An investigation of the effects of intratesticular alfaxalone and lidocaine during castration in piglets.

OBJECTIVE: To determine whether intratesticular injection of an alfaxalone-lidocaine combination can induce anesthesia and provide a rapid recovery in piglets undergoing surgical castration. STUDY DESIGN: Randomized experimental study. ANIMALS: A group of 30 male piglets, aged 2-10 days, weighing 1.3-4.6 kg. METHODS: Animals were randomly divided into three equal groups for intratesticular administration of alfaxalone + lidocaine: high dose (group HD; 8 mg kg-1 + 2.5 mg kg-1), medium dose (group MD; 6 mg kg-1 + 2 mg kg-1) and low dose (group LD; 4 mg kg-1 + 1.5 mg kg-1). Induction and recovery times, movement and vocalization were recorded. Pulse rate (PR), oxygen saturation, respiratory rate (fR), rectal temperature, blood pressure and end-tidal carbon dioxide were recorded until recovery. RESULTS: Induction time did not differ significantly among groups (p = 0.19); mean time of 2.2, 3.3 and 3.7 minutes for HD, MD and LD, respectively. Recovery time to sternal recumbency was significantly faster in LD compared with HD and MD (p = 0.005). Time to standing was mean 34.1, 31.6 and 29.6 minutes for HD, MD and LD, respectively (p = 0.58). Incidences of movement and vocalization during the castration procedure were decreased in HD and MD compared with LD, but were not statistically different. There were no differences in the physiologic data among the groups except for PR, which decreased in all three groups (p < 0.05), and fR, which increased in MD and LD (p < 0.05). CONCLUSIONS AND CLINICAL RELEVANCE: The alfaxalone-lidocaine combinations investigated in this study induced deep sedation in all piglets. Physiologic data remained within clinically acceptable ranges, suggesting that this drug combination by intratesticular injection prior to castration in neonatal piglets is well tolerated. The authors recommend the alfaxalone (6 mg kg-1) + lidocaine (2 mg kg-1) dose.

Effects of Azithromycin on Behavior, Pathologic Signs, and Changes in Cytokines, Chemokines, and Neutrophil Migration in C57BL/6 Mice Exposed to Dextran Sulfate Sodium.

Here we characterized the murine dextran sulfate sodium (DSS) model of acute colitis. Specifically, we evaluated azithromycin and metronidazole treatment regimens to assess their effects on animal wellbeing, pathologic changes, barrier function, cytokine and chemokine profiles, and neutrophil migration in colon tissue. Azithromycin treatment significantly reduced the severity of colitis, as assessed through body weight change, water consumption, macroscopic lesions, and animal behaviors (activity level, climbing, and grooming), but did not alter food consumption or feeding behavior. Mucosal barrier function (evaluated by using FITC-labeled dextran) was decreased after DSS exposure; azithromycin did not significantly alter barrier function in mice with colitis, whereas metronidazole exacerbated the colitis-related deficit in barrier function. In addition, metronidazole appeared to exacerbate disease as assessed through water consumption and animal behaviors (overall activity, climbing, grooming, and drinking) but had no effect on weight loss, macroscopic lesions, or eating behavior. Pathologic changes were typical for DSS treatment. Antibiotic treatment resulted in reduced levels of proinflammatory cytokines and chemokines and decreased neutrophil adhesion and emigration in DSS-exposed mice. The results highlight the importance of clinical and behavioral assessments in addition to laboratory evaluation as tools to evaluate animal welfare and therapeutic efficacy in disease models. Data from this study suggest that azithromycin may convey some benefits in the mouse DSS colitis model through modulation of the immune response, including neutrophil migration into tissues, whereas metronidazole may exacerbate colitis.

The human fetus preferentially secretes corticosterone, rather than cortisol, in response to intra-partum stressors.

CONTEXT: Fetal stress is relevant to newborn outcomes. Corticosterone is rarely quantified in human clinical endocrinology and is found at much lower concentrations than cortisol. However, fetal corticosterone is a candidate hormone as a fetal stress signal. OBJECTIVE: Test the hypothesis that preferential fetal corticosterone synthesis occurs in response to fetal intra-partum stress. DESIGN: Cross-sectional comparison of paired serum corticosteroid concentrations in umbilical artery and vein from 300 women providing consent at admission to a General Hospital Labor and Delivery unit. Pre-term and multiple births were excluded, leaving 265 healthy deliveries. MAIN OUTCOME MEASURES: Corticosterone and cortisol concentrations determined by LC-MS/MS for umbilical cord venous (V) and arterial (A) samples and used to calculate fetal synthesis (A-V) and proportional fetal synthesis ([A-V]/V). Chart-derived criteria stratified samples by type of delivery, maternal regional analgesia, augmentation of contractions, and clinical rationale for emergent Caesarian delivery. RESULTS: Cortisol concentrations were higher than corticosterone concentrations; however, the fetus preferentially secretes corticosterone (148% vs 49% proportional increase for cortisol) and differentially secretes corticosterone as fetal stress increases. Fetal corticosterone synthesis is elevated after passage through the birth canal relative to Caesarian deliveries. For vaginal deliveries, augmentation of contractions does not affect corticosteroid concentrations whereas maternal regional analgesia decreases venous (maternal) concentrations and increases fetal synthesis. Fetal corticosterone synthesis is also elevated after C-section indicated by cephalopelvic disproportion after labor, whereas cortisol is not. CONCLUSIONS: The full-term fetus preferentially secretes corticosterone in response to fetal stress during delivery. Fetal corticosterone could serve as a biomarker of fetal stress.