Validation of laser doppler flowmetry to measure dermal blood flow of the pinnae in dogs with pinnal alopecia.

BACKGROUND: Laser Doppler flowmetry (LDF) is a noninvasive method of measuring regional blood flow in humans. However, this method has not been widely applied to measure blood flow in dogs. HYPOTHESIS/OBJECTIVES: We hypothesised that LDF can measure changes in blood flow in canine pinnae accurately. The objectives were to determine whether LDF could accurately detect dermal blood flow changes in canine pinnae caused by haemodynamic drugs and characterize the dermal blood flow in dogs with pinnal alopecia. ANIMALS: Sixteen laboratory-owned healthy dogs, 25 client-owned healthy control dogs and six dogs with pinnal alopecia suspected to be secondary to ischaemic dermatoses. MATERIALS AND METHODS: Clinical doses of the haemodynamic drugs atropine, medetomidine and dibutyryl cyclic adenosine monophosphate (dBcAMP), as well as topical dBcAMP, were administered to healthy beagles. Subsequently, an LDF apparatus was attached to the pinnae to analyse changes in dermal blood flow. Finally, LDF was used to measure auricular dermal blood flow in dogs with pinnal alopecia compared to healthy dogs. RESULTS: Dermal blood flow increased after atropine injection, during dBcAMP infusion and after topical dBcAMP ointment application, and decreased after medetomidine injection. Auricular dermal blood flow (in mL/min/100 g tissue) was significantly (p < 0.05) lower in dogs with pinnal alopecia than in healthy dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Laser Doppler flowmetry is useful for measuring dermal blood flow in canine pinnae; it can be a noninvasive method to monitor ischaemic conditions of dog skin.

Impairment of nuclear F-actin formation and its relevance to cellular phenotypes in Hutchinson-Gilford progeria syndrome.

Hutchinson-Gilford progeria syndrome (HGPS) is a premature aging disorder caused by a mutation of lamin A, which contributes to nuclear architecture and the spatial organization of chromatin in the nucleus. The expression of a lamin A mutant, named progerin, leads to functional and structural disruption of nuclear organization. Since progerin lacks a part of the actin-binding site of lamin A, we hypothesized that nuclear actin dynamics and function are altered in HGPS cells. Nuclear F-actin is required for the organization of nuclear shape, transcriptional regulation, DNA damage repair, and activation of Wnt/ß-catenin signaling. Here we show that the expression of progerin decreases nuclear F-actin and impairs F-actin-regulated transcription. When nuclear F-actin levels are increased by overexpression of nuclear-targeted actin or by using jasplakinolide, a compound that stabilizes F-actin, the irregularity of nuclear shape and defects in gene expression can be reversed. These observations provide evidence for a novel relationship between nuclear actin and the etiology of HGPS.