Dermal malignant melanoma in a horse with multifocal pancytokeratin expression.

The current report describes a malignant melanoma in the dermis of a 13-year-old bay Thoroughbred mare. Microscopic examination revealed that tumor cells were arranged in cords and packets within an abundant collagenous stroma containing scattered myxomatous foci. Tumor cells stained positively for S-100, neuron-specific enolase, and vimentin and some contained melanin granules. Some clusters of tumor cells were also positive for pancytokeratin. Expression of epithelial cell markers has been described in small numbers of human melanomas but has not been reported previously in equine melanomas.     

Fentanyl or midazolam for co-induction of anaesthesia with propofol in dogs

ObjectivePropofol may cause adverse effects (e.g. apnoea, hypotension) at induction of anaesthesia. Co-induction of anaesthesia may reduce propofol requirements. The effect of fentanyl or midazolam on propofol dose requirements and cardiorespiratory parameters was studied.Study designRandomized, controlled, blinded clinical study.AnimalsSixty-six client owned dogs (35 male, 31 female, ASA I-II, age 6–120 months, body mass 4.7–48.0 kg) were selected.MethodsPre-medication with acepromazine (0.025 mg kg⁻¹) and morphine (0.25 mg kg⁻¹) was administered by intramuscular injection. After 30 minutes group fentanyl-propofol (FP) received fentanyl (2 μg kg⁻¹), group midazolam-propofol (MP) midazolam (0.2 mg kg⁻¹) injected over 30 seconds via a cephalic catheter and in a third group, control-propofol (CP), the IV catheter was flushed with an equivalent volume of heparinized saline. Anaesthesia was induced 2 minutes later, with propofol (4 mg kg⁻¹minute⁻¹) administered to effect. After endotracheal intubation anaesthesia was maintained with a standardized anaesthetic protocol. Pulse rate, respiratory rate (RR) and mean arterial pressure (MAP) were recorded before the co-induction agent, before induction, and 0, 2 and 5 minutes after intubation. Apnoea ≥30 seconds was recorded and treated. Sedation after pre-medication, activity after the co-induction agent, quality of anaesthetic induction and endotracheal intubation were scored.ResultsPropofol dose requirement was significantly reduced in FP [2.90 mg kg⁻¹(0.57)] compared to CP [3.51 mg kg⁻¹ (0.74)] and MP [3.58 mg kg⁻¹(0.49)]. Mean pulse rate was higher in MP than in CP or FP (p = 0.003). No statistically significant difference was found between groups in mean RR, MAP or incidence of apnoea. Activity score was significantly higher (i.e. more excited) (p = 0.0001), and quality of induction score was significantly poorer (p = 0.0001) in MP compared to CP or FP. Intubation score was similar in all groups.Conclusions and clinical relevanceFentanyl decreased propofol requirement but did not significantly alter cardiovascular parameters. Midazolam did not reduce propofol requirements and caused excitement in some animals.     

A critical role for the innate immune signaling molecule IRAK-4 in T cell activation

IRAK-4 is a protein kinase that is pivotal in mediating signals for innate immune responses. Here, we report that IRAK-4 signaling is also essential for eliciting adaptive immune responses. Thus, in the absence of IRAK-4, in vivo T cell responses were significantly impaired. Upon T cell receptor stimulation, IRAK-4 is recruited to T cell lipid rafts, where it induces downstream signals, including protein kinase C activation through the association with Zap70. This signaling pathway was found to be required for optimal activation of nuclear factor kappaB. Our findings suggest that T cells use this critical regulator of innate immunity for the development of acquired immunity, suggesting that IRAK-4 may be involved in direct signal cross talk between the two systems.     

In vitro bile acid binding activity within flour fractions from oat lines with typical and high beta-glucan amounts

Whole flours from four oat lines with different amounts of beta-glucan (4.8-8.1%) were examined for their antioxidant activity and total phenolic and lignin concentrations. These data, along with the beta-glucan percentages, were compared with bile acid (BA) binding. Only the lignin concentrations of the flours significantly (P < 0.01) correlated with the BA binding values. The oat flours also were fractionated into bran, protein concentrate, starch, layer above starch, and soluble beta-glucan (SBG)-free flour, and their BA binding capacities were evaluated. The bran fractions were the only fractions that bound greater BA than did the whole oat flours on dry matter basis. Extraction of the soluble beta-glucan to create the SBG-free flour significantly (P < 0.01) decreased the BA binding of the remaining flour. These data suggest that BA binding of the oat flours involves the synergistic interactions of the oat components, with beta-glucan and lignin (insoluble fiber) having a great impact.     

iRhom2 regulation of TACE controls TNF-mediated protection against Listeria and responses to LPS

Innate immune responses are vital for pathogen defense but can result in septic shock when excessive. A key mediator of septic shock is tumor necrosis factor-α (TNFα), which is shed from the plasma membrane after cleavage by the TNFα convertase (TACE). We report that the rhomboid family member iRhom2 interacted with TACE and regulated TNFα shedding. iRhom2 was critical for TACE maturation and trafficking to the cell surface in hematopoietic cells. Gene-targeted iRhom2-deficient mice showed reduced serum TNFα in response to lipopolysaccharide (LPS) and could survive a lethal LPS dose. Furthermore, iRhom2-deficient mice failed to control the replication of Listeria monocytogenes. Our study has identified iRhom2 as a regulator of innate immunity that may be an important target for modulating sepsis and pathogen defense.     

Factors Affecting the Glucose Response to Insulin Injection in Mares: Epinephrine, Short- and Long-Term Prior Feed Intake, Cinnamon Extract, and Omega-3 Fatty Acid Supplementation

Five experiments were conducted with mares to better define factors that might affect the assessment of insulin sensitivity via direct insulin injection, and to then apply this method of assessing insulin sensitivity to trials which tested two potential supplements for improving poor insulin sensitivity in horses. The experiments assessed the effects of the following: (1) previous administration of epinephrine, (2) overnight feed deprivation versus hay or pasture consumption, (3) 10-day acclimatization to hay in a dry lot versus pasture grazing, (4) cinnamon extract supplementation, and (5) fish oil supplementation on insulin sensitivity. Mares of known high and low insulin sensitivities were used in the first three experiments, whereas mares with low insulin sensitivities were used in the supplement trials. Epinephrine administration increased blood glucose concentrations (P < .05) and prevented the insulin-induced decrease in blood glucose concentrations in both sensitive and insensitive mares. Overnight feed deprivation decreased (P < .06) insulin sensitivity relative to overnight ad libitum access to hay, and both regimens resulted in reduced insulin sensitivity relative to overnight pasture availability; sensitive and insensitive mares responded similarly except when kept on pasture (P = .0854). Ten days of hay consumption in a dry lot reduced (P < .05) insulin sensitivity in insensitive mares, but not in sensitive mares, relative to pasture grazing. Supplementation with cinnamon extract or fish oil had no effect on insulin sensitivity of mares with known low insulin sensitivity under the conditions of these experiments.     

Anaesthetic complications in pigs undergoing MRI guided convection enhanced drug delivery to the brain: a case series

ObservationsA total of 13 intracerebral infusions were performed at approximately 1 month intervals in three NIH miniature pigs over the age range of 31–59 weeks. Pigs received azaperone and ketamine premedication to allow venous cannulation and propofol induction of anaesthesia. Anaesthesia was maintained with isoflurane throughout cranial surgery and MRI scanning. Physiological monitoring during surgery consisted of blood pressure, pulse, temperature and oxygen saturation monitoring, ECG and capnography. Analgesia consisted of meloxicam and morphine. However, during MRI scanning blood pressure and ECG monitoring had to be discontinued. Anaesthetized pigs underwent intermittent intraputamenal convection enhanced delivery (CED) of gadolinium with real-time magnetic resonance imaging. Progressive tachycardia was consistently observed in all pigs during CED with a mean ± SD maximum increase of 41 ± 22 beats minute^?1 from a baseline heart rate of 96 ± 9 minute^?1. The heart rate remained elevated until recovery. A mean reduction in body temperature of 2.8 ± 0.6 °C from the start of anaesthesia was also observed during the period of MRI scanning. All pigs recovered from anaesthesia smoothly and heart rates returned to normal during the recovery period.ConclusionsHypothermia is common in pigs undergoing this sedation and anaesthesia protocol. Convection enhanced delivery of drugs in healthy anaesthetized pigs may result in tachycardia.