A rabbit model for assessment of volatile metabolite changes observed from skin: a pressure ulcer case study.

Human skin presents a large, easily accessible matrix that is potentially useful for diagnostic applications based on whole body metabolite changes-some of which will be volatile and detected using minimally invasive tools. Unfortunately, identifying skin biomarkers that can be reliably linked to a particular condition is challenging due to a large variability of genetics, dietary intake, and environmental exposures within human populations. This leads to a paucity of clinically validated volatile skin biomarker compounds. Animal models present a very convenient and attractive way to circumvent many of the variability issues. The rabbit (Leporidae) is a potentially logistically useful model to study the skin metabolome, but very limited knowledge of its skin metabolites exists. Here we present the first comprehensive assessment of the volatile fraction of rabbit skin metabolites using polydimethylsiloxane sorbent patch sampling in conjunction with gas chromatography/mass spectrometry. A collection of compounds that are secreted from rabbit skin was documented, and predominantly acyclic long-chain alkyls and alcohols were detected. We then utilized this animal model to study differences between intact skin and skin with early pressure ulcers, as the latter are a major problem in intensive care units. Four New Zealand female white rabbits underwent ulcer formation on one ear with the other ear as a control. Early-stage ulcers were created with neodymium magnets. Histologic analysis showed acute heterophilic dermatitis, edema, and micro-hemorrhage on the ulcerated ears with normal findings on the control ears. The metabolomic analysis revealed subtle but noticeable differences, with several compounds associated with the oxidative stress-related degradation of lipids found to be present in greater abundances in ulcerated ears. The metabolomic findings correlate with histologic evidence of early-stage ulcers. We postulate that the Leporidae model recapitulated the vascular changes associated with ulcer formation. This study illustrates the potential usefulness of the Leporidae model for skin metabolome studies. Additionally, skin metabolome analysis may enhance an understanding of non-skin sources such as urine or breath.

Barbering (fur and whisker trimming) by laboratory mice as a model of human trichotillomania and obsessive-compulsive spectrum disorders.

Animal diseases that develop spontaneously in a limited subpopulation can provide powerful models of human disease because they provide a means to investigate the interaction of a broad range of biological and environmental etiologic processes. In contrast, with experimentally induced animal models, the etiology of the model is inherently fixed, and can only speak to a limited subset of those involved in the human disease. 'Barbering' (abnormal whisker- and fur-plucking behavior) in mice resembles human trichotillomania (compulsive hair plucking) in that barbering mice pluck focused areas of hair, and engage in post-plucking manipulatory and oral behaviors. We performed a cross-sectional epidemiologic survey of a population of 2,950 laboratory mice to further assess the face validity of barbering as a spontaneous model of trichotillomania. Patterns of hair loss and demographic and etiologic risk factors were recorded for each mouse, and were analyzed by use of logistic regression. Barbering paralleled trichotillomania in terms of phenomenology, demography, and etiology. Thus, similar to trichotillomania, barbers predominately plucked hair from the scalp and around the eyes and the genitals; barbering was female biased, and had its onset during puberty; and etiologic factors included reproductive status and genetic background. Therefore, barbering has excellent face validity as a model of trichotillomania, and may represent a refined and non-invasive model, especially for studies of the complex genetic/environmental etiologies of this disorder.