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Siska Croubels - One of the best experts on this subject based on the ideXlab platform.
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Immunomodulatory properties of Gamithromycin and ketoprofen in lipopolysaccharide-challenged calves with emphasis on the acute-phase response.
Veterinary immunology and immunopathology, 2016Co-Authors: Elke Plessers, Anneleen Watteyn, Heidi Wyns, Bart Pardon, Patrick De Backer, Siegrid De Baere, Stanislas Sys, Siska CroubelsAbstract:Abstract Macrolide antibiotics and non-steroidal anti-inflammatory drugs (NSAIDs) have been reported to be modulators of the innate immune response, irrespectively of their antimicrobial and anti-inflammatory actions. Therefore, it was our objective to evaluate whether the macrolide Gamithromycin (GAM) and the NSAID ketoprofen (KETO) attenuate the acute-phase response in calves, and whether their combined administration is beneficial due to synergistic and/or additive effects. To this end, both drugs, as well as their combination, were studied in a previously developed inflammation model, i.e., the induction of an acute-phase response by an intravenous lipopolysaccharide (LPS) challenge (0.5 μg/kg body weight). Sixteen 4-week-old Holstein–Friesian calves were randomized into 4 groups: a positive control (+CONTR) group, receiving LPS but no pharmacological treatment ( n = 4) and a GAM ( n = 4), a KETO ( n = 4) and a GAM–KETO ( n = 4) group, receiving the respective drugs 1 h prior to LPS administration. Clinical scoring and blood collection were performed at regular time points until 72 h post LPS challenge. Plasma concentrations of the selected cytokines (tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6)), acute-phase protein (serum amyloid A (SAA)) and prostaglandin E 2 (PGE 2 ) were subsequently quantified. Pre-treatment with GAM had no effect in the inflammation model compared to the +CONTR group. KETO, on the other hand, completely inhibited depression, anorexia and fever. This remarkable influence was associated with a significant reduction of PGE 2 synthesis by KETO, while the effect on TNF-α, IL-6 and SAA was not straightforward. The combined administration of GAM and KETO provided no synergistic or additive effects in this model, neither clinically nor regarding the studied inflammatory mediators. In conclusion, KETO entirely inhibited PGE 2 synthesis, fever development and depression, while GAM did not exert any effect in this model. These results promote the concomitant use of an antimicrobial drug and a NSAID in the treatment of calf diseases associated with LPS, both to enhance clinical recovery and to improve animal welfare.
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modulation by Gamithromycin and ketoprofen of in vitro and in vivo porcine lipopolysaccharide induced inflammation
Veterinary Immunology and Immunopathology, 2015Co-Authors: Heidi Wyns, Anneleen Watteyn, Elke Plessers, Evelyne Meyer, Patrick De Backer, Siegrid De Baere, Mathias Devreese, Thomas Van Bergen, Stijn Schauvliege, Siska CroubelsAbstract:The immunomodulatory properties of Gamithromycin (GAM), ketoprofen (KETO) and their combination (GAM-KETO) were investigated after both in vitro and in vivo lipopolysaccharide (LPS)-induced inflammation. The influence of these drugs was measured on the production of prostaglandin E2 (PGE2) and the pro-inflammatory cytokines tumour necrosis factor (TNF)-α, interleukin (IL)-6 and IL-1β in both LPS-stimulated porcine peripheral blood mononuclear cells (PBMCs) and LPS-challenged pigs. Additionally, effects on the production of acute phase proteins (APPs), including pig major acute phase protein (pig-MAP) and C-reactive protein (CRP), as well as on the development of fever, pulmonary symptoms and sickness behaviour were investigated. Dexamethasone was included as a positive control in the in vitro research. Following an 18h-incubation period with 1.25μg/mL LPS, the levels of TNF-α, IL-1β and IL-6 (p<0.05) measured in the PBMC supernatants were significantly increased. Incubation with a high concentration of both GAM and KETO significantly reduced the in vitro levels of all three cytokines. Maximal plasma concentrations of TNF-α and IL-6 were observed at 1h and 2.5h following LPS challenge in pigs, respectively. Neither GAM, nor KETO nor the combination GAM-KETO was able to inhibit the in vivo LPS-induced cytokine production. Furthermore, none of the drugs influenced the subsequent APPs production. In contrast, administration of KETO significantly reduced PGE2 production both in vitro and in vivo (p<0.05 and p<0.001, respectively) and prevented the development of fever and severe symptoms, including dyspnoea, anorexia, vomiting and lateral decubitus.
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Study of the immunomodulatory properties of Gamithromycin and dexamethasone in a lipopolysaccharide inflammation model in calves.
Research in veterinary science, 2015Co-Authors: Elke Plessers, Anneleen Watteyn, Heidi Wyns, P. De Backer, Bart Pardon, Siska CroubelsAbstract:The aim of this study was to define the in vivo immunomodulatory properties of the macrolide antibiotic Gamithromycin in calves, with respect to the acute phase response. Additionally, the corticosteroid dexamethasone was included as a positive control immunomodulatory drug. Both drugs, as well as their combination,were studied in a previously developed inflammation model,which was initiated by an intravenous lipopolysaccharide (LPS) challenge (0.5 μg/kg body weight). Twenty-four 4-week-old male Holstein Friesian calves were randomized into four groups: no pharmacological treatment (n = 6) or a pharmacological treatment with Gamithromycin (n= 6), dexamethasone (n= 6) or their combination (n= 6) 1 h prior to LPS administration. Blood collection and clinical scoring were performed at regular time points until 72 h post LPS challenge. Plasma concentrations of selected cytokines (tumour necrosis factor-α (TNF-α) and interleukin 6 (IL-6)) and acute phase proteins (serum amyloid A and haptoglobin) were subsequently determined. Gamithromycin did not have any beneficial effect on the LPS-induced clinical signs (dyspnea, fever, anorexia and depression), nor on the studied inflammatory mediators. In the dexamethasone and combination groups, the occurrence of dyspnea and fever was not prominently influenced, although the calves recovered significantly faster from the challenge. Moreover, dexamethasone significantly inhibited the levels of TNF-α and IL-6, suggesting a key role for these cytokines in sickness behaviour. In conclusion, unlike dexamethasone, Gamithromycin did not directly reduce cytokine release in an LPS inflammation model in calves.
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Modulation by Gamithromycin and ketoprofen of in vitro and in vivo porcine lipopolysaccharide-induced inflammation.
Veterinary immunology and immunopathology, 2015Co-Authors: Heidi Wyns, Anneleen Watteyn, Elke Plessers, Evelyne Meyer, Patrick De Backer, Siegrid De Baere, Mathias Devreese, Thomas Van Bergen, Stijn Schauvliege, Siska CroubelsAbstract:The immunomodulatory properties of Gamithromycin (GAM), ketoprofen (KETO) and their combination (GAM-KETO) were investigated after both in vitro and in vivo lipopolysaccharide (LPS)-induced inflammation. The influence of these drugs was measured on the production of prostaglandin E2 (PGE2) and the pro-inflammatory cytokines tumour necrosis factor (TNF)-α, interleukin (IL)-6 and IL-1β in both LPS-stimulated porcine peripheral blood mononuclear cells (PBMCs) and LPS-challenged pigs. Additionally, effects on the production of acute phase proteins (APPs), including pig major acute phase protein (pig-MAP) and C-reactive protein (CRP), as well as on the development of fever, pulmonary symptoms and sickness behaviour were investigated. Dexamethasone was included as a positive control in the in vitro research. Following an 18h-incubation period with 1.25μg/mL LPS, the levels of TNF-α, IL-1β and IL-6 (p
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pharmacokinetic and pharmacodynamic properties of Gamithromycin in turkey poults with respect to ornithobacterium rhinotracheale
Poultry Science, 2015Co-Authors: Anneleen Watteyn, Elke Plessers, Heidi Wyns, Patrick De Backer, Siegrid De Baere, Freddy Haesebrouck, Filip Boyen, Mathias Devreese, Siska CroubelsAbstract:The macrolide Gamithromycin (GAM) has the ability to accumulate in tissues of the respiratory tract. Consequently, GAM might be a suitable antibiotic to treat bacterial respiratory infections in poultry, such as Ornithobacterium rhinotracheale. As O. rhinotracheale infections are common in turkey flocks, the aim of this study was to determine the pharmacokinetic (PK) parameters of GAM in plasma, lung tissue, and pulmonary epithelial lining fluid (PELF) of turkeys and to correlate them with pharmacodynamic (PD) characteristics (PK/PD). The animal experiment was performed with 64 turkeys, which received either a subcutaneous (SC, n=32) or an oral (PO, n=32) bolus of 6 mg GAM/kg body weight (BW). GAM concentrations in plasma, lung tissue, and PELF were measured at different time points post administration (p.a.), and PK characteristics were determined using non-compartmental modeling. The maximum plasma concentration after PO administration was ten-fold lower than after SC injection (0.087 and 0.89 μg/mL, respectively), whereas there was no difference in lung concentrations between both routes of administration. However, lung concentrations at day 1 p.a. were significantly higher than plasma levels for both routes of administration (2.22 and 3.66 μg/g for PO and SC, respectively). Consequently, lung/plasma ratios were high, up to 50 and 80 after PO and SC administration, respectively. GAM could not be detected in PELF, although this might be attributed to the collection method of PELF in birds. The GAM minimum inhibitory concentration (MIC) was determined for 38 O. rhinotracheale strains; MIC50 and MIC90 were 2 and >32 μg/mL, respectively. PK/PD correlation for lung tissue demonstrated that the time above the MIC90 of the susceptible population (2 μg/mL) was 1 day after PO bolus and 3.5 days after SC administration. The area under the curve (AUClast)/MIC ratios for lung tissue after SC and PO administration were 233 and 90, respectively. To conclude, GAM is highly distributed to lung tissue in turkey poults, suggesting that it has the potential to be used to treat respiratory infections such as O. rhinotracheale.
Heidi Wyns - One of the best experts on this subject based on the ideXlab platform.
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efficacy of Gamithromycin against ornithobacterium rhinotracheale in turkey poults pre infected with avian metapneumovirus
Avian Pathology, 2016Co-Authors: Anneleen Watteyn, Elke Plessers, Heidi Wyns, Freddy Haesebrouck, Mathias Devreese, An Garmyn, Vishwanatha Reddy Avalakuppa Papi Reddy, Frank Pasmans, An Martel, Patrick De BackerAbstract:ABSTRACTOrnithobacterium rhinotracheale is an avian respiratory pathogen that affects turkeys. The objective of this study was to evaluate the clinical efficacy of Gamithromycin (GAM) against O. rhinotracheale in turkeys. The birds were inoculated oculonasally with 108 colony-forming units (cfu) of O. rhinotracheale, preceded by infection with avian metapneumovirus. In addition to a negative (CONTR−) and a positive control group (CONTR+) there were two treated groups administered GAM (6 mg/kg) either subcutaneously (GAM SC) or orally (GAM PO) by administration as a single bolus at one-day post-bacterial infection (p.b.i.). From the start of the avian metapneumovirus infection until the end of the experiment, the turkeys were examined clinically and scored daily. In addition, tracheal swabs were collected at several days p.b.i. Necropsy was performed at 4, 8 and 12 days p.b.i. to evaluate the presence of gross lesions, and to collect trachea and lung tissue samples and air sac swabs for O. rhinotracheale q...
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Immunomodulatory properties of Gamithromycin and ketoprofen in lipopolysaccharide-challenged calves with emphasis on the acute-phase response.
Veterinary immunology and immunopathology, 2016Co-Authors: Elke Plessers, Anneleen Watteyn, Heidi Wyns, Bart Pardon, Patrick De Backer, Siegrid De Baere, Stanislas Sys, Siska CroubelsAbstract:Abstract Macrolide antibiotics and non-steroidal anti-inflammatory drugs (NSAIDs) have been reported to be modulators of the innate immune response, irrespectively of their antimicrobial and anti-inflammatory actions. Therefore, it was our objective to evaluate whether the macrolide Gamithromycin (GAM) and the NSAID ketoprofen (KETO) attenuate the acute-phase response in calves, and whether their combined administration is beneficial due to synergistic and/or additive effects. To this end, both drugs, as well as their combination, were studied in a previously developed inflammation model, i.e., the induction of an acute-phase response by an intravenous lipopolysaccharide (LPS) challenge (0.5 μg/kg body weight). Sixteen 4-week-old Holstein–Friesian calves were randomized into 4 groups: a positive control (+CONTR) group, receiving LPS but no pharmacological treatment ( n = 4) and a GAM ( n = 4), a KETO ( n = 4) and a GAM–KETO ( n = 4) group, receiving the respective drugs 1 h prior to LPS administration. Clinical scoring and blood collection were performed at regular time points until 72 h post LPS challenge. Plasma concentrations of the selected cytokines (tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6)), acute-phase protein (serum amyloid A (SAA)) and prostaglandin E 2 (PGE 2 ) were subsequently quantified. Pre-treatment with GAM had no effect in the inflammation model compared to the +CONTR group. KETO, on the other hand, completely inhibited depression, anorexia and fever. This remarkable influence was associated with a significant reduction of PGE 2 synthesis by KETO, while the effect on TNF-α, IL-6 and SAA was not straightforward. The combined administration of GAM and KETO provided no synergistic or additive effects in this model, neither clinically nor regarding the studied inflammatory mediators. In conclusion, KETO entirely inhibited PGE 2 synthesis, fever development and depression, while GAM did not exert any effect in this model. These results promote the concomitant use of an antimicrobial drug and a NSAID in the treatment of calf diseases associated with LPS, both to enhance clinical recovery and to improve animal welfare.
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modulation by Gamithromycin and ketoprofen of in vitro and in vivo porcine lipopolysaccharide induced inflammation
Veterinary Immunology and Immunopathology, 2015Co-Authors: Heidi Wyns, Anneleen Watteyn, Elke Plessers, Evelyne Meyer, Patrick De Backer, Siegrid De Baere, Mathias Devreese, Thomas Van Bergen, Stijn Schauvliege, Siska CroubelsAbstract:The immunomodulatory properties of Gamithromycin (GAM), ketoprofen (KETO) and their combination (GAM-KETO) were investigated after both in vitro and in vivo lipopolysaccharide (LPS)-induced inflammation. The influence of these drugs was measured on the production of prostaglandin E2 (PGE2) and the pro-inflammatory cytokines tumour necrosis factor (TNF)-α, interleukin (IL)-6 and IL-1β in both LPS-stimulated porcine peripheral blood mononuclear cells (PBMCs) and LPS-challenged pigs. Additionally, effects on the production of acute phase proteins (APPs), including pig major acute phase protein (pig-MAP) and C-reactive protein (CRP), as well as on the development of fever, pulmonary symptoms and sickness behaviour were investigated. Dexamethasone was included as a positive control in the in vitro research. Following an 18h-incubation period with 1.25μg/mL LPS, the levels of TNF-α, IL-1β and IL-6 (p<0.05) measured in the PBMC supernatants were significantly increased. Incubation with a high concentration of both GAM and KETO significantly reduced the in vitro levels of all three cytokines. Maximal plasma concentrations of TNF-α and IL-6 were observed at 1h and 2.5h following LPS challenge in pigs, respectively. Neither GAM, nor KETO nor the combination GAM-KETO was able to inhibit the in vivo LPS-induced cytokine production. Furthermore, none of the drugs influenced the subsequent APPs production. In contrast, administration of KETO significantly reduced PGE2 production both in vitro and in vivo (p<0.05 and p<0.001, respectively) and prevented the development of fever and severe symptoms, including dyspnoea, anorexia, vomiting and lateral decubitus.
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Study of the immunomodulatory properties of Gamithromycin and dexamethasone in a lipopolysaccharide inflammation model in calves.
Research in veterinary science, 2015Co-Authors: Elke Plessers, Anneleen Watteyn, Heidi Wyns, P. De Backer, Bart Pardon, Siska CroubelsAbstract:The aim of this study was to define the in vivo immunomodulatory properties of the macrolide antibiotic Gamithromycin in calves, with respect to the acute phase response. Additionally, the corticosteroid dexamethasone was included as a positive control immunomodulatory drug. Both drugs, as well as their combination,were studied in a previously developed inflammation model,which was initiated by an intravenous lipopolysaccharide (LPS) challenge (0.5 μg/kg body weight). Twenty-four 4-week-old male Holstein Friesian calves were randomized into four groups: no pharmacological treatment (n = 6) or a pharmacological treatment with Gamithromycin (n= 6), dexamethasone (n= 6) or their combination (n= 6) 1 h prior to LPS administration. Blood collection and clinical scoring were performed at regular time points until 72 h post LPS challenge. Plasma concentrations of selected cytokines (tumour necrosis factor-α (TNF-α) and interleukin 6 (IL-6)) and acute phase proteins (serum amyloid A and haptoglobin) were subsequently determined. Gamithromycin did not have any beneficial effect on the LPS-induced clinical signs (dyspnea, fever, anorexia and depression), nor on the studied inflammatory mediators. In the dexamethasone and combination groups, the occurrence of dyspnea and fever was not prominently influenced, although the calves recovered significantly faster from the challenge. Moreover, dexamethasone significantly inhibited the levels of TNF-α and IL-6, suggesting a key role for these cytokines in sickness behaviour. In conclusion, unlike dexamethasone, Gamithromycin did not directly reduce cytokine release in an LPS inflammation model in calves.
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Modulation by Gamithromycin and ketoprofen of in vitro and in vivo porcine lipopolysaccharide-induced inflammation.
Veterinary immunology and immunopathology, 2015Co-Authors: Heidi Wyns, Anneleen Watteyn, Elke Plessers, Evelyne Meyer, Patrick De Backer, Siegrid De Baere, Mathias Devreese, Thomas Van Bergen, Stijn Schauvliege, Siska CroubelsAbstract:The immunomodulatory properties of Gamithromycin (GAM), ketoprofen (KETO) and their combination (GAM-KETO) were investigated after both in vitro and in vivo lipopolysaccharide (LPS)-induced inflammation. The influence of these drugs was measured on the production of prostaglandin E2 (PGE2) and the pro-inflammatory cytokines tumour necrosis factor (TNF)-α, interleukin (IL)-6 and IL-1β in both LPS-stimulated porcine peripheral blood mononuclear cells (PBMCs) and LPS-challenged pigs. Additionally, effects on the production of acute phase proteins (APPs), including pig major acute phase protein (pig-MAP) and C-reactive protein (CRP), as well as on the development of fever, pulmonary symptoms and sickness behaviour were investigated. Dexamethasone was included as a positive control in the in vitro research. Following an 18h-incubation period with 1.25μg/mL LPS, the levels of TNF-α, IL-1β and IL-6 (p
Anneleen Watteyn - One of the best experts on this subject based on the ideXlab platform.
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efficacy of Gamithromycin against ornithobacterium rhinotracheale in turkey poults pre infected with avian metapneumovirus
Avian Pathology, 2016Co-Authors: Anneleen Watteyn, Elke Plessers, Heidi Wyns, Freddy Haesebrouck, Mathias Devreese, An Garmyn, Vishwanatha Reddy Avalakuppa Papi Reddy, Frank Pasmans, An Martel, Patrick De BackerAbstract:ABSTRACTOrnithobacterium rhinotracheale is an avian respiratory pathogen that affects turkeys. The objective of this study was to evaluate the clinical efficacy of Gamithromycin (GAM) against O. rhinotracheale in turkeys. The birds were inoculated oculonasally with 108 colony-forming units (cfu) of O. rhinotracheale, preceded by infection with avian metapneumovirus. In addition to a negative (CONTR−) and a positive control group (CONTR+) there were two treated groups administered GAM (6 mg/kg) either subcutaneously (GAM SC) or orally (GAM PO) by administration as a single bolus at one-day post-bacterial infection (p.b.i.). From the start of the avian metapneumovirus infection until the end of the experiment, the turkeys were examined clinically and scored daily. In addition, tracheal swabs were collected at several days p.b.i. Necropsy was performed at 4, 8 and 12 days p.b.i. to evaluate the presence of gross lesions, and to collect trachea and lung tissue samples and air sac swabs for O. rhinotracheale q...
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Immunomodulatory properties of Gamithromycin and ketoprofen in lipopolysaccharide-challenged calves with emphasis on the acute-phase response.
Veterinary immunology and immunopathology, 2016Co-Authors: Elke Plessers, Anneleen Watteyn, Heidi Wyns, Bart Pardon, Patrick De Backer, Siegrid De Baere, Stanislas Sys, Siska CroubelsAbstract:Abstract Macrolide antibiotics and non-steroidal anti-inflammatory drugs (NSAIDs) have been reported to be modulators of the innate immune response, irrespectively of their antimicrobial and anti-inflammatory actions. Therefore, it was our objective to evaluate whether the macrolide Gamithromycin (GAM) and the NSAID ketoprofen (KETO) attenuate the acute-phase response in calves, and whether their combined administration is beneficial due to synergistic and/or additive effects. To this end, both drugs, as well as their combination, were studied in a previously developed inflammation model, i.e., the induction of an acute-phase response by an intravenous lipopolysaccharide (LPS) challenge (0.5 μg/kg body weight). Sixteen 4-week-old Holstein–Friesian calves were randomized into 4 groups: a positive control (+CONTR) group, receiving LPS but no pharmacological treatment ( n = 4) and a GAM ( n = 4), a KETO ( n = 4) and a GAM–KETO ( n = 4) group, receiving the respective drugs 1 h prior to LPS administration. Clinical scoring and blood collection were performed at regular time points until 72 h post LPS challenge. Plasma concentrations of the selected cytokines (tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6)), acute-phase protein (serum amyloid A (SAA)) and prostaglandin E 2 (PGE 2 ) were subsequently quantified. Pre-treatment with GAM had no effect in the inflammation model compared to the +CONTR group. KETO, on the other hand, completely inhibited depression, anorexia and fever. This remarkable influence was associated with a significant reduction of PGE 2 synthesis by KETO, while the effect on TNF-α, IL-6 and SAA was not straightforward. The combined administration of GAM and KETO provided no synergistic or additive effects in this model, neither clinically nor regarding the studied inflammatory mediators. In conclusion, KETO entirely inhibited PGE 2 synthesis, fever development and depression, while GAM did not exert any effect in this model. These results promote the concomitant use of an antimicrobial drug and a NSAID in the treatment of calf diseases associated with LPS, both to enhance clinical recovery and to improve animal welfare.
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modulation by Gamithromycin and ketoprofen of in vitro and in vivo porcine lipopolysaccharide induced inflammation
Veterinary Immunology and Immunopathology, 2015Co-Authors: Heidi Wyns, Anneleen Watteyn, Elke Plessers, Evelyne Meyer, Patrick De Backer, Siegrid De Baere, Mathias Devreese, Thomas Van Bergen, Stijn Schauvliege, Siska CroubelsAbstract:The immunomodulatory properties of Gamithromycin (GAM), ketoprofen (KETO) and their combination (GAM-KETO) were investigated after both in vitro and in vivo lipopolysaccharide (LPS)-induced inflammation. The influence of these drugs was measured on the production of prostaglandin E2 (PGE2) and the pro-inflammatory cytokines tumour necrosis factor (TNF)-α, interleukin (IL)-6 and IL-1β in both LPS-stimulated porcine peripheral blood mononuclear cells (PBMCs) and LPS-challenged pigs. Additionally, effects on the production of acute phase proteins (APPs), including pig major acute phase protein (pig-MAP) and C-reactive protein (CRP), as well as on the development of fever, pulmonary symptoms and sickness behaviour were investigated. Dexamethasone was included as a positive control in the in vitro research. Following an 18h-incubation period with 1.25μg/mL LPS, the levels of TNF-α, IL-1β and IL-6 (p<0.05) measured in the PBMC supernatants were significantly increased. Incubation with a high concentration of both GAM and KETO significantly reduced the in vitro levels of all three cytokines. Maximal plasma concentrations of TNF-α and IL-6 were observed at 1h and 2.5h following LPS challenge in pigs, respectively. Neither GAM, nor KETO nor the combination GAM-KETO was able to inhibit the in vivo LPS-induced cytokine production. Furthermore, none of the drugs influenced the subsequent APPs production. In contrast, administration of KETO significantly reduced PGE2 production both in vitro and in vivo (p<0.05 and p<0.001, respectively) and prevented the development of fever and severe symptoms, including dyspnoea, anorexia, vomiting and lateral decubitus.
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Study of the immunomodulatory properties of Gamithromycin and dexamethasone in a lipopolysaccharide inflammation model in calves.
Research in veterinary science, 2015Co-Authors: Elke Plessers, Anneleen Watteyn, Heidi Wyns, P. De Backer, Bart Pardon, Siska CroubelsAbstract:The aim of this study was to define the in vivo immunomodulatory properties of the macrolide antibiotic Gamithromycin in calves, with respect to the acute phase response. Additionally, the corticosteroid dexamethasone was included as a positive control immunomodulatory drug. Both drugs, as well as their combination,were studied in a previously developed inflammation model,which was initiated by an intravenous lipopolysaccharide (LPS) challenge (0.5 μg/kg body weight). Twenty-four 4-week-old male Holstein Friesian calves were randomized into four groups: no pharmacological treatment (n = 6) or a pharmacological treatment with Gamithromycin (n= 6), dexamethasone (n= 6) or their combination (n= 6) 1 h prior to LPS administration. Blood collection and clinical scoring were performed at regular time points until 72 h post LPS challenge. Plasma concentrations of selected cytokines (tumour necrosis factor-α (TNF-α) and interleukin 6 (IL-6)) and acute phase proteins (serum amyloid A and haptoglobin) were subsequently determined. Gamithromycin did not have any beneficial effect on the LPS-induced clinical signs (dyspnea, fever, anorexia and depression), nor on the studied inflammatory mediators. In the dexamethasone and combination groups, the occurrence of dyspnea and fever was not prominently influenced, although the calves recovered significantly faster from the challenge. Moreover, dexamethasone significantly inhibited the levels of TNF-α and IL-6, suggesting a key role for these cytokines in sickness behaviour. In conclusion, unlike dexamethasone, Gamithromycin did not directly reduce cytokine release in an LPS inflammation model in calves.
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Modulation by Gamithromycin and ketoprofen of in vitro and in vivo porcine lipopolysaccharide-induced inflammation.
Veterinary immunology and immunopathology, 2015Co-Authors: Heidi Wyns, Anneleen Watteyn, Elke Plessers, Evelyne Meyer, Patrick De Backer, Siegrid De Baere, Mathias Devreese, Thomas Van Bergen, Stijn Schauvliege, Siska CroubelsAbstract:The immunomodulatory properties of Gamithromycin (GAM), ketoprofen (KETO) and their combination (GAM-KETO) were investigated after both in vitro and in vivo lipopolysaccharide (LPS)-induced inflammation. The influence of these drugs was measured on the production of prostaglandin E2 (PGE2) and the pro-inflammatory cytokines tumour necrosis factor (TNF)-α, interleukin (IL)-6 and IL-1β in both LPS-stimulated porcine peripheral blood mononuclear cells (PBMCs) and LPS-challenged pigs. Additionally, effects on the production of acute phase proteins (APPs), including pig major acute phase protein (pig-MAP) and C-reactive protein (CRP), as well as on the development of fever, pulmonary symptoms and sickness behaviour were investigated. Dexamethasone was included as a positive control in the in vitro research. Following an 18h-incubation period with 1.25μg/mL LPS, the levels of TNF-α, IL-1β and IL-6 (p
Elke Plessers - One of the best experts on this subject based on the ideXlab platform.
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efficacy of Gamithromycin against ornithobacterium rhinotracheale in turkey poults pre infected with avian metapneumovirus
Avian Pathology, 2016Co-Authors: Anneleen Watteyn, Elke Plessers, Heidi Wyns, Freddy Haesebrouck, Mathias Devreese, An Garmyn, Vishwanatha Reddy Avalakuppa Papi Reddy, Frank Pasmans, An Martel, Patrick De BackerAbstract:ABSTRACTOrnithobacterium rhinotracheale is an avian respiratory pathogen that affects turkeys. The objective of this study was to evaluate the clinical efficacy of Gamithromycin (GAM) against O. rhinotracheale in turkeys. The birds were inoculated oculonasally with 108 colony-forming units (cfu) of O. rhinotracheale, preceded by infection with avian metapneumovirus. In addition to a negative (CONTR−) and a positive control group (CONTR+) there were two treated groups administered GAM (6 mg/kg) either subcutaneously (GAM SC) or orally (GAM PO) by administration as a single bolus at one-day post-bacterial infection (p.b.i.). From the start of the avian metapneumovirus infection until the end of the experiment, the turkeys were examined clinically and scored daily. In addition, tracheal swabs were collected at several days p.b.i. Necropsy was performed at 4, 8 and 12 days p.b.i. to evaluate the presence of gross lesions, and to collect trachea and lung tissue samples and air sac swabs for O. rhinotracheale q...
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Immunomodulatory properties of Gamithromycin and ketoprofen in lipopolysaccharide-challenged calves with emphasis on the acute-phase response.
Veterinary immunology and immunopathology, 2016Co-Authors: Elke Plessers, Anneleen Watteyn, Heidi Wyns, Bart Pardon, Patrick De Backer, Siegrid De Baere, Stanislas Sys, Siska CroubelsAbstract:Abstract Macrolide antibiotics and non-steroidal anti-inflammatory drugs (NSAIDs) have been reported to be modulators of the innate immune response, irrespectively of their antimicrobial and anti-inflammatory actions. Therefore, it was our objective to evaluate whether the macrolide Gamithromycin (GAM) and the NSAID ketoprofen (KETO) attenuate the acute-phase response in calves, and whether their combined administration is beneficial due to synergistic and/or additive effects. To this end, both drugs, as well as their combination, were studied in a previously developed inflammation model, i.e., the induction of an acute-phase response by an intravenous lipopolysaccharide (LPS) challenge (0.5 μg/kg body weight). Sixteen 4-week-old Holstein–Friesian calves were randomized into 4 groups: a positive control (+CONTR) group, receiving LPS but no pharmacological treatment ( n = 4) and a GAM ( n = 4), a KETO ( n = 4) and a GAM–KETO ( n = 4) group, receiving the respective drugs 1 h prior to LPS administration. Clinical scoring and blood collection were performed at regular time points until 72 h post LPS challenge. Plasma concentrations of the selected cytokines (tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6)), acute-phase protein (serum amyloid A (SAA)) and prostaglandin E 2 (PGE 2 ) were subsequently quantified. Pre-treatment with GAM had no effect in the inflammation model compared to the +CONTR group. KETO, on the other hand, completely inhibited depression, anorexia and fever. This remarkable influence was associated with a significant reduction of PGE 2 synthesis by KETO, while the effect on TNF-α, IL-6 and SAA was not straightforward. The combined administration of GAM and KETO provided no synergistic or additive effects in this model, neither clinically nor regarding the studied inflammatory mediators. In conclusion, KETO entirely inhibited PGE 2 synthesis, fever development and depression, while GAM did not exert any effect in this model. These results promote the concomitant use of an antimicrobial drug and a NSAID in the treatment of calf diseases associated with LPS, both to enhance clinical recovery and to improve animal welfare.
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modulation by Gamithromycin and ketoprofen of in vitro and in vivo porcine lipopolysaccharide induced inflammation
Veterinary Immunology and Immunopathology, 2015Co-Authors: Heidi Wyns, Anneleen Watteyn, Elke Plessers, Evelyne Meyer, Patrick De Backer, Siegrid De Baere, Mathias Devreese, Thomas Van Bergen, Stijn Schauvliege, Siska CroubelsAbstract:The immunomodulatory properties of Gamithromycin (GAM), ketoprofen (KETO) and their combination (GAM-KETO) were investigated after both in vitro and in vivo lipopolysaccharide (LPS)-induced inflammation. The influence of these drugs was measured on the production of prostaglandin E2 (PGE2) and the pro-inflammatory cytokines tumour necrosis factor (TNF)-α, interleukin (IL)-6 and IL-1β in both LPS-stimulated porcine peripheral blood mononuclear cells (PBMCs) and LPS-challenged pigs. Additionally, effects on the production of acute phase proteins (APPs), including pig major acute phase protein (pig-MAP) and C-reactive protein (CRP), as well as on the development of fever, pulmonary symptoms and sickness behaviour were investigated. Dexamethasone was included as a positive control in the in vitro research. Following an 18h-incubation period with 1.25μg/mL LPS, the levels of TNF-α, IL-1β and IL-6 (p<0.05) measured in the PBMC supernatants were significantly increased. Incubation with a high concentration of both GAM and KETO significantly reduced the in vitro levels of all three cytokines. Maximal plasma concentrations of TNF-α and IL-6 were observed at 1h and 2.5h following LPS challenge in pigs, respectively. Neither GAM, nor KETO nor the combination GAM-KETO was able to inhibit the in vivo LPS-induced cytokine production. Furthermore, none of the drugs influenced the subsequent APPs production. In contrast, administration of KETO significantly reduced PGE2 production both in vitro and in vivo (p<0.05 and p<0.001, respectively) and prevented the development of fever and severe symptoms, including dyspnoea, anorexia, vomiting and lateral decubitus.
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Study of the immunomodulatory properties of Gamithromycin and dexamethasone in a lipopolysaccharide inflammation model in calves.
Research in veterinary science, 2015Co-Authors: Elke Plessers, Anneleen Watteyn, Heidi Wyns, P. De Backer, Bart Pardon, Siska CroubelsAbstract:The aim of this study was to define the in vivo immunomodulatory properties of the macrolide antibiotic Gamithromycin in calves, with respect to the acute phase response. Additionally, the corticosteroid dexamethasone was included as a positive control immunomodulatory drug. Both drugs, as well as their combination,were studied in a previously developed inflammation model,which was initiated by an intravenous lipopolysaccharide (LPS) challenge (0.5 μg/kg body weight). Twenty-four 4-week-old male Holstein Friesian calves were randomized into four groups: no pharmacological treatment (n = 6) or a pharmacological treatment with Gamithromycin (n= 6), dexamethasone (n= 6) or their combination (n= 6) 1 h prior to LPS administration. Blood collection and clinical scoring were performed at regular time points until 72 h post LPS challenge. Plasma concentrations of selected cytokines (tumour necrosis factor-α (TNF-α) and interleukin 6 (IL-6)) and acute phase proteins (serum amyloid A and haptoglobin) were subsequently determined. Gamithromycin did not have any beneficial effect on the LPS-induced clinical signs (dyspnea, fever, anorexia and depression), nor on the studied inflammatory mediators. In the dexamethasone and combination groups, the occurrence of dyspnea and fever was not prominently influenced, although the calves recovered significantly faster from the challenge. Moreover, dexamethasone significantly inhibited the levels of TNF-α and IL-6, suggesting a key role for these cytokines in sickness behaviour. In conclusion, unlike dexamethasone, Gamithromycin did not directly reduce cytokine release in an LPS inflammation model in calves.
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Modulation by Gamithromycin and ketoprofen of in vitro and in vivo porcine lipopolysaccharide-induced inflammation.
Veterinary immunology and immunopathology, 2015Co-Authors: Heidi Wyns, Anneleen Watteyn, Elke Plessers, Evelyne Meyer, Patrick De Backer, Siegrid De Baere, Mathias Devreese, Thomas Van Bergen, Stijn Schauvliege, Siska CroubelsAbstract:The immunomodulatory properties of Gamithromycin (GAM), ketoprofen (KETO) and their combination (GAM-KETO) were investigated after both in vitro and in vivo lipopolysaccharide (LPS)-induced inflammation. The influence of these drugs was measured on the production of prostaglandin E2 (PGE2) and the pro-inflammatory cytokines tumour necrosis factor (TNF)-α, interleukin (IL)-6 and IL-1β in both LPS-stimulated porcine peripheral blood mononuclear cells (PBMCs) and LPS-challenged pigs. Additionally, effects on the production of acute phase proteins (APPs), including pig major acute phase protein (pig-MAP) and C-reactive protein (CRP), as well as on the development of fever, pulmonary symptoms and sickness behaviour were investigated. Dexamethasone was included as a positive control in the in vitro research. Following an 18h-incubation period with 1.25μg/mL LPS, the levels of TNF-α, IL-1β and IL-6 (p
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Comparisons of Metaphylactic Treatments of Zactran ® (Gamithromycin) vs. Excede ® (ceftiofur crystalline free acid) in High Risk, Stocker Calves
2014Co-Authors: David E. Amrine, Brad J. White, Dan R. Goehl, Shaun H. Sweiger, Bruce Nosky, Ronald K. TessmanAbstract:Bovine respiratory disease (BRD) complex is the most common disease occurring in backgrounding and feedlot cattle and is a significant source of losses from poor performance and death. Metaphylactic treatments are recognized as economically advantageous and have been associated with a 50% reduction in BRD associated morbidity. The multi-site study described here was conducted to compare health and performance parameters between newly received stocker calves treated metaphylactically with Zactran ® (6 mg Gamithromycin/kg subcutaneously) compared to Excede ® (6.6 mg ceftiofur/kg subcutaneously).
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Determination of the Antibacterial Activity of Gamithromycin Against Pathogens of Bovine Respiratory Disease
2014Co-Authors: Ronald K. Tessman, Donald J. BadeAbstract:A study was conducted to determine the time and concentration of Gamithromycin at which a 3-log kill (99.9%) of select H somni, M haemolytica, and P multocida isolates is achieved. Initially, 12 isolates each of H somni and M haemolytica and five isolates of P multocida were triplicate tested. Each isolate was previously identified and determined to have a Gamithromycin MIC equivalent to the MIC90 of the respective species. Isolates were triplicate susceptibil
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comparisons of metaphylactic treatments of zactran Gamithromycin vs excede ceftiofur crystalline free acid in high risk stocker calves
2014Co-Authors: David E. Amrine, Brad J. White, Dan R. Goehl, Shaun H. Sweiger, Bruce Nosky, Ronald K. TessmanAbstract:Bovine respiratory disease (BRD) complex is the most common disease occurring in backgrounding and feedlot cattle and is a significant source of losses from poor performance and death. Metaphylactic treatments are recognized as economically advantageous and have been associated with a 50% reduction in BRD associated morbidity. The multi-site study described here was conducted to compare health and performance parameters between newly received stocker calves treated metaphylactically with Zactran ® (6 mg Gamithromycin/kg subcutaneously) compared to Excede ® (6.6 mg ceftiofur/kg subcutaneously).
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Efficacy of Gamithromycin Injectable Solution for Control of Pneumonia in Cattle Challenged with Histophilus somni after Treatment
2011Co-Authors: Kelly Lechtenberg, Ronald K. Tessman, Davida RomanoAbstract:Recently weaned calves transported to the feedlot are at risk of infection, illness and even death from Histophilus somni and other pathogens associated with bovine respiratory disease (BRD) throughout the feeding period. Gamithromycin is an azalide 15-membered semi-synthetic macrolide antimicrobial that is licensed in the European Union and Canada for therapeutic and preventative treatment of BRD associated with Mannheimia haemolytica, Pasteurella multocida, and H. somni. This placebocontrolled study evaluates the efficacy of Gamithromycin injectable solution administered subcutaneously to cattle at 6.0 mg/kg body weight for control of the development of pneumonia in cattle challenged with H. somni approximately 6 hours post-treatment. Mean depression and respiratory scores were significantly lower (P
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efficacy of Gamithromycin injectable solution for control of pneumonia in cattle challenged with histophilus somni after treatment
2011Co-Authors: Kelly Lechtenberg, Ronald K. Tessman, Davida RomanoAbstract:Recently weaned calves transported to the feedlot are at risk of infection, illness and even death from Histophilus somni and other pathogens associated with bovine respiratory disease (BRD) throughout the feeding period. Gamithromycin is an azalide 15-membered semi-synthetic macrolide antimicrobial that is licensed in the European Union and Canada for therapeutic and preventative treatment of BRD associated with Mannheimia haemolytica, Pasteurella multocida, and H. somni. This placebocontrolled study evaluates the efficacy of Gamithromycin injectable solution administered subcutaneously to cattle at 6.0 mg/kg body weight for control of the development of pneumonia in cattle challenged with H. somni approximately 6 hours post-treatment. Mean depression and respiratory scores were significantly lower (P<0.01) for the Gamithromycin treated group than for the saline control group throughout the 7-day evaluation period. Mean rectal temperatures were significantly lower (P<0.01) for Gamithromycin treated calves from Day 1 through Day 6. Total weighted percentage lung consolidations were significantly (P<0.01) lower in the Gamithromycin group than in the saline group. In total, 16 calves in the saline control group, and seven from the Gamithromycin group had one or more bacterial pathogens cultured from lung samples collected at necropsy. In this study, Gamithromycin treated calves had an excellent safety and tolerability profile compared to those calves receiving saline. Results of this study indicate that Gamithromycin administered subcutaneously at 6.0 mg/kg was significantly efficacious in the prevention of clinical and pathological disease induced by
