OBJECTIVE To investigate the anti-inflammatory and immunomodulatory properties of tulathromycin in vitro and in experimental models of Actinobacillus pleuropneumoniae–induced pleuropneumonia and zymosan-induced pulmonary inflammation in pigs. ANIMALS Blood samples from six 8- to 30-week-old healthy male pigs for the in vitro experiment and sixty-five 3-week-old specific pathogen–free pigs. PROCEDURES Neutrophils and monocyte-derived macrophages were isolated from blood samples. Isolated cells were exposed to tulathromycin (0.02 to 2.0 mg/mL) for various durations and assessed for markers of apoptosis and efferocytosis. For in vivo experiments, pigs were inoculated intratracheally with A pleuropneumoniae, zymosan, or PBS solution (control group) with or without tulathromycin pretreatment (2.5 mg/kg, IM). Bronchoalveolar lavage fluid was collected 3 and 24 hours after inoculation and analyzed for proinflammatory mediators, leukocyte apoptosis, and efferocytosis. RESULTS In vitro, tulathromycin induced time- and concentration-dependent apoptosis in neutrophils, which enhanced their subsequent clearance by macrophages. In the lungs of both A leuropneumoniae– and zymosan-challenged pigs, tulathromycin promoted leukocyte apoptosis and efferocytosis and inhibited proinflammatory leukotriene B4 production, with a concurrent reduction in leukocyte necrosis relative to that of control pigs. Tulathromycin also attenuated the degree of lung damage and lesion progression in A pleuropneumoniae–inoculated pigs. CONCLUSIONS AND CLINICAL RELEVANCE Tulathromycin had immunomodulatory effects in leukocytes in vitro and anti-inflammatory effects in pigs in experimental models of A pleuropneumoniae infection and nonmicrobial-induced pulmonary inflammation. These data suggested that in addition to its antimicrobial properties, tulathromycin may dampen severe proinflammatory responses and drive resolution of inflammation in pigs with microbial pulmonary infections.

OBJECTIVE To compare blood glucose concentrations of black-tailed prairie dogs (Cynomys ludovicianus) measured by use of a variety of portable analyzers with results from a laboratory biochemistry analyzer. SAMPLE Venous blood samples (3 mL) obtained from each of 16 healthy black-tailed prairie dogs. PROCEDURES A portion of each blood sample was used to measure glucose concentrations by use of an amperometric human point-of-care glucometer and a colorimetric species-specific portable blood glucose meter designed for veterinary use with both canine (code 5) and feline (code 7) settings. The remainder of each blood sample was placed into 2 tubes (one contained lithium heparin and the other contained no anticoagulant). A portable veterinary chemistry analyzer (PVCA) and a handheld analyzer were used to measure glucose concentration in heparinized blood. Serum glucose concentration was measured in the remaining portion by use of a biochemistry analyzer. A general linear mixed models approach was used to compare glucose concentrations and measurement bias obtained with the various measurement methods. RESULTS Measurement bias and differences in mean glucose concentrations were apparent with all measurement methods. In particular, the veterinary glucometer, whether used on the canine or feline setting, overestimated mean glucose concentrations, whereas the human glucometer, PVCA, and handheld analyzer underestimated mean glucose concentrations relative to the concentration obtained with the biochemistry analyzer. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that none of the measurement methods provided consistently accurate blood glucose concentrations of black-tailed prairie dogs, compared with values determined with a biochemistry analyzer.

OBJECTIVE To compare gait mechanics and limb loading in Icelandic horses tölting and trotting at equal speeds and estimate their impact on orthopedic health. ANIMALS 12 orthopedically normal Icelandic horses. PROCEDURES Kinetic and kinematic gait variables were simultaneously recorded as each horse was ridden at a tölt and trot on an instrumented treadmill at 3.4 m/s and 3.9 m/s. Differences between gaits were tested via 1-factor repeated-measures ANOVA. RESULTS Horses had a higher stride rate and lower stride impulses at a tölt than at a trot. For forelimbs at a tölt, shorter relative stance duration resulted in higher peak vertical force (Fz(peak)). Conversely, for hind limbs, longer relative stance duration resulted in lower Fz(peak). The higher head-neck position at a tölt versus trot caused no weight shift to the hind limbs, but a higher forehoof flight arc and lower proretraction movement were identified. Stance durations for forelimbs were briefer than for hind limbs at a tölt, and the inverse was observed at a trot. Minimal height of the horse's trunk at the point of Fz(peak) of the respective limb suggested a spring-like mechanism for all limbs at a tölt. Hind limb measurements revealed no evidence of increased collection. Stride-to-stride limb timing varied more at a tölt than at a trot. At a trot, horses had brief or no suspension phases and a slightly 4-beated footfall rhythm was common. Post hoc energetic estimations revealed that tölting at the measured speeds was less advantageous than trotting. CONCLUSIONS AND CLINICAL RELEVANCE High forelimb action in Icelandic horses and higher head-neck position at a tölt were associated with more restricted limb proretraction, higher Fzpeak, and faster force onset than at a trot. The impact of these differences on orthopedic health needs to be investigated more in detail.

OBJECTIVE To determine whether high doses of enalapril and benazepril would be more effective than standard doses of these drugs in suppressing the furosemide-activated renin-angiotensin-aldosterone system (RAAS). ANIMALS 6 healthy Beagles. PROCEDURES 2 experiments were conducted; each lasted 10 days, separated by a 2-week washout period. In experiment 1, all dogs received furosemide (2 mg/kg, PO, q 12 h) and enalapril (1 mg/kg, PO, q 12 h) for 8 days (days 0 through 7). In experiment 2, dogs received furosemide (2 mg/kg, PO, q 12 h) and benazepril (1 mg/kg, PO, q 12 h) for 8 days. Effects on the RAAS were determined by assessing serum angiotensin-converting enzyme (ACE) activity on days −1, 3, and 7; serum aldosterone concentration on days −2, −1, 1, 3, and 7; and the urinary aldosterone-creatinine ratio (UAldo:C) in urine collected in the morning and evening of days −2, −1, 1, 3, and 7. RESULTS High doses of enalapril and benazepril caused significant reductions in serum ACE activity on all days but were not more effective than standard doses used in other studies. Mean UAldo:C remained significantly higher on days 2 through 7, compared with baseline values. Serum aldosterone concentration also increased after drug administration, which mirrored changes in the UAldo:C. CONCLUSIONS AND CLINICAL RELEVANCE In this study, administration of high doses of enalapril and benazepril significantly inhibited ACE activity, yet did not prevent increases in mean urine and serum aldosterone concentrations resulting from furosemide activation of RAAS. This suggested that aldosterone breakthrough from ACE inhibition was a dose-independent effect of ACE inhibitors.

OBJECTIVE To determine the pharmacokinetics and adverse effects at the injection site of ceftiofur crystalline-free acid (CCFA) following IM administration of 1 dose to red-tailed hawks (Buteo jamaicensis). ANIMALS 7 adult nonreleasable healthy red-tailed hawks. PROCEDURES In a randomized crossover study, CCFA (10 or 20 mg/kg) was administered IM to each hawk and blood samples were obtained. After a 2-month washout period, administration was repeated with the opposite dose. Muscle biopsy specimens were collected from the injection site 10 days after each sample collection period. Pharmacokinetic data were calculated. Minimum inhibitory concentrations of ceftiofur for various bacterial isolates were assessed. RESULTS Mean peak plasma concentrations of ceftiofur-free acid equivalent were 6.8 and 15.1 μg/mL for the 10 and 20 mg/kg doses, respectively. Mean times to maximum plasma concentration were 6.4 and 6.7 hours, and mean terminal half-lives were 29 and 50 hours, respectively. Little to no muscle inflammation was identified. On the basis of a target MIC of 1 μg/mL and target plasma ceftiofur concentration of 4 μg/mL, dose administration frequencies for infections with gram-negative and gram-positive organisms were estimated as every 36 and 45 hours for the 10 mg/kg dose and every 96 and 120 hours for the 20 mg/kg dose, respectively. CONCLUSIONS AND CLINICAL RELEVANCE Study results suggested that CCFA could be administered IM to red-tailed hawks at 10 or 20 mg/kg to treat infections with ceftiofur-susceptible bacteria. Administration resulted in little to no inflammation at the injection site. Additional studies are needed to evaluate effects of repeated CCFA administration.

OBJECTIVE To determine the minimum infusion rate (MIR) of propofol required to prevent movement in response to a noxious stimulus in dogs anesthetized with propofol alone or propofol in combination with a constant rate infusion (CRI) of ketamine. ANIMALS 6 male Beagles. PROCEDURES Dogs were anesthetized on 3 occasions, at weekly intervals, with propofol alone (loading dose, 6 mg/kg; initial CRI, 0.45 mg/kg/min), propofol (loading dose, 5 mg/kg; initial CRI, 0.35 mg/kg/min) and a low dose of ketamine (loading dose, 2 mg/kg; CRI, 0.025 mg/kg/min), or propofol (loading dose, 4 mg/kg; initial CRI, 0.3 mg/kg/min) and a high dose of ketamine (loading dose, 3 mg/kg; CRI, 0.05 mg/kg/min). After 60 minutes, the propofol MIR required to prevent movement in response to a noxious electrical stimulus was determined in duplicate. RESULTS Least squares mean ± SEM propofol MIRs required to prevent movement in response to the noxious stimulus were 0.76 ± 0.1 mg/kg/min, 0.60 ± 0.1 mg/kg/min, and 0.41 ± 0.1 mg/kg/min when dogs were anesthetized with propofol alone, propofol and low-dose ketamine, and propofol and high-dose ketamine, respectively. There were significant decreases in the propofol MIR required to prevent movement in response to the noxious stimulus when dogs were anesthetized with propofol and low-dose ketamine (27 ± 10%) or with propofol and high-dose ketamine (30 ± 10%). CONCLUSIONS AND CLINICAL RELEVANCE Ketamine, at the doses studied, significantly decreased the propofol MIR required to prevent movement in response to a noxious stimulus in dogs.

OBJECTIVE To evaluate the potency of vecuronium and duration of vecuronium-induced neuromuscular blockade in dogs with centronuclear myopathy (CNM). ANIMALS 6 Labrador Retrievers with autosomal-recessive CNM and 5 age- and weight-matched control dogs. PROCEDURES Dogs were anesthetized on 2 occasions (1-week interval) with propofol, dexmedetomidine, and isoflurane. Neuromuscular function was monitored with acceleromyography and train-of-four (TOF) stimulation. In an initial experiment, potency of vecuronium was evaluated by a cumulative-dose method, where 2 submaximal doses of vecuronium (10 μg/kg each) were administered IV sequentially. For the TOF's first twitch (T1), baseline twitch amplitude and maximal posttreatment depression of twitch amplitude were measured. In the second experiment, dogs received vecuronium (50 μg/kg, IV) and the time of spontaneous recovery to a TOF ratio (ie, amplitude of TOF's fourth twitch divided by amplitude of T1) ≥ 0.9 and recovery index (interval between return of T1 amplitude to 25% and 75% of baseline) were measured. RESULTS Depression of T1 after each submaximal dose of vecuronium was not different between groups. Median time to a TOF ratio ≥ 0.9 was 76.7 minutes (interquartile range [IQR; 25th to 75th percentile], 66.7 to 99.4 minutes) for dogs with CNM and 75.0 minutes (IQR, 47.8 to 96.5 minutes) for controls. Median recovery index was 18.0 minutes (IQR, 9.7 to 23.5 minutes) for dogs with CNM and 20.2 minutes (IQR, 8 to 25.1 minutes) for controls. CONCLUSIONS AND CLINICAL RELEVANCE For the study dogs, neither potency nor duration of vecuronium-induced neuromuscular blockade was altered by CNM. Vecuronium can be used to induce neuromuscular blockade in dogs with autosomal-recessive CNM.

OBJECTIVE To compare ultrasound biomicroscopy (UBM) with standard ocular ultrasonography for detection of canine uveal cysts and to determine the sensitivity, specificity, and interobserver agreement for detection of uveal cysts with UBM. SAMPLE 202 enucleated eyes from 101 dogs. PROCEDURES 2 examiners examined 202 eyes by means of UBM (50 MHz) to identify uveal cysts. A board-certified radiologist then examined 98 of the 202 eyes by means of standard ocular ultrasonography (7- to 12-MHz linear transducer). Subsequently, 1 examiner dissected all 202 eyes under magnification from an operating microscope to definitively identify uveal cysts. Each examiner was masked to other examiners’ findings. Sensitivity, specificity, and interobserver agreement were calculated for detection of cysts by UBM. RESULTS Cysts were detected by use of UBM in 55 of 202 (27%) eyes by one examiner and 29 of 202 (14%) eyes by the other. No cysts were detected in the 98 eyes examined with standard ocular ultrasonography. Dissection results revealed that cysts were present in 64 of 202 (32%) eyes, including 29 of 98 (30%) eyes examined by standard ocular ultrasonography. Mean sensitivity of UBM for cyst detection was 47%; mean specificity was 92%. Uveal cysts not identified with UBM were often small (mean diameter, 490 üm). Interobserver agreement was high (κP = 0.81). CONCLUSIONS AND CLINICAL RELEVANCE UBM was more effective than standard ocular ultrasonography for detection of uveal cysts in enucleated eyes. Small-diameter cysts were difficult to visualize even with UBM.

Sodium nitrite is widely used as a color fixative and preservative in meat and fish. Impairment of hepatic function and disturbances in lipid metabolism are well recognized adverse effects of sodium nitrite. The aim of this study is to investigate the role of bis [4-(4'-hydroxy-3'-methoxybezylidineaminophenyl)]telluride, a novel compound, in preventing the hepatic damage and disturbances of lipid metabolism induced by sodium nitrite toxicity in male albino rats. The estimated LD50 of [4-(4'-hydroxy-3'-methoxybezylidineaminophenyl)]telluride in adult male albino rats is 218.7 mg/kg body weight. Rats given sodium nitrite (0.2%) in the drinking water showed a significant increase in serum ALT, AST, ALP, Total cholesterol, TG. LDL and VLDL while HDL significantly reduced. These changes are reversed by administration of bis [4-(4'-hydroxy-3'-methoxybezylidineaminophenyl)]telluride in a dose of 11mg/kg body weight corresponding to 1/20 LD50. It is concluded that bis [4-(4'-hydroxy-3'-methoxybezylidineaminophenyl)]telluride is effective in preventing hepatic damage and dislipidemia in sodium nitrite intoxicated male rats.

Recurrent abortion is a worldwide problem, with undefined causes. Apoptosis could play a major role in the process. The Objective of the work to detect the expression of p53 protein at the materno-fetal interface in patients with recurrent pregnancy loss (RPL). Immunohistochemistry analysis of P53 protein using paraffin embedded sections of curate samples obtained from 40 women divided into three groups : 16 women with recurrent abortion as postive with toxoplasmosis,10 women with recurrent abortion negative of toxoplasmosis and14 women with no histry of abortion as control group . The mean value of the expression of P53 protein was (40.87± 7.54),which is significantly higher than that of the second group(28.2± 4.89),and the third group (13.07± 4.49). The high expression of p53 protein in women with RPL may have a role in accelerating placental apoptosis leading to failure of pregnancy.