MSD Animal Health Innovation

Beaucouzé, France

MSD Animal Health Innovation

Beaucouzé, France
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Jiang J.,National University of Singapore | Miyata M.,MSD Animal Health Innovation | Chan C.,National University of Singapore | Ngoh S.Y.,National University of Singapore | And 11 more authors.
PLoS ONE | Year: 2014

Vaccination is an important strategy in the protection of aquaculture species from major diseases. However, we still do not have a good understanding of the mechanisms underlying vaccine-induced disease resistance. This is further complicated by the presence of several lymphoid organs that play different roles when mounting an immune response. In this study, we attempt to elucidate some of these mechanisms using a microarray-based approach. Asian seabass (Lates calcarifer) were vaccinated against Streptococcus iniae and the transcriptomic changes within the spleen and head kidney at one and seven days post-vaccination were profiled. We subsequently challenged the seabass at three weeks post-vaccination with live S. iniae and similarly profiled the transcriptomes of the two organs after the challenge. We found that vaccination induced an early, but transient transcriptomic change in the spleens and a delayed response in the head kidneys, which became more similar to one another compared to un-vaccinated ones. When challenged with the pathogen, the spleen, but not the head kidneys, responded transcriptomically at 25-29 hours post-challenge. A unique set of genes, in particular those involved in the activation of NF-κB signaling, was up-regulated in the vaccinated spleens upon pathogen challenge but not in the unvaccinated spleens. A semi-quantitative PCR detection of S. iniae using metagenomic DNA extracted from the water containing the seabass also revealed that vaccination resulted in reduction of pathogen shedding. This result indicated that vaccination not only led to a successful immune defense against the infection, but also reduced the chances for horizontal transmission of the pathogen. In conclusion, we have provided a transcriptomic analysis of how the teleost spleen and head kidneys responded to vaccination and subsequent infection. The different responses from the two organs are suggestive of their unique roles in establishing a vaccine-induced disease resistance. © 2014 Jiang et al.


Smith P.,National University of Ireland | Endris R.,Merck Animal Health Summit | Thomas V.,MSD Animal Health Innovation | Verner-Jeffreys D.,CEFAS Weymouth Laboratory Weymouth | And 2 more authors.
Journal of Fish Diseases | Year: 2015

Epidemiological cut-off values were developed for application to antibiotic susceptibility data for Flavobacterium psychrophilum generated by standard CLSI test protocols. The MIC values for ten antibiotic agents against Flavobacterium psychrophilum were determined in two laboratories. For five antibiotics, the data sets were of sufficient quality and quantity to allow the setting of valid epidemiological cut-off values. For these agents, the cut-off values, calculated by the application of the statistically based normalized resistance interpretation method, were ≤16 mg L-1 for erythromycin, ≤2 mg L-1 for florfenicol, ≤0.025 mg L-1 for oxolinic acid (OXO), ≤0.125 mg L-1 for oxytetracycline and ≤20 (1/19) mg L-1 for trimethoprim/sulphamethoxazole. For ampicillin and amoxicillin, the majority of putative wild-type observations were 'off scale', and therefore, statistically valid cut-off values could not be calculated. For ormetoprim/sulphadimethoxine, the data were excessively diverse and a valid cut-off could not be determined. For flumequine, the putative wild-type data were extremely skewed, and for enrofloxacin, there was inadequate separation in the MIC values for putative wild-type and non-wild-type strains. It is argued that the adoption of OXO as a class representative for the quinolone group would be a valid method of determining susceptibilities to these agents. © 2014 John Wiley & Sons Ltd.


PubMed | Nanyang Technological University, National University of Singapore, Murdoch University and MSD Animal Health Innovation
Type: Journal Article | Journal: PloS one | Year: 2014

Vaccination is an important strategy in the protection of aquaculture species from major diseases. However, we still do not have a good understanding of the mechanisms underlying vaccine-induced disease resistance. This is further complicated by the presence of several lymphoid organs that play different roles when mounting an immune response. In this study, we attempt to elucidate some of these mechanisms using a microarray-based approach. Asian seabass (Lates calcarifer) were vaccinated against Streptococcus iniae and the transcriptomic changes within the spleen and head kidney at one and seven days post-vaccination were profiled. We subsequently challenged the seabass at three weeks post-vaccination with live S. iniae and similarly profiled the transcriptomes of the two organs after the challenge. We found that vaccination induced an early, but transient transcriptomic change in the spleens and a delayed response in the head kidneys, which became more similar to one another compared to un-vaccinated ones. When challenged with the pathogen, the spleen, but not the head kidneys, responded transcriptomically at 25-29 hours post-challenge. A unique set of genes, in particular those involved in the activation of NF-B signaling, was up-regulated in the vaccinated spleens upon pathogen challenge but not in the un-vaccinated spleens. A semi-quantitative PCR detection of S. iniae using metagenomic DNA extracted from the water containing the seabass also revealed that vaccination resulted in reduction of pathogen shedding. This result indicated that vaccination not only led to a successful immune defense against the infection, but also reduced the chances for horizontal transmission of the pathogen. In conclusion, we have provided a transcriptomic analysis of how the teleost spleen and head kidneys responded to vaccination and subsequent infection. The different responses from the two organs are suggestive of their unique roles in establishing a vaccine-induced disease resistance.


Saint-Dizier M.,CNRS Physiology of Reproduction and Behaviors | Legendre A.-C.,University Paris Est Creteil | Driancourt M.-A.,MSD Animal Health Innovation | Chastant-Maillard S.,National Polytechnic Institute of Toulouse
Reproduction in Domestic Animals | Year: 2014

Contents: Luteolysis before the time of maternal recognition of pregnancy is one cause of low fertility in high-producing dairy cows. The objective of this study was to assess whether induction of a secondary corpus luteum (CL) late in the luteal phase would delay the time of luteolysis. Twenty high-producing Holstein cows were synchronized to ovulation (Day 0) with the Ovsynch protocol and received hCG (1500 IU im) on Day 12. Corpora lutea formation (as evaluated by ultrasonography) and plasma P4 concentrations were monitored from Days 4 to 36. hCG treatment induced the formation of one secondary CL (CL2) in 11 of 20 cows (55%) from the dominant follicle (mean diameter: 14.2 ± 0.9 mm) of two-wave (3/11) and three-wave (8/11) cycles. The maximal diameter of the CL2 (23.3 ± 1.9 mm) was reached approximately 6 days after hCG treatment and was correlated with its structural lifespan (p < 0.01). Cows that formed a CL2 after hCG had higher mean plasma P4 concentrations on Day 14 (+4.5 ng/ml) and Day 18 (+3.0 ng/ml) compared with cows without CL2 (p < 0.05). The structural regression of CL2 begun approximately 8 days after that of the CL1, and the median time at which the first drop in circulating P4 levels occurred was later in cows that formed a CL2 than in those that did not (Day 26 vs Day 18; p < 0.01). Thus, the induction of a CL2 by hCG on Day 12 might reduce the risk of premature luteolysis in high-producing dairy cows after insemination. © 2014 Blackwell Verlag GmbH.


Sipka A.,Cornell University | Gurjar A.,Cornell University | Klaessig S.,Cornell University | Duhamel G.E.,Cornell University | And 4 more authors.
Journal of Dairy Science | Year: 2013

Mastitis in dairy cows is typically treated with intramammary antibiotics. The combination of antibiotics with corticosteroids tends to have a large market share where these products are registered. Our objective was to investigate the effect of prednisolone in combination with cefapirin on the inflammatory response of experimentally induced Escherichia coli mastitis. Six midlactating Holstein-Friesian cows were challenged in 3 quarters with E. coli and treated at 4, 12, 24, and 36. h postinfection with 300. mg of cefapirin in 1 quarter and a combination of 300. mg of cefapirin and 20. mg of prednisolone in another quarter. At 24. h (n = 3) or 48. h (n = 3) postinfection cows were euthanized for tissue sampling. Clinical scores, somatic cell count, and California mastitis test scores, as well as IL-1β, IFN-γ, IL-4, and IL-10 levels and bacterial growth in milk, were measured every 6. h. Experimental inoculation caused a moderate clinical mastitis in all cows in challenged, untreated quarters. The E. coli challenge strain was recovered from all infected quarters and confirmed by PCR-based fingerprinting. Challenged, untreated control quarters showed increased concentrations of all measured cytokines together with recruitment of polymorphonuclear neutrophilic leukocytes at 24 and 48. h postchallenge. Both treatments reduced udder swelling and sensitivity with no statistically significant difference between treatment groups. Administration of cefapirin alone or in combination with prednisolone resulted in significantly lower concentrations of IFN-γ, IL-1β, and IL-10 compared with challenged, untreated quarters. Treated quarters did show IL-4 production, but concentrations were significantly decreased compared with untreated, challenged quarters. Quarters treated with the combination of cefapirin and prednisolone showed a significantly lower concentration of IL-4 compared with cefapirin-only treatment. At both 24 and 48. h postinoculation, the level of polymorphonuclear neutrophilic leukocyte recruitment was lowest in challenged quarters treated with a combination of cefapirin and prednisolone, followed by cefapirin alone. Taken together, treatment with cefapirin alone inhibited bacterial growth in milk and reduced the host inflammatory responses. Addition of prednisolone to cefapirin had a synergistic effect, resulting in a lower density of leukocytes in tissue and milk and a quicker restoration of milk quality. © 2013 American Dairy Science Association.


Driancourt M.A.,MSD Animal Health Innovation | Cox P.,MSD Animal Health Innovation | Rubion S.,MSD Animal Health Innovation | Harnois-Milon G.,MSD Animal Health Innovation | And 2 more authors.
Theriogenology | Year: 2013

The aim of this study was to demonstrate successful breeding of sows with a single fixed-time insemination following ovulation induction by buserelin, a GnRH analogue. In a first step, the optimal dose of buserelin (6, 10, or 16 μg) injected at 77 hours after weaning was determined in weaned sows (N = 15, 11, and 12, respectively) using its ability to induce an LH surge of similar magnitude as in control sows (N = 15) and induce ovulation. In 29/38 treated sows (76%), ovulation was induced and synchronized between 32 and 44 hours after injection, and the proportion of females ovulating during this time window was similar between groups at 73%, 73%, and 83% (6, 10, or 16 μg, respectively). Interestingly, whereas ovulation of 100% multiparous sows was induced and synchronized in the 32 to 44 hours posttreatment time window, successful induction was achieved in a lower proportion of primiparous sows (50%, 50%, and 67% following 6, 10, or 16 μg, respectively), the dose effect being nonsignificant. The magnitude of the LH surge was similar between control and treated sows, irrespective of the buserelin dose injected. Neither ovulation rate nor the number of good embryos on Day 5 postovulation differed between groups. Interestingly, the frequency of follicular cysts at slaughter was significantly affected by treatment (P < 0.05), being minimal and maximal in sows treated with 10 or 6 μg buserelin, respectively. In a second step, 419 sows from commercial herds in Spain, Germany, and France were randomly allocated to a control or treated group. The control sows were inseminated twice 12 ± 4 hours apart once estrus was detected. Treated sows received 10 μg buserelin at 86 ± 3 hours after weaning and were inseminated once 30 to 33 hours later. Farrowing rate of treated sows (87%, 166/192) was similar to that of control sows (84.5%, 169/200). Litter size was also similar between treated and control sows (13.6 ± 3.8 vs. 13.7 ± 3.2). In multiparous sows, neither duration of lactation nor magnitude of the fat loss during lactation significantly affected treatment effects. It is concluded that ovulation of weaned multiparous sows can be tightly synchronized by buserelin (10 μg) administration at 86 hours postweaning. This allows breeding once at a fixed time following buserelin injection while maintaining reproductive performance at a level similar to that of sows bred twice during estrus. © 2013 Elsevier Inc.


van Dijl I.C.,University Utrecht | Le Traon G.,MSD Animal Health Innovation | van de Meulengraaf B.D.A.M.,University Utrecht | Burgaud S.,MSD Animal Health Innovation | And 2 more authors.
Journal of Veterinary Internal Medicine | Year: 2014

Background: Oral levothyroxine (l-T4) supplementation is commonly used to treat hypothyroid dogs. Objectives: Investigate the plasma profile and pharmacokinetics of total thyroxine (tT4) after PO administration of a l-T4 solution and its clinical efficacy in hypothyroid dogs. Animals: Ten dogs with naturally occurring hypothyroidism. Methods: After hypothyroidism diagnosis and supplementation with l-T4 solution PO q24h at 20 μg/kg BW for minimum 4 weeks, the plasma profile and pharmacokinetics of tT4 were determined over 34 hours and the clinical condition of the dogs was evaluated. Results: Before dosing for pharmacokinetic evaluation, mean tT4 concentration was 23 ± 9 nmol/L. l-T4 was absorbed rapidly (tmax, 5 hours), reaching a mean maximal tT4 concentration of 56 ± 11 nmol/L. The apparent terminal half-life was 11.8 hours. Clinical signs of hypothyroidism improved or resolved in all dogs after 4 weeks of treatment. The dosage of 20 μg/kg PO q24h was judged appropriate in 5 dogs, and 4 dogs required slight increases (9-16%). Twice daily treatment, with a 30% increase in dosage, was necessary for 1 dog. Conclusions and Clinical Importance: The pharmacokinetics of l-T4 in hypothyroid dogs was similar to that reported in healthy euthyroid dogs. Clinical and hormonal responses to l-T4 solution were rapid in all dogs. The starting dosage of 20 μg/kg PO q24h was suitable for maintenance supplementation in 50% of the dogs, minor dosage modification was required in 4 other dogs, and treatment q12h was required in 1 dog. © 2014 by the American College of Veterinary Internal Medicine.


PubMed | MSD Animal Health Innovation
Type: Journal Article | Journal: Theriogenology | Year: 2013

The aim of this study was to demonstrate successful breeding of sows with a single fixed-time insemination following ovulation induction by buserelin, a GnRH analogue. In a first step, the optimal dose of buserelin (6, 10, or 16 g) injected at 77 hours after weaning was determined in weaned sows (N = 15, 11, and 12, respectively) using its ability to induce an LH surge of similar magnitude as in control sows (N = 15) and induce ovulation. In 29/38 treated sows (76%), ovulation was induced and synchronized between 32 and 44 hours after injection, and the proportion of females ovulating during this time window was similar between groups at 73%, 73%, and 83% (6, 10, or 16 g, respectively). Interestingly, whereas ovulation of 100% multiparous sows was induced and synchronized in the 32 to 44 hours posttreatment time window, successful induction was achieved in a lower proportion of primiparous sows (50%, 50%, and 67% following 6, 10, or 16 g, respectively), the dose effect being nonsignificant. The magnitude of the LH surge was similar between control and treated sows, irrespective of the buserelin dose injected. Neither ovulation rate nor the number of good embryos on Day 5 postovulation differed between groups. Interestingly, the frequency of follicular cysts at slaughter was significantly affected by treatment (P < 0.05), being minimal and maximal in sows treated with 10 or 6 g buserelin, respectively. In a second step, 419 sows from commercial herds in Spain, Germany, and France were randomly allocated to a control or treated group. The control sows were inseminated twice 12 4 hours apart once estrus was detected. Treated sows received 10 g buserelin at 86 3 hours after weaning and were inseminated once 30 to 33 hours later. Farrowing rate of treated sows (87%, 166/192) was similar to that of control sows (84.5%, 169/200). Litter size was also similar between treated and control sows (13.6 3.8 vs. 13.7 3.2). In multiparous sows, neither duration of lactation nor magnitude of the fat loss during lactation significantly affected treatment effects. It is concluded that ovulation of weaned multiparous sows can be tightly synchronized by buserelin (10 g) administration at 86 hours postweaning. This allows breeding once at a fixed time following buserelin injection while maintaining reproductive performance at a level similar to that of sows bred twice during estrus.

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