Pharmacokinetics and pharmacodynamics of butorphanol in llamas after intravenous and intramuscular administration.

OBJECTIVE: To evaluate disposition of butorphanol after i.v. and i.m. administration, effects on physiologic variables, and analgesic efficacy after i.m. administration in llamas. DESIGN: Nonrandomized crossover study. ANIMALS: 6 healthy adult male llamas. PROCEDURE: Butorphanol (0.1 mg/kg [0.045 mg/lb] of body weight) was administered i.m. first and i.v. 1 month later. Blood samples were collected intermittently for 24 hours after administration. Plasma butorphanol versus time curves were subjected to pharmacokinetic analysis. Two months later, butorphanol (0.1 mg/kg) was administered i.m., and physiologic variables and analgesia were assessed. RESULTS: Extrapolated peak plasma concentrations after i.v. and i.m. administration were 94.8 +/- 53.1 and 34.3 +/- 11.6 ng/ml, respectively. Volume of distribution at steady state after i.v. administration was 0.822 +/- 0.329 L/kg per minute and systemic clearance was 0.050 +/- 0.014 L/kg per minute. Slope of the elimination phase was significantly different, and elimination half-life was significantly shorter after i.v. (15.9 +/- 9.1 minutes) versus i.m. (66.8 +/- 13.5 minutes) administration. Bioavailability was 110 +/- 49% after i.m. administration. Heart rate decreased and rectal temperature increased. Somatic analgesia was increased for various periods. Two llamas became transiently sedated, and 2 became transiently excited after butorphanol administration. CONCLUSIONS AND CLINICAL RELEVANCE: Although i.v. administration of butorphanol results in a short half-life that may limit its analgesic usefulness, the elimination half-life of butorphanol administered i.m. is likely to be clinically useful. The relationship among plasma butorphanol concentration, time, and analgesia differed with the somatic analgesia model; clinically useful analgesia may occur at lower plasma concentrations than those reported here.     

Footsteps from Insect Larvae Damage Leaf Surfaces and Initiate Rapid Responses

Plant resistance to insect herbivory involves gene expression in response to wounding and the detection of insect elicitors in oral secretions (Kessler and Baldwin, 2002, Ann. Rev. Plant/ Biol. 53: 299–328). However, crawling insect larvae stimulate the synthesis of 4-aminobutyrate within minutes and imprints of larval footsteps can be visualized within seconds through superoxide production or transient increases in chlorophyll fluorescence (Bown et al., 2002, Plant Physiol. 129: 1430–1434). Here cryo-scanning electron microscopy was used to demonstrate that larval feet, which are equipped with a perimeter row of hook-like crochets, damage leaf tissue and result in larval footprints. Staining for cell death shows that areas of wounding correspond to footsteps detected through increased chlorophyll fluorescence. Superoxide production in response to footsteps was inhibited by diphenyleneiodonium, an inhibitor of the plasma membrane NADPH oxidase enzyme. Inhibition of superoxide production, however, did not eliminate the detection of cell death. The results demonstrate that larval footsteps damage leaf tissue, and initiate rapid local responses which are not dependent on herbivory or oral secretions. It is proposed that superoxide production at the wound site prevents opportunistic pathogen infection.     

Long-term outcome of gonadectomy performed at an early age or traditional age in dogs

OBJECTIVE: To determine long-term results and complications of gonadectomy performed at an early age (prepubertal) or at the traditional age in dogs. DESIGN: Cohort study. ANIMALS: 269 dogs from animal shelters. PROCEDURE: Dogs that underwent gonadectomy were allotted to 2 groups on the basis of estimated age at surgery (traditional age, > or =24 weeks old; prepubertal, < 24 weeks old). Adoptive owner information was obtained from shelter records, and telephone interviews were conducted with owners to determine physical or behavioral problems observed in the dogs since adoption. Follow-up information was obtained from attending veterinarians for dogs with complex problems or when owners were uncertain regarding the exact nature of their dog's problem. RESULTS: Prepubertal gonadectomy did not result in an increased incidence of behavioral problems or problems associated with any body system, compared with traditional-age gonadectomy, during a median follow-up period of 48 months after gonadectomy. Rate of retention in the original adoptive household was the same for dogs that underwent prepubertal gonadectomy as those that underwent traditional-age gonadectomy. Infectious diseases, however, were more common in dogs that underwent prepubertal gonadectomy. CONCLUSIONS AND CLINICAL IMPLICATIONS: With the exception of infectious diseases, prepubertal gonadectomy may be safely performed in dogs without concern for increased incidence of physical or behavioral problems during at least a 4-year period after gonadectomy.     

Detection of portal and systemic bacteremia in dogs with severe induced hepatic disease and multiple portosystemic shunts

OBJECTIVE: To determine existence of portal and systemic bacteremia in dogs with induced severe hepatic disease, compared with clinically normal dogs, before and after vena caval banding. ANIMALS: 6 control dogs and 10 dogs with induced severe hepatic disease and multiple portosystemic shunts (PSS). PROCEDURE: Dogs of the diseased group were given dimethylnitrosamine (2 mg/kg of body weight, PO) twice weekly until multiple PSS developed. Surgery was performed on dogs of both groups, and blood for baseline aerobic and anaerobic bacterial culture was collected from catheters placed in the portal and hepatic veins and caudal vena cava. All dogs underwent vena caval banding, and blood for aerobic and anaerobic bacterial culture was collected from the portal and hepatic venous catheters at 120, 240, and 360 minutes after banding. RESULTS: Compared with control dogs (16% gram-positive and 84% gram-negative bacteria), diseased dogs had significantly higher percentage of gram-positive bacteria (42% of positive culture results, P < or = 0.01) and significantly lower percentage of gram-negative bacteria (58% of positive culture results, P < or = 0.01) isolated. Pseudomonas aeruginosa was isolated most frequently from dogs of both groups; more than 1 organism was isolated from 5 dogs of each group. Antimicrobial susceptibility included that to aminoglycosides (particularly amikacin), fluorinated quinolones, and imipenem. CONCLUSION: Portal and systemic, predominantly gram-negative, bacteremia is present in catheterized, clinically normal dogs and dogs with dimethylnitrosamine-induced hepatic disease and multiple PSS.     

Prevalence of cpb2, encoding beta2 toxin,in Clostridium perfringens field isolates: correlation of genotype with phenotype

Beta2 toxin, encoded by the cpb2 gene, has been implicated in the pathogenesis of porcine, equine and bovine enteritis by type A Clostridium perfringens. By incorporating primers to cpb2 into a multiplex genotyping PCR, we screened 3270 field isolates of C. perfringens. Of these, 37.2% were PCR positive for the cpb2 gene. The majority of isolates from cases of porcine enteritis were positive for cpb2 (>85%), and this was even more true for C. perfringens isolated from cases of porcine neonatal enteritis (91.8%). In contrast, isolates from normal pigs only contained cpb2 in 11.1% of cases. The correlation between enteritis in other animal species and the presence of cpb2 was not so strong. cpb2 was found in 21.4% of C. perfringens isolates from cattle with enteritis, and in 47.3% of isolates from calves with enteritis or abomastitis. The prevalence of cpb2 varied with genotype, with type A isolates being positive for this gene in 35.1% of cases. Furthermore, enterotoxigenic type D or type E strains almost always carried cpb2. We cloned a 6xHIS-tagged beta2 (HIS-beta2) and used this protein to raise antiserum against beta2. Culture supernatants from 68 cpb2-positive and 13 cpb2-negative strains were tested for the presence of beta2 by Western blotting. In cpb2-positive isolates of porcine origin, beta2 was almost always detected (96.9%). However, in cpb2-positive isolates from other animal species, only 50.0% expressed beta2 protein. The high rate of cpb2-positivity among strains from neonatal pigs with enteritis and the high correlation of genotype with phenotype, supports the contention that beta2 toxin plays a role in the pathogenesis of these infections. However, it may be important to consider the use of an additional method for the detection of beta2 toxin in non-porcine cpb2-positive isolates when making claims about the role of beta2 in enteritis in non-porcine species.     

Plasma pharmacokinetics of selamectin after a single topical administration in the American bullfrog (Rana catesbeiana).

Parasitism is common in wild and captive amphibians; however, pharmacologic data are lacking for anthelmintic drugs. This study was developed to determine the plasma pharmacokinetics of selamectin after topical administration in bullfrogs. Thirty-two adult American bullfrogs (Rana catesbeiana) were randomly assigned into eight groups of four with each group representing a different collection time point. Seven groups received selamectin (6 mg/ kg) topically and the remaining group served as the untreated control group. One group of frogs was euthanized and blood samples immediately collected on days 0 (control), 1, 5, 10, 15, 20, 25, and 30. Plasma was analyzed for selamectin using high performance liquid chromatography with fluorescence detection. Individual samples were analyzed, then data were reported as the mean of the four frogs at each time point. A histologic evaluation of the lung, liver, kidney, and skin tissues was performed and none of the frogs showed histologic evidence of toxicity due to selamectin administration. The mean peak plasma concentration was 162.5 +/- 42.3 ng/ml, area under the curve was 2,856 ng day/ml, mean residence time was 12.2 days, and disappearance half-life was 1.87 days. Based on the plasma pharmacokinetics, bullfrogs appear to absorb selamectin very efficiently, concentrations reach high levels in the plasma, and there were no apparent histologic effects from single dose administration.