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In vitro characterization of a formulation of butorphanol tartrate in a poloxamer 407 base intended for use as a parenterally administered slow-release analgesic agent Texte intégral
2017
Laniesse, Dalphine | Smith, Dale A. | Knych, Heather K. | Mosley, Cornelia | Sanchez-Migallon Guzman, David | Beaufrere, Huges
OBJECTIVE To assess rheological properties and in vitro diffusion of poloxamer 407 (P407) and butorphanol-P407 (But-P407) hydrogels and to develop a sustained-release opioid formulation for use in birds. SAMPLE P407 powder and a commercially available injectable butorphanol tartrate formulation (10 mg/mL). PROCEDURES P407 and But-P407 gels were compounded by adding water or butorphanol to P407 powder. Effects of various concentrations of P407 (20%, 25% and 30% [{weight of P407/weight of diluent} × 100]), addition of butorphanol, and sterilization through a microfilter on rheological properties of P407 were measured by use of a rheometer. In vitro diffusion of butorphanol from But-P407 25% through a biological membrane was compared with that of a butorphanol solution. RESULTS P407 20% and 25% formulations were easily compounded, whereas it was difficult to obtain a homogenous P407 30% formulation. The P407 was a gel at avian body temperature, although its viscosity was lower than that at mammalian body temperature. The But-P407 25% formulation (butorphanol concentration, 8.3 mg/mL) was used for subsequent experiments. Addition of butorphanol to P407 as well as microfiltration did not significantly affect viscosity. Butorphanol diffused in vitro from But-P407, and its diffusion was slower than that from a butorphanol solution. CONCLUSIONS AND CLINICAL RELEVANCE But-P407 25% had in vitro characteristics that would make it a good candidate for use as a sustained-release analgesic medication. Further studies are needed to characterize the pharmacokinetic and pharmacodynamic properties of But-P407 25% in vivo before it can be recommended for use in birds.
Afficher plus [+] Moins [-]Racing performance of Standardbred trotting horses undergoing surgery of the carpal flexor sheath and age- and sex-matched control horses Texte intégral
2017
Carmalt, James L. | Johansson, Bengt C. | Zetterstrom, Sandra M. | McOnie, Rebecca C.
OBJECTIVE To determine factors affecting race speed in Swedish Standardbred horses undergoing surgery of the carpal flexor sheath (CFS), to investigate whether preoperative racing speed was associated with specific intraoperative findings and whether horses returned to racing, and to compare the performance of horses undergoing surgery of the CFS with that of age- and sex-matched control horses. ANIMALS 149 Swedish Standardbred trotters undergoing surgery of the CFS and 274 age- and sex-matched control horses. PROCEDURES Medical records of CFS horses were examined. Racing data for CFS and control horses were retrieved from official online records. Generalizing estimating equations were used to examine overall and presurgery racing speeds and the association of preoperative clinical and intraoperative findings with preoperative and postoperative speeds. Multivariable regression analysis was used to examine career earnings and number of career races. Kaplan-Meier survival analysis was used to compare career longevity between CFS and control horses. RESULTS CFS horses were significantly faster than control horses. The CFS horses that raced before surgery were slower as they approached the surgery date, but race speed increased after surgery. There were 124 of 137 (90.5%) CFS horses that raced after surgery. No intrathecal pathological findings were significantly associated with preoperative racing speed. Career longevity did not differ between CFS and control horses. CONCLUSIONS AND CLINICAL RELEVANCE Horses undergoing surgery of the CFS had a good prognosis to return to racing after surgery. Racing careers of horses undergoing surgery of the CFS were not significantly different from racing careers of control horses.
Afficher plus [+] Moins [-]The role of active transport in the transcellular movement of the peripheral α2-adrenoceptor antagonist, MK-467: An in vitro pilot study Texte intégral
2017
Bennett, Rachel | Palviainen, Mari | Peltoniemi, Marikki | Vuorilehto, Lauri | Scheinin, Mika | Raekallio, Marja | Vainio, Outi
MK-467 is a peripherally acting α2-adrenoceptor antagonist due to its low lipid solubility and poor penetration of the blood-brain barrier (BBB). The aim of this study was to assess whether MK-467 could be a substrate of an active efflux transport mechanism. Using Madin-Darby Canine Kidney cells (MDCKII) and MDCKII cells transfected with the human multidrug resistance gene 1, drug transport was assessed in apical-basolateral and basolateral-apical directions. MK-467 was studied at 2 concentrations: 200 and 1000 ng/mL. Samples for analysis were taken at 15, 30, 45, 60, and 90 min after drug application. Drug concentrations were measured using liquid chromatography and mass spectrometry. MK-467 showed no apparent permeability in the apical-basolateral direction, transport in the basolateral-apical direction occurred in both cell lines. Efflux ratios were not calculated. However, MK-467 appeared to undergo active cellular transport. The identity of the transporter requires further investigation.
Afficher plus [+] Moins [-]Protective efficacy of a Salmonella Typhimurium ghost vaccine candidate constructed with a recombinant lysozyme-PMAP36 fusion protein in a murine model Texte intégral
2017
Moon, Ja Young | Kim, So Young | Kim, Won Kyong | Rao, Zhili | Park, Jung Hee | Mun, Ji Young | Boram, Kim | Choi, Hyo Sun | Hur, Jin
A Salmonella Typhimurium ghost vaccine was constructed with the use of a recombinant fusion protein consisting of lysozyme and porcine myeloid antimicrobial peptide 36 expressed by the Escherichia coli overexpression system. After confirmation of its effectiveness by transmission electron microscopy the vaccine was evaluated in a murine model. Of the 60 BALB/c mice equally divided into 4 groups, group A mice were intramuscularly inoculated with 100 μL of sterile phosphate-buffered saline, and the mice in groups B, C, and D were intramuscularly inoculated with approximately 1.0 × 10(4), 1.0 × 10(5), or 1.0 × 10(6) cells of the S. Typhimurium ghost vaccine, respectively, in 100-μL amounts. The serum I gG titers against S. Typhimurium outer membrane proteins were significantly higher in groups B to D than in group A, as were the concentrations of interleukin-10 and interferon gamma in supernatants of harvested splenocytes. After challenge with wild-type S. Typhimurium, all the vaccinated groups showed significant protection compared with group A, notably perfect protection in groups C and D. Overall, these results show that intramuscular vaccination with 1.0 × 10(5) cells of this ghost vaccine candidate provided efficient protection against systemic infection with virulent S. Typhimurium.
Afficher plus [+] Moins [-]Magnetic resonance imaging susceptibility artifacts in the cervical vertebrae and spinal cord related to monocortical screw–polymethylmethacrylate implants in canine cadavers Texte intégral
2017
Jones, B. G. | Fosgate, Geoffrey T. | Green, Eric M. | Habing, Amy M. | Hettlich, Bianca F.
OBJECTIVE To characterize and compare MRI susceptibility artifacts related to titanium and stainless steel monocortical screws in the cervical vertebrae and spinal cord of canine cadavers. SAMPLE 12 canine cadavers. PROCEDURES Cervical vertebrae (C4 and C5) were surgically stabilized with titanium or stainless steel monocortical screws and polymethylmethacrylate. Routine T1-weighted, T2-weighted, and short tau inversion recovery sequences were performed at 3.0 T. Magnetic susceptibility artifacts in 20 regions of interest (ROIs) across 4 contiguous vertebrae (C3 through C6) were scored by use of an established scoring system. RESULTS Artifact scores for stainless steel screws were significantly greater than scores for titanium screws at 18 of 20 ROIs. Artifact scores for titanium screws were significantly higher for spinal cord ROIs within the implanted vertebrae. Artifact scores for stainless steel screws at C3 were significantly less than at the other 3 cervical vertebrae. CONCLUSIONS AND CLINICAL RELEVANCE Evaluation of routine MRI sequences obtained at 3.0 T revealed that susceptibility artifacts related to titanium monocortical screws were considered mild and should not hinder the overall clinical assessment of the cervical vertebrae and spinal cord. However, mild focal artifacts may obscure small portions of the spinal cord or intervertebral discs immediately adjacent to titanium screws. Severe artifacts related to stainless steel screws were more likely to result in routine MRI sequences being nondiagnostic; however, artifacts may be mitigated by implant positioning.
Afficher plus [+] Moins [-]Texture analysis of magnetic resonance images to predict histologic grade of meningiomas in dogs Texte intégral
2017
Banzato, Tommaso | Bernardini, Marco | Cherubini, Giunio B. | Zotti, Alessandro
OBJECTIVE To predict histologic grade of meningiomas in dogs via texture analysis (TA) of MRI scans of the brain and spinal cord. SAMPLE 58 sets of MRI scans of the brain and spinal cord of dogs with histologically diagnosed meningioma. PROCEDURES MRI sequences were divided into a training set and a test set, and results of histologic assessment were obtained. Tumors were histologically grouped as benign (stage I) or atypical-anaplastic (stage II or III). Texture analysis was performed by use of specialized software on T2-weighted (T2W) and pre- and postcontrast T1-weighted (T1W) images. A set of 30 texture features that provided the highest discriminating power between the 2 histologic classes in the training set was automatically selected by the TA software. Linear discriminant analysis was performed, and the most discriminant factor (MDF) was calculated. The previously selected texture features were then used for linear discriminant analysis of the test set data, and the MDF was calculated. RESULTS For the training set, TA of precontrast T1W images provided the best diagnostic accuracy; a cutoff MDF of < 0.0057 resulted in a sensitivity of 97.4% and specificity of 95.0% for discriminating benign from atypical-anaplastic meningiomas. Use of postcontrast T1W and T2W images yielded poorer diagnostic performances. Application of the MDF cutoff calculated with the training set to the MDF calculated with the test set provided a correct classification rate of 96.8% for precontrast T1W images, 92.0% for postcontrast T1W images, and 78.9% for T2W images. CONCLUSIONS AND CLINICAL RELEVANCE Findings supported the potential clinical usefulness of TA of MRI scans for the grading of meningiomas in dogs.
Afficher plus [+] Moins [-]Evaluation of the new commercial recombinant chimeric subunit vaccine PRRSFREE in challenge with heterologous types 1 and 2 porcine reproductive and respiratory syndrome virus Texte intégral
2017
Jeong, J. | Park, C. | Choi, K. | Chae, C.
The objective of this study was to evaluate a new recombinant chimeric vaccine against porcine reproductive and respiratory syndrome virus (PRRSV). The subunit vaccine, PRRSFREE, from Reber Genetics, Taiwan, Republic of China, is based on a plasmid containing a detoxified Pseudomonas exotoxin carrying open reading frame (ORF) 7, 1b, and 5 and 6 chimeric subunits of types 1 and 2 PRRSV. Pigs were injected intramuscularly with 2.0 mL of the vaccine at 21 and 42 d of age, according to the manufacturer's recommendation. At the age of 63 d the pigs were inoculated intranasally with either type 1 or type 2 PRRSV. Regardless of the genotype of the challenging PRRSV, the vaccinated challenged pigs had significantly lower (P < 0.05) mean rectal temperature, respiratory score, lung lesion score, and amount of PRRSV antigen within areas of interstitial pneumonia, along with overall lower levels of viremia due to type 1 or type 2 PRRSV compared with the unvaccinated challenged pigs. The vaccinated challenged pigs also had significantly higher (P < 0.05) numbers of interferon-γ secreting cells compared with the unvaccinated challenged pigs. This study demonstrated that the new vaccine provides protection against respiratory disease from heterologous types 1 and 2 PRRSV challenge in growing pigs.
Afficher plus [+] Moins [-]Morphological evaluation of clefts of the lip, palate, or both in dogs Texte intégral
2017
Peralta, Santiago | Fiani, Nadine | Kan-Rohrer, Kimi H. | Verstraete, Frank J. M.
OBJECTIVE To systematically characterize the morphology of cleft lip, cleft palate, and cleft lip and palate in dogs. ANIMALS 32 client-owned dogs with clefts of the lip (n = 5), palate (23), or both (4) that had undergone a CT or cone-beam CT scan of the head prior to any surgical procedures involving the oral cavity or face. PROCEDURES Dog signalment and skull type were recorded. The anatomic form of each defect was characterized by use of a widely used human oral-cleft classification system on the basis of CT findings and clinical images. Other defect morphological features, including shape, relative size, facial symmetry, and vomer involvement, were also recorded. RESULTS 9 anatomic forms of cleft were identified. Two anatomic forms were identified in the 23 dogs with cleft palate, in which differences in defect shape and size as well as vomer abnormalities were also evident. Seven anatomic forms were observed in 9 dogs with cleft lip or cleft lip and palate, and most of these dogs had incisive bone abnormalities and facial asymmetry. CONCLUSIONS AND CLINICAL RELEVANCE The morphological features of congenitally acquired cleft lip, cleft palate, and cleft lip and palate were complex and varied among dogs. The features identified here may be useful for surgical planning, developing of clinical coding schemes, or informing genetic, embryological, or clinical research into birth defects in dogs and other species.
Afficher plus [+] Moins [-]Effectiveness of manual bladder expression in paraplegic dogs Texte intégral
2017
Carwardine, Darren R. | Rose, Jeremy H. | Harcourt-Brown, Thomas R. | Granger, Nicolas
OBJECTIVE To determine the effectiveness of manual bladder expression in paraplegic dogs by comparing urine volumes measured by use of intermittent catheterization and ultrasonography. ANIMALS 36 paraplegic dogs. PROCEDURES 93 measurements of bladder volume were collected for the 36 dogs. Residual urine volume was determined by use of intermittent urethral catheterization and estimated by use of ultrasonography. RESULTS Manual bladder expression voided a mean of 49% of urine from the bladder in this population of dogs. There was no correlation (R2, 0.06) between the effectiveness of manual bladder expression and body weight. Ultrasonographic estimation of bladder volume had good correlation (R2, 0.62) with bladder volume determined by use of intermittent bladder catheterization, but clinically unacceptable variation for predicting actual bladder volume (mean difference, 22 mL; 95% confidence interval, −96 to 139 mL). CONCLUSIONS AND CLINICAL RELEVANCE Manual bladder expression was ineffective at completely emptying urine from the bladder of paraplegic dogs, but the effectiveness of the procedure was not affected by body weight. Manual bladder expression would likely be a useful procedure to prevent increases in pressure within the bladder. Ultrasonographic estimation of bladder volume could be a useful predictor of actual bladder volume, but it was susceptible to wide variations among dogs, and results should therefore be interpreted with caution.
Afficher plus [+] Moins [-]Evaluation of two methods for topical application of contrast medium to the pharyngeal and laryngeal region of horses Texte intégral
2017
Colbath, Aimee C. | Valdes-Martinez, Alejandro | Leise, Britta S. | Hackett, Eileen S.
OBJECTIVE To determine the pharyngeal and laryngeal distribution of radiopaque contrast medium administered orally or via nasopharyngeal catheter to standing horses. ANIMALS 5 healthy adult horses. PROCEDURES A crossover study was conducted. Radiopaque contrast medium (12 mL) was administered orally and via nasopharyngeal catheter to each horse. Pharyngeal and laryngeal distribution of contrast medium was determined by examination of radiographs obtained immediately after administration of contrast medium, compared with those obtained before administration. Regional distribution of contrast medium was graded. Endoscopic examination of the nasopharynx, laryngopharynx, and larynx was performed to confirm radiographic results. RESULTS Examination of radiographs obtained after nasopharyngeal administration revealed contrast medium in the nasopharynx (n = 5), oropharynx (2), laryngopharynx (3), and larynx (5) of the 5 horses. Examination of radiographs obtained after oral administration revealed contrast medium in the oropharynx (n = 4) and larynx (1) of the 5 horses. Endoscopic examination confirmed radiographic findings and was found to be sensitive for detection of contrast medium in the laryngopharynx, whereby detection rates were higher for both administration methods. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that medication administered by use of a nasopharyngeal catheter will result in topical distribution within the nasopharynx, including the dorsal surface of the soft palate, and larynx, although distribution should be evaluated in horses with clinical airway disease to confirm these findings. Oral administration did not result in consistently detectable topical laryngeal distribution but could be used for selected conditions (eg, palatitis).
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