M-MODE AND DOPPLER ECHOCARDIOGRAPHIC FINDINGS IN NORMAL FERRETS SEDATED WITH KETAMINE HYDROCHLORIDE AND MIDAZOLAM

M-mode and Doppler echocardiographic values were obtained from 30 normal adult ferrets (14 neutered females, 13 neutered males, 3 intact males) sedated with an intramuscular combination of ketamine hydrochloride and midazolam. Routine M-mode measurements of the left and right ventricle, left atrium (LA) and aorta (AO) and Doppler measurements of aortic and pulmonic outflow, and mitral inflow were recorded. The following values were calculated: LA:AO diameter, ratio of peak E: peak A wave velocity (E:A ratio) for mitral inflow, and stroke volume (SV), cardiac output (CO) and cardiac index (CI) for both pulmonary and aortic outflow tracts. Maximal aortic velocities (AOmax) and velocity-time integral values (AO VTI) were significantly less than corresponding pulmonary outflow tract values (PAmax, PA VTI) but there was no difference in calculated values for SV, CO or CI. Calculated CO values were in the range expected based on the size of the species. Difficulties in aligning the aortic outflow tract for Doppler imaging may make pulmonary outflow Doppler values more consistent for use in estimating volume flow in ferrets.     

Effects of oral isosorbide and glycerol on intraocular pressure,serum osmolality,and blood glucose in normal dogs

Objective To evaluate and compare the effects of oral isosorbide and glycerol on intraocular pressure (IOP), serum osmolality (SOSM), and blood glucose (BG) in normal dogs. Methods Ten normal dogs were administered an oral dose of either isosorbide (1.5 g/kg), glycerol (1.5 g/kg) or control (water, 2 mL/kg) in a double blind protocol. Prior to dosing, baseline IOP, SOSM, and BG were measured in all dogs. IOP was subsequently evaluated every 30 min for 6 h post‐dosing. BG and SOSM were reassessed at times 1, 2, 4, and 6 h post‐dosing. After 1‐week washout periods, every dog was subject to each of the three treatments. The dogs were held NPO for 4 h after dosing. Results The maximal decrease in IOP was 17% by 1 h and 13.5% by 30 min after glycerol and isosorbide administration, respectively. However, the overall changes in IOP were not significant when compared to the controls. SOSM increased above baseline after dosing with glycerol but decreased after isosorbide, which difference was significant at 1, 2, and 4 h post‐administration. BG significantly increased after administration of glycerol relative to the control but was not significantly affected by isosorbide. Conclusions Neither glycerol nor isosorbide significantly affected IOP when compared to the control. However, glycerol induced significant elevations in both BG relative to the control and SOSM relative to isosorbide.     

Characterization of a factor from bovine intestine that protects against Cryptosporidium parvum infection

Cryptosporidium parvum is a protozoan parasite that causes intestinal infection in a variety of mammals. We have previously described a factor in adult rat or adult bovine intestinal mucosa that protects against C. parvum infection when fed to susceptible infant rats. This factor is absent in intestinal mucosa from bovine calves. In the present study we describe the further characterization of the active component of bovine intestinal mucosa. The ability to protect infant rats against C. parvum infection was found to be associated with the extrinsic membrane protein fraction of the intestinal mucosa. Extrinsic membrane preparations from adult cows, adult rats, and calves were separated by SDS-PAGE. A band with apparent molecular mass of 54 kDa was seen in preparations from adult rat and cow, but not calf. Protein was transferred to PVDF membrane and from this the band was excised and subjected to N-terminal sequence analysis using a gas-phase protein sequenator. A 15-amino acid consensus sequence was generated with homology to leucine aminopeptidase (LAP). Purified LAP was purchased from a commercial source and tested for ability to protect infant rats against C. parvum infection. Rats fed LAP from 7 to 11 days of age and challenged with C. parvum at 9 days were significantly less infected than controls upon necropsy at 15 days of age. These data suggest that a protein with N-terminal sequence homology to LAP may reduce susceptibility of infant rats to C. parvum infection.     

Application of different pharmacokinetic models to describe and predict pharmacokinetics of voriconazole in magellanic penguins following oral administration

Aspergillosis is a condition causing serious morbidity and mortality in captive penguins and other bird species. It can be treated with antifungal drugs, such as voriconazole. However, the pharmacokinetics of voriconazole are variable between different animal and bird species. Therefore, the pharmacokinetics of voriconazole were investigated in this study in Magellanic penguins. Pharmacokinetic models were constructed and applied to predict the pharmacokinetics of voriconazole during long‐term treatment in Magellanic penguins, since the voriconazole treatment duration in chronic aspergillosis cases can last up to several months. Plasma voriconazole concentration–time data from adult Magellanic penguins (Spheniscus magellanicus; n = 15) following a single oral (PO) dose of either 2.5 mg/kg or 5 mg/kg in a herring in three separate study periods 7–12 months apart were collected. Mean plasma voriconazole concentrations were above the targeted MIC for Aspergillus fumigatus for 2 hr following a single 2.5 mg/kg voriconazole dose while the plasma concentrations exceeded the MIC for least 24 hr following a 5 mg/kg dose. Nonlinear mixed‐effects modeling was used to fit two pharmacokinetic models, one with first‐order and another with saturable elimination, to the single‐dose data. Fits were good for both, as long as dose was included as a covariate for the first‐order model so that clearance was lower and the half‐life longer for animals receiving the 5 mg/kg dose. Although the single‐dose data suggested saturated elimination at higher concentrations, the model with saturable elimination did not predict plasma voriconazole concentrations well for a clinical aspergillosis case receiving long‐term treatment, possibly because of induction of metabolizing enzymes with chronic exposure. Pharmacokinetic models should accurately predict plasma drug concentrations for different dosage regimens in order to be applicable in the field. Future studies should focus on determining clearance at steady‐state to be able to refine the pharmacokinetic models presented here and improve model performance for long‐term oral voriconazole administration in Magellanic penguins.     

Multiple antimicrobial resistance region of a putative virulence plasmid from an Escherichia coli isolate incriminated in avian colibacillosis

Infections due to Escherichia coli have been costly to the poultry industry, but the exact virulence mechanisms used by these organisms to cause disease in birds remain undefined. Several factors have been shown to contribute to the virulence of avian E. coli, and many of the genes encoding these factors have been found on large conjugative plasmids. Because of the occurrence of antimicrobial resistance genes on these same plasmids, it is possible that the use of antimicrobial agents may select for persistence of E. coli containing such plasmids. In the present study, a subclone of one of these plasmids was identified as likely containing some virulence and antimicrobial resistance genes. In an effort to better understand the relationship between virulence and resistance in these plasmids, this subclone was sequenced and the sequence analyzed. Analysis of this 30-kilobase (kb) region of plasmid pTJ100 revealed a mosaic of virulence genes, insertion sequences, antimicrobial resistance cassettes, and their remnants. Many of the resistance genes found in this region were expressed under laboratory conditions, indicating that certain antimicrobial agents, including disinfectants, antibiotics, and heavy metals, could promote selection of E. coli containing such plasmids in the production environment. Also, analysis of the G + C content of this clone indicated that it is the likely consequence of a complex evolution with components derived from various sources. The occurrence of many mobile elements in conjunction with antimicrobial resistance and virulence genes in this 30-kb region may indicate that the genetic constitution of the clone is quite plastic. Although further study will be required to better define this plasmid's role in avian E. coli virulence, the sequence described here is, to our knowledge, the longest known contiguous sequence of a ColV plasmid yet presented. Analysis of this sequence indicates that this clone and its parent plasmid may be important to the pathogenesis of avian colibacillosis and the evolution of avian E. coli virulence.     

Associations between dry dietary factors and canine calcium oxalate uroliths

OBJECTIVE: To identify factors in dry diets associated with the occurrence of calcium oxalate (CaOx) uroliths in dogs. ANIMALS: 600 dogs with CaOx uroliths and 898 dogs without urinary tract diseases. PROCEDURE: Univariate and multivariate logistic regression were performed. RESULTS: Compared with diets with the highest concentrations of sodium, dry diets with the lowest concentrations of sodium, phosphorus, calcium, chloride, protein, magnesium, or potassium were linearly associated with increased risk of CaOx urolith formation. Significant nonlinear associations between increased occurrence of CaOx uroliths and urine acidifying potential and low moisture content were observed. Significant nonlinear associations between decreased occurrence of CaOx uroliths and carbohydrate and fiber contents were observed. A significant association between the occurrence of CaOx uroliths and dietary fat was not observed. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that dry diets formulated to contain high concentrations of protein, calcium, phosphorus, magnesium, sodium, potassium, and chloride may minimize formation of CaOx uroliths. In addition, comparison of risk and protective factors of various diet ingredients fed to dogs with CaOx uroliths suggests that although similar findings were observed in canned and dry formulations, in general, greater risk is associated with dry formulations. However, before these hypotheses about dietary modifications are adopted by food manufacturers, they must be investigated by use of appropriately designed clinical studies of dogs with CaOx urolithiasis.     

Hematologic Studies of Rinderpest-Infected Swine

Complete hematologic studies on swine inoculated with virulent rinderpest virus are reported. There was a 67 per cent reduction in total leukocyte counts on the third day postinoculation; counts returned to normal by the eighth day. The remainder of the hematologic values showed no significant changes. There was a febrile response at 3 days postinoculation; by the eighth day, temperature had returned to normal. Other clinical signs were less conspicuous and consisted of anorexia, stiff gait, and arched back occurring only on the third and fourth days after inoculation. The immunity of previously inoculated swine was challenged with virulent rinderpest virus 23 days after initial infection and no abnormal change in hemograms or body temperature resulted. The rinderpest-inoculated groups developed antibodies as demonstrated by the virus neutralization tests in rabbits.     

Matrix metalloproteinase activity in tumor, stromal tissue, and serum from cats with malignancies

Matrix metalloproteinases (MMPs) are enzymes that play key roles in angiogenesis, tumor invasion, and metastasis in a wide variety of species. The purpose of this study was to evaluate pro and active MMP 2 and 9 concentrations in tumor, normal stromal tissue, and serum from tumor-bearing cats. We hypothesized that serum concentrations of pro and active forms of MMPs 2 and 9 would be predictive of MMP concentrations in tumor tissue and that these MMP concentrations would correlate with the histopathologic grade of the malignancies. Pro and active forms of MMPs 2 and 9 were determined by gelatin zymography and subsequent computerized densitometry from tumor and nearby stromal tissue and serum from 49 cats with various malignancies. The serum concentrations of MMPs from these tumor-bearing cats were compared with serum concentrations of MMPs from 44 normal cats of similar age and gender. Measurable concentrations of MMPs 2 and 9 were found within tumor, stromal, and serum samples. Mean concentrations of total pro and active MMPs 2 and 9 within tumor tissue were significantly higher (P values <.0001, .0031, <.001, and .0064, respectively) when compared with stromal tissue from the same animals. Serum MMP concentrations from tumor-bearing cats were higher than those from normal cats. Poor correlation was found between serum MMP concentrations and tissue MMP concentrations of increasing histologic grades of malignancies.