Studies on the Animal Metabolism of Phenoxyacetic Herbicides

Gel filtration on Sephadex was applied to the study of plasma protein binding af 2,4-dichlorophenoxyacetic acid (2,4-D). Equilibrated with horse plasma and eluted with buffer pH 7.4, 2,4-D was recovered to 2 % in the plasma protein fraction (K_D 0), free 2,4-D being eluted at a K_D value of 2.2. When 50 % plasma in buffer was used as the eluant the mobility of 2,4-D increased considerably (K_D decreasing to 0.95), thus confirming the existence of a 2,4-D-protein interaction.Hydrolysis experiments in conjunction with thin-layer chromatography revealed no conjugation of 2,4-D in plasma of pigs and rats given 2,4-D amine orally and only slight conjugation, not exceeding 20 %, in urine of pigs, given 2,4-D amine orally.2,4-D butyl ester administered orally to pigs and rats was shown to be rapidly hydrolyzed to 2,4-D acid, only trace amounts of ester being detectable in body fluids and tissues.     

In vitro force mapping of normal canine humeroradial and humeroulnar joints

OBJECTIVE: To determine the distribution of force between the articular surfaces of the humerus and radius and between the humerus and ulna in normal canine forelimbs. SAMPLE POPULATION: 12 cadaveric canine right forelimbs. PROCEDURE: Transarticular force maps were created by placing a tactile array pressure sensor into the elbow joint cavity and loading cadaveric forelimbs in a materials testing system. Mean joint forces were determined at loads of 50, 100, 150, and 200 N. RESULTS: All tests produced 2 distinct areas of high load that corresponded with the proximal articular surfaces of the radius and ulna. Mean forces for the radial proximal articular surface were slightly but significantly greater than for the ulna, averaging 51% to 52% of total force for all applied loads. CONCLUSIONS AND CLINICAL RELEVANCE: The proximal articular surface of the ulna contributes substantially to load transfer through the canine elbow joint. Abnormalities, which increase this load, might contribute to canine elbow joint dysplasia, specifically fragmentation of the medial coronoid process and osteochondritis dissecans of the medial aspect of the humeral condyle. In the treatment of these conditions, the normal force distribution within the canine elbow joint should be taken into consideration.     

Dogs as carriers of the emerging pathogen Arcobacter

Dogs and cats living in a household have previously been identified as a risk factor for human infection with Campylobacter and Helicobacter. In this study, carried out between July 2006 to September 2007, feces and oral swabs from 267 dogs and 61 cats were examined for the presence of the emerging pathogen Arcobacter. Isolates, obtained by an Arcobacter selective isolation procedure, were identified with an Arcobacter species-specific multiplex-PCR and characterized by modified enterobacterial repetitive intergenic concensus PCR. No arcobacters were isolated from cats. Five dogs excreted arcobacters in the feces and two other dogs carried arcobacters in the mouth. In the follow-up, one dog excreted the same Arcobacter butzleri strain for at least 1 week. Six dogs carried each an unique A. cryaerophilus strain although three of them lived in the same family. Therefore, beside the consumption of food and water, contact with dogs is another potential source of Arcobacter infection.     

Antioxidant 1 copper chaperone gene expression and copper levels in dog osteosarcoma patients

Twenty-four dogs with OS underwent limb amputation. Serum, OS tumour, and normal bone were harvested at time of surgery. RNA was extracted and gene expression was performed using quantitative polymerase chain reaction (qPCR). Tissue and blood copper concentrations were also determined with spectrophotometry. Compared to bone, tumour samples had significantly higher expressions of antioxidant 1 copper chaperone (ATOX1, p = .0003). OS tumour copper levels were significantly higher than that of serum (p < .010) and bone (p = .038). Similar to our previous observations in mouse and human OS, dog OS demonstrates overexpression of genes that regulate copper metabolism (ATOX1), and subsequent copper levels. Dogs with OS may provide a robust comparative oncology platform for the further study of these factors, as well as potential pharmacologic interventions.     

Toxicological Studies of Phenoxyacetic Herbicides in Animals

The main purpose of the present work was to study the long-term effects of 2,4-dichlorophenoxyacetic acid (2,4-D) in swine, rats and chickens.In preliminary short-term experiments with calves and pigs, definite although reversible toxic effects were seen after single doses of 200 and 100 mg/kg, respectively. Rats and chickens seemed to tolerate 100 and 300 mg/kg, respectively, without ill-effects. On repeated administration daily doses of 50 mg/kg could be toxic to pigs, whereas chickens tolerated 300 mg/kg/day for several weeks without visible effects. Symptoms of acute poisoning in calves were dysphagia, anorexia, tympanites and muscular weakness. Anorexia was apparent also in acutely or subacutely poisoned pigs together with locomotory disturbances, transient diarrhoea and, in severe cases, vomiting, muscular weakness and general depression. In all animals showing symptoms of poisoning a reduced disappearance rate of 2,4-D from plasma was apparent. On autopsy the pigs showed signs of gastro-intestinal irritation and pneumonia and renal degeneration. In the rats and chickens no gross pathological changes were seen.In the long-term studies 5 young pigs were fed 2,4-D (500 p.p.m.) for up to 12 months. Main clinical signs were growth depression, locomotory disturbances, anaemia and albuminuria. Morphological changes included moderate hepatic and renal degeneration. In another experiment 2,4-D was fed to a pregnant sow throughout the gestation period and for 6 further weeks. The sow exhibited no characteristic signs, and on autopsy no changes attributable to 2,4-D were noted. The newborn piglets, however, were underdeveloped and apathetic. Ten out of 15 died within 24 hours. On continued feeding of 2,4-D to the survivors until 7–8 months of age the main effects were a marked growth depression, persistent anaemia and moderate degenerative changes of liver and kidneys.Pregnant rats were given 2,4-D (1000 p.p.m.) in the drinking water during the gestation and further for up to 10 months. The administration of 2,4-D was continued to the second generation rats for up to 2 years. Except for a retarded growth and an increased mortality in the second generation no unequivocal clinical or morphological changes were seen.In chickens continued administration of 2,4-D (500 p.p.m. in the feed or 1000 p.p.m. in the drinking water) caused a reduced eggproduction and pronounced kidney enlargement due to epithelial proliferations, this latter lesion appearing only when very young chicks were used as experimental animals.The experimental results indicate the chronic toxicity of 2,4-D for the species examined to be moderate. Apart from the nephrotoxicity demonstrated in chicks the long-term effects were non-specific. Of particular interest, however, are the high mortality in the newborn piglets and the reduced egg production in the chickens as indications of a possible interference with reproduction.     

Evaluation of the role of mallard ducks as vectors of porcine reproductive and respiratory syndrome virus

To assess the transmission of porcine reproductive and respiratory syndrome virus (PRRSV) from pigs to mallard ducks, 10 adult (one-year-old) female mallard ducks were housed with pigs infected experimentally with PRRSV, and allowed to be in close contact with them for 21 days. To evaluate the transmission of PRRSV from mallard ducks to pigs, two adult ducks were inoculated orally with PRRSV (total dose 10(6.0) TCID50) and allowed to drink PRRsv-infected water; 24 hours later, two four-week-old PRRsv-naive sentinel pigs were housed in pens below the cages housing the ducks for 14 days. In both experiments, cloacal and faecal samples were collected three times a week from the ducks and tested by PCR, virus isolation and a pig bioassay. Blood samples from the pigs were tested by ELISA, PCR and virus isolation. Sera from the ducks were tested by serum neutralisation. The ducks were examined postmortem and selected tissues were tested by PCR, virus isolation, histopathology and pig bioassay. In both experiments all the cloacal swabs, faecal samples, tissues and sera from the ducks were negative by all the tests. The sera from the pigs in the first experiment were PCR positive at three, seven, 14 and 21 days after infection and ELISA positive at 14 and 21 days. Sera from the pigs in the second experiment were negative by all the tests. The virus was isolated from the oral inoculum and the drinking water provided for the ducks in the second experiment. Under the conditions of this study, it was not possible to demonstrate the transmission of PRRSV either from the pigs to the ducks or from the ducks to the pigs.     

Retrospective analysis of canine miniature total hip prostheses

OBJECTIVE: To determine the practicality and clinical outcome of miniature total hip replacement (THR) in dogs. STUDY DESIGN: Retrospective study. Sample Population- Seventeen client-owned dogs that had miniature THR. METHODS: Patient data surveyed included signalment, body weight, diagnosis, implant size, surgical technique, and intraoperative and postoperative complications. Radiographic evaluation included angle of lateral opening of the acetabular component, implant positioning, cement mantle quality, and femoral displacement measurement and ratio. Client questionnaire and orthopedic examination were used to obtain long-term follow-up information. RESULTS: Miniature THR was performed to address hip dysplasia and secondary osteoarthritis. In 1 dog, a staged bilateral procedure was performed. Mean body weight was 19 kg (range, 12 to 25 kg). Penetration or fissure of the femoral cortex was the most common intraoperative complication and occurred in 3 dogs. In 3 dogs, there was excessive coxofemoral laxity after reduction of the prosthesis. This instability was addressed specifically in 2 dogs by capsulorrhaphy or capsular prosthesis. Postoperative convalescent complications (craniodorsal luxation, 2 dogs; acetabular cup displacement, 1 dog) were related to surgical errors. Aseptic loosening of the femoral implant was diagnosed in 1 dog at 18 months. Mean follow-up time was 17 months (range, 4 to 42 months). Fifteen of 18 (83%) miniature THRs had good or excellent outcomes. CONCLUSIONS: Miniature THR should be considered a satisfactory alternative to femoral head and neck ostectomy in medium-size dogs affected by hip dysplasia and secondary osteoarthritis. The population of medium-size dogs that might derive more benefit from THR than FHO has yet to be defined. CLINICAL RELEVANCE: Miniature THR is a viable treatment option in medium-size dogs with hip dysplasia.     

Live Brucella abortus rough vaccine strain RB51 stimulates enhanced innate immune response in vitro compared to rough vaccine strain RB51SOD and virulent smooth strain 2308 in murine bone marrow-derived dendritic cells

Brucella spp. are Gram-negative, coccobacillary, facultative intracellular pathogens. B. abortus strain 2308 is a pathogenic strain affecting cattle and humans. Rough B. abortus strain RB51, which lacks the O-side chain of lipopolysaccharide (LPS), is the live attenuated USDA approved vaccine for cattle in the United States. Strain RB51SOD, which overexpresses Cu–Zn superoxide dismutase (SOD), has been shown to confer better protection than strain RB51 in a murine model. Protection against brucellosis is mediated by a strong CD4+ Th₁ and CD8+ Tc₁ adaptive immune response. In order to stimulate a robust adaptive response, a solid innate immune response, including that mediated by dendritic cells, is essential. As dendritic cells (DCs) are highly susceptible to Brucella infection, it is possible that pathogenic strains could limit the innate and thereby adaptive immune response. By contrast, vaccine strains could limit or bolster the innate and subsequent adaptive immune response. Identifying how Brucella vaccines stimulate innate and adaptive immunity is critical for enhancing vaccine efficacy. The ability of rough vaccine strains RB51 and RB51SOD to stimulate DC function has not been characterized. We report that live rough vaccine strain RB51 induced significantly better (p ≤ 0.05) DC maturation and function compared to either strain RB51SOD or smooth virulent strain 2308, based on costimulatory marker expression and cytokine production.