Phenylalanine-linked pyrrolo[1,2-a]benzimidazoles were successfully designed to target melanoma cells in vitro. Our design utilised three molecular targets: a phenylalanine pump, the reducing enzyme DT-diaphorase, and IMP dehydrogenase. We describe the synthesis of these compounds as well as the results of in vitro, in vivo, and QSAR studies.
Tendons must be able to withstand the tensile forces generated by muscles to provide support while avoiding failure. The properties of tendons in mammal limbs must therefore be appropriate to accommodate a range of locomotor habits and posture. Tendon collagen composition provides resistance to loading that contributes to tissue strength which could, however, be modified to not exclusively confer large strength and stiffness for elastic energy storage/recovery. For example, sloths are nearly obligate suspenders and cannot run, and due to their combined low metabolic rate, body temperature, and rate of digestion, they have an extreme need to conserve energy. It is possible that sloths have a tendon ‘suspensory apparatus’ functionally analogous to that in upright ungulates, thus allowing for largely passive support of their body weight below-branch, while concurrently minimizing muscle contractile energy expenditure. The digital flexor tendons from the fore- and hindlimbs of two-toed (Choloepus hoffmanni) and three-toed (Bradypus variegatus) sloths were loaded in tension until failure to test this hypothesis. Overall, tensile strength and elastic (Young’s) modulus of sloth tendons were low, and these material properties were remarkably similar to those of equine suspensory ‘ligaments’. The results also help explain previous findings in sloths showing relatively low levels of muscle activation in the digital flexors during postural suspension and suspensory walking.
Achilles tendon rupture requires long recovery times and has the possibility of re‐rupture. The goal of this project is to improve healing in surgically repaired Achilles tendons in a Lewis rat model. Full thickness surgical transections were made 6 mm proximal to the calcaneus bone. Following suture repair, a 20 x 30 mm piece of CollatapeTM was wrapped around the tendon in groups receiving collagen and the skin closed. MSC or PRP or both (100 ml) was injected subcutaneously adjacent to the incision. Both test Achilles and control Achilles from the same animal were harvested and the biomechanical properties determined using a standard force‐extension analysis of tensile properties after 1 week or 2 weeks. A significant improvement in Strain at UTS and Strain at Failure (calculated as percent of control tendon) was seen at 1 week in rats receiving CollatapeTM, plus PRP and MSC. This project was approved by the Northeast Ohio Medical School IACUC. Support or Funding Information Supported by Mercy Health, Youngstown and Youngstown State University.
This study aims to biomechanically compare four different treatment methods for repair enhancement in Achilles tendon rupture in rats: collagen, collagen and platelet-rich plasma (PRP), collagen and mesenchymal stromal cells (MSC), and a combination of collagen, platelet-rich plasma and mesenchymal stromal cells (CPM) at one and two week healing periods. This study included ninety Lewis rats weighing approximately 200–300 g. Ten rats were used as donors for MSC and PRP. For the remaining eighty rats, the right leg was completely transected 6 mm proximal to the calcaneus bone, suture repaired, wrapped in CollaTape (CoTa), and then closed. An injection of PRP, MSC, or PRP and MSC was given at the wound site to the applicable groups. After one or two weeks recovery time, the rats were sacrificed and both Achilles tendons were removed. The left tendons were used as virgin tissue controls. It was found that the maximum stress at failure, the total strain energy, the average modulus of elasticity, and the elastic strain energy all increase significantly from one week to two week recovery time. However, there was no statistical difference between treatment groups in any of the mechanical properties.
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