Development and validation of the maximal electro-shock seizure model in dogs

The development and validation of the maximal electro-shock (MES) model using phenobarbital (Pb) as the positive control is described. This approach builds on previous work in rodent model systems, and has been adapted to dogs as a tool for pharmaceutical dose selection. Dogs, like rodents, exhibit generalized convulsions which manifest as progressive clinical signs in a dose (electrical current) dependent fashion. At the limit (300 mA, 200 msec) animals underwent clonic-tonic convulsions consistent with complete generalized (Grand Mal) seizures with a grade 3 clinical score (CS) and a menace response time of 98.5 +/- 24.4 sec (n = 8). Pretreatment of animals with Pb at 3, 10, and 30 mg/kg, in a 4-by-4 complete block crossover design (Latin-Square), resulted in a dose-dependant reduction in CS and menace response time. Estimates of plasma Pb concentration taken prior to MES induction showed a similar dose-dependent reduction in CS and menace response time with concentration. Using a cumulative logistic regression model, a predicted 50% probability of a CS = 1 was approximately 11.4 mg/kg. In addition, plasma Pb concentrations predicted a 50% probability of a CS = 1 occurs at plasma Pb concentration of approximately 16.0 mug/mL. Combined these data suggest that MES is a useful model for evaluating generalized convulsions in canines and may provide a tool for dose selection of novel pharmaceutical compounds.     

Spatial analysis of the exposure of dogs in rural north-coastal California to vectorborne pathogens

Between 0 and 50 per cent of the dogs in eight rural villages in far northern California with a high risk of tickborne diseases were seropositive for Anaplasma phagocytophilum and Bartonella vinsonii subspecies berkhoffii, and between 0 and 10 per cent were seropositive for Borrelia burgdorferi. The odds ratio for the co-exposure of individual dogs to B vinsonii berkhoffii and A phagocytophilum was 18.2. None of the diseases was associated with the sex of the dogs, whether they slept out of doors, or whether tick-preventive measures were taken. When the villages were assessed for landscape risk factors, a particularly high seroprevalence for B vinsonii berkhoffii and A phagocytophilum was observed in a village at a relatively high altitude and greater distance from the Pacific coast, and montane hardwood conifer woodland was most associated with a high seroprevalence for these two pathogens.     

Pharmacokinetics of cefquinome in healthy and Pasteurella multocida‐infected rabbits

The pharmacokinetics of cefquinome were studied in healthy and Pasteurella multocida‐infected rabbits after a single intramuscular (IM) injection at 2 mg/kg of its sulfate salt. Twelve female New Zealand white rabbits (2.0–2.5 kg) were used; six of them served as controls, and the other six had been infected with P. multocida; the experiments were conducted 1–2 days after nasal inoculation of P. multocida when rabbits showed the signs of respiratory infection. Plasma concentrations of cefquinome were determined using high‐performance liquid chromatography. The values of elimination half‐life, area under the curve, area under the first moment curve, and mean residence time were significantly lower in infected rabbits (0.48 hr, 4.54 hr*μg/ml, 3.63 hr* hr*μg/ml and 0.8 hr, respectively) than healthy rabbits (0.72 hr, 9.11 hr*μg/ml, 9.85 hr* hr*μg/ml and 1.1 hr, respectively), whereas total body clearance was significantly higher in infected than healthy rabbits. Therefore, P. multocida infection caused significant changes in some of the pharmacokinetic parameters of cefquinome in rabbits. These pharmacokinetic changes may affect dose regimen when used in P. multocida‐infected rabbits.     

Endocannabinoids as endometrial inflammatory markers in lactating Holstein cows

The objective of this study was to consider endocannabinoid system as inflammatory markers in bovine endometrium to better understand the role of this system in regulating many of the functions that are related to inflammatory condition. At day 26 post‐partum, fourteen cows were divided into two groups depending on the inflammatory condition: 1‐ subclinical endometritis (n = 7, with purulent or mucopurulent uterine discharge detectable in the vagina) and 2‐ healthy (n = 7, No (muco)) purulent discharge. Blood samples were collected at 26 and 30 days relative to calving to determine plasma tumour necrosis factor (TNF) and lipopolysaccharide‐binding protein (LBP) concentrations; moreover, uterine biopsy was carried out on day 26 post‐partum to measure mRNA abundance of TNF, interleukin‐1B (IL1B), interleukin‐6 (IL‐6), C‐X‐C motif chemokine ligand 8 (CXCL8), endocannabinoid receptor (CNR2), N‐acyl phosphatidylethanolamine phospholipase D (NAPEPLD), fatty acid amide hydrolase (FAAH), N‐acylethanolamine acid amidase (NAAA) and monoglyceride lipase (MGLL) by real‐time PCR. Results showed mean plasma concentrations of TNF and LBP were lower in healthy cows compared to subclinical endometritis cows (p < .05). Relative mRNA expression for NAAA and FAAH was decreased (p < .05), and relative mRNA expression for CNR2 and NAPEPLD increased in cows with subclinical endometritis compared to healthy cows. In conclusion, relative mRNA expression of TNF, IL1B and CXCL8 and plasma concentration of LBP increased during inflammatory condition along with decreased endocannabinoids hydrolyzing enzyme (NAAA and FAAH), increased enzymes that synthesize endocannabinoids (NAPEPLD) and relative gene expression of the endocannabinoid receptor; together, these contribute to increased endocannabinoids levels during inflammation. Overall, we provide evidence that endocannabinoid system is altered in endometrium tissue during inflammation through increased mRNA expression of CNR2 and synthesis enzyme and decreased mRNA expression of hydrolyzing enzymes interfere with pro‐cytokine production and signalling, which may interfere with the onset and progression of inflammation.     

Comparison of inhibition of polymerisation of mammalian tubulin and helminth ovicidal activity by benzimidazole carbamates

The correlation between the inhibition of hatching of Haemonchus contortus eggs and inhibition of mammalian tubulin polymerisation by benzimidazole carbamates has been investigated. The hatching process was observed to be independent of the biomass (eggs plus debris) over a 6-fold range and the early (E1-E3) stages of egg development, but was dependent on the concentration of co-solvent (DMSO) and time of incubation. Benzimidazole carbamates with strong inhibitory activity against mammalian tubulin were potent inhibitors of egg hatch, while non-inhibitors failed to prevent hatching. It is postulated that the primary mode of action of these drugs on nematode eggs is the inhibition of microtubule-dependent processes within the developing egg. The implications and limitations of this correlation are discussed.     

Clinical pathologic alterations in horses during a water deprivation test

A 72-hour water deprivation test was performed in 12 horses to determine clinical pathologic changes. Reference values for electrolyte (X) clearance, expressed as a percentage of creatinine clearance (CLCR; %CLCRX), were also determined. A comparison was made between urine concentration measurement techniques. Results of %CLCRX determination in 12 horses before water deprivation were 0.034 +/- 0.095 %CLCRNa, 42.4 +/- 9.8 %CLCRK, 0.352 +/- 0.190 %CLCRCl, and 0.710 +/- 0.250 %CLCRP. During water deprivation, there was individual variation for electrolyte clearances, but Na excretion increased significantly (P less than 0.01) at 24 and 48 hours. After 48 hours' water deprivation, %CLCRNa decreased significantly, but was still greater than the initial clearance. Plasma protein was a better indicator of water deprivation (dehydration) in the horse than was PCV. Electrolyte concentrations in serum and urine were determined. Little significant (P less than 0.01) change in acid-base values was noticed after 72 hours' water deprivation. Urine osmolality (as determined by osmometry) was compared with sp gr (determined by refractometry) in determining urine concentration. Initially, sp gr correlated well with urine osmolality determinations, but this correlation decreased after 48 hours.     

In Vitro Loss of Tensile Strength and Elasticity of Five Absorbable Suture Materials in Sterile and Infected Canine Urine

The loss of breaking strength and elasticity of five absorbable suture materials (polydioxanone [PDS-II], polyglycolic acid [PGA], polyglactin 910 [PG-910], polyglyconate [GTMC], and chromic gut) after in vitro incubation in sterile, Escherichia coli- and Proteus mirab/tfs-inoculated canine urine was studied. Biomechanical testing, in a controlled environment, was performed during the 28-day study period. Polydioxanone and chromic gut retained greater than 90% of their original strengths after 28 days of incubation in sterile urine and 87% of original strengths in E. co//-inoculated urine. Polyglyconate retained 24% and 18% of original strength, respectively, after incubation in sterile and E. co/i-inoculated urine for 28 days. Polyglycolic acid and PG-910 retained less than 30% of original strength in sterile urine and only 7% in E. co/i-inoculated urine after 21 days of incubation. In P. m/rabi/is-inoculated urine, loss of tensile strength and elongation was significant for all suture materials. Polyglycolic acid and PG-910 lost all strength after 24 hours of incubation. Polydioxanone lost all strength after 7 days of incubation, whereas GTMC retained 19% at day 7. Chromic gut retained 78% at day 7 and 16% after 21 days of incubation, however, the absence of normal phagocytic destruction of chromic gut in this in vitro study may have artificially elevated these values. In sterile urine with chemically modified pH, loss of strength and elongation was greater in alkaline urine than in neutral or acidic urine for all types of suture materials.     

Q fever (Coxiella burnetii) investigations in dairy cattle: persistence of antibodies after vaccination.

The immune response and persistence of antibodies were investigated in dairy cattle vaccinated with formalin-inactivated phase (ph) I Coxiella burnetii vaccine agglutinating antibody geometric mean titer (GMT) of 193.2 at 1 month after vaccination compared to a GMT of 2.0 for nonvaccinated calves. The agglutinating antibodies gradually decreased in vaccinated cattle, but the GMT remained approximately 4 times higher than that for the nonvaccinated group for at least 20 months. Results of serotests at 2 months after revaccination indicated a rapid increase in the GMT to 177.0 with agglutinating titers between 1:64 and 1:512.