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1.
J Physiol Sci ; 74(1): 26, 2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38654149

RESUMEN

Purines such as ATP are regulatory transmitters in motility of the gastrointestinal tract. The aims of this study were to propose functional roles of purinergic regulation of esophageal motility. An isolated segment of the rat esophagus was placed in an organ bath, and mechanical responses were recorded using a force transducer. Exogenous application of ATP (10-100 µM) evoked relaxation of the esophageal smooth muscle in a longitudinal direction under the condition of carbachol (1 µM) -induced precontraction. Pretreatment with a non-selective P2 receptor antagonist, suramin (500 µM), and a P2Y receptor antagonist, cibacron blue F3GA (200 µM), inhibited the ATP (100 µM) -induced relaxation, but a P2X receptor antagonist, pyridoxal phosphate-6-azophenyl-2,4-disulfonic acid (50 µM), did not affect it. A blocker of ATP-dependent potassium channels (KATP channels), glibenclamide (200 µM), inhibited the ATP-induced relaxation and application of an opener of KATP channels, nicorandil (50 µM), produced relaxation. The findings suggest that ATP is involved in inhibitory regulation of the longitudinal smooth muscle in the muscularis mucosae of the rat esophagus via activation of P2Y receptors and then opening of KATP channels.


Asunto(s)
Adenosina Trifosfato , Esófago , Canales KATP , Músculo Liso , Receptores Purinérgicos P2Y , Animales , Ratas , Músculo Liso/efectos de los fármacos , Músculo Liso/fisiología , Músculo Liso/metabolismo , Masculino , Receptores Purinérgicos P2Y/metabolismo , Esófago/efectos de los fármacos , Esófago/fisiología , Adenosina Trifosfato/metabolismo , Adenosina Trifosfato/farmacología , Canales KATP/metabolismo , Relajación Muscular/efectos de los fármacos , Relajación Muscular/fisiología , Ratas Wistar , Contracción Muscular/efectos de los fármacos , Contracción Muscular/fisiología , Antagonistas del Receptor Purinérgico P2Y/farmacología , Motilidad Gastrointestinal/efectos de los fármacos , Motilidad Gastrointestinal/fisiología , Ratas Sprague-Dawley
2.
Sci Rep ; 14(1): 9063, 2024 04 20.
Artículo en Inglés | MEDLINE | ID: mdl-38643221

RESUMEN

Vaginal laxity (VL) is a common condition among multiparous women, especially those who have delivered vaginally. Since pelvic floor muscles (PFMs) work synergistically with other core muscles, physical therapy protocols that aim to treat VL should train the PFMs in combination with other core muscles. To investigate the activity of core muscles in multiparous women with and without VL, and its relation to sexual function. An observational, cross-sectional study. The study included 100 multiparous women, who were divided into two groups according to their scores on the vaginal laxity questionnaire (VLQ). Women who scored between 1 and 3 on the VLQ were categorized as having VL (n = 48), while those who scored between 5 and 7 were placed in the control group (n = 52). The primary outcomes were PFM displacement, diaphragmatic excursion, transversus abdominis activation ratio, and lumbar multifidus thickness measured by ultrasound imaging. The secondary outcome was sexual functioning, evaluated using the Arabic female sexual function index (ArFSFI). The VL group had significantly lower PFM displacement (mean difference (MD) - 0.42; 95% confidence interval (CI) - 0.49 to - 0.33; p = 0.001), diaphragmatic excursion (MD - 2.75; 95% CI - 2.95 to - 2.55; p = 0.001), lumbar multifidus thickness (MD - 10.08; 95% CI - 14.32 to - 5.82; p = 0.02), and ArFSFI scores (MD - 9.2; 95% CI - 10.59 to - 7.81; p = 0.001) in comparison to the control group (p < 0.05). Nevertheless, the transversus abdominis activation ratio demonstrated no significant difference between the two groups (MD 0.06; 95% CI - 0.05 to 0.17; p = 0.33). Multiparous women with VL had significantly lower PFM displacement, diaphragmatic excursion, lumbar multifidus thickness, and sexual function index scores than women in the control group. The only exception was transversus abdominis activation, which did not differ significantly between the VL and control groups.


Asunto(s)
Músculos Abdominales , Diafragma Pélvico , Embarazo , Humanos , Femenino , Estudios Transversales , Diafragma Pélvico/fisiología , Músculos Abdominales/diagnóstico por imagen , Músculos Abdominales/fisiología , Contracción Muscular/fisiología , Paridad , Ultrasonografía/métodos
3.
Methods Mol Biol ; 2757: 315-359, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38668975

RESUMEN

Unlike in the Cnidaria, where muscle cells are coupled together into an epithelium, ctenophore muscles are single, elongated, intramesogleal structures resembling vertebrate smooth muscle. Under voltage-clamp, these fibers can be separated into different classes with different sets of membrane ion channels. The ion channel makeup is related to the muscle's anatomical position and specific function. For example, Beroe ovata radial fibers, which are responsible for maintaining the rigidity of the body wall, generate sequences of brief action potentials whereas longitudinal fibers, which are concerned with mouth opening and body flexions, often produce single longer duration action potentials.Beroe muscle contractions depend on the influx of Ca2+. During an action potential the inward current is carried by Ca2+, and the increase in intracellular Ca2+ concentration generated can be monitored in FLUO-3-loaded cells. Confocal microscopy in line scan mode shows that the Ca2+ spreads from the outer membrane into the core of the fiber and is cleared from there relatively slowly. The rise in intracellular Ca2+ is linked to an increase in a Ca2+-activated K+ conductance (KCa), which can also be elicited by iontophoretic Ca2+ injection. Near the cell membrane, Ca2+ clearance monitored using FLUO3, matches the decline in the KCa conductance. For light loads, Ca2+ is cleared rapidly, but this fast system is insufficient when Ca2+ influx is maintained. Action potential frequency may be regulated by the slowly developing KCa conductance.


Asunto(s)
Calcio , Ctenóforos , Músculo Liso , Animales , Músculo Liso/fisiología , Músculo Liso/metabolismo , Calcio/metabolismo , Ctenóforos/fisiología , Técnicas de Placa-Clamp/métodos , Potenciales de Acción/fisiología , Contracción Muscular/fisiología , Fenómenos Electrofisiológicos , Electrofisiología/métodos , Microscopía Confocal
4.
BMC Geriatr ; 24(1): 308, 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38565979

RESUMEN

BACKGROUND: The postural control and abdominal muscles' automatic activity were found to be impaired in subjects with low back pain (LBP) during static activities. However, the studies are predominantly conducted on younger adults and a limited number of studies have evaluated abdominal muscles' automatic activity during dynamic standing activities in subjects with LBP. The present study investigated the automatic activity of abdominal muscles during stable and unstable standing postural tasks in older adults with and without LBP. METHODS: Twenty subjects with and 20 subjects without LBP were included. The thickness of the transversus abdominis (TrA), internal oblique (IO), and external oblique (EO) muscles was measured during rest (in supine), static, and dynamic standing postural tasks. To estimate automatic muscle activity, each muscle's thickness during a standing task was normalized to its thickness during the rest. Standing postural tasks were performed using the Biodex Balance System. RESULTS: The mixed-model analysis of variance revealed that task dynamicity significantly affected thickness change only in the TrA muscle (P = 0.02), but the main effect for the group and the interaction were not significantly different (P > 0.05). There were no significant main effects of the group, task dynamicity, or their interaction for the IO and EO muscles (P > 0.05). During dynamic standing, only the TrA muscle in the control group showed greater thickness changes than during the static standing task (P < 0.05). CONCLUSIONS: Standing on a dynamic level increased the automatic activity of the TrA muscle in participants without LBP compared to standing on a static level. Further research is required to investigate the effects of TrA muscle training during standing on dynamic surfaces for the treatment of older adults with LBP.


Asunto(s)
Dolor de la Región Lumbar , Humanos , Anciano , Dolor de la Región Lumbar/diagnóstico , Estudios Transversales , Contracción Muscular/fisiología , Músculos Abdominales/diagnóstico por imagen , Músculos Abdominales/fisiología , Posición de Pie , Ultrasonografía
5.
J Physiol Sci ; 74(1): 25, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38622533

RESUMEN

The purpose of this study was the detection and characterization of synergistic muscle activity. Using T2-map MRI, T2 values for 10 forearm muscles in 11 healthy adult volunteers were obtained in the resting state and after isotonic forearm supination and pronation exercises with the elbow extended. T2 was normalized by Z = (T2e-T2r)/SDr, where T2e was T2 after exercise, while T2r and SDr were the reference values of 34 ms and 3 ms, respectively. Using the cumulative frequency curves of Z values (CFZ), we detected 2 and 3 synergistic muscles for supination and pronation, respectively, and divided these into 2 types, one activated by exercise strength dependently, and the other, independent of exercise strength, activated by only a smaller fraction of the participants. We also detected co-contraction for the supination. Thus, CFZ is a useful visualization tool to detect and characterize not only synergistic muscle, but also co-contraction muscle.


Asunto(s)
Antebrazo , Músculo Esquelético , Adulto , Humanos , Músculo Esquelético/diagnóstico por imagen , Músculo Esquelético/fisiología , Codo/fisiología , Contracción Muscular/fisiología , Imagen por Resonancia Magnética
6.
J Biomech ; 167: 112089, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38608614

RESUMEN

Skeletal muscles are complex structures with nonlinear constitutive properties. This complexity often requires finite element (FE) modeling to better understand muscle behavior and response to activation, especially the fiber strain distributions that can be difficult to measure in vivo. However, many FE muscle models designed to study fiber strain do not include force-velocity behavior. To investigate force-velocity property impact on strain distributions within skeletal muscle, we modified a muscle constitutive model with active and passive force-length properties to include force-velocity properties. We implemented the new constitutive model as a plugin for the FE software FEBio and applied it to four geometries: 1) a single element, 2) a multiple-element model representing a single fiber, 3) a model of tapering fibers, and 4) a model representing the bicep femoris long head (BFLH) morphology. Maximum fiber velocity and boundary conditions of the finite element models were varied to test their influence on fiber strain distribution. We found that force-velocity properties in the constitutive model behaved as expected for the single element and multi-element conditions. In the tapered fiber models, fiber strain distributions were impacted by changes in maximum fiber velocity; the range of strains increased with maximum fiber velocity, which was most noted in isometric contraction simulations. In the BFLH model, maximum fiber velocity had minimal impact on strain distributions, even in the context of sprinting. Taken together, the combination of muscle model geometry, activation, and displacement parameters play a critical part in determining the magnitude of impact of force-velocity on strain distribution.


Asunto(s)
Músculos Isquiosurales , Contracción Muscular , Contracción Muscular/fisiología , Simulación por Computador , Músculo Esquelético/fisiología , Contracción Isométrica/fisiología , Fibras Musculares Esqueléticas/fisiología , Modelos Biológicos
7.
J Biomech Eng ; 146(9)2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-38558115

RESUMEN

A previously developed model of a lymphatic vessel as a chain of lymphangions was investigated to determine whether lymphangions of unequal length reduce pumping relative to a similar chain of equal-length ones. The model incorporates passive elastic and active contractile properties taken from ex vivo measurements, and intravascular lymphatic valves as transvalvular pressure-dependent resistances to flow with hysteresis and transmural pressure-dependent bias to the open state as observed experimentally. Coordination of lymphangion contractions is managed by marrying an autonomous transmural pressure-dependent pacemaker for each lymphangion with bidirectional transmission of activation signals between lymphangions, qualitatively matching empirical observations. With eight lymphangions as used here and many nonlinear constraints, the model is capable of complex outcomes. The expected flow-rate advantage conferred by longer lymphangions everywhere was confirmed. However, the anticipated advantage of uniform lymphangions over those of unequal length, compared in chains of equal overall length, was not found. A wide variety of dynamical outcomes was observed, with the most powerful determinant being the adverse pressure difference, rather than the arrangement of long and short lymphangions. This work suggests that the wide variation in lymphangion length which is commonly observed in collecting lymphatic vessels does not confer disadvantage in pumping lymph.


Asunto(s)
Vasos Linfáticos , Modelos Biológicos , Sistema Linfático/fisiología , Vasos Linfáticos/fisiología , Linfa/fisiología , Presión , Contracción Muscular
8.
J Exp Biol ; 227(7)2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38563308

RESUMEN

Vocalisations play a key role in the communication behaviour of many vertebrates. Vocal production requires extremely precise motor control, which is executed by superfast vocal muscles that can operate at cycle frequencies over 100 Hz and up to 250 Hz. The mechanical performance of these muscles has been quantified with isometric performance and the workloop technique, but owing to methodological limitations we lack a key muscle property characterising muscle performance, the force-velocity relationship. Here, we quantified the force-velocity relationship in zebra finch superfast syringeal muscles using the isovelocity technique and tested whether the maximal shortening velocity is different between males and females. We show that syringeal muscles exhibit high maximal shortening velocities of 25L0 s-1 at 30°C. Using Q10-based extrapolation, we estimate they can reach 37-42L0 s-1 on average at body temperature, exceeding other vocal and non-avian skeletal muscles. The increased speed does not adequately compensate for reduced force, which results in low power output. This further highlights the importance of high-frequency operation in these muscles. Furthermore, we show that isometric properties positively correlate with maximal shortening velocities. Although male and female muscles differ in isometric force development rates, maximal shortening velocity is not sex dependent. We also show that cyclical methods to measure force-length properties used in laryngeal studies give the same result as conventional stepwise methodologies, suggesting either approach is appropriate. We argue that vocal behaviour may be affected by the high thermal dependence of superfast vocal muscle performance.


Asunto(s)
Pinzones , Laringe , Animales , Femenino , Masculino , Músculo Esquelético/fisiología , Pinzones/fisiología , Contracción Muscular/fisiología
9.
PLoS One ; 19(4): e0298958, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38564497

RESUMEN

Mental fatigue is common in society, but its effects on force production capacities remain unclear. This study aimed to investigate the impact of mental fatigue on maximal force production, rate of force development-scaling factor (RFD-SF), and force steadiness during handgrip contractions. Fourteen participants performed two randomized sessions, during which they either carried out a cognitively demanding task (i.e., a visual attention task) or a cognitively nondemanding task (i.e., documentary watching for 62 min). The mental fatigue was evaluated subjectively and objectively (performances and electroencephalography). Maximal voluntary contraction (MVC) force, RFD-SF, and force steadiness (i.e., force coefficient of variation at submaximal intensities; 25, 50, and 75% of MVC) were recorded before and after both tasks. The feeling of mental fatigue was much higher after completing the cognitively demanding task than after documentary watching (p < .001). During the cognitively demanding task, mental fatigue was evidenced by increased errors, missed trials, and decreased N100 amplitude over time. While no effect was reported on force steadiness, both tasks induced a decrease in MVC (p = .040), a force RFD-SF lower slope (p = .011), and a reduction in the coefficient of determination (p = .011). Nevertheless, these effects were not explicitly linked to mental fatigue since they appeared both after the mentally fatiguing task and after watching the documentary. The study highlights the importance of considering cognitive engagement and mental load when optimizing motor performance to mitigate adverse effects and improve force production capacities.


Asunto(s)
Fuerza de la Mano , Fatiga Muscular , Humanos , Electromiografía , Mano , Factores de Tiempo , Músculo Esquelético , Contracción Isométrica , Contracción Muscular , Fatiga Mental
10.
Sci Transl Med ; 16(741): eadg2841, 2024 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-38569017

RESUMEN

Troponin I (TnI) regulates thin filament activation and muscle contraction. Two isoforms, TnI-fast (TNNI2) and TnI-slow (TNNI1), are predominantly expressed in fast- and slow-twitch myofibers, respectively. TNNI2 variants are a rare cause of arthrogryposis, whereas TNNI1 variants have not been conclusively established to cause skeletal myopathy. We identified recessive loss-of-function TNNI1 variants as well as dominant gain-of-function TNNI1 variants as a cause of muscle disease, each with distinct physiological consequences and disease mechanisms. We identified three families with biallelic TNNI1 variants (F1: p.R14H/c.190-9G>A, F2 and F3: homozygous p.R14C), resulting in loss of function, manifesting with early-onset progressive muscle weakness and rod formation on histology. We also identified two families with a dominantly acting heterozygous TNNI1 variant (F4: p.R174Q and F5: p.K176del), resulting in gain of function, manifesting with muscle cramping, myalgias, and rod formation in F5. In zebrafish, TnI proteins with either of the missense variants (p.R14H; p.R174Q) incorporated into thin filaments. Molecular dynamics simulations suggested that the loss-of-function p.R14H variant decouples TnI from TnC, which was supported by functional studies showing a reduced force response of sarcomeres to submaximal [Ca2+] in patient myofibers. This contractile deficit could be reversed by a slow skeletal muscle troponin activator. In contrast, patient myofibers with the gain-of-function p.R174Q variant showed an increased force to submaximal [Ca2+], which was reversed by the small-molecule drug mavacamten. Our findings demonstrated that TNNI1 variants can cause muscle disease with variant-specific pathomechanisms, manifesting as either a hypo- or a hypercontractile phenotype, suggesting rational therapeutic strategies for each mechanism.


Asunto(s)
Enfermedades Musculares , Sarcómeros , Animales , Humanos , Calcio/metabolismo , Contracción Muscular , Músculo Esquelético/metabolismo , Enfermedades Musculares/genética , Sarcómeros/metabolismo , Troponina I/genética , Troponina I/metabolismo , Pez Cebra/metabolismo
11.
BMC Womens Health ; 24(1): 219, 2024 Apr 04.
Artículo en Inglés | MEDLINE | ID: mdl-38575899

RESUMEN

INTRODUCTION: Non-invasive biofeedback of pelvic floor muscle training (PFMT) is required for continuous training in home care. Therefore, we considered self-performed ultrasound (US) in adult women with a handheld US device applied to the bladder. However, US images are difficult to read and require assistance when using US at home. In this study, we aimed to develop an algorithm for the automatic evaluation of pelvic floor muscle (PFM) contraction using self-performed bladder US videos to verify whether it is possible to automatically determine PFM contraction from US videos. METHODS: Women aged ≥ 20 years were recruited from the outpatient Urology and Gynecology departments of a general hospital or through snowball sampling. The researcher supported the participants in their self-performed bladder US and videos were obtained several times during PFMT. The US videos obtained were used to develop an automatic evaluation algorithm. Supervised machine learning was then performed using expert PFM contraction classifications as ground truth data. Time-series features were generated from the x- and y-coordinate values of the bladder area including the bladder base. The final model was evaluated for accuracy, area under the curve (AUC), recall, precision, and F1. The contribution of each feature variable to the classification ability of the model was estimated. RESULTS: The 1144 videos obtained from 56 participants were analyzed. We split the data into training and test sets with 7894 time series features. A light gradient boosting machine model (Light GBM) was selected, and the final model resulted in an accuracy of 0.73, AUC = 0.91, recall = 0.66, precision = 0.73, and F1 = 0.73. Movement of the y-coordinate of the bladder base was shown as the most important. CONCLUSION: This study showed that automated classification of PFM contraction from self-performed US videos is possible with high accuracy.


Asunto(s)
Contracción Muscular , Diafragma Pélvico , Adulto , Femenino , Humanos , Diafragma Pélvico/diagnóstico por imagen , Diafragma Pélvico/fisiología , Contracción Muscular/fisiología , Vejiga Urinaria/diagnóstico por imagen , Biorretroalimentación Psicológica/métodos , Ultrasonografía
12.
J Neuroeng Rehabil ; 21(1): 47, 2024 04 04.
Artículo en Inglés | MEDLINE | ID: mdl-38575926

RESUMEN

Decoding movement intentions from motor unit (MU) activities to represent neural drive information plays a central role in establishing neural interfaces, but there remains a great challenge for obtaining precise MU activities during sustained muscle contractions. In this paper, we presented an online muscle force prediction method driven by individual MU activities that were decomposed from prolonged surface electromyogram (SEMG) signals in real time. In the training stage of the proposed method, a set of separation vectors was initialized for decomposing MU activities. After transferring each decomposed MU activity into a twitch force train according to its action potential waveform, a neural network was designed and trained for predicting muscle force. In the subsequent online stage, a practical double-thread-parallel algorithm was developed. One frontend thread predicted the muscle force in real time utilizing the trained network and the other backend thread simultaneously updated the separation vectors. To assess the performance of the proposed method, SEMG signals were recorded from the abductor pollicis brevis muscles of eight subjects and the contraction force was simultaneously collected. With the update procedure in the backend thread, the force prediction performance of the proposed method was significantly improved in terms of lower root mean square deviation (RMSD) of around 10% and higher fitness (R2) of around 0.90, outperforming two conventional methods. This study provides a promising technique for real-time myoelectric applications in movement control and health.


Asunto(s)
Contracción Muscular , Músculo Esquelético , Humanos , Electromiografía/métodos , Músculo Esquelético/fisiología , Contracción Muscular/fisiología , Potenciales de Acción , Redes Neurales de la Computación
13.
J Physiol Sci ; 74(1): 24, 2024 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-38600445

RESUMEN

Actin linked regulatory mechanisms are known to contribute contraction/relaxation in smooth muscle. In order to clarify whether modulation of polymerization/depolymerization of actin filaments affects relaxation process, we examined the effects of cytochalasin D on relaxation process by Ca2+ removal after Ca2+-induced contraction of ß-escin skinned (cell membrane permeabilized) taenia cecum and carotid artery preparations from guinea pigs. Cytochalasin D, an inhibitor of actin polymerization, significantly suppressed the force during relaxation both in skinned taenia cecum and carotid artery. The data fitting analysis of the relaxation processes indicates that cytochalasin D accelerates slow (latch-like) bridge dissociation. Cytochalasin D seems to directly disrupts actin filament organization or its length, resulting in modulation of actin filament structure that prevents myosin binding.


Asunto(s)
Actinas , Contracción Muscular , Cobayas , Animales , Contracción Muscular/fisiología , Actinas/metabolismo , Citocalasina D/farmacología , Citocalasina D/metabolismo , Ciego/metabolismo , Arterias Carótidas/metabolismo , Calcio/metabolismo
14.
Nat Commun ; 15(1): 3142, 2024 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-38605031

RESUMEN

TRAAK, TREK-1, and TREK-2 are mechanosensitive two-pore domain K+ (K2P) channels that contribute to action potential propagation, sensory transduction, and muscle contraction. While structural and functional studies have led to models that explain their mechanosensitivity, we lack a quantitative understanding of channel activation by membrane tension. Here, we define the tension response of mechanosensitive K2Ps using patch-clamp recording and imaging. All are low-threshold mechanosensitive channels (T10%/50% 0.6-2.7 / 4.4-6.4 mN/m) with distinct response profiles. TRAAK is most sensitive, TREK-1 intermediate, and TREK-2 least sensitive. TRAAK and TREK-1 are activated broadly over a range encompassing nearly all physiologically relevant tensions. TREK-2, in contrast, activates over a narrower range like mechanosensitive channels Piezo1, MscS, and MscL. We further show that low-frequency, low-intensity focused ultrasound increases membrane tension to activate TRAAK and MscS. This work provides insight into tension gating of mechanosensitive K2Ps relevant to understanding their physiological roles and potential applications for ultrasonic neuromodulation.


Asunto(s)
Canales de Potasio de Dominio Poro en Tándem , Canales de Potasio de Dominio Poro en Tándem/genética , Potenciales de Acción , Sensación , Contracción Muscular
15.
Dis Model Mech ; 17(4)2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38655653

RESUMEN

Steroid myopathy is a clinically challenging condition exacerbated by prolonged corticosteroid use or adrenal tumors. In this study, we engineered a functional three-dimensional (3D) in vitro skeletal muscle model to investigate steroid myopathy. By subjecting our bioengineered muscle tissues to dexamethasone treatment, we reproduced the molecular and functional aspects of this disease. Dexamethasone caused a substantial reduction in muscle force, myotube diameter and induced fatigue. We observed nuclear translocation of the glucocorticoid receptor (GCR) and activation of the ubiquitin-proteasome system within our model, suggesting their coordinated role in muscle atrophy. We then examined the therapeutic potential of taurine in our 3D model for steroid myopathy. Our findings revealed an upregulation of phosphorylated AKT by taurine, effectively countering the hyperactivation of the ubiquitin-proteasomal pathway. Importantly, we demonstrate that discontinuing corticosteroid treatment was insufficient to restore muscle mass and function. Taurine treatment, when administered concurrently with corticosteroids, notably enhanced contractile strength and protein turnover by upregulating the AKT-mTOR axis. Our model not only identifies a promising therapeutic target, but also suggests combinatorial treatment that may benefit individuals undergoing corticosteroid treatment or those diagnosed with adrenal tumors.


Asunto(s)
Dexametasona , Modelos Biológicos , Contracción Muscular , Enfermedades Musculares , Proteínas Proto-Oncogénicas c-akt , Transducción de Señal , Serina-Treonina Quinasas TOR , Taurina , Proteínas Proto-Oncogénicas c-akt/metabolismo , Humanos , Taurina/farmacología , Serina-Treonina Quinasas TOR/metabolismo , Contracción Muscular/efectos de los fármacos , Dexametasona/farmacología , Enfermedades Musculares/patología , Enfermedades Musculares/tratamiento farmacológico , Transducción de Señal/efectos de los fármacos , Receptores de Glucocorticoides/metabolismo , Fuerza Muscular/efectos de los fármacos , Complejo de la Endopetidasa Proteasomal/metabolismo , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/patología , Músculo Esquelético/metabolismo , Tamaño de los Órganos/efectos de los fármacos , Fosforilación/efectos de los fármacos , Corticoesteroides/farmacología , Ubiquitina/metabolismo , Fibras Musculares Esqueléticas/efectos de los fármacos , Fibras Musculares Esqueléticas/patología , Fibras Musculares Esqueléticas/metabolismo , Esteroides/farmacología
16.
J Vis Exp ; (205)2024 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-38587372

RESUMEN

The lymphatic vasculature, now often referred to as "the third circulation," is located in many vital organ systems. A principal mechanical function of the lymphatic vasculature is to return fluid from extracellular spaces back to the central venous ducts. Lymph transport is mediated by spontaneous rhythmic contractions of lymph vessels (LVs). LV contractions are largely regulated by the cyclic rise and fall of cytosolic, free calcium ([Ca2+]i). This paper presents a method to concurrently calculate changes in absolute concentrations of [Ca2+]i and vessel contractility/rhythmicity in real time in isolated, pressurized LVs. Using isolated rat mesenteric LVs, we studied changes in [Ca2+]i and contractility/rhythmicity in response to drug addition. Isolated LVs were loaded with the ratiometric Ca2+-sensing indicator Fura-2AM, and video microscopy coupled with edge-detection software was used to capture [Ca2+]i and diameter measurements continuously in real time. The Fura-2AM signal from each LV was calibrated to the minimum and maximum signal for each vessel and used to calculate absolute [Ca2+]i. Diameter measurements were used to calculate contractile parameters (amplitude, end diastolic diameter, end systolic diameter, calculated flow) and rhythmicity (frequency, contraction time, relaxation time) and correlated with absolute [Ca2+]i measurements.


Asunto(s)
Calcio , Vasos Linfáticos , Ratas , Animales , Vasos Linfáticos/fisiología , Linfa , Contracción Muscular/fisiología
17.
FASEB J ; 38(7): e23604, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38591106

RESUMEN

With no lysine/K kinases (WNKs) promote vasocontraction and vascular smooth muscle cell proliferation. In the prostate, smooth muscle contraction and growth may be critical for the development and medical treatment of voiding symptoms in benign prostatic hyperplasia. Here, we examined the effects of isoform-specific WNK silencing and of the WNK inhibitor WNK463 on growth-related functions and contraction in prostate stromal cells, and in human prostate tissues. Impacts of WNK silencing by transfection of cultured stromal cells with isoform-specific siRNAs were qualitatively and quantitatively similar for each WNK isoform. Effects of silencing were largest on cell death (3-5 fold increase in annexin V-positive/7-AAD-positive cells), on proliferation rate, Ki-67 mRNA expression and actin organization (reduced around two-thirds). Contraction in matrix contraction assays and viability were reduced to a lower degree (approximately half), but again to a similar extent for each WNK isoform. Effects of silencing were quantitatively and qualitatively reproduced by 10 µM WNK463, while 1 µM still induced cell death and breakdown in actin organization, without affecting proliferation or viability. Using 500 nM and 10 µM, WNK463 partly inhibited neurogenic and U46619-induced contractions of human prostate tissues (around half), while inhibition of α1-adrenergic contractions (around half) was limited to 10 µM. All four WNK isoforms suppress cell death and promote proliferation in prostate stromal cells. WNK-driven contraction of stromal cells appears possible, even though to a limited extent. Outcomes of isoform-specific WNK silencing can be fully reproduced by WNK463, including inhibition of smooth muscle contraction in human prostate tissues, but require high concentrations.


Asunto(s)
Actinas , Próstata , Masculino , Humanos , Actinas/metabolismo , Contracción Muscular/fisiología , Células del Estroma/metabolismo , Proliferación Celular , Isoformas de Proteínas/metabolismo
18.
Am J Obstet Gynecol ; 230(3S): S856-S864, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38462259

RESUMEN

Smaller pelvic floor dimensions seem to have been an evolutionary need to provide adequate support for the pelvic organs and the fetal head. Pelvic floor dimension and shape contributed to the complexity of human birth. Maternal pushing associated with pelvic floor muscle relaxation is key to vaginal birth. Using transperineal ultrasound, pelvic floor dimensions can be objectively measured in both static and dynamic conditions, such as pelvic floor muscle contraction and pushing. Several studies have evaluated the role of the pelvic floor in labor outcomes. Smaller levator hiatal dimensions seem to be associated with a longer duration of the second stage of labor and a higher risk of cesarean and operative deliveries. Furthermore, smaller levator hiatal dimensions are associated with a higher fetal head station at term of pregnancy, as assessed by transperineal ultrasound. With maternal pushing, most women can relax their pelvic floor, thus increasing their pelvic floor dimensions. Some women contract rather than relax their pelvic floor muscles under pushing, which is associated with a reduction in the anteroposterior diameter of the levator hiatus. This phenomenon is called levator ani muscle coactivation. Coactivation in nulliparous women at term of pregnancy before the onset of labor is associated with a higher fetal head station at term of pregnancy and a longer duration of the second stage of labor. In addition, levator ani muscle coactivation in nulliparous women undergoing induction of labor is associated with a longer duration of the active second stage of labor. Whether we can improve maternal pelvic floor relaxation with consequent improvement in labor outcomes remains a matter of debate. Maternal education, physiotherapy, and visual feedback are promising interventions. In particular, ultrasound visual feedback before the onset of labor can help women increase their levator hiatal dimensions and correct levator ani muscle coactivation in some cases. Ultrasound visual feedback in the second stage of labor was found to help women push more efficiently, thus obtaining a lower fetal head station at ultrasound and a shorter duration of the second stage of labor. The available evidence on the role of any intervention aimed to aid women to better relax their pelvic floor remains limited, and more studies are needed before considering its routine clinical application.


Asunto(s)
Distocia , Trabajo de Parto , Embarazo , Femenino , Humanos , Parto Obstétrico/métodos , Diafragma Pélvico/diagnóstico por imagen , Distocia/diagnóstico por imagen , Distocia/terapia , Ultrasonografía , Contracción Muscular/fisiología , Imagenología Tridimensional
19.
Scand J Med Sci Sports ; 34(3): e14591, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38429941

RESUMEN

The enigmatic benefits of acute limb ischemic preconditioning (IP) in enhancing muscle force and exercise performance have intrigued researchers. This study sought to unravel the underlying mechanisms, focusing on increased neural drive and the role of spinal excitability while excluding peripheral factors. Soleus Hoffmann (H)-reflex /M-wave recruitment curves and unpotentiated supramaximal responses were recorded before and after IP or a low-pressure control intervention. Subsequently, the twitch interpolation technique was applied during maximal voluntary contractions to assess conventional parameters of neural output. Following IP, there was an increase in both maximum normalized force and voluntary activation (VA) for the plantar flexor group, with negligible peripheral alterations. Greater benefits were observed in participants with lower VA levels. Despite greater H-reflex gains, soleus volitional (V)-wave and sEMG amplitudes remained unchanged. In conclusion, IP improves muscle force via enhanced neural drive to the muscles. This effect appears associated, at least in part, to reduced presynaptic inhibition and/or increased motoneuron excitability. Furthermore, the magnitude of the benefit is inversely proportional to the skeletal muscle's functional reserve, making it particularly noticeable in under-recruited muscles. These findings have implications for the strategic application of the IP procedure across diverse populations.


Asunto(s)
Precondicionamiento Isquémico , Músculo Esquelético , Masculino , Humanos , Electromiografía/métodos , Músculo Esquelético/fisiología , Contracción Muscular/fisiología , Neuronas Motoras/fisiología , Contracción Isométrica/fisiología , Reflejo H/fisiología , Estimulación Eléctrica
20.
Biofabrication ; 16(2)2024 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-38447227

RESUMEN

Engineered muscle fibers are attracting interest in bio-actuator research as they can contribute to the fabrication of actuators with a high power/size ratio for micro-robots. These fibers require to be stretched during culture for functional regulation as actuators and require a fixation on a rigid substrate for stretching in culture and evaluation of mechanical properties, such as Young's modulus and contraction force. However, the conventional fixation methods for muscle fibers have many restrictions as they are not repeatable and the connection between fixation part and the muscle fibers detaches during culture; therefore, the fixation becomes weak during culture, and direct measurement of the muscle fibers' mechanical properties by a force sensor is difficult. Therefore, we propose a facile and repeatable fixation method for muscle fibers by mixing magnetite nanoparticles at both ends of the muscle fibers to fabricate magnetic ends. The fiber can be easily attached and detached repeatedly by manipulating a magnet that applies a magnetic force larger than 3 mN to the magnetic ends. Thus, the muscle fiber can be stretched fiber during culture for functional regulation, transported between the culture dish and measurement system, and directly connected to the force sensor for measurement with magnetic ends. The muscle fiber connected with magnetic ends have a long lifetime (∼4 weeks) and the cells inside had the morphology of a skeletal muscle. Moreover, the muscle fiber showed a contraction (specific force of 1.02 mN mm-2) synchronized with electrical stimulation, confirming the muscle fiber fabricated and cultured using our method had similar morphology and function as bio-actuators in previous research. This research demonstrates the advantages of the fixation method using muscle fibers with magnetic ends; the fibers are stretched during culture, and the transportation and force measurement of weak and tiny muscle fibers could be finished in 1 min.


Asunto(s)
Contracción Muscular , Fibras Musculares Esqueléticas , Contracción Muscular/fisiología , Músculo Esquelético/fisiología , Fenómenos Mecánicos , Fenómenos Magnéticos
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