Effect of L-arginine infusion on glucose disposal during exercise in humans

Purpose: We have previously shown that local infusion of a nitric oxide synthase (NOS) inhibitor attenuates increases in leg glucose uptake during exercise in humans. We have also shown that infusion of the NOS substrate, L-arginine (L-Arg), increases glucose clearance, although the mechanisms involved were not determined. A potential mechanism for NO-mediated glucose disposal is via interactions with NOS and the energy sensor AMPactivated protein kinase (AMPK). The aim of this study was to determine the mechanism(s) by which L-Arg infusion increases glucose disposal during exercise in humans by examining total NOS activity and AMPK signaling.

Methods: Seven males cycled for 120 min at 64% T 1% V˙ O2peak, during which the [6,6-2H]glucose tracer was infused. During the final 60 min of exercise, either saline alone (Control, CON), or saline containing L-Arg HCl (L-Arg, 30 g at 0.5 gIminj1) was coinfused in a double-blind, randomized, counterbalanced order.

Results: L-Arg increased the glucose rate of disappearance and glucose clearance rate during exercise; however, this was accompanied by a 150% increase in plasma insulin concentration from 65 to 75 min (P G 0.05) that remained significantly elevated until 90 min of exercise. Skeletal muscle AMPK signaling, nNOSK phosphorylation by AMPK, and total NOS activity increased to a similar extent in the two trials.

Conclusions: The increase in glucose disposal after L-Arg infusion during exercise is likely due to the significantly higher plasma insulin concentration.

Two maximal isometric contractions attenuate the magnitude of eccentric exercise-induced muscle damage

This study investigated whether maximal voluntary isometric contractions (MVC-ISO) would attenuate the magnitude of eccentric exercise-induced muscle damage. Young untrained men were placed into one of the two experimental groups or one control group (n = 13 per group). Subjects in the experimental groups performed either two or 10 MVC-ISO of the elbow flexors at a long muscle length (20° flexion) 2 days prior to 30 maximal isokinetic eccentric contractions of the elbow flexors. Subjects in the control group performed the eccentric contractions without MVC-ISO. No significant changes in maximal voluntary concentric contraction peak torque, peak torque angle, range of motion, upper arm circumference, plasma creatine kinase (CK) activity and myoglobin concentration, muscle soreness, and ultrasound echo intensity were evident after MVC-ISO. Changes in the variables following eccentric contractions were smaller (P < 0.05) for the 2 MVC-ISO group (e.g., peak torque loss at 5 days after exercise, 23% ± 3%; peak CK activity, 1964 ± 452 IU·L^–1; peak muscle soreness, 46 ± 4 mm) or the 10 MVC-ISO group (13% ± 3%, 877 ± 198 IU·L^–1, 30 ± 4 mm) compared with the control (34% ± 4%, 6192 ± 1747 IU·L^–1, 66 ± 5 mm). The 10 MVC-ISO group showed smaller (P < 0.05) changes in all variables following eccentric contractions compared with the 2 MVC-ISO group. Therefore, two MVC-ISO conferred potent protective effects against muscle damage, whereas greater protective effect was induced by 10 MVC-ISO, which can be used as a strategy to minimize muscle damage.

In-situ dehydration studies of fully K-, Rb-, and Cs-exchanged natrolites

In-situ synchrotron X-ray powder diffraction studies of K-, Rb-, and Cs-exchanged natrolites between room temperature and 425 °C revealed that the dehydrated phases with collapsed frameworks start to form at 175, 150, and 100 °C, respectively. The degree of the framework collapse indicated by the unit-cell volume contraction depends on the size of the non-framework cation: K-exchanged natrolite undergoes an 18.8% unit-cell volume contraction when dehydrated at 175 °C, whereas Rb- and Cs-exchanged natrolites show unit-cell volume contractions of 18.5 and 15.2% at 150 and 100 °C, respectively. In the hydrated phases, the dehydration-induced unit-cell volume reduction diminishes as the cation size increases and reveals increasingly a negative slope as smaller cations are substituted into the pores of the natrolite structure. The thermal expansion of the unit-cell volumes of the dehydrated K-, Rb-, and Cs-phases have positive thermal expansion coefficients of 8.80 × 10⁻⁵ K⁻¹, 1.03 × 10⁻⁴ K⁻¹, and 5.06 × 10⁻⁵ K⁻¹, respectively. Rietveld structure refinements of the dehydrated phases at 400 °C reveal that the framework collapses are due to an increase of the chain rotation angles, ψ, which narrow the channels to a more elliptical shape. Compared to their respective hydrated structures at ambient conditions, the dehydrated K-exchanged natrolite at 400 °C shows a 2.2-fold increase in ψ, whereas the dehydrated Rb- and Cs-natrolites at 400 °C reveal increases of ψ by ca. 3.7 and 7.3 times, respectively. The elliptical channel openings of the dehydrated K-, Rb-, to Cs-phases become larger as the cation size increases. The disordered non-framework cations in the hydrated K-, Rb-, and Cs-natrolite order during dehydration and the subsequent framework collapse. The dehydrated phases of Rb- and Cs-natrolite can be stabilized at ambient conditions.

Oxygen dependency of hydrogen sulfide-mediated vasoconstriction in cyclostome aortas

Hydrogen sulfide (H₂S) has been proposed to mediate hypoxic vasoconstriction (HVC), however, other studies suggest the vasoconstrictory effect indirectly results from an oxidation product of H₂S. Here we examined the relationship between H₂S and O₂ in isolated hagfish and lamprey vessels that exhibit profound hypoxic vasoconstriction. In myographic studies, H₂S (Na₂S) dose-dependently constricted dorsal aortas (DA) and efferent branchial arteries (EBA) but did not affect ventral aortas or afferent branchial arteries; effects similar to those produced by hypoxia. Sensitivity of H₂S-mediated contraction in hagfish and lamprey DA was enhanced by hypoxia. HVC in hagfish DA was enhanced by the H₂S precursor cysteine and inhibited by amino-oxyacetate, an inhibitor of the H₂S-synthesizing enzyme, cystathionine β-synthase. HVC was unaffected by propargyl glycine, an inhibitor of cystathionine λ-lyase. Oxygen consumption (ṀO₂) of hagfish DA was constant between 15 and 115 mmHg P_O2 (1 mmHg=0.133 kPa), decreased when P_O2 <15 mmHg, and increased after P_O2 exceeded 115 mmHg. 10 μmol l^–1 H₂S increased and ⩾100μ mol l^–1 H₂S decreased ṀO₂. Consistent with the effects on HVC, cysteine increased and amino-oxyacetate decreased Ṁ_O2. These results show that H₂S is a monophasic vasoconstrictor of specific cyclostome vessels and because hagfish lack vascular NO, and vascular sensitivity to H₂S was enhanced at low P_O2, it is unlikely that H₂S contractions are mediated by either H₂S–NO interaction or an oxidation product of H₂S. These experiments also provide additional support for the hypothesis that the metabolism of H₂S is involved in oxygen sensing/signal transduction in vertebrate vascular smooth muscle.

Development and physiology of gastric dilation air sacculitis in Chinook salmon, Oncorhynchus tshawytscha (Walbaum)

The syndrome known as gastric dilation air sacculitis (GDAS) has previously been shown to affect Chinook salmon, Oncorhynchus tshawytscha, in seawater (SW) aquaculture. Feed and osmoregulatory stress have been implicated as potential epidemiological co-factors. The development and physiology of GDAS was investigated in SW and freshwater (FW) adapted smolts. Diet A (low-cohesion pellets) and diet B (high-cohesion pellets) were fed to both FW- and SW-adapted fish. GDAS was induced only in the SW trial on feeding diet A. Stimulated gastro-intestinal (GI) smooth muscle contractility, and fluid transport by the pyloric caeca were different in GDAS-affected fish, which also showed osmoregulatory dysfunction. Cardiac stomach (CS) smooth muscle contractility in response to acetylcholine and potassium chloride (KCl) was significantly reduced in fish fed diet A relative to controls from weeks 3–5. In contrast, maximal pyloric sphincter (PS) circular smooth muscle contraction in response to KCl was significantly elevated in fish fed diet A in weeks 4 and 5. Serum osmolality was elevated in GDAS-affected fish from week 2 of the SW trial. Fluid transport from the mucosal to serosal surface of isolated pyloric caeca was significantly reduced in weeks 3, 4 and 5 in SW fish fed diet A. Gastric evacuation from the stomach of healthy fish was shown to be significantly different when diets of low- and high-cohesion were fed. The results are consistent with the intestinal brake playing a role in the development of the disease.

Contribution of stretch to the change of activation properties of muscle fibers in the diaphragm at the transition from fetal to neonatal life

The transition from fetal to postnatal life involves clearance of liquid from the lung and airways, and rapid formation of a functional residual capacity. Despite the importance of the diaphragm in this process, the impact of birth on the mechanical and functional activity of its muscle fibers is not known. This study determined the contractile characteristics of individual “skinned” diaphragm fibers from 70 days (0.47) gestation to after birth in sheep. Based on differential sensitivity to the divalent ions calcium (Ca²⁺) and strontium (Sr²⁺), all fibers in the fetal diaphragm were classified as “fast,” whereas fibers from the adult sheep diaphragm exhibited a “hybrid” phenotype where both “fast” and “slow” characteristics were present within each single fiber. Transition to the hybrid phenotype occurred at birth, was evident after only 40 min of spontaneous breathing, and could be induced by simple mechanical stretch of diaphragm fibers from near-term fetuses (∼147 days gestation). Both physical stretch of isolated fibers, and mechanical ventilation of the fetal diaphragm in situ, significantly increased sensitivity to Ca²⁺ and Sr²⁺, maximum force generating capacity, and decreased passive tension in near-term and preterm fetuses; however, only fibers from near-term fetuses showed a complete transition to a “hybrid” activation profile. These findings suggest that stretch associated with the transition from a liquid to air-filled lung at birth induces physical changes of proteins determining the activation and elastic properties of the diaphragm. These changes may allow the diaphragm to meet the increased mechanical demands of breathing immediately after birth.

The effects of whole-body vibration on the cross-transfer of strength

This study investigated whether the use of superimposed whole-body vibration (WBV) during cross-education strength training would optimise strength transfer compared to conventional cross-education strength training. Twenty-one healthy, dominant right leg volunteers (21±3 years) were allocated to a strength training (ST, m = 3, f = 4), a strength training with WBV (ST + V, m = 3, f = 4), or a control group (no training, m = 3, f = 4). Training groups performed 9 sessions over 3 weeks, involving unilateral squats for the right leg, with or without WBV (35 Hz; 2.5mm amplitude). All groups underwent dynamic single leg maximum strength testing (1RM) and single and paired pulse transcranial magnetic stimulation (TMS) prior to and following training. Strength increased in the trained limb for the ST (41%; ES = 1.14) and ST + V (55%; ES = 1.03) groups, which resulted in a 35% (ES = 0.99) strength transfer to the untrained left leg for the ST group and a 52% (ES = 0.97) strength transfer to the untrained leg for the ST + V group, when compared to the control group. No differences in strength transfer between training groups were observed (P = 0.15). For the untrained leg, no differences in the peak height of recruitment curves or SICI were observed between ST and ST + V groups (P = 1.00). Strength training with WBV does not appear to modulate the cross-transfer of strength to a greater magnitude when compared to conventional cross-education strength training.

Anodal tDCS applied during strength training enhances motor cortical plasticity

Purpose:
The objective of this study was to assess the effect of anodal transcranial direct current stimulation (a-tDCS) on voluntary dynamic strength and cortical plasticity when applied during a 3-wk strength training program for the wrist extensors.

Methods:
Thirty right-handed participants were randomly allocated to the tDCS, sham, or control group. The tDCS and sham group underwent 3 wk of heavy-load strength training of the right wrist extensors, with 20 min of a-tDCS (2 mA) or sham tDCS applied during training (double blinded). Outcome measures included voluntary dynamic wrist extension strength, muscle thickness, corticospinal excitability, short-interval intracortical inhibition (SICI), and silent period duration.

Results:
Maximal voluntary strength increased in both the tDCS and sham groups (14.89% and 11.17%, respectively, both P < 0.001). There was no difference in strength gain between the two groups (P = 0.229) and no change in muscle thickness (P = 0.15). The tDCS group demonstrated an increase in motor-evoked potential amplitude at 15%, 20%, and 25% above active motor threshold, which was accompanied by a decrease in SICI during 50% maximal voluntary isometric contraction and 20% maximal voluntary isometric contraction (all P < 0.05). Silent period decreased for both the tDCS and sham groups (P < 0.001).

Conclusion:
The application of a-tDCS in combination with strength training of the wrist extensors in a healthy population did not provide additional benefit for voluntary dynamic strength gains when compared with standard strength training. However, strength training with a-tDCS appears to differentially modulate cortical plasticity via increases in corticospinal excitability and decreases in SICI, which did not occur following strength training alone

Short-interval intracortical inhibition is not affected by varying visual feedback in an isometric task in biceps brachiii muscle

Purpose : To establish if visual feedback and force requirements influence SICI.

Methods : SICI was assessed from 10 healthy adults (5 males and 5 females aged between 21 and 35 years) in three submaximal isometric elbow flexion torque levels [5, 20, and 40% of maximal voluntary contraction (MVC)] and with two tasks differing in terms of visual feedback. Single-pulse and paired-pulse motor-evoked potentials (MEPs), supramaximal M-wave, and background surface electromyogram (sEMG) were recorded from the biceps brachii muscle.

Results : Repeated measures MANOVA was used for statistical analyses. Background sEMG did not differ between tasks (F = 0.4, P = 0.68) nor was task × torque level interaction observed (F = 1.2, P = 0.32), whereas background sEMG increased with increasing torque levels (P = 0.001). SICI did not differ between tasks (F = 0.9, P = 0.43) and no task × torque level interaction was observed (F = 2.3, P = 0.08). However, less SICI was observed at 40% MVC compared to the 5 and 20% MVC torque levels (P = 0.01–0.001).

Conclusion : SICI was not altered by performing the same task with differing visual feedback. However, SICI decreased with increasing submaximal torque providing further evidence that SICI is one mechanism of modulating cortical excitability and plays a role in force gradation.

Comparative studies of structural transition between AlN nanocrystals and nanowires

The structural transition of AIN nanocrystals and nanowires were investigated simultaneously under pressures up to 37.2 GPa by in situ angle dispersive high-pressure x-ray diffraction using synchrotron radiation source and a single diamond anvil cell. The size of hexagonal AIN nanocrystals and the diameter of nanowires are 45 nm on average. A pressure-induced wurtzite to rocksalt phase transition starts at 21.5 GPa and completes at 27.8 GPa for the nanocrystals and nanowires, respectively. The high-pressure behaviors of AlN nanocrystals the same as the AIN nanowires might arise from the similar size and diameter in nanocrystals and nanowires. Hexagonal AIN nanocrystals (45 nm) display an apparent volumetric contraction as compared to the AlN nanocrystals (10 nm) which might induce the difference of transition pressure.

Skeletal muscle nitric oxide signalling and exercise: a focus on glucose metabolism

Nitric oxide (NO) is an important vasodilator and regulator in the cardiovascular system, and this link was the subject of a Nobel prize in 1998. However, NO also plays many other regulatory roles, including thrombosis, immune function, neural activity, and gastrointestinal function. Low concentrations of NO are thought to have important signaling effects. In contrast, high concentrations of NO can interact with reactive oxygen species, causing damage to cells and cellular components.

A less-recognized site of NO production is within skeletal muscle, where small increases are thought to have beneficial effects such as regulating glucose uptake and possibly blood flow, but higher levels of production are thought to lead to deleterious effects such as an association with insulin resistance.

This review will discuss the role of NO in skeletal muscle during and following exercise, including in mitochondrial biogenesis, muscle efficiency, and blood flow with a particular focus on its potential role in regulating skeletal muscle glucose uptake during exercise.

Xanthine oxidase inhibition attenuates skeletal muscle signaling following acute exercise but does not impair mitochondrial adaptations to endurance training.

The aim of this research was to examine the impact of the xanthine oxidase (XO) inhibitor allopurinol on the skeletal muscle activation of cell signaling kinases' and adaptations to mitochondrial proteins and antioxidant enzymes following acute endurance exercise and endurance training. Male Sprague-Dawley rats performed either acute exercise (60 min of treadmill running, 27 m/min, 5% incline) or 6 wk of endurance training (5 days/wk) while receiving allopurinol or vehicle. Allopurinol treatment reduced XO activity to 5% of the basal levels (P < 0.05), with skeletal muscle uric acid levels being almost undetectable. Following acute exercise, skeletal muscle oxidized glutathione (GSSG) significantly increased in allopurinol- and vehicle-treated groups despite XO activity and uric acid levels being unaltered by acute exercise (P < 0.05). This suggests that the source of ROS was not from XO. Surprisingly, muscle GSSG levels were significantly increased following allopurinol treatment. Following acute exercise, allopurinol treatment prevented the increase in p38 MAPK and ERK phosphorylation and attenuated the increase in mitochondrial transcription factor A (mtTFA) mRNA (P < 0.05) but had no effect on the increase in peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), nuclear respiratory factor-2, GLUT4, or superoxide dismutase mRNA. Allopurinol also had no impact on the endurance training-induced increases in PGC-1α, mtTFA, and mitochondrial proteins including cytochrome c, citrate synthase, and β-hydroxyacyl-CoA dehydrogenase. In conclusion, although allopurinol inhibits cell signaling pathways in response to acute exercise, the inhibitory effects of allopurinol appear unrelated to exercise-induced ROS production by XO. Allopurinol also has little effect on increases in mitochondrial proteins following endurance training.

The role and regulation of stars in skeletal muscle

STARS is a muscle specific protein that is upregulated in response to endurance exercise and may potentially increase skeletal muscle cell sensitivity to muscle contraction. STARS enhances the activation of intracellular signalling pathways involved in skeletal muscle growth, regeneration and oxidative metabolism.

State dependent asymmetric loss and the consensus forecast of real U.S. GDP growth

It has been well documented that the consensus forecast from surveys of professional forecasters shows a bias that varies over time. In this paper, we examine whether this bias may be due to forecasters having an asymmetric loss function. In contrast to previous research, we account for the time variation in the bias by making the loss function depend on the state of the economy. The asymmetry parameter in the loss function is specified to depend on set state variables which may cause forecaster to intentionally bias their forecasts. We consider both the Lin–Ex and asymmetric power loss functions. For the commonly used Lin–Ex and Lin–Lin loss functions, we show the model can be easily estimated by least squares. We apply our methodology to the consensus forecast of real U.S. GDP growth from the Survey of Professional Forecasters. We find that forecast uncertainty has an asymmetric effect on the asymmetry parameter in the loss function dependent upon whether the economy is in expansion or contraction. When the economy is in expansion, forecaster uncertainty is related to an overprediction in the median forecast of real GDP growth. In contrast, when the economy is in contraction, forecaster uncertainty is related to an underprediction in the median forecast of real GDP growth. Our results are robust to the particular loss function that is employed in the analysis.