Bio-Distribution and Pharmacokinetics of Topically Administered γ-Cyclodextrin Based Eye Drops in Rabbits.

The purpose of this study was to evaluate the ocular pharmacokinetics, bio-distribution and local tolerability of γ-cyclodextrin (γCD) based irbesartan 1.5% eye drops and candesartan 0.15% eye drops after single and multiple topical administration in rabbit eyes. In this randomized, controlled study, a total number of 59 New Zealand White albino rabbits were consecutively assigned to two study groups. Group 1 (n = 31) received irbesartan 1.5% and group 2 (n = 28) candesartan 0.15% eye drops. In both groups, single dose and multiple administration pharmacokinetic studies were performed. Rabbits were euthanized at five predefined time points after single-dose administration, whereas multiple-dose animals were dosed for 5 days twice-daily and then euthanized 1 h after the last dose administration. Drug concentration was measured by using liquid chromatography-tandem mass spectrometry (LC-MS/MS) in the retinal tissue, vitreous humor, aqueous humor, corneal tissue and in venous blood samples. Pharmacokinetic parameters including maximal drug concentration (Cmax), time of maximal drug concentration (Tmax), half-life and AUC were calculated. To assess local tolerability, six additional rabbits received 1.5% irbesartan eye drops twice daily in one eye for 28 days. Tolerability was assessed using a modified Draize test and corneal sensibility by Cochet Bonnet esthesiometry. Both γCD based eye drops were rapidly absorbed and distributed in the anterior and posterior ocular tissues. Within 0.5 h after single administration, the Cmax of irbesartan and candesartan in retinal tissue was 251 ± 142 ng/g and 63 ± 39 ng/g, respectively. In the vitreous humor, a Cmax of 14 ± 16 ng/g for irbesartan was reached 0.5 h after instillation while Cmax was below 2 ng/g for candesartan. For multiple dosing, the observed Cmean in retinal tissue was 338 ± 124 ng/g for irbesartan and 36 ± 10 ng/g for candesartan, whereas mean vitreous humor concentrations were 13 ± 5 ng/g and <2 ng/g, respectively. The highest plasma concentrations of both irbesartan (Cmax 5.64 ± 4.08 ng/mL) and candesartan (Cmax 4.32 ± 1.04 ng/mL) were reached 0.5 h (Tmax) after single administration. Local tolerability was favorable with no remarkable differences between the treated and the control eyes. These results indicate that irbesartan and candesartan in γCD based nanoparticle eye drops can be delivered to the retinal tissue of the rabbit's eye in pharmacologically relevant concentrations. Moreover, safety and tolerability profiles appear to be favorable in the rabbit animal model.

Deep learning differentiates between healthy and diabetic mouse ears from optical coherence tomography angiography images.

We trained a deep learning algorithm to use skin optical coherence tomography (OCT) angiograms to differentiate between healthy and type 2 diabetic mice. OCT angiograms were acquired with a custom-built OCT system based on an akinetic swept laser at 1322 nm with a lateral resolution of ∼13 µm and using split-spectrum amplitude decorrelation. Our data set consisted of 24 stitched angiograms of the full ear, with a size of approximately 8.2 × 8.2 mm, evenly distributed between healthy and diabetic mice. The deep learning classification algorithm uses the ResNet v2 convolutional neural network architecture and was trained on small patches extracted from the full ear angiograms. For individual patches, we obtained a cross-validated accuracy of 0.925 and an area under the receiver operating characteristic curve (ROC AUC) of 0.974. Averaging over multiple patches extracted from each ear resulted in the correct classification of all 24 ears.

Examination of anonymous canine faecal samples provides data on endoparasite prevalence rates in dogs for comparative studies.

Several endoparasites of dogs cannot only be detrimental to their primary host but might also represent a threat to human health because of their zoonotic potential. Due to their high dog population densities, metropolitan areas can be highly endemic for such parasites. We aimed to estimate the prevalence of endoparasites in dogs in the Austrian capital of Vienna by examining a representative number of canine faecal samples and to compare the prevalences with two neighbouring peri-urban and rural regions. In addition we analysed whether the density of dog populations and cleanliness of dog zones correlated with parasite occurrence. We collected 1001 anonymous faecal samples from 55 dog zones from all 23 districts of the federal state of Vienna, as well as 480 faecal samples from the Mödling district and Wolkersdorf with a peri-urban and rural character, respectively. Faeces were examined by flotation and by Baermann technique. Additionally we evaluated 292 Viennese, 102 peri-urban and 50 rural samples for Giardia and Cryptosporidium by GiardiaFASTest® and CryptoFASTest®. Samples from "clean" dog zones were compared to samples from "dirty" zones. The infection rate of Toxocara was surprisingly low, ranging from 0.6% to 1.9%. Trichuris was the most frequent helminth (1.8-7.5%) and Giardia the most frequent protozoan (4.0-10.8%). Ancylostomatidae, Crenosoma, Capillaria, Taeniidae, Cystoisospora and Sarcocystis were found in 1.8-2.2%, 0-0.9%, 0-0.9%, 0-0.6%, 0.3-3.1% and 0-0.6% of the samples, respectively. Samples from "dirty" dog zones in Vienna showed a significantly higher rate of parasites overall (p=0.003) and of Trichuris (p=0.048) compared to samples from "clean" dog zones. There were no statistically significant differences in densely vs. less densely populated areas of Vienna. Samples from the rural region of Wolkersdorf had significantly higher overall parasite, Trichuris and Cystoisospora prevalences than the peri-urban Mödling district and Vienna (p=0.000-0.039), while samples from the Mödling district had a significantly higher Giardia, Crenosoma and Capillaria prevalence than those from Vienna (p=0.002-0.047). Parasite excretion is dynamic and representative sampling and monitoring are necessary for parasite surveillance. Dog owners should be informed about the zoonotic risk and encouraged to remove dog faeces and dispose of them properly to reduce the infection risk for both other dogs and humans.