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.

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.

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.

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.

High-resolution computed tomography (HRCT) was performed in 21 isolated animal lungs, from 4 mammalian species (pigs, rabbits, dogs, sheep). Gross and subgross central and peripheral lung morphology was determined by HRCT. Three distinct types of lungs can be identified, principally based on the extent of interlobular septal development; the relationship of major vessels to airways; and the thickness of the visceral pleura. Type-I lung is found in pigs, sheep, and cattle; type-II lung is found in rabbits, dogs, cats, and monkeys; and type-III lung is found in human beings and horses. These mammalian lungs were compared with human lungs. The potential use of HRCT to investigate specific human lung diseases in the aforementioned species also was considered.

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.

Restriction endonuclease patterns of genomic fragments separated by use of pulsed-field gel electrophoresis were used to differentiate Brucella abortus strain RB51, a rifampin-resistant mutant of the standard virulent strain 2308, from other brucellae. Results were compared with results obtained by use of standard methods for characterizing brucellae. Electrophoretic patterns of the ATCC type strains allowed identification of the strains to the level of species. Genomic profiles of B abortus biovars 1, 2, and 4 were similar, as were those of biovars 5, 6, and 9. The profile of biovar 3 was similar to that of biovars 5, 6, and 9, except for a missing band at 93 kb and additional bands at 65 and 67 kb. A different fingerprint was detected in B abortus strain RB51, using the pulsed-field gel electrophoresis patterns of genomic DNA digested with restrictive endonuclease Xba I. The profile of B abortus strain RB51 contained a band at 104 kb, as opposed to a 109-kb fragment within profiles of B abortus isolates from naturally infected cattle, bison, and elk. Despite known biochemical and biological differences between RB51 and its parent strain (2308), restriction endonuclease analysis results were similar.

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 central arterial pharmacokinetics of alfentanil, a short-acting opioid agonist, were studied in rabbits, sheep, and dogs after short-duration infusion of the drug. Alfentanil was infused until a set end point (high-amplitude, slow-wave activity on the EEG) was reached. This required a larger alfentanil dose and a higher alfentanil arterial concentration in sheep, compared with rabbits and dogs. The plasma concentration-time data for each animal were fitted, using nonlinear regression, and in all animals, were best described by use of a triexponential function. In this study, differences in the disposition kinetics of alfentanil among the 3 species were found for only distribution clearance and initial distribution half-life. In dogs, compared with rabbits and sheep, the first distribution half-life was longer, probably because of pronounced drug-induced bradycardia (mean +/- SD, 48 +/- 21 beats/min). Distribution clearance was faster in sheep, compared with dogs, also probably because of better blood flow in sheep. Elimination half-life was similar in all species (rabbits, 62.4 +/- 11.3 minutes; sheep, 65.1 +/- 27.1 minutes; dogs, 58.3 +/- 10.3 minutes). This rapid half-life resulted from a small steady-state volume of distribution (rabbits, 908.3 +/- 269.0 ml/kg; sheep, 720.0 +/- 306.7 ml/kg; dogs, 597.7 +/- 290.2 ml/kg) and rapid systemic clearance (rabbits, 19.4 +/- 5.3 ml/min/kg; sheep, 13.3 +/- 3.0 ml/min/kg; dogs, 18.7 +/- 7.5 ml/min/kg). On the basis of these pharmacokinetic variables, alfentanil should have short duration of action in rabbits, sheep, and dogs. This may be beneficial in veterinary practice where rapid recovery would be expected after bolus administration for short procedures or after infusion for longer procedures.

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.