CorNeat KPro: Ocular Implantation Study in Rabbits.

Purpose: The purpose of this study was to evaluate surgical feasibility and long-term integration of the CorNeat Keratoprosthesis (KPro), a novel synthetic cornea, in rabbits.

Methods: The CorNeat KPro is a synthetic corneal implant designed to treat corneal blindness by using a polymeric scaffold for biointegration, consequently assimilating synthetic optics within ocular tissues. Eight New Zealand White rabbits were implanted unilaterally with the CorNeat KPro and observed for 6 months.

Treatment of contaminated radial fracture in Sprague-Dawley rats by application of a degradable polymer releasing gentamicin.

Fracture-related infections remain a leading cause of morbidity and mortality. We aimed to establish a simple contaminated radial osteotomy model to assess the efficacy of a biodegradable polymer poly(sebacic-co-ricinoleic acid) [p(SA-RA)] containing 20% w/w gentamicin. A unilateral transverse osteotomy was induced in Sprague-Dawley (SD) rats, followed by application of suspension over the fracture.

Local Tolerability and Performance Evaluation in Domestic Pigs of a Fractional Radiofrequency Device for Dermatologic Treatment.

Information on the safety of energy-based dermatological surgical devices in domestic pigs, and fractional radiofrequency (RF) devices in particular, is very limited. The aim of this study was to evaluate in a GLP-compliant study in domestic pigs the local reaction and performance of a novel fractional RF device. Five female domestic pigs were subjected to fractional RF pulses, using different energy and pulse durations and depth of penetration of the pulses.

Biodegradability and Safety Study of LifeMesh™, a Novel Self-adhesive Mesh, in Sprague-Dawley Rats.

Self-adhesive meshes are being developed to avoid complications due to traumatic fixation methods. LifeMesh™ is a novel self-adhesive mesh with a biodegradable gelatin adhesive layer developed for hernia repair. The aim of this study was to assess the safety and biodegradability of LifeMesh in Sprague-Dawley (SD) rats for 6 weeks, in comparison to a bare polypropylene (BPP) mesh fixed with sutures.

Long-term Local and Systemic Safety of Poly(L-lactide-co-epsilon-caprolactone) after Subcutaneous and Intra-articular Implantation in Rats.

The use of biodegradable materials is gaining popularity in medicine, especially in orthopedic applications. However, preclinical evaluation of biodegradable materials can be challenging, since they are located in close contact with host tissues and might be implanted for a long period of time. Evaluation of these compounds requires biodegradability and biocompatibility studies and meticulous pathology examination.

Self-activation of Caspase-6 in vitro and in vivo: Caspase-6 activation does not induce cell death in HEK293T cells.

Caspase-6 (Casp6) is a short pro-domain caspase that is activated early in Alzheimer disease, yet, little is known on the mechanism of activation of this caspase. In this study, critical proteolytic processing events required for Casp6 activation in vitro and in vivo were evaluated by site directed mutagenesis of the D23 pro-domain, and D179 and D193 linker processing sites. We found that (1) Casp6 was self-processed and activated in vitro and in vivo, (2) uncleavable Casp6 possessed low activity in vitro but not in vivo, (3) the pro-domain of Casp6 entirely prevented self-processing and activation in vivo but not in vitro, (4) removal of the pro-domain promoted Casp6 activation, (5) cleavage at either D179 or D193 was sufficient to generate activity in vitro and in vivo, and (6) Casp6 activity did not induce cell death in HEK293T cells.

Targets of caspase-6 activity in human neurons and Alzheimer disease.

Caspase-6 activation occurs early in Alzheimer disease and sometimes precedes the clinical manifestation of the disease in aged individuals. The active Caspase-6 is localized in neuritic plaques, in neuropil threads, and in neurofibrillary tangles containing neurons that are not morphologically apoptotic in nature. To investigate the potential consequences of the activation of Caspase-6 in neurons, we conducted a proteomics analysis of Caspase-6-mediated cleavage of human neuronal proteins.

Synthesis and evaluation of novel dipeptidyl benzoyloxymethyl ketones as caspase inhibitors.

We describe novel peptide-based caspase inhibitors. Potent and comparatively selective compounds containing a dipeptide scaffold and a substituted oxymethyl ketone as a warhead were developed. The newly synthesized compounds were tested for inhibition in in vitro enzymatic assays of caspases-1, -3, -6, -8, and -9.

Proteasomal degradation of caspase-6 in 17beta-estradiol-treated neurons.

In primary cultures of human neurons, 17beta-estradiol (17beta-E2) prevents caspase-6-mediated cell death and induces a caspase inhibitory factor (CIF) inhibiting active caspase-6 (Csp-6) in vitro. Here, we show that treatment of neurons with 17beta-E2 results in a proteasomal-dependent but ubiquitin-independent degradation of endogenous and exogenous active Csp-6 in live neurons and in cell free assays, respectively. We further show that the proteasomal-dependent degradation of Csp-6 is not required for its inhibition.