Hexyl Aminolaevulinate Is a More Effective Topical Photosensitiser Precursor than Methyl Aminolaevulinate and 5-Aminolaevulinic Acids When Applied in Equimolar Doses

Aminolaevulinic acid (ALA) is known to poorly penetrate into thick lesions, such as nodular basal cell carcinomas Short chain ALA esters, possessing increased lipophilicity relative to their hydrophilic parent, have previously been shown to be highly efficient at inducing protoporphyrin IX (PpIX) production in cell culture, at equimolar concentrations. In contrast, in vitro skin permeation and in vivo animal studies, which up to now have compared prodrugs on a % w/vv basis, have failed to demonstrate such benefits For the first time, equimolar concentrations of ALA, methyl-ALA (m-ALA) and hexyl-ALA (h-ALA) have been incorporated into an o/w cream preparation. In vitro penetration studies into excised porcine skin revealed that increased levels of h-ALA, compared to ALA and m-ALA were found in the upper skin layers, at all drug loadings studied. Topical application of the formulations to nude murine skin in vivo, revealed that creams containing h-ALA induced significantly higher levels of peak PpIX fluorescence (F-max = 289.0) at low concentrations compared to m-ALA (F-max = 159.2) and ALA (F-max = 191 9). Importantly, this study indicates that when compared on an equimolar basis, h-ALA has improved skin penetration, leading to enhanced PpIX production compared to the parent drug and m-ALA (C) 2010 Wiley-Liss, Inc and the American Pharmacists Association J Pharm Sci 99 3486-3498, 2010

Molecular diagnosis for heterogeneous genetic diseases with high-throughput DNA sequencing applied to retinitis pigmentosa

BACKGROUND:
The genetic heterogeneity of many Mendelian disorders, such as retinitis pigmentosa which results from mutations in over 40 genes, is a major obstacle to obtaining a molecular diagnosis in clinical practice. Targeted high-throughput DNA sequencing offers a potential solution and was used to develop a molecular diagnostic screen for patients with retinitis pigmentosa.
METHODS:
A custom sequence capture array was designed to target the coding regions of all known retinitis pigmentosa genes and used to enrich these sequences from DNA samples of five patients. Enriched DNA was subjected to high-throughput sequencing singly or in pools, and sequence variants were identified by alignment of up to 10 million reads per sample to the normal reference sequence. Potential pathogenicity was assessed by functional predictions and frequency in controls.
RESULTS AND CONCLUSIONS:
Known homozygous PDE6B and compound heterozygous CRB1 mutations were detected in two patients. A novel homozygous missense mutation (c.2957A?T; p.N986I) in the cyclic nucleotide gated channel ß1 (CNGB1) gene predicted to have a deleterious effect and absent in 720 control chromosomes was detected in one case in which conventional genetic screening had failed to detect mutations. The detection of known and novel retinitis pigmentosa mutations in this study establishes high-throughput DNA sequencing with DNA pooling as an effective diagnostic tool for heterogeneous genetic diseases.

Teaching and learning technologies in Higher Education: Applied behaviour analysis and autism.

Professionals on both international and national levels who work with children with autism are expressing the need for graduate-level training in applied behaviour analysis. The implementation of effective instruction in higher education for professionals working with children with autism and their families is a complex undertaking: the learner needs to acquire an understanding of the principles and procedures of applied behaviour analysis and also adapt this knowledge to the learning prerequisites of individuals with autism. In this paper we outline some current thinking about adult education and blended learning technologies and then describe and illustrate with examples emerging possibilities of multimedia technology in the development of teaching materials. We conclude that synergies between graduate-level curriculum requirements, knowledge of adult learning, and communication technology are necessary to establish comprehensive learning environments for professionals who specialize in autism intervention.