Abstract Objective To investigate the protective effects and molecular mechanisms of heat-inactivated Bifidobacterium adolescentis LA-20 (HT-LA20) against doxorubicin (DOX)-induced senescent injury in feline intestinal epithelial cells (FIECs). Methods This in vitro experimental study was conducted from November 1, 2025, through August 31, 2026, and involved only FIECs. No clinical patients or animals were included. The DOX-induced injury and senescence model was established in FIECs. The effects of HT-LA20 on cellular senescence and related proteins were evaluated by senescence-associated β-galactosidase staining, cell viability assays, and ELISA. Transcriptomic sequencing and untargeted metabolomics were integrated to elucidate the molecular regulatory mechanisms. Results Cell-based assays and transcriptomic and untargeted metabolomic analyses were performed with 4 independent biological replicates/group. HT-LA20 reversed DOX-induced reductions in cell viability and cellular senescence; upregulated tight junction proteins and mucins 1 and 2; suppressed release of IL-1β, tumor necrosis factor–α, IL-8, monocyte chemoattractant protein 1, and matrix metalloproteinase 1; and promoted VEGF and basic fibroblast growth factor (bFGF) secretion. Transcriptomic and metabolomic analyses showed that HT-LA20 reversed DOX-induced omic disturbances. Integrated multiomics Kyoto Encyclopedia of Genes and Genomes enrichment analysis indicated that its effects centered on the retinol metabolism–serotonergic synapse–intestinal immunoglobulin A immune network multitarget axis and regulation of inflammatory pathways, including nuclear factor κ B and Toll-like receptor signaling. Conclusions HT-LA20 effectively alleviates DOX-induced injury in FIECs by restoring intestinal epithelial barrier function and suppressing inflammatory senescence. Clinical Relevance These findings provide a theoretical basis for subsequent in vivo studies on postbiotics for chemotherapy-induced intestinal injury in veterinary medicine; clinical application requires further validation.
Abstract Objective To characterize echocardiographic findings of right heart and pulmonary artery remodeling in dogs with heartworm disease. Methods Medical records were searched for those of client-owned dogs with heartworm infection diagnosed from July 2020 through February 2023 and with no major systemic diseases not attributable to heartworm infection. Results for variables of interest were compared for dogs grouped by heartworm clinical class (classes 1 and 2 [mild] vs classes 3 and 4 [advanced]), pulmonary hypertension probability (low and intermediate vs high), and tricuspid regurgitation pressure gradient (mild, moderate, or severe). Pre- and postextraction variables were also compared for dogs with caval syndrome. Results 44 dogs were included. Compared with dogs with mild heartworm disease (n = 23), dogs with advanced heartworm disease (21) had greater right atrial and right ventricular enlargement, less right pulmonary artery distensibility, shorter pulmonary artery acceleration time, higher main pulmonary artery-to-aorta ratio, and lower right ventricular systolic function. Similar results were identified for dogs with high (vs intermediate or low) pulmonary hypertension probability. Normalized right atrial diameter had the highest discriminatory performance for identifying advanced heartworm disease (area under the curve, 0.95; 95% CI, 0.88 to 1.00), followed by tricuspid regurgitation pressure gradient, normalized right ventricular dimension, and other variables. Right atrial size significantly decreased after heartworm extraction (n = 8 dogs). Conclusions Advanced heartworm disease is associated with marked right heart and pulmonary artery remodeling. Clinical Relevance Echocardiographic assessment of right heart remodeling may assist clinicians in evaluating heartworm disease severity and identifying dogs with clinically important cardiopulmonary involvement.
Abstract Objective To describe the elimination kinetics of NSAIDs during carbon hemoperfusion (cHP) in dogs with toxicosis, specifically the apparent elimination rate constant, half-life, and plasma reduction. Methods 19 client-owned dogs (median age, 2.5 years; median body weight, 22 kg) with ibuprofen (n = 10), carprofen (5), or naproxen (4) toxicosis treated with cHP at 2 academic veterinary teaching hospitals from November 30, 2022, through July 7, 2024. Dogs were presented after known or suspected ingestion at median estimated maximum doses of 720, 200, and 325 mg/kg for ibuprofen, carprofen, and naproxen, respectively. The median interval from ingestion to cHP was 6.8 hours. Plasma concentrations were measured by LC-MS-MS in-serial samples collected during and, when available, after cHP. Results The median total plasma reduction was 58% (IQR, 51 to 80). The overall half-life during cHP was 1.3 hours (IQR, 1.1 to 1.8) by the 2-point method, concordant by regression (1.4 hours), and approximately 3.7-, 5.4-, and 52.0-fold shorter than respective therapeutic-dose half-lives. Among 5 dogs with posttreatment samples, plasma concentration rebounded after cHP in 1 naproxen-treated dog. The cHP-associated rate constant exceeded the intrinsic rate constant 11- to 40-fold in 4 of 5 dogs. Conclusions Carbon hemoperfusion was associated with substantial reductions in plasma NSAID concentrations during treatment in dogs with severe ibuprofen, carprofen, or naproxen toxicosis. Most of the decline occurred early in the session. Further studies are warranted to optimize treatment protocols. Clinical Relevance Carbon hemoperfusion markedly shortened NSAID elimination half-lives in dogs with severe toxicosis, accelerating removal well beyond endogenous elimination.
Abstract Objective To evaluate the sedative effects and pharmacokinetic profile of medetomidine and vatinoxan (Zenalpha) administered via the oral transmucosal (OTM) route. We hypothesized that sedation scores obtained from Zenalpha OTM (ZOTM) would not differ from Zenalpha IM (ZIM). Methods Dogs received 20 µg/kg ZIM or 80 µg/kg ZOTM. Sedation, anxiolytic, and handling scores were collected at 0, 15, 30, 30, 45, 60, 75, 90, 120, 150, and 180 minutes after administration of Zenalpha. Normality was tested using the Shapiro-Wilk test, and data were presented as median and range. Physiologic data were collected at 0, 5, 10, 15, 30, 45, 60, 90, 120, 240, 360, and 480 minutes. Plasma samples were collected at 0, 3, 5, 8, 8, 10, 15, 30, 45, 60, 90, 120, 240, 360, 480, 720, and 1,440 minutes and analyzed for concentration of medetomidine and vatinoxan using LC-MS-MS. Results 8 healthy adult Beagles participated in this study. Dogs in ZIM and ZOTM showed significant increases in sedation, anxiolysis, and handling scores compared to baselines. Medetomidine OTM was associated with a time to maximum concentration and relative bioavailability of 86 minutes (6 minutes ZIM) and 26.4%, respectively. Vatinoxan OTM was associated with a time to maximum concentration and relative bioavailability of 216 minutes (15 minutes ZIM) and 55.2%, respectively. Conclusions ZOTM (80 μg/kg) provided effective sedation, anxiolysis, and improved handling in healthy dogs comparable to ZIM (20 μg/kg) administration. Clinical Relevance Zenalpha administered OTM, at higher doses, may provide an attractive alternative to IM injection to achieve similar sedation.
