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Acute and sub-chronic toxicity study of recombinant bovine interferon alpha in rodents
2021
Yu, Hai-Yang | Gao, Dong-Mei | Zhou, Wei | Xia, Bing-Bing | He, Zhi-Yuan | Wu, Bo | Jiang, Min-Zhi | Wang, Mingli | Zhao, Jun
Recombinant bovine interferon alpha (rBoIFN-α) has been demonstrated to have antiviral activity. However, no conduct of acute or chronic toxicity tests has been reported. Specific pathogen-free Sprague Dawley rats were administered doses at different concentrations through intraperitoneal or intravenous injection. After the administration (single for an acute toxicity test over 14 days or daily for a sub-chronic toxicity test over 30 days), the rats’ behaviour and other indicators and the degree of toxic reaction were continuously monitored. Blood was collected for haematological and serum biochemical examinations. At the end of the experiments, the rats were sacrificed for necropsy and histopathological tissue analysis. The external performance, behaviour characteristics, and changes in body temperature and body weight of the rats in each subgroup were comparable to the normal control subgroup. Except for a few cases, there were no lesions in the viscera’s pathological structures, and the blood parameters and biochemical indicators were not noticeably different from those of the control subgroup. This study suggests that rBoIFN-α seems to be safe for rats, and its use may foster the development of the cattle industry in China by protecting livestock health.
Afficher plus [+] Moins [-]Clinical use of the parasympathetic tone activity index as a measurement of postoperative analgaesia in dogs undergoing ovariohysterectomy
2021
While the current tools to assess canine postoperative pain using physiological and behavioural parameters are reliable, an objective method such as the parasympathetic tone activity (PTA) index could improve postoperative care. The aim of the study was to determine the utility of the PTA index in assessing postoperative analgaesia. Thirty healthy bitches of different breeds were randomly allocated into three groups for analgaesic treatment: the paracetamol group (GPARAC, n = 10) received 15 mg/kg b.w., the carprofen group (GCARP, n = 10) 4 mg/kg b.w., and the meloxicam group (GMELOX, n = 10) 0.2 mg/kg b.w. for 48 h after surgery. GPARAC was medicated orally every 8 h, while GCARP and GMELOX were medicated intravenously every 24 h. The PTA index was used to measure the analgaesia–nociception balance 1 h before surgery (baseline), and at 1, 2, 4, 6, 8, 12, 16, 20, 24, 36, and 48 h after, at which times evaluation on the University of Melbourne Pain Scale (UMPS) was made. The baseline PTA index was 65 ± 8 for GPARAC, 65 ± 7 for GCARP, and 62 ± 5 for GMELOX. Postoperatively, it was 65 ± 9 for GPARAC, 63 ± 8 for GCARP, and 65 ± 8 for GMELOX. No statistically significant difference existed between baseline values or between values directly after treatments (P = 0.99 and P = 0.97, respectively). The PTA index showed a sensitivity of 40%, specificity of 98.46% and a negative predictive value of 99.07%. Our findings suggest that the PTA index measures comfort and postoperative analgaesia objectively, since it showed a clinical relationship with the UMPS.
Afficher plus [+] Moins [-]Cardiopulmonary effects of an intravenous infusion of fentanyl in cats during isoflurane anesthesia and with concurrent acepromazine or dexmedetomidine administration during anesthetic recovery
2021
Keating, Stephanie C. J. | Kerr, Carolyn L.
OBJECTIVE To determine the cardiopulmonary effects of IV administration of fentanyl to cats anesthetized with isoflurane and during anesthetic recovery with concurrent administration of acepromazine or dexmedetomidine. ANIMALS 6 healthy adult cats. PROCEDURES Cats received an IV bolus (5 μg/kg) followed by an IV infusion (5 μg/kg/h) of fentanyl for 120 minutes during isoflurane anesthesia and for 30 minutes after discontinuing isoflurane. Cats were randomly assigned in a crossover study to receive acepromazine (0.05 mg/kg) or dexmedetomidine (2.5 μg/kg), IV, when isoflurane was discontinued. Cardiopulmonary data were obtained during anesthesia and for 30 minutes during the anesthetic recovery period. RESULTS The administration of fentanyl during isoflurane anesthesia resulted in a transient increase in arterial blood pressure, mean pulmonary artery pressure, and oxygen delivery. Compared with values during isoflurane anesthesia, administration of dexmedetomidine during anesthetic recovery resulted in significant decreases in cardiac index, stroke index, and oxygen delivery and significant increases in arterial, central venous, and mean pulmonary artery pressures; systemic vascular resistance index; and oxygen extraction ratio. Administration of acepromazine resulted in increases in heart rate, cardiac index, oxygen uptake, and oxygen extraction ratio. Oxygen extraction ratio did not differ between acepromazine and dexmedetomidine. CONCLUSIONS AND CLINICAL RELEVANCE Fentanyl transiently improved indices of cardiopulmonary performance when administered to healthy cats anesthetized with isoflurane. The cardiovascular effects of acepromazine and dexmedetomidine in healthy cats receiving fentanyl during recovery from isoflurane anesthesia differed, but measured cardiopulmonary parameters remained within acceptable limits.
Afficher plus [+] Moins [-]Time required to achieve maximum amikacin concentration in the synovial fluid of the tarsocrural joint following administration of the drug by intravenous regional limb perfusion in horses
2021
OBJECTIVE To determine the median time to maximum concentration (tmax) of amikacin in the synovial fluid of the tarsocrural joint following IV regional limb perfusion (IVRLP) of the drug in a saphenous vein of horses. ANIMALS 7 healthy adult horses. PROCEDURES With each horse sedated and restrained in a standing position, a 10-cm-wide Esmarch tourniquet was applied to a randomly selected hind limb 10 cm proximal to the point of the tarsus. Amikacin sulfate (2 g diluted with saline [0.9% NaCl] solution to a volume of 60 mL) was instilled in the saphenous vein over 3 minutes with a peristaltic pump. Tarsocrural synovial fluid samples were collected at 5, 10, 15, 20, 25, and 30 minutes after completion of IVRLP. The tourniquet was removed after collection of the last sample. Amikacin concentration was quantified by a fluorescence polarization immunoassay. Median maximum amikacin concentration and tmax were determined. RESULTS 1 horse was excluded from analysis because an insufficient volume of synovial fluid for evaluation was obtained at multiple times. The median maximum synovial fluid amikacin concentration was 450.5 μg/mL (range, 304.7 to 930.7 μg/mL), and median tmax was 25 minutes (range, 20 to 30 minutes). All horses had synovial fluid amikacin concentrations ≥ 160 μg/mL (therapeutic concentration for common equine pathogens) at 20 minutes after IVRLP. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that, in healthy horses, maintaining the tourniquet for 20 minutes after IVRLP of amikacin in a saphenous vein was sufficient to achieve therapeutic concentrations of amikacin in the tarsocrural joint.
Afficher plus [+] Moins [-]Effects of perineural administration of ropivacaine combined with perineural or intravenous administration of dexmedetomidine for sciatic and saphenous nerve blocks in dogs
2021
Marolf, Vincent | Ida, Keila K. | Siluk, Danuta | Struck-Lewicka, Wiktoria | Markuszewski, Michael J. | Sandersen, Charlotte
OBJECTIVE To evaluate the effects of using ropivacaine combined with dexmedetomidine for sciatic and saphenous nerve blocks in dogs. ANIMALS 7 healthy adult Beagles. PROCEDURES In phase 1, dogs received each of the following 3 treatments in random order: perineural sciatic and saphenous nerve injections of 0.5% ropivacaine (0.4 mL/kg) mixed with saline (0.9% NaCl) solution (0.04 mL/kg; DEX0PN), 0.5% ropivacaine mixed with dexmedetomidine (1 μg/kg; DEX1PN), and 0.5% ropivacaine mixed with dexmedetomidine (2 μg/kg; DEX2PN). In phase 2, dogs received perineural sciatic and saphenous nerve injections of 0.5% ropivacaine and an IV injection of diluted dexmedetomidine (1 μg/kg; DEX1IV). For perineural injections, the dose was divided equally between the 2 sites. Duration of sensory blockade was evaluated, and plasma dexmedetomidine concentrations were measured. RESULTS Duration of sensory blockade was significantly longer with DEX1PN and DEX2PN, compared with DEX0PN; DEX1IV did not prolong duration of sensory blockade, compared with DEX0PN. Peak plasma dexmedetomidine concentrations were reached after 15 minutes with DEX1PN (mean ± SD, 348 ± 200 pg/mL) and after 30 minutes DEX2PN (816 ± 607 pg/mL), and bioavailability was 54 ± 40% and 73 ± 43%, respectively. The highest plasma dexmedetomidine concentration was measured with DEX1IV (1,032 ± 415 pg/mL) 5 minutes after injection. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that perineural injection of 0.5% ropivacaine in combination with dexmedetomidine (1 μg/kg) for locoregional anesthesia in dogs seemed to balance the benefit of prolonging sensory nerve blockade while minimizing adverse effects.
Afficher plus [+] Moins [-]Pharmacokinetics of mycophenolate mofetil following single-dose intravenous and single- and multiple-dose oral administration and clinicopathologic effects of mycophenolate mofetil following long-term oral administration in healthy horses
2021
Knych, Heather K. | McKemie, Daniel S. | Kanarr, Kirsten L. | White, Stephen D.
OBJECTIVE To characterize the pharmacokinetics of mycophenolate mofetil (MMF) following single-dose IV or PO administration, characterize the pharmacokinetics of MMF following long-term PO administration, and describe the clinicopathologic effects of long-term MMF administration in horses. ANIMALS 12 healthy adult horses. PROCEDURES In phase 1, 6 horses received a single IV (2.5 mg/kg) or PO (5 mg/kg) dose of MMF in a randomized balanced crossover assessment (≥ 2-week interval between administrations). In phase 2, 6 other horses received MMF for 60 days (5 mg/kg, PO, q 24 h for 30 days and then 5 mg/kg, PO, q 48 h for an additional 30 days). RESULTS Following IV (single-dose) or PO (single- or multiple-dose) administration, MMF was rapidly converted to mycophenolic acid. For single-dose PO administration, mean ± SD maximum plasma mycophenolic acid concentration was 1,778.3 ± 441.5 ng/mL at 0.71 ± 0.29 hours. For single-dose IV administration, mean systemic clearance and volume of distribution at steady state were 0.689 ± 0.194 L/h/kg and 1.57 ± 0.626 L/kg, respectively. Following single doses, mean terminal half-life was 3.99 ± 0.865 hours for IV administration and 4.02 ± 1.01 hours for PO administration. The accumulation index following long-term PO administration was 1.0 ± 0.002, and the terminal half-life was 4.59 ± 1.25 hours following the final dose on day 60. None of the horses developed abnormal clinical signs or had any consistently abnormal clinicopathologic findings. CONCLUSIONS AND CLINICAL RELEVANCE Further investigation of the clinical efficacy of long-term MMF treatment of horses with autoimmune diseases is warranted.
Afficher plus [+] Moins [-]Intravenous administration of allogeneic Wharton jelly-derived mesenchymal stem cells for treatment of dogs with congestive heart failure secondary to myxomatous mitral valve disease
2021
Yang, Vicky K. | Meola, Dawn M. | Davis, Airiel | Barton, Bruce | Hoffman, Andrew M.
OBJECTIVE To evaluate whether mesenchymal stem cells (MSCs) can be safely administered IV to dogs with congestive heart failure (CHF) secondary to myxomatous mitral valve disease (MMVD) to improve cardiac function and prolong survival time. ANIMALS 10 client-owned dogs with CHF secondary to MMVD. PROCEDURES Dogs with an initial episode of CHF secondary to MMVD were enrolled in a double-blind, placebo-controlled clinical trial. Five dogs in the MSC group received allogeneic Wharton jelly-derived MSCs (2 × 106 cells/kg, IV), and 5 dogs in the placebo group received a 1% solution of autologous serum (IV) for 3 injections 3 weeks apart. Cell-release criteria included trilineage differentiation, expression of CD44 and CD90 and not CD34 and major histocompatability complex class II, normal karyotype, and absence of contamination by pathogenic microorganisms. Patients were followed for 6 months or until death or euthanasia. Echocardiographic data, ECG findings, serum cardiac biomarker concentrations, CBC, and serum biochemical analysis results were obtained prior to and 4 hours after the first injection and every 3 months after the final injection. RESULTS Lymphocyte and eosinophil counts decreased significantly 4 hours after injection, and monocytes decreased significantly only in dogs that received an MSC injection. No significant differences were seen in the echocardiographic variables, ECG results, serum cardiac biomarker concentrations, survival time, and time to first diuretic drug dosage escalation between the 2 groups. CONCLUSIONS AND CLINICAL RELEVANCE This study showed that MSCs can be easily collected from canine Wharton jelly as an allogeneic source of MSCs and can be safely delivered IV to dogs with CHF secondary to MMVD.
Afficher plus [+] Moins [-]Assessment of the physical compatibility of injectable enrofloxacin with commonly used intravenous fluids and drugs during simulated Y-port administration
2021
Aghili, Anahita | Thomovsky, Elizabeth J. | Johnson, Paula A. | Brooks, Aimee C. | Pierce, Trinna J. | Gochenauer, Alexandria E.
OBJECTIVE To evaluate physical compatibility of small animal (SAE) and large animal (LAE) injectable formulations of enrofloxacin with select IV fluids and drugs. SAMPLE 162 admixtures containing SAE or LAE with saline (0.9% NaCl) solution, lactated Ringer solution (LRS), Plasma-Lyte A (PLA), 6% hydroxyethylstarch 130/0.4 (HES), metoclopramide, or ampicillin-sulbactam. PROCEDURES In the first of 2 simultaneously conducted experiments, admixtures containing enrofloxacin (10 mg/kg) and a volume of IV fluid that would be administered over a 20-minute period when dosed at the maintenance infusion rate (40 mL/kg/d for saline solution, LRS, and PLA and 20 mL/kg/d for HES) were created. In the second experiment, enrofloxacin (10 mg/kg) was admixed with saline solution (40 mL/kg/d) and metoclopramide (2 mg/kg/d) or ampicillin-sulbactam (30 mg/kg). In both experiments, admixture components were infused into a flask over 20 minutes assuming patient weights of 5, 10, and 20 kg. Admixtures were created by use of undiluted SAE and SAE diluted 1:1 with saline solution and undiluted LAE and LAE diluted 1:1 and 1:10 with saline solution. Admixtures were assessed for physical incompatibility at 0, 15, 30, and 60 minutes after completion of mixing. Physical incompatibility was defined as gross precipitation, cloudiness, Tyndall effect, or change in turbidity. RESULTS Admixtures containing undiluted SAE or LAE were physically incompatible with saline solution, PLA, LRS, and HES. Because saline solution was used to dilute SAE and LAE, all admixtures containing diluted SAE or LAE were also physically incompatible. Physical compatibility of enrofloxacin with metoclopramide or ampicillin-sulbactam could not be assessed because those admixtures also contained saline solution. CONCLUSIONS AND CLINICAL RELEVANCE Enrofloxacin was physically incompatible with all tested solutions.
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