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Biomedical subjects

A Pijpers

Publications and source records attributed to A Pijpers.

At least 37 records · Page 2Linked to original sources

Prophylaxis of pleuropneumonia in pigs by in-feed medication with oxytetracycline and the subsequent transmission of infection.

The prophylactic effect of in-feed medication with oxytetracycline was tested by using an Actinobacillus pleuropneumoniae aerosol challenge model. Groups of 10 conventional pigs were provided with feed containing 400, 800, 1200 or 1600 mg oxytetracycline/kg and fed ad libitum. After six days of medication the pigs were challenged and clinical signs were recorded. Two groups of four unmedicated pigs served as controls and were euthanased 36 to 48 hours after challenge and dissected. The feed medication was continued for nine days after the challenge, and the different treatment groups were then moved to separate accommodation where they were mixed with seronegative tracer pigs. The steady state concentrations of oxytetracycline in the pigs' serum after six days medication with feed containing 400, 800, 1200 or 1600 mg oxytetracycline/kg ranged from 0.07 to 0.13, 0.21 to 0.46, 0.27 to 0.46 and 0.35 to 0.56 microgram/ml, respectively. One of the eight unmedicated control pigs died, and the other seven showed signs of pleuropneumonia post mortem. Medication with feed containing 400 mg and 800 mg oxytetracycline/kg failed to prevent pleuropneumonia in the challenged pigs, and the mortality rates in these groups were two out of 10 and one out of nine pigs, respectively. All the pigs given feed containing 1200 and 1600 mg oxytetracycline/kg survived and only two of the pigs in the first treatment group showed mild clinical signs. No clinical signs were observed in the tracer pigs which were mixed with the pigs medicated with 400, 800 or 1200 mg oxytetracycline/kg.(ABSTRACT TRUNCATED AT 250 WORDS)

Actinobacillus Infections↗

The prevalence of patent lungworm infections in herds of dairy cows in The Netherlands.

The results of a survey on the prevalence of patent lungworm infections in herds of dairy cows in the Netherlands are presented. Low patent infections were recorded in February-March on six out of 40 farms in at least one out of 40 cows. Between mid-April and mid-June low patent infections were detected on 28 out of 39 of these farms in one to four of 40 cows. Two farms on which cows were positive in the first round were negative in the second round. One to three positive cows were found on six out of a total of 15 farms revisited in July-August. These results show that lungworm infections are cycled within herds of dairy cows in the Netherlands at a low level. This indicates that dairy cows are important as carriers for lungworm, particularly in spring. The increased patency of lungworm in cows from winter to spring may be explained by maturation of inhibited larvae.

Animals↗

The clinical recovery of fattening pigs from respiratory disease after treatment with two injectable oxytetracycline formulations.

A double blind randomized clinical trial was performed with pigs suffering from clinical respiratory disease. The goal of the trial was to test the null hypothesis that the clinical recovery after treatment with two oxytetracycline injectables with different pharmacokinetic profiles (high peak concentration and low persistence versus low peak concentrations and long persistence) was similar. Fattening pigs (n = 529) were treated intramuscularly with either product A or product B at a dose of 20 mg OTC per kg b.w. when they showed signs of acute pneumonia, i.e., coughing, tachypnoea or dyspnoea combined with a rectal temperature of 40 degrees C or higher. When necessary, treatment was given again after 3 and/or 6 days. Both treatments resulted in a rapid fall in mean temperature and an improved clinical condition. In this trial no significant differences were found in clinical recovery between the two therapies as measured by group mean temperature, number of pigs requiring retreatment, and time to recovery. The conclusion that there was no important difference in clinical recovery between the treatment groups was made with a power of at least 90%.

Animals↗

Effects of ketoprofen and flunixin in pigs experimentally infected with Actinobacillus pleuropneumoniae.

The antipyretic effect of the non-steroidal anti-inflammatory drugs (NSAIDs) ketoprofen (3 mg/kg) and flunixin (2 mg/kg) were studied in pigs. The drugs were administered intramuscularly at 8 and 32 h following endobronchial challenge with Actinobacillus pleuropneumoniae. Infected (non-medicated) and non-infected (non-medicated) controls were used. Endobronchial challenge with Actinobacillus pleuropneumoniae induced laboured breathing, coughing, fever, reduced food and water consumption and increased white blood cell counts. At autopsy, pleuropneumonia was evident. Ketoprofen showed a highly significant antipyretic effect but flunixin did not. The decrease in food consumption of ketoprofen-treated pigs was significantly less than that of the infected (non-medicated) controls. Blood parameters were not significantly influenced by either NSAID and, at necropsy, gastric and renal side-effects were not observed for either drug.

Actinobacillus Infections↗

An image analysis system: an objective and accurate alternative for reading the agar diffusion test.

A computerized image analysis system (IAS) has been used to develop a new method for reading the agar diffusion test automatically. In four experiments a total of 88 porcine plasma and 95 urine samples were screened for oxytetracycline by the agar diffusion test. The inhibition zones were measured by hand and by the IAS directly from the bioassay plate and by the IAS from the photo-negative taken from the plate. Both methods were positively correlated with the hand method for plasma (0.9716, 0.9669) and urine (0.9878, 0.9731) in the range tested for 0.1 to 2.0 micrograms/ml. Moreover, the coefficient of variation and the day-to-day-variation amounted to 1.72% and 1.47% respectively, for the method by hand and 1.10, 1.54% and 0.27, 0.38% respectively, for the IAS methods. It is concluded that the IAS method is an objective and accurate alternative for reading the agar diffusion test.

Agar↗

Dose-dependent pharmacokinetic interaction between antipyrine and paracetamol in vivo and in vitro when administered as a cocktail in pig.

1. The pharmacokinetic interactions between paracetamol (PA) and antipyrine (AP) were studied in pigs in order to investigate the usefulness of this combination for the simultaneous assessment of oxidative and conjugative metabolism. 2. When both drugs were given at a dose of 5 mg/kg, AP plasma clearance was reduced from 2.22 to 0.96 lh-1 kg-1. PA clearance was not changed in comparison with control values. 3. At a dose of 2 mg/kg no pharmacokinetic interaction between the two drugs was observed. 4. The only oxidative AP metabolite found in urine was 4-hydroxyantipyrine (4-OHA). It accounted for 80% of the dose and, like PA, it was completely glucuronidated. 5. The glucuronidation of PA has been studied in vitro in pig liver microsomes. The apparent Km value for PA glucuronidation was 40 mM with a Vmax = 54 nmol min-1 mg protein-1. To determine if 4-OHA and PA competed for the same UDP-glucuronosyl-transferase, the effect of 4-OHA and AP on PA glucuronidation was studied. It appeared that 4-OHA was a competitive inhibitor with a Ki app = 0.07 microM, whereas AP had no effect. 5. Results suggest a dose-dependent interaction between AP and PA, which may be due to competition at the level of glucuronidation. Therefore, the usefulness of AP and PA in vivo in a cocktail for metabolism studies is limited.

Acetaminophen↗

Porcine epidemic diarrhoea virus as a cause of persistent diarrhoea in a herd of breeding and finishing pigs.

A clinical and virological study of an outbreak of porcine epidemic diarrhoea in a combined breeding and finishing pig herd used ELISA techniques to detect porcine epidemic diarrhoea virus in faeces and antibodies in blood. No seropositive pigs were found at the start of the outbreak. The first signs of the disease were observed in fattening pigs and the infection spread rapidly to pregnant sows, farrowing sows and their suckling pigs, gilts and weaners housed in separate barns. Depression and diarrhoea in the fattening pigs and pregnant sows were the clearest clinical signs. An endemic form of the disease developed which would not normally have been recognised as epidemic diarrhoea because no typical signs were apparent. Eleven groups of seronegative replacement gilts, which were brought in monthly, became infected with the virus and most of the groups developed a profuse diarrhoea lasting a few days. The infections and diarrhoea persisted in six- to 10-week-old pigs in separate barns. The suckling pigs and young weaners appeared to be spared from the infections.

Animal Husbandry↗

Comparison of methods for in vitro testing of susceptibility of porcine Mycoplasma species to antimicrobial agents.

The MICs of 18 antimicrobial agents used against strains of three porcine Mycoplasma species were determined by a serial broth dilution method. Twenty field strains of M. hyorhinis, ten field strains of M. hyopneumoniae, six field strains of M. flocculare, and the type strains of these species were tested. Twelve field strains and the type strain of M. hyorhinis were also tested by an agar dilution method. Tests were read at various time points. When the broth dilution method was used, the final MIC had to be read 2 days after color changes had stopped. MICs of tetracycline, oxytetracycline, doxycycline, and minocycline were low for the three Mycoplasma species tested. MICs of chlortetracycline were 8 to 16 times higher than MICs of the other tetracyclines. Spiramycin, tylosin, kitasamycin, spectinomycin, tiamulin, lincomycin, and clindamycin were effective against all strains of M. hyorhinis and M. hyopneumoniae. The quinolones were highly effective against M. hyopneumoniae but less effective against M. hyorhinis. The susceptibility patterns for M. hyopneumoniae and M. flocculare were similar.

Animals↗

Plasma levels of oxytetracycline, doxycycline, and minocycline in pigs after oral administration in feed.

Steady-state plasma levels were determined for oxytetracycline (OTC), doxycycline (DC), and minocycline (MC) after medication with different in-feed concentrations. Each concentration of the three tetracyclines was examined in six pigs. The animals were housed in individual pens and fed twice daily with an interval of 12 h. All pigs consumed their feed within 1 h after it was provided. Concentrations of 400, 800, 1,600, and 2,400 mg of OTC per kilogram of feed induced steady-state plasma levels ranging from .13 to .22, .19 to .50, .39 to 1.43, and 1.41 to 2.14 micrograms/ml, respectively. On a feed intake basis, pigs received 13, 26, 54 to 81, and 108 mg of OTC per kilogram of BW per day, respectively. Steady-state plasma levels after medication with 200, 400, and 800 mg of DC or MC per kilogram of feed ranged from .37 to .89, .71 to 1.14, and 1.62 to 3.18 micrograms/ml for DC and from .21 to .60, .43 to 1.05, and 1.19 to 2.62 micrograms/ml for MC. Pigs consumed 7, 13, and 26 mg of DC and 9, 18, and 36 mg of MC per kilogram of BW per day, respectively. For all three tetracyclines there was an increase in steady-state plasma levels when concentrations in feed or per kilogram of BW increased. Plasma levels were determined with both a HPLC method and a microbiological method. A good correlation existed between the results obtained by both methods. It was concluded that based on plasma levels and known in vitro activity DC and MC could be good alternatives for OTC to treat respiratory tract infections in pigs.

Administration, Oral↗

The influence of disease on feed and water consumption and on pharmacokinetics of orally administered oxytetracycline in pigs.

In the present study the feed and water consumption and pharmacokinetic parameters of orally administered oxytetracycline were compared in clinically healthy pigs and in the same pigs following a challenge with Actinobacillus (Haemophilus) pleuropneumoniae toxins. Endobronchial challenge with A. pleuropneumniae toxins was accompanied by anorexia, increased lassitude, labored breathing, fever, and increased white blood cell counts. Pleuropneumonia was evident in all pigs on autopsy. Following the challenge, both feed and water consumption were markedly reduced. In contrast to recommendations in the literature, it is concluded that drugs should not be administered to pneumonic pigs via water. In healthy pigs the oral bioavailability of oxytetracycline (50 mg/kg), given on an empty stomach, was 4.8% and the elimination half-life (t1/2 beta) was 5.92 h. After challenge, the pigs showed great variation in oxytetracycline plasma concentrations. In addition, the mean computed elimination rate constant (beta), t1/2 beta, the area under the plasma concentration-time curve (AUC), and clearance in pneumonic pigs differed significantly (P less than .05) from the values found in healthy pigs. The elimination half-life (t1/2 beta), AUC, and volume of distribution (Vd area) were increased. In diseased pigs the mean of maximum plasma concentrations (.87 micrograms/ml) was reached after 7 h, in contrast to 1.74 h (1.87 micrograms/ml) in the healthy pigs.

Actinobacillus Infections↗

The role of drug lipophilicity in release from intra-adipose and intramuscular injection sites.

Release rates from intramuscular and intra-adipose injection sites are dependent upon several including injection depth. Little is known about the relationship between drug lipophilicity and transport rate of drugs through adipose and muscle tissue. The principal objective of the present study was to investigate to what extend drug lipophilicity affects release and release rate from adipose tissue. Nine pigs were given intravenous (0.1 mg/kg), intramuscular (0.2 mg/kg) and intra-adipose (0.2 mg/kg) injections of propranolol, alprenolol, carazolol, metoprolol and atenolol. The fraction not-absorbed versus time plots after intramuscular and intra-adipose injection showed a biphasic decline for all model compound with the exception of atenolol being the most hydrophilic drug. This biphasic decline indicates that two different mechanisms may be involved in drug release. Initial release rates after intra-adipose injection were negatively correlated (Kendall's rankorder test) with fat-buffer distribution constants. The extent of release after 24 h could be considered as a characteristic parameter for the second release phase. The amounts released after 24 h were lower for propranolol, alprenolol, carazolol and metoprolol than for atenolol. Incomplete release at 24 h can be explained by the decrease of the solvent drag after absorption of the vehicle is complete.

Adipose Tissue↗

The pharmacokinetics of oxytetracycline following intravenous administration in healthy and diseased pigs.

The pharmacokinetics of oxytetracycline (OTC) were studied in healthy pigs and in pigs endobronchially inoculated with Actinobacillus pleuropneumoniae toxins. In two groups of seven pigs OTC was administered intravenously in a single dose of 10 or 50 mg/kg, respectively. OTC was administered to clinically healthy pigs and 7 days later at 3 h after a challenge with A. pleuropneumoniae toxins. Pneumonia developed in toxin-treated pigs. In the challenged pigs there was a decreased distribution-rate constant (alpha) and a significantly increased elimination-rate constant (beta) (P less than 0.05). Moreover, the apparent volume of distribution (Vd beta) was decreased. The elimination half-lives (t1/2 beta) were approximately 6 h in the healthy pigs and 5 h in the diseased animals. There was no difference in the pharmacokinetic profile of OTC following administration of 50 mg/kg compared to 10 mg/kg.

Actinobacillus Infections↗

Pharmacokinetics of intravenously, intramuscularly and intra-adiposely administered carazolol in pigs.

The beta-blocking agent carazolol is used for the prevention of stress syndromes in pigs. Little is known of the pharmacokinetics of this drug, and therefore of its residue status in meat. In this study carazolol pharmacokinetics were investigated in a randomized three-way cross-over design in five pigs. A dose of 0.025 mg/kg was given intravenously, intramuscularly and intra-adiposely (in the subcutaneous fat layer). Carazolol was rapidly distributed and had a short half-life of 1.2-4.2 h. The distribution volume was calculated to be 0.22-0.65 l/kg. After intramuscular or intra-adipose administration the absorption pattern was biphasic. A rapid initial phase was followed by a slow second phase. Absorption was found to be incomplete at 24 h after intramuscular and intra-adipose administration ranging from 24 to 59% and 25 to 66%, respectively. The biphasic behaviour could be explained by retention of the drug in the tissues after absorption of the solvent was complete. A few hours after intravenous administration only negligible amounts of the drug were circulating in the body; however, considerable amounts of drug might have remained at the intramuscular or intra-adipose injection site.

Adipose Tissue↗

Intravenous catheterisation of conventional pigs without application of antimicrobial agents.

In six experiments 43 castrated male conventional pigs weighing 25-41 kg were catheterised by inserting a cannula via the jugular vein into the cranal caval vein. The catheters were taped to the spinal neck region where the tap stops were located. Antimicrobial agents were not applied. One pig died 32 hour after surgery from Porcine Stress Syndrome. The catheters remained patent for at least nine days in 38 of the remaining 42 animals (90%). In two animals the catheter by mistake was not inserted into the jugular vein. Two animals got catheters with a one-way blockage four days after surgery. In these animals autopsy revealed thrombosis and phlebitis of the occluded vein and a valve-like thrombus at the tip of the catheters. In seven of the 43 pigs the effects of anaesthesia, surgery and catherisation were followed using rectal temperature and haematological and some blood biochemical parameters for nine days after the surgery. It is concluded that this catheterisation technique, without application of antimicrobial agents, can be used well for experimental infections and pharmacokinetic studies.

Animals↗

In vitro activity of five tetracyclines and some other antimicrobial agents against four porcine respiratory tract pathogens.

The minimal inhibitory concentrations (MIC) of five tetracyclines and ten other antimicrobial agents were determined for four porcine bacterial respiratory tract pathogens by the agar dilution method. For the following oxytetracycline-susceptible strains, the MIC50 ranges of the tetracyclines were: P. multocida (n = 17) 0.25-0.5 micrograms/ml; B. bronchiseptica (n = 20) 0.25-1.0 micrograms/ml; H. pleuropneumoniae (n = 20) 0.25-0.5 micrograms/ml; S. suis Type 2 (n = 20) 0.06-0.25 micrograms/ml. For 19 oxytetracycline-resistant P. multocida strains the MIC50 of the tetracyclines varied from 64 micrograms/ml for oxytetracycline to 0.5 micrograms/ml for minocycline. Strikingly, minocycline showed no cross-resistance with oxytetracycline, tetracycline, chlortetracycline and doxycycline in P. multocida and in H. pleuropneumoniae. Moreover, in susceptible strains minocycline showed the highest in vitro activity followed by doxycycline. Low MIC50 values were observed for chloramphenicol, ampicillin, flumequine, ofloxacin and ciprofloxacin against P. multocida and H. pleuropneumoniae. B. bronchiseptica was moderately susceptible or resistant to these compounds. As expected tiamulin, lincomycin, tylosin and spiramycin were not active against H. pleuropneumoniae. Except for flumequine, the MIC50 values of nine antimicrobial agents were low for S. suis Type 2. Six strains of this species showed resistance to the macrolides and lincomycin.

Animals↗

The effect of dietary nitrite and nitrate on the metabolism of sulphadimidine administered orally to pigs.

The in vivo interaction of sulphadimidine (SDM) with nitrite and nitrate has been investigated in pigs. It was shown that the combined oral treatment with SDM and nitrite but not nitrate leads to the formation of a deaminated compound, which becomes the major metabolite in plasma soon after cessation of the treatment. The major in vitro reaction product, 1,3-di(4-[N(4,6-dimethyl-2-pyrimidinyl)]-sulphamoylphenyl)-triazen e, DDPSPT as has been reported previously, could not be detected in blood, urine or faeces of the exposed animals. No effect of nitrite or nitrate could be observed on the acetylation of SDM.

Administration, Oral↗

The role of endotoxin in the pathogenesis of coliform mastitis in sows.

Sows were made tolerant to Escherichia coli endotoxin by daily intravenous (IV) injection of the pyrogen. A refractory state was induced, characterised by a markedly decreased fever. In contrast, intramammary (IMM) infusion of only a quarter of the endotoxin dose to which the animals were made tolerant by IV injection produced a markedly increased fever. This finding suggests that inflammatory endogenous mediators were released in the mammary glands and that their subsequent absorption into the blood circulation, and not the absorption of endotoxin caused fever.

Animals↗