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Pyorala S.,University of Helsinki | Baptiste K.E.,National Board of Health | Catry B.,Scientific Institute of Public Health | van Duijkeren E.,National Institute for Public Health and the Environment | And 9 more authors.
Veterinary Journal | Year: 2014

Macrolides and lincosamides are important antibacterials for the treatment of many common infections in cattle and pigs. Products for in-feed medication with these compounds in combination with other antimicrobials are commonly used in Europe. Most recently approved injectable macrolides have very long elimination half-lives in both pigs and cattle, which allows once-only dosing regimens. Both in-feed medication and use of long-acting injections result in low concentrations of the active substance for prolonged periods, which causes concerns related to development of antimicrobial resistance.Acquired resistance to macrolides and lincosamides among food animal pathogens, including some zoonotic bacteria, has now emerged. A comparison of studies on the prevalence of resistance is difficult, since for many micro-organisms no agreed standards for susceptibility testing are available. With animal pathogens, the most dramatic increase in resistance has been seen in the genus Brachyspira. Resistance towards macrolides and lincosamides has also been detected in staphylococci isolated from pigs and streptococci from cattle. This article reviews the use of macrolides and lincosamides in cattle and pigs, as well as the development of resistance in target and some zoonotic pathogens. The focus of the review is on European conditions. © 2014.

Bouissou-Schurtz C.,Agence Nationale de Securite du Medicament ANSM | Houeto P.,Agence Nationale de Securite du Medicament ANSM | Guerbet M.,University of Rouen | Bachelot M.,Montpellier University | And 5 more authors.
Regulatory Toxicology and Pharmacology | Year: 2014

In this study, we focused on the list of 33 chemicals that was established through a French national prioritisation strategy. Assessing the potential risks to the environment was a step-wise procedure: (i) we determined the Predicted Environmental Concentration (PEC) of all molecules measured in the national survey based on the highest recommended dose used, (ii) we used the Measured Environmental Concentration (MEC) and the Predicted No-Effect Concentration (PNEC) to establish the Risk Quotient (RQ) based on either a PEC/PNEC (estimated risk) or MEC/PNEC (real risk) ratio. The risk assessment was performed using a binary ecological classification suggesting that appreciable risk is likely (RQ. ≥. 1). Of the 15 molecules quantified in the survey, 12 had a PEC higher than the action limit value of 0.01. μg/L. According to the EU Guideline, environmental risk was estimated as likely for the following five compounds: acetaminophen (RQ. = 1.6), ibuprofen (RQ. = 600), diclofenac (RQ. = 15), oxazepam (RQ. = 2.1) and carbamazepine (RQ. = 3.2). Only ibuprofen was identified as posing real environmental risk based on its MEC (RQ. = 1.9). © 2014.

Van Duijkeren E.,National Institute for Public Health and the Environment | Greko C.,National Veterinary Institute | Pringle M.,National Veterinary Institute | Baptiste K.E.,Danish Health and Medicines Authority | And 12 more authors.
Journal of Antimicrobial Chemotherapy | Year: 2014

Pleuromutilins (tiamulin and valnemulin) are antimicrobial agents that are used mainly in veterinary medicine, especially for swine and to a lesser extent for poultry and rabbits. In pigs, tiamulin and valnemulin are used to treat swine dysentery, spirochaete-associated diarrhoea, porcine proliferative enteropathy, enzootic pneumonia and other infections where Mycoplasma is involved. There are concerns about the reported increases in the MICs of tiamulin and valnemulin for porcine Brachyspira hyodysenteriae isolates from different European countries, as only a limited number of antimicrobials are available for the treatment of swine dysentery where resistance to these antimicrobials is already common and widespread. The loss of pleuromutilins as effective tools to treat swine dysentery because of further increases in resistance or as a consequence of restrictions would present a considerable threat to pig health, welfare and productivity. In humans, only one product containing pleuromutilins (retapamulin) is authorized currently for topical use; however, products for oral and intravenous administration to humans with serious multidrug-resistant skin infections and respiratory infections, including those caused by methicillin-resistant Staphylococcus aureus (MRSA), are being developed. The objective of this review is to summarize the current knowledge on the usage of pleuromutilins, resistance development and the potential impact of this resistance on animal and human health. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.

Nicot S.,Agence Nationale de Securite Sanitaire ANSES | Bencsik A.,Agence Nationale de Securite Sanitaire ANSES | Morignat E.,Agence Nationale de Securite Sanitaire ANSES | Mestre-Frances N.,Montpellier University | And 2 more authors.
Emerging Infectious Diseases | Year: 2012

We compared transmission characteristics for prions from L-type bovine spongiform encephalopathy and MM2- cortical sporadic Creutzfeldt-Jakob disease in the Syrian golden hamster and an ovine prion protein-transgenic mouse line and isolated distinct prion strains. Our fi ndings suggest the absence of a causal relationship between these diseases, but further investigation is warranted.

Kovacs G.G.,Medical University of Vienna | Wagner U.,AJ Roboscreen GmbH | Dumont B.,French National Center for Scientific Research | Pikkarainen M.,University of Eastern Finland | And 10 more authors.
Acta Neuropathologica | Year: 2012

α-Synuclein is the major protein associated with Lewy body dementia, Parkinson's disease and multiple system atrophy. Since α-synuclein is present in the brain in physiological conditions as a presynaptic protein, it is crucial to characterize disease-associated modifications to develop an in vivo biomarker. With the aim to develop antibodies showing high specificity and sensitivity for disease-associated α-synuclein, synthetic peptides containing different amino acid sequences were used for immunization of mice. After generation of α-synuclein aggregates, ELISA and immunoblotting were used to test the specificity of antibodies. Tissue microarray sections originating from different human α-synucleinopathies were used to compare immunostaining with other, commercially available antibodies. Immunization of mice with the peptide TKEGVVHGVATVAE (amino acid 44-57 of α-synuclein) resulted in the generation of a monoclonal antibody (5G4), which was able to bind aggregated α-synuclein preparation in sandwich ELISA or coated on magnetic beads. 5G4 proved to be superior to other antibodies in comparative immunohistochemical studies by revealing more widespread and distinct α-synuclein pathology. Immunoblotting of human brain tissue revealed an additional band seen in dementia with Lewy bodies, whereas the band representing monomeric α-synuclein was very weak or lacking. In summary, the 5G4 antibody is most promising for re-evaluation of archival material and may offer new perspective for the development of in vivo diagnostic assays for detecting disease-associated α-synuclein in body fluids. © 2012 Springer-Verlag.

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