Dexamethasone potentiates in vitro blood-brain barrier recovery after primary blast injury by glucocorticoid receptor-mediated upregulation of ZO-1 tight junction protein

Owing to the frequent incidence of blast-induced traumatic brain injury (bTBI) in recent military conflicts, there is an urgent need to develop effective therapies for bTBI-related pathologies. Blood-brain barrier (BBB) breakdown has been reported to occur after primary blast exposure, making restoration of BBB function and integrity a promising therapeutic target. We tested the hypothesis that treatment with dexamethasone (DEX) after primary blast injury potentiates recovery of an in vitro BBB model consisting of mouse brain endothelial cells (bEnd.3). DEX treatment resulted in complete recovery of transendothelial electrical resistance and hydraulic conductivity 1 day after injury, compared with 3 days for vehicle-treated injured cultures. Administration of RU486 (mifepristone) inhibited effects of DEX, confirming that barrier restoration was mediated by glucocorticoid receptor signaling. Potentiated recovery with DEX treatment was accompanied by stronger zonula occludens (ZO)-1 tight junction immunostaining and expression, suggesting that increased ZO-1 expression was a structural correlate to BBB recovery after blast. Interestingly, augmented ZO-1 protein expression was associated with specific upregulation of the α⁺ isoform but not the α⁻ isoform. This is the first study to provide a mechanistic basis for potentiated functional recovery of an in vitro BBB model because of glucocorticoid treatment after primary blast injury.     

The Dynamax system: a new orthopaedic appliance and case report

The Dynamax appliance is a treatment modality for the correction of the Skeletal II malocclusion characterized by a mandibular retrusion. Progressive mandibular advancement, maxillary expansion, control of maxillary growth, incisor torque and control of vertical facial development are incorporated into a two-part appliance. The design facilitates laboratory construction, clinical handling and patient acceptability. A prefabricated spring module forms the basis of the appliance, allowing both maxillary expansion and mandibular advancement. An easily adjustable progressive forward position of the lower jaw makes a construction bite unnecessary. The spring module provides most of the structure of the appliance so that minimal acrylic is required and the appliance is fully contained within the freeway space. Contact between the upper and lower parts of the appliance occurs posteriorly in the lingual sulcus. Here the depth permits an extended vertical contact, to maintain a protrusive mandibular position throughout the range of mandibular opening, including during sleep. The lower portion of the appliance may be fixed or removable and multibracket treatment can be carried out in one or both arches at the same time as the orthopaedics.     

Mechanisms of Killing of Newborn Larvae of Trichinella spiralis by Neutrophils and Eosinophils: KILLING BY GENERATORS OF HYDROGEN PEROXIDE IN VITRO

Eosinophil and/or neutrophil leukocytes appear to have important roles in host defense against invasive, migratory helminth infestations, but the mechanisms of larval killing by leukocytes are uncertain. This study examines killing of newborn (migratory phase) larvae of Trichinella spiralis during incubation with granule preparations of human eosinophils or neutrophils and generators of hydrogen peroxide (glucose-glucose oxidase) (G-GO) or superoxide and hydrogen peroxide (xanthine-xanthine oxidase). Larvae were killed by either hydrogen peroxide-generating system in a concentration-dependent manner. Direct enumeration of surviving larvae after incubation in microtiter wells containing the appropriate reagents was used in assess larval killing. Verification of the microplate assay was demonstrated by complete loss of larval ability to incorporate [(3)H]deoxyglucose and loss of infectivity after incubation in comparable concentrations of G-GO. Larvae were highly sensitive to oxidative products; significant killing occurred after incubation with 0.12 mU glucose oxidase and complete killing occurred with 0.5 mU. Comparable killing of bacteria required over 60 mU glucose oxidase. At 5 mU glucose oxidase, killing was complete after 6 h of incubation. Killing by G-GO was inhibited by catalase but not by boiled catalase or superoxide dismutase and was enhanced by azide. Addition of peroxidase in granule pellet preparations of eosinophils or neutrophils did not enhance killing by G-GO. These data indicate a remarkable susceptibility of newborn larvae of T. spiralis to the hydrogen peroxide generated by neutrophil and eosinophil leukocytes.     

Comparison of Human Eosinophils from Normals and Patients with Eosinophilia

Previous studies of the biochemistry and physiology of eosinophils have relied upon cells obtained from patients with eosinophilia (EE). It is unknown whether such cells might have been activated or partially exhausted by the pathological state causing eosinophilia. We examined cell surface charge, membrane transport of deoxyglucose, activation of lyso-somal acid phosphatase, and oxidative metabolism to provide a profile to compare EE with purified normal eosinophils (NE) and normal neutrophils.     

Creating an Academy of Medical Educators: How and Where to Start

Background

While most faculty members want to improve as teachers, they neither know where their educational strengths and weaknesses lie nor where or how to begin to effect a change in their teaching abilities. The lack of actionable, directed and specific feedback, and sensible and sensitive metrics to assess performance and improvement complicates the attainment of educational excellence.

Purpose

The purpose of this article was to outline a series of specific steps that medical education programs can take to enhance the quality of teaching, promote teaching excellence, elevate the status and value of medical educators, and stimulate the creation of innovative teaching programs and curricula.

Methods

To achieve these goals at the Hospital for Special Surgery, the Academy of Rheumatology Medical Educators was formed. The academy had the following goals: (1) create within our institution a mission which advances and supports educators, (2) establish a membership composed of distinguished educators, (3) create a formal organizational structure with designated leadership, (4) dedicate resources that fund mission-related initiatives and research, and (5) establish a plan for promoting teachers as well as enhancing and advancing educational scholarship.

Results

The Hospital for Special Surgery Academy of Rheumatology Medical Educators was recently formed to address these goals by promoting teaching and learning of musculoskeletal skills in an environment that is supportive to educators and trainees and provides much needed resources for teachers.

Summary

The development of a pilot academy of medical educators represents one of the high-priority goals of those institutions that wish to elevate and enrich their teaching through a structured, proven approach.