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Veterinary Quarterly Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/tveq20
Spread of Bovine Virus Diarrhoea virus in a herd of heifer calves a
b
b
G. H. Wentink , A. C. A. van Exsel , I. de Goey & J.A.H. van Lieshout
c
a
Department of Large Animal Medicine and Nutrition, Veterinary Faculty , State University Utrecht , Yalelaan 16, P.O. Box 80.152, Utrecht, 3508 TD, The Netherlands b
Animal Health Service of Zuid Nederland , Molenwijkseweg 48, Boxtel, 5282 SC, The Netherlands c
Centre of Artifical Insemination , St. Janstraat 24, Veldhoven, 5507 ND Published online: 01 Nov 2011.
To cite this article: G. H. Wentink , A. C. A. van Exsel , I. de Goey & J.A.H. van Lieshout (1991) Spread of Bovine Virus Diarrhoea virus in a herd of heifer calves, Veterinary Quarterly, 13:4, 233-236, DOI: 10.1080/01652176.1991.9694313 To link to this article: http://dx.doi.org/10.1080/01652176.1991.9694313
PLEASE SCROLL DOWN FOR ARTICLE Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the Content. Any opinions and views expressed in this publication are the opinions and views of the authors, and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and should be independently verified with primary sources of information. Taylor and Francis shall not be liable for any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of the Content. This article may be used for research, teaching, and private study purposes. Any substantial or systematic reproduction, redistribution, reselling, loan, sublicensing, systematic supply, or distribution in any form to anyone is expressly
Downloaded by [Stony Brook University] at 15:27 17 October 2014
forbidden. Terms & Conditions of access and use can be found at http:// www.tandfonline.com/page/terms-and-conditions
SHORT COMMUNICATIONS
Spread of Bovine Virus Diarrhoea virus in a herd of heifer calves
Downloaded by [Stony Brook University] at 15:27 17 October 2014
G. H. Wentinkl, A. C. A. van Exse12, I. de Goey2, and J. A. H. van Lieshout3 SUMMARY. A calf persistently infected and immunotolerant to Bovine Virus Diarrhoea virus (BVD virus) was, on purpose, introduced to a herd of heifer calves over 4 months of age that had been reared as recipients for embryo transplantation. All calves were brought in contact with the persistently infected animal. In total, 240 calves were involved in this experiment, 22 of which were serologically negative when introduced. These serologically negative animals developed antibodies against BVD virus within 5 months after introduction. At short distances from the persistently infected BVD virus shedder, negative calves seroconverted within 2 months, but at greater distances the moment of seroconversion was unpredictable. The calves that had undergone a natural infection with BVD virus received embryos after transportation to an allied farm. In total, 14 calves were born after embryo transplantation, all of which were free of BVD virus, in spite of the presence of BVD-virus on the latter farm. INTRODUCTION
Transmission of Bovine Virus Diarrhoea virus (BVD virus) to uninfected animals is thought to occur primarily by direct contact with animals that are persistently infected and immunotolerant for this virus (3, 4). Transmission of this virus at greater distances through the air is believed to occur less frequently. Animals in
the acute phase of postnatal infections only rarely transmit the virus to other animals (3).
This report describes the transmission of BVD virus in a herd of heifer calves to which a persistently infected animal was introduced. The persistently infected animal was introduced to induce immunity for BVD virus by natural infection before the animals reached breeding age. MATERIALS AND METHODS
This investigation was performed in a herd of about 100 heifer calves ranging in age from 4 to about 12 months. These heifer calves were reared to serve as recipients for imported embryos. All animals were identified with ear tags and individual registrations were kept of illness and treatment. The animals were housed in groups of six animals. The fences between the pen of each group consisted of iron bars, over which the animals could lick each other. Each month, new calves from different origins were added to the herd at ages between 4 and 10 months. When entering the farm, all animals were investigated for the presence or absence of BVD virus in peripheral blood leucocytes according methods described previously (5). A heifer calf persistently infected and immunotolerant to BVD virus (termed a BVD virus shedder) was introduced to achieve infection and immunity to BVD virus by natural routes in the heifer calves. I
2 3
Department of Large Animal Medicine and Nutrition, Veterinary Faculty, State University Utrecht, Yalelaan 16, P.O. Box 80.152, 3508 TD Utrecht, The Netherlands. Animal Health Service of Zuid Nederland, Molenwijkseweg 48, 5282 SC Boxtel, The Netherlands. Centre of Artifical Insemination, St. Janstraat 24, 5507 ND Veldhoven.
THE VETERINARY QUARTERLY, VOL.
13, No. 4, OCTOBER 1991
233
Monthly, all newly introduced animals older than 4 months and also the animals which had been found serologically negative on previous occasions were bled and monitored for the presence or absence of antibodies against BVD virus using an ELISA (6). In total, 240 calves were investigated once or more frequently for antibodies and the presence of BVD virus during the investigation period of 12 months. Each month all animals were redistributed over the pens, while the BVD virus shedder remained in its place. Sooner or later all animals were brought into close contact with the shedder. The oldest animals were transported to an allied farm where embryo transplantations were performed and the animals were kept until they had delivered their calves.
In total, 14 calves were born to heifers that had had contact with the BVD virus shedder for at least one month. These calves were investigated for the presence of BVD virus in peripheral blood lymphocytes in first week of life.
Downloaded by [Stony Brook University] at 15:27 17 October 2014
RESULTS
Clinical abnormalities were minimal. In the fifth month of the investigation most of the animals showed dullness, inappetence and some of them had fever up to 40° C. These symptoms also were seen in animals that were serologically positive for BVD virus. One case of pneumonia and one case of severe diarrhoea occurred in serologically positive animals, which both responded to antibiotic treatment. No diagnosis was established with routine clinical and laboratory investigations. In total 22 calves, serologically negative for BVD virus, were brought in. All 22 animals seroconverted to BVD virus within 5 months. The periods during which these animals remained serologically negative varied. In the near vicinity of the BVD virus shedder seroconversion occurred within 2 months. At greater distances four animals remained negative for 3 months (no. 1, 6, 7, 11), but when moved to the near vicinity of the BVD virus shedder, seroconversion
occurred within 2 months (table 1). Seven animals (no. 2, 3, 4, 12, 15, 16, 17) developed antibodies within 1 month at distances of 3 pens or more away from the BVD virus shedder.
On three occasions, seroconversion of negative animals placed in one pen at distances of three pens or more away from the BVD virus shedder did not occur in the same month (animals 5, 6 and 7; animals 12 and 13; animals 14 and 15). In the allied farm, no clinical abnormalities were seen. The 14 calves born from heifers that had seroconverted after contact with the BVD virus shedder were all free of BVD virus. However, two persistently infected calves were present on the latter farm, which had been born to heifers not involved in this experiment. DISCUSSION
In spite of the introduction of animals persistently infected and immunotolerant to BVD virus, few clinical abnormalities were observed. This is in accordance with
other reports, which did not mention deleterious clinical effects after the introduction of BVD virus to herds of animals older than 5 months, except for the effect of BVD virus on foetuses, especially on those below 125 days of gestation (2, 4). However, in younger calves various problems were reported by Barber et al. (1). The objective of this study was to follow the spread of the infection of the BVD virus over negative animals. Eight serologically negative animals, when put in the
near vicinity of the BVD virus shedder, seroconverted within 1 month. At a distance of two pens, eight animals seroconverted within 1 month, and only one animal seroconverted after 2 months. At distances of three pens or more, seroconversion occurred at various times. Seven animals developed antibodies within 1 month, but four escaped infection for a period of at least 3 months, after which they were moved to a pen closer to the BVD virus shedder. 234
THE VETERINARY QUARTERLY, VOL. 13, No. 4, OCTOBER 1991
.
Table I. Serology of animals that were negative for BVD virus when introduced to unit 4.
Month 2
3
4
5
-(d) +(d) +(d) +(d) -(d) -(d) -(d)
-(d)
+(a)
+(a)
+(d) -(d) -(d) -(d)
-(d) -(d) -(d)
+(c) -(c) +(d) -(d) -(d)
1
9
6
7
8
+(c) +(d) +(c) +(c) -(d) -(d) -(d) -(d) -(d)
-(e) +(e) -(e) -(d) +(d)
-(d)
+(b)
+(e) -(e)
+(e)
-(e) -(e)
+(e) +(e)
10
11
12
13
-(c) -(c) -(c) -(c)
+(c) +(c) +(c) +(c) -(c)
+(c)
Animal 1
2 3
4 5
6 7
-(d) -(d) -(d) -(d) -(d) -(d) -(d)
8
Downloaded by [Stony Brook University] at 15:27 17 October 2014
9 10 11
12 13
14 15 16 17 18
19
20 21
22
(a) in the same pen as the persistently infected animal (b) in the pen adjacent to that of the persistently infected animal (c) two pens away (d) three or more pens away (e) in a pen opposite to that of the persistently infected animal
If after 3 month no seroconversion had taken place in an animal, that individual was placed in the near vicinity of the BVD-virus shedder, i.e. from positions d and e after 3 months to positions a, b or c.
Whether animals in the viraemic stage may transmit the infection cannot be
answered. It can be concluded from this investigation that BVD virus
is
transmitted over short distances, but is less effective and unpredictable over greater distances.
BVD virus was present on the allied farm where embryo transplantations were carried out, because two persistently infected calves were born to heifers not involved in this experiment. The heifers in this experiment may, or may not, have been infected with BVD virus. Nevertheless, no persistently infected calves were born to these heifers. REFERENCES I. 2.
Barber DML, Nettleton PF, and Herring JA. Disease in a dairy herd associated with the introduction and spread of bovine virus diarrhoea virus. Vet Rec 1985; 117: 459-64. Duffell SJ, Harkness JW. Bovine virus diarrhoea-mucosal disease infection in cattle. Vet Rec 1985; 117: 240-5.
Meyling A, Houe H, and Jensen AM. Epidemiology of bovine virus diarrhoea virus. In: Rev Sci Techn Off Int Epizoot Bovine Virus Diarrhoea, ed Brownlie J and Clarke MC, 1990: 75-93. 4. Wentink GH, Zimmer GM, Strayer PJ, and Moerman A. Bovine virus diarree/mucosal diseasevirus: diagnostiek en benadering in de praktijk. Tijdschr Diergeneeskd 1989; 114: 877-85. 3.
THE VETERINARY QUARTERLY, VOL 13, No. 4, OCTOBER 1991
235
5.
Wentink GH, Remmen JLAM, and Exsel ACA van. Pregnancy Rate of heifers bred by an immunotolerant bull persistently infected with Bovine Virus Diarrhoea virus. Vet Quart 1989; 11: 171-4.
6.
Westenbrink F, Middel WGJ, Strayer PJ, and Leeuw PW de. A blocking Enzyme-linked Immunosorbent Assay (ELISA) for Bovine Virus Diarrhoea Virus Serology. J Vet Med B 1986; 33: 354-61.
Comparison of the metabolism of four sulphonamides between humans and pigs Downloaded by [Stony Brook University] at 15:27 17 October 2014
T.B. Vree1,2, E.W.J. Beneken Kolmerl, and A. Peeters3 SUMMARY. Pigs are unable to form Ni-glucuronides of sulphadimethoxine and sulphamethomidine, while humans are able to do so. Pigs and humans are able to oxidise sulphapyridine and form the 0-glucuronide. The double conjugate N4-acetylsulphapyridine-0-glucuronide is formed in humans but not in pigs. Sulphadiazine is mainly acetylated in both humans and pigs. A hypothesis about Ni-glucuronidation is presented. INTRODUCTION
Sulphonamides are metabolised via N4-acetylation, oxidation, N1-glucuronidation
and 0-dealkylation, depending upon the molecular structure and the enzymic composition of the animal species (4, 9, 14). Recently we were able to measure the N1-glucuronide conjugate of sulphadimethoxine and of sulfa-6-monomethoxine in the urine of man (10, 12), but we were unable to find this metabolite in the urine of pigs (6). Instead sulphadimethoxine was completely N4-acetylated.
This finding may lead to the conclusion that the composition of the UDPGtransferases in pigs differs from their composition in man, and that the pig is missing the specific isoenzyme that in man is able to glucuronidate sulphadimethoxine at the NI-position. This species-dependent metabolic pathway may not be restricted to glucuronidation, or acetylation of sulphonamides only, but may also apply to series of other drugs. When an analytical method has been developed
for the measurement of a specific drug with its specific metabolites, it can be utilised to compare the metabolic pathways of a series of compounds between animal species.
In this pilot study, the metabolic pathways of four sulphonamides in pigs were screened and compared with those observed in humans. The compounds and the metabolic pathways investigated were: Sulphapyridine, hydroxylation and 0-glucuronidation, N4-acetylation; Sulphadiazine, hydroxylation, N4-acetylation; Sulphadimethoxine, Ni-glucuronidation, N4-acetylation; Sulphamethomidine, N1-glucuronidation, N4-acetylation. MATERIALS AND METHODS
Animals
Four female pigs (16 kg, 3 months of age, F 1 NL Landrace x Yorkshire) were obtained from the Central Animal Laboratory (University of Nijmegen, The Netherlands). They were
housed in a metabolic cage and had free access to food and water.Each animal received one sulphonamide orally in a gelatine capsule. 1,43 Departments of 'Clinical Pharmacy,2Anaesthesiology, and 3Central Animal Laboratory, Academic Hospital Nijmegen Sint Radboud, Geert Grooteplein Zuid 8, 6525 GA Nijmegen, The Netherlands.
236
THE VETERINARY QUARTERLY, VOL. 13, No. 4, OCTOBER 1991
Veterinary Quarterly Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/tveq20
Spread of Bovine Virus Diarrhoea virus in a herd of heifer calves a
b
b
G. H. Wentink , A. C. A. van Exsel , I. de Goey & J.A.H. van Lieshout
c
a
Department of Large Animal Medicine and Nutrition, Veterinary Faculty , State University Utrecht , Yalelaan 16, P.O. Box 80.152, Utrecht, 3508 TD, The Netherlands b
Animal Health Service of Zuid Nederland , Molenwijkseweg 48, Boxtel, 5282 SC, The Netherlands c
Centre of Artifical Insemination , St. Janstraat 24, Veldhoven, 5507 ND Published online: 01 Nov 2011.
To cite this article: G. H. Wentink , A. C. A. van Exsel , I. de Goey & J.A.H. van Lieshout (1991) Spread of Bovine Virus Diarrhoea virus in a herd of heifer calves, Veterinary Quarterly, 13:4, 233-236, DOI: 10.1080/01652176.1991.9694313 To link to this article: http://dx.doi.org/10.1080/01652176.1991.9694313
PLEASE SCROLL DOWN FOR ARTICLE Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the Content. Any opinions and views expressed in this publication are the opinions and views of the authors, and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and should be independently verified with primary sources of information. Taylor and Francis shall not be liable for any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of the Content. This article may be used for research, teaching, and private study purposes. Any substantial or systematic reproduction, redistribution, reselling, loan, sublicensing, systematic supply, or distribution in any form to anyone is expressly
Downloaded by [Stony Brook University] at 15:27 17 October 2014
forbidden. Terms & Conditions of access and use can be found at http:// www.tandfonline.com/page/terms-and-conditions
SHORT COMMUNICATIONS
Spread of Bovine Virus Diarrhoea virus in a herd of heifer calves
Downloaded by [Stony Brook University] at 15:27 17 October 2014
G. H. Wentinkl, A. C. A. van Exse12, I. de Goey2, and J. A. H. van Lieshout3 SUMMARY. A calf persistently infected and immunotolerant to Bovine Virus Diarrhoea virus (BVD virus) was, on purpose, introduced to a herd of heifer calves over 4 months of age that had been reared as recipients for embryo transplantation. All calves were brought in contact with the persistently infected animal. In total, 240 calves were involved in this experiment, 22 of which were serologically negative when introduced. These serologically negative animals developed antibodies against BVD virus within 5 months after introduction. At short distances from the persistently infected BVD virus shedder, negative calves seroconverted within 2 months, but at greater distances the moment of seroconversion was unpredictable. The calves that had undergone a natural infection with BVD virus received embryos after transportation to an allied farm. In total, 14 calves were born after embryo transplantation, all of which were free of BVD virus, in spite of the presence of BVD-virus on the latter farm. INTRODUCTION
Transmission of Bovine Virus Diarrhoea virus (BVD virus) to uninfected animals is thought to occur primarily by direct contact with animals that are persistently infected and immunotolerant for this virus (3, 4). Transmission of this virus at greater distances through the air is believed to occur less frequently. Animals in
the acute phase of postnatal infections only rarely transmit the virus to other animals (3).
This report describes the transmission of BVD virus in a herd of heifer calves to which a persistently infected animal was introduced. The persistently infected animal was introduced to induce immunity for BVD virus by natural infection before the animals reached breeding age. MATERIALS AND METHODS
This investigation was performed in a herd of about 100 heifer calves ranging in age from 4 to about 12 months. These heifer calves were reared to serve as recipients for imported embryos. All animals were identified with ear tags and individual registrations were kept of illness and treatment. The animals were housed in groups of six animals. The fences between the pen of each group consisted of iron bars, over which the animals could lick each other. Each month, new calves from different origins were added to the herd at ages between 4 and 10 months. When entering the farm, all animals were investigated for the presence or absence of BVD virus in peripheral blood leucocytes according methods described previously (5). A heifer calf persistently infected and immunotolerant to BVD virus (termed a BVD virus shedder) was introduced to achieve infection and immunity to BVD virus by natural routes in the heifer calves. I
2 3
Department of Large Animal Medicine and Nutrition, Veterinary Faculty, State University Utrecht, Yalelaan 16, P.O. Box 80.152, 3508 TD Utrecht, The Netherlands. Animal Health Service of Zuid Nederland, Molenwijkseweg 48, 5282 SC Boxtel, The Netherlands. Centre of Artifical Insemination, St. Janstraat 24, 5507 ND Veldhoven.
THE VETERINARY QUARTERLY, VOL.
13, No. 4, OCTOBER 1991
233
Monthly, all newly introduced animals older than 4 months and also the animals which had been found serologically negative on previous occasions were bled and monitored for the presence or absence of antibodies against BVD virus using an ELISA (6). In total, 240 calves were investigated once or more frequently for antibodies and the presence of BVD virus during the investigation period of 12 months. Each month all animals were redistributed over the pens, while the BVD virus shedder remained in its place. Sooner or later all animals were brought into close contact with the shedder. The oldest animals were transported to an allied farm where embryo transplantations were performed and the animals were kept until they had delivered their calves.
In total, 14 calves were born to heifers that had had contact with the BVD virus shedder for at least one month. These calves were investigated for the presence of BVD virus in peripheral blood lymphocytes in first week of life.
Downloaded by [Stony Brook University] at 15:27 17 October 2014
RESULTS
Clinical abnormalities were minimal. In the fifth month of the investigation most of the animals showed dullness, inappetence and some of them had fever up to 40° C. These symptoms also were seen in animals that were serologically positive for BVD virus. One case of pneumonia and one case of severe diarrhoea occurred in serologically positive animals, which both responded to antibiotic treatment. No diagnosis was established with routine clinical and laboratory investigations. In total 22 calves, serologically negative for BVD virus, were brought in. All 22 animals seroconverted to BVD virus within 5 months. The periods during which these animals remained serologically negative varied. In the near vicinity of the BVD virus shedder seroconversion occurred within 2 months. At greater distances four animals remained negative for 3 months (no. 1, 6, 7, 11), but when moved to the near vicinity of the BVD virus shedder, seroconversion
occurred within 2 months (table 1). Seven animals (no. 2, 3, 4, 12, 15, 16, 17) developed antibodies within 1 month at distances of 3 pens or more away from the BVD virus shedder.
On three occasions, seroconversion of negative animals placed in one pen at distances of three pens or more away from the BVD virus shedder did not occur in the same month (animals 5, 6 and 7; animals 12 and 13; animals 14 and 15). In the allied farm, no clinical abnormalities were seen. The 14 calves born from heifers that had seroconverted after contact with the BVD virus shedder were all free of BVD virus. However, two persistently infected calves were present on the latter farm, which had been born to heifers not involved in this experiment. DISCUSSION
In spite of the introduction of animals persistently infected and immunotolerant to BVD virus, few clinical abnormalities were observed. This is in accordance with
other reports, which did not mention deleterious clinical effects after the introduction of BVD virus to herds of animals older than 5 months, except for the effect of BVD virus on foetuses, especially on those below 125 days of gestation (2, 4). However, in younger calves various problems were reported by Barber et al. (1). The objective of this study was to follow the spread of the infection of the BVD virus over negative animals. Eight serologically negative animals, when put in the
near vicinity of the BVD virus shedder, seroconverted within 1 month. At a distance of two pens, eight animals seroconverted within 1 month, and only one animal seroconverted after 2 months. At distances of three pens or more, seroconversion occurred at various times. Seven animals developed antibodies within 1 month, but four escaped infection for a period of at least 3 months, after which they were moved to a pen closer to the BVD virus shedder. 234
THE VETERINARY QUARTERLY, VOL. 13, No. 4, OCTOBER 1991
.
Table I. Serology of animals that were negative for BVD virus when introduced to unit 4.
Month 2
3
4
5
-(d) +(d) +(d) +(d) -(d) -(d) -(d)
-(d)
+(a)
+(a)
+(d) -(d) -(d) -(d)
-(d) -(d) -(d)
+(c) -(c) +(d) -(d) -(d)
1
9
6
7
8
+(c) +(d) +(c) +(c) -(d) -(d) -(d) -(d) -(d)
-(e) +(e) -(e) -(d) +(d)
-(d)
+(b)
+(e) -(e)
+(e)
-(e) -(e)
+(e) +(e)
10
11
12
13
-(c) -(c) -(c) -(c)
+(c) +(c) +(c) +(c) -(c)
+(c)
Animal 1
2 3
4 5
6 7
-(d) -(d) -(d) -(d) -(d) -(d) -(d)
8
Downloaded by [Stony Brook University] at 15:27 17 October 2014
9 10 11
12 13
14 15 16 17 18
19
20 21
22
(a) in the same pen as the persistently infected animal (b) in the pen adjacent to that of the persistently infected animal (c) two pens away (d) three or more pens away (e) in a pen opposite to that of the persistently infected animal
If after 3 month no seroconversion had taken place in an animal, that individual was placed in the near vicinity of the BVD-virus shedder, i.e. from positions d and e after 3 months to positions a, b or c.
Whether animals in the viraemic stage may transmit the infection cannot be
answered. It can be concluded from this investigation that BVD virus
is
transmitted over short distances, but is less effective and unpredictable over greater distances.
BVD virus was present on the allied farm where embryo transplantations were carried out, because two persistently infected calves were born to heifers not involved in this experiment. The heifers in this experiment may, or may not, have been infected with BVD virus. Nevertheless, no persistently infected calves were born to these heifers. REFERENCES I. 2.
Barber DML, Nettleton PF, and Herring JA. Disease in a dairy herd associated with the introduction and spread of bovine virus diarrhoea virus. Vet Rec 1985; 117: 459-64. Duffell SJ, Harkness JW. Bovine virus diarrhoea-mucosal disease infection in cattle. Vet Rec 1985; 117: 240-5.
Meyling A, Houe H, and Jensen AM. Epidemiology of bovine virus diarrhoea virus. In: Rev Sci Techn Off Int Epizoot Bovine Virus Diarrhoea, ed Brownlie J and Clarke MC, 1990: 75-93. 4. Wentink GH, Zimmer GM, Strayer PJ, and Moerman A. Bovine virus diarree/mucosal diseasevirus: diagnostiek en benadering in de praktijk. Tijdschr Diergeneeskd 1989; 114: 877-85. 3.
THE VETERINARY QUARTERLY, VOL 13, No. 4, OCTOBER 1991
235
5.
Wentink GH, Remmen JLAM, and Exsel ACA van. Pregnancy Rate of heifers bred by an immunotolerant bull persistently infected with Bovine Virus Diarrhoea virus. Vet Quart 1989; 11: 171-4.
6.
Westenbrink F, Middel WGJ, Strayer PJ, and Leeuw PW de. A blocking Enzyme-linked Immunosorbent Assay (ELISA) for Bovine Virus Diarrhoea Virus Serology. J Vet Med B 1986; 33: 354-61.
Comparison of the metabolism of four sulphonamides between humans and pigs Downloaded by [Stony Brook University] at 15:27 17 October 2014
T.B. Vree1,2, E.W.J. Beneken Kolmerl, and A. Peeters3 SUMMARY. Pigs are unable to form Ni-glucuronides of sulphadimethoxine and sulphamethomidine, while humans are able to do so. Pigs and humans are able to oxidise sulphapyridine and form the 0-glucuronide. The double conjugate N4-acetylsulphapyridine-0-glucuronide is formed in humans but not in pigs. Sulphadiazine is mainly acetylated in both humans and pigs. A hypothesis about Ni-glucuronidation is presented. INTRODUCTION
Sulphonamides are metabolised via N4-acetylation, oxidation, N1-glucuronidation
and 0-dealkylation, depending upon the molecular structure and the enzymic composition of the animal species (4, 9, 14). Recently we were able to measure the N1-glucuronide conjugate of sulphadimethoxine and of sulfa-6-monomethoxine in the urine of man (10, 12), but we were unable to find this metabolite in the urine of pigs (6). Instead sulphadimethoxine was completely N4-acetylated.
This finding may lead to the conclusion that the composition of the UDPGtransferases in pigs differs from their composition in man, and that the pig is missing the specific isoenzyme that in man is able to glucuronidate sulphadimethoxine at the NI-position. This species-dependent metabolic pathway may not be restricted to glucuronidation, or acetylation of sulphonamides only, but may also apply to series of other drugs. When an analytical method has been developed
for the measurement of a specific drug with its specific metabolites, it can be utilised to compare the metabolic pathways of a series of compounds between animal species.
In this pilot study, the metabolic pathways of four sulphonamides in pigs were screened and compared with those observed in humans. The compounds and the metabolic pathways investigated were: Sulphapyridine, hydroxylation and 0-glucuronidation, N4-acetylation; Sulphadiazine, hydroxylation, N4-acetylation; Sulphadimethoxine, Ni-glucuronidation, N4-acetylation; Sulphamethomidine, N1-glucuronidation, N4-acetylation. MATERIALS AND METHODS
Animals
Four female pigs (16 kg, 3 months of age, F 1 NL Landrace x Yorkshire) were obtained from the Central Animal Laboratory (University of Nijmegen, The Netherlands). They were
housed in a metabolic cage and had free access to food and water.Each animal received one sulphonamide orally in a gelatine capsule. 1,43 Departments of 'Clinical Pharmacy,2Anaesthesiology, and 3Central Animal Laboratory, Academic Hospital Nijmegen Sint Radboud, Geert Grooteplein Zuid 8, 6525 GA Nijmegen, The Netherlands.
236
THE VETERINARY QUARTERLY, VOL. 13, No. 4, OCTOBER 1991
