Ultrasound-based detection of glucocorticoid-induced impairments of muscle mass and structure in Cushing's disease.

PURPOSE: To investigate the glucocorticoid-induced impairments of muscle mass and structure in patients presenting different stages of steroid myopathy progression. METHODS: Thirty-three patients (28 women) affected by active (N = 20) and remitted (N = 13) Cushing's disease were recruited and the following variables were assessed: walking speed, handgrip strength, total body and appendicular muscle mass by bioelectrical impedance analysis (BIA), thickness and echo intensity of lower limb muscles by ultrasonography. RESULTS: The two groups of patients showed comparable values of both handgrip strength [median (interquartile range) values: active disease: 27.4 (7.5) kg vs. remitted disease: 26.4 (9.4) kg; P = 0.58] and walking speed [active disease: 1.0 (0.2) m/s vs. remitted disease: 1.1 (0.3) m/s; P = 0.43]. Also, the thickness of the four muscles and all BIA-derived sarcopenic indices were comparable (P > 0.05 for all comparisons) between the two groups. On the contrary, the echo intensity of vastus lateralis, tibialis anterior (lower portion), and medial gastrocnemius was significantly (P < 0.05 for all comparisons) higher in patients with active disease compared to patients with remitted disease. Finally, significant negative correlations were found in the whole group of patients between muscle echo intensity and muscle function assessments. CONCLUSIONS: We provided preliminary evidence that the ultrasound-derived measurements of muscle thickness and echo intensity can be useful to detect and track the changes of muscle mass and structure in patients with steroid myopathy and we suggest that the combined assessment of muscle mass, strength, and performance should be systematically applied in the routine examination of steroid myopathy patients.

Effectiveness of an innovative mattress overlay for improving rehabilitation in low back pain: A pilot randomized controlled study.

BACKGROUND AND OBJECTIVE: Sleep disorders should be routinely evaluated and treated in low back pain (LBP) patients because they represent an important contributor to pain. However, no study thus far has investigated the potential benefit to LBP management of a device improving the sleep quality. Therefore, aim of this study was to assess the effectiveness of an innovative mattress overlay as add-on treatment to LBP rehabilitation. METHODS: Thirty eight LBP patients were randomized to standard rehabilitation plus mattress overlay use (cases) or standard rehabilitation only (controls). The intervention duration was 2 months and the following assessments were performed before and after: pain intensity; level of perceived back disability and sleep health; spine mobility; thickness and echo intensity of the lumbar multifidus. RESULTS: Significant pre-post-intervention improvements were observed in cases for resting and movement pain, perceived back disability, sleep, fingertip-to-floor distance, multifidus thickness (∼ 6% increase) and echo intensity (∼ 13% decrease). On the contrary, all these variables remained constant between the two experimental phases in controls. CONCLUSIONS: A combination of rehabilitation and mattress overlay use seems an effective approach for improvement of pain, perceived back disability, sleep, spine mobility, and lumbar multifidus size and structure of LBP patients.

Structural and molecular adaptations to dexamethasone and unacylated ghrelin administration in skeletal muscle of the mice.

The central goal of this study was to identify the primary mechanisms triggering steroid atrophy. Adaptations of soleus (Sol) and vastus lateralis (VL) muscles of C57BL/6 female mice were studied following 3, 7 and 15 days of daily intraperitoneal injection (5 mg kg-1 day-1) of dexamethasone (dEx) (chronic treatment) and 1, 3 and 10 hours after a single dEx injection (acute treatment). In the chronic treatment, analyses were performed 24 hours after the last injection. Gene expression of major components of the intracellular signalling pathways controlling mass and metabolism were assessed. Analyses were repeated following dEx and unacylated ghrelin (uAG) (100 µg kg-1day-1), co-administration. We found a significant VL fibres atrophy after 7 (13%) and 15 (28%) days and a Sol fibres atrophy (23%) after 15 days of dEx treatment. The acute treatment showed, in both muscles, several responses in most signalling pathways, among which the enhanced gene expression of Murf-1 (6-fold change in VL and 3-fold in Sol) and myostatin (6-fold change in VL and 20-fold in Sol). In Sol, uAG administration was able to fully counteract muscle atrophy and Murf-1 upregulation, but not the upregulation of myostatin, suggesting a causal relationship between muscle atrophy and Murf-1. Results indicate that: a) the primary mechanism triggering steroid atrophy is an early transient activation of Murf-1; b) uAG inhibits Murf-1 induction counteracting steroid atrophy. The present work contributes to the understanding of the complexity of the muscle response to glucocorticoids.

Reproducibility and validity of the Italian version of the International Physical Activity Questionnaire in obese and diabetic patients.

PURPOSE: Aims of this study were to evaluate the agreement between the short and long versions of the International Physical Activity Questionnaire (IPAQ: Italian versions), their reproducibility (agreement and reliability) and construct validity (relative to pedometry) in a clinical population. METHODS: Ninety patients affected by obesity (N = 39), type 2 diabetes mellitus (N = 26) or both (N = 25) were recruited. They were asked to maintain their usual physical activity habits during two consecutive weeks and to fill the questionnaires twice (at the end of each week). They were also asked to wear a pedometer for 7 consecutive days after the first administration of the questionnaires. RESULTS: We found acceptable agreement between the IPAQ short and long versions (ICC2,1 values were 0.81 and 0.77 for the 1st and 2nd administration), uncertain reproducibility (acceptable reliability but poor agreement) and inadequate validity relative to pedometry (the correlation coefficients between all IPAQ scores and daily steps were <0.50) for both IPAQ short and IPAQ long. CONCLUSIONS: The IPAQ use may be justified in daily clinical practice and in clinical research (e.g., in cross-sectional studies) for a simple and rapid evaluation of the physical activity level for discriminative purposes. However, the use of these questionnaires does not appear suitable for prospective interventional studies in which the level of physical activity of the recruited patients has to be assessed over time.

The acute effect of a mineralocorticoid receptor agonist on corticotrope secretion in Addison's disease.

PURPOSE: Mineralocorticoid receptors (MR) in the hippocampus display an important role in the control of hypothalamic-pituitary-adrenal (HPA) axis, mediating the ''proactive'' feedback of glucocorticoids (GC). Fludrocortisone (FC), a potent MR agonist, has been shown to decrease HPA activity through a hippocampal mechanism. Since it has been demonstrated that FC shows a significant inhibition of the HPA axis response to hCRH stimulus in normal subjects, also at doses usually administered as replacement therapy in patients with Addison's disease, an FC effect at MRs in human pituitary or a GR-pituitary agonism stronger than believed until now has been postulated. METHODS: Ten patients affected by autoimmune Addison's disease received: (1) placebo p.o. + placebo i.v., (2) hydrocortisone (H) 10 mg p.o. + placebo i.v., (3) FC 0.1 mg p.o. + placebo i.v., (4) FC 0.1 mg and H 10 mg p.o. + placebo i.v. to verify a possible GR FC-mediated effect that might display a repercussion on the GC-replacement therapy. RESULTS: H reduced ACTH (p < 0.01) and increased cortisol levels (p < 0.01) with respect to the placebo session, while FC did not affect either ACTH or cortisol levels compared to placebo, and higher ACTH and lower cortisol levels (p < 0.03 and p < 0.01) were observed compared with the H session; furthermore the co-administration of FC + H showed ACTH and cortisol profiles similar to that observed during H alone. CONCLUSIONS: Our study showed a lack of FC effect on corticotrope secretion in Addison's disease, thus making unlikely the hypothesis of its GR pituitary agonism and the risk of glucocorticoid excess in primary adrenal insufficiency.

A non-erythropoietic peptide derivative of erythropoietin decreases susceptibility to diet-induced insulin resistance in mice.

BACKGROUND AND PURPOSE: The haematopoietic activity of erythropoietin (EPO) is mediated by the classic EPO receptor (EpoR) homodimer, whereas tissue-protective effects are mediated by a heterocomplex between EpoR and the ß-common receptor (ßcR). Here, we investigated the effects of a novel, selective ligand of this heterocomplex - pyroglutamate helix B surface peptide (pHBSP) - in mice fed a diet enriched in sugars and saturated fats. EXPERIMENTAL APPROACH: Male C57BL/6J mice were fed a high-fat high-sucrose diet (HFHS) for 22 weeks. pHBSP (30 µg·kg(-1) s.c.) was administered for the last 11 weeks. Biochemical assays, histopathological and immunohistochemical examinations and Western blotting were performed on serum and target organs (liver, kidney and skeletal muscle). KEY RESULTS: Mice fed with HFHS diet exhibited insulin resistance, hyperlipidaemia, hepatic lipid accumulation and kidney dysfunction. In gastrocnemius muscle, HFHS impaired the insulin signalling pathway and reduced membrane translocation of glucose transporter type 4 and glycogen content. Treatment with pHBSP ameliorated renal function, reduced hepatic lipid deposition, and normalized serum glucose and lipid profiles. These effects were associated with an improvement in insulin sensitivity and glucose uptake in skeletal muscle. Diet-induced overproduction of the myokines IL-6 and fibroblast growth factor-21 were attenuated by pHBSP and, most importantly, pHBSP markedly enhanced mitochondrial biogenesis in skeletal muscle. CONCLUSIONS AND IMPLICATIONS: Chronic treatment of mice with an EPO derivative, devoid of haematopoietic effects, improved metabolic abnormalities induced by a high-fat high-sucrose diet, by affecting several levels of the insulin signalling and inflammatory cascades within skeletal muscle, while enhancing mitochondrial biogenesis.

Differences in proprioception, muscle force control and comfort between conventional and new-generation knee and ankle orthoses.

The aim of this study was to compare muscle force control and proprioception between conventional and new-generation experimental orthoses. Sixteen healthy subjects participated in a single-blind controlled trial in which two different types of orthosis were applied to the dominant knee or ankle, while the following variables were evaluated: muscle force control (accuracy), joint position sense, kinesthesia, static balance as well as subjective outcomes. The use of experimental orthoses resulted in better force accuracy during isometric knee extensions compared to conventional orthoses (P=0.005). Moreover, the use of experimental orthoses resulted in better force accuracy during concentric (P=0.010) and eccentric (P=0.014) ankle plantar flexions and better knee joint kinesthesia in the flexed position (P=0.004) compared to conventional orthoses. Subjective comfort (P<0.001) and preference scores were higher with experimental orthoses compared to conventional ones. In conclusion, orthosis type affected static and dynamic muscle force control, kinesthesia, and perceived comfort in healthy subjects. New-generation experimental knee and ankle orthoses may thus be recommended for prophylactic joint bracing during physical activity and to improve the compliance for orthosis use, particularly in patients who require long-term bracing.

Accurate identification of motor unit discharge patterns from high-density surface EMG and validation with a novel signal-based performance metric.

OBJECTIVE: A signal-based metric for assessment of accuracy of motor unit (MU) identification from high-density surface electromyograms (EMG) is introduced. This metric, so-called pulse-to-noise-ratio (PNR), is computationally efficient, does not require any additional experimental costs and can be applied to every MU that is identified by the previously developed convolution kernel compensation technique. APPROACH: The analytical derivation of the newly introduced metric is provided, along with its extensive experimental validation on both synthetic and experimental surface EMG signals with signal-to-noise ratios ranging from 0 to 20 dB and muscle contraction forces from 5% to 70% of the maximum voluntary contraction. MAIN RESULTS: In all the experimental and simulated signals, the newly introduced metric correlated significantly with both sensitivity and false alarm rate in identification of MU discharges. Practically all the MUs with PNR > 30 dB exhibited sensitivity >90% and false alarm rates <2%. Therefore, a threshold of 30 dB in PNR can be used as a simple method for selecting only reliably decomposed units. SIGNIFICANCE: The newly introduced metric is considered a robust and reliable indicator of accuracy of MU identification. The study also shows that high-density surface EMG can be reliably decomposed at contraction forces as high as 70% of the maximum.

Variability in muscle adaptation to electrical stimulation.

The aims were to investigate the plasticity of the myosin heavy chain (MHC) phenotype following neuromuscular electrical stimulation (NMES) and to assess the correlation between MHC isoform distribution and muscle fibre conduction velocity (MFCV).14 men were subjected to 24 sessions of quadriceps NMES. Needle biopsies were taken from the dominant vastus lateralis and neuromuscular tests were performed on the dominant thigh before and after training. NMES significantly increased the quadriceps maximal force by 14.4±19.7% (P=0.02), vastus lateralis thickness by 10.7±8.6% (P=0.01), vastus lateralis MFCV by 11.1±3.5% (P<0.001), vastus medialis MFCV by 8.4±1.8% (P<0.001). The whole spectrum of possible MHC isoform adaptations to training was observed: fast-to-slow transition (4 subjects), bi-directional transformation from MHC-1 and MHC-2X isoforms toward MHC-2A isoform (7 subjects), shift toward MHC-2X (2 subjects), no MHC distribution change (1 subject). No significant correlation was observed between MHC-2 relative content and vastus lateralis MFCV (pre-training: R2=0.04, P=0.46; post-training: R2=0.02, P=0.67). NMES elicited distinct adaptations in the MHC composition and increased force, muscle thickness, and MFCV. The MHC isoform distribution did not correlate with MFCV, thus implying that the proportion of different fibre types cannot be estimated from this electrophysiological variable.

Steroid myopathy: some unresolved issues.

Steroid myopathy is a non-inflammatory toxic myopathy that occurs as side effect of exogenous and endogenous glucocorticoid excess. The purpose of this review is to examine issues that limit our understanding of this myopathy with respect to nosology, etiopathogenesis, conditioning factors, and muscle fiber selectivity. We suggest that if more data were available on these issues, the understanding of steroid myopathy would be enhanced substantially, thus allowing an early detection of its occurrence (before the appearance of clinical or laboratory signs) and a proper treatment of the patients.

Growth hormone/insulin-like growth factor-I axis in obstructive sleep apnea syndrome: an update.

Obstructive sleep apnea syndrome (OSAS) is a serious, prevalent condition that has significant mortality and morbidity when untreated. It is strongly associated with obesity and is characterized by changes in the serum levels or secretory patterns of several hormones. In particular, obese patients with OSAS show a peculiar reduction of both spontaneous and stimulated GH secretion coupled with reduced IGF-I concentrations and impaired peripheral sensitivity to GH. These endocrine abnormalities are more marked than those observed in non-apneic obese subjects, and are likely to be due to the effects of hypoxia and sleep fragmentation on hormone secretory pattern. The GH/IGF-I axis activity disruption can be responsible, at least in part, for metabolic alterations, which are common in OSAS and increase the risk of cardiovascular events as well as mortality. Effective assessment and management of OSAS may correct endocrine changes, improve quality of life, and prevent associated morbidity or death.

Time and frequency domain analysis of surface myoelectric signals during electrically-elicited cramps.

OBJECTIVES: To examine if different frequencies of electrical stimulation trigger different sized cramps in the abductor hallucis muscle and to analyze their surface electromyographic (EMG) behaviour in both time and frequency domains. METHODS: Fifteen subjects were studied. Stimulation trains of 150 pulses were applied to the muscle motor point. Frequency was increased (starting from 4pps with 2-pps steps) until a cramp developed. Current intensity was 30% higher than that eliciting maximal M-waves. After the first cramp ("threshold cramp"), a 30-minute rest was provided before a second cramp ("above-threshold cramp") was elicited with a frequency increased by 50% with respect to that eliciting the first cramp. RESULTS: We found greater EMG amplitude and a compression of the power spectrum for above-threshold cramps with respect to threshold cramps. M-wave changes (ranging between small decreases of M-wave amplitude to complete M-wave disappearance) occurred and progressively increased throughout stimulation trains. Significant positive correlations were found between estimates of EMG amplitude during cramps and estimated reductions of M-wave amplitude. CONCLUSIONS: Varying frequencies of electrical stimulation triggered different sized cramps. Moreover, decreases in M-wave amplitude were observed during both threshold and above-threshold stimulations. The choice of the stimulation frequency has relevance for optimizing electrical stimulation protocols for the study of muscle cramps in both healthy and pathological subjects.

Myoelectric fatigue profiles of three knee extensor muscles.

Aims of the present study were to: 1) investigate the differences between the myoelectric fatigue profiles of the vasti muscles of the quadriceps during electrically evoked contractions; 2) compare the myoelectric fatigue profiles of the vasti muscles between sedentary subjects and rowers; 3) analyze motor unit activation order during stimulation of the vasti muscles. In nine sedentary subjects and nine rowers surface EMG signals were detected during electrically elicited contractions of the following three muscles: vastus medialis obliquus (VMO), vastus lateralis (VL), and vastus medialis longus (VML). M-waves were recorded as the muscles were stimulated with both variable (increasing-decreasing) and constant stimulation intensities. Changes in M-wave conduction velocity (CV) during trains with non-constant current were adopted for the study of the motor unit recruitment order. Rates of change of myoelectric signal variables were adopted to assess myoelectric manifestations of fatigue during stimulation trains with constant current. We found that: 1) VL muscle was more fatigable than vastus medialis muscles; 2) VL and VML muscles of rowers resulted less fatigable than sedentary subjects; and 3) in the three muscles, motor units tended to be recruited in order of increasing CV and derecruited in order of decreasing CV with increasing/decreasing stimulation current.

Pulse charge and not waveform affects M-wave properties during progressive motor unit activation.

The aim of this study was to investigate changes in experimentally recorded M-waves with progressive motor unit (MU) activation induced by transcutaneous electrical stimulation with different pulse waveforms. In 10 subjects, surface electromyographic signals were detected with a linear electrode array during electrically elicited contractions of the biceps brachii muscle. Three different monophasic waveforms of 304-micros duration were applied to the stimulation electrode on the main muscle motor point: triangular, square, and sinusoidal. For each waveform, increasing stimulation current intensities were applied in 10 s (frequency: 20 Hz). It was found that: (a) the degree of MU activation, as indicated by M-wave average rectified value, was a function of the injected charge and not of the stimulation waveform, and (b) MUs tended to be recruited in order of increasing conduction velocity with increasing charge of transcutaneous stimulation. Moreover, the subjects reported lower discomfort during the contractions elicited by the triangular waveform with respect to the others. Since subject tolerance to the stimulation protocol must be considered as important as MU recruitment in determining the effectiveness of neuromuscular electrical stimulation (NMES), we suggest that both charge and waveform of the stimulation pulses should be considered relevant parameters for optimizing NMES protocols.

Changes in awakening cortisol response and midnight salivary cortisol are sensitive markers of strenuous training-induced fatigue.

The aim of the study was to examine the effects of strenuous training on the hypothalamic- pituitary-adrenal axis activity. Exercise tests and saliva collections for analysis of awakening cortisol response (ACR) and midnight cortisol were performed before and after a 7-day period of intensified training in a group of 15 soccer players. Intensified training resulted in a performance decrement as shown by the pre-post-training changes in maximal values of counter movement jump (CMJ) height (p=0.008). Cortisol assessment during the first 30 min after awakening showed significant increases both before and after the 7-day period and post-training ACR higher than pre-training ACR (p<0.001). Midnight cortisol also significantly increased after training (mean+/-SD, before: 3.0+/-0.7 nmol/l vs after: 5.9+/-3.3 nmol/l; p=0.017). The analysis of individual data showed an important inter-individual variability in the pre-post-training changes: several subjects increased post-awakening peak of cortisol, rate of cortisol increase from awakening to peak, and area under the curve (AUC) values, whereas other subjects showed no training-related increases. Significant correlations were observed between pre-post-training change in CMJ and in the following variables: awakening cortisol (r=0.74), post-awakening peak of cortisol (r=0.81), rate of cortisol increase (r=0.75), and AUC (r=0.79). Briefly, the lower the performance decrease, the higher the training-associated ACR increase. These data could indicate that a dysregulated adaptation to exercise occurred in athletes who experienced a higher performance decrease after training and lower (or absent) hormonal changes. Future studies are needed to elucidate the physiological determinants which underlie the exercise-elicited changes in ACR and in midnight cortisol levels and their value in predicting impaired adaptations to exercise.

Influence of the sample collection method on salivary interleukin-6 levels in resting and post-exercise conditions.

Previous studies demonstrated that no significant relationships exist between salivary and serum IL-6 in resting conditions and following exercise and that appropriate saliva collection procedures allow to avoid analytical drawbacks. This investigation aimed to: (a) compare the effects of two methods of saliva collection on IL-6 assay; (b) search for correlation between salivary and serum IL-6 in resting and post-exercise conditions; (c) evaluate the IL-6 response to isometric contractions. Seventeen sedentary subjects and fifteen athletes underwent one blood and two salivary draws: saliva was collected chewing on cotton salivettes and using a plastic straw (SA method and ST method, respectively). Afterwards, the athletes only completed a fatiguing isometric exercise of the knee extensors and blood and saliva were sampled after the exercise. In the entire group (n=32), ST method produced higher IL-6 levels than SA method and serum sampling. The exercise elicited significant responses of lactate, serum IL-6, salivary IL-6 (by ST method): salivary IL-6 values using the ST collection method were higher at each sampling point than with the SA method. The correlation analyses applied to both resting levels in the entire group and absolute changes above baseline in the athlete group showed that: (1) no significant relationships exist between serum and salivary IL-6 levels; (2) the greater the salivary IL-6 measurement, the higher the resultant inaccuracy of the SA method; (3) significant correlations exist between isometric force and mechanical fatigue during exercise and peaks of lactate and serum IL-6. These data provided demonstration of a cotton-interference effect for the results of salivary IL-6 assay and confirmed the lack of significant correlation between salivary and serum IL-6 in resting and post-exercise conditions.

Corticotroph axis sensitivity after exercise: comparison between elite athletes and sedentary subjects.

Strenuous exercise activates the hypothalamic-pituitary-adrenal (HPA) axis. Several reports showed that physical training is associated with a decreased efficiency of the feedback control of HPA axis. The aims of the present study were: 1) to evaluate the differences in the mechanical, hormonal, and lactate responses to a high-intensity isokinetic exercise among different groups of competitive athletes (CA, no.=20) of power and endurance disciplines and sedentary controls (SED, no.=10); 2) to determine the effects of the training status on the HPA axis responsiveness following exercise, as indirectly evaluated by the rates of ACTH, cortisol, and DHEA recovery after exercise. CA and SED fulfilled eight sets of twenty concentric contractions of the knee extensors at 180 degrees/sec angular velocity throughout a constant range of motion (100 degrees). There was a rest period of 30 sec between each set and a 3-min rest period between the two legs. Before, immediately after the isokinetic exercise and at different times in the subsequent 120 min of recovery, blood and saliva were sampled to determine plasma ACTH, salivary cortisol, serum DHEA, and serum lactate concentrations. CA showed a higher cortisol response to exercise than SED, whereas no differences were found in the responses of ACTH, DHEA and lactate. In the athlete group the exercise-induced increases of ACTH, cortisol, and lactate were higher in power athletes with respect to endurance athletes. No differences were observed between athletes and SED in the rates of hormonal recovery after exercise: this finding does not support the concept that a reduced feedback control of HPA axis can represent a feature of trained individuals.

Effects of the training status on the hormonal response and recovery from high-intensity isokinetic exercise: comparisons between endurance-trained athletes and sedentary subjects.

AIM: Aims of the study were: to determine the differences in the mechanical, hormonal and lactate responses to a high-intensity isokinetic exercise in two groups of endurance-trained athletes (EA, n = 11) and sedentary subjects (SED, n = 11); to evaluate the relationships between the hormonal and lactate responses; to evaluate the effects of the training status on the pituitary responsiveness to the exercise. METHODS: EA and SED completed, for each leg, 4 sets of 20 maximal concentric contractions of the knee extensor muscle groups at 180 degrees s-1 angular velocity. Blood and saliva for hormonal and lactate determinations were sampled before, immediately after the test and during the subsequent recovery of 2 hours. RESULTS: The exercise was completed by all subjects and elicited significant mechanical and biochemical responses both in EA and in SED subjects. No differences were found between the two groups both in the mechanical performances and in the increases of lactate and hormones of the pituitary-adrenal axis or in the comparison of the slopes of adrenocorticotropic hormone (ACTH), cortisol, and dehydroepiandrosterone recovery after the peak. The correlation analyses showed significant positive relationships between lactate peak values and percentages of change for ACTH (r2 = 0.16, P < 0.05), salivary cortisol (r2 = 0.42, P < 0.01), and serum cortisol (r2 = 0.56, P < 0.001). CONCLUSIONS: The adrenocortical activation was found, in this particular setting, at least partly dependent on the muscular lactate production, while no effect of the training status on the pituitary responsiveness to exercise was evident, as it was indirectly confirmed by no abnormalities in the rates of hormonal recovery after the exercise session.