Equine piroplasmosis in different geographical areas in France: Prevalence heterogeneity of asymptomatic carriers and low genetic diversity of Theileria equi and Babesia caballi.

Equine piroplasmosis is a worldwide tick-borne disease caused by the parasites Theileria equi sensu lato and Babesia caballi, with significant economic and sanitary consequences. These two parasites are genetically variable, with a potential impact on diagnostic accuracy. Our study aimed to evaluate the frequency of asymptomatic carriers of these parasites in France and describe the circulating genotypes.

Comparative bactericidal activity of four macrolides alone and combined with rifampicin or doxycycline against at concentrations achievable in foals.

Introduction: causes life-threatening respiratory disease in foals. The standard treatment typically involves a combination of rifampicin and a macrolide antibiotic. Although previous studies have demonstrated the activity of these antibiotics against , the tested concentrations often do not reflect those achievable in foals.

Predicted efficacy and tolerance of different dosage regimens of benzylpenicillin in horses based on a pharmacokinetic study with three IM formulations and one IV formulation.

Introduction: Benzylpenicillin (BP) is a first-line antibiotic in horses but there are discrepancies between manufacturers and literature recommendations regarding dosing regimen. Objectives of this study were to evaluate pharmacokinetics and local tolerance of four different formulations of BP in adult horses, and to suggest optimized dosing regimen according to the formulation.

Methods: A cross-over design was used in 3 phases for the intramuscular injection of three different products: procaine BP alone, procaine BP/ benzathine BP combination or penethamate hydriodide were administered IM in the gluteal muscles of 6 horses for 3 days.

Pharmacokinetic-pharmacodynamic cutoff values for benzylpenicillin in horses to support the establishment of clinical breakpoints for benzylpenicillin antimicrobial susceptibility testing in horses.

Introduction: The aim of this international project was to establish a species-specific Clinical Breakpoint for interpretation of Antimicrobial Susceptibility Testing of benzylpenicillin (BP) in horses.

Methods: A population pharmacokinetic model of BP disposition was developed to compute PK/PD cutoff values of BP for different formulations that are commonly used in equine medicine around the world (France, Sweden, USA and Japan). Investigated substances were potassium BP, sodium BP, procaine BP, a combination of procaine BP and benzathine BP and penethamate, a prodrug of BP.

Kinetic disposition of diazepam and its metabolites after intravenous administration of diazepam in the horse: Relevance for doping control.

In horses, the benzodiazepine diazepam (DIA) is used as sedative for pre-medication or as an anxiolytic to facilitate horse examinations. As the sedative effects can also be abused for doping purposes, DIA is prohibited in equine sports. DIA is extensively metabolized to several active metabolites such as nordazepam, temazepam and oxazepam (OXA).

Dynamic interactions between cephalexin and macrophages on different Staphylococcus aureus inoculum sizes: a tripartite in vitro model.

Background: The bactericidal activity of an antimicrobial drug is generally assessed by in vitro bacterial time-kill experiments which do not include any components of the immune system, even though the innate immunity, the primary host defence, is probably able to kill a large proportion of pathogenic bacteria in immunocompetent patients. We developed an in vitro tripartite model to investigate the joint action of C57Bl/6 murine bone-marrow-derived macrophages and cephalexin on the killing of Staphylococcus aureus.

Results: By assessing the bactericidal effects on four bacterial inoculum sizes, we showed that macrophages can cooperate with cephalexin on inoculum sizes lower than 10 CFU/mL and conversely, protect S.

Innate promiscuity of the CYP706 family of P450 enzymes provides a suitable context for the evolution of dinitroaniline resistance in weed.

Increased metabolism is one of the main causes for evolution of herbicide resistance in weeds, a major challenge for sustainable food production. The molecular drivers of this evolution are poorly understood. We tested here the hypothesis that a suitable context for the emergence of herbicide resistance could be provided by plant enzymes with high innate promiscuity with regard to their natural substrates.

Determination of the pharmacokinetic-pharmacodynamic cut-off values of marbofloxacin in horses to support the establishment of a clinical breakpoint for antimicrobial susceptibility testing.

Background: Marbofloxacin (MBX), a fluoroquinolone (FQ), is considered as a critical antibiotic requiring antimicrobial susceptibility testing (AST) for prudent use. No clinical breakpoint (CBP) currently exists to interpret the results of such tests in horses.

Objectives: To compute PK/PD cut-offs (PK/PD ) that is one of the three minimum inhibitory concentrations (MICs) considered establishing a CBP for antimicrobial susceptibility test interpretation.

Diffusion Tensor Imaging Tractography of White Matter Tracts in the Equine Brain.

Tractography, a noninvasive technique tracing brain pathways from diffusion tensor magnetic resonance imaging (DTI) data, is increasingly being used for brain investigation of domestic mammals. In the equine species, such a technique could be useful to improve our knowledge about structural connectivity or to assess structural changes of white matter tracts potentially associated with neurodegenerative diseases. The goals of the present study were to establish the feasibility of DTI tractography in the equine brain and to provide a morphologic description of the most representative tracts in this species.

Multinodular Malignant Cutaneous Mast Cell Tumor in a Horse With Generalized Pruritus and Reactive Fibrosis: A Case Report.

Mast cell tumor (MCT) has long been considered as an uncommon neoplasm in horses. Cytological and behavioral evidence of its malignancy is usually lacking, and only a few reports have described MCT displaying malignant behavior. An 18-year-old Friesian stallion presented with a one-year history of intermittent and progressive skin lesions on the left forelimb associated with intense, generalized pruritus and apathy temporarily responsive to glucocorticoids and antibiotics.

Degradation of Antimicrobials during Use of Broth Microdilution Method Can Increase the Measured Minimal Inhibitory and Minimal Bactericidal Concentrations.

The antibacterial activity of some antimicrobials may be under-estimated during microbiological susceptibility tests, due to their instability under such conditions. The degradation of seven widely used antimicrobials (amoxicillin, cephalexin monohydrate, cefotaxime sodium salt, ciprofloxacin, erythromycin hydrate, clarithromycin, and doxycycline hyclate) and its effect on MIC and MBC determinations was studied using the broth microdilution method, considered as the gold standard for MIC determinations. concentrations of antimicrobials, over a 24 h incubation period in the medium tested without bacteria, decreased from 33% for ciprofloxacin to 69% for clarithromycin.

Use of MALDI-TOF mass spectrometry after liquid enrichment (BD Bactec™) for rapid diagnosis of bone and joint infections.

Advantages of MALDI-TOF MS (MS) were evaluated for diagnosis of bone and joint infections after enrichment of synovial fluid (SF) or crushed osteoarticular samples (CSs). MS was performed after enrichment of SF or crushed osteoarticular samples CS (n = 108) in both aerobic and anaerobic vials. Extraction was performed on 113 vials (SF: n = 47; CS: n = 66), using the Sepsityper kit prior identification by MS.

MALDI-TOF MS performance compared to direct examination, culture, and 16S rDNA PCR for the rapid diagnosis of bone and joint infections.

The rapid identification of bacterial species involved in bone and joint infections (BJI) is an important element to optimize the diagnosis and care of patients. The aim of this study was to evaluate the usefulness of matrix-assisted laser desorption ionization mass spectrometry (MALDI-TOF MS) for the rapid diagnosis of bone infections, directly on synovial fluid (SF) or on crushed osteoarticular samples (CS). From January to October 2013, we prospectively analyzed 111 osteoarticular samples (bone and joint samples, BJS) from 78 patients in care at the University Hospital of Rennes, France.

Pharmacokinetics, pharmacodynamics and local tolerance at injection site of marbofloxacin administered by regional intravenous limb perfusion in standing horses.

Objective: To evaluate pharmacokinetic-pharmacodynamic variables and local tolerance at injection-site of marbofloxacin administered via regional intravenous limb perfusion (RIVLP) in standing horses.

Animals: Adult horses (n = 6).

Methods: RIVLP were performed with rubber tourniquets applied to the forelimbs of standing sedated horses.

Effects of in vitro low oxygen tension preconditioning of adipose stromal cells on their in vivo chondrogenic potential: application in cartilage tissue repair.

Purpose: Multipotent stromal cell (MSC)-based regenerative strategy has shown promise for the repair of cartilage, an avascular tissue in which cells experience hypoxia. Hypoxia is known to promote the early chondrogenic differentiation of MSC. The aim of our study was therefore to determine whether low oxygen tension could be used to enhance the regenerative potential of MSC for cartilage repair.

Minimal role for the circumsporozoite protein in the induction of sterile immunity by vaccination with live rodent malaria sporozoites.

Immunization with live Plasmodium sporozoites under chloroquine prophylaxis (Spz plus CQ) induces sterile immunity against sporozoite challenge in rodents and, more importantly, in humans. Full protection is obtained with substantially fewer parasites than with the classic immunization with radiation-attenuated sporozoites. The sterile protection observed comprised a massive reduction in the hepatic parasite load and an additional effect at the blood stage level.

Lymphopenia-induced spontaneous T-cell proliferation as a cofactor for autoimmune disease development.

Lymphopenia is thought to be a major cause of tolerance breakdown. In a lymphopenic environment, self-recognition events induce some T cells to expand strongly (a mechanism known as spontaneous proliferation). In this study, we show that in C57BL/6 mice, the repertoire resulting from lymphopenia-induced spontaneous CD4(+) T-cell proliferation included a proportion of regulatory T cells as large as that observed in a normal mouse, and no autoimmune disorder was observed.

Sterile protection against malaria is independent of immune responses to the circumsporozoite protein.

Background: Research aimed at developing vaccines against infectious diseases generally seeks to induce robust immune responses to immunodominant antigens. This approach has led to a number of efficient bacterial and viral vaccines, but it has yet to do so for parasitic pathogens. For malaria, a disease of global importance due to infection by Plasmodium protozoa, immunization with radiation-attenuated sporozoites uniquely leads to long lasting sterile immunity against infection.

Estimation of absolute oral bioavailability of moxidectin in dogs using a semi-simultaneous method: influence of lipid co-administration.

Moxidectin is a long-acting anthelmintic drug for which little is known about its kinetic behaviour in dogs and its oral absolute bioavailability has never been reported. We studied the pharmacokinetics of moxidectin in dogs, with a special emphasis on oral bioavailability and the influence of lipid co-administration, by using a semi-simultaneous method of administration. Ten Beagle dogs were dosed orally and then intravenously (i.

1,3,5-Triazepane-2,6-diones as structurally diverse and conformationally constrained dipeptide mimetics: identification of malaria liver stage inhibitors from a small pilot library.

The development of the 1,3,5-triazepane-2,6-dione system as a novel, conformationally restricted, and readily accessible class of dipeptidomimetics is reported. The synthesis of the densely functionalized 1,3,5-triazepane-2,6-dione skeleton was achieved in only four steps from a variety of simple linear dipeptide precursors. To extend the practical value of 1,3,5-triazepane-2,6-diones, a general polymer-assisted solution-phase synthesis approach amenable to library production in a multiparallel format was developed.

Contribution of lymphatic transport to the systemic exposure of orally administered moxidectin in conscious lymph duct-cannulated dogs.

Moxidectin, a macrocyclic lactone (ML), is a potent parasiticide widely used in veterinary medicine and currently under development for use in humans. The contribution of the lymphatic route to the intestinal absorption and transport of moxidectin to the systemic circulation was evaluated in lymph duct-cannulated dogs. Beagle dogs were operated for lymph duct cannulation and were orally dosed with 38g of corn oil and moxidectin (0.

Transgenic expression of CD95 ligand on thyroid follicular cells confers immune privilege upon thyroid allografts.

Constitutive Fas ligand (FasL) expression by specialized cells in the body participates in the immune privilege status of tissues containing these cells. This property has been used to prevent rejection of allogeneic grafts. Nevertheless, the mechanism responsible for such protection has not been fully elucidated.

A medical research council randomized trial of single agent carboplatin versus etoposide and cisplatin for advanced metastatic seminoma. MRC Testicular Tumour Working Party.

The UK Medical Research Council conducted this trial of carboplatin chemotherapy in advanced seminoma to compare single agent carboplatin with a standard combination of etoposide with cisplatin. The use of single agent carboplatin was expected to be associated with reduced toxicity. A total of 130 patients with advanced seminoma were randomly assigned to treatment with either single agent carboplatin (C) at a dose of 400 mg/m(2)to be corrected for glomerular filtration rate outside the range 81-120 ml min(-1)and to be administered on day 1 of a 21 day cycle to a total of 4 cycles or to etoposide + platinum (EP).

Impact of the treating institution on survival of patients with "poor-prognosis" metastatic nonseminoma. European Organization for Research and Treatment of Cancer Genito-Urinary Tract Cancer Collaborative Group and the Medical Research Council Testicular Cancer Working Party.

Background: Because metastatic nonseminomatous germ cell cancer is a rare but treatable cancer, we have explored whether there is an association between the experience of the treating institution with this disease and the long-term clinical outcome of the patients, particularly patients with a poor prognosis.

Methods: We analyzed data on 380 patients treated in one of 49 institutions participating in the European Organization for Research and Treatment of Cancer/ Medical Research Council randomized trial of four cycles of bleomycin-etoposide-cisplatin followed by two cycles of etoposide-cisplatin versus three cycles of bleomycin-vincristine-cisplatin followed by three cycles of etoposide-ifosfamide-cisplatin-bleomycin, both treatment regimens given with or without filgrastim (granulocyte colony-stimulating factor). Institutions were divided into four groups based on the total number of patients entered in the trial.

Filgrastim during combination chemotherapy of patients with poor-prognosis metastatic germ cell malignancy. European Organization for Research and Treatment of Cancer, Genito-Urinary Group, and the Medical Research Council Testicular Cancer Working Party, Cambridge, United Kingdom.

Purpose: To determine the effect of r-metHu granulocyte colony-stimulating factor (G-CSF) on the proportion of patients with metastatic poor-prognosis malignant germ cell tumors who receive full dose-intensity combination chemotherapy.

Patients And Methods: In a phase III study patients received six cycles of BEP/EP (etoposide, and cisplatin, plus or minus bleomycin) or six cycles of BOP/VIP-B (bleomycin, vincristine, cisplatin/etoposide, ifosfamide, cisplatin, bleomycin). A subset were secondarily randomized to receive or not receive filgrastim.