Maintenance of body weight is fundamental to maintain one’s health and to promote longevity. Nevertheless, it appears that the global obesity epidemic is still constantly increasing. Endocannabinoids (eCBs) are lipid messengers that are involved in overall body weight control by interfering with manifold central and peripheral regulatory circuits that orchestrate energy homeostasis. Initially, blocking of eCB signaling by first generation cannabinoid type 1 receptor (CB1) inverse agonists such as rimonabant revealed body weight-reducing effects in laboratory animals and men. Unfortunately, rimonabant also induced severe psychiatric side effects. At this point, it became clear that future cannabinoid research has to decipher more precisely the underlying central and peripheral mechanisms behind eCB-driven control of feeding behavior and whole body energy metabolism. Here, we will summarize the most recent advances in understanding how central eCBs interfere with circuits in the brain that control food intake and energy expenditure. Next, we will focus on how peripheral eCBs affect food digestion, nutrient transformation and energy expenditure by interfering with signaling cascades in the gastrointestinal tract, liver, pancreas, fat depots and endocrine glands. To finally outline the safe future potential of cannabinoids as medicines, our overall goal is to address the molecular, cellular and pharmacological logic behind central and peripheral eCB-mediated body weight control, and to figure out how these precise mechanistic insights are currently transferred into the development of next generation cannabinoid medicines displaying clearly improved safety profiles, such as significantly reduced side effects.

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Subject-specific finite element (FE) models could improve decision making in canine long bone fracture repair. However, it preliminary requires that FE models predicting the mechanical response of canine long bone are proposed and validated. We present here a combined experimental-numerical approach to test the ability of subjectspecific FE models to predict the bending response of seven pairs of canine humeri directly from medical images. Our results show that bending stiffness and yield load are predicted with a mean absolute error of 10.1% (±5.2%) for the fourteen samples.This study constitutes a basis for the forthcoming optimization of canine long bone fracture repair.

Distal humeral fractures are common fractures especially in immature small breed dogs. The pathogenesis is still unknown. For this study, a three-dimensional bone model of the canine elbow was created and finite element analysis performed in order to determine the relationship between fracture type and bone interactions. Fused and non-fused humeral condyles were considered. A failure criterion was implemented to simulate the pathogenesis until fracture. Our study results confirm the clinical observation that lateral condylar fracture is the most common fracture type, implying interaction with the radius. Medial and Y-fractures are less common and occur always in interaction with the ulna whereas the radius causes lateral condylar fracture. Additionally, the fracture type is sensitive to bone positioning during trauma. The pathogenesis of distal humeral fractures is more complex than generally reported in the literature.

Osteosynthesis for canine long bones is a complex process requiring knowledge of biology, surgical techniques and (bio)mechanical principles. Subject-specific finite element analysis constitutes a promising tool to evaluate the effect of surgical intervention on the global properties of a bone–implant construct, but suffers from a lack of validation. In this study, the biomechanical behavior of 10 canine humeri was compared before and after creation of a 10 mm bone defect stabilized with an eight-hole locking compression plate (Synthes®) and two locking screws on each fragment. The response under compression of both intact and plated samples was measured experimentally and reproduced with a finite element model. The experimental stiffness ratio between plated and intact bone was equal to 0.39 ± 0.06. A subject-specific finite element analysis including density-dependent elasto-plastic material properties for canine bone and automatic generation of orthopedic implants was then conducted to recover these experimental results. The stiffness of intact and plated samples could be predicted, with no significant differences with experimental data. The simulated stiffness ratio between plated and intact canine bone was equal to 0.43 ± 0.03. This study constitutes a first step toward the building of a virtual database of pre-computed cases, aiming at helping the veterinary surgeons to make decisions regarding the most suited orthopedic solution for a given dog and a given fracture.