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.     

Characterizing biological variability in livestock blood cholinesterase activity for biomonitoring organophosphate nerve agent exposure.

A biomonitoring protocol, using blood cholinesterase (ChE) activity in livestock as a monitor of potential organophosphate nerve agent exposure during the planned destruction of US unitary chemical warfare agent stockpiles, is described. The experimental design included analysis of blood ChE activity in individual healthy sheep, horses, and dairy and beef cattle during a 10- to 12-month period. Castrated and sexually intact males, pregnant and lactating females, and adult and immature animals were examined through at least one reproductive cycle. The same animals were used throughout the period of observation and were not exposed to ChE-inhibiting organophosphate or carbamate compounds. A framework for an effective biomonitoring protocol within a monitoring area includes establishing individual baseline blood ChE activity for a sentinel group of 6 animals on the bases of blood samples collected over a 6-month period, monthly collection of blood samples for ChE-activity determination during monitoring, and selection of adult animals as sentinels. Exposure to ChE-inhibiting compounds would be suspected when all blood ChE activity of all animals within the sentinel group are decreased greater than 20% from their own baseline value. Sentinel species selection is primarily a logistical and operational concern; however, sheep appear to be the species of choice because within-individual baseline ChE activity and among age and gender group ChE activity in sheep had the least variability, compared with data from other species. This protocol provides an effective and efficient means for detecting abnormal depressions in blood ChE activity in livestock and can serve as a valuable indicator of the extent of actual plume movement and/or deposition in the event of organophosphate nerve agent release.     

AN INTRATHORACIC MALIGNANT PERIPHERAL NERVE SHEATH TUMOR IN A DOG

A 7-year-old, neutered male Labrador Retriever presented for a persistent, productive cough and regurgitation. Radiography, ultrasonography, and computed tomography confirmed a large, smoothly marginated intrathoracic mass causing tracheal compression. The mass was removed via a thoracotomy, and a malignant peripheral nerve sheath tumor, most likely originating from the ventral spinal nerve roots, was confirmed using immunohistochemistry.     

Transport of serum IgA into bile of sheep infected with Fasciola hepatica

Sheep infected with Fasciola hepatica were studied for their ability to transport intravenously injected radiolabelled IgA from serum to bile. The results show that there was an apparent reduction in the selectivity of transport of IgA into bile in infected animals compared with uninfected controls. However, in infected animals the biliary flow rate was approximately twice that of uninfected animals, and the total amount of radiolabelled IgA transported was similar irrespective of infection status. The possible relevance of the elevated biliary flow rate is discussed with respect to the pharmacokinetics of drugs used for the chemotherapy of helminth infections in sheep.     

Macrophage clearance of 125I-labelled polyvinyl pyrrolidone in the horse: effect of ovarian steroids and persistent endometritis

The rate of clearance of 125I-labelled polyvinyl pyrrolidone (PVP) from blood was measured in mares as an indicator of macrophage function. In three out of four cycling mares, PVP clearance was slower during oestrus than dioestrus. Similarly, administration of oestrogen to four ovariectomised mares tended to depress PVP clearance compared with clearance from the same mares before they received oestrogen. However, the effect of oestrogen was not statistically significant. Mares susceptible to persistent endometritis had rates of PVP clearance which were similar to those of genitally normal mares.     

Cystic bone lesions in related Old English Sheepdogs

At 6 months of age, an Old English Sheepdog with swollen and painful distal radial/ulnar metaphyses was found to have multiple cystic lesions in left and right radius and ulna. Cystic bone lesions were also detected radio-graphically in two clinically normal littermates and in the sire and dam of the litter. Radiographic changes of nutritional secondary hyperparathyroidism were found in the three affected pups and in two other individuals from the litter of eight.
The cystic lesions in one pup were drained surgically and the cyst wall curetted, while the other two pups were not treated. The lesions in all three pups gradually resolved and had almost completely disappeared by 10 months of age.     

Atlantoaxial subluxation and absence of transverse ligament of the atlas in a dog

Absence of the transverse ligament of the atlas was diagnosed at necropsy in an 8-month-old Shih Tzu with radiographic signs of atlantoaxial subluxation. Symmetric ataxia, tetraparesis, and signs of pain in the vertebral canal suggested a lesion in the cervical portion of the spinal cord. Necropsy revealed absence of the transverse ligament of the atlas and malformation of dens and atlas. In addition, the alar ligaments were distinct and thick, and the atlanto-occipital and atlantoaxial joint capsules were markedly thicker than normal. Histologic examination revealed focal compressive myelopathy of the spinal cord at the level of the atlantoaxial joint.