Doramectin concentration profiles in the gastrointestinal tract of topically-treated calves: Influence of animal licking restriction

Endectocide compounds are extensively used for broad-spectrum parasite control and their topical administration to cattle is widespread in clinical practice. Pour-on formulations of moxidectin, ivermectin, eprinomectin and doramectin (DRM) are marketed internationally for use in cattle. However, variability in antiparasitic efficacy and pharmacokinetic profiles has been observed. Although the tissue distribution pattern for different endectocide molecules given subcutaneously to cattle has been described, only limited information on drug concentration profiles in tissues of parasite location after topical treatment is available. Understanding the plasma and target tissue kinetics for topically-administered endectocide compounds is relevant to optimise their therapeutic potential. The current work was designed to measure the plasma and gastrointestinal (GI) concentration profiles of DRM following its pour-on administration to calves. The influence of natural licking behaviour of cattle on DRM concentration in mucosal tissue and luminal content of different GI sections was evaluated. The trial was conducted in two experimental phases. In Phase I, the DRM plasma kinetics was comparatively characterised in free-licking and in 2-day licking-restricted (non-licking) calves. The pattern of distribution of topical DRM to mucosal and luminal contents from abomasum, duodenum, ileum, caecum and spiral colon was assessed in free-licking and non-licking calves restricted over 10 days post-administration (Phase II). The prevention of licking caused marked changes on the plasma and GI kinetics of DRM administered pour-on. In 2-day licking restricted calves, DRM systemic availability was significantly lower (29%) than in free licking animals during the first 9 days post-treatment. Following a 10-day long licking restriction period, DRM concentrations profiles in both mucosal tissue and luminal contents of the GI tract were markedly higher in animals allowed to lick freely. This enhancement in drug concentrations in free-licking compared to non-licking calves, was particularly pronounced in the abomasal (38-fold higher) and duodenal (six-fold higher) luminal content. As shown earlier for ivermectin, licking behaviour may facilitate the oral ingestion of topically-administered DRM in cattle. This would be consistent with the marked lower drug concentration profiles measured in the bloodstream and GI tract of the animals prevented from licking. The work reported here provides relevant information on the pattern of DRM distribution to the GI tract after pour-on treatment, and contributes to understand the variability observed in the antiparasitic persistence of topically-administered endectocides in cattle. The implications of natural licking in topical treatments are required to be seriously assessed to achieve optimal parasite control and to design parasitological and pharmacological studies within the drug approval process.     

Isolation of Cokeromyces recurvatus, initially misidentified as Coccidioides immitis, from peritoneal fluid in a cat with jejunal perforation.

Cokeromyces recurvatus, a zygomycete, was isolated by fungal culture from the peritoneal fluid of a cat with jejunal perforation secondary to intestinal lymphosarcoma. This organism has not been recovered previously from a veterinary patient. The tissue form of C. recurvatus is morphologically similar to those of Coccidioides immitis and Paracoccidioides brasiliensis and may be misdiagnosed as 1 of these organisms on the basis of cytologic or histopathologic specimens, particularly in geographic regions where these organisms are not endemic.     

Toxic shock syndrome in a horse with Staphylococcus aureus pneumonia

A 3-year-old Thoroughbred gelding was examined because of clinical signs of pneumonia and shock. Mucous membrane petechiation and ventral edema were observed and considered to be a result of vasculitis. Epidermal necrosis developed on the distal portions of the limbs. The horse had a persistent high fever that was unresponsive to nonsteroidal anti-inflammatory treatment, and Staphylococcus aureus was isolated from a nasal swab specimen and 2 transtracheal wash fluid samples. Antimicrobial, anti-inflammatory, and supportive treatment resulted in clinical improvement. However, resolution of the pulmonary infection required long-term (42 days) antimicrobial administration. Staphylococcus aureus strains isolated from this horse were positive for the toxic shock syndrome toxin-1 gene and were shown to produce toxic shock syndrome toxin-1, the causative factor in toxic shock syndrome in humans. The horse's clinical signs were attributed to toxic shock syndrome secondary to pulmonary S. aureus infection.     

Field trials of an immunization procedure against hemorrhagic enteritis of turkeys

The efficacy of oral vaccination for hemorrhagic enteritis of turkeys was assessed by comparing flocks raised on the same premises, under the same management, with and without vaccination. The immunizing virus, a strain of marble spleen disease virus of pheasants, was administered via the drinking water. Vaccinated and unvaccinated turkeys differed significantly in feed conversion rates and spleen weights after challenge.     

Influence of ambient temperature on prolactin concentrations in serum of Holstein and Brahman x Hereford heifers

Four Holstein and four Brahman x Hereford heifers about 8 mo of age were used in a study to determine whether breed influences the effects of ambient temperature on concentrations' of prolactin in serum. Two heifers of each breed were stanchioned in each of two environmental chambers at 21 C for 7 d, after which chamber temperatures were changed to 7 or 31 C during 6 h. After 5 d at 7, 21 or 31 C, heifers were injected with 60 micrograms thyrotropin-releasing hormone (TRH). A switch-back design was used and each heifer was exposed to all treatments. Concentrations of prolactin in serum of heifers during exposure to 7, 21 or 31 C for 5 d were related to ambient temperature (9.0, 20.9 and 29.5 ng/ml, respectively; P less than .001), but the response was not influenced by breed. Heifers of both breeds responded similarly to treatment with TRH, and prolactin in serum increased (P less than .001) within 5 min from 7.0 +/- 3.2 to 45.7 +/- 8.2 ng/ml in heifers at 7 C, from 13.1 +/- 1.6 to 97.2 +/- 9.6 ng/ml in heifers at 21 C and from 18.2 +/- 3.5 to 96.2 +/- 11.3 ng/ml in heifers at 31 C. We conclude that concentrations of prolactin in serum of heifers are positively associated with ambient temperature and that the effects of temperature on basal and TRH-stimulated concentrations of prolactin do not differ significantly between Holstein and Brahman x Hereford heifers. Thus, differences in tolerance to heat were not related to differences in prolactin secretion.     

EFFECT OF STRESS ON STEROID HORMONE LEVELS IN RACEHORSES

SUMMARY Cortisol and testosterone were measured by radioimmunoassay in plasma samples from race horses. None of 6 stressed male horses had Iow cortisol levels but testosterone levels (0.81 ± 0.15 nmol/l) were significantly lower than in healthy horses (1.86 ± 0.31 nmol/l). The conclusion was made that adrenocortical insufficiency is not a common association of stress in race horses. The reduction in testosterone levels is probably a nonspecific response similar to that seen in other species.     

The pharmacokinetics and tissue levels of polymyxin B, colistin and gentamicin in calves

Following a single intravenous injection of polymyxin B, colistin (5 mg/kg, each) and gentamicin (3 mg/kg) to calves, the decline in serum antibiotic concentration generally suggested a three-compartment (open system) pharmacokinetic model. Tissue binding is a dominant factor in the distribution and elimination kinetics of the drugs. Less than 65% of the dose of polymyxin B and colistin was recovered in the urine during 48 h after treatment. Concentrations of nonbound polymyxin B and colistin in the kidney, liver, lung, heart, and skeletal muscles were similar to total (free and bound) serum drug levels, but considerably higher concentrations were found, in bound form, in chloroform-ethanol extracts of these organs.
At 24 h after treatment, more than 50% of the doses of polymyxin B and colistin were present bound to the tissues; the largest amount was in the skeletal muscles. Gentamicin was concentrated in the kidney, predominantly in the free form. At 48 h after treatment the amount of gentamicin in the kidney was 6.3% of the administered dose, being more than five times greater than the corresponding amounts of polymyxin B and colistin.
The extent of tissue uptake of polymyxin B and colistin limits the usefulness of kinetic values, which are derived from the analysis of serum drug levels, for the purpose of designing dosage schedules. The strong affinity of the polymyxins to the muscle tissue, and gentamicin to the kidney, can result in drug residues persisting in the body for several weeks.     

Papillomatosis of the bovine teat (mammary papilla)

A 4th of 667 cattle examined at a Wisconsin abattoir had teat papillomas. Excised teat papillomas were sorted by gross morphologic characteristics into 3 groups: (i) atypical filiform, (ii) atypical flat, and (iii) typical fibropapilloma. Bovine papilloma virus capsid antigen was detected in thin-section slides of the 3 groups of teat papillomas by peroxidase-antiperoxidase assay. The bovine papilloma virus involved with the atypical papillomas could not be characterized by molecular hybridization, because enough pure virus could not be harvested. Homogenates of the 3 groups of teat papillomas were inoculated on 2 ponies and 4 calves. Typical fibropapillomas were produced on the 4 calves, and fibromas, on the 2 ponies. Atypical papillomas were produced only in 2 heifers.     

Effects of grain type, roughage level and monensin level on finishing cattle performance

Interactions among grain type (grain sorghum, corn or wheat), roughage level and monensin level were studied in four feedlot trials using pen-fed crossbred yearling cattle. In Trial 1, cattle fed high-moisture corn (HMC) were more efficient (.1537 vs .1406 for gain/feed; P less than .01) than cattle fed dry-rolled grain sorghum (DRGS). As level (0, 3, 6, 9%) of dietary roughage was increased, feed efficiency (gain/feed) decreased (.1566, .1461, .1479, .1382; linear, P less than .01). In Trial 2, a grain type (DRGS; dry-rolled corn, DRC; dry-rolled wheat, DRW) x roughage level interaction was observed for daily gain and feed efficiency. Feed efficiency (gain/feed) was decreased when roughage was added to diets containing DRC (.1608 vs .1750) or DRGS (.1674 vs .1465), but not to the diet containing DRW (.1664 vs .1607). In trial 3, a grain type x roughage level x monensin level interaction (P less than .08) was observed for feed efficiency. The addition of 27.5 mg of monensin per kilogram of the 0% roughage-DRC diet tended to improve feed efficiency (.1633 vs .1531), but the addition of monensin to the 7.5% roughage-DRC diet tended to depress feed efficiency (.1476 vs .1575). The addition of either roughage (.1493 vs .1420) or monensin (.1500 vs .1413) to the DRW diet improved feed efficiency. In Trial 4, cattle fed a combination of 75% DRW and 25% DRC were more efficient (.1618 vs .1591; P less than .06) than cattle fed DRC. As level of roughage (0, 3.75, 7.5%) increased, feed efficiency decreased linearly (.1645, .1599, .1569; P less than .0001). Monensin had no effect on feed efficiency. The value of feeding roughage and monensin was variable both across grain types and within similar grain types.