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Prof. Gunther Antonissen
Ghent University - Faculty of Veterinary Medicine - Department of Pathology, Bacteriology and Avian Diseases

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Journal article
Published: 19 May 2021 in Antibiotics
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Enrofloxacin is frequently administered via drinking water for the treatment of colibacillosis in broiler chickens. However, the EMA/CVMP has urged to re-evaluate historically approved doses, especially for antimicrobials administered via drinking water. In response, the objectives of this study were two-fold. First, to evaluate the pharmacokinetics (PK) of enrofloxacin following IV, PO and drinking water administration. Second, to predict the efficacy of a range of doses in the drinking water for the treatment of APEC infections. For the first objective, PK parameters were estimated by fitting a one-compartmental model with a zero-order IV infusion and an oral absorption lag function to the simultaneously modelled IV and PO data. After fixing these parameter values, a drinking behaviour pharmacokinetic (DBPK) model was developed for the description and prediction of drinking water PK profiles by adding three model improvements (different diurnal and nocturnal drinking rates, inter-animal variability in water consumption and taking account of dose non-proportionality). The subsequent simulations and probability of target attainment (PTA) analysis predicted that a dose of 12.5 mg/kg/24 h is efficacious in treating colibacillosis with an MIC up to 0.125 μg/mL (ECOFF), whereas the currently registered dose (10 mg/kg/24 h) reaches a PTA of 66% at ECOFF.

ACS Style

Robin Temmerman; Ludovic Pelligand; Wim Schelstraete; Gunther Antonissen; An Garmyn; Mathias Devreese. Enrofloxacin Dose Optimization for the Treatment of Colibacillosis in Broiler Chickens Using a Drinking Behaviour Pharmacokinetic Model. Antibiotics 2021, 10, 604 .

AMA Style

Robin Temmerman, Ludovic Pelligand, Wim Schelstraete, Gunther Antonissen, An Garmyn, Mathias Devreese. Enrofloxacin Dose Optimization for the Treatment of Colibacillosis in Broiler Chickens Using a Drinking Behaviour Pharmacokinetic Model. Antibiotics. 2021; 10 (5):604.

Chicago/Turabian Style

Robin Temmerman; Ludovic Pelligand; Wim Schelstraete; Gunther Antonissen; An Garmyn; Mathias Devreese. 2021. "Enrofloxacin Dose Optimization for the Treatment of Colibacillosis in Broiler Chickens Using a Drinking Behaviour Pharmacokinetic Model." Antibiotics 10, no. 5: 604.

Journal article
Published: 12 May 2021 in Food Research International
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Mycotoxin intoxication is in general an acknowledged and tackled issue in animals. However, in several parts of the world, mycotoxicoses in humans still remain a relevant issue. The efficacy of two mycotoxin detoxifying animal feed additives, an aflatoxin bentonite clay binder and a fumonisin esterase, was investigated in a human child gut model, i.e. the in vitro Simulator of the Human Intestinal Microbial Ecosystem (SHIME®). Additionally, the effect of the detoxifiers on gut microbiota was examined in the SHIME. After an initial two weeks of system stabilisation, aflatoxin B1 (AFB1) and fumonisin B1 (FB1) were added to the SHIME diet during one week. Next, the two detoxifiers and mycotoxins were added to the system for an additional week. The AFB1, FB1, hydrolysed FB1 (HFB1), partially hydrolysed FB1a and FB1b concentrations were determined in SHIME samples using a validated ultra-performance liquid chromatography-tandem mass spectrometry method. The short-chain fatty acid (SCFA) concentrations were determined by a validated gas chromatography–mass spectrometry method. Colonic bacterial communities were analysed using metabarcoding, targeting the hypervariable V1-V3 regions of the 16S rRNA genes. The AFB1 and FB1 concentrations significantly decreased after the addition of the detoxifiers. Likewise, the concentration of HFB1 significantly increased. Concentrations of SCFAs remained generally stable throughout the experiment. No major changes in bacterial composition occurred during the experiment. The results demonstrate the promising effect of these detoxifiers in reducing AFB1 and FB1 concentrations in the human intestinal environment, without compromising the gastrointestinal microbiota.

ACS Style

Kaat Neckermann; Gregor Claus; Siegrid De Baere; Gunther Antonissen; Sarah Lebrun; Céline Gemmi; Bernard Taminiau; Caroline Douny; Marie-Louise Scippo; Dian Schatzmayr; James Gathumbi; Silvio Uhlig; Siska Croubels; Véronique Delcenserie. The efficacy and effect on gut microbiota of an aflatoxin binder and a fumonisin esterase using an in vitro simulator of the human intestinal microbial ecosystem (SHIME®). Food Research International 2021, 145, 110395 .

AMA Style

Kaat Neckermann, Gregor Claus, Siegrid De Baere, Gunther Antonissen, Sarah Lebrun, Céline Gemmi, Bernard Taminiau, Caroline Douny, Marie-Louise Scippo, Dian Schatzmayr, James Gathumbi, Silvio Uhlig, Siska Croubels, Véronique Delcenserie. The efficacy and effect on gut microbiota of an aflatoxin binder and a fumonisin esterase using an in vitro simulator of the human intestinal microbial ecosystem (SHIME®). Food Research International. 2021; 145 ():110395.

Chicago/Turabian Style

Kaat Neckermann; Gregor Claus; Siegrid De Baere; Gunther Antonissen; Sarah Lebrun; Céline Gemmi; Bernard Taminiau; Caroline Douny; Marie-Louise Scippo; Dian Schatzmayr; James Gathumbi; Silvio Uhlig; Siska Croubels; Véronique Delcenserie. 2021. "The efficacy and effect on gut microbiota of an aflatoxin binder and a fumonisin esterase using an in vitro simulator of the human intestinal microbial ecosystem (SHIME®)." Food Research International 145, no. : 110395.

Journal article
Published: 04 January 2021 in Toxins
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Although previous studies have reported the use of nixtamalization for mycotoxins reduction in maize, the efficacy of calcium hydroxide and other nixtamalization cooking ingredients for mycotoxin reduction/decontamination in sorghum and other cereals still need to be determined. The current study investigated the effect of five nixtamalization cooking ingredients (wood ashes, calcium hydroxide, sodium hydroxide, potassium hydroxide, and calcium chloride) on the reduction of Fusarium mycotoxins in artificially contaminated maize and sorghum using liquid chromatography-tandem mass spectrometry. All tested cooking ingredients effectively reduced levels of mycotoxins in the contaminated samples with reduction initiated immediately after the washing step. Except for the calcium chloride nixtamal, levels of fumonisin B1, B2, and B3 in the processed sorghum nixtamal samples were below the limit of detection. Meanwhile, the lowest pH values were obtained from the maize (4.84; 4.99), as well as sorghum (4.83; 4.81) nejayote and nixtamal samples obtained via calcium chloride treatment. Overall, the results revealed that the tested cooking ingredients were effective in reducing the target mycotoxins. In addition, it pointed out the potential of calcium chloride, though with reduced effectiveness, as a possible greener alternative cooking ingredient (ecological nixtamalization) when there are environmental concerns caused by alkaline nejayote.

ACS Style

Julianah Odukoya; Sarah De Saeger; Marthe De Boevre; Gabriel Adegoke; Kris Audenaert; Siska Croubels; Gunther Antonissen; Karel Vermeulen; Sefater Gbashi; Patrick Njobeh. Effect of Selected Cooking Ingredients for Nixtamalization on the Reduction of Fusarium Mycotoxins in Maize and Sorghum. Toxins 2021, 13, 27 .

AMA Style

Julianah Odukoya, Sarah De Saeger, Marthe De Boevre, Gabriel Adegoke, Kris Audenaert, Siska Croubels, Gunther Antonissen, Karel Vermeulen, Sefater Gbashi, Patrick Njobeh. Effect of Selected Cooking Ingredients for Nixtamalization on the Reduction of Fusarium Mycotoxins in Maize and Sorghum. Toxins. 2021; 13 (1):27.

Chicago/Turabian Style

Julianah Odukoya; Sarah De Saeger; Marthe De Boevre; Gabriel Adegoke; Kris Audenaert; Siska Croubels; Gunther Antonissen; Karel Vermeulen; Sefater Gbashi; Patrick Njobeh. 2021. "Effect of Selected Cooking Ingredients for Nixtamalization on the Reduction of Fusarium Mycotoxins in Maize and Sorghum." Toxins 13, no. 1: 27.

Journal article
Published: 03 December 2020 in Toxins
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Mycotoxins are common in grains in sub-Saharan Africa and negatively impact human and animal health and production. This study assessed occurrences of mycotoxins, some plant, and bacterial metabolites in 16 dairy and 27 poultry feeds, and 24 feed ingredients from Machakos town, Kenya, in February and August 2019. We analyzed the samples using a validated multi-toxin liquid chromatography-tandem mass spectrometry method. A total of 153 mycotoxins, plant, and bacterial toxins, were detected in the samples. All the samples were co-contaminated with 21 to 116 different mycotoxins and/or metabolites. The commonly occurring and EU regulated mycotoxins reported were; aflatoxins (AFs) (70%; range 0.2–318.5 μg/kg), deoxynivalenol (82%; range 22.2–1037 μg/kg), ergot alkaloids (70%; range 0.4–285.7 μg/kg), fumonisins (90%; range 32.4–14,346 μg/kg), HT-2 toxin (3%; range 11.9–13.8 μg/kg), ochratoxin A (24%; range 1.1–24.3 μg/kg), T-2 toxin (4%; range 2.7–5.2 μg/kg) and zearalenone (94%; range 0.3–910.4 μg/kg). Other unregulated emerging mycotoxins and metabolites including Alternaria toxins, Aspergillus toxins, bacterial metabolites, cytochalasins, depsipeptides, Fusarium metabolites, metabolites from other fungi, Penicillium toxins, phytoestrogens, plant metabolites, and unspecific metabolites were also detected at varying levels. Except for total AFs, where the average contamination level was above the EU regulatory limit, all the other mycotoxins detected had average contamination levels below the limits. Ninety-six percent of all the samples were contaminated with more than one of the EU regulated mycotoxins. These co-occurrences may cause synergistic and additive health effects thereby hindering the growth of the Kenyan livestock sector.

ACS Style

David Chebutia Kemboi; Phillis E. Ochieng; Gunther Antonissen; Siska Croubels; Marie-Louise Scippo; Sheila Okoth; Erastus K. Kangethe; Johannes Faas; Barbara Doupovec; Johanna F. Lindahl; James K. Gathumbi. Multi-Mycotoxin Occurrence in Dairy Cattle and Poultry Feeds and Feed Ingredients from Machakos Town, Kenya. Toxins 2020, 12, 762 .

AMA Style

David Chebutia Kemboi, Phillis E. Ochieng, Gunther Antonissen, Siska Croubels, Marie-Louise Scippo, Sheila Okoth, Erastus K. Kangethe, Johannes Faas, Barbara Doupovec, Johanna F. Lindahl, James K. Gathumbi. Multi-Mycotoxin Occurrence in Dairy Cattle and Poultry Feeds and Feed Ingredients from Machakos Town, Kenya. Toxins. 2020; 12 (12):762.

Chicago/Turabian Style

David Chebutia Kemboi; Phillis E. Ochieng; Gunther Antonissen; Siska Croubels; Marie-Louise Scippo; Sheila Okoth; Erastus K. Kangethe; Johannes Faas; Barbara Doupovec; Johanna F. Lindahl; James K. Gathumbi. 2020. "Multi-Mycotoxin Occurrence in Dairy Cattle and Poultry Feeds and Feed Ingredients from Machakos Town, Kenya." Toxins 12, no. 12: 762.

Journal article
Published: 12 November 2020 in Antibiotics
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Fluoroquinolones are frequently used antimicrobials for the treatment of avian pathogenic Escherichia coli (APEC) infections. However, rapid development and selection of resistance to this class of antimicrobial drugs is a significant problem. The aim of this study was to investigate the occurrence and mechanisms of antimicrobial resistance against enrofloxacin (ENRO) in APEC strains in Flanders, Belgium. One hundred and twenty-five APEC strains from broilers with clinical colibacillosis were collected in Flanders from November 2017 to June 2018. The minimum inhibitory concentration (MIC) of all strains and the mutant prevention concentration (MPC) of a sample of sensitive isolates were determined using a commercial gradient strip test and via the agar dilution method, respectively. Non-wild type (NWT) isolates were further characterized using polymerase chain reaction (PCR), gel electrophoresis and gene sequencing. Forty percent of the APEC strains were NWT according to the epidemiological cut-off (ECOFF) measure (MIC > 0.125 μg/mL). With respect to clinical breakpoints, 21% were clinically intermediate (0.5 ≤ MIC ≤ 1 μg/mL) and 10% were clinically resistant (MIC ≥ 2). The MPC values of the tested strains ranged from 0.064 to 1 μg/mL, resulting in MPC/MIC ratios varying from 4 to 32. The majority (92%) of the NWT strains carried one or two mutations in gyrA. Less than a quarter (22%) manifested amino acid substitutions in the topoisomerase IV parC subunit. Only three of the NWT strains carried a mutation in parE. Plasmid mediated quinolone resistance (PMQR) associated genes were detected in 18% of the NWT strains. In contrast to the relatively large number of NWT strains, only a small percentage of APEC isolates was considered clinically resistant. The most common MPC value for sensitive strains was 0.125 μg/mL. Some isolates showed higher values, producing wide mutant selection windows (MSW). Chromosomal mutations in DNA gyrase and topoisomerase IV were confirmed as the main source of decreased antimicrobial fluoroquinolone susceptibility, de-emphasizing the role of PMQR mechanisms.

ACS Style

Robin Temmerman; An Garmyn; Gunther Antonissen; Gerty Vanantwerpen; Mia Vanrobaeys; Freddy Haesebrouck; Mathias Devreese. Evaluation of Fluoroquinolone Resistance in Clinical Avian Pathogenic Escherichia coli Isolates from Flanders (Belgium). Antibiotics 2020, 9, 800 .

AMA Style

Robin Temmerman, An Garmyn, Gunther Antonissen, Gerty Vanantwerpen, Mia Vanrobaeys, Freddy Haesebrouck, Mathias Devreese. Evaluation of Fluoroquinolone Resistance in Clinical Avian Pathogenic Escherichia coli Isolates from Flanders (Belgium). Antibiotics. 2020; 9 (11):800.

Chicago/Turabian Style

Robin Temmerman; An Garmyn; Gunther Antonissen; Gerty Vanantwerpen; Mia Vanrobaeys; Freddy Haesebrouck; Mathias Devreese. 2020. "Evaluation of Fluoroquinolone Resistance in Clinical Avian Pathogenic Escherichia coli Isolates from Flanders (Belgium)." Antibiotics 9, no. 11: 800.

Short communication
Published: 01 November 2020 in Journal of Applied Poultry Research
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Because European maximum guidance values of mycotoxins are only available for feed, mycotoxin exposure in animals is mainly monitored by feed analysis. However, proper sample collection is needed to ensure reliable results because of uneven distributions and disproportional spread of mycotoxins in feed which can hamper the evaluation of mycotoxin exposure in animals. A cross-sectional study was performed on 40 randomly selected broiler farms in Belgium. During a farm visit at the animal's age of 28 d, a pooled feed sample at the beginning and the end of the feed line was collected. Feed samples were analyzed by a validated multimycotoxin LC-MS/MS method. Moreover, serum samples were collected from 10 randomly selected chickens per farm. Serum concentrations of mycotoxins and major in vivo phase I metabolites were analyzed quantitatively, whereas the presence of phase II metabolites was determined in a qualitative approach by an UPLC-HRMS method. Deoxynivalenol (DON) was the most frequently occurring mycotoxin, being present in 74% of the feed samples, with an average concentration of 270 ± 171 μg/kg and a maximum concentration of 751 μg/kg in positive samples. Also the acetylated forms 3- and 15-acetyldeoxynivalenol (3 and 15ADON) were present in half of the samples, however, at lower concentrations (8 ± 3 μg 3ADON and 10 ± 7 μg 15ADON/kg). Only in 17.5% of the farms, DON was detected in serum samples at a mean serum concentration and standard deviation (SD) of 11 ± 19 ng/mL. The maximum serum concentration of 49 ng DON/mL was detected in broilers which were fed a diet that was contaminated with 191 μg DON/kg, whereas the maximum concentration of DON in feed was 751 μg/kg. Besides, 3 and 15ADON were only detected in 10% of the serum samples (max. 1.3 ng/mL). Sulfate conjugates of DON were only detected in a few serum samples. Qualitative screening for phase II metabolites of other mycotoxins showed similar results. Overall, correlations between feed and serum concentrations of all mycotoxins were lacking (R2 = 0.18 for DON).

ACS Style

Danica Den Hollander; Siska Croubels; Marianne Lauwers; Nele Caekebeke; Moniek Ringenier; Fien De Meyer; Nicole Reisinger; Filip Van Immerseel; Jeroen Dewulf; Gunther Antonissen. Applied Research Note: Biomonitoring of mycotoxins in blood serum and feed to assess exposure of broiler chickens. Journal of Applied Poultry Research 2020, 30, 100111 .

AMA Style

Danica Den Hollander, Siska Croubels, Marianne Lauwers, Nele Caekebeke, Moniek Ringenier, Fien De Meyer, Nicole Reisinger, Filip Van Immerseel, Jeroen Dewulf, Gunther Antonissen. Applied Research Note: Biomonitoring of mycotoxins in blood serum and feed to assess exposure of broiler chickens. Journal of Applied Poultry Research. 2020; 30 (1):100111.

Chicago/Turabian Style

Danica Den Hollander; Siska Croubels; Marianne Lauwers; Nele Caekebeke; Moniek Ringenier; Fien De Meyer; Nicole Reisinger; Filip Van Immerseel; Jeroen Dewulf; Gunther Antonissen. 2020. "Applied Research Note: Biomonitoring of mycotoxins in blood serum and feed to assess exposure of broiler chickens." Journal of Applied Poultry Research 30, no. 1: 100111.

Journal article
Published: 18 October 2020 in Toxins
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The goal of this study was to investigate the toxicokinetic characteristics of aflatoxin G1 (AFG1) in broiler chickens and the effect of calcination of a Tunisian montmorillonite clay on the in vivo absorption of AFG1. In this study, broiler chickens were randomly distributed into four groups of 10 animals. Group 1 was administered AFG1 (2 mg/kg body weight (BW)) by single intravenous injection (IV), group 2 received an intra-crop bolus (PO) of AFG1 without any clay, group 3 was dosed AFG1 PO together with an oral bolus of purified clay (CP), and group 4 received AFG1 PO with an oral bolus of calcined clay. A significant difference in the area under the curve (AUC0-t) was observed for group 4 (6.78 ± 4.24 h*ng/mL) in comparison with group 2 (12.83 ± 4.19 h*ng/mL). A significant reduction of the oral bioavailability of AFG1 was observed for group 4 (7.61 ± 4.76%) compared with group 2 (14.40 ± 4.70%), while no significant effect was observed of CP. In this experiment, no phase I nor phase II metabolites of AFG1 were observed. These findings confirm that calcination of the purified montmorillonite clay enhances the adsorption of AFG1 in the gastrointestinal tract after oral administration, thereby reducing its bioavailability, thus reducing its toxic effects.

ACS Style

Roua Rejeb; Siegrid De Baere; Mathias Devreese; Richard Ducatelle; Siska Croubels; Madiha Hadj Ayed; Achraf Ghorbal; Gunther Antonissen. Calcination Improves the In Vivo Efficacy of a Montmorillonite Clay to Bind Aflatoxin G1 in Broiler Chickens: A Toxicokinetic Approach. Toxins 2020, 12, 660 .

AMA Style

Roua Rejeb, Siegrid De Baere, Mathias Devreese, Richard Ducatelle, Siska Croubels, Madiha Hadj Ayed, Achraf Ghorbal, Gunther Antonissen. Calcination Improves the In Vivo Efficacy of a Montmorillonite Clay to Bind Aflatoxin G1 in Broiler Chickens: A Toxicokinetic Approach. Toxins. 2020; 12 (10):660.

Chicago/Turabian Style

Roua Rejeb; Siegrid De Baere; Mathias Devreese; Richard Ducatelle; Siska Croubels; Madiha Hadj Ayed; Achraf Ghorbal; Gunther Antonissen. 2020. "Calcination Improves the In Vivo Efficacy of a Montmorillonite Clay to Bind Aflatoxin G1 in Broiler Chickens: A Toxicokinetic Approach." Toxins 12, no. 10: 660.

Journal article
Published: 21 June 2020 in Toxins
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The toxicokinetics (TK) of hydrolyzed fumonisin B1 (HFB1) were evaluated in 16 broiler chickens after being fed either a control or a fumonisins-contaminated diet (10.8 mg fumonisin B1, 3.3 mg B2 and 1.5 mg B3/kg feed) for two weeks, followed by a single oral (PO) or intravenous (IV) dose of 1.25 mg/kg bodyweight (BW) of HFB1. Fumonisin B1 (FB1), its partially hydrolyzed metabolites pHFB1a and pHFB1b, and fully hydrolyzed metabolite HFB1, were determined in chicken plasma using a validated ultra-performance liquid chromatography–tandem mass spectrometry method. None of the broiler chicken showed clinical symptoms of fumonisins (FBs) or HFB1 toxicity during the trial, nor was an aberration in body weight observed between the animals fed the FBs-contaminated diet and those fed the control diet. HFB1 was shown to follow a two-compartmental pharmacokinetic model with first order elimination in broiler chickens after IV administration. Toxicokinetic parameters of HFB1 demonstrated a total body clearance of 16.39 L/kg·h and an intercompartmental flow of 8.34 L/kg·h. Low levels of FB1 and traces of pHFB1b were found in plasma of chickens fed the FBs-contaminated diet. Due to plasma concentrations being under the limit of quantification (LOQ) after oral administration of HFB1, no toxicokinetic modelling could be performed in broiler chickens after oral administration of HFB1. Moreover, no phase II metabolites, nor N-acyl-metabolites of HFB1 could be detected in this study.

ACS Style

Gunther Antonissen; Siegrid De Baere; Barbara Novak; Dian Schatzmayr; Danica Den Hollander; Mathias Devreese; Siska Croubels. Toxicokinetics of Hydrolyzed Fumonisin B1 after Single Oral or Intravenous Bolus to Broiler Chickens Fed a Control or a Fumonisins-Contaminated Diet. Toxins 2020, 12, 413 .

AMA Style

Gunther Antonissen, Siegrid De Baere, Barbara Novak, Dian Schatzmayr, Danica Den Hollander, Mathias Devreese, Siska Croubels. Toxicokinetics of Hydrolyzed Fumonisin B1 after Single Oral or Intravenous Bolus to Broiler Chickens Fed a Control or a Fumonisins-Contaminated Diet. Toxins. 2020; 12 (6):413.

Chicago/Turabian Style

Gunther Antonissen; Siegrid De Baere; Barbara Novak; Dian Schatzmayr; Danica Den Hollander; Mathias Devreese; Siska Croubels. 2020. "Toxicokinetics of Hydrolyzed Fumonisin B1 after Single Oral or Intravenous Bolus to Broiler Chickens Fed a Control or a Fumonisins-Contaminated Diet." Toxins 12, no. 6: 413.

Journal article
Published: 12 June 2020 in Animals
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The aim of the current study was to investigate the simultaneous measurement of plasma p-aminohippuric acid (PAH) clearance as a potential marker to assess effective renal plasma flow (eRPF) and tubular secretion (TS), and the plasma clearance of iohexol (IOH) as a marker of the glomerular filtration rate in poultry species. The PAH was administered intravenously (IV) to broiler chickens, layers, turkeys, Muscovy ducks, and pigeons. Each animal received successively a single bolus dose of 10 mg PAH/kg bodyweight (BW) and 100 mg PAH/kg BW to assess the eRPF and TS, respectively. Simultaneously with both PAH administrations, a single IV bolus of 64.7 mg/kg BW of IOH was administered. A high linear correlation (R2 = 0.79) between eRPF, based on the clearance of the low dose of PAH, and BW was observed for the poultry species. The correlation between TS, based on the clearance of the high dose of PAH, and BW was moderate (R2 = 0.50). Finally, a moderate correlation (R2 = 0.68) was demonstrated between GFR and eRPF and between GFR and TS (R2 = 0.56). This presented pharmacokinetic approach of the simultaneous administration of IOH and PAH enabled a simultaneous evaluation of eRPF/TS and GFR, respectively, in different poultry species.

ACS Style

Lenka Stroobant; Siska Croubels; Laura Dhondt; Joske Millecam; Siegrid De Baere; Elke Gasthuys; Joachim Morrens; Gunther Antonissen. Simultaneous Measurement of Glomerular Filtration Rate, Effective Renal Plasma Flow and Tubular Secretion in Different Poultry Species by Single Intravenous Bolus of Iohexol and Para-Aminohippuric Acid. Animals 2020, 10, 1 .

AMA Style

Lenka Stroobant, Siska Croubels, Laura Dhondt, Joske Millecam, Siegrid De Baere, Elke Gasthuys, Joachim Morrens, Gunther Antonissen. Simultaneous Measurement of Glomerular Filtration Rate, Effective Renal Plasma Flow and Tubular Secretion in Different Poultry Species by Single Intravenous Bolus of Iohexol and Para-Aminohippuric Acid. Animals. 2020; 10 (6):1.

Chicago/Turabian Style

Lenka Stroobant; Siska Croubels; Laura Dhondt; Joske Millecam; Siegrid De Baere; Elke Gasthuys; Joachim Morrens; Gunther Antonissen. 2020. "Simultaneous Measurement of Glomerular Filtration Rate, Effective Renal Plasma Flow and Tubular Secretion in Different Poultry Species by Single Intravenous Bolus of Iohexol and Para-Aminohippuric Acid." Animals 10, no. 6: 1.

Review
Published: 02 April 2020 in Toxins
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Mycotoxins are secondary metabolites of fungi that contaminate food and feed and have a significant negative impact on human and animal health and productivity. The tropical condition in Sub-Saharan Africa (SSA) together with poor storage of feed promotes fungal growth and subsequent mycotoxin production. Aflatoxins (AF) produced by Aspergillus species, fumonisins (FUM), zearalenone (ZEN), T-2 toxin (T-2), and deoxynivalenol (DON) produced by Fusarium species, and ochratoxin A (OTA) produced by Penicillium and Aspergillus species are well-known mycotoxins of agricultural importance. Consumption of feed contaminated with these toxins may cause mycotoxicoses in animals, characterized by a range of clinical signs depending on the toxin, and losses in the animal industry. In SSA, contamination of dairy feed with mycotoxins has been frequently reported, which poses a serious constraint to animal health and productivity, and is also a hazard to human health since some mycotoxins and their metabolites are excreted in milk, especially aflatoxin M1. This review describes the major mycotoxins, their occurrence, and impact in dairy cattle diets in SSA highlighting the problems related to animal health, productivity, and food safety and the up-to-date post-harvest mitigation strategies for the prevention and reduction of contamination of dairy feed.

ACS Style

David Chebutia Kemboi; Gunther Antonissen; Phillis E. Ochieng; Siska Croubels; Sheila Okoth; Erastus K. Kangethe; Johannes Faas; Johanna F. Lindahl; James K. Gathumbi. A Review of the Impact of Mycotoxins on Dairy Cattle Health: Challenges for Food Safety and Dairy Production in Sub-Saharan Africa. Toxins 2020, 12, 222 .

AMA Style

David Chebutia Kemboi, Gunther Antonissen, Phillis E. Ochieng, Siska Croubels, Sheila Okoth, Erastus K. Kangethe, Johannes Faas, Johanna F. Lindahl, James K. Gathumbi. A Review of the Impact of Mycotoxins on Dairy Cattle Health: Challenges for Food Safety and Dairy Production in Sub-Saharan Africa. Toxins. 2020; 12 (4):222.

Chicago/Turabian Style

David Chebutia Kemboi; Gunther Antonissen; Phillis E. Ochieng; Siska Croubels; Sheila Okoth; Erastus K. Kangethe; Johannes Faas; Johanna F. Lindahl; James K. Gathumbi. 2020. "A Review of the Impact of Mycotoxins on Dairy Cattle Health: Challenges for Food Safety and Dairy Production in Sub-Saharan Africa." Toxins 12, no. 4: 222.

Journal article
Published: 14 February 2020 in Poultry Science
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Oral administration of antibodies is a promising strategy against various infectious diseases. Previously, it was demonstrated that passive immunization by providing hyperimmune egg yolk through the feed reduces Campylobacter jejuni colonization in broilers. Campylobacteriosis is the most commonly reported bacterial foodborne zoonosis worldwide, and poultry products are the number one origin of these bacteria for human infection. To date, no effective control measures exist to limit Campylobacter colonization in the chicken's intestinal tract. Here, the effect of lyophilization of hyperimmune egg yolk on protection of broilers against C. jejuni was investigated. During an in vivo trial, broiler chickens were prophylactically given feed with lyophilized hyperimmune or non-immunized egg yolk powder starting from day 1 after hatch. At day 11, broilers were inoculated with C. jejuni according to a seeder model. Five days later, all broilers were euthanized and cecal content was examined for C. jejuni colonization. No decrease in C. jejuni colonization was found. The freeze-drying resulted in a 16-fold decrease of the antibody titer in the yolk powder compared to the fresh yolks, presumably caused by structural changes in the antibodies. In conclusion, applying freeze-dried hyperimmune egg yolk failed to protect broilers against C. jejuni colonization, possibly because lyophilization affected the antibodies' functionality.

ACS Style

Jasmien Vandeputte; An Martel; Gunther Antonissen; Marc Verlinden; Lieven De Zutter; Marc Heyndrickx; Freddy Haesebrouck; Frank Pasmans; An Garmyn. Research Note: Lyophilization of hyperimmune egg yolk: effect on antibody titer and protection of broilers against Campylobacter colonization. Poultry Science 2020, 99, 2157 -2161.

AMA Style

Jasmien Vandeputte, An Martel, Gunther Antonissen, Marc Verlinden, Lieven De Zutter, Marc Heyndrickx, Freddy Haesebrouck, Frank Pasmans, An Garmyn. Research Note: Lyophilization of hyperimmune egg yolk: effect on antibody titer and protection of broilers against Campylobacter colonization. Poultry Science. 2020; 99 (4):2157-2161.

Chicago/Turabian Style

Jasmien Vandeputte; An Martel; Gunther Antonissen; Marc Verlinden; Lieven De Zutter; Marc Heyndrickx; Freddy Haesebrouck; Frank Pasmans; An Garmyn. 2020. "Research Note: Lyophilization of hyperimmune egg yolk: effect on antibody titer and protection of broilers against Campylobacter colonization." Poultry Science 99, no. 4: 2157-2161.

Journal article
Published: 23 December 2019 in Scientific Reports
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Early diagnosis of kidney diseases in avian species is limited. Endogenous markers currently used in avian practice are not sensitive enough to identify early kidney failure. Consequently, alternative markers should be evaluated. To be able to evaluate these alternative markers, an accurate marker to estimate the GFR should be validated. This study determined the GFR, measured as clearance of exogenous creatinine and exo-iohexol, in six different bird species, i.e. broiler chickens, laying chickens, turkeys, Muscovy ducks, pigeons and African grey parrots (4♀/4♂). To be able to compare the six bird species, normalization to bodyweight (BW) of the GFR was performed, after a good correlation between BW and kidney weight was demonstrated (R² = 0.9836). Clearance of exo-iohexol normalized to BW (mL/min/kg) was determined in all bird species, i.e. 3.09 in broiler chickens; 2.57 in laying chickens; 1.94 in turkeys; 1.29 in pigeons; 2.60 in ducks and 1.11 in parrots. However, these results differed significantly with the clearance of exogenous creatinine: 8.41 in broiler chickens; 9.33 in laying chickens; 5.62 in turkeys; 14.97 in pigeons; 17.59 in ducks and 25.56 in parrots 25.56. Iohexol is preferred to measure the GFR, since it is not prone to tubular reabsorption nor secretion.

ACS Style

Elke Gasthuys; Andrés Montesinos; Nele Caekebeke; Mathias Devreese; Siegrid De Baere; Maria Ardiaca; Dominique Paepe; Siska Croubels; Gunther Antonissen. Comparative physiology of glomerular filtration rate by plasma clearance of exogenous creatinine and exo-iohexol in six different avian species. Scientific Reports 2019, 9, 1 -8.

AMA Style

Elke Gasthuys, Andrés Montesinos, Nele Caekebeke, Mathias Devreese, Siegrid De Baere, Maria Ardiaca, Dominique Paepe, Siska Croubels, Gunther Antonissen. Comparative physiology of glomerular filtration rate by plasma clearance of exogenous creatinine and exo-iohexol in six different avian species. Scientific Reports. 2019; 9 (1):1-8.

Chicago/Turabian Style

Elke Gasthuys; Andrés Montesinos; Nele Caekebeke; Mathias Devreese; Siegrid De Baere; Maria Ardiaca; Dominique Paepe; Siska Croubels; Gunther Antonissen. 2019. "Comparative physiology of glomerular filtration rate by plasma clearance of exogenous creatinine and exo-iohexol in six different avian species." Scientific Reports 9, no. 1: 1-8.

Toxicokinetics and metabolism
Published: 13 December 2019 in Archives of Toxicology
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Age-related differences in toxicokinetic processes of deoxynivalenol (DON) and deoxynivalenol-3-glucoside (DON3G) were studied. DON3G [55.7 µg/kg bodyweight (BW)] and an equimolar dose of DON (36 µg/kg BW) were administered to weaned piglets (4 weeks old) by single intravenous and oral administration in a double two-way cross-over design. Systemic and portal blood was sampled at different time points pre- and post-administration and plasma concentrations of DON, DON3G and their metabolites were quantified using validated liquid chromatography-tandem mass spectrometry (LC–MS/MS) and liquid chromatography–high-resolution mass spectrometry (LC–HRMS) methods. Data were processed using tailor-made compartmental toxicokinetic (TK) models to accurately estimate TK parameters. Results were statistically compared to data obtained in a previous study on 11-week-old pigs using identical experimental conditions. Significant age-related differences in intestinal and systemic exposure to both DON and DON3G were noted. Most remarkably, a significant difference was found for the absorbed fraction of DON3G, after presystemic hydrolysis to DON, in weaned piglets compared to 11-week-old piglets (83% vs 16%, respectively), assumed to be mainly attributed to the higher intestinal permeability of weaned piglets. Other differences in TK parameters could be assigned to a higher water/fat body ratio and longer gastrointestinal transit time of weaned piglets. Results may further refine current risk assessment concerning DON and DON3G in animals. Additionally, since piglets possibly serve as a human paediatric surrogate model, results may be extrapolated to human infants.

ACS Style

Amelie Catteuw; Mathias Devreese; Siegrid De Baere; Gunther Antonissen; Lada Ivanova; Silvio Uhlig; Ann Martens; Sarah De Saeger; Marthe De Boevre; Siska Croubels. Investigation of age-related differences in toxicokinetic processes of deoxynivalenol and deoxynivalenol-3-glucoside in weaned piglets. Archives of Toxicology 2019, 94, 417 -425.

AMA Style

Amelie Catteuw, Mathias Devreese, Siegrid De Baere, Gunther Antonissen, Lada Ivanova, Silvio Uhlig, Ann Martens, Sarah De Saeger, Marthe De Boevre, Siska Croubels. Investigation of age-related differences in toxicokinetic processes of deoxynivalenol and deoxynivalenol-3-glucoside in weaned piglets. Archives of Toxicology. 2019; 94 (2):417-425.

Chicago/Turabian Style

Amelie Catteuw; Mathias Devreese; Siegrid De Baere; Gunther Antonissen; Lada Ivanova; Silvio Uhlig; Ann Martens; Sarah De Saeger; Marthe De Boevre; Siska Croubels. 2019. "Investigation of age-related differences in toxicokinetic processes of deoxynivalenol and deoxynivalenol-3-glucoside in weaned piglets." Archives of Toxicology 94, no. 2: 417-425.

Journal article
Published: 01 December 2019 in Journal of Avian Medicine and Surgery
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Nonsteroidal anti-inflammatory drugs (NSAIDs) are used frequently in avian medicine for their antipyretic, analgesic, and anti-inflammatory properties during surgery and for diseases that cause tissue damage and inflammation. NSAIDs inhibit cyclooxygenase (COX) enzymes, which are responsible for the induction of pyresis, pain, and inflammation. In our study, a lipopolysaccharide-induced (LPS) pyresis model was optimized using cockatiels (Nymphicus hollandicus) as subject birds (four males/three females) and validated in two females and one male, characterized by an intravenous bolus injection of LPS (7.5 mg/kg) administered at T0 and T24 (24 hours following the first LPS injection). To demonstrate the feasibility of the model to assess pharmacodynamic (PD) parameters of different NSAIDs, mavacoxib 4 mg/kg (four males/four females), celecoxib 10 mg/kg (four males/four females) and meloxicam 1 mg/kg (four males/four females) were evaluated in the model at dosages used frequently in practice. The PD parameters (body temperature, mentation, posture, preference of location in the cage, and prostaglandin E2 [PGE2] plasma concentrations) were determined for 10 hours following the second LPS injection. At the doses evaluated, mavacoxib and celecoxib significantly reduced LPS-induced hypothermia, but had no clear effects on other clinical signs of illness. In contrast, no effect on hypothermia or clinical appearance was observed in the LPS-challenged cockatiels treated with meloxicam. All three NSAIDs were able to inhibit the increase in LPS-induced PGE2 plasma concentrations, yet the effect was most pronounced in the birds treated with meloxicam. Consequently, the presented model opens perspectives for future dose-effect PD studies to optimize analgesic protocols in cockatiels.

ACS Style

Elke Gasthuys; Renée Houben; Roel Haesendonck; Siegrid De Baere; Stanislas U. Sys; Joachim Morrens; Gunther Antonissen. Development of an in Vivo Lipopolysaccharide Inflammation Model to Study the Pharmacodynamics of COX-2 Inhibitors Celecoxib, Mavacoxib, and Meloxicam in Cockatiels (Nymphicus hollandicus). Journal of Avian Medicine and Surgery 2019, 33, 349 -360.

AMA Style

Elke Gasthuys, Renée Houben, Roel Haesendonck, Siegrid De Baere, Stanislas U. Sys, Joachim Morrens, Gunther Antonissen. Development of an in Vivo Lipopolysaccharide Inflammation Model to Study the Pharmacodynamics of COX-2 Inhibitors Celecoxib, Mavacoxib, and Meloxicam in Cockatiels (Nymphicus hollandicus). Journal of Avian Medicine and Surgery. 2019; 33 (4):349-360.

Chicago/Turabian Style

Elke Gasthuys; Renée Houben; Roel Haesendonck; Siegrid De Baere; Stanislas U. Sys; Joachim Morrens; Gunther Antonissen. 2019. "Development of an in Vivo Lipopolysaccharide Inflammation Model to Study the Pharmacodynamics of COX-2 Inhibitors Celecoxib, Mavacoxib, and Meloxicam in Cockatiels (Nymphicus hollandicus)." Journal of Avian Medicine and Surgery 33, no. 4: 349-360.

Journal article
Published: 01 November 2019 in Poultry Science
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Campylobacter jejuni and Campylobacter coli originating from poultry meat have been the most important causes of foodborne bacterial gastroenteritis in the European Union since 2005. In-feed application of maternal antibodies from vaccinated hens was shown to confer protection of broilers against Campylobacter infection. Here, it was investigated if these vaccines can be used to protect broilers against Campylobacter infection after in ovo vaccination. Embryos were immunized in ovo at day 18 with a bacterin or a subunit vaccine and at 19 D post hatch, these birds were inoculated with C. jejuni according to a seeder model. Quantification of C. jejuni in the broilers cecal content showed that the in ovo vaccinated birds were not protected against C. jejuni infection. Quantification of blood anti-Campylobacter antibody titers did not show any induction of Campylobacter-specific serological response in the vaccinated birds, which may explain the lack of protection in the vaccinated chicks.

ACS Style

Jasmien Vandeputte; An Martel; Nathalie Van Rysselberghe; Gunther Antonissen; Marc Verlinden; Lieven De Zutter; Marc Heyndrickx; Freddy Haesebrouck; Frank Pasmans; An Garmyn. In ovo vaccination of broilers against Campylobacter jejuni using a bacterin and subunit vaccine. Poultry Science 2019, 98, 5999 -6004.

AMA Style

Jasmien Vandeputte, An Martel, Nathalie Van Rysselberghe, Gunther Antonissen, Marc Verlinden, Lieven De Zutter, Marc Heyndrickx, Freddy Haesebrouck, Frank Pasmans, An Garmyn. In ovo vaccination of broilers against Campylobacter jejuni using a bacterin and subunit vaccine. Poultry Science. 2019; 98 (11):5999-6004.

Chicago/Turabian Style

Jasmien Vandeputte; An Martel; Nathalie Van Rysselberghe; Gunther Antonissen; Marc Verlinden; Lieven De Zutter; Marc Heyndrickx; Freddy Haesebrouck; Frank Pasmans; An Garmyn. 2019. "In ovo vaccination of broilers against Campylobacter jejuni using a bacterin and subunit vaccine." Poultry Science 98, no. 11: 5999-6004.

Journal article
Published: 16 October 2019 in Toxins
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Clays are known to have promising adsorbing characteristics, and are used as feed additives to overcome the negative effects of mycotoxicosis in livestock farming. Modification of clay minerals by heat treatment, also called calcination, can alter their adsorption characteristics. Little information, however, is available on the effect of calcination with respect to mycotoxin binding. The purpose of this study was to characterize a Tunisian clay before and after calcination (at 550 °C), and to investigate the effectiveness of the thermal treatment of this clay on its aflatoxin B1 (AFB1), G1 (AFG1), B2 (AFB2), G2 (AFG2), and zearalenone (ZEN) adsorption capacity. Firstly, the purified clay (CP) and calcined clay (CC) were characterized with X-ray Fluorescence (XRF), X-ray Diffraction (XRD), Fourier transform infrared spectroscopy (FTIR-IR), cation exchange capacity (CEC), specific surface area (SBET), and point of zero charge (pHPZC) measurements. Secondly, an in vitro model that simulated the pH conditions of the monogastric gastrointestinal tract was used to evaluate the binding efficiency of the tested clays when artificially mixed with aflatoxins and zearalenone. The tested clay consisted mainly of smectite and illite. Purified and calcined clay had similar chemical compositions. After heat treatment, however, some changes in the mineralogical and textural properties were observed. The calcination decreased the cation exchange capacity and the specific surface, whereas the pore size was increased. Both purified and calcined clay had a binding efficacy of over 90% for AFB1 under simulated poultry GI tract conditions. Heat treatment of the clay increased the adsorption of AFB2, AFG1, and AFG2 related to the increase in pore size of the clay by the calcination process. ZEN adsorption also increased by calcination, albeit to a more stable level at pH 3 rather than at pH 7. In conclusion, calcination of clay minerals enhanced the adsorption of aflatoxins and mostly of AFG1 and AFG2 at neutral pH of the gastrointestinal tract, and thus are associated with protection against the toxic effects of aflatoxins.

ACS Style

Roua Rejeb; Gunther Antonissen; Marthe De Boevre; Christ’L Detavernier; Mario Van De Velde; Sarah De Saeger; Richard Ducatelle; Madiha Hadj Ayed; Achraf Ghorbal; Roua Rejeb. Calcination Enhances the Aflatoxin and Zearalenone Binding Efficiency of a Tunisian Clay. Toxins 2019, 11, 602 .

AMA Style

Roua Rejeb, Gunther Antonissen, Marthe De Boevre, Christ’L Detavernier, Mario Van De Velde, Sarah De Saeger, Richard Ducatelle, Madiha Hadj Ayed, Achraf Ghorbal, Roua Rejeb. Calcination Enhances the Aflatoxin and Zearalenone Binding Efficiency of a Tunisian Clay. Toxins. 2019; 11 (10):602.

Chicago/Turabian Style

Roua Rejeb; Gunther Antonissen; Marthe De Boevre; Christ’L Detavernier; Mario Van De Velde; Sarah De Saeger; Richard Ducatelle; Madiha Hadj Ayed; Achraf Ghorbal; Roua Rejeb. 2019. "Calcination Enhances the Aflatoxin and Zearalenone Binding Efficiency of a Tunisian Clay." Toxins 11, no. 10: 602.

Journal article
Published: 04 October 2019 in Toxins
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Forages are important components of dairy cattle rations but might harbor a plethora of mycotoxins. Ruminants are considered to be less susceptible to the adverse health effects of mycotoxins, mainly because the ruminal microflora degrades certain mycotoxins. Yet, impairment of the ruminal degradation capacity or high ruminal stability of toxins can entail that the intestinal epithelium is exposed to significant mycotoxin amounts. The aims of our study were to assess i) the mycotoxin occurrence in maize silage and ii) the cytotoxicity of relevant mycotoxins on bovine intestinal cells. In total, 158 maize silage samples were collected from European dairy cattle farms. LC-MS/MS-based analysis of 61 mycotoxins revealed the presence of emerging mycotoxins (e.g. emodin, culmorin, enniatin B1, enniatin B, and beauvericin) in more than 70% of samples. Among the regulated mycotoxins, deoxynivalenol and zearalenone were most frequently detected (67.7%). Overall, 87% of maize silages contained more than five mycotoxins. Using an in vitro model with calf small intestinal epithelial cells B, the cytotoxicity of deoxynivalenol, nivalenol, fumonisin B1 and enniatin B was evaluated (0–200 µM). Absolute IC50 values varied in dependence of employed assay and were 1.2–3.6 µM, 0.8–1.0 µM, 8.6–18.3 µM, and 4.0–6.7 µM for deoxynivalenol, nivalenol, fumonisin B1, and enniatin B, respectively. Results highlight the potential relevance of mycotoxins for bovine gut health, a previously neglected target in ruminants.

ACS Style

Nicole Reisinger; Sonja Schürer-Waldheim; Elisabeth Mayer; Sandra Debevere; Gunther Antonissen; Michael Sulyok; Veronika Nagl. Mycotoxin Occurrence in Maize Silage—A Neglected Risk for Bovine Gut Health? Toxins 2019, 11, 577 .

AMA Style

Nicole Reisinger, Sonja Schürer-Waldheim, Elisabeth Mayer, Sandra Debevere, Gunther Antonissen, Michael Sulyok, Veronika Nagl. Mycotoxin Occurrence in Maize Silage—A Neglected Risk for Bovine Gut Health? Toxins. 2019; 11 (10):577.

Chicago/Turabian Style

Nicole Reisinger; Sonja Schürer-Waldheim; Elisabeth Mayer; Sandra Debevere; Gunther Antonissen; Michael Sulyok; Veronika Nagl. 2019. "Mycotoxin Occurrence in Maize Silage—A Neglected Risk for Bovine Gut Health?" Toxins 11, no. 10: 577.

Research article
Published: 26 June 2019 in Laboratory Animals
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The use of juvenile conventional pigs as a preclinical animal model to perform pharmacokinetic (PK), pharmacodynamic (PD) and safety studies for the paediatric population is increasing. Repetitive oral administration of drugs to juvenile pigs is however challenging. A representative method which can be used from birth till adulthood is necessary. The current study presents the placement and use of a gastrostomy button in pigs with a weight ranging from 2.4 to 161 kg. The surgical placement was performed via a laparotomic procedure on, each time, 12 pigs (six male, six female) of 1 week, 4 weeks, 8 weeks and 6–7 months old. For every age category, eight pigs were part of a PK study with a non-steroidal anti-inflammatory drug (NSAID) and four pigs served as a control group. No severe complications were observed during surgery. The button remained functional for 10 days in 40 out of 48 pigs. No significant differences in body temperature or white blood cell count were observed during the trial. Three control pigs showed signs of inflammation indicating a NSAID might be warranted. Autopsy revealed minimal signs of major inflammation in the abdominal cavity or the stomach. A limited number of pigs showed mucosal inflammation, ulcers or abscesses in the stomach or around the fistula. These results indicate that the laparotomic placement of a gastrostomy button might be considered safe and easy in growing pigs to perform repetitive oral dosing preclinical studies. However, the method is not advised in pigs weighing more than 100 kg.

ACS Style

Joske Millecam; Thomas Van Bergen; Mathias Devreese; Stijn Schauvliege; Ann Martens; Koen Chiers; Siska Croubels; Gunther Antonissen. Gastrostomy tube placement via a laparotomic procedure in growing conventional piglets to perform multi-dose preclinical paediatric drug studies. Laboratory Animals 2019, 54, 261 -271.

AMA Style

Joske Millecam, Thomas Van Bergen, Mathias Devreese, Stijn Schauvliege, Ann Martens, Koen Chiers, Siska Croubels, Gunther Antonissen. Gastrostomy tube placement via a laparotomic procedure in growing conventional piglets to perform multi-dose preclinical paediatric drug studies. Laboratory Animals. 2019; 54 (3):261-271.

Chicago/Turabian Style

Joske Millecam; Thomas Van Bergen; Mathias Devreese; Stijn Schauvliege; Ann Martens; Koen Chiers; Siska Croubels; Gunther Antonissen. 2019. "Gastrostomy tube placement via a laparotomic procedure in growing conventional piglets to perform multi-dose preclinical paediatric drug studies." Laboratory Animals 54, no. 3: 261-271.

Original research article
Published: 09 May 2019 in Frontiers in Pharmacology
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Pediatric drug development, especially in disease areas that only affect children, can be stimulated by using juvenile animal models not only for general safety studies, but also to gain knowledge on the pharmacokinetic and pharmacodynamic properties of the drug. Recently, the conventional growing piglet has been suggested as juvenile animal model. However, more studies with different classes of drugs are warranted to make a thorough evaluation whether the juvenile pig might be a suitable preclinical animal model. Ibuprofen is one of the most widely used non-steroidal anti-inflammatory drugs in human. The present study determined the PK parameters, gastro-intestinal and renal safety of 5 mg/kg BW ibuprofen after single intravenous, single oral and multiple oral administration to each time eight pigs (four males, four females) aging 1, 4, 8 weeks and 6–7 months. Oral administration was performed via a gastrostomy button. A jugular catheter was used for intravenous administration and blood sampling. To assess NSAID induced renal toxicity, renal function was evaluated using iohexol and p-aminohippuric acid as markers for glomerular filtration rate and renal plasma flow, respectively. After the trial, necropsy and histology was performed to evaluate macroscopic and microscopic gastro-intestinal as well as renal lesions. Both enantiomers, R-ibuprofen and S-ibuprofen, were determined in plasma using an in-house developed and validated UHPLC-MS/MS method. Pharmacokinetic parameters were estimated using compartmental analysis. Clearance and volume of distribution of total ibuprofen and both enantiomers increased with age as was observed in human. The rate of stereochemical conversion decreased with age. Multiple oral dosing decreased the absolute oral bioavailability and maximum plasma concentration of R-ibuprofen and food consumption did not influence drug absorption. Based on the limited available pediatric literature, the current study might suggest the conventional pig as suitable animal model to evaluate NSAIDs for pediatric use.

ACS Style

Joske Millecam; Thomas van Bergen; Stijn Schauvliege; Gunther Antonissen; Ann Martens; Koen Chiers; Ronette Gehring; Elke Gasthuys; Johan Vande Walle; Siska Croubels; Mathias Devreese. Developmental Pharmacokinetics and Safety of Ibuprofen and Its Enantiomers in the Conventional Pig as Potential Pediatric Animal Model. Frontiers in Pharmacology 2019, 10, 505 .

AMA Style

Joske Millecam, Thomas van Bergen, Stijn Schauvliege, Gunther Antonissen, Ann Martens, Koen Chiers, Ronette Gehring, Elke Gasthuys, Johan Vande Walle, Siska Croubels, Mathias Devreese. Developmental Pharmacokinetics and Safety of Ibuprofen and Its Enantiomers in the Conventional Pig as Potential Pediatric Animal Model. Frontiers in Pharmacology. 2019; 10 ():505.

Chicago/Turabian Style

Joske Millecam; Thomas van Bergen; Stijn Schauvliege; Gunther Antonissen; Ann Martens; Koen Chiers; Ronette Gehring; Elke Gasthuys; Johan Vande Walle; Siska Croubels; Mathias Devreese. 2019. "Developmental Pharmacokinetics and Safety of Ibuprofen and Its Enantiomers in the Conventional Pig as Potential Pediatric Animal Model." Frontiers in Pharmacology 10, no. : 505.

Toxicokinetics and metabolism
Published: 10 December 2018 in Archives of Toxicology
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A clinical case in Belgium demonstrated that feeding a feed concentrate containing considerable levels of deoxynivalenol (DON, 1.13 mg/kg feed) induced severe liver failure in 2- to 3-month-old beef calves. Symptoms disappeared by replacing the highly contaminated corn and by stimulating ruminal development via roughage administration. A multi-mycotoxin contamination was demonstrated in feed samples collected at 15 different veal farms in Belgium. DON was most prevalent, contaminating 80% of the roughage samples (mixed straw and maize silage; average concentration in positives: 637 ± 621 µg/kg, max. 1818 µg/kg), and all feed concentrate samples (411 ± 156 µg/kg, max. 693 µg/kg). In order to evaluate the impact of roughage provision and its associated ruminal development on the gastro-intestinal absorption and biodegradation of DON and its acetylated derivatives (3- and 15-ADON) in calves, a toxicokinetic study was performed with two ruminating and two non-ruminating male calves. Animals received in succession a bolus of DON (120 µg/kg bodyweight (BW)), 15-ADON (50 µg/kg BW), and 3-ADON (25 µg/kg) by intravenous (IV) injection or per os (PO) in a cross-over design. The absolute oral bioavailability of DON was much higher in non-ruminating calves (50.7 ± 33.0%) compared to ruminating calves (4.1 ± 4.5%). Immediately following exposure, 3- and 15-ADON were hydrolysed to DON in ruminating calves. DON and its acetylated metabolites were mainly metabolized to DON-3-glucuronide, however, also small amounts of DON-15-glucuronide were detected in urine. DON degradation to deepoxy-DON (DOM-1) was only observed to a relevant extent in ruminating calves. Consequently, toxicity of DON in calves is closely related to roughage provision and the associated stage of ruminal development.

ACS Style

Bonnie Valgaeren; Léonard Théron; Siska Croubels; Mathias Devreese; Siegrid De Baere; Els Van Pamel; Els Daeseleire; Marthe De Boevre; Sarah De Saeger; Arnau Vidal; José Diana Di Mavungu; Philipp Fruhmann; Gerhard Adam; Alfons Callebaut; Calixte Bayrou; Vincent Frisée; Anne-Sophie Rao; Emilie Knapp; Arnaud Sartelet; Bart Pardon; Piet Deprez; Gunther Antonissen. The role of roughage provision on the absorption and disposition of the mycotoxin deoxynivalenol and its acetylated derivatives in calves: from field observations to toxicokinetics. Archives of Toxicology 2018, 93, 293 -310.

AMA Style

Bonnie Valgaeren, Léonard Théron, Siska Croubels, Mathias Devreese, Siegrid De Baere, Els Van Pamel, Els Daeseleire, Marthe De Boevre, Sarah De Saeger, Arnau Vidal, José Diana Di Mavungu, Philipp Fruhmann, Gerhard Adam, Alfons Callebaut, Calixte Bayrou, Vincent Frisée, Anne-Sophie Rao, Emilie Knapp, Arnaud Sartelet, Bart Pardon, Piet Deprez, Gunther Antonissen. The role of roughage provision on the absorption and disposition of the mycotoxin deoxynivalenol and its acetylated derivatives in calves: from field observations to toxicokinetics. Archives of Toxicology. 2018; 93 (2):293-310.

Chicago/Turabian Style

Bonnie Valgaeren; Léonard Théron; Siska Croubels; Mathias Devreese; Siegrid De Baere; Els Van Pamel; Els Daeseleire; Marthe De Boevre; Sarah De Saeger; Arnau Vidal; José Diana Di Mavungu; Philipp Fruhmann; Gerhard Adam; Alfons Callebaut; Calixte Bayrou; Vincent Frisée; Anne-Sophie Rao; Emilie Knapp; Arnaud Sartelet; Bart Pardon; Piet Deprez; Gunther Antonissen. 2018. "The role of roughage provision on the absorption and disposition of the mycotoxin deoxynivalenol and its acetylated derivatives in calves: from field observations to toxicokinetics." Archives of Toxicology 93, no. 2: 293-310.