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Biomedical subjects

J H Verheijden

Publications and source records attributed to J H Verheijden.

At least 19 recordsLinked to original sources

Implications derived from a mathematical model for eradication of pseudorabies virus.

Simple mathematical models based on experimental and observational data were applied to evaluate the feasibility of eradicating pseudorabies virus (PRV) regionally by vaccination and to determine which factors can jeopardise eradication. As much as possible, the models were uncomplicated and our conclusions were based on mathematical analysis. For complicated situations, Monte-Carlo simulation was used to support the conclusions. For eradication, it is sufficient that the reproduction ratio R (the number of units infected by one infectious unit) is < 1. However, R can be determined at different scales: at one end the region with the herds as units and at the other end compartments with the pigs as units. Results from modelling within herds showed that contacts between groups within a herd is important whenever R between individuals (R(ind)) is > 1 in one or more groups. This is the case within finishing herds. In addition, if the R(ind) is more than 1 within a herd, the size of the herd determines whether PRV can persist in the herd and determines the duration of persistence. Moreover, when reactivation of PRV in well-vaccinated sows is taken into account, R(ind) in sow herds is still less than 1. In sow herds with group-housing systems, it is possible that in those groups R(ind) is > 1. Results from modelling between herds showed that whether or not Rherd is < 1 in a particular region is determined by two factors: (1) the transmission of infection between nucleus herds and rearing herds through transfer of animals and (2) contacts among finishing herds and among rearing herds. The transmission between herds can be reduced by reduction of the contact rate between herds. reduction of the herd size, and reduction of the transmission within herds.

Animals

New GnRH-like peptide construct to optimize efficient immunocastration of male pigs by immunoneutralization of GnRH.

Castration of male pigs is routinely performed in order to prevent the occurrence of boar taint in pig carcasses. However, boar taint can also be eliminated by immunological castration using a synthetic peptide vaccine against GnRH. For pig farming, to make immunocastration a feasible alternative method to surgical castration, the composition of the vaccine has to be not only reliable and effective but also cost-efficient and safe. Previously the authors have developed an effective immunocastration vaccine by replacing the monomer GnRH by a much more immunogenic tandem peptide. However, this tandem-GnRH vaccine preparation needs Complete Freund's adjuvant and to be applied at a relatively high dose. Therefore, alternative antigens were designed to cope with this problem and tested with different adjuvants and dosages. An effective new antigen was designed based on a GnRH-tandem peptide, which was dimerized and modified in one amino acid position of the decapeptide to allow conjugation of this tandem-dimer to ovalbumin. In mild adjuvants and in low dosage, this antigen was very effective in reducing testis weight, serum LH and androstenone level in backfat. Thus, an improved immunocastration vaccine has been designed that is relatively cost-efficient and highly efficacious in two vaccinations at low dose.

Adjuvants, Immunologic

No massive spread of pseudorabies virus in vaccinated sow herds.

In this study, we quantified transmission of PRV in 99 sow herds in which the sows were vaccinated three times a year with strain 783 O/W and found that the reproduction ratio R was 0.66, which is significantly below one. This implies that massive spread of PRV cannot occur in such herds.

Animals

Seroprevalence of porcine reproductive and respiratory syndrome virus in Dutch weaning pigs.

To determine whether under Dutch field conditions PRRSV infection occurs in weaning pigs before the finishing period, a cross-sectional study was performed on 32 breeding farms to estimate the seroprevalence of antibodies directed against PRRSV in 4- to 5-week-old and 8- to 9-week-old pigs. Farms were visited twice within 5 months, and during each sampling an average of 20 sera were randomly collected from a unit of 4- to 5-week-old and a unit of 8- to 9-week-old pigs. The sera (n = 2568) were tested in the IDEXX-ELISA for the presence of antibodies directed against PRRSV. The seroprevalence of PRRSV in 4- to 5-week-old pigs and 8- to 9-week-old pigs varied between both samplings for each farm. The seroprevalence in the younger pigs was significantly higher than in the older pigs for both samplings (p < 0.05), suggesting the presence of maternal antibodies. In addition, a longitudinal study was performed to evaluate the IDEXX-ELISA in detecting maternal antibodies directed against PRRSV and to determine the rate of decline of these antibodies in field sera. From serological results of eight litters, an average decay function was computed to quantify the maternal immunity to PRRSV. A seroprevalence in 8- to 9-weeks-old pigs of > or = 0.20 was calculated to indicate an active immune response to PRRSV. In the cross-sectional study in the pigs twenty-three percent of the units with 8- to 9-week-old pigs were considered to have an active serological response against PRRSV. We conclude that most Dutch pigs are seronegative for PRRSV at the start of the finishing period, since the results of this study showed that 77% of the units with 8- to 9-week-old pigs had a seroprevalence < 0.20.

Aging

No major outbreaks of pseudorabies virus in well-immunized sow herds.

In this study we quantified the transmission of pseudorabies virus (PRV) in well-immunized sow herds in The Netherlands. In three herds, sows were tested for antibodies to gE of PRV every time after they had been transported to another barn (survey A). In 99 other herds, sows were tested simultaneously once or twice yearly (survey B). We observed six introductions in survey A and 53 in survey B. None of these introductions resulted in extensive spread of the virus. The reproduction ratio R, which is defined as the mean number of secondary infections caused by one infectious sow, was significantly less than one. We conclude that PRV can be eliminated from sow herds by vaccination.

Animals

In-vivo buccal delivery of fluorescein isothiocyanate-dextran 4400 with glycodeoxycholate as an absorption enhancer in pigs.

Buccal delivery of fluorescein isothiocyanate labeled dextran 4400 (FD4) was investigated in-vivo in pigs. The delivery device consisted of an application chamber with a solution of FD4 and was adhered to the buccal mucosa for 4 h using an adhesive patch. A randomized crossover study including intravenous administration and buccal delivery without and with 10 mM sodium glycodeoxycholate (GDC) as absorption enhancer was performed in five pigs. After buccal administration, steady state plasma levels were rapidly reached. Coadministration of 10 mM GDC increased the absolute bioavailability of FD4 from 1.8 +/- 0.5% to 12.7 +/- 2.0%. Since FD4 is a macromolecular and hydrophilic compound such as peptide and protein drugs, buccal delivery would provide an adequate alternative to the parenteral administration of these drugs.

Absorption

In vivo buccal delivery of the peptide drug buserelin with glycodeoxycholate as an absorption enhancer in pigs.

PURPOSE: To study the potential of buccal delivery of the peptide drug in pigs. METHODS: Intravenous administration and buccal delivery without and with 10 mM sodium glycodeoxycholate (GDC) as absorption enhancer were investigated as a randomised cross-over study in six pigs. The buccal delivery device consisted of an application chamber with a solution of buserelin and was attached to the buccal mucosa for 4 hours using an adhesive patch. RESULTS: Buccal administration of buserelin resulted in rapidly reached steady state plasma levels. The absolute bioavailability of the peptide after buccal delivery for 4 hours could be increased from 1.0 +/- 0.3 to 5.3 +/- 1.1% (mean +/- SD.) by co-administration of 10 mM GDC (0.45% w/v)). CONCLUSIONS: The results of this study demonstrate that buccal administration with the use of absorption enhancers is a useful approach for the delivery of peptide drugs such as buserelin.

Administration, Oral

A lipopolysaccharide-induced acute phase response in the pig is associated with a decrease in hepatic cytochrome P450-mediated drug metabolism.

Drug disposition, including hepatic drug metabolism, is markedly affected by infection, inflammation and other conditions that invoke the acute phase response. In the present study, an Escherichia coli lipopolysaccharide (LPS)-induced acute phase response model was developed in pigs. This model was used to study the effects of the acute phase response on drug disposition and hepatic drug metabolism in vivo and in microsomal preparations. The results obtained were compared with those from Actinobacillus pleuropneumoniae-infected pigs. Intermittent intravenous administration of LPS induced a mild acute phase response as evidenced by increased rectal body temperatures, anorexia and increased cytokine (TNF-alpha and IL-6) serum levels within 1-2 h after the first LPS injection. The acute phase response is associated with a pronounced decrease of antipyrine plasma clearance (control 8.5 +/- 0.8 vs. LPS 2.2 +/- 0.7 mL/min.kg). Furthermore, total cytochrome P450 content and microsomal cytochrome P450-dependent activities were significantly decreased after 24 h. The decrease in cytochrome P450 activities was accompanied by losses of cytochrome P4501A and P4503A apoproteins. The microsomal glucuronidation rate of 1-naphthol was not affected in LPS-treated pigs. Comparing the LPS model with our previous findings in the Actinobacillus pleuropneumoniae model showed a remarkable similarity with regard to the effects on hepatic drug metabolism.

Animals

Risk of recurrence of repeat breeding in sows with a repeat breeding in the first parity.

Risk of recurrence of repeat breeding in sows with a repeat breeding in the 1st parity was investigated in 241 sow herds (1985-1990). The association between repeat breeding in the 1st and subsequent parities was examined using data on 9,120 sows. Each sow contributed only one pair of observations to the total data set. Occurrence of repeat breeding in the 1st and higher parities was presented in terms of recurrent risk rates (rRR), adjusted for different strata of herds. Sows with a repeat breeding in the 1st parity did not have a significantly higher risk rate for recurrence of a repeat breeding in the 2nd parity (rRR = 1.12, 95% confidence interval .97-1.29) and in the 3rd parity (rRR = 1.10, 95% confidence interval .86-1.41) compared to sows without a repeat breeding in the 1st parity. Sows with a repeat breeding in the 1st parity had a slightly higher risk rate for recurrence of a repeat breeding in the 4th or higher parity (rRR = 1.07, 95% confidence interval 1.03-1.10), compared to sows without a repeat breeding in the 1st parity. However, this risk is, in a biological sense, very small.

Animals

Susceptibility to Actinobacillus pleuropneumoniae infection in pigs from an endemically infected herd is related to the presence of toxin-neutralizing antibodies.

Our objective was to identify pigs of an endemically infected herd that were susceptible to pleuropneumonia due to Actinobacillus pleuropneumoniae. The presence of toxin-neutralizing antibodies was studied in serum of 36 pigs from birth until 24 weeks of age. Titers gradually declined during the first twelve weeks of life and increased thereafter. Sera from one-hundred 3-weeks-old piglets and one-hundred 20-weeks-old pigs were sampled and neutralization titers were determined. From each group we selected 5 pigs with the lowest titers and 5 pigs with the highest titers. These selected pigs (n = 20) were inoculated endobronchially with A. pleuropneumoniae. Pigs that survived from infection were necropsied after 48 h. Pigs with low neutralization titers had severe lung lesions, whereas pigs with high titers had no or minor lung lesion. These differences were significant (P < 0.05). From this field study we conclude that susceptibility to Actinobacillus pleuropneumoniae can be predicted by absence of toxin-neutralizing antibodies.

Actinobacillus Infections

Prevalence and development of antibodies neutralizing the haemolysin and cytotoxin of Actinobacillus pleuropneumoniae in three infected pig herds.

Sero-epidemiological studies were carried out in pigs aged 1 to 24 weeks in three herds in which Actinobacillus pleuropneumoniae was endemic. The sera were tested in the complement-fixation test and for their ability to neutralize the haemolytic and cytotoxic activities of the A. pleuropneumoniae serotypes isolated from the herds. Almost all (98%) sera from 1-week-old piglets neutralized the haemolytic and cytotoxic activities but only 21% fixed complement. At the end of the finishing period, most pigs (82%) had sera that neutralized haemolytic and cytotoxic activities and only 22% fixed complement. In longitudinal studies the neutralization titres decreased during the first 12-13 weeks of age. Thereafter, 75% of the pigs had increased titres in the haemolysin- and cytotoxin-neutralization tests and only 5% of the pigs had increased titres in the complement-fixation test. In none of these pigs were clinical signs of pleuropneumonia seen. Thus in these endemically infected herds the prevalence of complement-fixing antibodies was low, whereas the prevalence of neutralizing antibodies was high. The fact that serum-neutralizing titres are low in 12-week-old pigs might be the reason that pigs of this age are the most vulnerable to the disease.

Actinobacillus Infections

Pharmacokinetics of sulfadimethoxine and sulfamethoxazole in combination with trimethoprim after intravenous administration to healthy and pneumonic pigs.

The pharmacokinetics of two sulfonamide/trimethoprim combinations were investigated after intravenous administration to clinically healthy pigs and to the same pigs following a challenge with Actinobacillus pleuropneumoniae toxins. Endobronchial challenge with A. pleuropneumoniae toxins resulted in fever, increased white blood cell counts and decreased water and feed consumption. Healthy, as well as febrile, pigs were given sulfadimethoxine (SDM) or sulfamethoxazole (SMX) intravenously at a dose of 25 mg/kg b.w. in combination with 5 mg trimethoprim (TMP) per kg body weight. The pharmacokinetic parameters of the sulfonamides as well as their main metabolites (acetyl sulfonamides) were not significantly different in healthy and febrile pigs. In healthy and pneumonic pigs, the mean elimination half-lives of SDM were 12.9 h and 13.4 h, respectively, those of SMX 2.5 h and 2.7 h, respectively, and those of TMP 2.8 h and 2.6 h, respectively. Distribution volumes in healthy and febrile pigs of SDM and SMX varied between 0.2 and 0.4 L/kg, and those of TMP between 1.1 and 1.6 L/kg. The mean AUC of TMP was decreased and the volume of distribution and total body clearance of TMP were increased in febrile pigs. Protein binding of the drugs and metabolites studied were not significantly changed after toxin-induced fever. The extent of protein binding of SDM, SMX and TMP was in the range 94-99%, 45-56% and 40-50%, respectively. Based on knowledge of in vitro antimicrobial activity of the drug combinations against A. pleuropneumoniae it was concluded that after intravenous administration of the dose administered (30 mg/kg of the combination preparations) to healthy and pneumonic pigs, plasma concentrations of SMX and TMP were above the concentration required for growth inhibition of 50% of A., pleuropneumoniae strains for approximately 16 h, whereas bacteriostatic plasma concentrations of SDM were still present after TMP had been eliminated from plasma. Because of similar elimination half-lives of SMX and TMP in pigs this combination is preferred to the combination of SDM with TMP.

Actinobacillus Infections

Convalescent pigs are protected completely against infection with a homologous Actinobacillus pleuropneumoniae strain but incompletely against a heterologous-serotype strain.

To study whether Actinobacillus pleuropneumoniae induces a species-specific immunity, we infected pigs in the left lung with serotype 3 or 9 and after 3 weeks we infected their right lungs with serotype 9. Convalescent pigs were protected against homologous strain reinfection, but after heterologous strain reinfection the degree of protection varied. Neutralizing antibodies were not essential for protection.

Actinobacillus Infections

Selective effects of a bacterial infection (Actinobacillus pleuropneumoniae) on the hepatic clearances of caffeine, antipyrine, paracetamol, and indocyanine green in the pig.

1. In order to investigate the effect of a bacterial acute phase response model on drug disposition in vivo, plasma clearances of antipyrine, caffeine, paracetamol and indocyanine green were investigated in the healthy and Actinobacillus pleuropneumoniae-infected pig. 2. Indocyanine green plasma and endogenous creatinine clearance were not changed during the infection, which indicates that hepatic blood flow and renal function were not significantly affected. 3. In the A. pleuropneumoniae-infected pig, plasma clearances of antipyrine and caffeine, both marker substrates for hepatic oxidative biotransformation, were decreased by 72 and 68% respectively. The clearance of paracetamol, a drug mainly glucuronidated in the pig, was reduced by 39%. 4. It is concluded that the most important change in drug elimination during an acute phase response induced by A. pleuropneumoniae is a suppression of oxidative hepatic biotransformation.

Acetaminophen

Infection (Actinobacillus pleuropneumoniae)-mediated suppression of oxidative hepatic drug metabolism and cytochrome P4503A mRNA levels in pigs.

The effect of Actinobacillus pleuropneumoniae infection, a well-characterized pig infection model, on both phase I (oxidative) and phase II (conjugative) microsomal enzyme activities was investigated in castrated male conventional pigs. A. pleuropneumoniae infection resulted after 24 hr in a significant suppression of 33% or more of all oxidative enzyme activities determined. After 40 hr, the activities were still suppressed, but did not differ from the results after 24 hr. On the contrary, all glucuronosyltransferase activities measured were not affected by A. pleuropneumoniae infection after both 24 and 40 hr. To elucidate further the mechanism of the suppression of oxidative enzyme activities, analysis of mRNA were conducted by dot-blot analysis using a human cytochrome P4503A4 cDNA probe. The results indicated that A. pleuropneumoniae infection suppressed oxidative enzyme activities. The reduction in cytochrome P4503A activity, specific for 6 beta-hydroxylation of testosterone is at a pretranslational level as measured by a decrease in the amount of mRNA.

Actinobacillus Infections

[The changing role of the veterinarian in primary production (demands with respect to diagnostic tests, risk analysis and the need for certification of farms)].

Various new developments in livestock production confront the veterinarian. In addition to Integrated Food Chain Quality Control, certification of farms for animal health status and also for production methods is becoming increasingly important. Certification for veterinary practices is forthcoming. In order to optimize national herd health, quantitative information is needed and certain methods have to be improved. The veterinarian must be able to apply new techniques adequately and to interpret disease- and environment-related data properly. Problem areas are highlighted and different ways of dealing with them are elaborated upon. It is concluded that the veterinarian is strategically positioned to solve these problems, but that suitable, complementary training is needed, as well as new quantitative research.

Animal Diseases