Influence of low muscle activation levels on the ankle torque and muscle shear modulus during plantar flexor stretching

During stretching studies, surface electromyography (sEMG) is used to ensure the passive state of the muscle, for the characterization of passive muscle mechanical properties. Different thresholds (1%, 2% or 5% of maximal) are indifferently used to set “passive state”. This study aimed to investigate the effects of a slight activity on the joint and muscle mechanical properties during stretching.The joint torque and muscle shear modulus of the triceps surae muscles were measured in fifteen healthy volunteers during ankle dorsiflexions: (i) in a “fully relaxed” state, (ii) during active conditions where participants were asked to produce an sEMG amplitude of 1%, 2% or 5% of their maximal sEMG amplitude of the triceps surae. The 1% condition was the only that did not result in significant differences in joint torque or shear modulus compared to the relaxed condition. In the 2% condition, increases in joint torque were found at 80% of the maximal angle in dorsiflexion, and in the shear modulus of gastrocnemius medialis and gastrocnemius lateralis at the maximal angle in dorsiflexion. During the 5% condition, joint torque and the shear modulus of gastrocnemius medialis were higher than during relaxed condition at angles larger than 40% of maximal angle in dorsiflexion. The results provide new insights on the thresholds that should be considered for the design of stretching studies. A threshold of 1% seems much more appropriate than a 2% or 5% threshold in healthy participants. Further studies are required to define similar thresholds for patients.     

mTOR pathway inhibition attenuates skeletal muscle growth induced by stretching

The present study has aimed to verify the influence of calcineurin and mTOR pathways in skeletal muscle longitudinal growth induced by stretching. Male Wistar rats were treated with cyclosporin-A or rapamycin for 10 days. To promote muscle stretching, casts were positioned so as completely to dorsiflex the plantar-flexor muscles at the ankle in one hind limb during the last 4 days of treatment with either cyclosporin-A or rapamycin. Thereafter, we determined soleus length, weight, protein content, and phenotype. In addition, NFATc1, Raptor, S6K1, 4E-BP1, iNOS, and nNOS gene expression in the soleus were determined by real-time polymerase chain reaction. Soleus length, weight, and protein content were significantly reduced by rapamycin treatment in animals submitted to stretching (P<0.05). In contrast, cyclosporin-A treatment did not alter these parameters. In all cyclosporin-A treated groups, there was a significant reduction in NFATc1 expression (P<0.001). Similarly, a significant reduction was noted in Raptor (P<0.001) and S6K1 (P<0.01) expression in all rapamycin-treated groups. No alteration was observed in 4E-BP1 gene expression among rapamycin-treated groups. Stretching increased gene expression of both NOS isoforms in skeletal muscle. Rapamycin treatment did not interfere with NOS gene expression (P<0.05). Cyclosporin-A treatment did not impair muscle growth induced by stretching but instead caused a marked slow-to-fast fiber shift in the soleus; this was attenuated by stretching. The data presented herein indicate that mTOR pathway is involved in skeletal muscle longitudinal growth. We gratefully acknowledge the financial support given by FAPESP.     

On the kinematics and efficiency of advective mixing during gastric digestion – A numerical analysis

The mixing performance of gastric contents during digestion is expected to have a major role on the rate and final bioavailability of nutrients within the body. The aim of this study was to characterize the ability of the human stomach to advect gastric contents with different rheological properties. The flow behavior of two Newtonian fluids (10⁻³ Pa s, 1 Pa s) and a pseudoplastic solution (K=0.223 Pa s^0.59) during gastric digestion were numerically characterized within a simplified 3D model of the stomach geometry and motility during the process (ANSYS-FLUENT). The advective performances of each of these gastric flows were determined by analyzing the spatial distribution and temporal history of their stretching abilities (Lagrangian analysis). Results illustrate the limited influence that large retropulsive and vortex structures have on the overall dynamics of gastric flows. Even within the distal region, more than 50% of the flow experienced velocity and shear values lower than 10% of their respective maximums. While chaotic, gastric advection was always relatively poor (with Lyapunov exponents an order of magnitude lower than those of a laminar stirred tank). Contrary to expectations, gastric rheology had only a minor role on the advective properties of the flow (particularly within the distal region). As viscosity increased above 1 St, the role of fluid viscosity became largely negligible. By characterizing the fluid dynamic and mixing conditions that develop during digestion, this work will inform the design of novel in vitro systems of enhanced biomechanical performance and facilitate a more accurate diagnosis of gastric digestion processes.     

Measurement of active muscle stiffness with and without the stretch reflex

The purpose of the present study was to evaluate active muscle stiffness with the stretch reflex according to changes (in 110-ms period after stretching) in torque and fascicle length during slower angular velocity (peak angular velocity of 100 deg·s⁻¹) in comparison with active muscle stiffness without the stretch reflex (in 60-ms period after stretching) during slower and faster (peak angular velocity of 250 deg·s⁻¹) angular velocities. Active muscle stiffness in the medial gastrocnemius muscle was calculated according to changes in estimated muscle force and fascicle length with slower and faster stretching during submaximal isometric contractions (10–90% maximal voluntary contractions). Active muscle stiffness significantly increased for both angular velocities and analyzed periods as torque levels exerted became higher. The effects of angular velocities and the interaction between angular velocities and torque levels were not significantly different between 250 deg·s⁻¹ (in 60-ms period after stretching) and 100 deg·s⁻¹ (in 110-ms period after stretching) conditions. The effects of the analyzed periods and the interaction between analyzed periods and torque levels were not significantly different between the analyzed periods (60-ms and 110-ms periods after stretching) for the 100 deg·s⁻¹ condition. Furthermore, active muscle stiffness measured during the same angular velocity had significant correlations between those calculated in the different analyzed periods, whereas those under 250 deg·s⁻¹ (60-ms period after stretching) did not correlate with those under 100 deg·s⁻¹ (110-ms period after stretching). These results suggest that active muscle stiffness is not influenced by the stretch reflex.     

2-Substituted 4-hydroxybutanamides as potential inhibitors of γ-aminobutyric acid transporters mGAT1–mGAT4: Synthesis and biological evaluation

A series of 2-substituted 4-hydroxybutanamide derivatives has been synthesized by the aminolysis of appropriate 2-substituted dihydrofuran-2(3H)-one derivatives with various substituted benzylamines. The final compounds have been evaluated for their capability of inhibiting the GABA transport proteins GAT1-4 stably expressed in HEK-239 cell lines. The pIC₅₀ values determined were in the range 4.21–5.14. Two compounds (16a and 16d), which displayed the most interesting profiles in in vitro tests, have also been subjected to further preliminary behavioral studies, evaluating their antinociceptive activity in hot-plate, writhing, and formalin tests. Their influence on motor coordination has also been assessed.     

Effects of ankle position during static stretching for the hamstrings on the decrease in passive stiffness

Static stretching is frequently performed to improve flexibility of the hamstrings, although the ankle position during hamstring stretching has not been fully investigated. We investigated the effects of ankle position during hamstring stretching on the decrease in passive stiffness. Fourteen healthy men performed static stretching for the hamstrings with the ankle dorsiflexed and plantar-flexed in a randomized order on different days. The hip was passively flexed to the maximum angle which could be tolerated without stretch pain with the knee fully extended; this was maintained for 5 min, with 1-min stretching performed in 5 sessions. Final angles and passive stiffness were measured before and after stretching. The final angle was defined as that formed by the tibia and horizontal plane when the knee was passively extended from hip and knee angles at 90° flexion to the maximum extension angle which could be tolerated without stretch pain. Passive stiffness was determined by the slope of torque–angle curve during the measurement of the final angle. The final angle significantly increased after stretching with the ankle dorsiflexed and plantar-flexed, whereas passive stiffness significantly decreased only after stretching with the ankle planter-flexed. The results suggest that passive stiffness decreases after stretching with the ankle planter-flexed but not after stretching with the ankle dorsiflexed, although the range of joint motion increases regardless of the ankle position during 5-min stretching for the hamstrings. These results indicate that static stretching should be performed with the ankle plantar-flexed when aiming to decrease passive stiffness of the hamstrings.     

X-Ray Studies on Crystalline Complexes Involving Amino Acids and Peptides XXXI. Effect of Chirality on Ionization State,Stoichiometry and Aggregation in the Complexes of Oxalic Acid with L-and DL-histidine

Abstract

Crystals of the oxalic acid complex of L-histidine (orthorhombic P2₁2₁2₁; a=5.535(4), b=6.809(4), c=26.878(3) Å) R= 3.6% for 1188 observed reflections) contain histidine molecules and semi-oxalate ions in the 1:1 ratio, while the ratio is 1:2 in the crystals of the DL-histidine complex (monoclinic P2₁ lc; a=6.750(7), b=10.139(2), c=19.352(2) Å, β= 90.8°; R= 3.7% for 3176 observed reflections). The histidine molecule in the latter has an unusual ionization state with positively charged amino and imidazole groups and a neutral carboxyl group. The molecule has the sterically least favourable allowed conformation with the side chain imidazole ring staggered between the α-amino and the α- carboxyl (carboxylate) groups, in both the structures. The unlike molecules aggregate into separate alternating layers in both of them. There are elements of similarity in the aggregation patterns in the semi-oxalate layers in the two complexes, but the patterns in the amino acid layers are entirely different. Interestingly, the crystal structure of L-histidine semi-oxalate has broad similarities with that of DL-histidine glycolate, demonstrating how broad features of aggregation could be retained inspite of changes in chirality and composition. The unusual ionization state of the amino acid molecule in the DL-histidine complex is reflected in a hitherto unobserved aggregation pattern in its crystal structure.     

A dystroglycan/plectin scaffold mediates mechanical pathway bifurcation in lung epithelial cells

In alveolar epithelial cells (AECs), the membrane-anchored proteoglycan dystroglycan (DG) is a mechanoreceptor that transmits mechanical stretch forces to activate independently the ERK1/2 and the adenosine 5'-monophosphate-activated protein kinase (AMPK) signaling cascades in a process called pathway bifurcation. We tested the hypothesis that the cytoskeleton cross-linker plectin, known to bind both DG and AMPK in muscle cells, acts as a scaffold to regulate DG-mediated mechanical stimulation and pathway bifurcation. We demonstrate that plectin and DG form a complex in AECs and that this complex interacts with ERK1/2 and AMPK. Plectin knockdown reduces DG interaction with AMPK but not with ERK1/2. Despite this, mechanoactivation of both signaling pathways is significantly attenuated in AECs deficient in plectin. Thus, DG has the dual role of mechanical receptor and scaffold for ERK1/2, whereas plectin acts as a scaffold for AMPK signaling but is also required for DG-mediated ERK1/2 activation. We conclude that the DG-plectin complex plays a central role in transmitting mechanical stress from the extracellular matrix to the cytoplasm.