Pilot Studies on the Novel Hypothesis that TSPO (Peripheral Benzodiazepine Receptor) Is Involved in Benzodiazepine/“Z-Drug” Physical Dependence and/or Withdrawal

Benzodiazepines and other benzodiazepine receptor agonists, such as the “Z” drugs, are widely prescribed medications mainly used for treating anxiety and seizures, and for inducing sedation. Unfortunately, despite their popularity, benzodiazepine prescribing often exceeds recommendations and the consequences can be severe. On September 23, 2020, the United States FDA announced a new requirement for a Boxed Warning for benzodiazepines prescribing. Along with this announcement, the FDA stated that relevant information regarding the initiation, continuation, and discontinuation of benzodiazepines is lacking. Here, we describe initial pilot studies intended to investigate the questions 1) can animal models be developed that demonstrate benzodiazepine physical dependence and/or withdrawal symptoms, and 2) determine whether translocator protein (TSPO) plays a role in benzodiazepine dependence and/or withdrawal processes. The former was demonstrated, methodological limitations prevented the latter.

In vitro and in vivo degradation behavior of Mg-2Sr-Ca and Mg-2Sr-Zn alloys

Magnesium alloys with integration of degradability and good mechanical performance are desired for orthopedic implants.In this paper,Mg-2Sr-Ca and Mg-2Sr-Zn alloys were prepared and the degradation as well as the bone response were investigated.Compared with the binary Mg-2Sr alloys,the addition of Ca and Zn improved the in vitro and in vivo corrosion resistance.Mg-2Sr-Ca and Mg-2Sr-Zn alloys exhibited more uniform corrosion and maintained the configuration of the implants 4 weeks post-implantation.The in vivo corrosion rates were 0.85 mm/yr for Mg-2Sr-Zn and 1.10 mm/yr for Mg-2Sr-Ca in comparison with 1.37 mm/yr for Mg-2Sr.The in vitro cell tests indicated that Mg-2Sr-Ca and Mg-2Sr-Zn alloys exhibited higher MG63 cell viability than Mg-2Sr alloy.Furthermore,these two alloys can promote the mineralization and new bone formation without inducing any significant adverse effects and this sound osteogenic properties suggest its attractive clinical potential.

In Vivo and In Vitro Degradation Behavior of Magnesium Alloys as Biomaterials

The corrosion behavior of pure Mg,AZ31,and AZ91D were evaluated in various in vitro and in vivo environments to investigate the potential application of these metals as biodegradable implant materials.DC polarization tests and immersion tests were performed in different simulated body solutions,such as distilled（DI） water,simulated body fluid（SBF） and phosphate buffered solution（PBS）.Mg/Mg alloys were also implanted in different places in a mouse for in vivo weight loss and biocompatibility investigations.The in vivo subcutis bio-corrosion rate was lower than the corrosion rate for all of the in vitro simulated corrosive environments.The Mg/Mg alloys were biocompatible based on histology results for the liver,heart,kidney,skin and lung of the mouse during the two months implantation.Optical microscopy and scanning electron microscopy were carried out to investigate the morphology and topography of Mg/Mg alloys after immersion testing and implantation to understand the corrosion mechanisms.

In vivo biocompatibility and degradability of a Zn-Mg-Fe alloy osteosynthesis system

Zinc is generally considered to be one of the most promising materials to be used in biodegradable implants,and many zinc alloys have been optimized to improve implant biocompatibility,degradation,and mechanical properties.However,long-term degradation leads to the prolonged presence of degradation products,which risks foreign body reactions.Herein,we investigated the in vivo biocompatibility and degradation of a biodegradable Zn-Mg-Fe alloy osteosynthesis system in the frontal bone,mandible,and femur in beagles for 1 year.Results of the routine blood,biochemical,trace element,and histological analyses of multiple organs,peripheral blood CD4/CD8a levels,and serum interleukin 2 and 4 levels showed good biocompatibility of the Zn-Mg-Fe alloy.Zinc content analysis revealed zinc accumulation in adjacent bone tissue,but not in the liver,kidney,and spleen,which was related to the degradation of the Zn-Mg-Fe alloy.The alloy demonstrated a uniform slowing degradation rate in vivo.No degradation differences in the frontal bone,mandible,and femur were observed.The degradation products included zinc oxide[ZnO],zinc hydroxide[Zn(OH)_(2)],hydrozincite[Zn_(5)(OH)_(6)(CO_(3))_(2)],and hopeite[Zn_(3)(PO_(4))_(2)⋅4H_(2)O].The good biocompatibility and degradation properties of the Zn-Mg-Fe alloy render it a very attractive osteosynthesis system for clinical applications.