Publications by authors named "Patrick A Lester"

17 Publications

  • Page 1 of 1

Anesthetic agents affect urodynamic parameters and anesthetic depth at doses necessary to facilitate preclinical testing in felines.

Sci Rep 2020 07 9;10(1):11401. Epub 2020 Jul 9.

Biointerfaces Institute, University of Michigan, Ann Arbor, MI, USA.

Urodynamic studies, used to understand bladder function, diagnose bladder disease, and develop treatments for dysfunctions, are ideally performed with awake subjects. However, in small and medium-sized animal models, anesthesia is often required for these procedures and can be a research confounder. This study compared the effects of select survival agents (dexmedetomidine, alfaxalone, and propofol) on urodynamic (Δpressure, bladder capacity, bladder compliance, non-voiding contractions, bladder pressure slopes) and anesthetic (change in heart rate [∆HR], average heart rate [HR], reflexes, induction/recovery times) parameters in repeated cystometrograms across five adult male cats. The urodynamic parameters under isoflurane and α-chloralose were also examined in terminal procedures for four cats. Δpressure was greatest with propofol, bladder capacity was highest with α-chloralose, non-voiding contractions were greatest with α-chloralose. Propofol and dexmedetomidine had the highest bladder pressure slopes during the initial and final portions of the cystometrograms respectively. Cats progressed to a deeper plane of anesthesia (lower HR, smaller ΔHR, decreased reflexes) under dexmedetomidine, compared to propofol and alfaxalone. Time to induction was shortest with propofol, and time to recovery was shortest with dexmedetomidine. These agent-specific differences in urodynamic and anesthetic parameters in cats will facilitate appropriate study-specific anesthetic choices.
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http://dx.doi.org/10.1038/s41598-020-68395-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7347647PMC
July 2020

Intramuscular Administration of Alfaxalone Alone and in Combination for Sedation and Anesthesia of Rabbits ().

J Am Assoc Lab Anim Sci 2019 03 28;58(2):216-222. Epub 2019 Feb 28.

Unit for Laboratory Animal Medicine; University of Michigan, Ann Arbor, Michigan, USA.

This study compared alfaxalone, alone and in combination with other medications, for sedative and anesthetic properties after intramuscular administration in New Zealand white rabbits. In the main portion of the study, 6 female rabbits were assigned to 5 treatment regimens in a blinded crossover design. Alfaxalone (6 mg/kg IM) was administered alone and in combination with each of the following: 0.3 mg/kg butorphanol; 1 mg/kg midazolam; 0.2 mg/kg dexmedetomidine; and both 0.3 mg/kg butorphanol and 0.2 mg/kg dexmedetomidine. An additional 6 rabbits received 0.2 mg/kg dexmedetomidine for comparison. The median time to onset of recumbency ranged from 2.0 to 5.5 min, with times significantly shorter for animals that received alfaxalone with either midazolam or dexmedetomidine than for those given dexmedetomidine only. Duration of sedation (mean ± 1 SD) was: alfaxalone only, 40 ± 7.3 min; alfaxalone with butorphanol, 47.8 ± 9.9 min; alfaxalone with midazolam, 65.2 ± 6.5 min; alfaxalone with dexmedetomidine, 157.5 ± 22.4 min; alfaxalone with butorphanol and dexmedetomidine, 157.7 ± 22.3 min, and dexmedetomidine only, 93.7 ± 11.9 min. Response to noxious stimuli was absent in 2 of the rabbits given dexmedetomidine only, 4 of those given alfaxalone with dexmedetomidine, and all 6 of the animals dosed with alfaxalone, butorphanol, and dexmedetomidine; this last group displayed the longest absence of a toe-pinch response (57 ± 3 min).
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http://dx.doi.org/10.30802/AALAS-JAALAS-18-000078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6433347PMC
March 2019

Safety Considerations When Working with Humanized Animals.

ILAR J 2018 12;59(2):150-160

Unit for Laboratory Animal Medicine, University of Michigan Medical School in Ann Arbor, Michigan.

Research using laboratory animals has been revolutionized by the creation of humanized animal models, which are immunodeficient animals engrafted with human cells, tissues, or organs. These animal models provide the research community a unique and promising opportunity to mimic a wide variety of disease conditions in humans, from infectious disease to cancer. A vast majority of these models are humanized mice like those injected with human CD34+ hematopoietic stem cells and patient-derived xenografts. With this technology comes the need for the animal research enterprise to understand the inherent and potential risks, such as exposure to bloodborne pathogens, associated with the model development and research applications. Here, we review existing humanized animal models and provide recommendations for their safe use based on regulatory framework and literature. A risk assessment program-from handling the human material to its administration to animals and animal housing-is a necessary initial step in mitigating risks associated with the use of humanized animals in research. Ultimately, establishing institutional policies and guidelines to ensure personnel safety is a legal and ethical responsibility of the research institution as part of the occupational health and safety program and overall animal care and use program.
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http://dx.doi.org/10.1093/ilar/ily012DOI Listing
December 2018

Effects of subcutaneous alfaxalone alone and in combination with dexmedetomidine and buprenorphine in guinea pigs (Cavia porcellus).

Vet Anaesth Analg 2018 Sep 2;45(5):658-666. Epub 2018 Jul 2.

Unit for Laboratory Animal Medicine, University of Michigan, Ann Arbor, MI, USA. Electronic address:

Objective: To characterize alfaxalone administered subcutaneously (SC) in guinea pigs, both alone and in combination with dexmedetomidine and buprenorphine.

Study Design: Prospective, blinded, crossover study.

Animals: A total of 15 healthy female guinea pigs weighing 400-600 g.

Methods: Alfaxalone (10, 20 and 40 mg kg) was administered SC to three guinea pigs as a pilot dose-finding study. Alfaxalone (20 mg kg; A) was selected for comparison against combination protocols of alfaxalone (15 and 20 mg kg) with dexmedetomidine (0.25 mg kg) and buprenorphine (0.05 mg kg; ADB, ADB). Each protocol was randomly administered to 12 guinea pigs separated by ≥7 days. Time and quality of induction and recovery, heart rate, respiratory rate, peripheral hemoglobin oxygen saturation, rectal temperature, pedal withdrawal reflex and adverse effects were recorded.

Results: The median time to induction for A, ADB and ADB was 6.8-8.0 minutes with no significant difference between treatments. Mean duration of recumbency for A was 73.6 ± 19.6 minutes. Recumbency duration for ADB and ADB extended to 90 minutes, at which time dexmedetomidine was antagonized using atipamezole (0.025 mg kg SC). Physiological variables were within normal limits with the exception of one animal that died 45 minutes following treatment with ADB. Pedal withdrawal reflex remained intact with all treatments. Minor side effects such as twitching or bruxism occurred sporadically with treatment A but not with ADB and ADB.

Conclusions And Clinical Relevance: SC alfaxalone produced uncomplicated sedation that may be recommended for nonpainful procedures that do not require complete immobility. The addition of dexmedetomidine and buprenorphine increased the duration of sedation and immobility, but did not result in general anesthesia. This combination sedation protocol may be useful for nonpainful procedures requiring extended immobility.
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http://dx.doi.org/10.1016/j.vaa.2018.06.004DOI Listing
September 2018

Analgesic Efficacy and Hematologic Effects of Robenacoxib in Mice.

J Am Assoc Lab Anim Sci 2018 05;57(3):258-267

Unit for Laboratory Animal Medicine, Department of Surgery, Vascular Surgery, University of Michigan Medical School, Ann Arbor, Michigan.

NSAID analgesics may confound models that require inflammation to mimic disease development in humans. This effect presents a challenge for veterinary staff and investigators, because surgery is often necessary to create mouse models of disease and NSAID are first-line analgesics used to treat postoperative pain. We evaluated robenacoxib, a NSAID highly selective for cyclooxygenase 2, in a carrageenan paw edema (CPE) assay and surgical model of venous thrombosis (VT). We generated a mouse-specific dose-response curve by using the CPE assay for robenacoxib doses of 3.2, 10, 32 and 100 mg/kg SC. Electronic von Frey assay, calipers, and novel software for measuring open-field activity revealed that all robenacoxib doses provided, identified effective analgesia at 3 and 6 h, compared with saline. In addition, the 100-mg/kg dose had measurable antiinflammatory effects but yielded adverse clinical side effects. Because the 32-mg/kg dose was the highest analgesic dose that did not decrease paw swelling, we evaluated it further by using the same nociceptive and behavioral assays in addition to a novel nest-consolidation test, and assessment of blood clotting and hematologic parameters in the surgical VT model. A single preemptive dose of either 32 mg/kg SC robenacoxib or 5 mg/kg SC carprofen protected against secondary hyperalgesia at 24 and 48 h. Neither drug altered clot formation or hematology values in the VT model. The open-field activity software and our novel nest consolidation test both identified significant postoperative discomfort but did not differentiate between saline and analgesia groups. In light of these data, a single preemptive subcutaneous dose of 32 mg/kg of robenacoxib or 5 mg/kg of carprofen did not impede this VT mode but also failed to provide sufficient postoperative analgesia.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5966233PMC
May 2018

Refinement of Perioperative Feeding in a Mouse Model of Vertical Sleeve Gastrectomy.

J Am Assoc Lab Anim Sci 2018 05 24;57(3):295-301. Epub 2018 Apr 24.

Unit for Laboratory Animal Medicine, University of Michigan, Ann Arbor, Michigan.

Provision of liquid enteral nutrition (LEN) during the perioperative period is standard practice for rodents undergoing bariatric surgery, yet these diets are associated with several challenges, including coagulation of the liquid diet within the delivery system and decreased postoperative consumption. We investigated the use of a commercially available high-calorie dietary gel supplement (DG) as an alternative food source for mice during the perioperative period. C57BL/6J male mice were fed high-fat diet for 8 to 10 wk prior to surgery. The study groups were: vertical sleeve gastrectomy (VSG) +DG, VSG+LEN, sham surgery+DG, and sham+LEN. Food and water intakes, body weight, and body fat composition was monitored throughout the study. Mice that received DG lost significantly more weight preoperatively than those fed LEN. However, during the postoperative period, body weight, body fat composition, and water and caloric intake were similar among all experimental diet groups. Three mice in the VSG+LEN group were euthanized due to clinical illness during the course of the study. In summary, feeding a high-calorie DG to mice undergoing VSG surgery is a viable alternative to LEN, given that DG does not significantly affect the surgical model of weight loss or result in adverse clinical outcomes. We recommend additional metabolic characterization of DG supplementation to ensure that this novel diet does not confound specific research goals in the murine VSG model.
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http://dx.doi.org/10.30802/AALAS-JAALAS-17-000162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5966239PMC
May 2018

Methods of Pairing and Pair Maintenance of New Zealand White Rabbits (Oryctolagus Cuniculus) Via Behavioral Ethogram, Monitoring, and Interventions.

J Vis Exp 2018 03 16(133). Epub 2018 Mar 16.

Unit for Laboratory Animal Medicine, University of Michigan; Refinement and Enrichment Advancements Laboratory, University of Michigan.

New Zealand White (NZW) laboratory rabbits (Oryctolagus cuniculus), as well as their ancestors the European Rabbit, are a social species that exhibit numerous benefits to being housed accordingly. Although these rabbits are innately gregarious, certain behaviors can still arise when kept in captivity, which if left unchecked, can confound research results or lead to wounding, which in extreme cases can be severe. To prevent these issues, there must be a well-structured plan for the monitoring and maintenance of paired laboratory rabbits. The purpose of this protocol is to present effective procedures for establishing newly paired NZW rabbits as well as methods for successful maintenance. Multiple methods have been tested for the creation of newly paired female rabbits from the vendor, but the most efficacious technique emphasizes capitalizing on the stress bonding from transport, urine marking, pairing in a neutral cage with no forced sharing of resources and a system of monitoring and intervention. To determine the best method of housing paired rabbits in a standard caging environment, data were collected to generate a behavioral ethogram. Behaviors were then quantified as positive, neutral or negative and were tracked across the lifespan of the pair to determine which behaviors indicated pair success or failure. With the newfound knowledge of socially housed laboratory NZW rabbit behavior, enrichment intervention was applied to alleviate aggression and prevent wounding, thus resulting in a higher percentage of successful pairs. Through several years of trialing different pairing methods, the development of the ethogram and the resulting enrichment interventions, understanding of the highly complex social constructs that dominate pair housed rabbit behavior has dramatically increased and allowed for the provision of more species-specific care and increased standards of welfare.
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http://dx.doi.org/10.3791/57267DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5931771PMC
March 2018

Bacterial and Infections in the Lungs of Gene-Knockout Rabbits with Severe Combined Immunodeficiency.

Front Immunol 2018 9;9:429. Epub 2018 Mar 9.

Center for Advanced Models for Translational Sciences and Therapeutics, University of Michigan Medical Center, University of Michigan Medical School, Ann Arbor, MI, United States.

Using the CRISPR/Cas9 gene-editing technology, we recently produced a number of rabbits with mutations in immune function genes, including FOXN1, PRKDC, RAG1, RAG2, and IL2RG. Seven founder knockout rabbits (F0) and three male IL2RG null (-/y) F1 animals demonstrated severe combined immunodeficiency (SCID), characterized by absence or pronounced hypoplasia of the thymus and splenic white pulp, and absence of immature and mature T and B-lymphocytes in peripheral blood. Complete blood count analysis showed severe leukopenia and lymphocytopenia accompanied by severe neutrophilia. Without prophylactic antibiotics, the SCID rabbits universally succumbed to lung infections following weaning. Pathology examination revealed severe heterophilic bronchopneumonia caused by in several animals, but a consistent feature of lung lesions in all animals was a severe interstitial pneumonia caused by , as confirmed by histological examination and PCR analysis of genes. The results of this study suggest that these SCID rabbits could serve as a useful model for human SCID to investigate the disease pathogenesis and the development of gene and drug therapies.
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http://dx.doi.org/10.3389/fimmu.2018.00429DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5854650PMC
June 2019

Pharmacokinetics of a Transdermal Fentanyl Solution in Suffolk Sheep ().

J Am Assoc Lab Anim Sci 2017 Sep;56(5):550-557

Unit for Laboratory Animal Medicine (ULAM), University of Michigan, Ann Arbor, Michigan;, Email:

Sheep used as surgical models require appropriate pain management, and the commonly used transdermal fentanyl patches require a long predosing period to achieve adequate plasma concentrations. The aim of this study was to assess the pharmacokinetic parameters of an FDA-approved transdermal fentanyl solution (TFS) that has yet to be tested in sheep. In this study, we compared TFS at 2.7 mg/kg (n = 2), 1.7 mg/kg (n = 3), and 0.5 mg/kg (n = 3) with the control fentanyl patch at 2 μg/kg/h (n = 1); both products were applied topically to the intrascapular region. Plasma concentrations showed significant interanimal variability. Severe adverse effects occurred at both 2.7 and 1.7 mg/kg TFS and mild to moderate adverse effects were noted at 0.5 mg/kg. At all 3 doses, TFS had greater maximal concentration, clearance rate, and volume of distribution; shorter time to maximal concentration; and similar half-lives to those of the patch. In addition, we validated the use of a commercial human fentanyl ELISA kit, which positively correlated with the liquid chromatography-mass spectroscopy data, but absolute values did not match. Overall, at all 3 dosages tested (0.5, 1.7, and 2.7 mg/kg), TFS delivered fentanyl plasma concentrations that exceeded the minimal effective concentration; however, adverse effects were noted at all 3 dosages. Caution and further study are required before the use of TFS in sheep can be recommended fully.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5605180PMC
September 2017

Apixaban Versus Warfarin for Mechanical Heart Valve Thromboprophylaxis in a Swine Aortic Heterotopic Valve Model.

Arterioscler Thromb Vasc Biol 2017 05 23;37(5):942-948. Epub 2017 Feb 23.

From the Unit for Laboratory Animal Medicine (P.A.L., D.D.M.) and Conrad Jobst Vascular Research Laboratories (P.A.L., D.M.C., J.A.D., T.O.J., A.E.H., A.R.M., B.T.G., T.W.W., D.D.M.), University of Michigan, Ann Arbor; and Global Clinical Research, Research & Development (R.M.K., E.R.) and Exploratory Clinical and Translational Research (C.E.F., Y.S.), Bristol-Myers Squibb Company, Princeton, NJ.

Objective: Warfarin is the current standard for oral anticoagulation therapy in patients with mechanical heart valves, yet optimal therapy to maximize anticoagulation and minimize bleeding complications requires routine coagulation monitoring, possible dietary restrictions, and drug interaction monitoring. As alternatives to warfarin, oral direct acting factor Xa inhibitors are currently approved for the prophylaxis and treatment of venous thromboembolism and reduction of stroke and systemic embolization. However, no in vivo preclinical or clinical studies have been performed directly comparing oral factor Xa inhibitors such as apixaban to warfarin, the current standard of therapy.

Approach And Results: A well-documented heterotopic aortic valve porcine model was used to test the hypothesis that apixaban has comparable efficacy to warfarin for thromboprophylaxis of mechanical heart valves. Sixteen swine were implanted with a bileaflet mechanical aortic valve that bypassed the ligated descending thoracic aorta. Animals were randomized to 4 groups: control (no anticoagulation; n=4), apixaban oral 1 mg/kg twice a day (n=5), warfarin oral 0.04 to 0.08 mg/kg daily (international normalized ratio 2-3; n=3), and apixaban infusion (n=4). Postmortem valve thrombus was measured 30 days post-surgery for control-oral groups and 14 days post-surgery for the apixaban infusion group. Control thrombus weight (mean) was significantly different (1422.9 mg) compared with apixaban oral (357.5 mg), warfarin (247.1 mg), and apixiban 14-day infusion (61.1 mg; <0.05).

Conclusions: Apixaban is a promising candidate and may be a useful alternative to warfarin for thromboprophylaxis of mechanical heart valves. Unlike warfarin, no adverse bleeding events were observed in any apixaban groups.
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http://dx.doi.org/10.1161/ATVBAHA.116.308649DOI Listing
May 2017

P-selectin inhibition therapeutically promotes thrombus resolution and prevents vein wall fibrosis better than enoxaparin and an inhibitor to von Willebrand factor.

Arterioscler Thromb Vasc Biol 2015 Apr 5;35(4):829-37. Epub 2015 Feb 5.

From the Section of Vascular Surgery, Department of Surgery, Conrad Jobst Vascular Research Laboratories (J.A.D., S.K.W., C.M.A., A.E.H., N.K.D., J.E.G., K.J.R., P.K.H., T.W.W., D.D.M.), Unit for Laboratory Animal Medicine (C.M.A., P.A.L., D.D.M.), and Department of Radiology (S.E.L.), University of Michigan, Ann Arbor; and Research and Development, Archemix Corporation, Cambridge, MA (R.G.S.).

Objective: Aptamers are oligonucleotides targeting protein-protein interactions with pharmacokinetic profiles and activity reversal options. Although P-selectin and von Willebrand factor (vWF) have been implicated in the development of venous thrombosis (VT), no studies have directly compared aptamer efficacy with standard of care in VT. In this study, ARC5692, an anti-P-selectin aptamer, and ARC15105, an anti-vWF aptamer, were compared with low-molecular-weight heparin, enoxaparin, to test the efficacy of P-selectin or vWF inhibition in promoting thrombus resolution and preventing vein wall fibrosis, in a baboon model of VT.

Approach And Results: Groups were as follows: treatment arm: animals received P-selectin or vWF aptamer inhibitors or enoxaparin (n=3 per group). Controls received no treatment (n=3). Prophylactic arm: animals received P-selectin inhibitor (n=4) or vWF inhibitor (n=3). Treatment arm: P-selectin-inhibitor demonstrated a significant improvement in vein recanalization by magnetic resonance venography (73% at day 21), and significantly decreased vein wall collagen, compared with all groups. Anti-P-selectin equaled enoxaparin in maintaining valve competency by ultrasound. All control animals had compromised valve competency post thrombosis. Prophylactic arm: animals receiving P-selectin and vWF inhibitors demonstrated improved vein recanalization by magnetic resonance venography versus controls (80% and 85%, respectively, at day 21). Anti-P-selectin protected iliac valve function better than anti-vWF, and both improved valve function versus controls. No adverse bleeding events were observed.

Conclusions: The P-selectin inhibitor aptamer promoted iliac vein recanalization, preserved valve competency, and decreased vein wall fibrosis. The results of this work suggest that P-selectin inhibition maybe an ideal target in the treatment and prophylaxis of deep VT, warranting clinical trials.
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http://dx.doi.org/10.1161/ATVBAHA.114.304457DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4489932PMC
April 2015

Effects of analgesic use on inflammation and hematology in a murine model of venous thrombosis.

J Am Assoc Lab Anim Sci 2014 Sep;53(5):485-93

Unit for Laboratory Animal Medicine, University of Michigan, Ann Arbor, Michigan, USA.

Venous thrombosis (VT) is a significant cause of morbidity and mortality in humans. Surgical animal models are crucial in studies investigating the pathogenesis of this disease and evaluating VT therapies. Because inflammation is critical to both the development and resolution of VT, analgesic medications have the potential to adversely affect multiple parameters of interest in VT research. The objective of this study was to determine how several common analgesics affect key variables in a murine ligation model of deep vein thrombosis. Male C57BL/6 mice were randomly assigned to receive either local (bupivacaine) or systemic parenteral analgesia (buprenorphine, tramadol, or carprofen) or 0.9% NaCl (control). All mice underwent laparotomy and ligation of the inferior vena cava, and treatment was continued until euthanasia at 6 or 48 h after surgery. Analysis of harvested tissues and blood included: hematology, thrombus weight, serum and vein-wall cytokines (IL1β, IL6, IL10, TNFα), soluble P-selectin, and vein-wall leukocyte infiltration. Compared with 0.9% NaCl, all of the analgesics affected multiple parameters important to VT research. Carprofen and tramadol affected the most parameters and should not be used in murine models of VT. Although they affected fewer parameters, a single dose of bupivacaine increased thrombus weight at 6 h, and buprenorphine was associated with reduced vein wall macrophages at 48 h. Although we cannot recommend the use of any of the evaluated analgesic dosages in this mouse model of VT, buprenorphine merits additional investigation to ensure the highest level of laboratory animal care and welfare.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4181690PMC
September 2014

Inflammation and thrombosis: new insights.

Front Biosci (Schol Ed) 2012 Jan 1;4:620-38. Epub 2012 Jan 1.

Unit for Laboratory Animal Medicine, University of Michigan Medical Center, Ann Arbor, MI, USA.

Vessel wall endothelial damage initiates a local inflammatory response, which promotes a prothrombotic state driven by tissue factor, adhesion molecules, and pro-inflammatory cytokines. Understanding how natural inflammatory mechanisms promote a procoagulant state, may lead to the development of new pharmacological interventions targeted at thrombosis.
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http://dx.doi.org/10.2741/s289DOI Listing
January 2012

Comparison of the in vitro efficacy of mu, delta, kappa and ORL1 receptor agonists and non-selective opioid agonists in dog brain membranes.

Brain Res 2006 Feb 27;1073-1074:290-6. Epub 2006 Jan 27.

Department of Pharmacology, University of Michigan Medical School, Ann Arbor, MI 48109-0632, USA.

Morphine and related opioid agonists are frequently used in dogs for their analgesic properties, their sedative effects and as adjuncts to anesthesia. Such compounds may be effective through a combined action at mu-, delta- and kappa-opioid receptors. In this work, the in vitro relative agonist efficacy of ligands selective for mu (DAMGO)-, delta (SNC80)- and kappa (U69593)-opioid receptors as well as the opioid receptor-like receptor ORL(1) (orphaninFQ/nociceptin) which may mediate nociceptive or antinociceptive actions was determined using the [35S]GTPgammaS binding assay in membrane homogenates from the frontal cortex, thalamus and spinal cord of beagle dogs. In addition, other analgesics commonly used in the dog were investigated. For the receptor-selective compounds, maximum stimulation of [35S]GTPgammaS binding decreased in the order kappa > ORL1 > delta > mu in cortical homogenates, compared with mu > ORL1 > kappa > delta in thalamic and spinal cord homogenates. For other opioids examined, efficacy decreased in the order etorphine > morphine > fentanyl = oxymorphine > butorphanol = oxycodone = nalbuphine. There was no significant difference in the potency of compounds to stimulate [35S]GTPgammaS binding between cortex and thalamus, with the exception of etorphine. Buprenorphine, the partial mu-opioid receptor agonist and kappa-, delta-opioid receptor antagonist, which does have analgesic efficacy in the dog, showed no agonism in any tissue but was an effective mu-opioid receptor > ORL1 receptor antagonist. The results show that the ability of agonists to stimulate [35S]GTPgammaS binding relates to the receptor distribution of opioid and ORL1 receptors in the dog.
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http://dx.doi.org/10.1016/j.brainres.2005.12.066DOI Listing
February 2006

Renal transitional cell carcinoma and choristoma in a degu (Octodon degus).

Contemp Top Lab Anim Sci 2005 May;44(3):41-4

Unit for Laboratory Animal Medicine, University of Michigan, Ann Arbor, Michigan 48109-0614, USA.

A 4.5-year-old female degu (Octodon degus) was minimally responsive with a poor body condition, a rough haircoat, and moderate dehydration. Blood was present around its urethral orifice and on the cage bedding. Laboratory analyses revealed leukocytosis with neutrophilia and anemia; hypoproteinemia and hypoalbuminemia; hyperglycemia, hyperphosphatemia, and elevated alanine aminotransferase, blood urea nitrogen, and creatinine; and hematuria and pyuria with occasional squamous and transitional epithelial cells. A urine culture was positive for coagulase-negative Staphylococcus sp. On gross necropsy, the right kidney was enlarged, cystic, and greenish-brown, with a 10-mm, hemorrhagic, granular mass extending from the renal pelvis into the cranial cortex. Only a small amount of renal cortex appeared normal. The urinary bladder had focal areas of hemorrhage and contained frank blood. Histologically, the papillary mass in the right renal pelvis comprised basophilic, moderately anaplastic, clustered epithelial transition cells consistent with a transitional cell carcinoma. Internally, the tumor showed squamous metaplasia and moderate multifocal interstitial fibrosis. The right kidney cortex contained a choristoma comprising trabecular bone, mature adipocytes, and cellular infiltrates suggestive of osteocytes, lymphocytes, and plasma cells. The urinary bladder had mild to moderate, focal, hemorrhage with neutrophilic inflammation and contained focal areas of mild transitional cell epithelial hyperplasia; these changes may have been secondary to irritation by hemorrhage in the renal pelvis. There was no evidence of metastasis. Renal transitional cell tumors are rare in rodents. This is the first report of both a renal transitional cell carcinoma and a renal choristoma in a degu.
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May 2005

What is your diagnosis? Uterine leiomyoma.

J Am Vet Med Assoc 2004 Oct;225(8):1179-80

Unit for Laboratory Animal Medicine, University of Michigan, 018 Animal Research Facility, 1150 W Medical Center Dr, Ann Arbor, MI 48109-0614, USA.

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http://dx.doi.org/10.2460/javma.2004.225.1179DOI Listing
October 2004

The sedative and behavioral effects of nalbuphine in dogs.

Contemp Top Lab Anim Sci 2003 Jul;42(4):27-31

Unit for Laboratory Animal Medicine, 018 Animal Research Facility, University of Michigan, 1301 E. Catherine Street, Ann Arbor, MI 48109-0614, USA.

We compared the degree of sedation and frequency and intensity of adverse behaviors in dogs associated with nalbuphine when combined with acepromazine or xylazine compared with those of acepromazine or xylazine alone. Twenty-four dogs (13 female, 11 male) undergoing routine ovariohysterectomy or castration were randomly assigned to one of four groups. Group NX received 0.5 mg/kg nalbuphine and 0.5 mg/kg xylazine subcutaneously (s.c.). Group X received 0.5 mg/kg xylazine s.c. Group NA received 0.5 mg/kg nalbuphine and 0.05 mg/kg acepromazine s.c. Group A received 0.05 mg/kg acepromazine s.c. All dogs received 0.01 mg/kg glycopyrrolate s.c. All doses were administered preoperatively. Preoperative resting measurements of heart rate, respiratory rate, rectal temperature, and body weight were obtained. Sedation was scored both inside and outside a kennel prior to drug administration and at 10, 20, and 30 min after drug administration. Dogs were assessed for behavioral responses (leg withdrawal, shivering, rigidity, orienting, panting, struggling, vocalization, wide-eyed facial expression, breath holding, salivating, hiding, biting, or requiring a muzzle) during three time periods: placing the dog on the table, clipping and prepping of forelimb, and intravenous catheterization. Postoperative recovery behaviors were scored. Expired halothane concentrations were recorded at 15, 30, and 45 min postinduction. Significant differences occurred in the level of sedation at 30 min between dogs receiving nalbuphine and xylazine or xylazine only compared with dogs receiving acepromazine. There was a significant difference in behavioral scores with respect to leg withdrawal and orienting during clipping/prepping between dogs receiving nalbuphine and xylazine compared with dogs receiving xylazine. The combination of nalbuphine and xylazine is a useful premedicant which provided greater sedation than acepromazine and reduced some anxiety behaviors more than did xylazine alone. Nalbuphine is an inexpensive opioid and currently is not a controlled substance in the U.S.
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July 2003