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Wendy A. Goodwin Kirby Pasloske Helen L. Keates Millaganamada Gedara Ranasinghe Solomon Woldeyohannes Nigel Perkins 《Veterinary anaesthesia and analgesia》2019,46(2):188-199
Objective
To determine the suitability of alfaxalone total intravenous (IV) anaesthesia in horses and concurrently evaluate infusion rates, cardiovascular effects, pharmacokinetics and the quality of the anaesthetic recovery period.Study design
Prospective, experimental study.Animals
Eight Standardbred horses.Methods
Horses were premedicated with IV acepromazine (0.03 mg kg–1) and xylazine (1 mg kg–1) and anaesthesia was induced with guaifenesin (35 mg kg–1) and alfaxalone (1 mg kg–1). Anaesthesia was maintained for 180 minutes using an IV infusion of alfaxalone at a rate determined by a horse’s response to a supramaximal electrical noxious stimulus. Venous blood samples were regularly collected to determine alfaxalone plasma concentrations and for pharmacokinetic analysis. Cardiopulmonary variables were monitored and the quality of the anaesthetic recovery period scored.Results
The median (range) alfaxalone infusion rate was 3.1 (2.4–4.3) mg kg–1 hour–1. The mean ± standard deviation plasma elimination half-life, plasma clearance and volume of distribution for alfaxalone were 41 minutes, 25 ± 6.3 mL minute–1 kg–1 and 1.6 ± 0.5 L kg–1, respectively. During anaesthesia, mean arterial blood pressure was maintained above 70 mmHg in all horses. Cardiac index reached a minimum value (68% of baseline values) immediately after induction of anaesthesia and was maintained between 74% and 90% of baseline values for the remainder of the anaesthetic protocol. Following the cessation of the alfaxalone infusion, six of eight horses exhibited muscle tremors and paddling. All horses stood without incident on the first or second attempt with a median recovery score of 4.5 (good to excellent).Conclusions and clinical relevance
Anaesthesia in horses can be maintained with an infusion of alfaxalone at approximately 3 mg kg–1 hour–1. The alfaxalone infusion rates used resulted in minimal haemodynamic changes and good recovery quality. Mean alfaxalone plasma concentration was stable over the infusion period and clearance rates were similar to previously published single-dose alfaxalone studies in horses. 相似文献3.
Barbara Glanemann Karen Humm Mariana Abreu Sophie Aspinall David Buckeridge Hope Carveth Hannah Darcy Jessica Florey Polly Frowde Isuru Gajanayake Kate Green Emma Holmes Alenka Hrovat Anne-Katherine Jasensky Bryn A Jones Vasiliki Lantzaki Eve JY Lo Kirsty MacDonald Kevin O'Brien Alejandro Suárez-Bonnet Nele Van den Steen Balazs Szladovits Annelies Willems Helen Wilson 《Journal of veterinary internal medicine / American College of Veterinary Internal Medicine》2023,37(1):126-132
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Marine snails of the genus Conus are a large family of predatory gastropods with an unparalleled molecular diversity of pharmacologically active compounds in their venom. Cone snail venom comprises of a rich and diverse cocktail of peptide toxins which act on a wide variety of ion channels such as voltage-gated sodium- (NaV), potassium- (KV), and calcium- (CaV) channels as well as nicotinic acetylcholine receptors (nAChRs) which are classified as ligand-gated ion channels. The mode of action of several conotoxins has been the subject of investigation, while for many others this remains unknown. This review aims to give an overview of the knowledge we have today on the molecular pharmacology of conotoxins specifically interacting with nAChRs along with the structure–function relationship data. 相似文献
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Congestive heart failure associated with a large transverse left ventricular moderator band in a cat
Cardiomyopathy associated with abnormal trabecular bands of tissue traversing one or both ventricles is reported rarely in cats. The case of a 9-year-old cat which presented in congestive heart failure is reported. Multiple cardiac abnormalities were found, including a large trabecular tissue bridge which bisected the left ventricle. Other findings included arrhythmia, thrombocytopaenia and raised serum creatine kinase. The cat was euthanased due to clinical deterioration. Necropsy findings included increased cardiac weight, the division of the left ventricle by a large trabecular band composed of connective tissue and cardiac myofibres consistent with a moderator band, nodular thickening of the mitral valve, left atrial dilation, and fibroplasia/fibrosis of the left ventricular myocardium associated with widespread myofibre necrosis due to infarction. Pathological findings in this case differ from previous reports of ventricular transverse bridging tissue in cats with cardiac disease. 相似文献
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Arachchige Maheshika Kumari Jayasinghe Kirinde Gedara Isuru Sandanuwan Kirindage Ilekuttige Priyan Shanura Fernando Eui Jeong Han Gun-Woo Oh Won-Kyo Jung Ginnae Ahn 《Marine drugs》2022,20(2)
Recent studies have revealed that marine brown seaweeds contain numerous bioactive compounds which exhibit various bioactivities. The present study investigated the effect of low molecular weight fucoidan (SCF) isolated from Sargassum confusum, a brown alga, on inflammatory responses and oxidative stress in HaCaT keratinocytes stimulated by tumor necrosis factor (TNF)-α/interferon (IFN)-γ. SCF significantly increased the cell viability while decreasing the intracellular reactive oxygen species (ROS) production in TNF-α/IFN-γ-stimulated HaCaT keratinocytes. In addition, SCF effectively reduced inflammatory cytokines (interleukin (IL)-1β, IL-6, IL-8, IL-13, TNF-α, and IFN-γ) and chemokines (Eotaxin, macrophage-derived chemokine (MDC), regulated on activation, normal T cell expressed and secreted (RANTES), and thymus and activation-regulated chemokine (TARC)) expression, by down-regulating the expression of epithelial and epidermal innate cytokines (IL-25, IL-33, and thymic stromal lymphopoietin (TSLP)). Furthermore, SCF suppressed the activation of TNF-α/IFN-γ-stimulated mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) signaling pathways, while activating the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway. The cytoprotective effect of SCF against TNF-α/IFN-γ stimulation was considerably reduced upon inhibition of HO-1 activity by ZnPP. Overall, these results suggest that SCF effectively suppressed inflammatory responses and oxidative stress in TNF-α/IFN-γ-stimulated HaCaT keratinocytes via activating the Nrf2/HO-1 signaling pathway. 相似文献
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Goodwin WA Keates HL Pasloske K Pearson M Sauer B Ranasinghe MG 《Veterinary anaesthesia and analgesia》2011,38(5):431-438
ObjectiveTo determine the pharmacokinetics and pharmacodynamics of the neurosteroidal anaesthetic, alfaxalone, in horses after a single intravenous (IV) injection of alfaxalone, following premedication with acepromazine, xylazine and guaiphenesin.Study designProspective experimental study.AnimalsTen (five male and five female), adult, healthy, Standardbred horses.MethodsHorses were premedicated with acepromazine (0.03 mg kg?1 IV). Twenty minutes later they received xylazine (1 mg kg?1 IV), then after 5 minutes, guaiphenesin (35 mg kg?1 IV) followed immediately by IV induction of anaesthesia with alfaxalone (1 mg kg?1). Cardiorespiratory variables (pulse rate, respiratory rate, pulse oximetry) and clinical signs of anaesthetic depth were evaluated throughout anaesthesia. Venous blood samples were collected at strategic time points and plasma concentrations of alfaxalone were assayed using liquid chromatography-mass spectrometry (LC/MS) and analysed by noncompartmental pharmacokinetic analysis. The quality of anaesthetic induction and recovery was scored on a scale of 1–5 (1 very poor, 5 excellent).ResultsThe median (range) induction and recovery scores were 4 (3–5) (good: horse slowly and moderately gently attained recumbency with minimal or no rigidity or paddling) and 4 (1–5) (good: horse stood on first attempt with some knuckling and ataxia) respectively. The monitored cardiopulmonary variables were within the range expected for clinical equine anaesthesia. The mean ± SD durations of anaesthesia from induction to sternal recumbency and from induction to standing were 42.7 ± 8.4 and 47 ± 9.6 minutes, respectively. The mean ± SD plasma elimination half life (t1/2), plasma clearance (Clp) and volume of distribution (Vd) for alfaxalone were 33.4 minutes, 37.1 ± 11.1 mL minute?1 kg?1 and 1.6 ± 0.4 L kg?1, respectively.Conclusions and clinical relevanceAlfaxalone, in a 2-hydroxypropyl-beta-cyclodextrin formulation, provides anaesthesia with a short duration of recumbency that is characterised by a smooth induction and satisfactory recovery in the horse. As in other species, alfaxalone is rapidly cleared from the plasma in the horse. 相似文献
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