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Background: Elevated levels of CD23, a natural regulator of IgE production, have been shown to decrease the signs of lung inflammation in mice. The aim of this study was to study the involvement of ADAM10, the primary CD23 sheddase, in experimental asthma. Methods: ADAM10 was blocked either by using mice with a B-cell-specific deletion of the protease or pharmacologically by intranasal administration of selective ADAM10 inhibitors. Airway hypersensitivity (AHR) and bronchoaveolar lavage fluid (BALF) eosinophilia and select BALF cytokine/chemokine levels were then determined. Results: Using an IgE and mast cell–dependent mouse model, B-cell-specific ADAM10-/- mice (C57B/6 background) exhibited decreased eosinophilia and AHR when compared with littermate (LM) controls. Treatment of C57B/6 mice with selective inhibitors of ADAM10 resulted in an even further decrease in BALF eosinophilia, as compared with the ADAM10-/- animals. Even in the Th2 selective strain, Balb/c, BALF eosinophilia was reduced from 60% to 23% respectively. In contrast, when an IgE/mast cell–independent model of lung inflammation was used, the B-cell ADAM10-/- animals and ADAM10 inhibitor treated animals had lung inflammation levels that were similar to the controls. Conclusions: These results thus show that ADAM10 is important in the progression of IgE-dependent lung inflammation. The use of the inhibitor further suggested that ADAM10 was important for maintaining Th2 levels in the lung. These results thus suggest that decreasing ADAM10 activity could be beneficial in controlling asthma and possibly other IgE-dependent diseases.

Summary Post anaesthetic myelopathy is a rare but devastating complication of equine anaesthesia and there is a need for better understanding of the condition and to raise veterinary awareness. The aim of this study was to collect data on unreported cases and combine those with reported cases to better identify possible risk factors and early clinical signs and outcomes of horses developing post anaesthetic myelopathy (PAM). A survey was conducted to identify cases of equine PAM. Records were also requested via the American College of Veterinary Anaesthesiologists listserve. Additional cases of PAM were located through review of the literature. Eighteen new cases and 12 published cases were identified. Large-framed breeds between 6–24 months of age were more commonly affected (23/30). The majority of horses were positioned in dorsal recumbency during anaesthesia. Lack of movement and deep pain of the rear limbs, loss of anal tone and lack of panniculus response from the mid to caudal thorax distally were the most common clinical findings. Reported treatments resulted in no improvement of clinical signs and all horses died or were subjected to euthanasia from a few hours to 8 days post operatively. Poliomyelomalacia of the caudal spinal cord is the most common histopathological finding. Although a rare complication it is a catastrophic risk that can be eliminated by performing a standing operation. Hopefully in the future better understanding of this condition will lead to prevention and treatment strategies.

Interleukin-4 (IL-4) acts on cultured cells in a species-specific fashion, although several reports have suggested that human (h) IL-4 may be functionally active in rodents in vivo. The latter finding, if true, would not only offer possibilities for pre-clinical testing of novel hIL-4-targeting therapies in animals, but also suggests new opportunities for mechanistic studies of IL-4 and its receptors. Conventional IL-4 is encoded by four exons, whereas its poorly studied alternatively spliced isoform is encoded by exons 1, 3 and 4 (IL-4δ2). Replication-deficient adenovirus-mediated gene delivery of hIL-4 isoforms (hIL-4 or hIL-4δ2) to mouse lungs caused similar pulmonary infiltration of T and B lymphocytes, but not eosinophils. There were significant differences in the changes of pulmonary cytokine milieu induced by hIL-4 compared with hIL-4δ2, with hIL-4δ2 inducing higher levels of pro-inflammatory (tumour necrosis factor-α, IL-1, and monocyte chemotactic protein-1) and T helper type 1 (IL-12 and interferon-γ) cytokines. There was no elevation in endogenous mouse (m) IL-4 or mIL-4δ2 mRNAs, and germ-line deficiency of mIL-4 did not affect the degree of pulmonary infiltration. When combined with an ovalbumin model of asthma, hIL-4δ2 stimulated a greater accumulation of lymphocytes than did hIL-4. Pulmonary infiltration of lymphocytes induced by expression of hIL-4 or hIL-4δ2 was attenuated, but not completely abrogated, by germ-line deficiency of mIL-4Rα or murine signal transducer and activator of transcription 6, suggesting that these signalling molecules mediate the in vivo effects of hIL-4 isoforms in mice. These findings suggest that splice isoforms of human IL-4 are functionally active in vivo in mice, and partially share the effects of the corresponding species-specific isoforms.

Summary Reasons for performing study: Horses experience major perturbations in acid-base balance during supramaximal exercise. Ion movement in and out of erythrocytes (RBCs) is believed to be important in maintaining acid-base balance but it is unclear as to the extent to which this happens, nor how it affects single measurements of ion concentrations in arterial and venous blood. Objectives: To clarify the role RBCs play in mitigating perturbations in acid-base balance during high speed exercise in horses, and to describe associated differences in arterial (a) and mixed venous (v) concentrations of key ions. Methods: Six exercise-trained Thoroughbreds galloped to fatigue at speeds calculated to have an oxygen demand that was 115% of the VO2max. Blood samples (a and v) were collected pre-exercise, during warm-up, at fatigue, and immediately post exercise. Packed cell volume (PCV), pH, PCO2, and plasma concentrations of bicarbonate (HCO3−), chloride (Cl−), sodium (Na+), potassium (K+), and lactate (Lac−) and strong ion difference (SID) were determined, and RBC concentrations of Lac− and electrolytes calculated for each sample. Data were analysed using a 2-way ANOVA for repeated measures testing for effects of sampling time and site (P

This investigation was carried out to compare the postoperative analgesia and plasma morphine concentrations in dogs given epidural morphine or epidural morphine combined with medetomidine prior to surgery. Twelve dogs (seven males and five females) with ruptured cranial cruciate ligaments presented to the Washington State University Veterinary Teaching Hospital. Six dogs received an epidural injection of morphine (0.1 mg/kg) and six dogs received epidural morphine (0.1 mg/kg) combined with medetomidine (0.005 mg/kg). Numeric rating scale (NRS) pain scores and cumulative pain scores (CPS) were assigned to 10-min segments of video. Video segments, heart rates and respiratory rates were recorded prior to premedication and at 4, 8, 12, 18 and 24 h after epidural injection. Blood was sampled from the cephalic vein at each of these times and during anesthesia at 0.5, 1, 2 and 3 h after epidural injection. Data were analyzed using either Friedman's test or one-way anova for repeated measures. In the morphine group, significant increases compared with premedication values were detected at 4, 8 and 12 h after epidural injection for NRS and at 4 and 12 h after epidural injection for CPS. In the morphine plus medetomidine group, NRS was significantly higher at 4 and 8 h whereas there were no differences from baseline values for CPS. Plasma morphine concentrations were not significantly different between treatment groups, but were significantly increased compared with preinjection values at 0.5, 1, 12, 18, and 24 h in the morphine plus medetomidine group. Epidurally administered morphine combined with medetomidine was associated with only minor benefits based on subjective pain scoring when compared with morphine alone in these dogs undergoing repair of a ruptured cranial cruciate ligament.

Lateral rostrotentorial and caudal suboccipital approaches to the brain were performed on six beagles. Intracranial pressure (ICP) was measured as the two craniectomies were connected by removing the bone of the nuchal crest and occluding the transverse venous sinus. Intracranial pressure remained constant after acute occlusion of the sinus with bone wax and there was no gross evidence of brain edema. All six dogs survived the surgery and five dogs survived for a minimum of 3 months. One dog died acutely during the postoperative period. The exact cause of the cerebellar hemorrhage and infarction found at necropsy in the latter dog was not evident. Anemia occurred in three of the six dogs as a result of intraoperative hemorrhage. All dogs surviving the perioperative period had mild, transient hypermetria and conscious proprioceptive deficits, but were neurologically normal 72 hours after surgery. Results of this study indicate that acute, unilateral transverse sinus occlusion is possible without an increase in ICP. The ability to do this allows access to the rostral aspect of the ipsilateral cerebellum and brain stem.

Longitudinal division of the corpus callosum was performed in six normal beagles to determine surgical morbidity. The corpus callosum was divided sagittally on the midline and the effect on neurological function was determined. Five of six dogs were clinically normal within 14 days or less after surgery. One dog had persistent but improving clinical signs consistent with a forebrain disturbance at 30 days after surgery. Overall, minimal morbidity and no mortality was associated with this surgical procedure. Further study is indicated to determine the efficacy of this surgical treatment for seizure control in dogs with idiopathic epilepsy.

Quantitative EEG was assessed in six dogs anaesthetized with 1.8% end-tidal isoflurane concentration and following diazepam (0.2 mg/kg i.v.) administration. Ventilation was controlled to maintain normocapnia. Five dogs were subsequently given the benzodiazepine antagonist, flumazenil (0.04 mg/kg i.v.), and quantitative EEG was recorded. One dog received a saline injection following diazepam (as a control) and quantitative EEG was recorded for an additional 2.5 h. Heart rate, arterial blood pressure, esophageal temperature, arterial pH and blood gas tensions, end-tidal CO2 tension and end-tidal isoflurane concentration were monitored throughout the study. A 21 lead linked-ear montage was used for recording EEG. Quantitative EEG data were stored on an optical disc for analysis at a later date. Values for absolute power of EEG were determined for theta, delta, alpha, and beta frequencies. Cardiovascular parameters remained stable throughout the study. Diazepam administration was associated with decreased absolute power in all frequencies of EEG at all electrode sites. The duration of diazepam-induced decreased absolute power of EEG was at least 3 h in one dog. Administration of flumazenil antagonized diazepam-induced decreased absolute power of EEG in all frequencies at all electrode sites. We conclude that quantitative EEG provides a relatively non-invasive, objective measure of diazepam- and flumazenil-induced changes in cortical activity during isoflurane anaesthesia.