Removal and repositioning of urinary tract implants by use of an endovascular snare system in dogs and cats (2013-2019).

OBJECTIVE: To report the fluoroscopic removal or repositioning of urinary tract implants in dogs and cats by use of an endovascular snare system (ESS) and to report procedural usefulness and complications in dogs and cats. ANIMALS: 3 cats and 14 dogs. PROCEDURES: A medical records review was performed to identify dogs and cats that underwent removal or repositioning of urinary tract foreign bodies or implants by use of an ESS with fluoroscopic guidance at a veterinary teaching hospital from 2013 to 2019. RESULTS: Dogs had a median weight of 25 kg (55 lb) with a range of 3.5 to 60.6 kg (7.7 to 133.3 lb), and cats had a median weight of 5 kg (11 lb) with a range of 4.2 to 5.4 kg (9.2 to 11.9 lb). By use of an ESS, 12 patients (2 cats and 10 dogs) underwent transurethral retrieval of retained vesicourethral implants or ureteral stents, 2 dogs underwent transurethral ureteral stent repositioning, 1 cat and 2 dogs underwent transnephric retrieval of ureteral stents, and 1 dog underwent cystoscopic-assisted transureteral ureteral stent retrieval. All procedures were successfully performed, and there were no associated procedural complications. CONCLUSIONS AND CLINICAL RELEVANCE: Retained vesicourethral implants or ureteral stents were successfully retrieved by use of an ESS in dogs and cats transurethrally or with an open or percutaneous transnephric approach and fluoroscopic guidance. These techniques should be considered as an alternative or adjunct to more invasive methods for implant retrieval or manipulation.

In vitro hepatic metabolism of mefloquine using microsomes from cats, dogs and the common brush-tailed possum (Trichosurus vulpecula).

Feline infectious peritonitis (FIP) is a systemic, fatal, viral-induced, immune-mediated disease of cats caused by feline infectious peritonitis virus (FIPV). Mefloquine, a human anti-malarial agent, has been shown to inhibit FIPV in vitro. As a first step to evaluate its efficacy and safety profile as a potential FIP treatment for cats, mefloquine underwent incubation in feline, canine and common brush-tailed possum microsomes and phase I metabolism cofactors to determine its rate of phase I depletion. Tramadol was used as a phase I positive control as it undergoes this reaction in both dogs and cats. Using the substrate depletion method, the in vitro intrinsic clearance (mean ± S.D.) of mefloquine by pooled feline and common brush-tailed possum microsomes was 4.5 ± 0.35 and 18.25 ± 3.18 µL/min/mg protein, respectively. However, phase I intrinsic clearance was too slow to determine with canine microsomes. Liquid chromatography-mass spectrometry (LC-MS) identified carboxymefloquine in samples generated by feline microsomes as well as negative controls, suggesting some mefloquine instability. Mefloquine also underwent incubation with feline, canine and common brush-tailed possum microsomes and phase II glucuronidative metabolism cofactors. O-desmethyltramadol (ODMT or M1) was used as a positive control as it undergoes a phase II glucuronidation reaction in these species. The rates of phase II mefloquine depletion by microsomes by all three species were too slow to estimate. Therefore mefloquine likely undergoes phase I hepatic metabolism catalysed by feline and common brush-tailed possum microsomes but not phase II glucuronidative metabolism in all three species and mefloquine is not likely to have delayed elimination in cats with clinically normal, hepatic function.

Repurposing of commercially available anti-coccidials identifies diclazuril and decoquinate as potential therapeutic candidates against Besnoitia besnoiti infection.

Repurposing of currently marketed compounds with proven efficacy against apicomplexan parasites was used as an approach to define novel candidate therapeutics for bovine besnoitiosis. Besnoitia besnoiti tachyzoites grown in MARC-145 cells were exposed to different concentrations of toltrazuril, diclazuril, imidocarb, decoquinate, sulfadiazine and trimethoprim alone or in combination with sulfadiazine. Drugs were added either just prior to infection of MARC-145 cells (0 h post infection, hpi) or at 6 hpi. A primary evaluation of drug effects was done by direct immunofluorescence staining and counting. Potential effects on the host cells were assessed using a XTT kit for cell proliferation. Compounds displaying promising efficacy were selected for IC50 and IC99 determination by qPCR. In addition, the impact of drugs on the tachyzoite ultrastructure was assessed by TEM and long-term treatment assays were performed. Cytotoxicity assays confirmed that none of the compounds affected the host cells. Decoquinate and diclazuril displayed invasion inhibition rates of 90 and 83% at 0 h pi and 73 and 72% at 6 h pi, respectively. The remaining drugs showed lower efficacy and were not further studied. Decoquinate and diclazuril exhibited IC99 values of 100 nM and 29.9 µM, respectively. TEM showed that decoquinate primarily affected the parasite mitochondrium, whilst diclazuril interfered in cytokinesis of daughter zoites. The present study demonstrates the efficacy of diclazuril and decoquinate against B. besnoiti in vitro and further assessments of safety and efficacy of both drugs should be performed in the target species.

Vinorelbine rescue therapy for dogs with primary urinary bladder carcinoma.

The goal of this study was to evaluate the anti-tumour activity and toxicoses of vinorelbine as a palliative rescue therapy for dogs with primary urinary bladder carcinoma. Thirteen dogs refractory to prior chemotherapeutics and one dog naïve to chemotherapeutic treatment were enrolled. Vinorelbine (15 mg m(-2) IV) was administered intravenously along with concurrent oral anti-inflammatory drugs, if tolerated. A median of six doses of vinorelbine (range: 1-16) was administered. Two dogs (14%) had partial responses, and eight (57%) experienced stable disease. Subjective improvement in clinical signs was noted in 11 dogs (78%). Adverse events were mild and primarily haematological in nature. Median time to progression was 93 days (range: 20-239 days). Median survival time for all dogs was 187 days; median survival for 13 pre-treated dogs was 207 days. Vinorelbine may have utility in the management of canine primary urinary bladder carcinoma and should be evaluated in a prospective study.