农林科学最新文献

Bleomycin (BLM) is a cytotoxic antibiotic used in veterinary oncology, primarily in electrochemotherapy (ECT), a local ablative therapy where electric pulses increase drug uptake in tumours. BLM is administered intravenously or intratumourally, with the standard intravenous dose for dogs being 15,000 IU/m², followed by electric pulses 8-10 minutes later. This protocol is derived from human oncology and lacks extensive pharmacological data in dogs. We studied BLM pharmacokinetics in 29 dogs with various tumours treated with intravenous BLM and ECT between 2017 and 2023. Samples were collected from serum of 15 dogs, serum and tumours of 8 dogs, and tumours of 6 dogs. The mean volume of distribution (Vd) of BLM was 224.5 ± 75.02 ml/kg, clearance (CL) was 7.04 ± 2.05 ml/kg/min, and area under the curve (AUC) was 65.87 ± 2.11 µg·min/l. The half-life (t₁_/₂) of BLM in dogs was 22.03 ± 0.88 minutes. No significant difference was found in tumour BLM concentrations between 8 minutes post-administration and 2 minutes after pulse completion. These results support the recommended 8-28-minute window for applying electric pulses following intravenous BLM administration and may indicate no need for dose adjustments based on body weight or age.

Lower urinary tract carcinomas in dogs are rare conditions with a poor prognosis. This prospective clinical study evaluated the safety, feasibility, and therapeutic efficacy of transarterial chemoembolization (TACE) using quick-soluble gelatin microparticles (QS-GMP) in 29 client-owned dogs with lower urinary tract carcinomas. Tumors primarily involved the bladder and urethra. Following selective catheterization of tumor-feeding vessels, intra-arterial carboplatin was administered prior to QS-GMP embolization. All patients underwent follow-up computed tomography (CT) scanning 4 weeks post-TACE. Tumor volume decreased in all cases, with a median reduction of 76.41% (95% confidence interval: 65.06-78.41%, p < 0.001). Partial remission was observed in 96.5% of patients; one case showed stable disease. Clinical signs, including pollakiuria, hematuria and stranguria, improved. No major complications occurred during the procedure or within two weeks after the procedure, and minor adverse effects were self-limiting. Repeat TACE was performed in 28/29 patients. The median survival time was 569 days for all patients and 534 days when non-tumor-related deaths were excluded. These findings suggest that TACE with QS-GMP may be an option for dogs with unresectable lower urinary tract carcinomas, with potential for repeated interventions and prolonged survival.

The architecture of bone defects presents a challenge in designing scaffolds that support structural integrity and enhance osteoinduction. To address this, a noninvasive injectable silk fibroin (SF)-based hydrogel incorporating magnetic nanohydroxyapatite (MHAp) and osteogenic growth peptide (OGP) was developed. This study investigated the osteogenic differentiation potential of the hydrogel and its underlying mechanism on canine periodontal ligament stem cells (cPDLSCs). The incorporation of MHAp and/or OGP significantly enhanced osteogenic differentiation as evidenced by increased alkaline phosphatase activity, osteogenic marker expression, and biomineralization. Proteomics analysis revealed that TGF-β, BMP, and Notch signaling pathways were involved in hydrogel-induced osteogenic differentiation, which was further validated by an inhibition assay. Overall, the injectable SF hydrogel containing MHAp and OGP demonstrates strong potential for clinical application in the treatment of alveolar bone defects.

As in humans, therapeutic plasma exchange (TPE) has been investigated in veterinary medicine for managing immune-mediated diseases such as canine visceral leishmaniasis (CVL). TPE may improve clinical outcomes by removing circulating immune complexes and excess antibodies; however, its physiological effects must be understood to ensure safety. Given the scarcity of studies in animals, this study evaluated the effects of centrifugation-based TPE in dogs with CVL receiving fresh frozen plasma (FFP) as replacement fluid. Thirty-one dogs with CVL that failed to respond to conventional therapy were allocated to two groups: clinical treatment alone (n = 18) and clinical treatment plus TPE (n = 13). The TPE group underwent one daily session for three consecutive days. Coagulation profiles were assessed before and after each session. A progressive decrease in platelet counts occurred across sessions, but without significant thrombocytopenia or critical alterations in activated partial thromboplastin time (aPTT) or prothrombin time (PT), which remained within reference ranges. Transient hypocalcemia occurred after the first session and was promptly corrected with calcium gluconate supplementation. Fibrinogen levels decreased mildly without clinical evidence of bleeding. Clinical complications were minimal and effectively managed. In conclusion, TPE was well tolerated, producing predominantly transient and controllable effects on hemostasis and overall clinical homeostasis under the conditions of this study.

This study compared liquid chromatography-mass spectrometry (LC-MS), micro-bioassay (MBa), and enzyme-linked immunosorbent assay (ELISA) for quantification of lincomycin (10 mg/kg BW) in porcine serum and evaluated lincomycin pharmacokinetic (PK) data in healthy piglets also co-infected with Actinobacillus pleuropneumoniae and Pasteurella multocida. All methods satisfied standard bioanalytical validation criteria, including low limits of detection and quantification, acceptable intra-assay imprecision and error, and strong linearity across clinically relevant concentration ranges. Serum concentrations measured by MBa and ELISA showed high correlation with LC-MS in both healthy and infected models (Pearson r ≥ 0.97, low bias on Bland-Altman analysis); they produced comparable PK parameters (Cmax, Tmax, area under the curve [AUC], clearance, and mean residence time), indicating suitability for PK/pharmacodynamic (PD)-based dose optimization. PK analysis demonstrated rapid absorption after intramuscular administration and disease-associated alterations in selected distribution and disposition parameters. AUC and clearance were nearly similar across analytical methods and largely consistent between software platforms (WinNonlin and PKSolver). Thus, lower-cost MBa and ELISA-combined with freely available PKSolver-can generate robust, decision-relevant PK/PD data for lincomycin in swine, providing a practical framework for antimicrobial dose refinement and stewardship in resource-limited veterinary and farm settings.

Canine mammary tumors (CMT), the most common neoplasms in intact female dogs, lack effective treatments for advanced cases. Newcastle disease virus (NDV), an oncolytic virus, kills tumor cells directly and stimulates antitumor immunity. However, NDV also activates Type I interferon (IFN-I) signaling, which restricts its replication via the JAK-STAT pathway. This study investigated whether propranolol, known to suppress antiviral responses, could enhance NDV's oncolytic effect in CMT. In vitro, using the CMT-U27 cell line, the combination reduced cell viability, migration, and invasion. Propranolol increased NDV replication and suppressed NDV-induced IFN-I release and JAK-STAT signaling pathway activation. In the CMT-U27 xenograft model, both NDV alone and the combination therapy prolonged the survival and suppressed tumor growth, with no significant difference between the two. However, the combination markedly enhanced intratumoral NDV replication by inhibiting IFN-I production and the JAK-STAT signalling pathway. These findings indicate that propranolol enhances NDV-mediated oncolysis in CMT by inhibiting the IFN-I/JAK-STAT pathway, increasing viral load, and represents a promising combined therapeutic strategy.

African swine fever (ASF) continues to expand worldwide. Recent detection in wild boar in Spain highlights the urgent need for effective control tools, with oral vaccination as a key priority. Following previous evaluation of the attenuated Lv17/WB/Rie1 strain, we assess an improved derivative, Lv17/WB/Rie1-ΔCD, lacking EP402R (CD2v) and EP153R, replaced by GFP to abrogate haemadsorption and enable Differentiating-Infected-from-Vaccinated-Animals (DIVA) diagnostics. Vaccinated animals received either a single high dose (10⁴ TCID₅₀) or a prime and re-exposure regimen (10² TCID₅₀ plus a 10⁴ TCID₅₀). Animals were challenged intramuscularly with the virulent Armenia07 genotype II strain. The ΔCD vaccine was well tolerated, inducing only transient low-grade fever. Prime-re-exposure vaccination induced earlier seroconversion (mean 12 ± 4 dpv) and sterilizing immunity in 5/6 animals in the high dose group. Overall protection reached 90%, while all unvaccinated controls died within 7 days. Quantitative PCR revealed >10³-fold reductions in viral genome copies in blood and tissues versus controls. DIVA ELISA reliably distinguished vaccine-induced antibodies from infection-derived responses. These findings identify Lv17/WB/Rie1-ΔCD as a safer oral ASFV vaccine candidate, addressing concerns raised with the parental Lv17/WB/Rie1 by increasing attenuation and supporting multi-gene deletion strategies. Further studies on safety, transmission, genetic stability, and environmental behaviour are required before large-scale field trials.

To investigate the influence of probiotic supplementation on parameters of renal function, dogs with chronic kidney disease (CKD) received a commercial probiotic formulation containing Enterococcus lactis SF68 (n = 8) or placebo (n = 8) for 60 days. Gut microbiome was investigated by comparing with healthy dogs (n = 10). Blood biochemistry, urinalysis, inflammatory and oxidative markers, uremic toxins and blood pressure were monitored. Higher presence of Lachnospiraceae family, Blautia bacterial species and Ruminococcus gnavus group was observed in dogs with CKD when compared with healthy dogs. Adding the probiotic to the diet decreased the abundance of Ruminococcus gnavus. Probiotic treatment resulted in a significant reduction in plasma concentrations of symmetric dimethylarginine (SDMA), from 1.50 ± 0.18 to 1.35 ± 0.16 µmol/l (p = 0.008), and indoxyl sulfate (IxS), from 19.1 ± 6.8 to 12.8 ± 4.8 µmol/l (p = 0.04). Cytokine inflammatory markers did not show significant changes. An increase in urine protein-to-creatine ratio, 1.5 ± 0.6 vs 1.2 ± 0.5, and in systolic blood pressure, 163 ± 11 vs 144 ± 6 mmHg (p = 0.033), was observed in the placebo group but not in dogs receiving probiotic. In conclusion, feeding Enterococcus lactis SF68 to dogs with CKD results in changes in intestinal microbiota that are associated with a decrease in plasma concentrations of IxS and SDMA and a reduction in proteinuria and systolic blood pressure.

Neonatal calf diarrhea (NCD) is a major contributor to morbidity and mortality in calves. Growing concern about antimicrobial resistance has spurred interest in phytotherapeutic alternatives, particularly polyphenol-rich extracts. Hazelnut skin (HS), a by-product of the confectionery sector, is a sustainable and underutilized source of polyphenols; however, its therapeutic efficacy in calves with NCD remains insufficiently investigated. This randomized, parallel-group clinical trial evaluated the effects of oral HS extract supplementation as an adjunct to standard medical therapy in hospitalized dairy calves with NCD. Sixty female Holstein calves were randomly allocated to a control group (CTRL; n = 30) or a treatment group (HS; n = 30) receiving 10 g/day of HS extract with milk for 5 days. All calves received standardized clinical management, including fluid therapy and antimicrobial administration. Clinical parameters, milk intake, body weight, hospitalization outcomes, sepsis scores, and blood oxidative stress biomarkers were monitored. No significant differences were detected between groups for clinical recovery, fecal score, hydration status, milk intake, weight gain, hospitalization duration, mortality, or oxidative stress markers. Clinical improvement over time was evident in both groups and was attributable to standard therapy. In conclusion, short-term oral supplementation with HS extract did not confer additional clinical or antioxidant benefits when added to conventional treatment in calves with NCD.