Pilot study of the suitability of dorsal vulval skin as a transposition flap: vascular anatomic study and clinical application.

OBJECTIVE: To identify the blood supply to the vulval fold and adjacent skin, and evaluate it as a transposition flap for closing perineal wounds in dogs. STUDY DESIGN: Prospective study. ANIMALS OR SAMPLE POPULATION: Five female canine cadavers and 2 cases referred for excision of mast cell tumors adjacent to the vulva. METHODS: Dissection was performed to identify the vascular supply to the vulval fold in two cadavers following arterial injection of red latex and methylene blue, respectively. In three cadavers, barium sulfate mixed 1:1 with water was injected into the terminal aorta. The vulval fold and surrounding perineal skin was excised and radiographed. Transposition flaps using the vulval fold and adjacent skin were used to close skin defects in two dogs presented for wide excision of mast cell tumors situated ventro-lateral and dorso-lateral to the vulva, respectively. RESULTS: The vulval fold and adjacent skin was perfused bilaterally by branches of the ventral perineal and external pudendal arteries, which entered dorsally and ventrally, respectively. As incisions used to create a transposition flaps from the skin surrounding the vulval fold transect these vessels, the flap is dependent on the sub-dermal plexus for survival. There was 100% survival of transposition flaps in the 2 clinical cases and healing proceeded uneventfully with acceptable cosmetic and functional results. CONCLUSIONS: The vulval fold and surrounding skin can be used as a subdermal plexus flap to close large perineal defects in dogs. CLINICAL RELEVANCE: Availability of a defined local skin flap will improve treatment of diseases resulting in large perineal skin defects in female dogs.

Spongiform encephalopathy in transgenic mice expressing a point mutation in the ß2-α2 loop of the prion protein.

Transmissible spongiform encephalopathies are fatal neurodegenerative diseases attributed to misfolding of the cellular prion protein, PrP(C), into a ß-sheet-rich, aggregated isoform, PrP(Sc). We previously found that expression of mouse PrP with the two amino acid substitutions S170N and N174T, which result in high structural order of the ß2-α2 loop in the NMR structure at pH 4.5 and 20°C, caused transmissible de novo prion disease in transgenic mice. Here we report that expression of mouse PrP with the single-residue substitution D167S, which also results in a structurally well ordered ß2-α2 loop at 20°C, elicits spontaneous PrP aggregation in vivo. Transgenic mice expressing PrP(D167S) developed a progressive encephalopathy characterized by abundant PrP plaque formation, spongiform change, and gliosis. These results add to the evidence that the ß2-α2 loop has an important role in intermolecular interactions, including that it may be a key determinant of prion protein aggregation.

Prion strain interactions are highly selective.

Various misfolded and aggregated neuronal proteins commonly coexist in neurodegenerative disease, but whether the proteins coaggregate and alter the disease pathogenesis is unclear. Here, we used mixtures of distinct prion strains, which are believed to differ in conformation, to test the hypothesis that two different aggregates interact and change the disease in vivo. We tracked two prion strains in mice histopathologically and biochemically, as well as by spectral analysis of plaque-bound PTAA (polythiophene acetic acid), a conformation-sensitive fluorescent amyloid ligand. We found that prion strains interacted in a highly selective and strain-specific manner, with (1) no interaction, (2) hybrid plaque formation, or (3) blockage of one strain by a second (interference). The hybrid plaques were maintained on additional passage in vivo and each strain seemed to maintain its original conformational properties, suggesting that one strain served only as a scaffold for aggregation of the second strain. These findings not only further our understanding of prion strain interactions but also directly demonstrate interactions that may occur in other protein aggregate mixtures.