Effects of Intraventricular Methotrexate on Neuronal Injury and Gene Expression in a Rat Model: Findings From an Exploratory Study.

Central nervous system (CNS)-directed treatment for acute lymphoblastic leukemia, used to prevent disease recurrence in the brain, is essential for survival. Systemic and intrathecal methotrexate, commonly used for CNS-directed treatment, have been associated with cognitive problems during and after treatment. The cortex, hippocampus, and caudate putamen, important brain regions for learning and memory, may be involved in methotrexate-induced brain injury. Objectives of this study were to (1) quantify neuronal degeneration in selected regions of the cortex, hippocampus, and caudate putamen and (2) measure changes in the expression of genes with known roles in oxidant defense, apoptosis/inflammation, and protection from injury. Male Sprague Dawley rats were administered 2 or 4 mg/kg of methotrexate diluted in artificial cerebrospinal fluid (aCSF) or aCSF only into the left cerebral lateral ventricle. Gene expression changes were measured using customized reverse transcription (RT)(2) polymerase chain reaction arrays. The greatest percentage of degenerating neurons in methotrexate-treated animals was in the medial region of the cortex; percentage of degenerating neurons in the dentate gyrus and cornu ammonis 3 regions of the hippocampus was also greater in rats treated with methotrexate compared to perfusion and vehicle controls. There was a greater percentage of degenerating neurons in the inferior cortex of control versus methotrexate-treated animals. Eight genes involved in protection from injury, oxidant defense, and apoptosis/inflammation were significantly downregulated in different brain regions of methotrexate-treated rats. To our knowledge, this is the first study to investigate methotrexate-induced injury in selected brain regions and gene expression changes using a rat model of intraventricular drug administration.

Composite hydrogel scaffolds with controlled pore opening via biodegradable hydrogel porogen degradation.

Poly(ß-amino ester) (PBAE) biodegradable hydrogel systems have garnered much attention in recent years due to their appealing properties for biomedical applications. These hydrogel systems exhibit properties similar to natural soft tissue, degrade in aqueous environments, and have easily tunable properties that have been well studied and understood. In most cases, tissue engineering scaffolds must possess a three-dimensional interconnected porous network for tissue ingrowth and construct vascularization. Here, PBAE properties were explored and systems were selected to serve as both the pore-forming agent and the outer matrix of a scaffold that exhibits controlled pore opening upon degradation. To our knowledge, this is the first demonstration of a biodegradable hydrogel porogen system entrapped in a degradable hydrogel outer matrix. Scaffolds were prepared, and the degradation, compressive moduli, and porosity were analyzed. An added advantage of a degradable porogen is the potential for controlled drug release, and a model protein was released from the porogen particles to demonstrate this application. Finally, pluripotent cells seeded onto predegraded scaffolds were viable during the first 24 h of exposure, and furthermore, cell tracking confirmed the presence of cells within the pores of the scaffold. Overall, these present studies demonstrate the possibility of using these biodegradable hydrogel porogen-matrix systems as tissue engineering scaffolding materials.

Magnetic nanocomposite sol-gel systems for remote controlled drug release.

The remote heating of iron oxide nanoparticles in an alternating magnetic field is used to drive a thermoresponsive sol-gel block copolymer, Pluronic® F-127, through the upper phase transition temperature. This phase change triggers an accelerated release rate of a model drug. Actuation and return to baseline levels are demonstrated for multiple AMF doses.

Synthesis and analysis of degradation, mechanical and toxicity properties of poly(ß-amino ester) degradable hydrogels.

Biodegradable hydrogels have been studied extensively in recent years for biomedical applications, including tissue engineering and drug delivery, due to their tunable properties and similarities to natural soft tissue. In this work, two poly(ß-amino ester) biodegradable hydrogel systems were synthesised and studied in vitro. Different degradation profiles were observed, ranging from 7 h to 4 months, and the compressive modulus was shown to decrease as degradation proceeded. MTT cytotoxicity analysis was used to analyze the cellular response to the degradation products, and the hydrogel systems exhibited similar toxicity to poly(dl-lactide-co-glycolide) degradation products. Finally, cell attachment was studied by seeding pluripotent mesenchymal cells directly onto the hydrogel surfaces followed by a live/dead assay and fluorescent imaging. Cells showed significant viability at 24h (98%) and slightly lower, but still substantial viability, at 48 h (72%). These hydrogels exhibited a range of properties and favorable cellular responses, all which indicate that these materials could be viable materials for tissue regeneration and other biomedical applications.

Nanocomposite degradable hydrogels: demonstration of remote controlled degradation and drug release.

PURPOSE: To demonstrate remote controlled degradation of degradable nanocomposite hydrogels by application of an alternating magnetic field (AMF). Further, it was desired to study the AMF effect on the drug release properties of these systems. METHODS: Degradable nanocomposite hydrogels were synthesized by incorporating iron oxide nanoparticles into a degradable hydrogel that exhibited temperature dependent degradation. Heating, degradation, and drug release studies were conducted by application of an AMF to determine if modulation of degradation and drug release could be attained. RESULTS: Hydrogels were successfully prepared, shown to have temperature dependent degradation, and shown to heat when exposed to the AMF. The degradation rate of the exposed samples was demonstrated to be higher than control samples, thus modulation of degradation was obtained. The release of a model drug from the system was modulated by exposure to the AMF. CONCLUSIONS: This is the first demonstration of remote controlled degradation using an AMF stimulus. Here, the proof of the concept has been presented, and there is great potential to enhance this effect through various methods. The ability to remotely control degradation of an implanted device opens a new area of improved medical devices.

Knowledge, resilience, and effectiveness of education in a young teen asthma camp.

A young teen asthma camp was developed as a 3-day residential experience in a traditional camp setting offering activities such as swimming, canoeing, horseback riding, ropes, course crafts, and games. The overall purpose, goals and plans for the camp experience were developed by a team of nurse educators, nurse practitioners, clinicians (nurses and physicians) with experience in asthma management, and camp directors. Feasibility and outcomes were measured for the camp using materials in the Power Breathing Program for teens developed by the Asthma and Allergy Foundation of America (AAFA) and questionnaires developed by the Consortium of Children's Asthma Camps.