Simulation of double-leg stance in conditions of limited hip mobility

Hip osteoarthritis is one of the most common and disabling conditions affecting the elderly. Coxarthrosis is accompanied by impairment of the amortization properties of cartilage, its thinning and destruction, the appearance of pain syndrome, impaired motor functions due to a decrease in muscle strength and the development of stable flexion-adduction contractures, which change congenital motor programs, and, with a prolonged course of degenerative disease, lead to the formation of pathological habits. Objective: to determine the required strength of the muscles of the lower limb in conditions of limited hip mobility to support an upright posture in double-leg stance. Materials and methods. The work of the muscles of the lower extremities under conditions of restricted hip mobility was simulated using the OpenSim 4.0 software. It is based on the ToyLandingModel, which has contact geometry objects to fix the model on the support area. Four models were created: norm (without limitation of joint mobility), model 2 — adduction of 5°, model 3 — adduction of 7°, flexion of 10°, model 4 — adduction of 10°, flexion of 20°, shortening of the femur bones by 2 cm. Results. It was found that with insignificant adduction contractures of the hip joint, the work of the muscles of the lower limb changes slightly during double-leg stance. With flexion-adduction contractures, changes are observed in almost all muscles of the lower limb. There are some peculiarities in the work of muscles under contractures. All the muscles around the thigh reduce the strength necessary to maintain balance, while the lower leg muscles, on the contrary, increase the required strength several times. For example, m.medial gastrocnemius with flexion-adduction contracture and limb shortening develops10 times higher compensatory force (200 N) than in normal conditions (20 N), and although muscle resources are 1500 N, it is very demanding to maintain an upright posture. Similarly, m.tibialis posterior require an increase in strength (threefold), but the antagonist muscle m.tibialis anterior, on the contrary, reduces the force of contraction by an average of 100 N. Conclusions. According to the data of the conducted modeling of double-leg stance with limited hip mobility, it was proved that an increase in limited movements changes the nature of muscle contraction of the entire lower limb and pelvis. The analysis of the obtained results showed that restriction of movements reduces the required force of muscle stabilization around the hip joint, and increases the required force of contraction of the leg muscles. That is, there is an imbalance in the muscles.

Functional interaction of H2-receptors and 5HT4-receptors in atrial tissues isolated from double transgenic mice and from human patients

In the past, we generated transgenic mice that overexpress the human histamine 2 (H2)-receptor (H2-TG) or that overexpress the human serotonin 4 (5-HT4)-receptor (5-HT4-TG) in the heart. Here, we crossbred these lines of mice to generate double transgenic mice that overexpress both receptors (DT). This was done to study a conceivable interaction between these receptors in the mouse heart as a model for the human heart. When in left atria, initially, force of contraction was elevated maximally with 1 µM serotonin, and subsequently, histamine was cumulatively applied; a biphasic effect of histamine was noted: the force of contraction initially decreased, maximally at 10 nM histamine, and thereafter, the force of contraction increased again at 1 µM histamine. Notably, functional interaction between 5-HT and histamine was also identified in isolated electrically stimulated trabeculae carneae from human right atrium (obtained during cardiac surgery). These functional and biochemical data together are consistent with a joint overexpression of inotropically active H2-receptors and 5-HT4-receptors in the same mouse heart. We also describe an antagonistic interaction on the force of contraction of both receptors in the mouse atrium (DT) and in the human atrial muscle strips. We speculate that via this interaction, histamine might act as a “brake” on the cardiac actions of 5-HT via inhibitory GTP-binding proteins acting on the activity of adenylyl cyclase.

Known data on applied regenerative medicine in tendon healing

Tendons and ligaments are important structures in the musculoskeletal system. Ligaments connect various bones and provide stability in complex movements of joints in the knee. Tendon is made of dense connective tissue and transmits the force of contraction from muscle to bone. They are injured due to direct trauma in sports or roadside accidents. Tendon healing after repair is often poor due to the formation of fibro vascular scar tissues with low mechanical property. Regenerative techniques such as PRP (platelet-rich plasma), stem cells, scaffolds, gene therapy, cell sheets, and scaffolds help augment repair and regenerate tissue in this context. Therefore, it is of interest to document known data (repair process, tissue regeneration, mechanical strength, and clinical outcome) on applied regenerative medicine in tendon healing.

Cerebellum: Its Anatomy, Functions and Diseases

Cerebellum is the largest part of the hindbrain and weighs about 150 g. It is enshrined in posterior cranial fossa behind the pons and medulla oblongata and separated from these structures by cavity of fourth ventricle. It is connected to brainstem by three fibre tracts known as cerebellar peduncles. Cerebellum controls the same side of body. It precisely coordinates skilled voluntary movements by controlling strength, duration and force of contraction, so that they are smooth, balanced and accurate. It is also responsible for maintaining equilibrium, muscle tone and posture of the body. This is achieved through the use of somatic sensory information in modulating the motor output from the cerebrum and brainstem. Sherrington regarded cerebellum as the head ganglion of the proprioceptive system. Dysfunction of cerebellum along with degenerative diseases of cerebellum such as spinocerebellar ataxia, multiple sclerosis, malignant tumours, etc. may culminate into disequilibrium, hypotonia, difficulty in talking, sleeping, maintaining muscular coordination and dyssynergia which at times may be life threatening. Hence, knowledge of anatomy of cerebellum is imperative for neuroanatomists and neurosurgeons.

Aplicabilidade da toxina botulínica na Odontologia

A botulinum toxin (BT) was the first toxin used in the history of human medicine, it is a toxin used by the bacterium Clostridium botulinum, which later isolated the demonstration used to solve some problems caused by musculature, because BT being applied to the muscle promotes a reduction in the force of contraction. Among the eight known serotypes of this toxin, those currently used in medicine are types A and B. This review article discusses mainly BT type A (BTA), because it is used in dentistry. Still within facial use, we can highlight the application in cases of gingival smile associated with muscle strength, without assistance in the treatment of temporomandibular disorders, without bruxism and orthodontics.

Hypotensive Effect Of The Plant Alkaloid Digitaalisen On The Functional Activity Of Mmc Aortic Chrysallida Of Dihydroemetine On The Functional Activity Of Smc In The Aorta Of The Rat

Effect of dihydroatizin (5–250 μmol / L) on the contractile activity of rat smooth aorta muscle cells (SMC). Isometric tensile forces were recorded. Using a force transducer FT - 03 (Grass Instrument Co., USA). In it was found by experiments that the vasodilating effect of dihydroatizin mainly associated with the blockade of the Ca2 + L-channel. Methods-Preparation of the aortic vessel muscle preparation, and recording the force of contraction. Results- KCI-induced contraction of the aortic MMC is associated with the activation of potential–dependent Ca2+L channels of the plasma membranes of the MMC Conclusions- The data obtained as a result of studying the mechanisms of action of the alkaloid dihydroathysine are of great practical importance and can be recommended for optimizing the process of purposeful creation of a new generation of vasorelaxant drugs

Novel approaches to restore parasympathetic activity to the heart in cardiorespiratory diseases

Neural control of the heart is regulated by sympathetic and parasympathetic divisions of the autonomic nervous system, both opposing each other to maintain cardiac homeostasis via regulating heart rate, conduction velocity, force of contraction, and coronary blood flow. Sympathetic hyperactivity and diminished parasympathetic activity are the characteristic features of many cardiovascular disease states including hypertension, myocardial ischemia, and arrhythmias that result in heart failure. Restoring parasympathetic activity to the heart has recently been identified as the promising approach to treat such conditions. However, approaches that used vagal nerve stimulation have been shown to be unsuccessful in heart failure. This review focuses on novel chemogenetic approaches used to identify the cardioprotective nature of activating neural points along the vagal pathway (both central and peripheral) while being selectively therapeutic in heart failure and obstructive sleep apnea.

Selective beta-3 adrenergic receptor blockade increases contractility of human ventricular trabeculae from HFrEF donors

Background Alterations of the beta-adrenergic system have been extensively described in the setting of heart failure (HF). Upregulation of beta-3 adrenergic receptor (β3-AdrR) expression in human failing hearts depresses myocardial contractility and, during an acute decompensation event, can be considered a maladaptive compensatory mechanism that exacerbates cardiac dysfunction. APD418 is a selective β3-AdrR antagonist currently in development for patients who have acute heart failure with reduced ejection fraction (HFrEF). APD418 is designed to improve myocardial contractility by selectively antagonizing the β3-AdrR and thereby avoiding the cAMP/Ca2+ signaling pathway stimulated by current inotropes. Purpose This study evaluated the effect of a selective β3-AdrR antagonist (APD418) on contractile responses in explanted human ventricular trabeculae obtained from normal and HFrEF hearts. Methods Left ventricular trabeculae from normal and HFrEF donors were electrically stimulated (1 Hz) ex-vivo to analyze force generated during contractions. First, BRL37344, a selective β3-AdrR agonist, was applied at increasing concentrations (0.01–10 μM) to confirm β3-AdrR mediated negative inotropy in human myocardial tissue. To test the effect of a selective β3-AdrR antagonist on contractile force, myocardial tissue was pre-treated with APD418 or vehicle for 5 minutes, followed by treatment with non-selective β-AdrR agonists isoproterenol (10 nM) or norepinephrine (5 μM). Results In heart tissue from normal donors, the β3-AdrR agonist BRL37344 did not affect contractile function at 0.01 and 0.1 μM. However, in heart tissue from HFrEF donors, BRL37344 induced a significant decrease in contractility at 0.01, 0.1 and 1 μM (85.9±1.8% with 0.1 μM BRL37344 vs 104.1±2.9% with vehicle). Selective blockade of β3-AdrR with APD418 had no effect on force of contraction induced by norepinephrine in cardiac tissue from normal donors. In contrast, APD418 potentiated the force of contraction induced by either isoproterenol (49.1±20.6% increase with 0.1 μM APD418 compared to baseline) or norepinephrine (26.5±4.9% increase with 0.01 μM APD418 compared to baseline) in cardiac tissue from HFrEF patients. Conclusion This is, to our knowledge, the first evidence showing that selective blockade of β3-AdrR increases contractility of human ventricular trabeculae from HFrEF donors and suggests that further studies evaluating the therapeutic benefit of APD418 in patients with HFrEF are warranted. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Arena Pharmaceuticals

Implementation and experimental validation of surface electromyogram and force model of Tibialis Anterior muscle for examining muscular factors

This study reports a surface electromyogram and force of contraction model. The objective was to investigate the effect of changes in the size, type and number of motor units in the Tibialis Anterior muscle to surface electromyogram and force of dorsiflexion. A computational model to simulate surface electromyogram and associated force of contraction by the Tibialis Anterior muscle was developed. This model was simulated for isometric dorsiflexion, and comparative experiments were conducted for validation. Repeated simulations were performed to investigate the different parameters and evaluate inter-experimental variability. An equivalence statistical test and the Bland–Altman method were used to observe the significance between the simulated and experimental data. Simulated and experimentally recorded data had high similarity for the three measures: maximal power of power spectral density ( p < 0.0001), root mean square of surface electromyogram ( p < 0.0001) and force recorded at the footplate ( p < 0.03). Inter-subject variability in the experimental results was in-line with the variability in the repeated simulation results. This experimentally validated computational model for the surface electromyogram and force of the Tibialis Anterior muscle is significant as it allows the examination of three important muscular factors associated with ageing and disease: size, fibre type and number of motor units.

The Effect of Ivabradine on the Human Atrial Myocardial Contractility in an In Vitro Study

Purpose. Ivabradine has emerged as a new antiarrhythmic agent that could compete with the traditional ones, such as beta-blockers. This experimental study aims to ascertain whether ivabradine directly interferes with the myocardial contractility in an in vitro environment. Methods. Myocardial tissues from the right atrial appendages of patients undergoing cardiac surgery were dissected to obtain 40 specimens from 20 patients (length: 3 mm), which were exposed to electrical impulses at a frequency of 75 bpm for 30 min to reach a steady state. Specimens were then categorised into four groups (each including five patients). The first group was the control, whereas the second, third, and fourth were treated with 60 nM, 200 nM, and 2 μM ivabradine, respectively. We assessed five different contraction parameters before and after a 15 min treatment and calculated their relative changes, which were then compared to the control group. Results. Ivabradine has affected the force of contraction significantly in vitro (p=0.009). However, force of contraction decreased in both the control group (93.5 ± 4.7%) and the second group (94.1 ± 4.5%, p=0.8) and force of contraction remained unchanged in the third group (101.0 ± 4.1%, p=0.24) and increased significantly in the fourth group (108.9 ± 11.6%, p=0.008). There was no change in other contraction parameters, such as passive tension force (97.1 ± 5.1%, p=0.368), duration of contraction (99.1 ± 4.3%, p=0.816), time to peak (96.6 ± 3.0%, p=0.536), and time to relaxation (101.2 ± 7.0%, p=0.564). Conclusions. Ivabradine did not interfere with the contractile behaviour of human atrial tissue when it was used in therapeutic dosages in vitro. However, it increased the contractility slightly, when it was used in supratherapeutic dosage.