Pharmacokinetics of ketorolac in wild Eastern box turtles (Terrapene carolina carolina) after single intramuscular administration

Ketorolac is a nonsteroidal anti‐inflammatory drug that possesses potent analgesic activity comparable to morphine. The opioid shortage in the United States has led to an unreliable supply of opioids for use in rehabilitation facilities, thus underscoring the need for research on the safe and effective use of nonopioid alternatives. The goal of this study was to determine the pharmacokinetics of ketorolac after a single 0.25 mg/kg intramuscular injection administered to injured Eastern box turtles (Terrapene carolina carolina). A sparse blood sampling protocol was used to collect samples from 32 wild turtles that presented to the Turtle Rescue Team at North Carolina State University for traumatic injuries. Blood was collected from 0 to 24 hr after injection and analyzed via high‐pressure liquid chromatography (HPLC). A nonlinear mixed‐effects (NLME) model was fitted to the data to obtain typical values for population parameters. Using this approach, we identified a long half‐life (T_1/2) of 9.78 hr and a volume of distribution (V_ss) of 0.26 L/kg. We have concluded that this long T_1/2 for a dose of 0.25 mg/kg ketorolac‐injected IM provides plasma levels above a previously published target level for 24‐hour analgesia to allow for once daily dosing.     

Quantifying visual acuity of Terrapene carolina triunguis utilizing optokinetic response

Objective

Quantify visual acuity of a semi-aquatic turtle species, Terrapene carolina triunguis (three-toed box turtles), utilizing optokinetic response/reflex/nystagmus.

Methods

Ten turtles were placed on a custom platform and an image of white and black gratings of varying sized widths was projected onto a white screen in front of the turtles. Optokinetic response (OKR) was observed through a web camera as well as physically by an observer. The grating sizes were decreased until OKR could not be elicited. The size of grating was recorded and was used to calculate visual acuity.

Results

The average visual acuity was 0.26 cycle per degree (cpd) with the highest recorded value being 0.43 cpd and lowest being 0.15 cpd. Neither sex nor weight were significantly associated with visual acuity (p = .24 and .98, respectively).

Conclusions

Visual acuity of these semi-aquatic turtles was much lower than previously reported visual acuities of aquatic turtles. This could be due to differences in refractive indices between water and air, behavioral adaptations for the different species and/or method of obtaining visual acuity.     

RADIOGRAPHIC ANATOMY AND BARIUM SULFATE CONTRAST TRANSIT TIME OF THE GASTROINTESTINAL TRACT OF BEARDED DRAGONS (Pogona vitticeps)

The positive contrast gastrointestinal study is a common non‐invasive diagnostic technique that does not require anesthesia and enables good visualization of the digestive tract. Radiographic anatomy and reference intervals for gastrointestinal contrast transit time in inland bearded dragons (Pogona vitticeps) were established using seven animals administered 15 ml/kg of a 35% w/v suspension of barium by esophageal gavage. Dorso‐ventral and lateral radiographic views were performed at 0, 15, 30 min, 1, 2, 4, 6, 8, 12 h, and then every 12 h up to 96 h after barium administration. Gastric emptying was complete at a median time of 10 h (range 4–24 h). Median jejunum and small intestinal emptying times were 1 h (range 30 min–2 h) and 29 h (range 24–48 h), respectively. Median transit time for cecum was 10 h (range 8–12 h). Median time for contrast to reach the colon was 31 h (range 12–72 h) after administration. Results were compared to those obtained in other reptilian species. This technique appeared safe in fasted bearded dragons and would be clinically applicable in other lizard species.     

Ranavirus-associated morbidity and mortality in a group of captive eastern box turtles (Terrapene carolina carolina).

Seven captive eastern box turtles (Terrapene carolina carolina) from a large collection of North American chelonians in North Carolina became acutely ill in the fall of 2002. Five of the turtles died. Clinical signs included cutaneous abscessation, oral ulceration or abscessation (or both), respiratory distress, anorexia, and lethargy. The predominant postmortem lesion was fibrinoid vasculitis of various organs, including skin, mucous membranes, lungs, and liver. No inclusion bodies were detected by histopathology or electron microscopy of formalin-fixed tissue. An iridovirus was isolated from tissues obtained postmortem from two of the box turtles that died. The virus was characterized by electron microscopy, polymerase chain reaction, and sequence analysis of a portion of the major capsid protein as a member of the genus Ranavirus.     

Ingesta passage and gastric emptying times in loggerhead sea turtles (Caretta caretta)

Ingesta passage times of soft flat foam dishes and gastric emptying time of barium-impregnated polyethylene spheres (BIPS) were measured in 22 and 8 loggerhead sea turtles (Caretta caretta), respectively. Transit time (T(1)) was considered as the time between ingestion and first elimination, and retention time (T(50)) and total transit time (T(85)) the expulsion time of 50% and 85% of the markers, respectively. The experiments were carried out at different times of the year and water temperature was recorded. A set of dorso-ventral radiographs was taken to locate the BIPS, and the gastrointestinal anatomy of 5 dead turtles was studied to help with interpretation of the radiographs. No significant correlation was observed between T(1), T(50), T(85) and minimum straight carapace length (SCLmin) or body mass and no statistical difference was found in ingesta passage transit times between juvenile (n = 6) and sub-adult turtles (n = 16). Mean passage times of the dishes (in days) were: T(1) = 9.05, T(50) = 12.00 and T(85) = 13.19. Gastric emptying time using BIPS was 24-48 h. The transit time (T(1)) for the BIPS was longer (13.25 +/- 4.86 days) than the foam markers (8.5 +/- 2.73 days) in 8 turtles studied simultaneously. Although the total transit time tended to be faster in turtles submitted to water temperatures between 20 degrees C and 23.6 degrees C no significant correlation was observed between T(1), T(50) and T(85) and the temperature.     

RADIOGRAPHIC ASSESSMENT OF GASTRIC EMPTYING AND GASTROINTESTINAL TRANSIT TIME IN HYBRID TILAPIA (OREOCHROMIS NILOTICUS×O. MOSSAMBICUS)

Hybrid tilapias (Oreochromis niloticus x O. mossambicus) were studied to determine gastric emptying and gastrointestinal transit time. The fish were divided into two groups. All fish were fasted for 12 h. The first experiment consisted of 11 fish fed with commercial food pellets and then administration of barium sulfate directly into the stomach using a blunt-end needle. Fish were then radiographed at different time intervals. The second experiment consisted of eight fish, which were given only barium sulfate after 12 h of fasting. In the first experiment, the stomach emptied completely, ranging from 4 to 15h postcontrast medium administration, whereas the gastrointestinal transit time ranged between 10 and 26 h. As for the second experiment, the contrast medium was still retained in the stomach in 50% of the fish after 24 h. The study did not proceed beyond 24 h as fish were considered stressed after this period of time. Thus, no data for the gastrointestinal transit time was obtained.     

GASTROINTESTINAL STUDIES IN THE GREEN IGUANA: TECHNIQUE AND REFERENCE VALUES

Five healthy green iguana (Iguana iguana) were used to determine appropriate technique and normal transit times for gastrointestinal contrast studies and to describe normal radiographic anatomy. The animals were maintained at 27-29 degrees C. There was rapid transit through a U shaped stomach, with a median gastric emptying time of 8 h, and median small intestinal transit and small intestine emptying times of 4 h and 16 h respectively. Median large colon transit and emptying times were 15 h and 66 h. Maintaining the iguana at a reduced ambient temperature increased all of these times. The vaso-vagal response or mechanical methods were adequate for restraint. A 25 ml/kg dose of a 25% w/v suspension of barium administered by stomach tube gave the best results. Lateral and ventrodorsal projections of the abdomen should be made immediately following the administration of the barium and at 1-hour intervals for the first 6 h and at 12-hour intervals thereafter until barium can be identified in the distal descending small colon.     

Clostridium perfringens epsilon toxin inhibits the gastrointestinal transit in mice

Epsilon toxin produced by Clostridium perfringens type B and D is a potent toxin that is responsible for a highly fatal enterotoxemia in sheep and goats. In vitro, epsilon toxin produces contraction of the rat ileum as the result of an indirect action, presumably mediated through the autonomic nervous system. To examine the impact of epsilon toxin in the intestinal transit, gastric emptying (GE) and gastrointestinal transit (GIT) were evaluated after intravenous and oral administration of epsilon toxin in mice. Orally administered epsilon toxin produced a delay on the GIT. Inhibition of the small intestinal transit was observed as early as 1 h after the toxin was administered orally but the effects were not observed after 1 week. Epsilon toxin also produced an inhibition in GE and a delay on the GIT when relatively high toxin concentrations were given intravenously. These results indicate that epsilon toxin administered orally or intravenously to mice transitorily inhibits the GIT. The delay in the GIT induced by epsilon toxin could be relevant in the pathogenesis of C. perfringens type B and D enterotoxemia.     

Comparative Efficacy of the Prokinetic Effects of Cisapride and Tegaserod in Equines

The aim of this study was to compare the effects of cisapride and tegaserod on intestinal smooth muscle activity in equines. Efficacy was evaluated through measurement of gastrointestinal transit time, bowel movements per day, stool weight, and bowel sounds. Drug safety was evaluated via heart rate, respiratory rate, and rectal temperature. Records were obtained throughout three periods: a control phase without treatment, a period of cisapride administration at a dose of 0.22 mg/kg, and a period of tegaserod treatment at a dose of 0.27 mg/kg. Gastrointestinal transit time, bowel movements per day, and stool weight were significantly improved on administration of both cisapride and tegaserod, as compared with the control phase. With tegaserod administration, gastrointestinal transit time accelerates more than to cisapride administration; however, no significant difference was seen in bowel movements per day and stool weight. In terms of heart rate, respiratory rate, and rectal temperature, no significant variations were seen between the three sample phases. Because of the above findings, tegaserod can be considered an effective stimulant of intestinal smooth muscle, accelerating gastrointestinal transit time in healthy horses and representing a potential therapeutic agent similar to cisapride.     

Pharmacokinetics of levamisole in the red‐eared slider turtles (Trachemys scripta elegans)

The pharmacokinetics and bioavailability of levamisole were determined in red‐eared slider turtles after single intravenous (IV), intramuscular (IM), and subcutaneous (SC) administration. Nine turtles received levamisole (10 mg/kg) by each route in a three‐way crossover design with a washout period of 30 days. Blood samples were collected at time 0 (pretreatment), and at 0.25, 0.5, 1, 1.5, 3, 6, 9, 12, 18, 24, 36, and 48 hr after drug administration. Plasma levamisole concentrations were determined by a high‐performance liquid chromatography assay. Data were analyzed by noncompartmental methods. The mean elimination half‐life was 5.00, 7.88, and 9.43 hr for IV, IM, and SC routes, respectively. The total clearance and volume of distribution at steady state for the IV route were 0.14 L hr^?1 kg^?1 and 0.81 L/kg, respectively. For the IM and SC routes, the peak plasma concentration was 9.63 and 10.51 μg/ml, respectively, with 0.5 hr of T_max. The bioavailability was 93.03 and 115.25% for the IM and SC routes, respectively. The IM and SC route of levamisole, which showed the high bioavailability and long t_1/2?z, can be recommended as an effective way for treating nematodes in turtles.     

EVALUATION OF THE GASTROINTESTINAL TRACT IN DOGS USING COMPUTED TOMOGRAPHY

Abdominal computed tomography (CT) studies of 19 dogs with no history or clinical signs of gastrointestinal disease, and two dogs with a histological diagnosis of gastrointestinal neoplasia were examined retrospectively. Gastrointestinal segments were evaluated subjectively for conspicuity, contrast enhancement, and wall layering after contrast medium administration. In dogs without gastrointestinal disease, there were 62.8% of gastrointestinal segments (serosa to serosa) and 77.7% of gastrointestinal walls (serosa to mucosa) visualized. Wall layering on postcontrast images was seen in 21.8% of gastrointestinal segments. There was significant association between gastrointestinal diameter and wall thickness. There was significant association between weight and gastrointestinal wall thickness in the following regions: gastric fundus, gastric body, gastric pylorus, gastric pyloric antrum, duodenal cranial flexure, jejunum and ascending colon, and between patient weight and gastrointestinal diameter in cranial duodenal flexure, descending duodenum, transverse duodenum, ascending duodenum, and jejunum. Measurements acquired from CT studies correlated well with previously published normal reference ranges for radiographic and ultrasonographic studies. Gastrointestinal neoplasia, diagnosed in two dogs, had a gastrointestinal wall thickness greater than the range of the dogs without gastrointestinal disease. Computed tomography offers identification of the gastrointestinal tract segments in dogs, allows for evaluation of gastrointestinal diameter and aids in investigation of gastrointestinal wall thickness.     

Evaluation of lidocaine for brachial plexus blockade in eastern box turtles (Terrapene carolina carolina)

ObjectiveTo evaluate latency and duration of a brachial plexus block technique in eastern box turtles performed with 2% lidocaine at three dose rates.Study designProspective, randomized, blinded crossover study.AnimalsAdult eastern box turtles, two for drug dose evaluation and a group of six (three male, three female) weighing 432 ± 40 g (mean ± standard deviation) for the main study.MethodsAnimals were randomly assigned to four brachial plexus blocks with lidocaine at 5, 10 and 20 mg kg^–1 or 0.9% saline (treatments LID5, LID10, LID20 and CON, respectively), separated by 1 week. Treatment side was randomized and blocks were performed unilaterally. Baseline observations of mentation, heart rate (HR), respiratory rate (f_R), skin temperature and limb response to manipulation or toe pinch were evaluated. Assessments were made every 10 minutes until 1 hour of normal sensory and motor function to the treated thoracic limb, or for a total of 2 hours if no block was evident.ResultsMotor and sensory blockade was achieved in treatments LID10 and LID20 in one turtle, with a latency of 10 minutes and duration of 50 minutes for both doses. Raising of the ipsilateral lower palpebra occurred with both blocks. Turtles administered lidocaine experienced higher HR compared with CON, and HR decreased over time for all individuals. Mentation and f_R were not changed with any lidocaine dose.ConclusionsThe technique was unreliable in producing brachial plexus motor and sensory blockade at the lidocaine doses evaluated in this study. HR was higher in lidocaine-administered turtles but remained within normal limits for the species. No change in mentation or f_R was observed among treatments.Clinical relevanceGeneral anesthesia with systemic analgesia is recommended for surgical procedures involving the chelonian thoracic limb. Further studies are needed to optimize a brachial plexus block in this species.     

CONTRAST RADIOGRAPHY OF THE GASTROINTESTINAL TRACT IN SEA TURTLES

Intestinal obstruction by radiolucent foreign bodies is common in sea turtles. The absence of clinical signs and the extended fasting periods in these animals means that intestinal obstructions may not be diagnosed early. Digestive tract radiographic contrast procedures were performed to evaluate the gastrointestinal transit time and intestinal obstructions in loggerhead sea turtles. Barium sulfate and nonionic iodinate contrast medium were used for radiographic contrast procedures. Contrast medium was administered via a gastric tube or into the colon. These procedures are often necessary and are useful to document intestinal obstruction and foreign objects. The diagnostic procedures were not easily performed in some turtles, but often they were adequate for the diagnosis.     

USE OF IOHEXOL AS A GASTROINTESTINAL CONTRAST MEDIUM IN THE DOG

Iohexol was administered orally in five dogs. The dose, gastrointestinal (GI) transit time, appearance of mucosal patterns and side effects were studied. Three different doses (525, 700, 875 mgI/kg) were used in each dog at 1-week intervals. GI transit time was rapid. In each dose, gastric emptying commenced immediately after administration of the contrast medium, and was completed within 30–60 min with doses of 525–700 mgI/kg and 90–120 min with 875 mgI/kg. Large intestinal filling was observed within 60-90 min. In the majority of studies, the mucosal border appeared as a thin homogeneous halo of lucency surrounding the more opaque bowel lumen contents. The contrast intensity was not adequate with the lowest dose. The image quality did not deteriorate along the GI tract. No adverse reactions were found. Iohexol is an alternative GI contrast medium in the dog when contrast media are contraindicated.     

Identification of a novel herpesvirus in captive Eastern box turtles (Terrapene carolina carolina)

Herpesviruses are significant pathogens of chelonians which most commonly cause upper respiratory tract disease and necrotizing stomatitis. Herpesvirus infection was identified in two populations of captive Eastern box turtles (Terrapene carolina carolina) using histopathology and polymerase chain reaction (PCR) with DNA sequencing. Necrotizing lesions with eosinophilic to amphophilic intranuclear inclusion bodies were identified in the tissues of one hatch-year individual in January 2013, which was herpesvirus positive by PCR. A separate captive group of adults had an observed herpesvirus prevalence of 58% using PCR in July 2011. In these cases, a novel herpesvirus, Terrapene herpesvirus 1 (TerHV1), was identified and serves as the first herpesvirus sequenced in the genus Terrapene. Similar to the other herpesviruses of the Order Testudines, TerHV1 clusters with the genus Scutavirus of the subfamily Alphaherpesvirinae.     

How does dietary particle size affect carnivore gastrointestinal transit: A dog model

The effect of dietary particle size on gastrointestinal transit in carnivores has not been studied and might offer more insight into their digestive physiology. This study evaluated the effect of two dietary particle sizes (fine = 7.8 mm vs. coarse = 13 mm) of chunked day‐old chicks on transit parameters in dogs. Six beagle dogs were fed both dietary treatments in a crossover design of 7 days with transit testing on the fifth day. Transit parameters were assessed using two markers, that is a wireless motility capsule (IntelliCap^®) and titanium oxide (TiO₂). Dietary particle size did not affect gastric emptying time (GRT), small bowel transit time (SBTT), colonic transit time (CTT) and total transit time (aTTT) of the capsule (p > .05). There was no effect of dietary particle size on TiO₂ mean retention time (MRT) (p > .05). The time of last TiO₂ excretion (MaxRT) differed (p = .013) between diets, being later for the coarse diet. Both MRT (R = 0.617, p = .032) and MaxRT (R = 0.814; p = .001) were positively correlated to aTTT. The ratio MRT/aTTT tended towards a difference between diets (p = .059) with the coarse diet exceeding fine diet values. Results show that the difference between capsule measurements and TiO₂ is larger for the fine than the coarse diet suggesting that the capsule becomes more accurate when dietary particle size approaches marker size. Dietary particle size might have affected transit parameters but differences are too small to claim major physiological consequences.