Novel Canine Tumour Suppressor Gene p53 Mutations in Cases of Skin and Mammary Neoplasms

Exons 4 to 8 of the tumour suppressor gene p53 were analysed in 25 skin and 25 mammary tumours of 50 dogs. A 1 bp deletion (ACCAC) was detected in codon 89 in exon 4 in a squamous cell carcinoma. A missense mutation CGCCAC (argininehistidine) was present in codon 162 in exon 5 in a mammary adenocarcinoma. Moreover, a silent mutation occurred in codon 103 (serine) of exon 4 in a mammary adenoma. The somatic nature of the three mutations was demonstrated.     

Canine Tumour Suppressor Gene p53 - Mutation in a Case of Adenoma of Circumanal Glands

Highly conserved regions of the tumour suppressor gene p53, including the typical human tumour hot spots (codons 175, 245, 248, 249, 273 and 282), were investigated in various canine neoplasms. A mutation CGG TGG (arginine tryptophan) was detected in codon 249 in an adenoma of the circumanal gland.     

Food intake and rumen motility in dwarf goats. Effects of atipamezole on the inhibitory effects induced by detomidine,medetomidine and romifidine

The effects of some ₂-adrenoceptor agonists and of the ₂-adrenoceptor antagonist atipamezole on food intake and ruminal contractions were studied in dwarf goats. Detomidine, 0.2 µg/kg per min for 10 min, failed to modify food intake during either the first or second observation period (0–30 min and 180–210 min after drug infusion, respectively). Given at a higher dose rate (0.4 µg/kg per min for 10 min), the drug inhibited food consumption during the first observation period, but stimulated food intake during the second period. A similar pattern was observed after IV infusion with medetomidine (0.2 µg/kg per min for 10 min), romifidine (0.4 µg/kg per min for 10 min) or xylazine (1 µg/kg per min for 10 min). The ₂-antagonist atipamezole (2 µg/kg per min for 10 min) failed to modify food intake during either the first or second observation period. After treatment with atipamezole, the effects of ₂-agonists on feeding behaviour were completely antagonized.The ₂-agonists administered at similar dose rates to those used in the food intake experiments induced bradycardia, decreases in body temperature and inhibition of ruminal contractions. The inhibition of ruminal contractions induced by romifidine was partly antagonized by atipamezole pre-treatment. These findings demonstrate that the ₂-agonist-induced changes in ruminal contractions do not simply cause changes in feeding behaviour. The drop in body temperature induced by ₂-agonists was prevented by atipamezole pre-treatment, whereas the induced bradycardia was not modified by this ₂-antagonist.Abbreviations IV intravenous - SEM standard error of the mean     

Reduced Ovulatory and Oestrous Activity in Zebu Heifers Following Trypanosoma vivax Infection

This paper describes a study on the oestrous and ovarian activity and responses to prostaglandin F2 (PGF2) administration and artificial insemination in zebu heifers.Four cycling heifers were artificially infected with 5×106 Trypanosoma vivax organisms. Two heifers served as controls. Two injections of PGF2 were given 11 days apart, commencing at the peak of parasitaemia in the infected animals, followed by artificial insemination 72 and 96 h after the second administration of PGF2. Sera were analysed for progesterone by radioimmunoassay, while ovarian activity and oestrus were determined by rectal palpation and visual observation, respectively. All the infected heifers developed the clinical disease. All control and infected heifers had progesterone profiles consistent with luteolysis and the occurrence of oestrus following the second administration of PGF2. Progesterone levels did not return to normal luteal values in infected animals, however, whilst they did so in control animals. No control or infected heifers became pregnant.The findings suggest that PGF2 will induce a non- fertile oestrus in zebu heifers acutely infected with T. vivax. Re-ovulation is also inhibited within 22 days in a majority of infected animals.     

Antibody Responses in Sheep Vaccinated against Staphylococcus aureus Mastitis: A Comparison of Two Experimental Vaccines Containing Different Adjuvants

A double-blind, placebo-controlled study was conducted to compare two vaccines using different adjuvants with regard to their ability to stimulate antibody production against the - and -toxins and the exopolysaccharide of Staphylococcus aureus. The vaccines contained identical antigens, consisting of inactivated whole bacteria of two strains of S. aureus in addition to - and -toxoid. One vaccine contained mineral oil, while the other used a water-soluble acrylic acid polymer resin (Carbopol) as adjuvant. Saline served as the placebo. One hundred and forty ewes were vaccinated twice before lambing, by subcutaneous injection with vaccine or placebo in the region of the supramammary lymph node, and were observed and sampled over a period of 6 months. The vaccine containing mineral oil as adjuvant induced significantly greater immune responses to the - and -toxins than did the vaccine containing Carbopol. The latter vaccine induced higher levels of antibodies to exopolysaccharide. The degree of local adverse reactions did not differ between the two groups. The results indicate differences between the oil-adjuvanted and Carbopol-adjuvanted vaccines with regard to their ability to stimulate antibody production against S. aureus protein antigens in sheep.     

Safety of the attenuated anticoccidial vaccine ‘Paracox’ in broiler chickens isolated from extraneous coccidial infection

A trial was carried out in 1-day-old broiler chicks raised for 54 days in floorpens under simulated commercial conditions, but isolated from all extraneous virulent coccidial infections, to demonstrate the safety of Paracox attenuated vaccine administered at the recommended dose when chicks were 7 days old. The vaccine did not adversely affect the water consumption, faecal moisture or litter condition of the broilers. Recycling of the attenuated coccidia occurred in vaccinated birds, oocysts being present in the litter between 5 and 33 days after vaccination; a single peak of oocysts was detectable 5 or 12 days after vaccination. Unvaccinated medicated control birds did not produce oocysts, indicating freedom from both between-pen contamination by the vaccine and invasion of the chicken-house by extraneous coccidial infection. A small proportion (4%) of vaccinated birds had mild coccidial lesions when sampled at 26, 33 or 40 days after vaccination. Despite this, the vaccinated birds performed better than control (unvaccinated, nicarbazin-treated) birds and there was no post-vaccinal check in their weight gain. Their mean finishing weight was 10.4% greater, their food conversion ratio 7.2% lower and their mortality 44.4% lower than the unvaccinated control birds, reflecting the safety of Paracox vaccine.Abbreviation FCR food conversion ratio     

Disposition kinetics and distribution of demeclocycline in various biological fluids in female goats

A pharmacokinetic study of demeclocycline was carried out following intravenous administration at 5 mg/kg body weight in lactating goats. Demeclocycline appeared within 5 min in plasma, interstitial fluid (isf) and urine, while it appeared at 1 h in milk. Peak concentrations of 21.70±4.06, 2.67±0.23, 5.65±0.45 and 82.23±10.06 g/ml were attained at 5 min and at 6, 8 and 8 h in plasma, isf, milk and urine respectively. A potentially therapeutic concentration of 0.5 g/ml was maintained from 5 min–36 h, 30 min–30 h, 1–36 h and 5 min–48 h in plasma, isf, milk and urine respectively. The drug was detectable in all the above biological fluids for at least 48 h. A low distribution half life (t_1/2) of 0.44±0.04 h and a high elimination half life (t_1/2) of 19.24±1.22 h denote rapid distribution but very slow elimination of the drug in goats. A high tissue plasma concentration ratio [K₁₂:(K_2I–)] of 5.12±0.97 during the elimination phase and a Vd_area of 1.59±0.18 L/kg indicate uniform distribution of demeclocycline in the tissues and body fluids of goats. The dosage regimen for maintaining minimum plasma concentration (C min = MIC) of 0.5, 1.0 and 1.5 g/ml at selected dosage intervals of 12 and 24 h was also calculated.     

Identification of Functional α-Adrenoceptor Subtypes in the Bovine Female Genital Tract During Different Phases of the Oestrous Cycle

The concentration and functionality of the -adrenoceptor (-AR) subtypes in the genital tract of cyclic heifers were investigated. In each tissue sample, a single class of ₁-ARs was observed, whereas two distinct classes of ₂-ARs were discriminated: low-affinity (LA) and high-affinity (HA) ₂-ARs. Statistical analysis showed the presence of significantly (p < 0.05) higher concentrations of all -AR subtypes in the follicle than in the corpus luteum. No significant differences were found in the ovary or myometrium between the luteal and follicular phases. In the ovary, the density of ₁-ARs was significantly (p < 0.05) higher than that of ₂-ARs. By contrast, there were significantly (p < 0.05) more ₂-ARs than ₁-ARs in the myometrium. As far as ₂-ARs are concerned, LA ₂-ARs were significantly (p < 0.05) higher than HA ₂-ARs in all tested tissues. Competition studies suggested that the rank order of potency of antagonists for ₁-ARs was prazosin > phentolamine > yohimbine, whereas for ₂-ARs the order of potency was yohimbine phentolamine > prazosin. Functional assays performed on myometrium showed that noradrenaline, phenylephrine and clonidine elicited concentration-dependent contractions only in dioestrus and pro-oestrus preparations and that clonidine was more effective than phenylephrine as a contractile agent. It appeared that there were no significant modifications in -AR affinity or concentration during the different stages of bovine oestrous cycle, whereas the uterine spontaneous activity and the responsiveness to -adrenergic stimulation was strongly influenced by hormonal levels. The modifications of uterine contractility observed during the oestrous cycle may be related to modifications induced in the transductional mechanisms of -ARs.     

Leukocyte and Cytokine Accumulation in the Ovine Teat and Udder during Endotoxin-Induced Inflammation

Persson Waller, K., Colditz, I.G., Flapper, P. and Seow, H.-F., 1997. Leukocyte and cytokine accumulation in the ovine teat and udder during endotoxin-induced inflammation. Veterinary Research Communications, 21 (2), 101-115The accumulation of leukocytes, ovine serum albumin and the cytokines interleukin-1 (IL-1), tumour necrosis factor- (TNF-), interleukin-8 (IL-8), granulocyte-macrophage colony-stimulating factor (GM-CSF) and interferon- (IFN-) was studied during endotoxin-induced inflammation in lactating and dry ovine udders, and in the teat cisterns of dry ewes after surgical closure of the passage between the teat and udder cisterns. Samples were taken before infusion and hourly up to 10 h after infusion of 0.1, 1 or 10 µg of endotoxin, or infusion of pyrogen-free saline (PFS) as a control. Rectal temperatures were measured.A significant dose- and time-dependent accumulation of leukocytes, mainly neutrophils, was observed in the lactating udders and in the teat cisterns. In the dry udders, the leukocyte accumulation was significant for time but not for dose. Peak numbers of cells were reached at 3-4 h in the dry udders and in the teat cisterns, but not until 10 h after infusion in the lactating udders. The changes in the ovine serum albumin concentrations mostly paralleled changes in leukocyte numbers.A role was indicated for TNF-, IL-8 and GM-CSF, but not for IL-1 and IFN-, during endotoxin-induced inflammation in the ovine udder. Release of TNF-, IL-8 and GM-CSF was most prominent in lactating udders, peaking at 2 or 3 h after infusion, but was also detected in dry udders and teat cisterns. Detectable levels of IL-1 and IFN- were occasionally found in all three groups.     

Plasma,Urinary and Biliary Residues in Cattle Following Intramuscular Injection of Nortestosterone Laurate

The synthetic androgen 19-nortestosterone (-NT) has been used illegally as a growth promoter in cattle production in the European Union. Elimination of -NT and its metabolites in plasma, urine and bile was studied in three cattle with cannulated gallbladders following intramuscular injection at a single site of 500 mg of the laurate ester (NTL) containing 300.5 mg -NT. Using enzyme immunoassay quantification, plasma Cmax of free -NT was 0.5±0.15 g/L (mean±SEM). Concentrations of free -NT in plasma were consistently greater than the assay limit of quantification (0.12 g/L) for 32.7±13.42 days. Mean residence time for free -NT in plasma was 68.5±20.75 days. Following sample preparation by immunoaffinity chromatography, high-resolution GC-MS was used to quantify -NT and -NT in urine and bile. -NT was detected irregularly in urine from two of the three animals post injection. The principal metabolite present in the urine, -NT, was detected for 160.3±22.67 days post injection. Cmax for -NT in urine was 13.7±5.14 g/L. Mean urinary AUC0–183 days for -NT was 845.7±400.90 (g h)/L.In bile, -NT was the only metabolite detected for 174.3±8.67 days post treatment. Cmax for -NT in bile was 40.8±12.70 g/L and mean biliary AUC0–183 days for -NT was 1982.6±373.81 (g h)/L. Concentrations of -NT in bile samples were greater than those in urine samples taken at the same time. The mean ratio of biliary:urinary AUC0–183 days was 3.0±0.72. It is concluded that bile is a superior fluid for detection of -NT following injection of NTL, owing to the longer period during which residues may be detected after administration.     

Reflections on viruses and cancer

In recent years human and animal cancers have increasingly been shown to have a viral component in their aetiology. Oncogenic viruses will continue to be discovered although with certain cancers there is also an important environmental component, and with others — congenital cancers and cancers of early childhood — an important genetic component. There is thus the probability that cancer may not be an entity. Rather it may be a syndrome, the phenotypic expression of alteration of cellular metabolism, differentiation and cell death. More information is needed on the mathematics of cell division and destruction,in vivo andin vitro, and the involvement of biological clocks, i.e. ageing processes. These data, when available, should help us to understand better the nature of cancer and lead us to more effective methods of prevention and cure.Abbreviations AIDS acquired immunodeficiency syndrome - ALV avian leukosis virus - COFAL complement-fixation test for avian leukosis viruses - FeLV feline leukaemia virus - kb kilobases - L/S viruses leukosis/sarcoma viruses - MMTV mouse mammary tumour virus - MuLV mouse leukaemia virus - wt wild type     

Uterine motility of the sow during the oestrous cycle and early pregnancy

With electromyography and strain gauges the uterine motility of the sow during the oestrous cycle and early pregnancy was studied. Special attention was paid to characterization of myometrial activity at the time of intrauterine migration of blastocysts.From recordings of 4 animals (3 became pregnant) 3 types of electrical spiking activity (each could be correlated with an elevation of the strain gauge tension) were discerned. Two of them appeared regularly and were suitable for analysis: High Voltage Slow Acticity (with relative high amplitude and low frequency of spikes) and Low Voltage Fast Activity (with relative low aplitude and high frequency of spikes).The sexual status markedly influenced myometrial activity: during prooestrus and oestrus only one type of electrical activity was present whereas the myoelectrical complex (an episode of this activity and the subsequent interval of inactivity) was shorter than 10 min. During dioestrus the myoelectrical complex was longer than 10 min and High Voltage Slow Activity (solely on the cervix and bifurcation) and Low Voltage Fast Activity occurred simultaneously in episodes which mainly appeared to originate on the bifurcation.The characteristics of uterine activity during pregnancy were similar to those of a cyclic sow until day 12. It was only on day 12 that gestation appeared from an increased frequency of myoelectrical complexes.It is concluded that Low Voltage Fast Activity as it was found on the uterine horn at days 8–9 might be involved in the process of intra-uterine migration of blastocysts. In cyclic and in pregnant animals the patterns of Low Voltage Fast Activity were similar. Therefore, the occurrence of Low Voltage Fast Activity is independent of the actual presence of blastocysts. It seems to be exhibited in dependence on the ovarian hormones.     

Measurement of Cortisol Metabolites in Faeces of Ruminants

Twenty-one metabolites were detected in faecal samples collected after infusion of (¹⁴C)cortisol into the jugular vein of sheep, using high-performance liquid chromatography/radiometric analysis plus mass spectrometry. One group of metabolites had molecular weights of between 302 and 308, and another group of 350, which indicates that the substances have a C₁₉O₃ or a C₂₁O₄ structure. Therefore, an enzyme immunoassay against 5-androstane-3-o1-11,17-dione-17-CMO:BSA was established. Faecal samples were collected from 10 cows immediately after transport and then during a course in which non-invasive diagnostic procedures were being taught (course 1). For comparison, faeces were sampled from another 5 cows that were being used for teaching invasive procedures (course 2). Six cows from a university farm served as controls. In the animals used in course 1, the highest concentrations of cortisol metabolites were measured immediately after transport to the university (median value: 2.2 mol/kg faeces). During the first 5 days at the university, the concentrations decreased to 0.52 mol/kg (median) and remained at this level during the rest of the course. The median concentration in the samples that were taken during course 2 (collected about 2 months after transport) was 0.48 mol/kg. There was no significant difference in the excretion of cortisol metabolites between these cows and the controls. We conclude from these data that, using the enzyme immunoassay against 5-androstane-3-o1-11,17-dione-17-CMO, we were able to detect transport/novel environment stress but not the potential disturbance that cows experience during diagnostic procedures.     

Evaluation of Synchronization of Oestrus Based on Gonadotrophin-releasing Hormone and Its Potential Use for Fixed-Time Breeding in Tuli Beef Cows

The objective of the experiment was to compare the reproductive post-partum performance of beef cows synchronized for oestrus using prostaglandin F₂ (PGF₂) alone or with a gonadotrophin-releasing hormone (GnRH)-based drug. Fifty-five post-partum lactating Tuli cows were randomly allocated to three groups. Two groups were synchronized using either two injections of PGF₂ (500 g Prosolvin per injection) given 11 days apart (group 1), or GnRH (12.5 g Receptal per injection) followed 6 days later by an injection of 500 g PGF₂ (group 2). The cows were bred by artificial insemination 12 h after they were observed in oestrus. Group 3 was synchronized as for group 2, but a second injection of GnRH was given 54 h after the PGF₂ injection, at which time the cows were bred by artificial insemination (AI) without detection of oestrus. Blood samples were taken from the cows in group 3 and analysed for progesterone concentration to establish which cows were cycling and in oestrus before and at the time of breeding. Detection of oestrus and breeding by AI was done over 60 days. There were no significant differences (p>0.05) among the three groups in the first service and total conception rates. The percentage of cows in oestrus within 10 days of the synchronization treatment was not significantly different (p>0.05) between groups 1 and 2. The progesterone concentrations in the cows in group 3 showed that only those that were cycling at the start of the experiment responded to the synchronization treatment and conceived after fixed-time breeding. These results suggest that combinations of PGF₂ and GnRH may be of value in synchronizing oestrus and controlling breeding in Tuli cows. However, the benefit might be greater if only cows that are known to be cycling are bred in this way.     

Scrapie in the sheep and laboratory animals: Suitability of the sheep model for the study of slow virus diseases

After briefly summarizing the information available on sheep scrapie, the authors explain the value of using the sheep in the study of slow virus diseases, since it is particularly prone to diseases of this type. It may be affected not only by scrapie but also by other similar diseases such as visna, maedi and jaagsiekte. These disorders may therefore be used as models to which the most recent pathogenic concepts can be applied. A study of them will lead to a better understanding of the virus-host relationship in the pathology of infection.

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Kurzfassung Im Anschluss an die Darstellung der Traberkrankheit bei Schafen und eine kurze Zusammenfassung aller bisher darüber vorliegenden Erkenntnisse wiesen die Autoren auf die Bedeutung des Schafes als Versuchstier bei der Untersuchung der durch langsame Viren verursachten Krankheiten hin, da Schafe eine ausgeprägte Disposition für diese Art von Störungen aufweisen. Sie können neben Traberkrankheit ausserdem von weiteren Erkrankungen des gleichen Typs wie Visna, Maedi und Jaagsiekte befallen werden. Diese Erkrankungen eignen sich daher als Modelle, an denen sich die jüngsten Erkentnisse über die Pathogenese praktisch erproben lassen. Solche Untersuchungen führen zweifellos zu einem besseren Verständnis des Verhältnisses zwischen Wirtstier und Virus im Rahmen der infektiösen Pathologie.

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Resume Après avoir montré l'importance et résumé brièvement l'ensemble des connaissances relative à la tremblante du mouton, les auteurs montre l'intérêt de l'utilisation du mouton pour l'étude des maladies à virus lents, celui-ci montrant une particulière prédisposition à présenter ce type de désordres. Il peut être atteint non seulement de tremblante mais aussi d'autres maladies de même type comme le visna, le maedi et la jaagsiekte. Ces affections constituent donc des modèles auxquels les plus récents concepts pathogéniques peuvent être appliqués. Leur étude permettra certainement de mieux comprendre la relation virus-hôte en pathologie infectieuse.

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Riassunto Gli autori, dopo aver sottolineato l'importanza e riassunto brevemente il complesso dei dati disponibili sulla malattia del trotto (prurigo lombare accompagnata da disturbi neuromotori) degli ovini, rilevano l'interesse che può avere l'impiego di ovini nello studio delle malattie da virus lenti, in quanto questi animali sembrano particolarmente predisposti a tale tipo di affezioni. Essi possono essere colpiti non soltanto dalla malattia del trotto, ma anche da altre malattie affini quali il visna, il maedi e la jaagsiekte. Lo studio di queste malattie, che rappresentano modelli ai quali possono essere applicati i più recenti concetti patogenetici, consentirà certamente di comprendere più a fondo la relazione virusospite nella patologia infettiva.

     

Localization of glycoconjugates in dog parotid gland by lectin histochemistry

Parotid glands from adult dogs were stained with a battery of seven horseradish peroxidase-conjugated lectins (PNA, UEA, LTA, DBA, SBA, WGA and ConA). In some cases (PNA and DBA) neuraminidase digestion was followed by lectin staining. Acinar cells contained conspicuous quantities of oligosaccharides with terminal sialic acid radicals. Galactosil-(13)N-acetylgalactosamine was the most abundant penultimate sugar linked toN-acetylneuraminic acid. Sialylated components having the terminal dimer sialic acid-N-acetylgalactosamine were found in the acinar cells. Secretory cells presented a heterogeneous distribution of glycoconjugates with terminal fucose and -N-acetylgalactosamine. Fucose,N-acetylglucosamine and -N-acetylgalactosamine were present on the apical cytoplasm and surface of the striated and interlobular duct cells. This glycosidic composition was unaffected by extensive selective breeding. The role of abundant amounts of sialic acid radicals in the oral mucosa was considered.Abbreviations HRP horseradish peroxidase - PBS phosphate-buffered saline see also Tables I and III     

Lymphoid leukosis viruses,their recognition as ‘persistent’ viruses and comparisons with certain other retroviruses of veterinary importance

Diseases caused by lymphoid leukosis virus (LLV), a retrovirus, take a long time after infection to develop and have a wide variety of pathological manifestations. This long latent period is characteristic of persistent virus infections. Disease produced by LLV infection and its underlying mechanisms is compared with persistent infections caused by other retroviruses in birds and mammals of veterinary importance. The diseases considered for comparison are those caused by reticuloendotheliosis, feline leukaemia, bovine leukosis and equine infectious anaemia viruses. There are significant changes in the immunological status in all diseases caused by these viruses. LLV infections follow this trend with, in manifestations of neoplastic disease, a perturbation of the normal switch that occurs from IgM to IgG synthesis. There are also indications of other immunological disturbances.Factors other than immunological disturbances may contribute to the length of time after infection required for the many forms of LLV infection to appear. Such additional factors may include the operation of biological clocks, such as the arrival of sexual maturity, and also the very nature of retroviruses. These factors, like the immunological changes, play major roles in the maintenance and progression of persistent retrovirus infections.Abbreviations ACTH adrenocorticotropic hormone - AEV avian erythroblastosis virus - AMV avian myeloblastosis virus - BLV bovine leukaemia virus - CAV chicken anaemia virus - EBL enzootic bovine leukaemia - EIAV equine infectious anaemia virus - env envelope gene - FeLV feline leukaemia virus - FeSV feline sarcoma virus - FOCMA feline oncovirus membrane-associated antigen; gag, group antigen gene - HTLV human T-cell leukaemia virus - LLV lymphoid leukosis virus - L/S leukosis/sarcoma - LTR long terminal repeat - MAV myeloblastosis-associated virus - MDV Marek disease virus - MuLV mouse leukaemia virus - ORF open reading frame; pol, polymerase gene - REV reticuloendotheliosis virus - RIF resistance-inducing factor - RSV Rous sarcoma virus     

Preliminary findings of altered follicular activity in Holstein cows with coagulation factor XI deficiency

Factor XI (F XI) deficiency is an autosomal recessive coagulopathy found in Holstein cattle. Affected animals have a 50% greater prevalence of repeat breeding. Therefore, several parameters describing ovarian function were studied. Daily blood sampling revealed that progesterone concentrations were slower to decline from a peak at day 16 (p<0.01) to values less than 3 nmol/L in F XI-deficient cows (5.14±0.69 days (mean ± SD) versus 4.05±0.63 days in control animals), resulting in an oestrous cycle length of 24.7±2.1 days compared to 22.9±3.0 days, respectively. This was not due to an alteration in the availability of prostaglandin F₂ (PGF₂) or oxytocin (OT) involved in luteolysis. No significant differences (p>0.05) were seen between normal (n=7) and F XI-deficient (n=7) cows in the peak values or the area under the curve for the pulse in 13,14-dihydro-15-keto PGF₂ in response to OT challenge or in the parameters describing the pulse of ovarian OT secretion after PGF₂ injection (n=7 for each) between days 12 and 14. Ovulatory follicular development was assessed by ultrasound monitoring and plasma 17-oestradiol values at 8-h intervals after a luteolytic injection of cloprostenol (n=6 for each). Follicular diameter was smaller (p<0.05) and accompanied by lower peak oestradiol values near the time of ovulation in F XI-deficient cows. The results suggest that the oestrous cycle in F XI-deficient cows is characterized by a slower process of luteolysis that may be associated with smaller follicular development.Abbreviations F XI factor XI - OT oxytocin - PGF₂ prostaglandin F₂ - PGFM 13,14-dihydro-15-keto-prostaglandin F₂ - i.m. intramuscularly     

PATHOGENICITY AND IMMUNOSUPPRESSIVE PROPERTIES OF INFECTIOUS BURSAL DISEASE VIRUS FIELD ISOLATES AND COMMERCIAL VACCINES IN INDIA

The pathogenicity and immunosuppressive properties of two field isolates of infectious bursal disease virus (IBDV) and five commercial IBDV live virus vaccines marketed in India were evaluated in this study. The pathogenicity of the wild type viruses and vaccines were based on mortality, the bursa:body weight ratio and microscopic lesions in the bursa in 3-week-old chicks that received these viruses. The immunosuppressive effects of these viruses were evaluated by measuring the antibody responses to sheep red blood cells, Brucella abortus plain antigen and Newcastle disease virus (NDV) vaccine in one-day-old chicks. One field isolate (N35/93) was found to be more pathogenic and immunosuppressive than the other (N45/92) while none of the commercial mild Lukert type vaccines were found to be pathogenic. One of the vaccine strains marked as Mild Lukert type was highly immunosuppressive; one was moderate and one could be classified as mild. Both the intermediate vaccines tested were highly immunosuppressive.     

Novobiocin Inhibits Both UDP-Glucuronosyltransferase and Cytochrome P450-Mediated Enzyme Activities in Pig Liver Microsomes

The effects of novobiocin (range 0.0125–2 mmol/L) on the hydroxylation of testosterone, the N-demethylation of erythromycin, and the glucuronidation of -naphthol and paracetamol were studied using pig hepatic microsomes, pooled from five animals. The final concentrations of these substrates in the incubation mixtures were selected to meet V_max conditions. Novobiocin caused a concentration-dependent inhibition of the glucuronidation of paracetamol; the formation of -naphthol-glucuronide was reduced to a lesser degree. These results confirm and extend earlier findings in laboratory animal species that novobiocin inhibits UDP-glucuronosyltransferases (UDPGTs). Moreover, novobiocin strongly inhibited 6-hydroxylation of testosterone. The microsomal N-demethylation of erythromycin and hydroxylation of testosterone at the 15 position were less affected by novobiocin. These results suggest that novobiocin inhibits not only UDPGTs, but also cytochrome P450 (CYP) enzyme activities, probably those belonging to the CYP3A subfamily. More research is needed to reveal which CYPs and UDPGTs are affected by novobiocin in vivo, in order to improve the understanding and probably the predictability of potential drug interactions with this antibiotic.