Human uterine smooth muscle exhibits a very low phosphocreatine/ATP ratio as assessed by in vitro and in vivo measurements

The purpose of the study was to investigate by in vitro and in vivo methods the phosphocreatine (PCr)/ATP ratio as an expression of the energy metabolic state of human myometrium in comparison with striated skeletal muscle. The contents of PCr and adenylates in biopsies of uterine smooth muscle and m. rectus abdominis from seven term pregnant women were determined in vitro and compared with results obtained in vivo by phosphorus magnetic resonance spectroscopy (³¹P-MRS) in the uterus and m. gastrocnemius of eight non-pregnant women. The PCr/ATP ratio in the striated skeletal muscle was about three times higher than that of the myometrium. The results of the in vitro biopsy part of the study and the in vivo ³¹P-MRS part conformed with each other. In the biopsies both PCr and ATP concentrations were significantly lower in the myometrium than in the rectus muscle, but the difference for PCr was more pronounced, accounting for the significantly lower PCr/ATP ratio in the uterine smooth muscle. The energy metabolic pattern of uterine smooth muscle differs from that of striated skeletal muscle regarding the contents of high-energy phosphocompounds and the PCr/ATP ratio. This in vivo finding is the first report on human smooth muscle using ³¹P-MRS.     

Functional implication of spare ATP-sensitive K(+) channels in bladder smooth muscle cells

ATP-sensitive K(+) (K(ATP)) channels play important roles in the regulation of excitability in urinary bladder smooth muscle cells. Patch-clamp studies revealed that the current density was about 9-fold higher in the pig bladder smooth muscle cells, compared with guinea pig, although the rank order of potencies for suppression of electrical field-stimulated contraction of bladder strips by K(ATP) channel openers (KCOs) showed a nearly 1:1 correlation between pig and guinea pig. To investigate the existence of spare K(ATP) channels, P1075-evoked current and membrane potential responses were studied in bladder smooth muscle cells. During a 10-min exposure to P1075 (10 microM), K(ATP) currents ran down by approximately 30.5%, whereas membrane hyperpolarization remained constant. P1075 evoked membrane hyperpolarization with an EC(50) value of 0.20 +/- 0.02 microM, comparable to that required for smooth muscle relaxation (EC(50) = 0.11 +/- 0.01 microM). However, these potencies are 6-fold higher than those required for current activation (EC(50) = 0.73 +/- 0.4 microM). These findings demonstrate that the reduction in membrane excitability by KCOs is associated with membrane hyperpolarization, and that a low amount of K(ATP) channel opening is sufficient to suppress bladder smooth muscle contraction.     

ATP breakdown products in human skeletal muscle during prolonged exercise to exhaustion

Summary. To study changes in muscle energy state during prolonged exercise, especially in relation to fatigue, muscle biopsies were obtained from seven healthy males working until exhaustion on a cycle ergometer at 68% (63–74%) of their maximal oxygen uptake. Biopsies were taken at rest, after 15 and 45 min of exercise and at exhaustion, and analysed for ATP, ADP, AMP, inosine monophosphate (IMP) and hypoxanthine content by high performance liquid chromatography (HPLC), and for creatine phosphate (CP), lactate and glycogen by enzymatic fluorometric techniques. Glycogen content at exhaustion was approximately 30% of the pre-exercise level. The CP content decreased steeply during the first 15 min of exercise (P<0·01) and continued to decrease during the rest of the exercise period (P<0·05). Pronounced increases in contents of IMP (64%P<0·001) and hypoxanthine (69%, P<0·05) were found when exhaustion was approaching. Furthermore, energy charge [EC; (ATP+0·5 ADP)/(ATP+ADP+AMP)] was decreased at exhaustion (P<0·05). The increases in IMP and hypoxanthine which occurred when exhaustion was approaching during prolonged submaximal exercise together with the decrease in EC during this phase of exercise suggest a failure of the exercising skeletal muscle to regenerate ATP at exhaustion.     

Functional characterization of adenosine receptors and coupling to ATP-sensitive K+ channels in Guinea pig urinary bladder smooth muscle

Although multiple adenosine receptors have been identified, the subtype and underlying mechanisms involved in the relaxation response to adenosine in the urinary bladder remain unclear. The present study investigates changes in the membrane potential, as assessed by fluorescence-based techniques, of bladder smooth muscle cells by adenosine receptor agonists acting via ATP-sensitive potassium (K(ATP)) channels. Membrane hyperpolarization evoked by adenosine and various adenosine receptor subtype-selective agonists was attenuated or reversed by the K(ATP) channel blocker glyburide. Comparison of adenosine receptor agonist potencies eliciting membrane potential effects showed a rank order of potency 5'-N-ethyl-carboxamido adenosine (NECA; -log EC50 = 7.97) approximately 2-p-(2-carboxethyl)phenethyl-amino-5'-N-ethylcarboxamidoadenosine hydrochloride (CGS-21680; 7.65) > 2-chloro adenosine (5.90) approximately 2-chloro-N6-cyclopentyladenosine (CCPA; 5.51) approximately N6-cyclopentyladenosine approximately N6-(R)-phenylisopropyladenosine > 2-chloro- N6-(3-iodobenzyl)-adenosine-5'-N-methyl-carboxamide (2Cl-IBMECA; 4.78). Membrane potential responses were mimicked by forskolin, a known activator of adenylate cyclase, and papaverine, a phosphodiesterase inhibitor. The A(2A)-selective antagonist 4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-yl-amino] ethyl)phenol (ZM-241385), and the adenylate cyclase inhibitor N-(cis-2-phenyl-cyclopentyl) azacyclotridecan-2-imine-hydrochloride (MDL-12330A) inhibited the observed change in membrane potential evoked by adenosine and adenosine-receptor agonists. The rank order potency for relaxation of K+-stimulated guinea pig bladder strips, NECA (-log EC50 = 6.41) approximately CGS-21680 (6.38) > 2-chloro adenosine (5.90) > CCPA approximately 2Cl-IBMECA (>4.0) was comparable to that obtained from membrane potential measurements. Collectively, these studies demonstrate that adenosine-evoked membrane hyperpolarization and relaxation of bladder smooth muscle is mediated by A(2A) receptor-mediated activation of K(ATP) channels via adenylate cyclase and elevation of cAMP.     

Use of bladder pressure to correct for the effect of expiratory muscle activity on central venous pressure

Objective To assess whether subtracting the expiratory change in intra-abdominal (bladder) pressure (ΔIAP) from central venous pressure (CVP) provides a reliable estimate of transmural CVP in spontaneously breathing patients with expiratory muscle activity. Design and setting Prospective observational study in a medical ICU. Patients Twenty-four spontaneously breathing patients with central venous and bladder catheters: 18 with no clinical evidence of active expiration (group 1) and 6 with active expiration (group 2). Interventions Patients in group 1 were coached to change their breathing pattern to one of active expiration for several breaths; those in group 2 were asked to sip water through a straw to briefly interrupt active expiration. Measurements and results During active expiration end-expiratory CVP (uncorrected CVP) and ΔIAP were measured; ΔIAP was subtracted from uncorrected CVP to obtain corrected CVP. End-expiratory CVP during relaxed breathing (best CVP) was assumed to represent the best estimate of transmural CVP. The absolute difference between corrected CVP and best CVP was much less than the difference between uncorrected CVP and best CVP (2.3 ± 2.0 vs. 12.5 ± 4.7 mmHg). Conclusions In patients with active expiration, subtracting ΔIAP from end-expiratory CVP yields a more reliable (and lower) estimate of transmural CVP than does the uncorrected CVP value. This article is discussed in the editorial available at: .     

Energy dependence of cytosolic enzyme efflux from rat skeletal muscle

(1) A recirculating isolated superfused skeletal muscle preparation has been developed for the study of rat soleus muscles at physiological temperature using 31P Nuclear Magnetic Resonance (NMR). (2) This system has been used to study intracellular muscle high energy phosphate content and pH during experimental damage to the muscle induced by 2,4-dinitrophenol, deoxycholate and the calcium ionophore, A23187. (3) Results indicate that release of intracellular cytosolic enzymes from damaged skeletal muscle may be induced by phosphocreatine (PCr) and adenosine trisphosphate (ATP) depletion, but under certain circumstances intracellular enzymes can be released from skeletal muscle without any fall in muscle PCr or ATP content.     

Physical activity,skeletal muscle β-adrenoceptor changes and oxidative metabolism in experimental chronic heart failure†

Summary— In chronic heart failure (CHF), changes in sympathetic nervous activity and skeletal muscle metabolism contribute to a limitation in the capacity for exercise. The aim of this study was to investigate the potential relationships between physical deconditioning, skeletal muscle β-adrenoceptor (β-AR) characteristics and muscle metabolic changes in rats with coronary ligation-induced experimental CHF. Muscle β-AR and norepinephrine levels were assessed in rats with CHF that had been treated with propranolol at 28 mg/kg/day and compared with rats with CHF that had not been treated and those that had undergone sham operations. The soleus muscle was investigated because of its predominantly oxidative fibre-type composition. Measurements of spontaneous locomotion activity were carried out using telemetry. After 85 days, muscle energetic phosphate levels were assessed using ³¹P-magnetic resonance spectroscopy. The phosphocreatine resynthesis rate was decreased in the untreated CHF rats (15 ± 3 vs 33 ± 5 mmol L^?1 min^?1 in the sham-operated rats, p < 0.05), but this had been partially reversed in the rats given propranolol (22 ± 3 mmol L^?1 min^?1, non-significant (NS) when compared with the sham-operated rats). Spontaneous activity did not differ among the three groups of animals. Soleus β-adrenoceptor density was decreased in rats with CHF (8.8 ± 3.0 fM/mg of protein vs 22.0 ± 7.0 fM/mg of protein in the sham-operated rats, p < 0.05) and normalized in the propranolol-treated rats (31.9 ± 7.0 fM/mg of protein, NS vs the sham-operated rats; p < 0.05 vs the untreated rats with CHF). Unchanged spontaneous activity in the rats with CHF suggests that physical deconditioning could not account for the muscle metabolic changes. Changes in skeletal muscle energy metabolism were accompanied by changes in β-AR density, occurring in typically oxidative β-AR-rich muscles, reversible after β-blocker therapy and therefore suggestive of β-AR downregulation.     

In cirrhotic patients reduced muscle strength is unrelated to muscle capacity for ATP turnover suggesting a central limitation

Background and aims: We investigated whether in patients with liver cirrhosis reduced muscle strength is related to dysfunction of muscle mitochondria. Methods: The mitochondrial respiratory capacity of the tibial anterior muscle was evaluated in seven patients and eight healthy control subjects by ³¹P nuclear magnetic resonance spectroscopy (³¹PMRS) to express ATP turnover in vivo and by respirometry of permeabilized fibres from the same muscle to express the in vitro capacity for oxygen consumption. Results: Maximal voluntary contraction force for plantar extension was low in the patients (46% of the control value; P<0·05), but neither the capacity for mitochondrial ATP synthesis, V_max‐ATP (0·38 ± 0·26 vs. 0·50 ± 0·07 mM s^?1; P = 0·13) nor the in vitro VO_2max (0·52 ± 0·21 vs. 0·48 ± 0·21 μmol O₂ (min g wet wt.)^?1P = 0·25) were lowered correspondingly. Also, the activity of citrate synthesis and the respiratory chain complexes II and IV were similar in patients and controls. However during the contractions, the contribution to initial anaerobic ATP production from glycolysis relative to that from PCr was reduced in the patients (0·73 ± 0·22 vs. 0·99 ± 0·09; P<0·01). Conclusions: These results demonstrate that the markedly lower capacity for force generation in patients with liver cirrhosis is unrelated to their capacity for muscle ATP turnover, but the attenuated initial acceleration of anaerobic glycolysis suggests that these patients could be affected by a central limitation to force generation.     

Detrusor muscle and sphincteric response to anorectal stimulation in spinal cord injury.

Twelve patients with spinal cord injuries were studied to determine whether the anal sphincter could be used as an index of urethral sphincter activity and to determine the bladder and striated sphincter response to anal and rectal stimulation. Electromyogram (emg) needle electrodes were placed in the external urethral sphincter, external anal sphincter and levator ani. The output of a cystometer was simultaneously recorded on the printout so that the relationship of the striated muscle response to distension of the bladder could be observed. The response to inserting a finger into the external anal canal, external anal sphincter stretch and rectal balloon distension was also observed. The external urethral and anal sphincter activity was closely linked during bladder contraction and anorectal stimulation. The levator ani showed divergent activity. Stretch of the external anal sphincter caused an initial period of increased striated muscle activity, then in 10 of 12 patients abrupt and often marked inhibition of both sphincters and levator ani developed with continued stretch. Ongoing bladder contractions were inhibited and a decrease in bladder tone developed in 7 of 12. Stretch of the rectum produced results similar to those with anal stretch except that bladder facilitation was seen in 4 of 12 patients.     

Excitatory and inhibitory purinergic control of neck muscle nociception in anaesthetized mice

Tension-type headache is associated with noxious input from neck muscles. Due to the importance of purinergic mechanisms in muscle nociception, experimental studies typically inject α,β-methyleneadenosine 5'-triphosphate (α,β-meATP). In contrast to native adenosine 5'-triphosphate (ATP), α,β-meATP has a narrow receptor profile and remains stable in tissue. The present study administered α,β-meATP or ATP in semi-spinal neck muscles in anaesthetized mice ( n  = 65) in order to address different effects in neck muscle nociception. The jaw-opening reflex monitored the impact of neck muscle noxious input on brainstem processing. Injection of α,β-meATP induced reflex facilitation in a dose-dependent manner. In contrast, only the lowest ATP dosage evoked facilitation. Preceding P2Y₁ receptor blockade revealed facilitation even under high-dosage ATP. Ongoing facilitation after α,β-meATP injection neutralized under subsequent activation of P2Y₁ receptors. Results demonstrate opposing excitatory P2X and inhibitory P2Y effects of ATP in neck muscle nociception. These mechanisms may be involved in the pathophysiology of neck muscle pain in man.     

经会阴二维及三维超声诊断女性膀胱颈梗阻

目的 探讨经会阴二维、三维超声诊断女性膀胱颈梗阻（BNO）的应用价值。方法 对36例BNO患者（BNO组）和30名正常女性（正常对照组）行经会阴超声及三维超声,测量膀胱颈厚度,并进行统计学分析。结果 经会阴超声能清晰显示膀胱颈形态、厚度。正常对照组膀胱颈部光滑,无隆起,尿道内口光滑,前、后唇厚度分别为（0.45±0.07）cm、（0.52±0.09）cm;BNO组膀胱颈前唇和（或）后唇增厚呈唇样突入膀胱,膀胱颈前、后唇厚度分别为（0.66±0.05）cm、（0.68±0.05）cm,尿道括约肌回声紊乱,尿道内口黏膜表面不光滑。结论 经会阴二维超声可清晰显示并测量女性尿道结构,三维超声能提供女性尿道及盆底结构的更加丰富的三维空间信息;二者联合应用对诊断BNO具有重要临床应用价值。     

膀胱平滑肌细胞与聚氨酯膜体外复合培养的实验研究

目的以聚氨酯材料为衬底进行膀胱平滑肌细胞的种植和培养,与在培养瓶中的膀胱平滑肌细胞进行对比,了解聚氨酯材料的组织相容性和细胞毒性。方法采用组织块培养法,在膀胱平滑肌细胞体外生长增殖的过程中用倒置显微镜观察其形态和大体表现,用酶标仪CCK8法检测细胞增殖的数量。结果透射电镜下在不同的倍率下观察聚氨酯膜,可以看到在不同的倍率下聚氨酯膜的表面是光滑的,材料性质单一。组织块培养法原代培养获取人膀胱平滑肌细胞稳定可靠,细胞形态良好。抗α-肌动蛋白免疫组织化学染色证实培养细胞为膀胱平滑肌细胞。膀胱平滑肌细胞在PU表面能黏附、生长和增殖。体外复合培养7 d后,膀胱平滑肌细胞铺满PU表面。5 d,7 d的细胞形态与1 d相似。两组5 d细胞计数差异有统计学意义(P<0.05)。结论膀胱平滑肌细胞在聚氨酯材料上的生长增殖与培养瓶中对比没有明显的差异,聚氨酯材料是具有良好组织相容性的生物工程材料。     

Haemodynamic changes and skeletal muscle oxygen tension during complete blood exchange with ultrapurified polymerized bovine haemoglobin

Objective: The study investigates the effect of continuous blood exchange with ultrapurified, polymerized bovine haemoglobin (UPBH) in comparison to hetastarch on haemodynamics, oxygen transport and skeletal muscle oxygen tension in a canine model. Design: Sixteen anaesthetized beagle dogs underwent haemodilution with lactated Ringer's to a starting haematocrit of 20 % followed by progressive blood exchange with 6 % hetastarch 200,000/0.5 (HES, group 1) or UPBH (haemoglobin 13 ± 1 g · dl⁻¹, molecular weight (MW) 32–500,000, group 2) to haematocrit target levels of 15 %, 10 % and 5 % or less. Measurements and results: Besides haemodynamics, skeletal muscle tissue oxygen tension (tPO₂) was measured using a polarographic needle probe. In HES-treated animals, heart rate, cardiac output and blood flow were higher while systemic vascular resistance, systemic and regional arterio-venous oxygen difference (avDO₂) and oxygen extraction ratios were lower when compared to the UPBH group. In spite of a higher final haematocrit of 5 % in group 1, in comparison to group 2 with 2 %, final muscular oxygen uptake (4.7 ± 4 vs 10.1 ± 2 ml · min⁻¹) and mean tPO₂ (11.8 ± 2.3 vs 51.1 ± 2.9 mm Hg) were lower in group 1 than in group 2. While tPO₂ histograms were continuously shifted to lower oxygen tensions during progressive haemodilution with HES, UPBH-exchanged animals showed tPO₂ histograms shifted to higher values than baseline. Conclusion: In spite of vasoconstriction, UPBH provided more haemodynamic stability and enhanced skeletal muscle tPO₂ during progressive blood exchange when compared to HES. Received: 30 December 1996 Accepted: 16 June 1997     

Effects of trimetazidine and selenium on high-frequency fatigue in isolated rat diaphragm muscle

Trimetazidine (TMZ), which has been used in numerous experimental studies, is applied nowadays with the aim of reducing myocardial ischemia. The aim of this study was to determine the prefatigue and postfatigue contractile characteristics associated with the relationship between the force and frequency of contraction in muscle. The study was conducted using diaphragm muscle isolated from 40 male Wistar rats weighing 230 to 270 g. The rats were divided into 4 groups of 10 animals each: controls and TMZ-, selenium (Se)-, and TMZ+Se-treated groups. The rats in the control group were treated with 2 mL of physiologic serum (SF), those in the second group with Se 30 μg/kg in 2mL of SF, those in the third group with TMZ 5 mg/kg in 2 mL of SF, and those in the fourth group with a combination of TMZ 5 mg/kg + Se 30 μg/kg in 2 mL of SF. All rats were treated twice daily for 15 days by means of gastric lavage. The rats were then killed by cervical dislocation. The diaphragm muscle bands were removed and placed in an organ bath. After a 2-hour thermoregulatory period, muscles were fatigued with 5-ms pulses at a frequency of 40 Hz. Force-frequency relationships were studied after the application of 10, 50, and 100 Hz and the development of contraction curves. Contraction forces for the groups treated with TMZ, Se, and TMZ+Se (1 6.1 ±1.2, 13.2±1.3, and 14.9±1.0 g, respectively) were significantly lower than for the control group (17.0±1.4 g) during the prefatigue period (P<.001). Similarly, postfatigue contraction forces for the treated groups (15.7±1.3, 8.8±1.0, and 12.0±1.4g, respectively) were significantly lower than for the control group (12.4±1.2 g, P<.001, P<.001, and P<.05, respectively). A significant decrease was noted in postfatigue contraction forces and contraction and relaxation rates in the Se-and TMZ+Se-treated groups compared with prefatigue values (P<.001), but the difference was not significant. Force-frequency relationships were evaluated at 10, 50, and 100 Hz. The tetanic contraction forces for the control, Se-, TMZ-, and TMZ+Se-treated groups at 100 Hz were 81 3±5.7, 91.6±6.8, 65.3±5.0, and 84.9±7.5 g, respectively. In the TMZ-treated group, a significant increase was observed in tetanic contraction forces at 100 Hz compared with controls (P<.001); no significant changes were seen in the force-frequency relationships at 10 and 50 Hz. The decrease in the contraction force in the postfatigue period was prevented to a larger extent in the TMZ-treated group than in the TMZ+Se-and Se-treated groups.     

Erythrocyte sodium-lithium countertransport,adenosine triphosphatase activity and sodium-potassium fluxes in insulin-dependent diabetes

Summary Increased erythrocyte sodium-lithium countertransport activity has been implicated in the pathogenesis of diabetic nephropathy. However, its relationship to other cation membrane transport systems in incipient nephropathy is not yet clear. The present study was thus performed to: (1) explore associations between sodium-lithium countertransport and changes in the activity of other cation transport pathways and (2) to compare the sodium transport activities with clinical characteristics of insulin-dependent diabetic patients with and without evidence of incipient diabetic nephropathy. We measured erythrocyte sodium-lithium countertransport, passive sodium/ potassium flux (at 1°C), adenine nucleotide content in intact erythrocytes and sodium/potassium-, magnesium-and calciumdependent ATPase activity in erythrocyte membrane preparations from 34 insulin-dependent diabetic patients without microalbuminuria, 8 diabetic patients with microalbuminuria, and 8 age-matched healthy control subjects. Sodium-lithium countertransport was elevated in diabetic patients with normo- and microalbuminuria compared with control subjects [268±99 and 299(277–465), respectively, vs. 166±65 μmol/(l cells×h)] and was positively correlated (r=0.36,P<0.05) with the albumin excretion rate. However, the activity of erythrocyte membrane ATPases was significantly decreased compared with control subjects. The ATP and ADP content was found to be significantly higher (P<0.001) in erythrocytes from diabetic patients compared with control subjects (1,196±276 vs. 833±253 μmol/l cells and 353±97 vs. 255±64 μmol/l cells, respectively). The extent of erythrocyte potassium leakage correlated with hemoglobin A_1c (r=0.39,P<0.05). These results demonstrate that changes in the activity of membrane cation transport, occurring in early nephropathy, are not confined to sodium-lithium countertransport, but involve various pathways, thus reflecting underlying membrane alterations which are at least partially influenced by the diabetic milieu.     

ATP and IMP in single human muscle fibres after high intensity exercise

Summary. Within a muscle there is large variation in the activity of various enzymes among single fibres. It is reasonable, therefore, to expect a corresponding variation in their metabolic response to exercise. This was examined by obtaining muscle biopsies from five men at rest and after intense short-term exercise consisting of three bouts of 30 knee extensions each and intervened by 60 s rest. Freeze-dried dissected single fibres identified as type 1 or type 2 were analysed for ATP and IMP contents by liquid chromatography. Rest. Average ATP tended to be higher in type 2 than in type 1 fibres. The ATP range was 14–30 and 14–32 mmol × kg^-1 dry muscle (dm) in type 1 and 2 fibres, respectively. IMP was less than 1 mmol × kg^-1 dm in most fibres and similar in types 1 and 2. Exercise. Muscle force decreased 70% during exercise. The average decrease in ATP content was significant for both fibre types with somewhat larger response for type 2 (20%) than type 1 (10%) fibres. The ATP range was 10–28 and 10–30 mmol × kg^-1 dm in type 1 and 2 fibres, respectively. Average IMP content increased substantially in both fibre types, more so for type 2, and the range for individual fibres was 0–13 (type 1) and 0–21 (type 2) mmol × kg^-1 dm. Conclusion. After exhaustive short-term exercise, a large variation in ATP and IMP contents was evident among single type 1 and type 2 fibres. None of the fibres, however, showed an ATP content lower than 10 mmol × kg^-1 dm. It is suggested that the muscle force loss, demonstrated in the present study, is not attributed to a lowered ATP content per se.     

Cellular energetics in hypothyroid muscle

Skeletal muscle of seven hypothyroid patients was investigated in the resting state and during exercise and recovery using 31P magnetic resonance spectroscopy. The bioenergetics and intracellular pH of the hypothyroid muscle were thus evaluated and compared with results from normal muscle and muscle of patients with mitochondrial myopathy. In resting hypothyroid muscle there were significant elevations in the concentration ratios of phosphocreatine/ATP and inorganic phosphate/ATP, while phosphocreatine/inorganic phosphate and intracellular pH were lower than normal. In exercising hypothyroid muscle, energy stores were depleted more rapidly and acidification began later than in normal muscle. Recovery of phosphocreatine to the pre-exercise value was normal, but intracellular pH recovered slowly. The data suggest that in the hypothyroid state, glycogen breakdown in skeletal muscle was delayed thereby limiting the substrate supply for both glycolytic and oxidative production of ATP at the beginning of exercise. There was no evidence for a decrease in the oxidative capacity of the muscle of our patients, but elevated ADP may have stimulated oxidative metabolism and helped to compensate for low mitochondrial content. The low intracellular pH in resting muscle and the slow pH recovery after exercise imply that proton handling was abnormal in the hypothyroid muscle.     

Acute lymphoblastic leukemia and obesity: increased energy intake or decreased physical activity?

Background  Obesity is a well-known problem in children with acute lymphoblastic leukemia (ALL), and it might be the result of an excess in energy intake, reduced energy expenditure, or both. The aim of this study is to describe energy intake and physical activity during treatment for ALL with intermittent dexamethasone (DEXA). Methods  Body mass index (BMI), energy intake, and physical activity were measured in 16 ALL patients on maintenance treatment and in 17 healthy controls. ALL patients were measured during (“on DEXA”) and in between (“off DEXA”) DEXA treatments. Results  In patients, the mean increase in BMI z-score was 1.4 ± 1.1. Energy intake on DEXA was higher (2,125.9 ± 476.0 vs 1,775.1 ± 426.1 kcal/24 h, p < 0.05) and energy intake off DEXA was lower (1,305.0 ± 249.4 vs 1,775.1 ± 426.1 kcal/24 h, p < 0.05), compared to healthy controls. Physical activity on DEXA was lower compared to healthy controls (30.0 ± 3.9 vs 40.0 ± 6.0 kcal kg⁻¹ 24 h⁻¹, p < 0.001 and 7,303.1 ± 4,622.9 vs 13,927.2 ± 3,822.7 steps, p < 0.05). Physical activity off DEXA was not different compared to healthy controls. Conclusion  Weight gain in patients on ALL treatment might be owing to increased energy intake and decreased physical activity during treatment with DEXA.     

Forearm composition and muscle function in trained and untrained limbs

Summary. The influence of a period of training, which lasts for several years, on the proportions of muscle, fat and bone present in the human forearm has been investigated by comparing trained and untrained limbs of nine experienced male tennis players. Ten healthy but untrained males of similar age served as a control group. Computed tomography (CT) scans of the forearm were made at intervals along its length to identify fat, muscle and bone and to calculate the volumes occupied by each of these components. Total forearm volume was greater in the dominant limb compared with the contralateral side in both trained (by 135±59 cm³, mean±SD, P<0·001) and untrained subjects (by 41±45 cm³, P<0·02). Forearm muscle volume was also greater in dominant limbs of trained (by 117±52 cm³, P<0·001) and untrained by 35±41 cm³, P<0·025) subjects. Muscle accounted for 75·4±2·7% of the total volume in the dominant arm of trained subjects compared with 71·4±4·2% in the control group (P<0·05). There was a greater proportion of muscle (P<0·05) and a smaller proportion of fat (P<0·001) in the trained limb compared with the contralateral limb of the same subjects. No differences in proportions of fat, muscle and bone were observed in dominant and non-dominant limbs of the control subjects. Trained subjects were able to exert a greater isometric force with the dominant limb (549±76N) than with the non-dominant limb (496±48N; P<0·005). There was no difference in grip strength between the arms of the untrained group (dominant: 516±107N; non-dominant: 491±91N). The ratio of strength to muscle volume was, however, the same in dominant and non-dominant arms of both groups of subjects.