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Tyler M. Hockman Alvaro F. Cisternas Bryan Jones Mark T. Butt Kent G. Osborn Joanne J. Steinauer Shelle A. Malkmus Tony L. Yaksh 《Veterinary anaesthesia and analgesia》2018,45(2):212-226
Objective
To evaluate target engagement of intracisternally (IC) delivered TRPV1 agonist, resiniferatoxin (RTX), as measured by primary afferent and dorsal horn substance P immunoreactivity (sP-IR), histopathology and thermal escape latencies in dogs.Study design
Prospective experimental trial.Animals
Fourteen adult male Beagle dogs, weighing 10.3–13.2 kg; 11 dogs surviving to scheduled euthanasia.Methods
Anesthetized dogs were randomly assigned to be administered IC RTX (3.6 μg, 0.1 mL kg–1) in a hyperbaric (hRTX, n = 6), normobaric (nRTX, n = 4) vehicle or a hyperbaric vehicle (hVehicle, n = 4). Over 16 days, animals were examined for thoracic and pelvic limb paw thermal withdrawal latencies and neurologic function. Spinal cords, trigeminal ganglia and dorsal root ganglia (DRGs) were assessed for morphologic changes and sP-IR.Results
IC RTX in anesthetized dogs resulted in a < 1 hour increase in blood pressure. Acute reactions leading to euthanasia within 8 hours occurred in three dogs (two hRTX, one nRTX). All other animals recovered with normal neurologic, bowel and bladder function. Final groups were: vehicle n = 4, hRTX n = 4 and nRTX n = 3. Animals in nRTX and hRTX showed increases in escape latencies in thoracic paws and, to a lesser extent, in pelvic paws, correlating to a loss of sP-IR in cervical cord with smaller reductions in thoracic and lumbar cord. In animals surviving to euthanasia, thickening of the arachnoid membrane (predominantly in the cervical region) was the most consistent change. This change, present in controls, was interpreted to be vehicle related. There was no evidence of structural changes in brain and spinal cord.Conclusions and clinical relevance
IC RTX produced localized loss of spinal and DRG sP with a corresponding thermal analgesia, absent motor impairment or spinal pathology. Loss of three animals emphasizes the need to refine the use of this promising therapeutic modality in managing companion animal pain. 相似文献166.
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Six livers from one-year-old sheep were each sampled at 27 different sites and the concentrations of copper, vitamin B12 and zinc determined for each sample. The distribution of these components was uniform throughout the liver, indicating that analysis of a single liver biopsy sample would give an accurate assessment of their hepatic concentration. 相似文献
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Osborn HF 《Science (New York, N.Y.)》1886,8(185):167-168
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Osborn HF 《Science (New York, N.Y.)》1914,39(1015):863-864