SINGLE-DOSE, MULTIPLE-DOSE, AND THERAPEUTIC DRUG MONITORING PHARMACOKINETICS OF FIROCOXIB IN ASIAN ELEPHANTS (ELEPHAS MAXIMUS).

Firocoxib is a COX-2-selective nonsteroidal anti-inflammatory drug (NSAID) with limited effects on COX-1, which means it likely has fewer side effects than typically associated with other NSAIDs. This study determined possible doses of firocoxib based on single- and multidose pharmacokinetic trials conducted in 10 Asian elephants (Elephas maximus). Initially, two single oral dose trials (0.01 and 0.1 mg/kg) of a commercially available tablet (n = 6) and paste (n = 4) formulation were used to determine a preferred dose. The 0.1 mg/kg dose was further evaluated via IV single dose (n = 3) and oral multidose trials (tablets n = 6; paste n = 4). Serum peak and trough firocoxib concentrations were also evaluated in Asian elephants (n = 4) that had been being treated for a minimum of 90 consecutive days. Key pharmacokinetic parameters for the 0.1 mg/kg single-dose trials included mean peak serum concentrations of 49 ± 3.3 ng/ml for tablets and 62 ± 14.8 ng/ml for paste, area under the curve (AUC) of 1,332 ± 878 h*mg/ml for tablets and 1,455 ± 634 h*mg/ml for paste, and half-life (T1/2) of 34.3 ± 30.3 h for tablets and 19.9 ± 12.8 h for paste. After 8 d of dosing at 0.1 mg/kg every 24 h, pharmacokinetic parameters stabilized to an AUC of 6,341 ± 3,003 h*mg/ml for tablets and 5,613 ± 2,262 for paste, and T1/2 of 84.4 ± 32.2 h for tablets and 62.9 ± 2.3 h for paste. Serum COX inhibition was evaluated in vitro and ex vivo in untreated elephant plasma, where firocoxib demonstrated preferential inhibition of COX-2. No adverse effects from firocoxib administration were identified in this study. Results suggest administering firocoxib to Asian elephants at a dose of 0.1 mg/kg orally, using either tablet or paste formulations, every 24 h.

SERUM DISPOSITION OF A SINGLE DOSE OF ORALLY ADMINISTERED FIROCOXIB IN AFRICAN ELEPHANTS (LOXODONTA AFRICANA).

The time course of serum firocoxib concentrations was described after administration of two single oral doses (0.01 and 0.1 mg/kg) of commercially available firocoxib tablet (n = 4) and paste (n = 2) formulations to six healthy adult female African (Loxodonta africana) elephants. Firocoxib was quantitated by high-performance liquid chromatography. Firocoxib serum concentrations were below detectable levels after administration of 0.01 mg/kg of both formulations. A dose of 0.1 mg/kg (n = 4) of the tablet formulation had the following mean ± SD of pharmacokinetic parameters: area under the curve (AUC) 1,588 ± 362 h × ng/ml, maximum plasma concentration (Cmax) 31 ± 6.6 ng/ml at 6.4 ± 1.8 h, and disappearance half-life (T1/2) 66 ± 59 h, Elephant compliance to oral administration of the paste formulation was challenging, with only two elephants accepting administration of the paste at 0.1 mg/kg. Pharmacokinetic parameters determined included AUC of 814 h × ng/ml, Cmax of 44 ng/ml at Tmax of 7.0 h, and T1/2 of 36.4 h. Based on mean AUC, the relative bioavailability of paste compared to tablet formulations was 50%. Limitations of this study were the small number of participants and elephant compliance with the paste formulation. This study supports an oral dose of 0.1 mg/kg every 24 h. Multidose and IV trials are indicated to confirm firocoxib dosing requirements for African elephants.

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.

Argentine Black and White Tegu (Salvator merianae) can survive the winter under semi-natural conditions well beyond their current invasive range.

The Argentine Black and White Tegu (Salvator merianae, formerly Tupinambis merianae) is a large lizard from South America. Now established and invasive in southern Florida, and it poses threats to populations of many native species. Models suggest much of the southern United States may contain suitable temperature regimes for this species, yet there is considerable uncertainty regarding either the potential for range expansion northward out of tropical and subtropical zones or the potential for the species establishing elsewhere following additional independent introductions. We evaluated survival, body temperature, duration and timing of winter dormancy, and health of wild-caught tegus from southern Florida held in semi-natural enclosures for over a year in Auburn, Alabama (> 900 km northwest of capture location). Nine of twelve lizards emerged from winter dormancy and seven survived the greater-than-one-year duration of the study. Average length of dormancy (176 d) was greater than that reported in the native range or for invasive populations in southern Florida and females remained dormant longer than males. Tegus grew rapidly throughout the study and the presence of sperm in the testes of males and previtellogenic or early vitellogenic follicles in female ovaries at the end of our study suggest the animals would have been capable of reproduction the following spring. The survival and overall health of the majority of adult tegus in our study suggests weather and climate patterns are unlikely to prevent survival following introduction in many areas of the United States far from their current invasive range.

PHARMACOKINETICS OF ORALLY ADMINISTERED FLUNIXIN MEGLUMINE IN AFRICAN (LOXODONTA AFRICANA) AND ASIAN (ELEPHAS MAXIMUS) ELEPHANTS.

Flunixin meglumine is the most commonly used nonsteroidal anti-inflammatory drug used to treat elephants; however, no pharmacokinetic study for flunixin has yet been conducted in these species, and dosages used range widely. Pharmacokinetic parameters of flunixin were determined in African (Loxodonta africana) and Asian (Elephas maximus) elephants after single-dose oral administration of 0.8 and 1.5 mg/kg flunixin paste in each species. Elephant compliance to oral administration of banamine was occasionally challenging, especially among older, female African elephants. After administration of 0.8 mg/kg flunixin, mean serum concentrations peaked in approximately 1.3 hr at 2.1 ± 0.8 µg/ml for Asian (n = 8) and 2.8 hr at 2.5 ± 0.7 µg/ml for African (n = 8) elephants. Dosages of 1.5 mg/kg flunixin resulted in mean serum concentration peaks of 7.2 ± 1.5 µg/ml in Asian elephants (n = 7) and 4.4 ± 0.7 µg/ml in African elephants (n = 6). However, multiple-dose trials using 1.1 mg/kg flunixin resulted in peak serum concentrations that were again less in Asian than African elephants (2.7 µg/ml versus 4.4 µg/ml, respectively). Asian elephants consistently had lower time to maximal concentration, greater area under the curve, and longer mean residence times compared with African elephants. In other species, flunixin is excreted unchanged primarily via hepatic routes with small amounts in the urine. Asian elephants may engage in some level of enterohepatic recycling of flunixin, as was previously reported for phenylbutazone. This study supports that different oral dosing regimens should be used for Asian (1.0 mg/kg SID) and African (1.2 mg/kg SID) elephants, and oral administration techniques used should ensure complete dosage delivery.

Meta-analysis of the Effect of Treatment Strategies for Nephrosplenic Entrapment of the Large Colon.

A variety of treatment strategies for nephrosplenic entrapment of the large colon are reported, with conflicting evidence in the published literature as to the preferred treatment option. The aim of this study is to provide a systematic meta-analytical assessment of the efficacy of different treatment strategies in horses with confirmed or suspected nephrosplenic entrapment. This study involves meta-analysis including nonrandomized studies. A comprehensive literature search was performed from January 1970 to January 2017. Inclusion criteria were retrospective studies involving horses with confirmed and suspected nephrosplenic entrapment. A meta-analysis was performed using a random effects model, with the effect size calculated as an odds ratio (OR) with 95% confidence intervals. Statistical significance was P < .05. Out of 84 peer reviewed publications that met the search criteria, 19 relevant studies were identified. Using an OR as the effect size, the meta-analysis noted that the choice of medical or surgical therapy had no statistically significant effect on survival (P = .134). Patients treated via the rolling technique were no more likely to resolve with medical management than those treated via jogging (P = .187). Patients treated with phenylephrine were no more likely to exhibit medical resolution than patients that did not receive phenylephrine, either when all medical treatment methods were considered (P = .290), or when rolling under general anesthesia was used (P = .331). Treatment strategy, including medical versus surgical therapy, does not affect the likelihood of resolution of nephrosplenic entrapment. However, the lack of randomized trials means the results should be treated with caution and case selection remains important..

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 lidocaine on postoperative reflux in the horse.

OBJECTIVE: To determine the efficacy of lidocaine at reducing incidence of postoperative reflux (POR) in horses by using quantitative statistical analysis. STUDY DESIGN: Systematic meta-analytical review. SAMPLE POPULATION: Studies on horses undergoing gastrointestinal surgery for small intestinal lesions, identified by systematic search between 2001 and 2017. METHODS: A search with PubMed/MEDLINE, Web of Science, and Google Scholar was performed, followed by secondary searches of veterinary trade journals and bibliographies of relevant articles. The primary outcome measure for this study was the effect of lidocaine therapy on the odds of POR. Subgroup analysis assessed included the timing of lidocaine therapy, incidence of mortality, and incidence of repeat celiotomy. A meta-analysis was performed with 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: Among 1933 peer reviewed publications that met the initial search criteria, 12 relevant studies were available for analysis. Lidocaine was associated with an increased incidence of diagnosis of POR (OR 6.3, 95% CI [1.4, 27.0], P = .01). Horses treated with lidocaine were more likely to survive to discharge (OR 6.8, 95% CI [3.9, 11.7], P < .01). CONCLUSION: Lidocaine was associated with an increased survival rate in horses undergoing exploratory celiotomy for small intestinal disease according to this meta-analysis of the recent literature. CLINICAL SIGNIFICANCE: This body of published evidence provides support to administer lidocaine in horses to improve survival rather than preventing POR.

RECURRENT EAR MITE (OTODECTES CYNOTIS) INFESTATION IN THREE RELATED GROUPS OF PATAGONIAN CAVIES (DOLICHOTIS PATAGONUM).

: Two of three groups of Patagonian cavies ( Dolichotis patagonum ) contracted Otodectes cynotis infestations after exposure to mite-infested feral cats. Otodectes cynotis infestations were initially identified in 9 of 10 cavies in group 1. Multiple feral cats with O. cynotis infestations were observed in the vicinity of the Patagonian cavies and were subsequently removed. The Patagonian cavies were initially treated with ivermectin (0.4 mg/kg s.q.) every 2 wk, but ivermectin was discontinued after the third treatment due to injury to one of the Patagonian cavies during capture. Sixteen months after initial treatment, clinical signs of scratching the pinnae, hemorrhagic lesions on the ear margins, head shaking, and O. cynotis mites in the auricular canal were again noted in all Patagonian cavies in group 1. Repeated administration of ivermectin (0.4 mg/kg s.q. every 2 wk for three treatments) failed to eliminate the mites in two of the Patagonian cavies. Selamectin administered (20 mg/kg, topically between the shoulder blades) to all Patagonian cavies eliminated the mite infestation after a single application. The Patagonian cavies remained O. cynotis mite free for 2 yr, until males (group 2) and females (group 3) were separated for population control. Three months after separation, 8 of the 12 females in group 3 again were infestated with O. cynotis mites. Feral cats with O. cynotis infestations were again noted in the vicinity of group 3. A single dose of selamectin applied topically eliminated all mites in all treated Patagonian cavies. Group 2 was not exposed to feral cats and remained mite free.

Enhancing captive Indian rhinoceros genetics via artificial insemination of cryopreserved sperm.

The objective of this study was to design an artificial insemination (AI) protocol using cryopreserved spermatozoa to obtain pregnancies in captive Indian rhinoceroses (Rhinoceros unicornis). Four methods developed varied by timing and approach, as follows; Method 1: females (n=2) were inseminated pre- and post-ovulation under general anesthesia, Method 2: females (n=2) were inseminated pre-ovulation without anesthetic via endoscopy, Method 3: females (n=1) were inseminated pre-ovulation without anesthetic via manual insertion of an insemination catheter, Method 4: females (n=2) were inseminated same as Method 3 with the addition of standing sedation. Semen deposition site varied as a result of changes in AI technology and experience. All females conceived following intrauterine AI using three methods. Four pregnancies (n=3 females) produced via Method 3 and 4 resulted in term births (n=2 male calves, n=2 female calves) at 481.8±12.8days post-AI. Unfortunately, two early pregnancy losses were documented in a fourth female conceiving via Method 2. Pregnancy rates were 0%, 22%, 17%, and 50% for Method 1-4, respectively. Method 3 and 4 rates improved to 29% and 67%, respectively when accounting for AI's conducted only on ovulatory estrous cycles. Spermatozoa (n=5 males) were cryopreserved 0.3-9.3 y prior to successful AI procedures. The lowest dose of frozen-thawed sperm resulting in conception was 500×10(6) motile sperm. Mean time from AI to ovulation in conceptive and non-conceptive cycles was 26±11.8h and 66±80.7h, respectively.

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.

RESULTS OF THE MEGAVERTEBRATE ANALGESIA SURVEY: ELEPHANTS AND RHINO.

An online survey utilizing Survey Monkey linked through the American Association of Zoo Veterinarians listserve examined current practices in megavertebrate analgesia. Data collected included drugs administered, dosing regimens, ease of administration, efficacy, and adverse events. Fifty-nine facilities (38 housing elephants, 33 housing rhinoceroses) responded. All facilities administered nonsteroidal anti-inflammatory drugs (NSAIDs), with phenylbutazone (0.25-10 mg/kg) and flunixin meglumine (0.2-4 mg/kg) being most common. Efficacy was reported as "good" to "excellent" for these medications. Opioids were administered to elephants (11 of 38) and rhinoceroses (7 of 33), with tramadol (0.5-3.0 mg/kg) and butorphanol (0.05-1.0 mg/kg) being most common. Tramadol efficacy scores were highly variable in both elephants and rhinoceroses. While drug choices were similar among institutions, substantial variability in dosing regimens and reported efficacy between and within facilities indicates the need for pharmacokinetic studies and standardized methods of analyzing response to treatment to establish dosing regimens and clinical trials to establish efficacy and safety.

RESULTS OF THE MEGAVEREBRATE ANALGESIA SURVEY: GIRAFFE AND HIPPOPOTAMUS.

Results of an online survey posted on the American Association of Zoo Veterinarians listserv examined the patterns of analgesic medication and pain management modalities used for captive giraffe and hippopotami. Compiled data included signalment, drugs administered, dosing regimens, subjective efficacy scores, ease of administration, and adverse events. Nineteen institutions exhibiting hippopotami ( Hippopotamus amphibious ) and pygmy hippopotami (Choeropsis liberiensis) and 45 exhibiting giraffe ( Giraffa camelopardalis spp.) responded. Phenylbutazone was the most-commonly administered nonsteroidal anti-inflammatory drug (NSAID), followed by flunixin meglumine, but doses varied widely. Eight institutions reported adverse events from NSAID administration. Tramadol was the most-commonly administered opioid followed by butorphanol. Only one adverse event was reported for opioids. Twenty-three of 45 institutions exhibiting giraffe utilized alternative analgesia methods including gabapentin, glucosamine-chondroitin, local anesthetics, and low level laser therapy. Six of 19 institutions exhibiting hippopotami administered omega 3-6 fatty acids, gabapentin, glucosamine-chondroitin, and α-2 adrenergics to provide analgesia. While all reporting zoological institutions administered similar drugs, there was substantial variation and diversity in both dosing regimens and frequencies, indicating the need for both preclinical and clinical studies supporting dosing regimens.

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.

DISPOSITION OF CEFTIOFUR AND ITS ACTIVE METABOLITES IN FALLOW DEER (DAMA DAMA) FOLLOWING SINGLE-DOSE INTRAVENOUS AND INTRAMUSCULAR ADMINISTRATION.

Septicemia and foot infections associated with Fusobacterium necrophorum , Pasturella multocida, and Streptococcus suis in captive fallow deer (Dama dama) are reasonably treated with ceftiofur hydrochloride. This study describes the disposition of ceftiofur after single-dose intravenous and intramuscular administration of 3.65±0.1678 mg/kg in six female adult fallow deer using a nonrandomized crossover design and a 7-day washout period. Serial blood samples were collected for 12 hr postdrug administration. Ceftiofur bioactivity, including its active metabolite desfuroylceftiofur, was quantitated in serum using a microbiologic assay. After i.v. administration, the extrapolated serum drug concentration reported as median (range) was 52.83 (43.32-57.49) µg/ml and elimination half-life was 178.36 (19.75-217.22) min. The volume of distribution at steady-state was 0.171 (0.101-0.229) L/kg and serum clearance was 0.97 (0.48-4.3) ml/min per kg. After i.m. administration, median peak plasma concentration (Cmax) was 14.37 (9.00-32.00) µg/ml at 54.5 (11.00-95.00) min. The median elimination half-life and mean residence time were 128.32 (38.03-242.40) and 203.65 (62.48-347.15) min, respectively. The median absorption time after i.m. administration was 14.77 (-57.74 to 94.79) min. Bioavailability of ceftiofur following i.m. administration was 78.00 (58.00-137.00) percent. Based on this study, a mean i.m. dose of ceftiofur of 3.65±0.1678 mg/kg every 12 hr is recommended for maintaining serum concentrations above MIC90 levels for infections associated with F. necrophorum, P. multocida, and S. suis, in addition to other susceptible infectious bacteria.

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.