Intravenous Infusion of Cereport Increases Uptake and Efficacy of Acyclovir in Herpes Simplex Virus-Infected Rat Brains

The outcome of herpes simplex virus (HSV) infections manifesting as encephalitis in healthy or immunocompromised individuals is generally very poor with mortality rates of about 8 to 28% with treatment. The long-term prognosis of survivors is often problematic, posing the need for alternative treatments that may decrease the mortality and morbidity associated with herpes encephalitis. This study addresses one such approach that includes a temporary permeabilization of the blood-brain barrier during treatment with acyclovir (ACV). In these studies we utilized a synthetic bradykinin analog, Cereport (RMP-7), in conjunction with ACV to treat HSV infection of the brain in a rat model. Cereport, infused intravenously via the jugular vein, was shown to increase [(14)C]ACV uptake in both the HSV-1-infected and -uninfected rat brain by approximately two- to threefold, correlating with enhanced efficacy of ACV in various brain compartments. In another series of experiments to determine efficacy, various doses of unlabeled ACV were administered during infusion with RMP-7. The decrease in viral titers in the temporal regions of the brain after 5 days of treatment suggested that this approach enhanced the efficacy of ACV treatment. These data indicated that Cereport infused with ACV enhances both the penetration and efficacy of this drug in the treatment of an experimental HSV-1 infection of the rat brain

Review of emerging temporomandibular joint total joint replacement systems.

Total temporomandibular joint (TMJ) replacement has been documented as a viable option for the management of end-stage TMJ disease, but data on long-term outcomes have been reported for only two established systems: TMJ Concepts, and Zimmer Biomet. Other devices are now emerging globally, but reports of preclinical laboratory and clinical outcomes are limited. We retrieved information on the design, material composition, preclinical laboratory tests, regulatory status, and clinical outcomes of new TMJ replacement systems from PubMed and Google, and from personal correspondence with surgeons worldwide. Fifteen countries have developed, or are developing, 27 TMJ replacement systems, of which 21 are custom-designed, but to date, only four have been given regulatory approval. All the devices are designed to have both a skull-based glenoid fossa component and a mandibular ramus or condyle, and 22/27 are similar to the designs of the two established systems. Twenty-one devices use an ultra-high-molecular-weight polyethylene (UHMWPE) fossa-bearing surface, and 10 have a titanium alloy condyle. Nineteen manufacturers report that a titanium alloy is used for the ramus portion of the condyle/ramus component. Preclinical laboratory tests on 12 of the systems have been reported but, to our knowledge, no outcomes have yet been reported on nine of the 27 reviewed. Not all systems are equal in terms of design, material composition, preclinical laboratory testing, manufacturing methods, regulatory status, and reports of clinical outcomes