Muscle Contractile Properties Research Articles

Maximal shortening velocity during plantar flexion: Effects of pre-activity and initial stretching state.

We investigated the effects of the initial length of the muscle-tendon unit (MTU) and muscle pre-activation on muscle-tendon interactions during plantarflexion performed at maximal velocity. Ultrasound images of gastrocnemius medialis were obtained on 11 participants in three conditions: (a) active plantarflexion performed at maximal velocity from three increasingly stretched positions (10°, 20°, and 30° dorsiflexion), (b) passive plantarflexion induced by a quick release of the ankle joint from the same three positions, and (c) pre-activation, which consisted of a maximal isometric contraction of the plantarflexors at 10° of dorsiflexion followed by a quick release of ankle joint. During the active condition at maximal velocity, initial MTU stretch positively influenced ankle joint velocity (+15.3%) and tendinous tissues shortening velocity (+37.6%) but not the shortening velocity peak value reached by muscle fascicle. The muscle fascicle was shortened during the passive condition; however, its shortening velocity never exceeded peak velocity measured in the active condition. Muscle pre-activation resulted in a considerable increase in ankle joint (+114.7%) and tendinous tissues velocities (+239.1%), although we observed a decrease in muscle fascicle shortening velocity. During active plantarflexion at maximal velocity, initial MTU length positively influences ankle joint velocity by increasing the contribution of tendinous tissues. Although greater initial stretch of the plantarflexors (ie, 30° dorsiflexion) increased the passive velocity of the fascicle during initial movement, its peak velocity was not affected. As muscle pre-activation prevented reaching the maximal muscle fascicle shortening velocity, this condition should be used to characterize tendinous tissues rather than muscle contractile properties.

Effect of Dietary Nitrate on Force Production and Sarcoplasmic Reticulum Ca<sup>2+</sup> Handling in Rat Fast-Twitch Muscles Following Eccentric Contraction

Impaired excitation-contraction coupling occurs in eccentric contraction (ECC)-induced damaged muscles. It has been suggested that sarcoplasmic reticulum (SR) is susceptible to damage in the overstretched regions possibly marking the basis of excitation-contraction coupling damage. Recent studies have shown that dietary nitrate supplementation enhances SR function in fast-twitch muscles. In this study, we aimed to investigate whether dietary nitrate supplementation can alleviate a decline in muscle contractile properties and SR function following ECC. To this end, force production, Ca2+ uptake, Ca2+ release, and Ca2+-ATPase activity of the SR were examined in rat fast-twitch muscles immediately following ECC for 200 repetitions. In comparison with contralateral resting muscles, nitrate supplementation for up to 3 days resulted in an obvious decline in force production. However, there were no differences in terms of force production between 6-day nitrate-treated and contralateral muscles. Similar to the observations regarding force production, the SR Ca2+ release rate changed from an obvious decrease following the 0- and 3-day dietary nitrate supplementation to no difference following the 6-day nitrate supplementation. In contrast, ECC decreased the Ca2+-ATPase activity and Ca2+ uptake rate, irrespective of the period of dietary nitrate supplementation. Overall, these results indicate that dietary nitrate supplementation can alleviate ECC-related decreases in force production mediated through inhibited reductions in the SR Ca2+ release function.

Castration induces satellite cell activation that contributes to skeletal muscle maintenance

Sarcopenia, the age-related loss of skeletal muscle, is a side effect of androgen deprivation therapy (ADT) for prostate cancer patients. Resident stem cells of skeletal muscle, satellite cells (SCs), are an essential source of progenitors for the growth and regeneration of skeletal muscle. Decreased androgen signaling and deficits in the number and function of SCs are features of aging. Although androgen signaling is known to regulate skeletal muscle, the cellular basis for ADT-induced exacerbation of sarcopenia is unknown. Furthermore, the consequences of androgen deprivation on SC fate in adult skeletal muscle remain largely unexplored. We examined SC fate in an androgen-deprived environment using immunofluorescence and fluorescence-activated cell sorting (FACS) with SC-specific markers in young castrated mice. To study the effects of androgen deprivation on SC function and skeletal muscle regenerative capacity, young castrated mice were subjected to experimental regenerative paradigms. SC-derived-cell contributions to skeletal muscle maintenance were examined in castrated Pax7CreER/+; ROSA26mTmG/+ mice. SCs were depleted in Pax7CreER/+; ROSA26DTA/+ mice to ascertain the consequences of SC ablation in sham and castrated skeletal muscles. Confocal immunofluorescence analysis of neuromuscular junctions (NMJs), and assessment of skeletal muscle physiology, contractile properties, and integrity were conducted. Castration led to SC activation, however this did not result in a decline in SC function or skeletal muscle regenerative capacity. Surprisingly, castration induced SC-dependent maintenance of young skeletal muscle. The functional dependence of skeletal muscles on SCs in young castrated mice was demonstrated by an increase in SC-derived-cell fusion within skeletal muscle fibers. SC depletion was associated with further atrophy and functional decline, as well as the induction of partial innervation and the loss of NMJ-associated myonuclei in skeletal muscles from castrated mice. The maintenance of skeletal muscles in young castrated mice relies on the cellular contributions of SCs. Considering the well-described age-related decline in SCs, the results in this study highlight the need to devise strategies that promote SC maintenance and activity to attenuate or reverse the progression of sarcopenia in elderly androgen-deprived individuals.

The mitochondrial metabolic reprogramming agent trimetazidine as an 'exercise mimetic' in cachectic C26-bearing mice.

BackgroundCancer cachexia is characterized by muscle depletion and exercise intolerance caused by an imbalance between protein synthesis and degradation and by impaired myogenesis. Myofibre metabolic efficiency is crucial so as to assure optimal muscle function. Some drugs are able to reprogram cell metabolism and, in some cases, to enhance metabolic efficiency. Based on these premises, we chose to investigate the ability of the metabolic modulator trimetazidine (TMZ) to counteract skeletal muscle dysfunctions and wasting occurring in cancer cachexia.MethodsFor this purpose, we used mice bearing the C26 colon carcinoma as a model of cancer cachexia. Mice received 5 mg/kg TMZ (i.p.) once a day for 12 consecutive days. A forelimb grip strength test was performed and tibialis anterior, and gastrocnemius muscles were excised for analysis. Ex vivo measurement of skeletal muscle contractile properties was also performed.ResultsOur data showed that TMZ induces some effects typically achieved through exercise, among which is grip strength increase, an enhanced fast‐to slow myofibre phenotype shift, reduced glycaemia, PGC1α up‐regulation, oxidative metabolism, and mitochondrial biogenesis. TMZ also partially restores the myofibre cross‐sectional area in C26‐bearing mice, while modulation of autophagy and apoptosis were excluded as mediators of TMZ effects.ConclusionsIn conclusion, our data show that TMZ acts like an ‘exercise mimetic’ and is able to enhance some mechanisms of adaptation to stress in cancer cachexia. This makes the modulation of the metabolism, and in particular TMZ, a suitable candidate for a therapeutic rehabilitative protocol design, particularly considering that TMZ has already been approved for clinical use.

Investigation of Spinal nerve Ligation Effect on Muscular Neurotrophin-4 Gene Expression in Male Wistar Rats

Introduction: Motor neurons in spinal cord dictate the structural and contractile properties of muscles. Damage to motor neurons change muscles gene expression pattern. Given that Neurotrophin-4 (NT-4) is required for survival and normal function of muscle fibers, the aim of present study is investigation effect of Decreased activity model as Spinal Nerve Ligation on muscular NT-4 gene expression. Materials & methods: Ten adult male wistar rats in the weight range of 250±20 gr randomly were divided into two groups including healthy control (C), Spinal nerve ligation (SNL). Over the six weeks after SNL, neuropathic pain behavior tests were conducted continually in groups. In the end of Sixth weeks, change of NT-4 gene expression in soleus muscle was measured with Real time technique. Findings: Behavioral tests demonstrated that spinal nerve ligation induce thermal Hyperalgesia and mechanical Allodynia in the SNL group which decreased pain threshold seen in allover period of study (P≤0.05). Also, compared to the C group, NT-4 gene expression in soleus muscle was higher in SNL group significantly (P≤0.05). Discussion & conclusions: The present study demonstrated that decreased activity in the form of SNL is associated with increased NT-4 gene expression in soleus muscle. However, the mechanisms and pathophysiologic issues of this increase are remaining elusive.

Effects of N-acetylcysteine on isolated skeletal muscle contractile properties after an acute bout of aerobic exercise

AimsThe current study tested the hypotheses that 1) an acute bout of aerobic exercise impairs isolated skeletal muscle contractile properties and 2) N-acetylcysteine (a thiol antioxidant; NAC) administration can restore the impaired muscle contractility after exercise. Main methodsAt rest or immediately after an acute bout of aerobic exercise, extensor digitorum longus (EDL) and soleus muscles from male Wistar rats were harvested for ex vivo skeletal muscle contraction experiments. Muscles from exercised animals were incubated in Krebs Ringer's buffer in absence or presence of 20mM of NAC. Force capacity and fatigue properties were evaluated. Key findingsExercised EDL and soleus displayed lower force production across various stimulation frequencies (p<0.001), indicating that skeletal muscle force production was impaired after an acute bout of exercise. However, NAC treatment restored the loss of force production in both EDL and soleus after fatiguing exercise (p<0.05). Additionally, NAC treatment increased relative force production at different time points during a fatigue-induced protocol, suggesting that NAC treatment mitigates fatigue induced by successive contractions. SignificanceNAC treatment improves force capacity and fatigue properties in ex vivo skeletal muscle from rats submitted to an acute bout of aerobic exercise.

Impact of Resistance Training on Skeletal Muscle Mitochondrial Biogenesis, Content, and Function.

Skeletal muscle metabolic and contractile properties are reliant on muscle mitochondrial and myofibrillar protein turnover. The turnover of these specific protein pools is compromised during disease, aging, and inactivity. Oppositely, exercise can accentuate muscle protein turnover, thereby counteracting decay in muscle function. According to a traditional consensus, endurance exercise is required to drive mitochondrial adaptations, while resistance exercise is required to drive myofibrillar adaptations. However, concurrent practice of traditional endurance exercise and resistance exercise regimens to achieve both types of muscle adaptations is time-consuming, motivationally demanding, and contended to entail practice at intensity levels, that may not comply with clinical settings. It is therefore of principle interest to identify effective, yet feasible, exercise strategies that may positively affect both mitochondrial and myofibrillar protein turnover. Recently, reports indicate that traditional high-load resistance exercise can stimulate muscle mitochondrial biogenesis and mitochondrial respiratory function. Moreover, fatiguing low-load resistance exercise has been shown capable of promoting muscle hypertrophy and expectedly entails greater metabolic stress to potentially enhance mitochondrial adaptations. Consequently, fatiguing low-load resistance exercise regimens may possess the ability to stimulate muscle mitochondrial adaptations without compromising muscle myofibrillar accretion. However, the exact ability of resistance exercise to drive mitochondrial adaptations is debatable, not least due to some methodological challenges. The current review therefore aims to address the evidence on the effects of resistance exercise on skeletal muscle mitochondrial biogenesis, content and function. In prolongation, a perspective is taken on the specific potential of low-load resistance exercise on promoting mitochondrial adaptations.

Correction: Tensiomyographic Assessment of Muscle Contractile Properties in 9- to 14-Year Old Children.

Correction: Tensiomyographic Assessment of Muscle Contractile Properties in 9- to 14-Year Old Children.

Skeletal muscle contractile properties in a novel murine model for limb girdle muscular dystrophy 2i.

Limb-girdle muscular dystrophy (LGMD) 2i results from mutations in fukutin-related protein and aberrant α-dystroglycan glycosylation. Although this significantly compromises muscle function and ambulation, the comprehensive characteristics of contractile dysfunction are unknown. Therefore, we quantified the in situ contractile properties of the medial gastrocnemius in young adult P448L mice, an affected muscle of a novel model of LGMD2i. Normalized maximal twitch force, tetanic force, and power were significantly smaller in P448L mice, compared with sex-matched, wild-type mice. These differences were consistent with the replacement of contractile fibers by passive tissue. The shape of the active force-length relationships were similar in both groups, regardless of sex, consistent with an intact sarcomeric structure in P448L mice. Passive force-length curves normalized to maximal isometric force were steeper in P448L mice, and passive elements contribute disproportionately more to total contractile force in P448L mice. Sex differences were mostly noted in the force-velocity curves, as normalized values for maximal and optimal velocities were significantly slower in P448L males, compared with wild-type, but not in P448L females. This suggests that the dystrophic phenotype, which may include possible changes in cross-bridge kinetics and fiber-type proportions, progresses more quickly in P448L males. These results together indicate that active force and power generation are compromised in both sexes of P448L mice, while passive forces increase. More importantly, the results identified several functional markers of disease pathophysiology that could aid in developing and assessment of novel therapeutics for LGMD2i and possibly other dystroglycanopathies as well. NEW & NOTEWORTHY Comprehensive assessments of muscle contractile function have, until now, never been performed in an animal model for any dystroglycanopathy. This study suggests that skeletal muscle contractile properties are significantly compromised in a recently developed model for limb-girdle muscular dystrophy 2i, the P448L mouse. It further identifies novel pathological markers of muscle function that are suitable for developing therapeutics and for better understanding of disease pathogenesis.

Filamin actin-binding and titin-binding fulfill distinct functions in Z-disc cohesion.

Many proteins contribute to the contractile properties of muscles, most notably myosin thick filaments, which are anchored at the M-line, and actin thin filaments, which are anchored at the Z-discs that border each sarcomere. In humans, mutations in the actin-binding protein Filamin-C result in myopathies, but the underlying molecular function is not well understood. Here we show using Drosophila indirect flight muscle that the filamin ortholog Cheerio in conjunction with the giant elastic protein titin plays a crucial role in keeping thin filaments stably anchored at the Z-disc. We identify the filamin domains required for interaction with the titin ortholog Sallimus, and we demonstrate a genetic interaction of filamin with titin and actin. Filamin mutants disrupting the actin- or the titin-binding domain display distinct phenotypes, with Z-discs breaking up in parallel or perpendicularly to the myofibril, respectively. Thus, Z-discs require filamin to withstand the strong contractile forces acting on them.

Tensiomyographic Assessment of Muscle Contractile Properties in 9- to 14-Year Old Children.

While there are numerous data on the skeletal muscle fiber type composition in adults, little is known about the changes in fiber type composition and contractile properties during maturational growth in children. Using noninvasive tensiomyography, we measured contraction time (Tc), an indirect estimate of the myosin heavy chain I (MHC-I) proportion, to assess the longitudinal changes of the biceps brachii (BB), biceps femois (BF), vastus lateralis (VL), and erector spinae (ES) muscles in 53 boys and 54 girls. The children were 9 years at the start of the study and returned for 5 follow-up measurements until the age of 14 years. The ES has the shortest and the BF has the longest Tc. The VL and ES of boys have shorter Tc than those of girls. When applying the relationship between proportion of MHC-I and Tc established in adults to children's TMG data, we found a slow-to-fast transition in the VL between, at least, the ages of 6 to 10 years, when it stabilized to adult proportions. Regular participation in sports was associated with a faster BF, but not in the VL. Our data represents a first non-invasive indication of the developmental changes in muscle fiber type composition in children.

POSTURAL MUSCLES WEAKNESS IN OLDER ADULTS WITH FALL HISTORY: A NEURAL OR A MECHANICAL DEFICIT?

AbstractThe decline in torque production of postural muscles during aging is considered as a key factor in the risk of falling. Recent works showed that the maximal torque of plantar flexor muscles (PF) was lower in older adults with recent fall history (OF) than in older non-fallers (ONF). The present study aimed to investigate the neural and mechanical factors associated with the lower maximal PF torque production in OF. Fifteen young adults (YA) (22 ± 4 years), 15 OF (84 ± 4 years) and 15 ONF (83 ± 4 years) were included in this study. Torque and electromyographic activity of soleus, gastrocnemii and tibialis anterior (TA coactivation) muscles were recorded during maximal voluntary contractions of the PF. Electrical nerve stimulation was used to assess the voluntary activation level (neural factor) during maximal plantar-flexion and the muscle contractile properties (mechanical factor). The results showed that the maximal PF torque was significantly lower (P<0.05) for OF (51 ± 12 Nm) than ONF (70 ± 15 Nm) and YA (119 ± 40 Nm). The voluntary activation level was lower (P<0.05) for OF (73 ± 18%) than ONF (82 ± 19%) and YA (90 ± 14%). A similar trend was observed for the maximal PF electromyographic activity. No difference in TA coactivation was reported among the three groups. While age affected the mechanical properties of ankle muscles (P<0.001), no difference was observed between ONF (13 ± 3 Nm) and OF (12 ± 3 Nm).These results suggest that the alteration of muscle force production observed in OF could be mainly related to a deficit in muscle activation capability rather than reduced muscle contractile properties.

Tensiomyographic Markers Are Not Sensitive for Monitoring Muscle Fatigue in Elite Youth Athletes: A Pilot Study.

Objective: Tensiomyography (TMG) is an indirect measure of a muscle's contractile properties and has the potential as a technique for detecting exercise-induced skeletal muscle fatigue. Therefore, the aim of this study was to assess the sensitivity of tensiomyographic markers to identify reduced muscular performance in elite youth athletes.Methods: Fourteen male junior tennis players (age: 14.9 ± 1.2 years) with an international (International Tennis Federation) ranking position participated in this pre-post single group trial. They completed a 4-day high-intensity interval training (HIT) microcycle, which was composed of seven training sessions. TMG markers; countermovement jump (CMJ) performance (criterion measure of fatigue); delayed onset muscle soreness; and perceived recovery and stress were measured 24 h before and after the training program. The TMG measures included maximal radial deformation of the rectus femoris muscle belly (Dm), contraction time between 10 and 90% Dm (Tc) and the rate of deformation until 10% (V10) and 90% Dm (V90), respectively. Diagnostic characteristics were assessed with a receiver-operating curve (ROC) analysis and a contingency table, in which the area under the curve (AUC), Youden's index, sensitivity, specificity, and the diagnostic effectiveness (DE) of TMG measures were reported. A minimum AUC of 0.70 and a lower confidence interval (CI) >0.50 classified “good” diagnostic markers to assess performance changes.Results: Twenty-four hours after the microcycle, CMJ performance was observed to be significantly (p < 0.001) reduced (Effect Size [ES] = −0.68), and DOMS (ES = 3.62) as well as perceived stress were significantly (p < 0.001) increased. In contrast, Dm (ES = −0.35), Tc (ES = 0.04), V10 (ES = −0.32), and V90 (ES = −0.33) remained unchanged (p > 0.05) throughout the study. ROC analysis and the data derived from the contingency table revealed that none of the tensiomyographic markers were effective diagnostic tools for detecting impaired muscular performance in elite youth athletes (AUC, 95% CI, DE%; Dm: 0.46, 0.15–0.77, 35.7%; Tc: 0.29, 0.03–0.59, 35.7%; V10: 0.71, 0.27–1.00, 35.7%; V90: 0.37, 0.10–0.65, 35.7%).Conclusion: The tensiomyographic parameters that were assessed in this study were not sensitive enough to detect muscular performance changes in elite youth athletes.However, due to the preliminary nature of the study, further research is needed to investigate the sensitivity of TMG in this population.

AAV9 delivered bispecific nanobody attenuates amyloid burden in the gelsolin amyloidosis mouse model.

Gelsolin amyloidosis is a dominantly inherited, incurable type of amyloidosis. A single point mutation in the gelsolin gene (G654A is most common) results in the loss of a Ca2+ binding site in the second gelsolin domain. Consequently, this domain partly unfolds and exposes an otherwise buried furin cleavage site at the surface. During secretion of mutant plasma gelsolin consecutive cleavage by furin and MT1-MMP results in the production of 8 and 5 kDa amyloidogenic peptides. Nanobodies that are able to (partly) inhibit furin or MT1-MMP proteolysis have previously been reported. In this study, the nanobodies have been combined into a single bispecific format able to simultaneously shield mutant plasma gelsolin from intracellular furin and extracellular MT1-MMP activity. We report the successful in vivo expression of this bispecific nanobody following adeno-associated virus serotype 9 gene therapy in gelsolin amyloidosis mice. Using SPECT/CT and immunohistochemistry, a reduction in gelsolin amyloid burden was detected which translated into improved muscle contractile properties. We conclude that a nanobody-based gene therapy using adeno-associated viruses shows great potential as a novel strategy in gelsolin amyloidosis and potentially other amyloid diseases.

Skeletal Muscle Contraction Time and Tone Decrease After 8 Weeks of Plyometric Training.

The aim of the study was to examine whether an improvement in jumping performance after 8 weeks of plyometric training (PT) runs in parallel with changes in lower-limb skeletal muscle contractile properties. Using noninvasive tensiomyography (TMG), we assessed contraction time (Tc) and the maximal amplitude of radial displacement (Dm) in 20 subjects (50% men; age 22.4 ± 4.7 years of age), randomly divided in PT group (N = 10; PLYO) and a control group (N = 10; CTRL). The PLYO performed 8 weeks of PT. Tensiomyography was measured in 5 leg skeletal muscles: vastus lateralis (VL), biceps femoris (BF), tibialis anterior (TA), gastrocnemius medialis (GM), and gastrocnemius lateralis (GL). Additionally, we evaluated countermovement jump (CMJ) height improvement on a ground force plate. Assessments were repeated before and after PT. After 8 weeks of PT, CMJ height increased by 12.2% in PLYO (p = 0.015), but not in CRTL. Contraction time, which is related to myosin heavy-chain type 1 (MHC-1) proportion, decreased in VL (-8.7%; p < 0.001), BF (-26.7%; p = 0.032), TA (-32.9%; p = 0.004), and GL (-25.8%; p = 0.044), but not in GM (-8.1%; p = 0.158). The estimated VL MHC-1 proportion decreased by -8.2% (p = 0.041). The maximal amplitude of radial displacement, inversely related to muscle tone, decreased in BF (-26.5%; p = 0.032), GM (-14.9%; p = 0.017), GL (-31.5%; p = 0.017), but not in TA (-16.8%; p = 0.113) and VL (-6.0%; p = 0.654). After PT, jumping performance increased, which was paralleled by decreased Tc and decreased muscle tone. Additionally, adaptations to contractile properties were muscle specific, which is important for future studies. It seems that adjustments were dose dependent, being higher in muscles with lower habitual load.

Acute Effects Of Cooling On Muscle Contractile Properties

In order to complement sport training and to induce regeneration processes of muscle, ice pack application (IPA) is often used by athletes. Physiological mechanisms are relatively well investigated while there is faintly research aimed at investigating muscle contractile properties (MCP) after IPA treatment. To test the acute effects of IPA cooling on MCP, we used tensiomyography (TMG), as a non-invasive and selective method of neuromuscular assessment. PURPOSE: To investigate the influence of IPA on MCP by TMG method. METHODS: Sixteen healthy participants (50% males; 19-20 yr) participated in this study. Tensiomyographic assessment was performed before and immediately after 15 minutes of IPA treatment on vastus medialis. From tensiomyographic response we extracted and analysed delay time (Td), contraction time (Tc), sustain time (Ts), half-relaxation time (Tr), and maximal displacement/Dm). RESULTS: After IPA we found that Td, Tc, Ts and Tr values increased (p< 0.010) by 6.2% (ES= 2.61), 6.0% (ES= 2.06), 29.7% (ES= 1.99), and 26.6% (ES= 2.01), respectively, while Dm decreased (p = 0.001) by 12.7% (ES=2.61). CONCLUSION: Our results suggest that IPA treatment significantly altered MCP after only 15 minutes of exposure. This plays an important role in skeletal muscle behavior immediately after cooling procedures and should be taken into account when planning training or rehabilitation programs.

Impact of Aspartate and Sodium Bicarbonate Supplementation Upon Muscle Contractile Properties within Trained Men

Impact of Aspartate and Sodium Bicarbonate Supplementation Upon Muscle Contractile Properties within Trained Men

Effect of acute peritonitis on rocuronium-induced intraperitoneal pressure reduction and the uptake function of the sarcoplasmic reticulum.

Previous studies have reported the incomplete relaxation effect of neuromuscular blockers on skeletal muscles in acute peritonitis (AP) and other inflammatory processes; however, the underlying mechanisms responsible for this effect have not yet been satisfactorily identified. The impaired removal of cytosolic Ca2+ through sarcoendoplasmic Ca2+-ATPase (SERCA) and defects in sarcoplasmic reticulum (SR) Ca2+ uptake are the major contributing factors to diastolic dysfunction. Previous studies on the effects of neuromuscular blockers have primarily focused on neuromuscular transmission. Because of the reduced calcium uptake in the SR itself, even when neuromuscular transmission is fully blocked, the muscle is not able to relax effectively. In the present study, the impact of AP on rocuronium-induced intraperitoneal pressure reduction and rectus abdominal muscle relaxation, and SERCA uptake function was investigated. AP was induced via gastric perforation and changes in the intraperitoneal pressure before and after the administration of rocuronium were recorded. Muscle contractile properties, uptake and release functions and SERCA activity in the rectus abdominal muscles of AP model rats were measured. The half-relaxation time in the AP group was significantly prolonged compared with that in the control group (P<0.01). The peak rate of SR Ca2+ uptake for whole muscle homogenates was significantly reduced (P<0.05) in AP model rats without reduction of the rate of Ca2+ release evoked through AgNO3. In conclusion, gastric perforation-induced AP attenuates the intraperitoneal pressure-reducing effect of rocuronium, and AP induces diastolic dysfunction of the rectus abdominal muscle. The SR Ca2+-ATPase uptake rate was also reduced by AP.

Tensiomyography, sonoelastography, and mechanosensitivity differences between active, latent, and control low back myofascial trigger points: A cross-sectional study.

The myofascial pain syndrome (MPS) is considered the most common musculoskeletal condition. The lumbopelvic pain (LPP) is established as one of the most prevalent musculoskeletal disorders. Nevertheless, previous research has not yet studied the contractibility changes by tensiomyography between myofascial trigger point (MTrP) types and normal tissue. Therefore, the aim of this study was to determine the tensiomyography, sonoelastography, and pressure pain threshold (PPT) differences between the palpation area of active and latent MTrPs with regards to control points in the lumbar erector spinae muscles of subjects with LPP. A cross-sectional descriptive study was performed. A convenience sample of 60 points (20 active MTrPs, 20 latent MTrPs, and 20 control points) was registered bilaterally in the lumbar erector spinae muscles from subjects with nonspecific LPP. The palpation order of active MTrPs, latent MTrPs, or control points was randomized for each side. The outcome assessors were blinded to the order or point type. The outcome measurements order for each point was sonoelastography manual strain index, tensiomyography, and PPT, separated by 15 minutes. Five contractile objective parameters were: maximal radial displacement (Dm), contraction time (Tc), sustain time (Ts), delay time (Td), and half-relaxation time (Tr). Tensiomyography parameters did not show any statistically significant difference (P > 0.05) between active MTrPs, latent MTrPs, and control points. Nevertheless, PPT and sonoelastography showed statistically significant differences (P < 0.05) between all point types, except for active and latent MTrPs PPT comparison (P = 0.091). Regarding the active MTrPs, a moderate positive correlation was observed between PPT and Dm (P = 0.047; τB = 0.450). Considering the control points, a moderate positive correlation was shown between sonoelastography and Td (P = 0.044; τB = 0.328). The tensiomyography contractile properties did not seem to show differences, while the sonoelastography and mechanosensitivity presented a higher stiffness and a lower PPT, respectively, between the palpation area of active and latent MTrPs with regards to control points in the lumbar erector spinae muscles of subjects with LPP. Considering the correlations, further research is needed regarding the muscle contractile properties modifications under MPS treatments, especially Dm in active MTrPs and Td in normal sites.

AAV9 delivered bispecific nanobody attenuates amyloid burden in the gelsolin amyloidosis mouse model.

Gelsolin amyloidosis is a dominantly inherited, incurable type of amyloidosis. A single point mutation in the gelsolin gene (G654A is most common) results in the loss of a Ca2+ binding site in the second gelsolin domain. Consequently, this domain partly unfolds and exposes an otherwise buried furin cleavage site at the surface. During secretion of mutant plasma gelsolin consecutive cleavage by furin and MT1-MMP results in the production of 8 and 5 kDa amyloidogenic peptides. Nanobodies that are able to (partly) inhibit furin or MT1-MMP proteolysis have previously been reported. In this study, the nanobodies have been combined into a single bispecific format able to simultaneously shield mutant plasma gelsolin from intracellular furin and extracellular MT1-MMP activity. We report the successful in vivo expression of this bispecific nanobody following adeno-associated virus serotype 9 gene therapy in gelsolin amyloidosis mice. Using SPECT/CT and immunohistochemistry, a reduction in gelsolin amyloid burden was detected which translated into improved muscle contractile properties. We conclude that a nanobody-based gene therapy using adeno-associated viruses shows great potential as a novel strategy in gelsolin amyloidosis and potentially other amyloid diseases.