Further development of an in vitro model for studying the penetration of chemicals through compromised skin

A new in vitro model based on the electrical resistance properties of the skin barrier has been established in this laboratory. The model utilises a tape stripping procedure in dermatomed pig skin that removes a specific proportion of the stratum corneum, mimicking impaired barrier function observed in humans with damaged skin. The skin penetration and distribution of chemicals with differing physicochemical properties, namely; Benzoic acid, 3-Aminophenol, Caffeine and Sucrose has been assessed in this model. Although, skin penetration over 24 h differed for each chemical, compromising the skin did not alter the shape of the time course profile, although absorption into receptor fluid was higher for each chemical. Systemic exposure (receptor fluid, epidermis and dermis), was marginally higher in compromised skin following exposure to the fast penetrant, Benzoic acid, and the slow penetrant Sucrose. The systemically available dose of 3-Aminophenol increased to a greater extent and the absorption of Caffeine was more than double in compromised skin, suggesting that Molecular Weight and Log Pow, are not the only determinants for assessing systemic exposure under these conditions. Although further investigations are required, this in vitro model may be useful for prediction of dermal route exposure under conditions where skin barrier is impaired

Antimicrobial efficacy and mechanism of action of poly(amidoamine) (PAMAM) dendrimers against opportunistic pathogens.

The aim of this study was to investigate a range of poly(amidoamine) (PAMAM) dendrimer generations against Gram-positive and Gram-negative skin pathogens and to determine any differences in antimicrobial potency for different generations, characterising how differences in physicochemical properties influence antimicrobial efficacy. A range of tests were carried out, including viable count assays to determine IC50 values for each dendrimer, membrane integrity studies and an inner membrane permeabilisation assay. This is supported by scanning electron microscopy imaging of the interactions observed between dendrimers and bacteria. The results of this study indicate that the antimicrobial efficacy of native PAMAM dendrimers is dependent on generation, concentration and terminal functionalities, for example the MIC50 (υg/mL) against S. aureus was between 26.77 for the G2-PAMAM-NH2 dendrimer and 2.881 for the G5-PAMAM-NH2 dendrimer. There was a strong correlation between membrane disruption and the determined biocidal activity, making it a key contributing mechanism of action. This study demonstrates that selection of the type of PAMAM dendrimer is important as their inherent antimicrobial efficacy varies according to their individual physicochemical properties. This understanding may pave the way for the development of enhanced dendrimer-based antimicrobial formulations and drug delivery systems

Evaluation of marking of peer marking in oral presentation.

BACKGROUND: Peer marking is an important skill for students, helping them to understand the process of learning and assessment. This method is increasingly used in medical education, particularly in formative assessment. However, the use of peer marking in summative assessment is not widely adopted because many teachers are concerned about biased marking by students of their peers. OBJECTIVE: The aim of this study was to investigate whether marking of summative peer assessment can improve the reliability of peer marking. METHODS: In a retrospective analysis, the peer-marking results of a summative assessment of oral presentations of two cohorts of students were compared. One group of students was told that their peer marks would be assessed against a benchmark consisting of the average of examiner marks and that these scores together with the peer and examiner marks would form their final exam results. The other group of students were just informed that their final exam results would be determined based on the examiner and peer marks. RESULTS: Based on examiner marks, both groups of students performed similarly in their summative assessment, agreement between student markers was less consistent and more polar than the examiners. When compared with the examiners, students who were told that their peer marking would be scored were more generous markers (their average peer mark was 2.4 % points higher than the average examiner mark) while students who were not being scored on their marking were rather harsh markers (their average peer mark was 4.2 % points lower than the average examiner mark), with scoring of the top-performing students most affected. CONCLUSIONS: Marking of peer marking had a small effect on the marking conduct of students in summative assessment of oral presentation but possibly indicated a more balanced marking performance

Histological evidence for a supraspinous ligament in sauropod dinosaurs

Supraspinous ossified rods have been reported in the sacra of some derived sauropod dinosaurs. Although different hypotheses have been proposed to explain the origin ofthis structure, histological evidence has never been provided to support or reject any of them. In order to establish its origin, we analyse and characterize the microstructure of thesupraspinous rod of two sauropod dinosaurs from the Upper Cretaceous of Argentina. The supraspinous ossified rod is almost entirely formed by dense Haversian bone. Remains ofprimary bone consist entirely of an avascular tissue composed of two types of fibre-like structures, which are coarse and longitudinally (parallel to the main axis of the element) oriented. These structures are differentiated on the basis of their optical properties under polarized light. Very thin fibrous strands are also observed in some regions. These small fibres are all oriented parallel to one another but perpendicular to the element main axis. Histological features of the primary bone tissue indicate that the sacral supraspinous rod corresponds to an ossified supraspinous ligament. The formation of this structure appears to have been a non-pathological metaplastic ossification, possibly induced by the continuous tensile forces applied to the element.Fil: Cerda, Ignacio Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigación en Paleobiología y Geología; Argentina. Universidad Nacional de Río Negro; ArgentinaFil: Casal, Gabriel. Universidad Nacional de la Patagonia; ArgentinaFil: Martínez, Rubén Darío. Universidad Nacional de la Patagonia ; ArgentinaFil: Ibiricu, Lucio Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Nacional Patagónico; Argentin

Development of an in vitro model for studying the penetration of chemicals through compromised skin.

The conventional safety approach that includes dermal absorption of pharmaceutical or consumer products uses models that are based on intact skin. However, when products are intended for application to skin with a less effective barrier, such as in new-born infants, or in cases where the skin is mildly damaged or diseased, there are instances where absorption through compromised skin is also important. A tape stripping procedure was investigated using dermatomed pig skin to assess if an in vitro model could replicate the typical changes in barrier function observed in humans with compromised skin. The relationship between Trans-Epidermal Water Loss (TEWL), Electrical Resistance (ER) and Tritiated Water Flux(TWF), markers of skin barrier function in OECD 428 studies was investigated. There was a step-wise reduction in ER from normal (control) skin following 5, 10, 15 or 20 tape strips. This was mirrored by increases in both TWF and TEWL. An in vitro experimental protocol using 5 tape strips, ER and dermatomed pig skin provided a rapid, robust and reproducible approach equivalent to the 3–4-fold increases in TEWL observed clinically in compromised skin