Pharmacokinetics and plasma protein binding of a single dose of clodronate disodium are similar for juvenile sheep and horses.

OBJECTIVE: To determine the single-dose pharmacokinetics of clodronate disodium (CLO) in juvenile sheep and the plasma protein binding (PPB) of CLO in juvenile sheep and horses. ANIMALS: 11 juvenile crossbred sheep (252 ± 6 days) for the pharmacokinetic study. Three juvenile crossbred sheep (281 ± 4 days) and 3 juvenile Quarter Horses (599 ± 25 days) for PPB analysis. METHODS: CLO concentrations were determined using liquid chromatography-mass spectrometry. Pharmacokinetic parameters were calculated by noncompartmental analysis from plasma samples obtained at 0, 0.5, 1, 3, 6, 12, 24, 48, and 72 hours after CLO administered IM at 0.6 mg/kg. PPB was determined using equine and ovine plasma in a single-use rapid equilibrium dialysis system. RESULTS: The mean and range for maximum plasma concentration (Cmax: 5,596; 2,396-8,613 ng/mL), time of maximal concentration (Tmax: 0.5; 0.5-1.0 h), and area under the curve (AUCall: 12,831; 7,590-17,593 h X ng/mL) were similar to those previously reported in horses. PPB in sheep and horses was moderate to high, with unbound fractions of 26.1 ± 5.1% in sheep and 18.7 ± 7.5% in horses, showing less than a 1.4-fold difference. CLINICAL RELEVANCE: The pharmacokinetic parameters and PPB of CLO in juvenile sheep were similar to those previously reported in horses. The results suggest that juvenile sheep can be utilized as an animal model for studying the potential risks and/or benefits of bisphosphonate use in juvenile horses.

Ex vivo evaluation of a novel suture loop method for equine intestinal biopsies.

OBJECTIVE: To compare a novel suture loop method for intestinal biopsies (SLB) with a two-layer, hand-sutured biopsy (HSB) technique in equine small and large intestines. STUDY DESIGN: Experimental, randomized, ex vivo study. ANIMALS: Eight healthy adult horses. METHODS: The duodenum, aboral jejunum, and ventral and dorsal large colon were harvested after euthanasia and divided into three sections each. The sections were randomized to SLB, HSB, or control (C, no biopsy) groups. Tissue samples were excised after placement of a suture loop formed by a 4S Roeder knot and oversewn with a Cushing pattern using barbed suture (SLB), or a simple continuous pattern oversewn with a Cushing pattern (HSB). Intraluminal diameter was assessed with contrast radiographs; bursting pressure and wall tension were determined using a solid-state sensor after instillation of fluid. Tissue samples were evaluated by a board-certified pathologist. RESULTS: Tissue samples were full thickness with similar depth and quality (p > .3). Changes in intraluminal diameter did not differ between methods (p > .16). The bursting pressures were higher for controls than biopsied sections (p < .009) but were not different between biopsy methods (p = .998). Bursting wall tension was higher for controls (p < .02) and was similar for both biopsy methods (p = .852). CONCLUSION: The SLB was equivalent to HSB in strength and effect on intraluminal diameter. The HSB samples were larger and more likely to contain mucosa/villi for histologic diagnosis. CLINICAL SIGNIFICANCE: The SLB method can be adapted for laparoscopic surgery to obtain both small and large intestinal biopsies. Further investigation is needed before clinical use.

An Evaluation of Three Diet Conversion Methods in Psittacine Birds Converting from Seed-Based Diets to Pelleted Diets.

The nutritional deficiencies of popular seed-based diets for captive psittacine birds have been linked to physical and psychological disease conditions in these species. However, bird owners often reject transitioning their pets to nutritionally complete pelleted diets because of concerns over the difficulty of diet conversion. To assess dietary conversion of psittacine birds from seed-based to pelleted diets, avian veterinarians presented 3 diet conversion methods to owners with birds of varying ages and species. The owners implemented their chosen conversion method at home and then received a survey when they successfully completed diet conversion or abandoned their attempt. "Birdies Choice" was a reward-based method in which birds were offered 3 different pelleted diets on a tabletop. If there was a positive interaction and the bird ate one or more of the diets, the bird was rewarded. The preferred pellet was then gradually transitioned into their food dishes. In the "Slow and Steady" method, pellets were alternated with familiar food at varying intervals to increase the birds' exposure to the pellets. The "Tough Love" method maximized exposure to new pellets by introducing a small portion of familiar food for a limited time, along with multiple dishes of new pellets. Survey results showed 96% of birds converted regardless of method, with 57.5% converting within the first 7 days. When conversion times were evaluated by life stage (juvenile, adult, and geriatric), sex, or bird family (Psittacidae, Cacatuidae, and Psittaculidae), differences noted between groups were not significant. The only variable significantly affecting time to conversion was method used, with Tough Love converting birds faster than the other methods. Ultimately, all 3 methods of dietary conversion were successful with the majority of birds during the first month of implementation. These results provide evidence-based information to owners and veterinarians to facilitate pellet conversion attempts for psittacine birds.

Administration of Altrenogest to Maintain Pregnancy in Asian Elephants (Elephas maximus).

Progesterone and progesterone derivatives are key hormones in pregnancy maintenance in mammalian species. Cessation of pregnancy, including birth or miscarriage, is certain if levels of these hormones drop below a given species-specific requirement necessary to maintain pregnancy. The synthetic progestin, altrenogest, is FDA-approved in the United States for suppression of estrus or synchronization and is administered extra-label to multiple species to maintain pregnancies in cases of luteal deficiency or otherwise abnormally low progesterone levels. Three pregnant Asian elephants received altrenogest from 41 to 131 days during the final trimester of pregnancy, with parturition occurring from 15 to 31 days after altrenogest administration stopped. A single dose of 0.2 mg/kg altrenogest administered to two nonpregnant Asian elephants provided pilot pharmacokinetic data. Serum samples from two of the three clinical cases and the two pilot study elephants were analyzed using Ultra Performance Liquid chromatography coupled to a triple quadruple mass spectrometer (UPLC-MS). Small sample numbers limited analysis; however, the following were determined: AUC∞ of 635.4 ± 73.8 ng*h/mL, Cmax of 30.2 ± 14.4 ng/mL at a Tmax of 4 ± 2.8 h, terminal T1/2 of 47.5 ± 3.0 h, MRT of 36.0 + 3.4 h and Vd/F of 1243.8 + 275.0 L/kg. These data and the three described cases serve as an indication that altrenogest can be administered to Asian elephants as an exogenous progestin to support pregnancy in elephant pregnancies with low endogenous progestin levels.

MYONECROSIS AND DEATH DUE TO PRESUMED MICROCYSTIN TOXICOSIS IN AMERICAN WHITE PELICANS (PELECANUS ERYTHRORHYNCOS).

Over a period of 5 mo, seven out of eight American white pelicans (Pelecanus erythrorhynchos) housed on a spring-fed pond at a zoo died or were euthanized. Clinical signs included inability to stand, anorexia, and weight loss. Clinicopathologic findings included heterophilic leukocytosis and elevated creatine kinase and aspartate aminotransferase. Histopathologic findings on all pelicans demonstrated severe, chronic, diffuse rhabdomyofiber degeneration and necrosis, making vitamin E deficiency a differential diagnosis despite routine supplementation. Based on tissue and pond water assays for the cyanobacterial toxin, microcystin, toxicosis is suspected as the inciting cause of death in these cases. We hypothesize that vitamin E exhaustion and resultant rhabdomyodegeneration and cardiomyopathy were sequelae to this toxicosis.

Meta-Analysis of the Effects of Adhesion Barriers on Adhesion Formation in the Horse.

OBJECTIVE: To determine the efficacy of adhesion barriers in horses using quantitative statistical analysis. STUDY DESIGN: Meta-analytical review. METHODS: A search using PubMed/MEDLINE and Google Scholar was performed, followed by secondary searches of veterinary trade journals, bibliographies of relevant articles, manufacturer websites, and technical reference guides. Randomized experimental trials in healthy horses were considered that included both a treatment and control group. The endpoint required was euthanasia or laparoscopy to identify adhesion formation. A meta-analysis was performed using a random effects model, with the effect size calculated as an odds ratio (OR) with 95% confidence intervals (CI). Statistical significance was set at P<.05. RESULTS: Out of 354 peer reviewed publications that met the search criteria, a total of 9 relevant studies were identified and investigated the use of sodium carboxymethylcellulose (CMC) solutions, sodium hyaluronate/carboxymethylcellulose (HA/CMC) membranes, hyaluronate (HA), and fucoidan solutions. The odds of adhesions in horses treated with an adhesion barrier were significantly lower than untreated controls (OR=0.102; 95% CI [0.041, 0.254]; P<.001). When analyzed as subsets for each type of barrier, horses treated with HA/CMC membranes and CMC solutions had significant OR for fewer adhesions (OR=0.061; 95% CI [0.013, 0.292]; OR=0.119; 95% CI [0.034, 0.415], respectively; P<.001). CONCLUSION: The meta-analysis demonstrated adhesion barriers provide a positive effect on the odds of adhesion formation. These results are tempered by the limitations of the study, including the small sample size and a bias towards publication of studies with only positive findings.

Neocortical neuronal morphology in the newborn giraffe (Giraffa camelopardalis tippelskirchi) and African elephant (Loxodonta africana).

Although neocortical neuronal morphology has been documented in the adult giraffe (Giraffa camelopardalis tippelskirchi) and African elephant (Loxodonta africana), no research has explored the cortical architecture in newborns of these species. To this end, the current study examined the morphology of neurons from several cortical areas in the newborn giraffe and elephant. After cortical neurons were stained with a modified Golgi technique (N = 153), dendritic branching and spine distributions were analyzed by using computer-assisted morphometry. The results showed that newborn elephant neurons were considerably larger in terms of all dendritic and spine measures than newborn giraffe neurons. Qualitatively, neurons in the newborns appeared morphologically comparable to those in their adult counterparts. Neurons in the newborn elephant differed considerably from those observed in other placental mammals, including the giraffe, particularly with regard to the morphology of spiny projection neurons. Projection neurons were observed in both species, with a much larger variety in the elephant (e.g., flattened pyramidal, nonpyramidal multipolar, and inverted pyramidal neurons). Although local circuit neurons (i.e., interneurons, neurogliaform, Cajal-Retzius neurons) resembled those observed in other eutherian mammals, these were usually spiny, which contrasts with their adult, aspiny equivalents. Newborn projection neurons were smaller than the adult equivalents in both species, but newborn interneurons were approximately the same size as their adult counterparts. Cortical neuromorphology in the newborn giraffe is thus generally consistent with what has been observed in other cetartiodactyls, whereas newborn and adult elephant morphology appears to deviate substantially from what is commonly observed in other placental mammals.

Formalizing the definition of meta-analysis in Molecular Ecology.

Meta-analysis, the statistical synthesis of pertinent literature to develop evidence-based conclusions, is relatively new to the field of molecular ecology, with the first meta-analysis published in the journal Molecular Ecology in 2003 (Slate & Phua 2003). The goal of this article is to formalize the definition of meta-analysis for the authors, editors, reviewers and readers of Molecular Ecology by completing a review of the meta-analyses previously published in this journal. We also provide a brief overview of the many components required for meta-analysis with a more specific discussion of the issues related to the field of molecular ecology, including the use and statistical considerations of Wright's FST and its related analogues as effect sizes in meta-analysis. We performed a literature review to identify articles published as 'meta-analyses' in Molecular Ecology, which were then evaluated by at least two reviewers. We specifically targeted Molecular Ecology publications because as a flagship journal in this field, meta-analyses published in Molecular Ecology have the potential to set the standard for meta-analyses in other journals. We found that while many of these reviewed articles were strong meta-analyses, others failed to follow standard meta-analytical techniques. One of these unsatisfactory meta-analyses was in fact a secondary analysis. Other studies attempted meta-analyses but lacked the fundamental statistics that are considered necessary for an effective and powerful meta-analysis. By drawing attention to the inconsistency of studies labelled as meta-analyses, we emphasize the importance of understanding the components of traditional meta-analyses to fully embrace the strengths of quantitative data synthesis in the field of molecular ecology.

Bovine Viral Diarrhea Virus in Zoos: A Perspective from the Veterinary Team.

The many different species in close proximity make zoological collections a unique environment for disease transmission. Bovine Viral Diarrhea Virus (BVDV) is of special concern with zoos due to the numerous exotic ruminant species that this virus can infect. BVDV occurs as both a non-cytopathic and a cytopathic strain both of which are capable of infecting exotic ruminants. The cytopathic strain causes mucosal disease (MD) and death. Infection with the non-cytopathic strain may produce persistently infected (PI) animals. PI individuals may show vague clinical signs, including abortion. Management of BVDV in zoos should focus on identification of PI individuals and prevention of infection of other animals of the collection. Variability makes serological testing as the sole method of screening for BVDV infection undesirable in exotic ruminants. Combination testing provides a definitive answer, especially in sensitive wildlife. Use of a combination of antigen-capture ELISA (ACE) with haired skin, Real Time-PCR (RT-PCR) on whole blood, and antibody detection via serum neutralization has the greatest potential to identify PI animals. An animal that is positive on both ACE and RT-PCR, but is negative on serology should be considered highly suspicious of being a PI, and should be isolated and undergo repeat testing 4-6 weeks later to confirm positive status. This testing methodology also allows screening of pregnant and newborn animals. Isolation or culling may need to be considered in animals determined to be positive via combination testing. These decisions should only be made after careful consideration and evaluation, especially with endangered species.

Angiostrongylus cantonensis infection in captive Geoffroy's tamarins (Saguinus geoffroyi).

CASE DESCRIPTION: 3 Geoffroy's tamarins (Saguinus geoffroyi) in a zoo in east central Alabama developed neurologic signs shortly after a tamarin kept in the same enclosure was found dead. CLINICAL FINDINGS: Neurologic abnormalities varied among animals and were progressive. One female tamarin with a head tilt, nystagmus, mild ataxia, and paresis of a thoracic limb had gram-positive cocci present in an ear canal with otitis media and interna suspected. Another female with mild ataxia attributed to previous tail amputation developed seizures, and a male tamarin with tail tip trauma also developed ataxia. TREATMENT AND OUTCOME: The tamarin with suspected otitis received cephalexin and prednisolone, but neurologic signs worsened, and the patient died. Preliminary examination of necropsy samples revealed severe meningoencephalitis in both deceased tamarins. Prednisolone and phenobarbital treatment was initiated for the tamarin with seizures, but rapid neurologic deterioration led to euthanasia. Further histologic examination of the 3 deceased tamarins revealed meningitis and acute perivascular hemorrhage in the meninges. Parasites morphologically consistent with Angiostrongylus (Parastrongylus) cantonensis were present in the lungs of 1 animal and in the meninges of 2. The surviving tamarin received cephalexin for tail tip trauma and prednisolone and albendazole for presumed meningoencephalitis and parasitic infection but had permanent neurologic deficits. CLINICAL RELEVANCE: To our knowledge, these represent the first cases of A cantonensis infection in Geoffroy's tamarins and the first report of its presence in the United States not associated with a major shipping port. The presence of a mature worm in the lungs of 1 tamarin suggested completion of the parasite life cycle, previously reported only in rats.

Recognition of an important water quality issue at zoos: prevalence and potential threat of toxic cyanobacteria.

Zoo animals may be particularly vulnerable to water sources contaminated with cyanobacterial toxins given their nonvoluntary close association with this resource. However, the prevalence and potential threat of toxic cyanobacteria in this setting are unknown. Several otherwise unexplained yellow-bellied slider (Trachemys scripta scripta) deaths were documented in a zoo moat with recurring blooms of toxic Microcystis aeruginosa. Furthermore, an extremely high and potentially lethal concentration of the hepatotoxin microcystin (166 ng/g) was found in the liver of a necropsied turtle that died in this moat. A subsequent monthly survey of water quality revealed detectable concentrations of microcystin in all moats (0.0001 to 7.5 microg/L), with moats higher than 1 microg/L being significantly higher than the threshold for safe drinking water recommended by the World Health Organization. These results demonstrate that cyanobacterial blooms are an important water quality issue in zoos, and future research is necessary to identify potential associations among water quality, zoo animal health, and moat management strategies.

Nonbacterial thrombotic endocarditis in a ferret (Mustela putorius furo).

A 4-yr-old male ferret (Mustela putorius furo) was presented with a 3-day history of pelvic limb ataxia and weakness. A cellulitis associated with a deep bite wound was identified and initially treated with antibiotics and anti-inflammatory medication. Two weeks later, a grade IV/VI cardiac murmur was identified on physical examination. Echocardiographic examination revealed irregular thickening of the aortic valve leaflets, with normal chamber dimensions and normal systolic function. The ferret's physical condition rapidly deteriorated and it was subsequently euthanatized. Myxomatous degeneration of the aortic valve leaflets, with ulceration and vegetative lesions, and multiorgan infarctions were identified during necropsy. A bacterial etiologic agent was not identified from blood culture or histopathology. Lesions present were consistent with nonbacterial thrombotic endocarditis, a novel condition in the ferret.

Heart failure caused by toxoplasmosis in a fennec fox (Fennecus zerda).

A male fennec fox (Fennecus zerda) kit was examined for lethargy, inappetence, and weight loss. Clinical findings included respiratory distress, a gallop rhythm, and retinochoroiditis. Radiography indicated pleural effusion and cardiomegaly. Echocardiographic findings included left ventricular dilatation, low left ventricular ejection fraction, and atrioventricular valvular regurgitation. Necropsy findings were compatible with a diagnosis of congestive heart failure caused by myocarditis. Histopathology showed a disseminated infection with Toxoplasma gondii causing myocarditis, skeletal polymyositis, gastrointestinal myositis, and panuveitis. Toxoplasma-induced myocarditis should be included in the differential diagnosis of heart failure and retinochoroiditis in the fennec fox.