Treating brain diseases using systemic parenterally-administered protein therapeutics: Dysfunction of the brain barriers and potential strategies.

The parenteral administration of protein therapeutics is increasingly gaining importance for the treatment of human diseases. However, the presence of practically impermeable blood-brain barriers greatly restricts access of such pharmaceutics to the brain. Treating brain disorders with proteins thus remains a great challenge, and the slow clinical translation of these therapeutics may be largely ascribed to the lack of appropriate brain delivery system. Exploring new approaches to deliver proteins to the brain by circumventing physiological barriers is thus of great interest. Moreover, parallel advances in the molecular neurosciences are important for better characterizing blood-brain interfaces, particularly under different pathological conditions (e.g., stroke, multiple sclerosis, Parkinson's disease, and Alzheimer's disease). This review presents the current state of knowledge of the structure and the function of the main physiological barriers of the brain, the mechanisms of transport across these interfaces, as well as alterations to these concomitant with brain disorders. Further, the different strategies to promote protein delivery into the brain are presented, including the use of molecular Trojan horses, the formulation of nanosystems conjugated/loaded with proteins, protein-engineering technologies, the conjugation of proteins to polymers, and the modulation of intercellular junctions. Additionally, therapeutic approaches for brain diseases that do not involve targeting to the brain are presented (i.e., sink and scavenging mechanisms).

Releasable and traceless PEGylation of arginine-rich antimicrobial peptides.

Arginine-rich antimicrobial peptides (AMPs) are emerging therapeutics of interest. However, their applicability is limited by their short circulation half-life, caused in part by their small size and digestion by blood proteases. This study reports a strategy to temporarily mask arginine residues within AMPs with methoxy poly(ethylene glycol). Based on the reagent used, release of AMPs occurred in hours to days in a completely traceless fashion. In vitro, conjugates were insensitive to serum proteases, and released native AMP with full in vitro bioactivity. This strategy is thus highly relevant and should be adaptable to the entire family of arginine-rich AMPs. It may potentially be used to improve AMP-therapies by providing a more steady concentration of AMP in the blood after a single injection, avoiding toxic effects at high AMP doses, and reducing the number of doses required over the treatment duration.

Intense THz Pulses with large ponderomotive potential generated from large aperture photoconductive antennas.

We report the generation of free space terahertz (THz) pulses with energy up to 8.3 ± 0.2 µJ from an encapsulated interdigitated ZnSe Large Aperture Photo-Conductive Antenna (LAPCA). An aperture of 12.2 cm2 is illuminated using a 400 nm pump laser with multi-mJ energies at 10 Hz repetition rate. The calculated THz peak electric field is 331 ± 4 kV/cm with a spectrum characterized by a median frequency of 0.28 THz. Given its relatively low frequency, this THz field will accelerate charged particles efficiently having very large ponderomotive energy of 15 ± 1 eV for electrons in vacuum. The scaling of the emission is studied with respect to the dimensions of the antenna, and it is observed that the capacitance of the LAPCA leads to a severe decrease in and distortion of the biasing voltage pulse, fundamentally limiting the maximum applied bias field and consequently the maximum energy of the radiated THz pulses. In order to demonstrate the advantages of this source in the strong field regime, an open-aperture Z-scan experiment was performed on n-doped InGaAs, which showed significant absorption bleaching.

Oxygen inhibition in dental resins.

Oxygen inhibits free radical polymerization and yields polymers with uncured surfaces. This is a concern when thin layers of resin are being polymerized, or in circumstances where conventional means of eliminating inhibition are inappropriate. In this study, we tested the hypothesis that viscosity, filler content, and polymerization temperature modify oxygen diffusion in the resin or the reactivity of radical species, and affect the degree of conversion near the surface. Confocal Raman micro-spectroscopy was used to measure monomer conversion from the surface to the bulk of cured resins. Increased viscosity was shown to limit oxygen diffusion and increase conversion near the surface, without necessarily modifying the depth of inhibition. The filler material was shown to increase, simultaneously, oxygen diffusivity and the viscosity of the resin, which have opposite effects on conversion. Polymerization at a temperature above approximately 110 degrees C was shown to eliminate oxygen inhibition.

Gaining and sustaining minority participation in longitudinal research projects.

African-Americans are often not enthusiastic about participating in Alzheimer disease research due to past exploitation from medical and public health studies. To assure adequate representation from the African-American community, and to investigate the health needs of this population, strategies to recognize the problems and address the issues have been developed. The recruitment approach used existing connections in an urban community using culturally sensitive strategies. These strategies recruited elderly patients from an existing relationship with the Boston University Medical Center Geriatric Service. They built on the researchers' association with a neighborhood health center located in one of the Boston communities and utilized the services of an outreach worker. The outreach worker was from the community, aware of the health care needs of the elderly, and had a relationship with existing elderly community groups. Several methods were used to recruit patients. These included one-on-one discussions, posters, existing relationships with elderly groups, and direct phone calls. To develop trust carefully with the community's elders, multiple trust-building strategies were used. A multifaceted recruitment approach and strong linkages between the research team and the community were essential to successful recruitment and retention of participants.

The role of empowerment in neighborhood-based nursing education.

It is a challenge to prepare nursing students for practice in the rapidly changing healthcare arena. A longitudinal clinical education experience, external to tertiary institutions and supportive of lifelong learning, creative and critical thinking is one way to empower students to provide appropriate care within a diverse population and evolving healthcare system. Nursing faculty, nursing students, community providers and neighborhood residents participate as colleagues in a joint venture of assessment, intervention, and learning.