerosis rate and albuminuria showed negative correlations with filtration slit length (r=–0.8180 and r=–0.8598). These findings suggest that under some circumstances, glomerular hypertrophy may prevent or ameliorate the early stages of glomerular injury after subtotal nephrectomy.     

Effects of 84‐days of bedrest and resistance training on single muscle fibre myosin heavy chain distribution in human vastus lateralis and soleus muscles

Aim: This investigation determined the effects of 84 days of bedrest on the composition of myosin heavy chain (MHC) in single skeletal muscle fibres with and without a resistance‐training countermeasure programme. Methods: Muscle biopsies were obtained from the m. vastus lateralis (VL) and m. soleus (SOL) before and after 84 days of bedrest. While control (BR) subjects (VL n = 9; SOL n = 3) refrained from exercise, BRE subjects (VL n = 8; SOL n = 3) performed knee extensor and plantar flexor resistance exercise every third day. Approximately 110 fibres per sample were analysed for MHC composition using SDS‐PAGE. Results: BR–VL had 16 and 14% decreases (P < 0.05) in MHC I and IIa fibres, respectively. There were 10% increases (P < 0.05) in MHC I/IIa, IIa/IIx, I/IIa/IIx, and a ～30% increase (P < 0.05) in total hybrid fibres. BRE‐VL showed a 15% reduction (P < 0.05) in MHC I fibres, no change in MHC IIa fibres, and a 13% increase (P < 0.05) in total hybrids. BR–SOL had a 19% decrease (P < 0.05) in MHC I fibres with a 22% increase in total hybrids. BRE–SOL showed no change in MHC composition across all fibre types. Conclusion: These data suggest that the exercise countermeasures programme prevented MHC shifts in the SOL and mitigated MHC shifts in the VL. Furthermore, in the VL it appears that the resistance training programme employed in this investigation during bedrest, emphasized the use of MHC IIa phenotype muscle fibres.     

Effects of 4 Weeks Recombinant Human Growth Hormone Administration on Insulin Resistance of Skeletal Muscle in Rats

Purpose

Effect of recombinant human growth hormone (rhGH) administration on lipid storage, and its subsequent effect on insulin sensitivity have not yet been adequately examined. Thus, we investigated the effects of rhGH treatment on muscle triglyceride (TG) and ceramide content, and insulin sensitivity after 4 weeks of rhGH administration in rats.

Materials and Methods

Fourteen rats were randomly assigned to two groups: rhGH injection group (GH, n = 7) and saline injection group (CON, n = 7). GH received rhGH by subcutaneous injections (130 µg·kg^-1·day^-1, 6 days·week^-1) for 4 weeks, while CON received saline injections that were equivalent in volume to GH group. Intramuscular TG and ceramide content and hepatic TG content were measured. To determine insulin sesitivity, oral glucose tolerance test (OGTT) and muscle incubation for glucose transport rate were performed in rats, and used as indicators of insulin sensitivity. We also examined plasm lipid profiles.

Results

After 4 weeks of rhGH treatment, the GH group had higher muscle and liver TG contents than the CON (p < 0.05). Ceramide content in GH was significantly greater than that in CON (p < 0.05). GH also had higher plasma levels of FFA (p < 0.05), glucose and insulin responses during OGTT (p < 0.05), and lower glucose transport rates in submaximal insulin concentration (p < 0.05) as compared with CON. Results indicate that rhGH treatment is associated with insulin resistance in rats.

Conclusion

rhGH treatment elevated muscle TG and ceramide content, and hepatic TG content. Thus, elevation of these compounde by rhGH treatment could contribute to the development of insulin resistance in rats.     

Sustained low‐dose growth hormone therapy optimizes bioactive insulin‐like growth factor‐I level and may enhance CD4 T‐cell number in HIV infection

High‐dose recombinant human growth hormone (rhGH) (2–6 mg/day) regimes may facilitate T‐cell restoration in patients infected with human immunodeficiency virus (HIV) on highly active antiretroviral therapy (HAART). However, high‐dose rhGH regimens increase insulin‐like growth factor‐I (IGF‐I) to supra‐physiological levels associated with severe side effects. The present study investigated whether lower doses of rhGH may improve T‐cell restoration in patients infected with HIV following an expedient response of total and bioactive (i.e., free) IGF‐I. A previous 16‐week pilot‐study included six HIV‐infected patients on stable HAART to receive rhGH 0.7 mg/day, which increased total (+117%, P < 0.01) and free (+155%, P < 0.01) IGF‐I levels. The study was extended to examine whether continuous use of low‐dose rhGH (0.7 mg/day until week 60; 0.4 mg/day from week 60 to week 140) would maintain expedient IGF‐I levels and improve CD4 T‐cell response. Total and free IGF‐I increased at week 36 (+97%, P < 0.01 and +125%, P < 0.01, respectively) and week 60 (+77%, P = 0.01 and +125%, P < 0.01) compared to baseline levels (161 ± 15 and 0.75 ± 0.11 µg/L). CD4 T‐cell number increased at week 36 (+15%, P < 0.05) and week 60 (+31%, P = 0.01) compared to baseline levels (456 ± 55 cells/µL). Following rhGH dose reduction, total IGF‐I and CD4 T‐cell number remained increased at week 88 (+44%, P = 0.01 and +33%, P < 0.01) and week 140 (+46%, P = 0.07 and +36%, P = 0.02) compared to baseline levels. These data support the notion that low‐dose rhGH regimens may increase expediently total and bioactive IGF‐I and improve T‐cell restoration in patients infected with HIV on HAART. J. Med. Virol. 82:197–205, 2010. © 2009 Wiley‐Liss, Inc.     

Cellular patterns of the atrophic response in murine <Emphasis Type="Italic">soleus</Emphasis> and <Emphasis Type="Italic">gastrocnemius</Emphasis> muscles submitted to simulated weightlessness

The purpose of the present study was to investigate the mechanisms of cell death (apoptosis vs. necrosis) during muscle atrophy induced by 1 week of hindlimb suspension. Biochemical and morphological parameters were examined in murine soleus and gastrocnemius muscles. A total of 70 male Charles River CD1 mice were randomly assigned to seven groups (n = 10/group): Cont (loading control conditions) and 6HS, 12HS, 24HS, 48HS, 72HS and 1wkHS with respect to the period of hindlimb suspension (HS). Compared to the Cont, skeletal muscle atrophy was confirmed by a significant decrease of 44 and of 17% in fiber cross-sectional areas in the gastrocnemius and soleus, respectively. A significant increase in caspase-3 activity was noticed in 6HS (196%, P < 0.05) and in 12HS (201%, P < 0.05), as well as the amount of cytosolic mono- and oligonucleosomes at 12HS (142%, P < 0.05) and 24HS (203%, P < 0.05) in the gastrocnemius and soleus, respectively. The profile of necrotic markers showed a peak of myeloperoxidase activity at 24HS (170%, P < 0.05) and at 72HS (114%, P < 0.05) in the gastrocnemius and soleus, respectively. The analysis of N-acetylglucosaminidase activity evidenced more increment in the soleus at 72HS (60%, P < 0.05). The analysis of the basal values of these parameters suggested that apoptosis prevailed in the slow-twitch muscle analyzed, whereas lysosomic activity seemed to be more pronounced in the gastrocnemius. The morphological data supported the biochemical results pointing towards a shift from apoptosis to necrosis, which seems to corroborate the aponecrosis theory.     

Effects of hindlimb suspension and androgen treatment on testosterone receptors in rat skeletal muscles

This study tested the specific and combined effects of testosterone treatment and hindlimb suspension (HS) on the properties of steroid receptors in skeletal muscle. Male rats were either administered weekly high doses of testosterone heptylate (10?mg?·?kg^?1) or olive oil placebo, and were either tail-suspended or acted as controls. After 3 weeks of treatment, three muscles were excised from each animal, soleus (SOL), extensor digitorum longus (EDL), and plantaris. The results showed that the testosterone treatment was unable to minimise the HS-induced atrophy of skeletal muscle. As expected, HS altered the fibre-type composition of SOL muscles (?33% of type I, +188% and +161% of type IIa and intermediate fibres respectively, P?P?相似文献   

Muscle damage induced by running training during recovery from hindlimb suspension: the effect of dantrolene sodium

We examined the extent of morphological alterations and the myosin heavy chain (MHC) distribution in the rat soleus muscle after a 4-week period of spontaneous recovery or retraining after hindlimb suspension (HS). Moreover, we tested the hypothesis that dantrolene sodium, which affects the flux of calcium over the sarcoplasmic reticulum membrane, was able to attenuate muscle damage. Three groups of rats were submitted to 3 weeks of HS, followed by either 4 weeks of unrestricted cage activity (HC, n?=?7), or running training for the same period and were compared to age-matched animals (C, n?=?8). Trained rats were treated with either placebo or dantrolene sodium (HTP, HTD, n?=?8 each, respectively). Four weeks after HS recovery, the percentage of myofibres with internal nuclei (%in) was determined by histological staining with hematoxylin and eosin. %in was affected by the individual rat (P?P?P?r?=??0.65, P?相似文献   

Effects of endurance training at high altitude on diaphragm muscle properties

The biochemical, histochemical, and structural changes induced by endurance training and long-term exposure to high altitude were studied in the diaphragm muscle of rats exposed to simulated altitude (HA: n = 16; P _b = 62 kPa, 463 Torr; 4000 m) and compared to animals maintained at sea-level (SL: n = 16). Half of the animals in each group were trained (T) by swimming for 12 weeks, the other half were kept sedentary (S). Except for a small decrease in type I fibres in the HA-S group (–7%, P<0.05), in favour of type IIab and type IIb fibres, neither high-altitude exposure nor endurance training had an overall effect on fibre type distribution. The mean fibre cross-sectional area was found to be unaffected by altitude and/or chronic exercise. Capillary density was shown to be increased by both high-altitude exposure (P<0.02) and training (P<0.001), whereas capillary growth, estimated by the capillary/fibre ratio, was unaffected in both cases. Following endurance training, a modest increase in citrate synthase was shown to occur to the same extent in the HA-T and SL-T groups (+15% and + 16% respectively, NS). Hexokinase increased following training (P<0.05) and high-altitude exposure (P<0.001). In normoxic and hypoxic animals, endurance training enhanced the ratio of the heart-specific lactate dehydrogenase isozyme LDH1 to total LDH activity (+59%, P<0.01; +92%, P<0.05 respectively). It may be hypothesized that the increased glucose phosphorylation capacity observed in diaphragm muscle contributes to the reduction of glycogen utilization during exercise.     

Hypoxia-induced fibre type transformation in rat hindlimb muscles

Summary Twelve male Sprague-Dawley rats (21 days old) were randomly assigned into two experimental groups: sea level control (CONT) and hypobaric hypoxia (HYPO). The HYPO rats were kept in an hypobaric chamber maintaining a simulated altitude of 4000 m (61.1 kPa). After 10 weeks of treatment, the rat hindlimb muscles [soleus (SOL) and extensor digitorum longus (EDL)] were subjected to histochemical and electro-mechanical analyses. Results indicated that compared to CONT the HYPO SOL muscle had a significantly greater relative distribution of fast-twitch-oxidative-glycolytic (FOG) fibres (28.9% SEM 2.0 vs 18.3% SEM 1.8,P<0.01) with a significant decrease in slow twitch oxidative fibre distribution (69.5% SEM 2.4 vs 82.9% SEM 3.1,P<0.01). Compared to CONT the HYPO EDL muscle also manifested a significant increase in FOG fibre distribution (51.6% SEM 0.8 vs 46.6% SEM 1.1,P<0.01), but this was accompanied by a significant decrease in fast twitch glucolytic fibres (44.3% SEM 0.9 vs 49.2% SEM 1.7,P<0.05). These histochemical fibre type transformations accompanied significant and expected changes in the electro-mechanical parameters tested in situ, e.g. maximal twitch force, maximal rate of force development, contraction time, half relaxation time, force:frequency curve, and fatigability. It was concluded that chronic hypobaric hypoxia could have a potent influence upon the phenotype expression of muscle fibres.     

Letter to the Editor: Comparison of Lopinavir Level Between the Two Formulations (Soft-Gel Capsule and Tablet) in HIV-Infected Pregnant Women

Abstract

Purpose: Treatment options for HIV-associated lipodystrophy syndrome (HALS) remain limited. The objective of this randomized open-label study was to compare three emerging therapies, rosiglitazone, pravastatin, and growth hormone alone and together, in men and women with HALS. Method: Sixty-four subjects received daily rosiglitazone (4 mg, n = 14), pravastatin (40 mg, n = 11), or rosiglitazone plus pravastatin (n = 13) for 48 weeks or recombinant human growth hormone (rhGH; Serostim® 2 mg, 12 weeks, n = 13) alone or combined with rosiglitazone (n = 13). Primary endpoint was body composition change by dual X-ray absorptiometry (DXA) and computed tomography (CT). Results: Rosiglitazone resulted in slow accrual of limb fat detected by DXA (+444 ± 186 g; p < .05) but not CT. Pravastatin had no consistent significant effects on body composition, although it reduced total and LDL cholesterol. Negative interactions were observed between pravastatin and rosiglitazone. rhGH reduced abdominal fat by CT (?31 ± 15 cm², 26%; p < .05) and DXA (?1597 ± 383 g, 27%; p < .05) and increased trunk and limb lean mass (+10% and +12%, respectively). However, effects largely disappeared within 12 weeks post treatment. rhGH alone impaired insulin sensitivity but not when combined with rosiglitazone. Conclusion: Prolonged rosiglitazone treatment slowly improves lipoatrophy. rhGH rapidly and selectively reduces visceral fat, although effects are short-lived; co-administered rosiglitazone abrogates rhGH-related insulin resistance.     

Effects of protein supplementation during prolonged exercise at moderate altitude on performance and plasma amino acid pattern

Summary The effects of two levels of protein intake on muscle performance and energy metabolism were studied in humans submitted to repeated daily sessions of prolonged exercise at moderate altitude. For this purpose, 29 healthy males, were exposed to seven successive stages of ski-mountaineering at altitudes between 2500 and 3 800 m, and to an isocaloric diet (4000 kcal·day^–1, 16760 kJ·day^–1) with either 1.5g·kg^–1·day^–1 (C group,n =14), or 2.5 g·kg^–1·day^–1 (PR group,n =15) protein intake. Measurements made after the ski-mountaineering programme did not show any change in body mass. The peak torque during maximal isometric voluntary contraction (MVC) of the quadriceps muscle was unaffected by the repeated exercises, whereas the endurance time at 50% MVC was decreased in PR subjects (–26.8%,P<0.001). Increased levels of both free fatty acids (+147%,P<0.001) and glycerol (+170%,P<0.001) observed in C subjects would suggest that lipolysis was enhanced after the repeated exercise. The plasma amino acid pattern was altered after completion of the ski-mountaineering programme; the plasma concentration of the three branched-chain amino acids (BCAA) was significantly decreased in C subjects, whereas the higher level of protein intake (PR group) greatly minimized the exercise-induced decrease in serum BCAA.     

Effect of a growth hormone treatment on bone orthotropic elasticity in dwarf rats

A refinement of the current ultrasonic elasticity technique was used to measure the orthotropic elastic properties of rat cortical bone as well as to quantify changes in elastic properties, density, and porosity of the dwarf rat cortex after a treatment with recombinant human growth hormone (rhGH). The ultrasonic elasticity technique was refined via optimized signal management of high-frequency wave propagation through cubic cortical specimens. Twenty dwarf rats (37 days old) were randomly assigned to two groups (10 rats each). The dwarf rat model (5–10% of normal GH) was given subcutaneous injections of either rhGH or saline over a 14-day treatment period. Density was measured using Archimedes’ technique. Porosity and other microstructural characteristics were also explored via scanning electron microscopy and image analysis. Statistical tests verified significant decreases in corticla orthotropic Young’s (−26.7%) and shear (−16.7%) moduli and density (−2.42%) concomitant with an increase in porosity (+125%) after rhGH treatments to the dwarf model (p<0.05). A change in material symmetry from orthotropy toward planar isotropy within the radial-circumferential plane after GH treatments was also noted. These results demonstrate some alteration in bone properties at this time interval. Structural implications of these changes throughout physiological loading regimens should be explored. Presented in part at the ASME Summer Bioengineering Conference in Breckenridge, CO, June, 1993, the Second World Congress of Biomechanics in Amsterdam, The Netherlands, July, 1994, and the Orthopaedic Research Society Meeting in Orlando, FL, February, 1995 (New Investigator Research Award finalist).     

Effects of chronic hypoxia and endurance training on muscle capillarity in rats

Skeletal muscle capillarity expressed as capillary density (CD), and number of capillaries per fibre (C/F), as well as the mean fibre cross-sectional area (FCSA), were determined in the extensor digitorum longus (EDL), plantaris (PLA) and soleus (SOL) muscles of four groups of eight rodents trained on a swimming exercise programme (T) or maintained sedentary (S), at sea level (SL) or at simulated altitude (HA), barometric pressure 61.7 kPa (463 torr) for 12 weeks. It was shown that both HA exposure and endurance training decreased body and skeletal muscles weights (P<0.001). However, neither HA exposure nor endurance training induce any variation in relative importance in the skeletal muscle mass. Altitude exposure and endurance training had increasing effects on CD in all muscles studied (P<0.001). This study confirms the fact that altitude exposure has no direct effect on capillary development. On the other hand, the capillary supply of the several slow- and fast- twitch skeletal muscles studied is increased by endurance training. This real enhancement in capillary network is ascertained by an increase in the C/F ratio (+7%, +26%, +16%, in PLA, EDL, and SOL muscles, respectively at sea level, and +19.5%, +30%, and +14% respectively at HA). These results indicate that the effects of chronic exercise on skeletal muscle capillarity estimated by the C/F ratio, are greater in an hypobaric environment than in a SL environment.     

The effects of high-intensity exercise on skeletal muscle neutrophil myeloperoxidase in untrained and trained rats

The primary purpose of this study was to examine the effects of high-intensity acute exercise on neutrophil infiltration in different muscle fiber types of untrained rats and to compare postexercise neutrophil accumulation in muscles of untrained and trained animals. The effect of high-intensity acute exercise on blood neutrophil degranulation reaction in trained animals was also elucidated. Neutrophil enzyme myeloperoxidase (MPO) was determined as a measure of neutrophil migration into muscles and blood neutrophil degranulation. Male albino rats were subjected to acute exercise and 5 weeks of training. The used model of intensive acute exercise consisted of 5, 15, and 25 intermittent swimming bouts with the addition of weight (8% of total body mass) for 1-min each, followed by 1.5-min rest intervals. MPO was analyzed in quadriceps muscle (white and red portion) and in soleus muscle 24 h after acute exercise. MPO content in resting blood plasma and neutrophils was determined 48-h following the completion of a training process. In addition, MPO content in the trained rats was measured immediately (in blood plasma and neutrophils) after and 24 h (in muscles) following a single-bout of exercise to exhaustion. The remaining two-third of the trained animals were exposed to a single-bout of nonstop swimming with the addition of 6% body mass until exhaustion. These animals were sacrificed immediately and 24 h after loaded swimming to analyze leukocyte count, MPO content in blood plasma and neutrophils and in muscles, respectively. About 24 h after exercise MPO concentrations in the red portion of quadriceps muscle and in soleus muscle were 4–7-fold higher as compared to the white portion of m. quadriceps. There was an association between the quantity of repetitive bouts of swimming and MPO content in the muscles. The duration of swimming to exhaustion of trained rats was 3.8-fold longer than untrained sedentary control. At rest, plasma MPO concentration was found to be 40% higher in trained rats compared to untrained controls (P < 0.05). Postexercise plasma MPO concentrations were significantly higher both in untrained (+137%; P < 0.05) and trained (+81%; P < 0.05) rats compared to resting values. At rest neutrophil MPO concentration was found to be 33% lower in trained rats compared to untrained controls (P < 0.05). There were no significant differences in muscle MPO concentrations between untrained and trained rats at rest. A single-bout of exercise to exhaustion produced a greater increase in MPO content in untrained compared to trained rats. The data suggest that postexercise neutrophil infiltration is more intensive in red fibers types compared to white fiber types. A smaller neutrophil infiltration in muscles of trained animals after exhaustive exercise suggests a protective effect of previous training to muscle injury.Portions of this paper were presented by V. Morozov in 2003 at the 6th ISEI Symposium on Exercise Muscle Metabolism and Immune Function, Copenhagen.     

Neural adaptations underlying cross-education after unilateral strength training

The purpose of this study was to investigate the effects of 4-week (16 sessions) unilateral, maximal isometric strength training on contralateral neural adaptations. Subjects were randomised to a strength training group (TG, n = 15) or to a control group (CG, n = 11). Both legs of both groups were tested for plantar flexion maximum voluntary isometric contractions (MVCs), surface electromyogram (EMG), H-reflexes and V-waves in the soleus (SOL) and gastrocnemius medialis (GM) superimposed during MVC and normalised by the M-wave (EMG/M_SUP, H_SUP/M_SUP, V/M_SUP, respectively), before and after the training period. For the untrained leg, the TG increased compared to the CG for MVC torque (33%, P < 0.01), SOL EMG/M_SUP (32%, P < 0.05) and SOL V/M_SUP (24%, P < 0.05). For the trained leg, the TG increased compared to the CG for MVC torque (40%, P < 0.01), EMG/M_SUP (SOL: 38%, P < 0.05; GM: 60%, P < 0.05) and SOL V/M_SUP (72%, P < 0.01). H_SUP/M_SUP remained unchanged for both limbs. No changes occurred in the CG. These results reinforce the concept that enhanced neural drive to the contralateral agonist muscles contributes to cross-education of strength.     

Quadriceps muscle function characteristics in severely obese and nonobese adolescents

The purpose of this cross-sectional study was to compare quadriceps muscle strength and fatigue between severely obese (body mass index 34 kg/m²) and nonobese adolescents. Maximal isokinetic torque and angle of peak torque as well as isometric torque at short (40° of knee flexion) and long (80° of knee flexion) muscle length were measured using an isokinetic dynamometer. Muscle fatigue was quantified as the percent torque loss during an isokinetic voluntary protocol and an electrical stimulation isometric protocol. Obese adolescents produced greater absolute isokinetic (+16%; P < 0.05) and isometric torque at short (+25%; P < 0.01) but not at long muscle length (P > 0.05) compared to their lean counterparts. The angle of peak torque was significantly lower in obese than in nonobese subjects (−11%; P < 0.05), i.e., obese produced their maximal strength at shorter muscle length. Isokinetic and isometric torque normalized to the fat-free mass were not significantly different between the two groups. No significant difference in voluntary and stimulated torque loss was observed between groups. Muscle strength per unit of fat-free mass and muscle fatigue were similar in the obese and nonobese adolescents tested in this study, therefore suggesting that obesity has little or no effect on quadriceps muscle function characteristics. On the other hand, it remains to be confirmed whether the observed quadriceps muscle length specificity contributes to the reduced functional capacity of obese adolescents during complex motor tasks involving deep knee flexion (squatting, kneeling).     

Muscle-specific effects of hindlimb suspension and clenbuterol in mature male rats

Anabolic agents are useful tools for probing the mechanisms by which muscle fibers perceive and respond to disuse. beta(2)-Adrenergic agonists exert protective, and/or reparative, effects on atrophying muscle tissue. The effects of one such agent, clenbuterol (Cb), were examined on muscle mass, total protein content, and myofibrillar protein content in selected hindlimb muscles [adductor longus (ADL), extensor digitorum longus (EDL), plantaris (PLAN), soleus (SOL)] of mature male rats, under different loading conditions. Pair-fed rats were divided into four experimental groups: vehicle- and Cb-treated nonsuspended, vehicle- and Cb-treated hindlimb suspended (HLS). Experiments lasted 14 days, during which the rats received subcutaneous injections of 1 mg/kg Cb or 1 ml/kg vehicle. HLS induced significant atrophy in all muscles, except the EDL, in a generally fiber type-related pattern. However, myofibrillar protein content was affected in a more regional pattern. Cb treatment of nonsuspended rats induced hypertrophy in all muscles, in a generally uniform pattern. However, myofibrillar protein content was affected in a more fiber type-related pattern. Cb treatment of HLS rats reduced or eliminated HLS-induced atrophy in all muscles, in a muscle-specific pattern. Overall, the ADL and SOL were most susceptible to HLS-induced atrophy. The PLAN had the greatest magnitude of Cb-induced sparing of atrophy. The results show that, in mature male rats, Cb exerts anabolic effects that are load-dependent and muscle-specific. Responses to this drug cannot be reliably predicted by fiber-type composition alone.     

Control of erythropoiesis after high altitude acclimatization

Erythropoiesis was studied in 11 subjects submitted to a 4-h hypoxia (HH) in a hypobaric chamber (4,500 m, barometric pressure 58.9 kPa) both before and after a 3-week sojourn in the Andes. On return to sea level, increased red blood cells (+3.27%), packed cell volume (+4.76%), haemoglobin (+6.55%) (P<0.05), and increased arterial partial pressure of oxygen (+8.56%), arterial oxygen saturation (+7.40%) and arterial oxygen blood content (C_aO₂) (+12.93%) at the end of HH (P<0.05) attested high altitude acclimatization. Reticulocytes increased during HH after the sojourn only (+36.8% vs +17.9%, P<0.01) indicating a probable higher reticulocyte release and/or production despite decreased serum erythropoietin (EPO) concentrations (–46%, P<0.01). Hormones (thyroid, catecholamines and cortisol), iron status (serum iron, ferritin, transferrin and haptoglobin) and renal function (creatinine, renal, osmolar and free-water clearances) did not significantly vary (except for lower thyroid stimulating hormone at sea level, P<0.01). Levels of 2,3-diphosphoglycerate (2,3-DPG) increased throughout HH on return (+14.7%, P<0.05) and an inverse linear relationship was found between 2,3-DPG and EPO at the end of HH after the sojourn only (r=–0.66, P<0.03). Inverse linear relationships were also found between C_aO₂ and EPO at the end of HH before (r=–0.63, P<0.05) and after the sojourn (r=–0.60, P=0.05) with identical slopes but different ordinates at the origin, suggesting that the sensitivity but not the gain of the EPO response to hypoxia was modified by altitude acclimatization. Higher 2,3-DPG levels could partly explain this decreased sensitivity of the EPO response to hypoxia. In conclusion, we show that altitude acclimatization modifies the control of erythropoiesis not only at sea level, but also during a subsequent hypoxia.