The effect of immaturity of the calf on immunological responses to strain 19 and killed 45/20 adjuvant vaccines.

Thirty brucellosis free calves with zero titres to the serum agglutination test (SAT), complement fixation test (CFT) and antiglobulin test (ABGT) were vaccinated with strain 19 at ages from seven hours to 198 days. Calves 75 days of age and older responded with normal serological patterns, developing high titres to all three tests. At 45 days and younger most calves responded with much reduced titres, some were negative to the SAT and CFT but all develped titres to the ABGT. Two of the younger group were subjected to an anamnestic test at about a year old and gave a positive response, indicating that the calf may be effectively primed with S19 as early as the first day of life. Three of the group were colostrumdeprived yet the patterns of their responses were similar to those of the colostrum-fed calves. Seventy-four zero titres calves were vaccinated with killed 45/20 adjuvant vaccine at ages from 60 to 320 days. Up to 200 days of age only seven of 33 calves gave positive response. From 200 to 280 days 18 of 29 responded and from 280 days of age all calves a positive response. The late development of competence to respond to this adjuvant vaccine is somewhat unusual and is discussed. It is suggested that the rough strain 45/20 may be a very weak antigen in cattle.     

Heritability of racing performance in thoroughbred horses

The héritabilitý of performance in thoroughbreds was studied using the Timeform Ratings for horses which raced during 1970. Timeform Ratings are based on the relative performance of all horses racing in a given year. 794 Individual three year old records, representing 96 sires which had five or more progeny, were used.The mean ratings for sires, dams and progeny were 128.5, 93.6 and 81.4 respectively; among the progeny the ratings for colts, fillies and geldings were 88.3, 79.1 and 77.1 respectively. Calculations made suggest that while stallion selection is effective in selecting sires with high performance ratings it does not appear that the selection of dams is very closely related to performance. There was no evidence of assortative mating.Paternal half sib and regression of offspring on sire analyses of the data yielded heritability estimates of 0.35 ± 0.11 and 0.74 ± 0.20 respectively. Further regression analyses on a reduced set of data (553 progeny records) of offspring on sire, offspring on dam and offspring on mid parent value gave heritabilities 0.56 ± 0.20, 0.36 ± 0.10 and 0.34 ± 0.08respectively. The possible reason for the substantially higher heritability estimates from the regressions of offspring on sire are discussed. It is concluded that the best measure of heritability of performance is 35%.     

The effect of changing the sex ratio on the efficiency of cattle breeding operations

The direct effect of sex control in providing a higher proportion of male calves for beef production can increase the beef output of a dual-purpose population by up to 5%. The actual increase depends on the rate of cow turnover and on the net superiority of males over females in the population concerned. Control of the sex ratio also permits an increase in the intensity of selection, particularly in the paths dams-sons and dams-daughters. The total effect could be an improvement of the order of 10% in the rate of genetic change in the population. Thirdly, control of the sex ratio increases the possibilities for beef crossing in dairy or dual-purpose cattle populations. This can increase the beef output of the population by up to 4%, depending on the rate of cow turnover and the superiority of the beef strains used. If these opportunities are pursued they are likely to drive the population into specialised strains of dairy and beef cattle.     

Differential inhibition of equine neutrophil function by phosphodiesterase inhibitors

Neutrophils are recruited to the lungs of horses with chronic obstructive pulmonary disease (COPD) and exhibit increased activity after antigen challenge, which may contribute to inflammation and lung damage. Inhibition of phosphodiesterase isoenzymes (PDEs) has been shown to attenuate human neutrophil functions including superoxide production, leukotriene (LT)B4 biosynthesis, enzyme and chemokine release. As equine neutrophils contain predominantly the isoenzyme, PDE4, the present study was undertaken to investigate the effects of rolipram, a PDE4 inhibitor, on equine neutrophil function. For comparison, the effects of the nonselective PDE inhibitor, theophylline, were examined. Cells from both normal horses and COPD horses in remission were used. Superoxide production was significantly inhibited by both rolipram [32.2 +/- 2.6 vs. 10.1 +/- 1.1 nmol/10(6) cells and 49.8 +/- 6.8 vs. 22.7 +/- 2.2 nmol/10(6) cells for normal and COPD susceptible horses, respectively, in response to 10(-7) M human recombinant (hr) C5a] and theophylline (19.0 +/- 0.6 vs. 10.2 +/- 0.6 nmol/10(6) cells and 24.3 +/- 2.1 vs. 10.7 +/- 0.9 nmol/10(6) cells for normal and COPD susceptible horses, respectively, in response to 10(-7) M C5a). However, superoxide production induced by serum treated zymosan was inhibited only by theophylline (10(-3) M). Neither hrC5a- nor platelet activating factor (PAF)-induced neutrophil adherence to fibronectin coated plastic was reduced by rolipram (10(-5) M). These results demonstrate that the effects of PDE inhibitors on equine neutrophils are both stimulus and function dependent. The PDE4 inhibitors may reduce neutrophil activation in vivo in horses with COPD.     

Principles of pharmacodynamics and their applications in veterinary pharmacology

Pharmacodynamics (PDs) is the science of drug action on the body or on microorganisms and other parasites within or on the body. It may be studied at many organizational levels--sub-molecular, molecular, cellular, tissue/organ and whole body--using in vivo, ex vivo and in vitro methods and utilizing a wide range of techniques. A few drugs owe their PD properties to some physico-chemical property or action and, in such cases, detailed molecular drug structure plays little or no role in the response elicited. For the great majority of drugs, however, action on the body is crucially dependent on chemical structure, so that a very small change, e.g. substitution of a proton by a methyl group, can markedly alter the potency of the drug, even to the point of loss of activity. In the late 19th century and first half of the 20th century recognition of these facts by Langley, Ehrlich, Dale, Clarke and others provided the foundation for the receptor site hypothesis of drug action. According to these early ideas the drug, in order to elicit its effect, had to first combine with a specific 'target molecule' on either the cell surface or an intracellular organelle. It was soon realized that the 'right' chemical structure was required for drug-target site interaction (and the subsequent pharmacological response). In addition, from this requirement, for specificity of chemical structure requirement, developed not only the modern science of pharmacology but also that of toxicology. In relation to drug actions on microbes and parasites, for example, the early work of Ehrlich led to the introduction of molecules selectively toxic for them and relatively safe for the animal host. In the whole animal drugs may act on many target molecules in many tissues. These actions may lead to primary responses which, in turn, may induce secondary responses, that may either enhance or diminish the primary response. Therefore, it is common to investigate drug pharmacodynamics (PDs) in the first instance at molecular, cellular and tissue levels in vitro, so that the primary effects can be better understood without interference from the complexities involved in whole animal studies. When a drug, hormone or neurotransmitter combines with a target molecule, it is described as a ligand. Ligands are classified into two groups, agonists (which initiate a chain of reactions leading, usually via the release or formation of secondary messengers, to the response) and antagonists (which fail to initiate the transduction pathways but nevertheless compete with agonists for occupancy of receptor sites and thereby inhibit their actions). The parameters which characterize drug receptor interaction are affinity, efficacy, potency and sensitivity, each of which can be elucidated quantitatively for a particular drug acting on a particular receptor in a particular tissue. The most fundamental objective of PDs is to use the derived numerical values for these parameters to classify and sub-classify receptors and to compare and classify drugs on the basis of their affinity, efficacy, potency and sensitivity. This review introduces and summarizes the principles of PDs and illustrates them with examples drawn from both basic and veterinary pharmacology. Drugs acting on adrenoceptors and cardiovascular, non-steroidal anti-inflammatory and antimicrobial drugs are considered briefly to provide a foundation for subsequent reviews in this issue which deal with pharmacokinetic (PK)-PD modelling and integration of these drug classes. Drug action on receptors has many features in common with enzyme kinetics and gas adsorption onto surfaces, as defined by Michaelis-Menten and Langmuir absorption equations, respectively. These and other derived equations are outlined in this review. There is, however, no single theory which adequately explains all aspects of drug-receptor interaction. The early 'occupation' and 'rate' theories each explain some, but not all, experimental observations. From these basic theories the operational model and the two-state theory have been developed. For a discussion of more advanced theories see Kenakin (1997).     

Antibodies to prion and Acinetobacter peptide sequences in bovine spongiform encephalopathy

An amino acid sequence homology has been identified between the bovine prion sequence (RPVDQ) and the Acinetobacter calcoaceticus enzyme, uridine-diphosphate-N-acetyl glucosamine-1-carboxy-vinyl-transferase which also contains (RPVDQ). Class-specific IgA, IgG and IgM antibodies against synthetic peptides containing the structurally related sequences present in bovine prion and A. calcoaceticus were measured in 189 bovine spongiform encephalopathy (BSE) positive cattle, 127 BSE negative cattle and 87 healthy control animals using an ELISA technique. Class-specific IgA, IgG and IgM antibodies against the structurally related synthetic peptides were significantly elevated in BSE positive cattle when compared to BSE negative cattle (P < 0.001) and healthy control animals (P < 0.001). These autoantibodies may have a role in the pathogenesis of BSE.     

Actions and interactions of ADP, 5- HT, histamine and PAF on equine platelets

Platelets are thought to play a role in equine diseases such as acute laminitis and verminous arteritis and may be involved in allergic disease. Mediators implicated in the pathophysiology of these conditions activate platelets and responses may be enhanced by interactions between mediators. The present study compared platelet aggregation, thromboxane production and release of radiolabelled [(3)H]5- HT in response to 5- HT, histamine, ADP and PAF alone and in combination in vitro.PAF caused concentration-related aggregation, [(3)H]5- HT release and thromboxane production. In contrast, ADP caused aggregation and 5- HT induced the release of [(3)H]5- HT with little effect on other platelet functions. Histamine had little or no effect on equine platelets. Addition of 5- HT (10 microM) prior to ADP significantly displaced the aggregation response curve to the left.The profile of responses to PAF, ADP and 5- HT suggests differential activation of intracellular signalling pathways regulating these events. The enhanced response to ADP in the presence of 5- HT may have implications in thromboembolic disease in the horse.