An animal model to evaluate skin–implant–bone integration and gait with a prosthesis directly attached to the residual limb

Background

Despite the number of advantages of bone-anchored prostheses, their use in patients is limited due to the lack of complete skin–implant integration. The objective of the present study was to develop an animal model that would permit both detailed investigations of gait with a bone-anchored limb prosthesis and histological analysis of the skin–implant–bone interface after physiological loading of the implant during standing and walking.

Methods

Full-body mechanics of walking in two cats were recorded and analyzed before and after implantation of a percutaneous porous titanium pylon into the right tibia and attachment of a prosthesis. The rehabilitation procedures included initial limb casting, progressively increasing loading on the implant, and standing and locomotor training. Detailed histological analysis of bone and skin ingrowth into implant was performed at the end of the study.

Findings

The two animals adopted the bone-anchored prosthesis for standing and locomotion, although loads on the prosthetic limb during walking decreased by 22% and 62%, respectively, 4 months after implantation. The animals shifted body weight to the contralateral side and increased propulsion forces by the contralateral hindlimb. Histological analysis of the limb implants demonstrated bone and skin ingrowth.

Interpretation

The developed animal model to study prosthetic gait and tissue integration with the implant demonstrated that porous titanium implants may permit bone and skin integration and prosthetic gait with a bone-anchored prosthesis. Future studies with this model will help optimize the implant and prosthesis properties.     

Circadian Mechanisms in Alcohol Use Disorder and Tissue Injury

Heavy use of alcohol can lead to addictive behaviors and to eventual alcohol‐related tissue damage. While increased consumption of alcohol has been attributed to various factors including level of alcohol exposure and environmental factors such as stress, data from behavioral scientists and physiological researchers are revealing roles for the circadian rhythm in mediating the development of behaviors associated with alcohol use disorder as well as the tissue damage that drives physiological disease. In this work, we compile recent work on the complex mutually influential relationship that exists between the core circadian rhythm and the pharmacodynamics of alcohol. As we do so, we highlight implications of the relationship between alcohol and common circadian mechanisms of effected organs on alcohol consumption, metabolism, toxicity, and pathology.     

The four As associated with pathological Parkinson disease gamblers: anxiety, anger, age, and agonists

Several studies have related pathological gambling in PD to dopamine agonist therapy. A mail-in survey was sent to PD patients seen at the University of Florida Movement Disorders Center to determine gambling frequency and behavior, and any lifestyle or environmental factors associated with compulsive gambling in PD. 462 surveys were sent and 127 completed surveys were returned, of which ten were from patients who met criteria for compulsive gambling. All ten were taking dopamine agonists coincident with the compulsive gambling. Compulsive gamblers were younger, and psychological distress measures revealed that compulsive gamblers exhibited higher levels of anxiety, anger, and confusion. Thus in this cohort, we have uncovered the several characteristics of the most likely PD compulsive gambler, namely: (young) age, “angry”, “anxious”, and using a (dopamine) agonist.     

Triiodothyronine Increases Contractility Independent of beta-Adrenergic Receptors or Stimulation of Cyclic-3',5'-Adenosine Monophosphate

Background: Triiodothyronine regulates cardiac contractility; however, the mechanisms by which it produces its acute contractile effects remains unknown. We compared the acute effects of thyroid hormones (triiodothyronine [T3] and thyroxine [T4]) and of isoproterenol on the contractility of isolated rat hearts. In addition, we sought to determine whether the acute inotropic effects of thyroid hormones were mediated by beta-adrenergic receptors or by increased production of cyclic-3',5'-adenosine monophosphate (cAMP).

Methods: A Langendorff heart preparation harvested from euthyroid male Sprague-Dawley rats was used. Drugs were administered through an aortic perfusion catheter. A pressure-transduced left-ventricular balloon catheter measured pressure and heart rate changes. Changes in the maximum positive rate of change in pressure (dP/dT) and maximum negative dP/dT were determined. Responses to varying doses of T3, T sub 4, and isoproterenol were assessed in the presence and absence of beta-adrenergic receptor blockade with propranolol, cAMP production, measured by radioimmunoassay, was determined in myocardial cell suspensions after incubation with T3 or isoproterenol.

Results: T3 0.74 nmol rapidly and significantly increased maximum dP/dT by 335 plus/minus 38 mmHg/s within 30 s after bolus injection; however, contractility was unchanged after as much as 12.9 nmol T4. The maximal increase in dP/dT after 0.8 nmol isoproterenol was comparable to that produced by T3. However, the cardiotonic actions of isoproterenol were significantly slower to develop (peaking at 60 vs. 15 s) and lasted longer than those of T3. Pretreatment with propranolol 1 micro mol diminished the contractile effects of isoproterenol but had no effect on those of T3. Concentrations of isoproterenol that increase contractility also significantly increased cAMP production in isolated rat myocardial cells. However, T3 failed to increase cAMP production.     

C‐terminal agrin fragment is inversely related to neuromuscular fatigue in older men

Introduction: The aim of this study was to examine the relationship between serum C‐terminal agrin fragment (CAF) concentrations and neuromuscular fatigue in older adults. Methods: Twenty‐two healthy older men and women volunteered for this study. Resting fasted blood samples were collected and prepared for measurement of serum CAF concentration by a commercially available ELISA kit. The onset of neuromuscular fatigue was measured by monitoring electromyographic fatigue curves from the vastus lateralis muscle using the physical working capacity at fatigue threshold (PWC_FT) test. Results: A significant inverse correlation for men was observed between CAF and PWC_FT (r = ?0.602; P = 0.05), but not for women (r = 0.208; P = 0.54). After controlling for age and body mass index, significant correlations (r = ?0.69; P = 0.042) remained for men, but not for women (r = 0.12; P = 0.76). Conclusions: These data suggest that serum CAF concentrations were significantly related to the onset of neuromuscular fatigue independent of age and BMI in men only. Muscle Nerve 51 : 132–133, 2015