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

New Zealand White (NZW) laboratory rabbits (Oryctolagus cuniculus), as well as their ancestors the European Rabbit, are a social species that exhibit ...

University of Michigan

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.

The sedative and behavioral effects of nalbuphine in dogs.

What is your diagnosis? Uterine leiomyoma.

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.

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

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.

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

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Da&#xF1;o a los vasos de la pared endotelial se inicia una respuesta inflamatoria local, que promueve un estado protromb&#xF3;tico impulsado por el factor tisular, mol&#xE9;culas de adhesi&#xF3;n y las citoquinas pro-inflamatorias. La comprensi&#xF3;n de c&#xF3;mo los mecanismos inflamatorios naturales promover un estado procoagulante, puede conducir al desarrollo de nuevas intervenciones farmacol&#xF3;gicas dirigidas a la trombosis.

La inflamaci&#xF3;n y la trombosis: Nuevas perspectivas

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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.

Inflammation and thrombosis: new insights.

La paroi vasculaire des l&#xE9;sions endoth&#xE9;liales d&#xE9;clenche une r&#xE9;ponse inflammatoire locale, qui favorise un &#xE9;tat prothrombotique entra&#xEE;n&#xE9;e par le facteur tissulaire, des mol&#xE9;cules d&#x26;#39;adh&#xE9;sion, et cytokines pro-inflammatoires. Comprendre comment les m&#xE9;canismes naturels de inflammatoires promouvoir un &#xE9;tat procoagulant, peut conduire &#xE0; l&#x26;#39;&#xE9;laboration de nouvelles interventions pharmacologiques cibl&#xE9;es &#xE0; la thrombose.

Inflammation et thrombose: Nouvelles perspectives

Schiff Wand endotheliale Sch&auml;den initiiert eine lokale entz&uuml;ndliche Reaktion, die einen Prothrombotic Zustand getrieben von Gewebe-Faktor, Adh&auml;sionsmolek&uuml;le und Pro-inflammatorische Zytokine f&ouml;rdert. Verst&auml;ndnis, wie nat&uuml;rliche entz&uuml;ndliche Mechanismen einen Prokoagulans Staat, f&ouml;rdern kann zur Entwicklung neuer pharmakologischer Interventionen zur Thrombose f&uuml;hren.

Entz&uuml;ndung und Thrombose: neue Einsichten.

Danno endoteliale vaso muro avvia una risposta infiammatoria locale, che promuove uno stato protrombotico guidato dal fattore di tessuti, molecole di adesione e citochine pro-infiammatorie. Comprensione come meccanismi infiammatori naturali promuovere uno stato procoagulante, pu&ograve; portare allo sviluppo di nuovi interventi farmacologici mirati alla trombosi.

Infiammazione e trombosi: nuove intuizioni.

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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.

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

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.

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

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.

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

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.

Patrick A. Lester

Unit for Laboratory Animal Medicine,
Refinement and Enrichment Advancements Laboratory

University of Michigan

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

Patrick A. Lester

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}Unit for Laboratory Animal Medicine,Refinement and Enrichment Advancements Laboratory

University of Michigan

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

Unit for Laboratory Animal Medicine,
Refinement and Enrichment Advancements Laboratory