Renal pelvic dilatation is often recognized sonographically in dogs and cats, but ranges of measurements expected with different urologic conditions remain unknown. Ultrasound images of 81 dogs and 66 cats with renal pelvic dilatation were reviewed, and six groups were formed based on medical records: (I) clinically normal renal function, and (II) clinically normal renal function with diuresis; (III) pyelonephritis; (IV) noninfectious renal insufficiency; (V) outflow obstruction; (VI) miscellaneous nonobstructive anomalies. Medians for maximal pelvic width (range) for group I was 2.0 mm (1.0-3.8) in 11 dogs, and 1.6 mm (0.8-3.2) in 10 cats; for group II, 2.5 mm (1.3-3.6) in 15 dogs, and 2.3 mm (1.1-3.4) in 16 cats; for group III, 3.6 mm (1.9-12.0) in nine dogs, and 4.0 mm (1.7-12.4) in seven cats; for group IV, 3.1 mm (0.5-10.8) in 33 dogs, and 2.8 mm (1.2-7.3) in 13 cats; for group V, 15.1 mm (5.1-76.2) in six dogs, and 6.8 mm (1.2-39.1) in 17 cats; and for group VI, 3.8 mm (1.2-7.6) in seven dogs, and 3.0 mm (1.3-7.5) in three cats. Pelvic width in group I was lower than in groups III-V (P ¼ 0.0001), but did not significantly differ from group II. Pelvic width !13 mm always indicated obstruction. While the proportion of bilateral pelvic dilatation was not different among groups, the difference in pelvic width (maximal-minimal) was greater in group V vs. groups I, II, and IV (P ¼ 0.0009). These results confirm that renal pelvic dilatation can be detected sonographically in dogs and cats with clinically normal renal function, and that it increases with renal insufficiency, pyelonephritis, or outflow obstruction. Nevertheless, renal pelvic width varies substantially within groups and should be interpreted with caution. r

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Inflammatory bowel disease (IBD) is a complex disease which leads to life-threatening complications and decreased quality of life. The dextran sulfate sodium (DSS) colitis model in mice is known for rapid screening of candidate compounds. Efficacy assessment in this model relies partly on microscopic semiquantitative scoring, which is time-consuming and subjective. We hypothesized that deep learning artificial intelligence (AI) could be used to identify acute inflammation in H&E-stained sections in a consistent and quantitative manner. Training sets were established using ×20 whole slide images of the entire colon. Supervised training of a Convolutional Neural Network (CNN) was performed using a commercial AI platform to detect the entire colon tissue, the muscle and mucosa layers, and 2 categories within the mucosa (normal and acute inflammation E1). The training sets included slides of naive, vehicle-DSS and cyclosporine A-DSS mice. The trained CNN was able to segment, with a high level of concordance, the different tissue compartments in the 3 groups of mice. The segmented areas were used to determine the ratio of E1-affected mucosa to total mucosa. This proof-of-concept work shows promise to increase efficiency and decrease variability of microscopic scoring of DSS colitis when screening candidate compounds for IBD.

Osteoarthritis (OA) is a disabling, degenerative disease characterized by progressive cartilage and bone damage. There remains a need for local therapies that, following a single injection, can provide long-term pain relief and functional improvement and potentially delay disease progression. FX201 is a novel, intra-articular (IA), interleukin-1 receptor antagonist (IL-1Ra) gene therapy in development for the treatment of OA. In this study, we assessed the efficacy, biodistribution, and safety of helper-dependent adenovirus (HDAd)-ratIL-1Ra, the rat surrogate of FX201, and the biodistribution of FX201, in the anterior cruciate ligament transection (ACLT) rat OA model. A single IA injection of HDAd-ratIL-1Ra administered 7 days post-ACLT mitigated OA-related changes to cartilage, bone, and the synovial membrane at week 12 following surgery. Furthermore, FX201 and HDAd-ratIL-1Ra persisted for at least 92 days in the injected joint and proximal tissues with minimal evidence of vector spreading peripherally. Finally, HDAd-ratIL-1Ra showed a favorable safety profile without any local or systemic adverse effects. In conclusion, HDAd-ratIL-1Ra demonstrated local therapeutic and disease-modifying effects and was well tolerated, supporting further clinical development of FX201.

Salt forms of pharmaceutical compounds can have unique pharmacokinetic and toxicity properties. MDV1634 was evaluated for neurology indication and also demonstrated blood pressure (BP)-lowering effects in nonclinical studies. During the chemistry manufacturing campaign, 2 salt forms, dihydrochloride (2HCl) and maleate (MAL), which improved chemical stability and water solubility of the free base were identified. MDV1634.MAL showed better chemical attributes and was evaluated in toxicology studies for further development. A 28-day oral toxicity study in dogs with MDV1634.MAL demonstrated partially reversible renal toxicity. Although MAL salt is generally regarded as safe, renal toxicity is sometimes observed in rats and dogs. To evaluate contribution of each salt form to renal toxicity and BP lowering, an additional 28-day study was conducted with MDV1634.2HCL and MDV1634.MAL, which included toxicokinetics, continuous BP measurement in a subset of dogs, and sensitive urinary biomarker evaluation for temporal monitorability and reversibility of potential renal findings. In the repeat study, both salt forms showed similar exposures during the dosing period, but renal tubular toxicity was observed only with MDV1634.MAL and not with MDV1634.2HCl. The renal findings with MDV1634.MAL included early urinary biomarker changes (increase in albumin, clusterin, β2 microglobulin, and neutrophil gelatinase-associated lipocalin); elevations in serum blood urea nitrogen and creatinine; and microscopic findings of partially reversible tubular basophilia, single cell necrosis, pigmentation, and mineralization. The renal findings in contrast to the BP findings were MAL-specific and considered not related to MDV1634, thereby under scoring the importance of salt forms in pharmaceutical development.

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