Clinical and antiviral effect of a single oral dose of famciclovir administered to cats at intake to a shelter.

Although famciclovir is efficacious in feline herpesvirus type 1 (FHV-1)-infected cats, effects of a single dose early in disease course have not been reported. In this two part, randomized, masked, placebo controlled study, cats received a single dose of 125 mg famciclovir (n = 43) or placebo (n = 43; pilot study), or 500 mg famciclovir (n = 41) or placebo (n = 40; clinical trial) on entering a shelter. FHV-1 PCR testing was performed, bodyweight and food intake were recorded, and signs of respiratory disease were scored prior to and 7 days following treatment. FHV-1 DNA was detected in 40% of cats in both parts at study entry. In the pilot study, ocular and nasal discharge scores increased from days 1 to 7 in famciclovir and placebo treated cats. Sneezing scores increased and bodyweight decreased in famciclovir-treated cats. The proportion of cats in which FHV-1 DNA was detected increased over time in all cats in the pilot study. In the clinical trial, food intake and median clinical disease scores for nasal discharge and sneezing increased from days 1 to 7 in both groups and demeanor scores worsened in famciclovir-treated cats. The proportion of cats shedding FHV-1 DNA was greater on day 7 than on day 1 in cats receiving 500 mg famciclovir. A single dose of famciclovir (125 or 500 mg) administered at shelter intake was not efficacious in a feline population in which 40% were already shedding FHV-1

Effects of 0.2% brimonidine and 0.2% brimonidine-0.5% timolol on intraocular pressure and pupil size in normal equine eyes.

BackgroundBrimonidine is an α2 -adrenergic agonist that decreases aqueous humour production and may increase uveoscleral outflow. It has not been evaluated in normal or glaucomatous equine eyes.ObjectivesTo evaluate the efficacy and safety of brimonidine in lowering intraocular pressure (IOP), alone and in conjunction with timolol, as a treatment for equine glaucoma by comparing IOP in normal equine eyes treated with brimonidine and brimonidine-timolol, respectively, with IOP in control eyes.Study designA balanced crossover design with 16 horses receiving one of two treatments, brimonidine and brimonidine-timolol, during each of two 10-day study phases, was used. Four horses were randomly assigned to each of four combinations of treated eye (right or left) and drug order within the two 10-day study phases (brimonidine first or brimonidine-timolol first).MethodsPupil size and conjunctival hyperaemia were assessed twice per day and IOP was measured three times per day using rebound tonometry in both eyes of 16 normal horses throughout two 10-day study periods (brimonidine and brimonidine-timolol) separated by an 18-day washout period. One eye of each horse was treated with brimonidine or brimonidine-timolol and the opposite eye was treated with balanced salt solution (BSS).ResultsThere were no adverse effects and no significant changes in pupil size in normal equine eyes treated with brimonidine or brimonidine-timolol. Average IOP in normal equine eyes treated with brimonidine (25.6 mmHg) was statistically higher than in eyes treated with brimonidine-timolol (24.6 mmHg) or BSS (24.5 mmHg). However, IOP differences were of ≤1 mmHg and thus not clinically important.Main limitationsHorses with normal eyes may not be as sensitive to the IOP-lowering effects of treatment as horses with glaucoma.ConclusionsBrimonidine and brimonidine-timolol are well tolerated in normal horses but do not decrease IOP

Comparison of ultrasonic pachymetry and Fourier-domain optical coherence tomography for measurement of corneal thickness in dogs with and without corneal disease.

Several ultrasonic and Fourier-domain optical coherence tomography (FD-OCT) pachymeters are used to measure corneal thickness in canine patients and research subjects. This study assessed the reliability of and consistency between two ultrasonic pachymetry (USP) devices, Pachette 3 and Accupach VI, as well as automated and manual measurements obtained using FD-OCT in dogs with and without corneal disease. Corneal thickness measurements were compiled from 108 dogs and analyzed using mixed effects linear regression, with Bonferonni adjustments for post-hoc comparisons, to determine the effects of age, weight and disease state. Data are presented as predicted mean±standard error. Canine corneal disease can result in marked increases in thickness that frequently exceed the upper limits of measurement of some pachymetry devices developed for human use. In this study, the corneas of dogs with endothelial disease or injury frequently exceeded the upper limits of quantitation of 999 and 800μm for the Accupach VI and automated FD-OCT pachymeters, respectively. Using values <800μm, the Pachette 3 generated significantly greater values for central corneal thickness (CCT) than the Accupach VI, manual FD-OCT and automated FD-OCT at 625±7.0, 615±7.2, 613±7.2, and 606±7.4μm respectively (P<0.001). Of the two devices where measurements >1000μm were obtained, manual FD-OCT demonstrated less variability than the Pachette 3. Corneal thickness increased linearly with age and weight with an increase of 6.9±1.8μm/year and 1.6±0.8μm/kg body weight (P<0.005 and P=0.038, respectively)

Nuclear/Cytoplasmic fractionation to study Hippo effectors.

The translocation or shuttling of Hippo proteins between the nucleus and cytoplasm is a rapid event following cytoskeletal or mechanical cues as well as stimulation with extracellular growth factors. Here we describe an experimental procedure for a simple and fast separation of nuclear and cytoplasmic fractions which maintains protein integrity and integrity of protein-protein complexes, indicating that it should be applicable to many experimental questions

Bovine and degenerated human annulus fibrosus: a microstructural and micromechanical comparison.

The complex structure of the annulus fibrosus is strongly related to its mechanical properties. Recent work showed that it is possible to observe the relative movement of fibre bundles in loaded cow tail annulus; the aim of this work was to describe and quantify annulus fibrosus micromechanics in degenerated human disc, and compare it with cow tail annulus, an animal model often used in the literature. Second harmonic generation was used to image the collagen matrix in twenty strips of annulus fibrosus harvested from intervertebral disc of seven patients undergoing surgery. Samples were loaded to 6% tensile strain in 1% steps. Elastic modulus was calculated from loading curves, and micromechanical strains were calculated from the images using custom software. The same protocol was applied to twenty strips of annulus harvested from cow tail discs. Significant morphological differences were found between human and cow tail samples, the most striking being the lack of collagen fibre crimp in the former. Fibres were also observed bending and running from one lamella to the other, forming a strong flexible interface. Interdigitation of fibre bundles was also present at this interface. Quantitative results show complex patterns of inter-bundle and inter-lamellar behaviour, with inter-bundle sliding being the main strain mechanism. Elastic modulus was similar between species, and it was not affected by the degree of degeneration. This work gives an insight into the complex structure and mechanical function of the annulus fibrosus, which should be accounted for in disc numerical modelling.Accepted manuscript - 12 month embarg