[show abstract][hide abstract] ABSTRACT: The objective of this study was to determine the pharmacodynamics effects of the anaesthetic alfaxalone in 2-hydroxypropyl- β -cyclodextrin in pregnant sheep after the intravenous injection of a 2 mg/kg weight dose. Six pregnant Ripollesa sheep, weighing 47.1 ± 4.4 kg, were used. Twenty-four hours after instrumentation, sheep were anaesthetized with intravenous alfaxalone in cyclodextrin. Time to standing from anaesthesia was 30.0 ± 10.81 min. Foetal heart rate increased significantly during the first 5 min after alfaxalone administration. Significant differences were observed in maternal diastolic arterial blood pressure between minute 10 and minutes 90, 120, 150, 180, 210, and 240. Significant differences were observed for foetal systolic arterial blood pressure between 5 and 30 min after alfaxalone administration. Significant differences in foetal pH were detected during the entire study period, whereas maternal pH returned to baseline values by 60 min after alfaxalone administration. The present study indicated that alfaxalone in 2-hydroxypropyl- β -cyclodextrin administered as an intravenous bolus at 2 mg/kg body weight produced minimal adverse effects and an uneventful recovery from anaesthesia in pregnant sheep and their foetus.
The Scientific World Journal 01/2013; 2013:189843. · 1.73 Impact Factor
[show abstract][hide abstract] ABSTRACT: The "One world, one health" initiative emphasizes the need for new strategies to control human and animal tuberculosis (TB) based on their shared interface. A good example would be the development of novel universal vaccines against Mycobacterium tuberculosis complex (MTBC) infection. This study uses the goat model, a natural TB host, to assess the protective effectiveness of a new vaccine candidate in combination with Bacillus Calmette-Guerin (BCG) vaccine. Thirty-three goat kids were divided in three groups: Group 1) vaccinated with BCG (week 0), Group 2) vaccinated with BCG and boosted 8 weeks later with a recombinant adenovirus expressing the MTBC antigens Ag85A, TB10.4, TB9.8 and Acr2 (AdTBF), and Group 3) unvaccinated controls. Later on, an endobronchial challenge with a low dose of M. caprae was performed (week 15). After necropsy (week 28), the pulmonary gross pathology was quantified using high resolution Computed Tomography. Small granulomatous pulmonary lesions (< 0.5 cm diameter) were also evaluated through a comprehensive qualitative histopathological analysis. M. caprae CFU were counted from pulmonary lymph nodes. The AdTBF improved the effects of BCG reducing gross lesion volume and bacterial load, as well as increasing weight gain. The number of Ag85A-specific gamma interferon-producing memory T-cells was identified as a predictor of vaccine efficacy. Specific cellular and humoral responses were measured throughout the 13-week post-challenge period, and correlated with the severity of lesions. Unvaccinated goats exhibited the typical pathological features of active TB in humans and domestic ruminants, while vaccinated goats showed only very small lesions. The data presented in this study indicate that multi-antigenic adenoviral vectored vaccines boosts protection conferred by vaccination with BCG.
PLoS ONE 01/2013; 8(11):e81317. · 3.73 Impact Factor
[show abstract][hide abstract] ABSTRACT: Alfaxalone in a 2-hydroxypropyl-β-cyclodextrin (HPCD) formulation is an intravenous (IV) hypnotic agent characterised by the stability of cardiorespiratory effects after a single-bolus administration. The objective of this study was to investigate the cardiovascular, respiratory, and acid-base effects of alfaxalone-HPCD administered during a continuous rate infusion in six Ripollesa sheep. After instrumentation, a 2mg/kg IV bolus of alfaxalone followed by a continuous infusion of 10mg/kg/h was administered to the sheep. Heart rate, arterial blood pressure, respiratory rate and arterial blood gases were recorded. Occasional side effects and time to standing were also noted. No significant changes were observed in arterial blood pressure, but during the infusion and the initial stages of recovery, a significant increase in heart rate occurred during the last 120min of the study. Significant respiratory depression was detected during the infusion period and the first 15min of recovery. This study showed that a constant rate infusion alfaxalone in un-premedicated sheep produced clinically acceptable haemodynamic results and a mild respiratory depression that may require intermittent positive pressure ventilation.
The Veterinary Journal 10/2012; · 2.42 Impact Factor
[show abstract][hide abstract] ABSTRACT: The objective of this prospective study was to determine the effects of a single intravenous bolus of alfaxalone in 2-hydroxypropyl-β-cyclodextrin and propofol on the intraocular pressure (IOP) in sheep. Ten Ripollesa sheep with a bodyweight of 48.5 (6.8) kg (mean [sd]) were used in the study. Twenty-four hours before the experimental procedure, a complete ophthalmic examination was performed in all animals. The day of the study, intravenous alfaxalone (2 mg/kg) or propofol (6 mg/kg) was randomly administered in a cross-over design, with a washout period of two weeks. Measurements of IOP, globe position and pupil size were obtained at basal time, before induction (time 0) and at two, five, 10, 15, 20, 30, 45, 60, 90 and 120 minutes after drug administration. Occasional side effects and time to standing were also noted. Intravenous administration of alfaxalone and propofol in sheep resulted in no alteration of IOP. Nevertheless, a decrease in the pupil size was observed in both groups. This present study shows that alfaxalone and propofol, administrated as a single intravenous bolus, are good options for maintaining IOP during anaesthesia in sheep, although marked miosis was observed after administration.
[show abstract][hide abstract] ABSTRACT: Developmental competence of oocytes from prepubertal females is lower than those from adult females. Oocyte development competence is positively related to follicular diameter. Most of the follicles of prepubertal goat ovaries are smaller than 3 mm. The aim of this study was to compare oocytes of two follicle sizes (< 3 mm and ≥ 3 mm) from prepubertal goats with oocytes from adult goats in relation to their in vitro production and quality of blastocysts. Oocytes from prepubertal goats were obtained from slaughterhouse ovaries and selected according to the follicle diameter whereas oocytes from adult goats were recovered in vivo by LOPU technique without prior selection of follicle size. COCs were IVM for 27 h, IVF at the conventional conditions with fresh semen and presumptive zygotes were cultured in SOF medium for 8 days. Blastocysts obtained were vitrified and after warming their blastocoele re-expansion and the ploidy by FISH technique were assessed. We found significant differences between blastocysts yield of oocytes recovered from follicles smaller than 3 mm of prepubertal goats compared to those from adult goats (5.45% vs 20. 83%, respectively) however, these differences disappear if oocytes were recovered form large follicles (18.07%). A total of 28 blastocysts were analysed and 96.43% showed mixoploidy. Age did not affect the number of embryos with abnormal ploidy or blastocyst re-expansion after warming. Furthermore, the percentage of diploid blastomeres per embryo was similar in the 3 groups studied, adult, prepubertal from follicles ≥ 3 mm and < 3 mm (68.6%, 80.8% and 73.6%, respectively). In conclusion, IVP of blastocysts coming from follicles larger than 3 mm of goats 45 days old were not different to the blastocysts produced from adult goats, both in terms of quantity and quality.
[show abstract][hide abstract] ABSTRACT: The clinical efficacy of a 70 microg/h transdermal buprenorphine patch and of 20 microg/kg of buprenorphine administered subcutaneously (SC) for the relief of post-operative pain was determined in 24 healthy female dogs undergoing elective ovariohysterectomy (OHE). Dogs were randomly assigned to three groups: (1) a control group that received no analgesics, (2) a BSC group that received buprenorphine SC (20 microg/kg), and (3) a BP group that received buprenorphine by a 70 microg/h transdermal patch. Dogs were scored for signs of pain at 0, 2, 4, 6, 8, 10, 14, 20, 26, 32 and 38 h after extubation using the Numerical Rating Scale (NRS) and a modified University of Melbourne Pain Scale (UMPS). Mean NRS and UMPS scores for dogs in the BSC group (2.56 ± 0.23 and 3.05 ± 0.27, respectively) and the BP group (2.02 ± 0.24 and 2.67 ± 0.23, respectively) were significantly lower (P<0.05) compared with dogs in the control group (5.42 ± 0.38 and 7.89 ± 0.44, respectively), whereas differences between the two buprenorphine treatment groups were not significant. The results indicated that the analgesia produced by the 70 microg/h patch was similar to that induced by SC administration of 20 microg/kg of buprenorphine in dogs undergoing OHE, suggesting that the transdermal buprenorphine patch may be a useful alternative for pain management in dogs.
The Veterinary Journal 01/2011; 187(1):124-8. · 2.42 Impact Factor
[show abstract][hide abstract] ABSTRACT: The objective of the present study was to evaluate the plasma concentrations and pharmacokinetics of buprenorphine after transdermal application in dogs (n = 4). A 70 microg/h transdermal buprenorphine patch was applied to the ventral abdomen of four healthy beagles. Blood samples were collected through a preplaced jugular catheter before and at 1, 2, 4, 8, 12, 24, 36, 48 and every 6 h until 108 h after the patch application. Plasma buprenorphine concentrations were measured using a (125)I-labelled radioimmunoassay (RIA) assay. No adverse effects were observed in any of the dogs. Concentrations of buprenorphine were detected in plasma after the application of the transdermal buprenorphine patch on the four experimental animals. Buprenorphine plasma concentrations increased during the first 36 h and then remained in the 0.7-1.0 ng/mL range during the study period. A decrease in plasma buprenorphine concentration was not observed during the study. Although analgesia could not be demonstrated the present study shows the ability of buprenorphine transdermal delivery systems developed for human use to deliver measurable concetrations of buprenorphine in dogs.
Journal of Veterinary Pharmacology and Therapeutics 10/2009; 32(5):503-5. · 1.35 Impact Factor
[show abstract][hide abstract] ABSTRACT: Benign prostatic hyperplasia (BPH) is an age-dependent prostatic disease affecting male humans and dogs. In dogs, the combined administration of estrogens and androgens synergistically increases prostate weight, and continued treatment leads to the development of glandular hyperplasia. The aim of the present study was to examine the immunohistochemical expression of androgen receptor (AR), estrogen receptor alpha (ER alpha), and estrogen receptor beta (ER beta) in the different cell types of the prostate gland in an experimental model. Five male beagle dogs were castrated and treated with 25 mg of 5 alpha-androstane-3 alpha and 17beta-diol and 0.25 mg 17beta-estradiol for 30 weeks. Prostate specimens were surgically obtained every 45 days (experimental stages M0 to M6: 0, 12, 18, 24, 30, and 36 weeks from the beginning of the hormonal treatment). The control group consisted of 3 noncastrated dogs treated with a vehicle, from which specimens were only taken at the time points M0, M1, M4, and M6. Immunohistochemical data revealed high AR and ER alpha expression in the epithelial and stromal cell nuclei of all the experimental and control specimens. Weak staining of the cytoplasm was observed only in epithelial cells. The suspension of hormone treatment led to a significant reduction in the expression of both receptors. On the contrary, ER beta was expressed only in epithelial cell nuclei, with no significant differences in the percentages of stained nuclei between control and hormonally treated or atrophic prostates. Results indicate that AR, ER alpha, and ER beta are differently expressed in canine prostate tissue and that they show specific expression patterns in response to the hormonal induction of BPH.
Journal of Andrology 02/2009; 30(3):240-7. · 2.53 Impact Factor
[show abstract][hide abstract] ABSTRACT: Etomidate is an intravenous (IV) hypnotic agent characterised by its cardiovascular stability. Although etomidate has been satisfactorily used in veterinary and human obstetrics, little is known about its effects on the fetus. This study determined the cardiovascular and acid-base effects of etomidate administration in the pregnant ewe and her fetus. The effects of etomidate were evaluated in two separate studies. In the first study, etomidate was administered as a 1mg/kg IV bolus; in the second, the drug was administered as a continuous infusion of 100 microg/kg/min for 1h, preceded by a 1mg/kg IV bolus. Etomidate administration did not depress cardiovascular function in the pregnant ewe or fetus. When administered as a continuous infusion, maternal heart rate and blood pressure increased during the second half of the infusion and the initial stages of recovery. Acid-base alterations led to transient but slight respiratory depression in both mother and fetus, probably reflecting the combined effects of etomidate on respiration and the positioning of the animal.
The Veterinary Journal 08/2008; 177(1):94-103. · 2.42 Impact Factor
[show abstract][hide abstract] ABSTRACT: The purpose of this study was to evaluate plasma concentrations and pharmacokinetic parameters of buprenorphine in dogs following intravenous (IV) administration of clinical doses of the opioid. An IV bolus of 0.02mg/kg buprenorphine was administered to six healthy Beagles and blood samples were collected through a jugular catheter before and at 1, 5, 10, 15, 20, 30 and 45 min, and 1, 2, 4, 6, 8 and 12h after administration. Plasma buprenorphine concentrations, measured using a commercial radioimmunoassay (RIA), decreased following a three-exponential curve. The two distribution and the elimination half-lives were 2.9+/-1.8min, 16.5+/-3.7min, and 266.6+/-82.0min, respectively; the clearance was 329.6+/-62.2mL/min, and the steady state volume of distribution was 83.7+/-26.5L. The results demonstrated the feasibility of the RIA assay to analyse buprenorphine in dog plasma samples. Following IV administration buprenorphine showed a three-compartment kinetic profile, as has been described previously in humans, rabbits and cats. The relationship between plasma concentrations and dynamic effects in dogs remains to be established.
The Veterinary Journal 06/2008; 181(3):299-304. · 2.42 Impact Factor
[show abstract][hide abstract] ABSTRACT: Etomidate (ETO) is a short-acting intravenous (IV) anaesthetic characterised by cardiopulmonary stability and favourable pharmacokinetics. Although ETO has been used satisfactorily in obstetrical anaesthesia, little is known about placental transfer and the drug's pharmacokinetics in the fetus. Placental transfer in pregnant ewes has been evaluated following the administration of an IV bolus of 1mg/kg ETO; and after a 1-h infusion of 100 microg/kg min(-1) ETO preceded by an IV bolus of 1mg/kg. In ewes, ETO concentration and AUC were higher than those found in fetuses. After the ETO bolus dose, the fetus:ewe AUC ratio was 0.45+/-0.32, and the mean residence time (MRT) was 20+/-7 min for dams and 22+/-3 min for the fetuses. After ETO infusion, the AUC ratio was 0.37+/-0.08, and MRT was 46+/-12 min for ewes and 46+/-22 min for fetuses. Although ETO crosses the placenta very rapidly and reaches the fetus in high amounts, a certain placental barrier effect limits its transfer. There is no evidence of cumulative effects of the drug in the fetus as fetal ETO elimination was as rapid as in the dam.
The Veterinary Journal 04/2008; 175(3):395-402. · 2.42 Impact Factor