Search results for "Contract"

Considerations for an In Vitro, Cell-Based Testing Platform for Detection of Drug-Induced Inotropic Effects in Early Drug Development. Part 2: Design…

2019

Contractility of the myocardium engines the pumping function of the heart and is enabled by the collective contractile activity of its muscle cells: cardiomyocytes. The effects of drugs on the contractility of human cardiomyocytes in vitro can provide mechanistic insight that can support the prediction of clinical cardiac drug effects early in drug development. Cardiomyocytes differentiated from human-induced pluripotent stem cells have high potential for overcoming the current limitations of contractility assays because they attach easily to extracellular materials and last long in culture, while having human- and patient-specific properties. Under these conditions, contractility measureme…

The actin remodeling protein cofilin is crucial for thymic αβ but not γδ T-cell development

2018

Cofilin is an essential actin remodeling protein promoting depolymerization and severing of actin filaments. To address the relevance of cofilin for the development and function of T cells in vivo, we generated knock-in mice in which T-cell–specific nonfunctional (nf) cofilin was expressed instead of wild-type (WT) cofilin. Nf cofilin mice lacked peripheral αβ T cells and showed a severe thymus atrophy. This was caused by an early developmental arrest of thymocytes at the double negative (DN) stage. Importantly, even though DN thymocytes expressed the TCRβ chain intracellularly, they completely lacked TCRβ surface expression. In contrast, nf cofilin mice possessed normal numbers of γδ T cel…

Smooth muscle and neural dysfunction contribute to different phases of murine postoperative ileus.

2015

Background Postoperative ileus (POI) is characterized by a transient inhibition of gastrointestinal (GI) motility after abdominal surgery mediated by the inflammation of the muscularis externa (ME). The aim of this study was to identify alterations in the enteric nervous system that may contribute to the pathogenesis of POI. Methods Gastrointestinal transit, contractility of isolated smooth muscle strips and inflammatory parameters were evaluated at different time points (1.5 h to 10 days) after intestinal manipulation (IM) in mice. Immune-labeling was used to visualize changes in myenteric neurons. Key Results Intestinal manipulation resulted in an immediate inhibition of GI transit recove…

Neurotrophic and neuroprotective effects of muscle contraction

2016

Background: Physical activity has been shown to be associated with reduced risk of coronary heart disease but the same effect seems to be produced in neurological diseases. Objective: In this review, we focused on the interplay between physical activity and some neurological conditions (Stroke, dementia, epilepsy, headache, Parkinson’ s disease, amyotrophic lateral sclerosis, multiple sclerosis, insomnia, depression and anxiety) with the aim of describing the potential role of physical activity in the prevention of such diseases and the physiological mechanisms involved in these processes. Results: Despite a growing body of evidence which reveals that physical activity is able to reduce the…

2016

In humans, the amount of spinal homonymous recurrent inhibition during voluntary contraction is usually assessed by using a peripheral nerve stimulation paradigm. This method consists of conditioning the maximal M-wave (SM stimulus) with prior reflex stimulation (S1), with 10 ms inter-stimulus interval (ISI). The decrease observed between unconditioned (S1 only) and conditioned (S1+SM) reflex size is then attributed to recurrent inhibition. However, during a voluntary contraction, a superimposed SM stimulation leads to a maximal M-wave followed by a voluntary (V) wave at similar latency than the H-reflex. This wave can therefore interfere with the conditioned H-reflex when two different sti…

Preventive and Therapeutic Role of Muscle Contraction Against Chronic Diseases.

2016

Background: Due to the continuing increase of the elderly population in the western countries, the prevalence of the main chronic diseases (obesity, type 2 diabetes and related metabolic disorders, arterial hypertension, vascular damage due to atherosclerotic process, cancer, chronic obstructive pulmonary disease, neurodegenerative diseases, chronic kidney disease, immune-mediated diseases) is increasing. There is incontrovertible evidence that regular physical activity contributes to the primary and secondary prevention of several chronic diseases and is associated with a reduced risk of premature death. Methods: In this review the most prevalent chronic pathologic conditions are discussed…

Urinary Bladder Weight and Function in a Rat Model of Mild Hyperglycemia and Its Treatment With Dapagliflozin

2019

Hypertrophy and dysfunction of the urinary bladder are consistently observed in animal models of type 1 and less consistently in those of type 2 diabetes. We have tested the effects of mild hyperglycemia (n = 10 per group) in a randomized, blinded study and, in a blinded pilot study, of type 2 diabetes (n = 6 per group) and its treatment with dapagliflozin (1 mg/kg per day) on weight, contraction, and relaxation of the rat bladder. Based on a combination of high-fat diet and a low dose of streptozotocin, animals in the main study reached a mean peak blood glucose level of about 300 mg/dl, which declined to 205 mg/dl at study end. This was associated with a small, if any, increase in bladder…

Redox modulation of muscle mass and function

2020

Muscle mass and strength are very important for exercise performance. Training-induced musculoskeletal injuries usually require periods of complete immobilization to prevent any muscle contraction of the affected muscle groups. Disuse muscle wasting will likely affect every sport practitioner in his or her lifetime. Even short periods of disuse results in significant declines in muscle size, fiber cross sectional area, and strength. To understand the molecular signaling pathways involved in disuse muscle atrophy is of the utmost importance to develop more effective countermeasures in sport science research. We have divided our review in four different sections. In the first one we discuss t…

Modulation of muscle-tendon interaction in the human triceps surae during an energy dissipation task.

2017

The compliance of elastic elements allows muscles to dissipate energy safely during eccentric contractions. This buffering function is well documented in animal models but our understanding of its mechanism in humans is confined to non-specific tasks, requiring a subsequent acceleration of the body. The present study aimed to examine the behaviour of the human triceps surae muscle-tendon unit (MTU) during a pure energy dissipation task, under two loading conditions. Thirty-nine subjects performed a single-leg landing task, with- and without added mass. Ultrasound measurements were combined with 3D kinematics and kinetics to determine instantaneous length changes of MTUs, muscle fascicles, A…

Differential PI3K signal transduction in obesity-associated cardiac hypertrophy and response to ischemia

2014

Objective Elevated insulin and inflammatory cytokine levels in obesity may chronically activate signaling pathways regulating cardiac growth and contractility. Our aim was to examine the effect of obesity on cardiac PI3K isoform and Akt activation during left ventricular (LV) hypertrophy and heart failure. Methods Wild-type mice were fed normal chow or high-fat diet (HFD) for 2, 4, or 6 months. A subset of mice was subjected to chronic myocardial ischemia (MI). Results Echocardiography revealed a progressive increase in LV mass, wall thickness, and diameters in obese mice. Systolic pump function was not impaired. Increased cardiac levels of PI3Kγ, phosphorylated Akt, GSK3β, and Epac were ob…