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PubMed2002

Disposition kinetics of enrofloxacin (Baytril 5%) in sheep and goats following intravenous and intramuscular injection using a microbiological assay.

The pharmacokinetics of enrofloxacin were determined in Desert sheep and Nubian goats after intravenous and intramuscular administration of Baytril at the dose of 5mgkg(-1) bodyweight. A two compartment open model best represented the intravenous plasma concentration versus time data in both species. Comparisons between the means of the pharmacokinetic parameters obtained after intravenous administration of enrofloxacin (Baytril) revealed a significantly smaller distribution rate constant (lambda(1)) and consequently a shorter half-life time of distribution in sheep (P<0.05). A larger volume of the central compartment (Vc) was observed in goats (P<0.05). Similar values were obtained for sheep and goats for the remaining parameters. Plasma concentrations versus time data of enrofloxacin after 5mgkg(-1) intramuscular administration of Baytril in sheep and goats were adequately described by one-compartment open model with first order absorption and elimination. There were no significant differences between sheep and goats in any of the estimated pharmacokinetic parameters. The results indicate that the pharmacokinetics of enrofloxacin did not differ significantly between sheep and goats; similar intravenous and intramuscular dose rates of enrofloxacin should therefore be applicable to both species. Owing to the high variations in MIC (minimal inhibitory concentration) of sensitive veterinary pathogens, it is recommended that enrofloxacin dosage regimens be calculated according to the sensitivity of the individual pathogen, site of infection and clinical response, than by following a preset dosage regimen.

Animals↗
PubMed2003

Molecular epidemiology of foot-and-mouth disease virus.

Foot-and-mouth disease (FMD) is the most economically important veterinary pathogen due to its highly infectious nature, ability to cause persistent infections and long term effects on the condition and productivity of the many animal species it affects. Countries which have the disease have many trade restrictions placed upon them. In the last 15 years there have been significant advances in the understanding of FMD epidemiology. These have largely been due to the application of the molecular biological techniques of polymerase chain-reaction amplification and nucleotide sequencing. In the World Reference Laboratory for FMD (Pirbright, UK), a large sequence database has been built up. This database has been used to aid in the global tracing of virus movements. It has been possible to genetically group many FMDV's based on their geographic origin and this has led to their being referred to as topotypes. The implications of this are that inter-regional spread of viruses can often be easily recognised and any evolutionary changes which subsequently occur can be monitored. Using these techniques, for the first time, we have been able to unequivocally show the recent pandemic spread of a FMDV type O strain through the whole of Asia and into Africa and Europe. This type of surveillance will become increasingly important as further globalisation of markets occurs. An increased understanding of how FMDV strains move between geographic regions will play a pivotal role in the development of future disease control strategies.

Animals↗
PubMed2001

PCR-based typing of Mycobacterium avium isolates in an epidemic among farmed lesser white-fronted geese (Anser erythropus).

Mycobacterium avium is an important veterinary pathogen causing avian tuberculosis in birds. The aim of the study was to evaluate the genetic relatedness in M. avium isolates from deep tissues of farmed lesser white-fronted geese with avian tuberculosis and in samples from the farm environment. The strains were analyzed by two PCR-based typing methods, inverted repeat (IR) typing and random amplified polymorphic DNA (RAPD) analysis. The primers for the inverted repeats of the insertion sequences IS1245 and IS1311 were used in IR typing, and the RAPD analysis was performed with six primers. Seven of the nine avian strains yielded an identical pattern in the IR typing, but they could be divided into two groups in the RAPD analysis. The remaining two bird isolates had an identical IR pattern (IR cluster II) which they shared with two environmental isolates. However, the RAPD analysis revealed that these environmental isolates had a RAPD pattern (RAPD cluster VI) distinct and different from either of the bird isolates (RAPD clusters II and IV). In all, four M. avium strains were verified as being inducers of avian tuberculosis in birds, and all were distinct from the three environmental strains identified. Thus, the results did not confirm the preliminary idea that a single strain had caused the epidemic. The polymorphism among M. avium strains highlighted the great biodiversity among an M. avium population even in a limited environmental setting during a short time span, and indicated the high susceptibility to avian tuberculosis of lesser white-fronted geese.

Animal Husbandry↗
PubMed2000

Antibiotic resistance in bacteria of animal origin: methods in use to monitor resistance in EU countries.

A study on the ongoing monitoring programmes in 13 European countries was made as part of a concerted action funded by the European Commission. Five main reference systems were used in the surveyed countries and three categories of bacteria were monitored, zoonotic agents, indicator bacteria and veterinary pathogens. The five reference systems and an overview of the national monitoring programmes are described. Differences exist and there is a real need for standardisation at the European level. This harmonisation could be set up both for microbiological methods and the epidemiological results derived from common methods. Disk diffusion methods are most widely used and many of the monitored species and control strains are similar in the action's participating countries.

Animal Population Groups↗
PubMed1997

A plastid organelle as a drug target in apicomplexan parasites.

Parasites of the phylum Apicomplexa include many important human and veterinary pathogens such as Plasmodium (malaria), Toxoplasma (a leading opportunistic infection associated with AIDS and congenital neurological birth defects), and Eimeria (an economically significant disease of poultry and cattle). Recent studies have identified an unusual organelle in these parasites: a plastid that appears to have been acquired by secondary endosymbiosis of a green alga. Here we show that replication of the apicomplexan plastid (apicoplast) genome in Toxoplasma gondii tachyzoites can be specifically inhibited using ciprofloxacin, and that this inhibition blocks parasite replication. Moreover, parasite death occurs with peculiar kinetics that are identical to those observed after exposure to clindamycin and macrolide antibiotics, which have been proposed to target protein synthesis in the apicoplast. Conversely, clindamycin (and functionally related compounds) immediately inhibits plastid replication upon drug application-the earliest effect so far described for these antibiotics. Our results directly link apicoplast function with parasite survival, validating this intriguing organelle as an effective target for parasiticidal drug design.

Animals↗
PubMed1997

Structure-activity relationships between antibacterial activities and physicochemical properties of sulfonamides.

Relationships between the antimicrobial activities of sulfonamides and physicochemical properties including the acid dissociation constant (pKa) and the hydrophobicity constant (pi) were determined. The minimal inhibitory concentrations (MIC) of sulfonamides against Actinobacillus pleuropneumoniae, a gram-negative veterinary pathogen, were used. High performance liquid chromatography was applied for the determination of the electronic and hydrophobic parameters. Empirically determined relationships pointed out the dominant role of the degree of ionization on the antimicrobial activity. The data indicate that hydrophobic properties of sulfonamides, characterized by pi, are of minor importance for the in vitro antibacterial activity. Because of the restricted pKa range (4.9-7.7) it could not be established whether the relationship between pKa and activity was linear or bilinear. Whenever o,m-disubstituted sulfonamides were included correlations decreased substantially. Relationships based on multicompartment equilibrium models were derived and indicated a bilinear relation between pKa and MIC. Model-based equations showed that the antibacterial activity was governed by the extracellular ionic concentration of the sulfonamides whenever different intra and extracellular pH values were assumed in the equilibrium model. The antimicrobial activities of the sulfonamides against gram-positive organisms were also related to the degree of ionization of the sulfonamides in the agar medium.

Actinobacillus pleuropneumoniae↗
PubMed2006

X-ray structure of a native calicivirus: structural insights into antigenic diversity and host specificity.

Caliciviruses, grouped into four genera, are important human and veterinary pathogens with a potential for zoonosis. In these viruses, capsid-related functions such as assembly, antigenicity, and receptor interactions are predominantly encoded in a single protein that forms an icosahedral capsid. Understanding of the immunologic functions and pathogenesis of human caliciviruses in the Norovirus and Sapovirus genera is hampered by the lack of a cell culture system or animal models. Much of our understanding of these viruses, including the structure, has depended on recombinant capsids. Here we report the atomic structure of a native calicivirus from the Vesivirus genus that exhibits a broad host range possibly including humans and map immunological function onto a calicivirus structure. The vesivirus structure, despite a similar architectural design as seen in the recombinant norovirus capsid, exhibits novel features and indicates how the unique modular organization of the capsid protein with interdomain flexibility, similar to an antibody structure with a hinge and an elbow, integrates capsid-related functions and facilitates strain diversity in caliciviruses. The internally located N-terminal arm participates in a novel network of interactions through domain swapping to assist the assembly of the shell domain into an icosahedral scaffold, from which the protruding domain emanates. Neutralization epitopes localize to three hypervariable loops in the distal portion of the protruding domain surrounding a region that exhibits host-specific conservation. These observations suggest a mechanism for antigenic diversity and host specificity in caliciviruses and provide a structural framework for vaccine development.

Amino Acid Sequence↗
PubMed1993

Herbicides to curb human parasitic infections: in vitro and in vivo effects of trifluralin on the trypanosomatid protozoans.

Leishmaniasis is a major tropical disease for which current chemotherapies, pentavalent antimonials, are inadequate and cause severe side effects. It has been reported that trifluralin, a microtubule-disrupting herbicide, is inhibitory to Leishmania amazonensis. In this study, the in vitro effect of trifluralin on different species of trypanosomatid protozoans was determined. In addition to L. amazonensis, trifluralin is effective against Leishmania major and Leishmania tropica, which cause cutaneous infections, Leishmania donovani, which causes visceral disease, Leishmania panamensis, which may cause mucocutaneous infection, and Trypanosoma brucei, an important human and veterinary pathogen. Moreover, most encouragingly, trifluralin is effective in vivo as a topical ointment against L. major and Leishmania mexicana murine cutaneous leishmaniasis. Thus, trifluralin is a promising lead drug for several related, prevalent tropical diseases: leishmaniasis, trypanosomiasis of animals, and, possibly, African trypanosomiasis in humans.

Animals↗
PubMed2002

Bordetella bronchiseptica pleural infection in a patient with AIDS.

Bordetella bronchiseptica is an important veterinary pathogen but a rare cause of opportunistic respiratory tract infection in humans. We describe a case of pleural effusion caused by B. bronchiseptica in a patient with AIDS who was coinfected with Mycobacterium tuberculosis. To the best of our knowledge this is the first case in the medical literature in which the microorganism has been isolated from pleural fluid.

AIDS-Related Opportunistic Infections↗
PubMed2001

Isolation of single-chain antibody fragments against Venezuelan equine encephalomyelitis virus from two different immune sources.

Venezuelan equine encephalomyelitis (VEE) virus is an important human and veterinary pathogen of Central and South America. The virus can cause widespread epidemics, affecting hundreds of thousands of horses, and thousands of humans. Detection of the virus early in infection and in mosquito populations may allow epidemics to be predicted such that suitable prophylaxis, such as vaccination, can be used to reduce disease severity and transmission. The sensitivity and specificity of current immunoassays, based on conventional monoclonal and polyclonal antibodies, needs to be improved for the diagnosis of infection. We have examined phage display libraries expressing single-chain antibodies (scFv) produced from two different immune sources, a hybridoma cell line and an immunized mouse spleen. The libraries were panned against VEE virus to select for specific scFvs. scFvs isolated from both libraries were specific for the same epitope on the VEE virus and sequence analysis showed that the scFvs were almost identical apart from the CDR3 region of the heavy chain. The data presented in this article suggest that although scFvs may be useful tools for the detection of viruses, there are serious limitations with the use of phage display as a tool for the isolation of specific antibodies.

Amino Acid Sequence↗
PubMed2004

Structural analysis of the lipopolysaccharide from Pasteurella multocida genome strain Pm70 and identification of the putative lipopolysaccharide glycosyltransferases.

Pasteurella multocida is an important multispecies veterinary pathogen. The cell surface lipopolysaccharide (LPS) is an important virulence factor and forms the basis of the serotyping scheme, although little structural information about it is known. The structure of the LPS from the Pasteurella multocida genome strain Pm70 was elucidated in this study. The LPS was subjected to a variety of degradative procedures. The structures of the purified products were established by monosaccharide and methylation analyses, NMR spectroscopy, and mass spectrometry. The structure of the core oligosaccharide was determined on the basis of the combined data from these experiments. Identification of the core oligosaccharide structure enabled a search for glycosyltransferase homologs in the Pm70 genome and revealed a clustering of the genes putatively responsible for outer core oligosaccharide biosynthesis.

Carbohydrate Conformation↗
PubMed1990

Ehrlichiosis--a disease of animals and humans.

Ehrlichiae are one of several kinds of obligate intracellular bacteria. Taxonomically, they are grouped with rickettsiae, but they can be distinguished by their unique tropism for circulating leukocytes. Ehrlichia canis causes a pancytopenia in dogs that becomes chronic if untreated. Certain breeds develop severe infections, characterized by fever, anorexia, dramatic weight loss, marked pancytopenia, anemia, peripheral edema, and hemorrhage. Ehrlichia risticii, a recently discovered species, is the cause of a serious diarrheal disease of horses. Other species of ehrlichiae have been documented as being veterinary pathogens. Recent data indicate that E. canis or a closely related species causes an acute febrile illness in humans. Clinically, the disease is similar to Rocky Mountain spotted fever, except that most patients do not have a rash. Human ehrlichiosis appears to be tickborne and is prevalent primarily in the southern Atlantic and south-central states. A mild from of ehrlichiosis has also been documented.

Animals↗
PubMed1998

Mosquito feeding-induced enhancement of Cache Valley Virus (Bunyaviridae) infection in mice.

Cache-Valley (CV) virus, an arthropod-borne bunyavirus, recently has emerged as a significant veterinary pathogen causing infertility and congenital malformations in North American ruminants. To investigate the role of vector feeding on CV infection, adult mice were injected subcutaneously with CV, CV and vector thorax extract (a source of vector saliva), or CV into the site of intense, noninfected-mosquito feeding. Mice did not become infected after injection of CV or CV and vector saliva, nor did they produce antibodies to CV. However, injection of CV into sites of mosquito feeding resulted in viremia and production of anti-CV antibody by 2 wk after infection. This enhancement of CV infection resulted after feeding by Aedes triseriatus (Say), Ae. aegypti (L.), or Culex pipiens (L.). Enhancement occurred when injection was delayed up to 4 h after mosquito feeding, but it was not observed when virus injection was performed at a site distant from mosquito feeding. These results indicate that arbovirus infection may be enhanced by mosquito-vertebrate host interactions and that replication of arboviruses in arthropod vectors may not be responsible for increased virulence of infections mediated by infected arthropods. Enhanced CV infection in pregnant mice did not result in infertility or malformed pups, indicating that the mouse is not a suitable model to study CV-induced malformations.

Aedes↗
PubMed2001

Salmonella dublin infection: a rare cause of spontaneous bacterial peritonitis and chronic colitis in alcoholic liver cirrhosis.

Salmonella dublin is a veterinary pathogen which rarely causes human illness, although reported human isolates have increased over the past two decades. This serovar of salmonella is unusually invasive and life-threatening, although the clinical pattern of human infection is not well known. We describe a 51-year-old cirrhotic patient who presented with severe liver failure, chronic diarrhoea and left-sided segmental colitis. Radiological and endoscopic findings suggested Crohn's colitis. During the hospital stay he developed a spontaneous bacterial peritonitis (SBP) and S. dublin was isolated in the ascitic fluid. Our report supports the view that this salmonella serovar should be kept in mind as a rare cause of SBP in cirrhotic patients, especially in those cases with chronic colitis resembling Crohn's disease.

Chronic Disease↗
PubMed1988

Retroviruses.

First brought to scientific attention as infectious cancer-causing agents nearly 80 years ago, retroviruses are popular in contemporary biology for many reasons. (i) The virus life cycle includes several events--in particular, reverse transcription of the viral RNA genome into DNA, orderly integration of viral DNA into host chromosomes, and utilization of host mechanisms for gene expression in response to viral signals--which are broadly informative about eukaryotic cells and viruses. (ii) Retroviral oncogenesis usually depends on transduction or insertional activation of cellular genes, and isolation of those genes has provided the scientific community with many of the molecular components now implicated in the control of normal growth and in human cancer. (iii) Retroviruses include many important veterinary pathogens and two recently discovered human pathogens, the causative agents of the acquired immunodeficiency syndrome (AIDS) and adult T cell leukemia/lymphoma. (iv) Retroviruses are genetic vectors in nature and can be modified to serve as genetic vectors for both experimental and therapeutic purposes. (v) Insertion of retroviral DNA into host chromosomes can be used to mark cell lineages and to make developmental mutants. Progress in these and other areas of retrovirus-related biology has been enormous during the past two decades, but many practical and theoretical problems remain to be solved.

Animals↗
PubMed2003

Evaluation of broiler litter with reference to the microbial composition as assessed by using 16S rRNA and functional gene markers.

Very little is known about the microbial composition of animal bedding wastes, including poultry litter, and what is known has been deduced from standard culture methods, by which some fastidious organisms that exist in the environment may not be detected. We evaluated the bacterial composition of poultry litter by using a combination of culture and molecular detection. Total aerobic bacteria in poultry litter were detected by culture at 10(9) CFU/g of material. Enteric bacteria such as Enterococcus spp. and coliforms composed 0.1 and 0.01%, respectively, of the total aerobic cultivatable bacteria in poultry litter; no Salmonella strains were detected by culture. In order to characterize the most abundant bacterial groups, we sequenced 16S ribosomal DNA (rDNA) genes amplified by PCR with microbial community DNA isolated from poultry litter as the template. From the 16S rDNA library, 31 genera were identified. Twelve families or groups were identified with lactobacilli and Salinococcus spp. forming the most abundant groups. In fact, 82% of the total sequences were identified as gram-positive bacteria with 62% of total belonging to low G+C gram-positive groups. In addition to detection of 16S rDNA sequences associated with the expected fecal bacteria present in manure, we detected many bacterial sequences for organisms, such as Globicatella sulfidofaciens, Corynebacterium ammoniagenes, Corynebacterium urealyticum, Clostridium aminovalericum, Arthrobacter sp., and Denitrobacter permanens, that may be involved in the degradation of wood and cycling of nitrogen and sulfur. Several sequences were identified in the library for bacteria associated with disease in humans and poultry such as clostridia, staphylococci, and Bordetella spp. However, specific PCR targeting other human and veterinary pathogens did not detect the presence of Salmonella, pathogenic Escherichia coli, Campylobacter spp., Yersinia spp., Listeria spp., or toxigenic staphylococci. PCR and DNA hybridization revealed the presence of class 1 integrons with gene cassettes that specify resistance to aminoglycosides and chloramphenicol. Only from understanding the microbial community of animal wastes such as poultry litter can we manage animal disease and limit the impact of animal waste on the environment and human and animal health.

Animals↗