Evaluation of concentration of voriconazole in aqueous humor after topical and oral administration in horses

OBJECTIVE: To determine penetration of topically and orally administered voriconazole into ocular tissues and evaluate concentrations of the drug in blood and signs of toxicosis after topical application in horses. ANIMALS: 11 healthy adult horses. PROCEDURE: Each eye in 6 horses was treated with a single concentration (0.5%, 1.0%, or 3.0%) of a topically administered voriconazole solution every 4 hours for 7 doses. Anterior chamber paracentesis was performed and plasma samples were collected after application of the final dose. Voriconazole concentrations in aqueous humor (AH) and plasma were measured via high-performance liquid chromatography. Five horses received a single orally administered dose of voriconazole (4 mg/kg); anterior chamber paracentesis was performed, and voriconazole concentrations in AH were measured. RESULTS: Mean +/- SD voriconazole concentrations in AH after topical administration of 0.5%, 1.0%, and 3.0% solutions (n = 4 eyes for each concentration) were 1.43 +/- 0.37 microg/mL, 2.35 +/- 0.78 microg/mL, and 2.40 +/- 0.29 microg/mL, respectively. The 1.0% and 3.0% solutions resulted in significantly higher AH concentrations than the 0.5% solution, and only the 3.0% solution induced signs of ocular toxicosis. Voriconazole was detected in the plasma for 1 hour after the final topically administered dose of all solutions. Mean +/- SD voriconazole concentration in AH after a single orally administered dose was 0.86 +/- 0.22 microg/mL. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that voriconazole effectively penetrated the cornea in clinically normal eyes and reached detectable concentrations in the AH after topical administration. The drug also penetrated noninflamed equine eyes after oral administration. Low plasma concentrations of voriconazole were detected after topical administration.     

Anti-Inflammatory Components of the Starfish Astropecten polyacanthus

Inflammation is important in biomedical research, because it plays a key role in inflammatory diseases including rheumatoid arthritis and other forms of arthritis, diabetes, heart disease, irritable bowel syndrome, Alzheimer’s disease, Parkinson’s disease, allergies, asthma, and even cancer. In the present study, we describe the inhibitory effect of crude extracts and steroids isolated from the starfish Astropecten polyacanthus on pro-inflammatory cytokine (Interleukin-12 (IL-12) p40, interleukin-6 (IL-6), and tumor necrosis factor α (TNF-α)) production in lipopolysaccharide (LPS)-stimulated bone marrow-derived dendritic cells (BMDCs). Among those tested, compounds 5 and 7 showed potent inhibitory effects on the production of all three pro-inflammatory cytokines with IC₅₀ values ranging from 1.82 ± 0.11 to 7.00 ± 0.16 μM. Potent inhibitory activities were also observed for compound 1 on the production of IL-12 p40 and IL-6 with values of 3.96 ± 0.12 and 4.07 ± 0.13 μM, respectively, and for compounds 3 and 4 on the production of IL-12 p40 with values of 6.55 ± 0.18 and 5.06 ± 0.16 μM, respectively. Moreover, compounds 2 (IC₅₀ = 34.86 ± 0.31 μM) and 6 (IC₅₀ = 79.05 ± 2.05 μM) exhibited moderate inhibitory effects on the production of IL-12 p40, whereas compounds 3 (IC₅₀ = 22.80 ± 0.21 μM) and 4 (IC₅₀ = 16.73 ± 0.25 μM) moderately inhibited the production of TNF-α and IL-6, respectively.     

Molecular epidemiology of Mycobacterium avium subsp. avium and Mycobacterium intracellulare in captive birds

Mycobacterium avium subsp. avium and Mycobacterium intracellulare are primary causes of mycobacteriosis in captive birds throughout the world, but little is known about how they are transmitted. To define the local epidemiology of infection, we strain-typed 70 M. avium subsp. avium and 15 M. intracellulare culture isolates obtained over a 4-year period from captive birds. Typing was performed using randomly amplified polymorphic DNA (RAPD) PCR, amplified fragment length polymorphic (AFLP) fragment analyses, and for a subset of isolates, DNA sequencing of a segment of the 16S-23S rRNA internal transcribed spacer region. Six strain clusters comprising 43 M. avium subsp. avium, isolates were identified; 42 isolates had unique typing patterns, including all M. intracellulare isolates. Phylo-geographical analyses using RAPD and AFLP fingerprints and animal confinement histories showed no correlation between housing of infected birds and mycobacterial strain-type, except for two animals. The diversity of M. avium subsp. avium and M. intracellulare isolates and minimal evidence for bird-to-bird transmission suggest that environmental reservoirs may be important sources of infection in captivity.     

Epibulbar melanoma in a foal

A case of epibulbar melanoma in a 6-month-old, gelded, chestnut Hanoverian foal is reported. The location and clinical appearance upon initial presentation led to the tentative diagnosis of staphyloma or a congenital mass of unknown origin. An attempt was made to surgically excise the mass under general anesthesia, but due to its infiltrative nature and intraoperative appearance, most, but not all was removed without compromising the integrity of the globe. Histopathological evaluation revealed a multinodular to packeted, poorly demarcated, unencapsulated, infiltrative exophytic melanocytic neoplasm composed of bundles and nests of plump spindloid to polygonal heavily pigmented epithelioid neoplastic cells interspersed with pigment-laden macrophages within a fine fibrovascular stroma. Upon examination after enucleation, neoplastic cells were found to infiltrate into the lateral cornea, sclera and the choroid. This is a unique case of an epibulbar melanoma with choroidal invasion in a foal. Based on the sudden onset and rapid growth as well as the histological evidence of invasion, well-differentiated features, heavy pigmentation, and no apparent mitoses, this neoplasm was considered to be a low-grade malignant melanoma. At 14 months after excision there is no evidence of recurrence.     

Isolation of Escherichia fergusonii from the feces and internal organs of a goat with diarrhea

A fecal sample from a 42-year-old goat with a 2-month history of poor weight gain and diarrhea yielded a moderate growth of an organism resembling Salmonella spp. on MacConkey agar. The organism was identified as Escherichia fergusonii. The animal was euthanized. Samples of intestine, lung, liver, and kidney yielded the same organism, E. fergusonii.     

Vavilov wheat accessions provide useful sources of resistance to tan spot (syn. yellow spot) of wheat

Host genetic resistance is the most effective and sustainable means of managing tan spot or yellow spot of wheat. The disease is becoming increasingly problematic due to the adoption of minimum tillage practices, evolution of effector‐mediated pathogenicity, and widespread cultivation of susceptible cultivars from a narrow genetic base. This highlights the importance of broadening the diversity of resistance factors in modern breeding germplasm. This study explored 300 genetically diverse wheat accessions, originally sourced from the N. I. Vavilov Institute of Plant Genetic Resources (VIR), St Petersburg, Russia. The collection was screened for resistance to tan spot at seedling and adult stage under controlled conditions, and in the field across 2 years. The phenotypic datasets, coupled with ToxA bioassay screening, identified a number of accessions with useful sources of resistance. Seedling disease response corresponded well with ToxA sensitivity (r = 0.49, P < 0.000), but not adult responses (r = ?0.02 to ?0.19, P < 0.002), and overall reactions to ToxA appeared to show poor correspondence with disease response at the adult stage. ToxA‐insensitive accessions were generally found resistant across different growth stages (all‐stage resistance, ASR) in all experiments (seedling and adult stage under controlled conditions and field). ToxA‐sensitive accessions that were susceptible at seedling stage, but resistant at both adult‐plant stages, were deemed to carry adult‐plant resistance (APR). This study provides detailed information on the degree of tan spot resistance in the Vavilov wheat collection and discusses strategies to harness these sources to boost the diversity of resistance factors in modern wheat breeding germplasm.