Summary: Background: In horses castration with primary intention healing is usually performed under balanced inhalation anaesthesia. To optimise analgesia, the use of local anaesthesia was tested. Objectives: To investigate the effect of local mepivacaine before castration with first intention healing under balanced medetomidine‐isoflurane anaesthesia and flunixin meglumine, morphine analgesia on perioperative cytokine levels and pain in horses. Study design: Prospective blinded clinical study. Methods: Twenty stallions were randomly assigned to control or mepivacaine groups. Flunixin meglumine was administered before sedation with medetomidine and followed by ketamine/diazepam intravenously (i.v.). Anaesthesia was maintained with isoflurane and 3.5 μg/kg per hour medetomidine. Mepivacaine horses were given mepivacaine 2% (3.5 mL SC, 1 mL/100 kg intrafunicularly, 2 mL/100 kg intratesticularly) on each side. For recovery, horses were given 2 μg/kg medetomidine i.v. and 0.1 mg/kg morphine i.m. and oral phenylbutazone (0.02 mg/kg q12h) for post‐operative analgesia. One hour before premedication and 4, 8 and 24 h post‐incision, pain was scored with three different pain scales (Equine Utrecht University Scale for Facial Assessment of Pain, Horse Grimace Scale, Equine Utrecht University Scale for Composite Pain Assessment) and plasma cytokines (interleukin‐6 and tumour necrosis factor alpha) were measured. Data were analysed using repeated measures ANOVA, linear regression and unpaired t ‐test, significance level P≤0.05. Results: Horses in both groups showed a significant increase in pain scores and cytokines compared to baseline. Post‐operatively the mepivacaine group exhibited significantly lower pain scores and cytokine levels. Mean heart rate during anaesthesia was significantly lower in the mepivacaine group compared to control group (28.8 ± 1 and 33.2 ± 1.7 respectively). Otherwise there were no differences between the groups. Main limitations: The decision to provide additional analgesia was based on the attending surgeon's assessment rather than a standardised rescue analgesia plan based on pain scores. The study was only conducted for 24 h post‐castration and complications were not recorded. Conclusion: Local mepivacaine before castration with primary wound closure improved anaesthesia quality, attenuated post‐operative increases in cytokines and reduced post‐operative pain despite balanced anaesthesia with multimodal analgesia in control horses.

The current study aimed to determine how palm date aqueous fruit extracts (AFE) affected the autistic-like behaviors brought on by valproic acid (VPA) injection, as well as any potential contributions from Sirt-1, oxidative stress, apoptosis, and autophagy. The pregnant Sprague Dawley females were treated with VPA at 12.5th gestation day and pregnant females and their offspring were treated with AFE orally at doses of 4 mg/Kg by gastric gavage for 45 days after birth. The elevated plus-T maze, water maze, and rotarod tests were used to examine autism-like behaviors. At the end of the study, the expression of Nrf2, heme oxygenase (HO-1), Sirt-1, caspase-3 (a marker of apoptosis), LC3 (a marker of autophagy), and NFκB (inflammatory cytokines) were evaluated along with the oxidative stress in brain tissues and the histological changes in the cerebellum and hippocampus. The neurobehavioral assessments significantly declined due to VPA, which also significantly increased oxidative stress in the brain tissues and significantly decreased Nrf2 and HO-1 expression. Additionally, VPA administration caused significant increase in the expression of caspase-3 in the cerebellar cortex, not in the hippocampus; LC3 and NFκB in the hippocampus, not in the cerebellar cortex; and significant reduction in the expression of Sirt-1 in the hippocampus, not in the cerebellum. On the other hand, AFE treatment significantly improved the neurobehavioral changes as well as it improved significantly the oxidative stress and the expression of LC3, NFκB, NrF2, HO-1, and Sirt-1 in the cerebellum and hippocampus. Conclusions: AFE administration might improve the autistic-like symptoms induced by VPA in rats via attenuation of the oxidative stress, upregulation of Nrf2 and HO-1, Sirt-1 and LC3 expression with downregulation of caspase-3, and NFκB expression in the cerebellum and hippocampus.

Aim: This study aimed to investigate the efficiency of topically applied pycnogenol (PYC) in healing the standardized alkaline corneal ulcer in diabetic and normal rats. Materials and methods: The corneal alkali-burn injury (CA-I) model was unilaterally developed in Wistar rats by filter paper saturated with 0.01 M of NaOH and touching the eyes for 45 s. Rats were divided into four groups: Normal control (NC), normal PYC (NPYC), diabetic control (DC), and diabetic PYC (DPYC). Both NPYC and DPYC groups were daily treated with PY eye drops three times, whereas NC and DC ones were treated with ordinary saline for six successive days. Results: The wound healing of corneal epithelial was improved in the NPYC group compared to the NC group. Meanwhile, it was significantly improved (P < 0.05) in the DPYC group than in the DC group. Histological examination revealed that corneal re-epithelialization was more accomplished in the DPYC group than in the DC group. In addition, the inflammatory cells were augmented in the DC group more than those in the DPYC one. Conclusion: The findings obtained revealed the efficiency of PYC for enhancing the corneal re-epithelialization and reducing the inflammatory reaction post alkali burn in rats, and thus it could be beneficially valuable as a treatment for the diabetic keratopathy.

Wound healing is a complex procedure that requires the coordination of several factors, so this study aimed to assess the zinc oxide nanoparticles' regenerated effect and stem cell exosomes on full-thickness wounds in rats. Seventy-two Wistar male rats were subjected to a full-thickness skin defect (20 mm2) on the dorsal surface of each rat between two shoulder joints. The rats were randomized into four groups (18/group) according to wound treatments. The wounds were irrigated with normal saline (Control group), or the wound's edges were subcutaneously injected daily with 0.3 ml of exosome (Exo-group), or 1 ml of zinc oxide nanoparticles (ZnO2-NPs group), or 0.3 ml of exosome in combined with 1 ml of zinc oxide nanoparticles (Exo/ZnO2-NPs group). On the 7th, 14th, and 21st days post-wounding, the weight of the rats, the wound healing breaking strength, the wound size, and the contraction percent were evaluated. Six rats in each group were euthanized at each time point for histopathological, immunohistochemical examination of collagen, the levels of alpha-smooth muscle actin (α-SMA), and epidermal growth factor receptor (EGFR). additionally, the gene expression analysis of the relative renal nuclear factor erythroid 2-related factor2 (Nrf2 mRNA), Transforming growth factor beta-1 (TGFβ1), fibroblast growth factor-7 (FGF7), Transforming growth factor beta-1 (TGFβ1), Lysyl oxidase (LOX), and Vascular endothelial growth factor (VEGF) were applied. The Exo-group exhibited a significant decrease in wound size and a significant increase in wound contraction compared with other groups. Histopathologically evaluation during the three intervals revealed that the Exo-group had the highest collagen deposition area with a significant reduction of the granulation tissue. Moreover, upregulated gene expression profiles of the growth factors genes at all time points post-wounding. The exosomes-treated group revealed superior wound healing and contraction, with minimal inflammatory signs, higher angiogenesis, and myofibroblasts, and associated with higher growth factor expression genes compared to the other groups. Exosome-based therapy demonstrates potential as a treatment method to promote and accelerate wound healing by modulating angiogenesis, re-epithelialization, collagen deposition, and gene expression profiles.

Aim: The current research aimed to evaluate the potential effect of adding platelet-rich fibrin (PRF) to the decellularized bovine pericardium (DBP) on the distal limb of donkeys’ full-thickness cutaneous wounds healing (Equus asinus).Materials and Methods: Healthy male donkeys (n = 12) were used in this study. Under general anesthesia, 6 cm2 full-thickness incisions were made on the middle dorsolateral surface of both forelimbs’ metacarpi. The left forelimbs were control wounds, while the right wounds were treated with PRF/DBP. Control wounds were bandaged with a standard dressing after saline irrigation and were evaluated at days 4, 7, 10, 13, 16, 19, 22, 25, and 28 post-wounding. PRF/DBP-treated wounds were dressed with a combination of PRF/DBP at the first, second, and third weeks post-wounding. Clinical and histopathological examinations of the wounds were performed to assess the healing process. Additionally, the immunohistochemical evaluation and gene expression profiles of myofibroblastic and angiogenic genes (transforming growth factor-β1, vascular endothelial growth factor-A, fibroblast growth factor 7 (FGF-7), and collagen type 3α1) were analyzed.Results: PRF/DBP wounds had a significantly faster healing process (61.3 ± 2.6 days) than control wounds (90.3 ± 1.4 days) (p < 0.05). The immunohistochemical examination and gene expression profile revealed significant enrichment in PRF/DBP wounds compared to control wounds.Conclusion: PRF/DBP dressing can be considered a natural and cost-effective biomaterial for enhancing the recovery of donkeys’ distal limb injuries.

Aim: The current study aimed to evaluate the antinociceptive effect of lidocaine, tramadol, and their combination for lumbosacral epidural analgesia in rabbits undergoing knee surgery. Materials and methods: This study was performed on 24 male New Zealand white rabbits weighing 2.8 to 3.0 kg and was allocated into three groups. All groups were anaesthetized by intramuscular (IM) injection of 35 mg/kg ketamine and 5 mg/kg xylazine, 0.1 mg/kg butorphanol. Rabbits in Group A received epidural analgesia of 4 mg/kg lidocaine 2%; Group B rabbits received epidural analgesia of 4 mg/kg tramadol 5%, and Group C rabbits received epidural analgesia of a combination of 4 mg/kg lidocaine and 4 mg/kg tramadol. Prior to and during surgery, the following parameters were recorded in a regular pre-set time interval: onset time of analgesia (OT), duration of flaccid paralysis (DFP), duration of analgesia (DA), onset and duration of sensory blockade, onset and duration of motor blockade, heart rate (HR), respiratory rate (RR), and rectal temperature (RT). Results: The mean OT demonstrated a significant decrease (P < 0.05) in Group C (46.5 ± 1.4 sec) compared to Group A and B (61.0 ± 2.4 and 54.5 ± 3.5 sec), respectively. DFP was significantly lower (P < 0.05) in Group C (35.5 ± 2.9 min) than in Group A and B (17.6 ± 1.4 and 21.8 ± 3.6), respectively. DA showed a significant increase (P < 0.05) in group C (45.8 ± 3.3 min) compared to groups A and B, respectively (23.3 ± 1.1 and 31.5 ± 2.3). Heart rate, RR, and RT significantly decreased in Group C compared to the other groups. Conclusion: According to the current study findings, lumbosacral epidural administration of lidocaine combined with tramadol could be a better choice for potentiating the analgesia than administration of either drug separately and may be safely used in rabbits undergoing knee surgery.