Comparison of the pharmacokinetic profiles of two different amphotericin B formulations in healthy dogs

This study was conducted to compare the pharmacokinetic profiles of conventional (Fungizone^®) and liposomal amphotericin B (AmBisome^®) formulations in order to predict their therapeutic properties, and evaluate their potential differences in veterinary treatment. For this purpose, twelve healthy mixed breed dogs received both drugs at a dose of 0.6 mg/kg by intravenous infusion over a 4‐min period in a total volume of 40 ml. Blood samples were collected at 0, 0.5, 1, 1.5, 2, 3, 4, 8, 12, 24, 48, 72 and 96 hr after dosing, and concentrations of drug in plasma were determined by high‐performance liquid chromatography (HPLC). Pharmacokinetics was described by a two‐compartment model. Although both formulations were administered at the same doses (0.6 mg/kg), the plasma pharmacokinetics of liposomal amphotericin B differed significantly from those of amphotericin B deoxycholate in healthy dogs (p < .05). Liposomal amphotericin B showed markedly higher peak plasma concentrations (approximately ninefold greater) and higher area under the plasma concentration curve values (approximately 14‐fold higher) compared to conventional formulation. It is concluded that AmBisome^® reached higher plasma concentration and lower distribution volume and had a longer half‐life compared to Fungizone^®, and therefore, AmBisome^® is reported to be an appropriate and effective choice for the treatment of systemic mycotic infections in dogs.     

Recovery of brodifacoum in vomitus following induction of emesis in dogs that had ingested rodenticide bait

AIM: To assess the benefit of inducing emesis in dogs that have ingested rodenticide bait containing brodifacoum (BDF), by determining the amount of BDF in bait recovered from the vomitus relative to the estimated amount consumed.

METHODS: Between 2014 and 2015 samples of vomitus from seven dogs that ingested rodenticide baits containing BDF were submitted by veterinarians in New Zealand. All seven dogs had been given apomorphine by the veterinarian and vomited within 1 hour of ingesting the bait. Some or all of the bait particles were retrieved from each sample and were analysed for concentrations of BDF using HPLC. Based on estimations of the mass of bait consumed, the concentration of BDF stated on the product label, and the estimated mass of bait in the vomitus of each dog, the amount of BDF in the vomited bait was calculated as a percentage of the amount ingested.

RESULTS: For five dogs an estimation of the mass of bait ingested was provided by the submitting veterinarian. For these dogs the estimated percentage of BDF in the bait retrieved from the vomitus was between 10–77%. All dogs were well after discharge but only one dog returned for further testing. This dog had a normal prothrombin time 3 days after ingestion.

CONCLUSIONS AND CLINICAL RELEVANCE: The induction of emesis within 1 hour of ingestion can be a useful tool in reducing the exposure of dogs to a toxic dose of BDF. The BDF was not fully absorbed within 1 hour of ingestion suggesting that the early induction of emesis can remove bait containing BDF before it can be fully absorbed.     

Effect of benazepril and pimobendan on serum angiotensin‐converting enzyme activity in dogs

To support their combined use, the objective of the study was to evaluate the effects of benazepril and pimobendan on serum angiotensin‐converting enzyme (ACE) activity in dogs. A total of 48 healthy beagle dogs were randomized into four groups (n = 12 per group) in a parallel‐group design study: A (control, placebo twice daily (BID)); B (0.5–1.0 mg/kg benazepril once daily (SID) in the morning, placebo in the evening); C (0.25–0.5 mg/kg benazepril BID); D (0.25–0.5 mg/kg benazepril and 0.125–0.25 mg/kg pimobendan, both BID). The test items were administered orally for 15 days. Serum ACE activity was measured on days 1 and 15. Groups B, C and D had significantly lower average serum ACE activity compared to baseline and to the control group, on both days 1 and 15. There were no significant differences in average ACE activity between groups B, C and D. Noninferiority of group C to B was demonstrated. In conclusion, 0.25–0.5 mg/kg benazepril administered BID produced noninferior inhibition of serum ACE activity compared to 0.5–1.0 mg/kg benazepril dosed SID. Pimobendan had no significant effect on benazepril's action on serum ACE activity. The results support the use of benazepril BID in dogs and in combination with pimobendan.     

Categorization of the pelvic limb standing posture in nine breeds of dogs

The objective of the study was to categorize objectively nine breeds of healthy dogs according to pelvic limb standing posture. A total of 135 dogs from different breeds were used and the standing angles of the hip, stifle, and tarsal joints, together with the percentages of the greater trochanter, patella and tuber calcanei heights, with respect to crista iliaca height, were used as discriminant variables for the categorization of pelvic limb posture. All included breeds were allocated to three groups of the standing pelvic limb posture. The best discriminant variables between the three groups were the percentage of patellar height, and the standing angles of the stifle and tarsal joints. German shepherds, Anatolian shepherds, golden retrievers, Rottweilers, Belgian Malinois and Dobermann pinschers were well separated between 89% and 100% success rate for the categorization. The minimal success rate was determined in Berner sennenhunds as the ratio of 75%. It was also determined that Dobermann pinschers had the straightest pelvic limbs, while German shepherds had the most angulated pelvic limbs. Further studies are required to document the impact of postural differences in active and passive structure diseases of the locomotor system of the pelvic limb among dog breeds.     

A fast,low‐cost and efficient method for the diagnosis of sperm DNA fragmentation in several species

Sperm DNA fragmentation is a condition that interferes directly in the reproductive efficiency. Currently, there are several methods for assessing the sperm DNA integrity, such as Alkaline Comet, TUNEL and Sperm Chromatin Structure Assay. However, many of these techniques are laborious and require high‐precision equipment. Thus, the development of new techniques can optimize the evaluation of sperm DNA damage. Therefore, the aim of this study was to standardize the toluidine blue (TB) stain technique for the analysis of DNA fragmentation of dog, cat, bull, stallion and ram spermatozoa. For this purpose, we used six animals of each specie (n = 30), in reproductive age. Sperm was collected by different methods according to the particularities of each species, and such samples were divided into two aliquots: a sperm sample was kept at 5°C (considered as intact sperm DNA), and the remaining samples were submitted to the induction of DNA fragmentation by exposure to ultraviolet light for 4 hr. Samples were then mixed with the intact sample to obtain known and progressive proportions of sperm with fragmented DNA (0%, 25%, 50%, 75% and 100%). Semen smears were performed and subjected to staining with TB. Blue‐stained spermatozoa were considered to have DNA fragmentation. We observed high linear regression coefficients between the expected proportion of damaged DNA and the results of TB for dog, cat, ram, bull and stallion samples. In conclusion, TB stain was considered a fast and effective technique for the study of spermatozoa DNA in several species.     

Colour Flow Mapping examination: An useful screening test for the early diagnosis of ductus venosus patency in canine newborns

Ductus venosus (DV) closure plays a key role in hepatic circulation adaptation to postnatal metabolic function, and DV patency might develop a congenital portosystemic shunt (CPSS). The noninvasive Color Flow Mapping (CFM) examination, a validated method to diagnose CPSS in adult dogs, is routinely performed to assess DV closure after birth in humans. This study aimed to describe the feasibility of the ultrasonographic evaluation of the DV after birth and to determine its closure time in healthy Great Dane neonates. Patency of DV in serial Color Flow Mapping (CFM) examinations and bodyweight (BW) were recorded on Days 0‐3‐6‐9 in 24 neonates that were classified as having patent (PDV) or closed ductusvenosus (CDV) basing on CFM signal presence/absence. Since the 3rd day, DV diameter was recorded. Data were analysed by ANOVA (p < 0.05). All dogs resulted healthy 1 year later. The number of PDV and CDV puppies at birth was not different on Day 3 (24 and 0 vs. 22 and 2, PDV and CDV, respectively), whereas it resulted different on Days 6 (24 and 0 vs. 14 and 10) and 9 (24 and 0 vs. 0 and 24); on Day 3, it was different compared to Days 6 and 9; on Day 6, it was different from Day 9. Reduction of DV diameter resulted positively related to neonatal BW growth. The CFM evaluation of DV closure after birth in Great Dane puppies represents a feasible technique. Present results suggest the time of functional closure in normal neonates within 9 days after birth. Thus, CFM examination, as an early screening test for DV patency evaluation, performed 10 days after birth, may identify suspicious dogs at risk that would require further investigations. Further studies are needed to deepen the role of a delayed closure in low bodyweight and preterm puppies.