Residues of veterinary drugs at injection sites

Residues of veterinary drugs have potential implications for human food safety and international trade in animal-derived food commodities. A particular concern is the slow depletion of residues of some injectable formulations from the site of administration. Licensing authorities have adopted different approaches to the human food safety assessment of injection site residues. European agencies apply the maximum residue limit (MRL) for muscle to muscle at the injection site and specify a withdrawal period sufficient to ensure the ingestion of a 300 g portion of muscle, if comprised entirely of injection site tissue, does not exceed the acceptable daily intake. The agencies in Australia, Canada and the USA also exclude injection site residues from the MRL-setting process. These agencies evaluate the risk to consumers posed by potential acute manifestations resulting from the infrequent ingestion of injection site residues based on acute dietary exposure considerations. While all of these approaches protect the safety of consumers, the adoption of different approaches has potential implications for residue surveillance programs in the international trade in meat. In particular, when an exporting country establishes standards for residues at injection sites based on acute dietary exposure considerations and the importing country assesses these residues against the MRL for muscle, the unnecessary condemnation of meat and disruption to market access may result. The latter may represent a potential economical impost to the exporting country. An internationally harmonized approach to the risk analysis of residues of veterinary drugs at injection sites, which protects the safety of consumers and facilitates the international trade in meat, is needed.     

Escherichia coli and selected veterinary and zoonotic pathogens isolated from environmental sites in companion animal veterinary hospitals in southern Ontario

Hospital-based infection control in veterinary medicine is emerging and the role of the environment in hospital-acquired infections (HAI) in veterinary hospitals is largely unknown. This study was initiated to determine the recovery of Escherichia coli and selected veterinary and zoonotic pathogens from the environments of 101 community veterinary hospitals. The proportion of hospitals with positive environmental swabs were: E. coli--92%, Clostridium difficile--58%, methicillin-resistant Staphylococcus aureus (MRSA)--9%, CMY-2 producing E. coli--9%, methicillin-resistant Staphylococcus pseudintermedius--7%, and Salmonella--2%. Vancomycin-resistant Enterococcus spp., canine parvovirus, and feline calicivirus were not isolated. Prevalence of antimicrobial resistance in E. coli isolates was low. Important potential veterinary and human pathogens were recovered including Canadian epidemic strains MRSA-2 and MRSA-5, and C. difficile ribotype 027. There is an environmental reservoir of pathogens in veterinary hospitals; therefore, additional studies are required to characterize risk factors associated with HAI in companion animals, including the role of the environment.     

Mucosal immunology: overview and potential in the veterinary species

A large part of the immune system is dedicated to protection from infection at mucosal surfaces. The concept of the common mucosal immune system has been investigated in several veterinary species where traffic of mucosally activated lymphocytes from induction to effector sites has been demonstrated. The dominant isotype found in secretions of the upper respiratory tract and gut of normal healthy and diseased animals is IgA. B lymphocytes have a relatively short half-life and there is continuous production of IgA at these sites, which is achieved by constant secretion from T helper and epithelial cells of cytokines that are critical for B cell maturation and IgA secretion. Specific stimulation of mucosal immune responses using intranasal presentation of live and inactivated antigens (with adjuvants active at mucosal surfaces) has shown great promise for inducing protective immunity to respiratory pathogens.     

Prevalence of canine enteric coronavirus in a cross-sectional survey of dogs presenting at veterinary practices

In order to determine the prevalence of canine enteric coronavirus (CECoV) in the general dog population, faecal samples were obtained in a cross-sectional study of 249 dogs presenting for any reason at veterinary practices randomly selected from across the UK. Demographic and clinical data was obtained for each of the samples, including signalment, number of dogs in the household, reason for visiting the practice, and any recent history of diarrhoea. The samples were tested by RT-PCR for the presence of both type I and type II CECoV. Seven samples were positive (three from dogs in the same household), a prevalence of 2.8% (95% confidence intervals 1.1–5.7). Phylogenetic analysis of partial M gene sequences revealed that all seven positive samples grouped with type I CECoV, the first report of this virus in the UK. None of the positive dogs presented for gastrointestinal disease. Interestingly five of the positive dogs from three separate households were aged over 6 years, suggesting that older dogs may play an important role in the persistence of CECoV in such populations.     

Pharmacodynamics and pharmacokinetics of nonsteroidal anti-inflammatory drugs in species of veterinary interest

This review summarises selected aspects of the pharmacokinetics (PK) and pharmacodynamics (PD) of nonsteroidal anti-inflammatory drugs (NSAIDs). It is not intended to be comprehensive, in that it covers neither minor species nor several important aspects of NSAID PD. The limited objective of the review is to summarise those aspects of NSAID PK and PD, which are important to an understanding of PK-PD integration and PK-PD modelling (the subject of the next review in this issue). The general features of NSAID PK are: usually good bioavailability from oral, intramuscular and subcutaneous administration routes (but with delayed absorption in horses and ruminants after oral dosing), a high degree of binding to plasma protein, low volumes of distribution, limited excretion of administered dose as parent drug in urine, marked inter-species differences in clearance and elimination half-life and ready penetration into and slow clearance from acute inflammatory exudate. The therapeutic effects of NSAIDs are exerted both locally (at peripheral inflammatory sites) and centrally. There is widespread acceptance that the principal mechanism of action (both PD and toxicodynamics) of NSAIDs at the molecular level comprises inhibition of cyclooxygenase (COX), an enzyme in the arachidonic acid cascade, which generates inflammatory mediators of the prostaglandin group. However, NSAIDs possess also many other actions at the molecular level. Two isoforms of COX have been identified. Inhibition of COX-1 is likely to account for most of the side-effects of NSAIDs (gastrointestinal irritation, renotoxicity and inhibition of blood clotting) but a minor contribution also to some of the therapeutic effects (analgesic and anti-inflammatory actions) cannot be excluded. Inhibition of COX-2 accounts for most and possibly all of the therapeutic effects of NSAIDs. Consequently, there has been an intensive search to identify and develop drugs with selectivity for inhibition of COX-2. Whole blood in vitro assays are used to investigate quantitatively the three key PD parameters (efficacy, potency and sensitivity) for NSAID inhibition of COX isoforms, providing data on COX-1:COX-2 inhibition ratios. Limited published data point to species differences in NSAID-induced COX inhibition, for both potency and potency ratios. Members of the 2-arylpropionate sub-groups of NSAIDs exist in two enantiomeric forms [R-(-) and S-(+)] and are licensed as racemic mixtures. For these drugs there are marked enantiomeric differences in PK and PD properties of individual drugs in a given species, as well as important species differences in both PK and PD properties.     

Forms of employment and species caseload of veterinary practitioners in New Zealand

A survey by means of a postal questionnaire was undertaken to investigate the patterns of work and the need for information of veterinary practitioners in New Zealand. Of the 670 eligible veterinarians, 399 practitioners (60 per cent) participated in the survey. Of these, 38 per cent were in large animal practice (less than 20 per cent of work devoted to cats and dogs) and 31 per cent were in small animal practice (more than 80 per cent of work with cats and dogs). The remaining 31 per cent were in mixed practice, with a workload intermediate between the other two groups. Across the entire sample of practitioners, cats and dogs took up the largest number of veterinary hours per person (1092 hours per year). Dairy cattle were second (438 hours), and horses third (302 hours). Deer and goats ranked next, and each used more veterinary hours per person than did either sheep or beef cattle. Other species comprised very minor parts of the overall workload. Women spent a much higher proportion of their working hours with small animals and a much lower proportion with horses than did men. For other species workload patterns were similar between men and women. In relation to employment of the practitioner group, women were under represented, compared with men, among those with responsibilities for the management of practices, even when account was taken of the fact that the women in the sample were younger. Fewer than one per cent of men in the sample were not employed full-time, whereas 15 per cent of the women were in part-time employment. The survey indicates that there has been a substantial change in the demographic structure of the veterinary profession and the forms of veterinary work carried out. It also shows that the differences in work and career patterns between men and women need more intensive study to improve the accuracy of predictions of future requirements for veterinary manpower.     

ABCG2 transporter: therapeutic and physiologic implications in veterinary species

Drug transporters significantly influence drug pharmacokinetics and pharmacodynamics. While P-glycoprotein, the product of the MDR1 (ABCB1) gene, is the most well-characterized ABC transporter, the pharmacological importance of a related transporter, ABCG2, is starting to be realized in veterinary medicine. Based primarily on human and rodent studies, a number of clinically relevant, structurally and functionally unrelated drugs are substrates for ABCG2. ABCG2 is expressed by a variety of normal tissues including the intestines, renal tubular cells, brain and retinal capillary endothelial cells, biliary canalicular cells, and others, where it functions to actively extrude substrate drugs. In this capacity, ABCG2 limits oral absorption of substrate drugs and restricts their distribution to privileged sites such as the brain and retina. ABCG2 is also expressed by tumor cells where it functions to limit the intracellular accumulation of cytotoxic agents, contributing to multidrug resistance. Several ABCG2 polymorphisms have been described in human patients, some of which result in altered drug disposition, increasing susceptibility to adverse drug reactions. Additionally, ABCG2 polymorphisms in humans have been associated with disease states such as gout. Feline ABCG2 has recently been demonstrated to have several amino acid differences at conserved sites compared with 10 other mammalian species. These amino acid differences adversely affect transport function of feline ABCG2 relative to that of human ABCG2. Furthermore, these differences appear to be responsible for fluoroquinolone-induced retinal toxicity in cats and may play a role in acetaminophen toxicity as well. Studies in rodents and sheep have determined that ABCG2 expressed in mammary tissue is responsible for the secretion of many compounds (both therapeutic and toxic) into milk. Finally, data in rodent models suggest that ABCG2 may play an important role in regulating a number of physiologic pathways involved in protecting erythrocytes from oxidative damage.     

Staphylococcal colonization of mucosal and lesional skin sites in atopic and healthy dogs

Staphylococcal colonization was compared in healthy dogs and in dogs with atopic dermatitis. Bacterial swabs were collected from the nasal mucosa, ear and perineum of 43 healthy and 24 atopic dogs and also from potentially infected skin lesions of the atopic dogs. Coagulase positive staphylococcal isolates were identified to the species level. At the time of this study Staphylococcus intermedius was considered a single species but has since been recognized as comprising at least three species with canine isolates believed to belong to Staphylococcus pseudintermedius . Of atopic dogs, 87.5% were colonized with S. intermedius compared to only 37.2% of healthy dogs. The ear was the only carriage site that showed any significant difference in S. intermedius isolation between healthy and atopic dogs. The perineum represented the most frequently colonized mucosal site for both groups. Sampling the nasal mucosa alone identified 71.4% of atopic and 37.5% of healthy S. intermedius carriers. Inclusion of a perineal swab identified 100% of atopic and 93.8% of healthy carriers. S. intermedius was isolated from all the lesional sites sampled from atopic dogs. Significantly fewer dogs were colonized by Staphylococcus aureus than S. intermedius , and there was no significant difference between S. aureus colonization of atopic and healthy dogs. S. aureus was not recovered from any lesions in atopic dogs. The results show that S. intermedius carriage is more prevalent in atopic dogs compared to healthy dogs and that to identify staphylococcal carriers both the nasal mucosa and the perineum should be sampled.     

The scientific basis for establishing solubility criteria for veterinary species

The relationship between factors influencing the in vitro and in vivo drug solubilization is highly dependent upon the physiology of the individual animal species and the physico-chemical properties of the drug. The solubilization of a drug in an aqueous medium is controlled by the strength of the interaction between a molecule of the active pharmaceutical ingredient (API) and the molecules of the solvent. In this regard, the stronger this interaction, the greater the likelihood that the drug will go into solution. Counteracting this solubilization process is the strength of the affinity of the solute for itself, or how tightly bound the compound is to its own solid state form. The stronger affinity of a solute for itself, the more difficult it will be for that molecule to go into solubility. However, solubility is not a universal value. Rather, it should be considered from the perspective of the interactions between the API in its solid form and the solution conditions such as: pH, the nature of the primary solvent, the presence of co-solvents, the presence of solubilizing additives, the ionic strength of the medium, incubation time, and temperature. Each of these factors needs to be considered when evaluating potential interspecies differences in drug solubility.     

Infections caused by fungi of the Scedosporium/Pseudallescheria complex in veterinary species

Fungi belonging to the Scedosporium/Pseudallescheria complex (SPCF) have been known to cause human infections for nearly a century and are important human pathogens, with an increasing frequency of infection in patients with underlying conditions. There appears to be a lower incidence of infections with SPCF in veterinary species, although this may be related to a lack of awareness of these diseases. Important recent taxonomic changes in this group of fungi include the classification of Pseudallescheria boydii and Scedosporium apiospermum as two distinct species and the identification of new pathogenic species of SPCF. In this article, the literature on natural and experimental infections caused by SPCF in veterinary species is reviewed. The importance of an accurate identification of veterinary isolates by molecular methods is stressed, especially since virulence and susceptibility to antimycotic drugs of different species may vary.     

Interstitial cells of Cajal and their role in veterinary gastrointestinal pathologies

This study highlights the importance of interstitial cells of Cajal (ICs) in gastrointestinal disease. Human research is already considering IC pathologies but in veterinary research IC pathologies are rarely studied. Nevertheless, recent studies of ICs show a growing interest in the pathophysiology of gastrointestinal diseases and emphasize the consideration of this cell type in the pathophysiology of veterinary gastrointestinal malfunctions.     

Interaction of antigen presenting cells with mycobacteria

The interaction of mycobacteria with antigen presenting cells is a key feature in the pathogenesis of tuberculosis and the outcome of this interaction is pivotal in determining whether immunity or disease ensues. Human and mouse macrophages and dendritic cells (DC) have been shown to become infected with mycobacteria and to produce a response to infection that reflects their suggested role in immunity. Thus, macrophages elicit anti-microbial mechanisms for elimination of mycobacteria and DC up-regulate expression of molecules that aid their stimulation of T lymphocytes. We have examined the effects of infection with the avirulent strain Mycobacterium bovis BCG and with virulent M. bovis on bovine antigen presenting cells. Differences in the intracellular survival of bacteria within DC and macrophages were observed with higher numbers of bacteria maintained within DC following infection compared to macrophages. BCG was killed more effectively than M. bovis. Alterations in the expression of cell surface molecules involved in antigen presentation and the stimulation of T cells, including MHC II and CD40, were observed following infection of bovine antigen presenting cells. In addition infected DC secreted IL-12, TNF and IL-10 whereas macrophages produced TNF, IL-10 and little IL-12. Generally responses were more marked when virulent M. bovis was used compared to BCG. These studies indicate that infection of bovine antigen presenting cells by mycobacterial species results in the induction of both innate and adaptive immune responses that are critical for the outcome of infection.     

对微血管内皮细胞的研究及其在中药针灸研究中的应用

微血管内皮细胞的研究是当今生命科学领域的一大热点，其功能的多样性日益受到研究者的重视；同样，微血管内皮细胞在中（兽）医学的现代研究中也已逐渐得到应用，显现了其在中（兽）医学的研究中的重要价值。     

Endothelial cells as active participants in veterinary infections and inflammatory disorders

Endothelial cells were once viewed as relatively inert cells lining the vasculature. They are now recognized as active and responsive regulators of coagulation, platelet adhesion, fluid homeostasis, wound healing, leukocyte extravasation and vascular tone. Endothelial cells play a key role in the host response to infectious agents by regulating leukocyte trafficking, producing inflammatory cytokines and presenting antigen in association with major histocompatibility class II (MHC II) molecules. A number of infectious agents have a tropism for endothelial cells. Infection of endothelial cells can promote thrombosis, vascular leakage, and increased adherence and emigration of leukocytes. Furthermore, activation of a systemic inflammatory response, in the absence of direct endothelial cell infection, can also lead to endothelial cell dysfunction. The purpose of this review is to highlight the interactions between endothelial cells and infectious or inflammatory agents that contribute to coagulation disturbances, vasculitis and edema. A select group of viral and bacterial pathogens will be used as examples to demonstrate how endothelial cell dysfunction contributes to the pathogenesis of infectious and inflammatory disorders.