Disposition kinetic variables of HI-6, a bispyridinium oxime, have been determined in mice, rats, rabbits, Rhesus monkeys, Beagles, sheep, and human beings. The drug has a short half-life, small apparent volume of distribution and high body clearance in these species, and is eliminated mainly by renal excretion. Using regression analysis and double logarithmic plots of the pharmacokinetic variables vs body weight of the various species, it was observed that body (systemic) clearance is the pharmacokinetic variable to use for interspecies comparison of elimination of the drug. The allometric exponent denoting the proportionality of body clearance of HI-6 to body weight of the 7 species studied was 0.76, which may be related to the renal excretion process for the drug. The apparent volume of distribution was similar (260 to 304 ml/kg of body weight) in the various species. The results indicate that volume of distribution, body clearance, and with less confidence, half-life might be used for interspecies scaling and for predicting these variables in other mammalian species. On the basis of the pharmacokinetic variables in selected species (rats and mice excluded), IV administration of III-6 at a dosing rate of 20 to 25 mg/kg at 4-hour intervals should provide an average steady-state plasma concentration of 16 to 20 micrograms/ml in domestic animals. The short half-life of III-6 precludes increasing the dosage interval.

The cause of species difference in the susceptibility of erythrocytes to L-sorbose, and the difference in the hemolytic effect of sorbose on high potassium-containing (HK) and low potassium-containing (LK) canine erythrocytes were examined. L-sorbose was phosphorylated in canine erythrocytes, but not in human erythrocytes. Furthermore, sorbose-1-phosphate, a metabolite of L-sorbose, strongly inhibited the hexokinase of LK canine erythrocytes, but not that of HK canine erythrocytes. These results strongly indicated that inhibition of hexokinase by sorbose-1-phosphate in LK erythrocytes induced severe glycolytic limitation in these cells, resulting in hemolysis, and that HK erythrocytes are resistant to sorbose-induced hemolysis because these cells have a high hexokinase activity.

Replication of bluetongue virus (BTV) in leukocytes from the blood of sheep, cattle, elk, and mule deer inoculated with BTV serotype 10 or 17 was assessed by immunocytochemical staining and dot blot northern hybridization to determine if differences in the prevalence of infection in this blood fraction might account for the differences in clinical disease among these species. Viremia was confirmed by virus isolation in all inoculated animals. Analysis of leukocytes with monoclonal antibodies specific for BTV proteins revealed low numbers of infected leukocytes in only 2 sheep 8 days after inoculation with BTV serotype 10. Most of the cells expressing BTV were identified morphologically as monocytes; approximately 10% of infected cells were lymphocytes. Bluetongue virus was not detected by use of dot-blot hybridization on samples of blood. Our results suggest that differential infection of leukocytes does not account for the pronounced differences in clinical signs and pathologic changes among ruminants.

Isoelectric focusing was performed on the soluble proteins of whole-body and excretory-secretory products (ESP) of Fasciola hepatica and Fascioloides magna. Adult F hepatica flukes were recovered from experimentally infected sheep and ESP obtained from the flukes; portions of liver were cut and frozen at -70 C. Fascioloides magna adults were collected from naturally infected white-tailed deer and ESP obtained; portions of liver were collected from noninfected white-tailed deer. Adult flukes and their host tissues were homogenized and centrifuged; protein concentrations with their ESP were determined and adjusted to < 2.50 mg/ml. Seven ESP samples from F hepatica and 1 from Fascioloides magna were subjected to isoelectric focusing with the 2 species of fluke and their respective host liver homogenates. After separation, gels were stained with silver and scanned on a laser densitometer. Protein banding patterns of the 2 species of flukes were dissimilar. In the pH range of 3.5 to 9.6, the body protein had approximately 30 peaks and ESP about 23 peaks in both species. Overall banding patterns of the body protein and ESP of both species were distinct from those of respective host tissues. Of the peaks reported as dominant, 3 of the body protein and 2 of ESP were shared between the 2 species. Fascioloides magna had more dominant peaks than F hepatica. This technique of soluble protein isoelectric focusing is simple and reproducible, and the 2 fluke species can easily be differentiated by this technique, as well as by morphologic characteristics.

The assessment of cutaneous microcirculation by laser-Doppler velocimetry (LDV) has been primarily limited to human studies. The purpose of this investigation was to establish normal values in various species and anatomic sites for blood flow, velocity, and volume as determined by LDV. Microcirculation was measured with a laser-Doppler velocimeter in 54 animals, 6 healthy animals from each of 9 species. The standard sites used were the buttocks, convex surface of the ear, metacarpal pad, humeroscapular junction, thoracolumbar junction, ventral portion of the abdomen, dorsal metacarpus (hooved animals), and ventral surface of the tail (horse). Significant differences in blood flow, velocity, and volume were measured between species and sites within species. The ventral portion of the abdomen consistently had the highest relative blood flow across all species except the monkey. Measurements in the canine metacarpal pad had a high SD, possibly indicating the stratum corneum and epidermis to be too thick for LDV. Our findings provide baseline data in several species, with application of LDV in comparative dermatologic research.

Vaccina virus (VV) infection induces specific antibodies and cytotoxic T cells in various animal species. Therefore, helper T cells also should be induced that stimulate the humoral and cellular immune responses. We determined such helper T-cell activity in 2 species after VV infection. Rabbits and rhesus macaques were infected with the Copenhagen strain of VV or with recombinant VV expressing retroviral proteins. Animals of both species developed antibodies and specific proliferative T-cell response. This reactivity could be enhanced by booster infection with VV. The proliferating macaque cells were CD4+ and major histocompatability complex class II-restricted. These data confirm the broad immunogenicity of VV. Expression of additional polypeptides expressed from a recombinant VV does not lead to altered immune response to VV antigens. However, strength of the helper T-cell response, as well as clinical reactions, differed between macaques and rabbits. Infection with recombinant VV as delivery vectors offers the opportunity for combined vaccination against recombinant proteins and does not diminish cellular and humoral immune responses to VV itself.

Results of testing of 19,731 samples from a serologic survey of cattle with bluetongue virus (BTV) infections in Australia were analyzed for association between age, species, or sex and test result. Bivariate analysis indicated that all 3 host factors were associated with test result. After adjusting for confounding caused by the location of each animal in the study (high, moderate, and low BTV prevalence regions), cattle greater than or equal to 4 years old had an odds ratio of 4.33 (95% confidence interval, 3.99, 4.71) for a positive test result, compared with that for cattle < 2 years old. Cattle 2 to 4 years had an odds ratio of 2.28 (2.14, 2.54), compared with cattle < 2 years old. Bos taurus cattle had an odds ratio of 1.76 (1.63, 2.05) of a positive test result, compared with crossbred cattle, and B indicus cattle had an odds ratio of 1.20 (1.09, 1.33), compared with crossbred cattle. Sexually intact (+) male cattle were found to have an odds ratio of 3.13 (2.66, 3.49) for a positive test result, compared with castrated male (-) cattle, and female cattle were found to have an odds ratio of 1.38 (1.29, 1.48), compared with male (-) cattle. Multivariate analysis of BTV testing results was performed, using stepwise logistic regression. The most parsimonious model selected included age, species, and sex factors, and first-order interaction terms between these factors. This model was only able to be fit to data from cattle restricted to the high (> 25%) BTV prevalence region. Odds ratios were found to increase with age for male (-) cattle of all species. Odds ratios were found to be greatest at 2 to 4 years of age for female cattle of all species and for B taurus and crossbred male (+) cattle.

An applanation tonometer was used to estimate intraocular pressure in normal eyes of several species of raptors. No bird had active injury or illness, though some were nonreleasable to the wild because of previous injury. Mean (+/- SD) intraocular pressure was 20.6 (+/- 3.4) mm of Hg in red-tailed hawks (Buteo jamaicensis, n = 10), 20.8 (+/- 2.3) mm of Hg in Swainson's hawks (Buteo swainsoni, n = 6), 21.5 (+/- 3.0) mm of Hg in golden eagles (Aquila chrysaetos, n = 7), 20.6 (+/- 2.0) mm of Hg in bald eagles (Haliaeetus leucocephalus, n = 3), and 10.8 (+/- 3.6) mm of Hg in great horned owls (Bubo virginianus, n = 6). There was no significant difference in intraocular pressure between hawks and eagles. Mean pressure in great horned owls was significantly (P < 0.01) lower than pressure in hawks or eagles. Reliable intraocular pressure readings could not be obtained in barn owls (Tyto alba).

We used size-exclusion high-performance liquid chromatography (HPLC) to investigate the properties of the 2 isoforms of vitamin A-containing (holo) retinol-binding protein (RBP) in animals: the form that is bound to transthyretin (holo-TTR-RBP), and the form that does not bind to TTR (holo-free RBP). We also used radial immunodiffusion to measure immunologically active RBP (apo+ holo RBP). We compared the isoforms of RBP in animals with those of human beings to determine which animal is the best model of human RBP. Size-exclusion HPLC detected holo-free and holo-TTR-RBP in every animal species studied. Apparent concentration of holo-TTR-RBP varied among species: that of rabbits and dogs much greater than that of apes, sheep, goats, monkeys, rhinoceroses, felids, rats, human beings, and deer greater than that of pigs, zebra, and bison greater than that of penguins. Dogs have unusual RBP chromatograms; they have high concentration of RBP, but also appear to transport much of their vitamin A on proteins other than RBP, Human RBP antibody preparations could detect apo + holo RBP immunologic activity only in apes, monkeys, and felids. Apes and monkeys appeared to have complete cross-reactivity to human RBP antibodies. Felids may have substantial, but partial, cross-reactivity. Apes and monkeys appear to be the most relevant animal models for study of human RBP transport. However, there is a need for less-expensive models. Further research is needed, but in the interim, rats or sheep may be satisfactory for some purposes.

Plasma disposition and urinary recovery of sulfamethazine (SMZ), its N4-acetylated metabolite (N4AcSMZ), and 2 of its hydroxylated metabolites--5-hydroxysulfamethazine 5OHSMZ) and 6-hydroxymethylsulfamethazine (6CH2OHSMZ)--were determined in either sex of 4 animal species: rats, dwarf goats, rabbits, and cattle. Rats, rabbits, and dwarf goats had significant (P < 0.01) sex difference in SMZ plasma clearance. Male rats had higher plasma clearance than did female rats, and excreted higher amounts of the hydroxy metabolites and lower amounts of N4AcSMZ. The N4AcSMZ metabolite was predominant in plasma and urine of rabbits. Male rabbits had higher plasma clearance than did female rabbits, but differences in metabolite profile were not apparent. With regard to plasma SMZ elimination, the situation in goats was opposite to that in rats. Male goats had considerably lower clearance than did female goats. This was associated with a lower hydroxylation rate in males. Plasma half-life of SMZ in cows was lower than that in bulls, probably because of a smaller distribution volume in cows. Compared with elimination via urine, elimination via milk was negligible in cows. Significant differences in metabolite profiles were not found between bulls and cows. Similar to those in rats and mice, hormone-dependent xenobiotic metabolic pathways may exist in other species. Depending on species and xenobiotic compound residue concentrations of xenobiotics, their metabolites, or both may differ with sex of the animal, or may be altered after treatment with anabolic hormones.