Parenchymal injury and biliary obstruction in relation to photosensitization in sporidesmin-intoxicated lambs

The hepatic changes were compared in lambs photosensitized or not photosensitized after exposure to sporidesmin. Injury to both the parenchyma and the biliary system was more severe in the photosensitized than in the non-photosensitized lambs. The activities of -glutamyltransferase and glutamate dehydrogenase, and the total, conjugated and unconjugated bilirubin concentrations were significantly higher in sera from the photosensitized than from the non-photosensitized lambs. Hepatic glycogen levels were decreased in both the photosensitized and the non-photosensitized lambs, but were significantly lower in the former. Hence it is possible that lesions in hepatocytes contribute to retention of phylloerythrin and so to photosensitization.     

Failure to induce toxicity in lambs by administering saponins from Narthecium ossifragum

It has been suggested that saponins produced by Narthecium ossifragum (Bog asphodel) may be the direct cause of the toxicity leading to the hepatogenous photosensitivity disease alveld seen in Norwegian lambs. Lambs fed large quantities of freeze-dried N. ossifragum did not develop alveld. Chemical investigations on the freeze-dried material and fresh N. ossifragum showed no difference in their saponin content. These results indicate that alveld is not caused solely by the saponins produced by N. ossifragum.     

Fungi onNarthecium ossifragum leaves and their possible involvement in alveld disease of Norwegian lambs

Spores ofPithomyces chartarum (Berk. & Curt.) M.B. Ellis were only rarely seen on leaves ofNarthecium ossifragum (L.) Hudson collected in summer from five areas in western Norway in which alveld, a photosensitization disease of lambs, is endemic.Cladosporium magnusianum (Jaap) M.B. Ellis was found on all 118 leaf samples collected in the summers of 1990 and 1991. The hypothesis thatP. chartarum contributes to the aetiology of alveld could not be supported, but it is possible thatC. magnusianum may have a role in the causation of the disease.     

Comparison of a novel form of zinc with zinc oxide bolus licensed for prevention of facial eczema,and interaction with copper oxide in sheep

To evaluate a novel elemental zinc bolus compared with a registered positive control zinc oxide bolus and assess serum zinc concentrations following concomitant treatment with a capsule containing copper oxide needles. Forty Romney-cross ewes were randomly allocated in a 2 × 2 factorial design study. On Day 0, 20 ewes received novel boluses containing elemental zinc (Investigational Veterinary Product, IVP) while 20 received a zinc oxide bolus (control; CP). Half the animals in each zinc treatment group (n = 10) were treated with a copper oxide needle capsule [Copasure® - Ewe]. Weekly, from Day −7 to 56, all ewes were assessed for signs of photosensitization, and for 10 ewes from each zinc treatment groups, samples were collected for analysis of serum GGT activity, serum zinc concentrations, faecal zinc concentrations and on Days −7 and 56, liver copper concentrations. Multivariable random-effects models assessed the effects of zinc treatment, copper treatment, treatment interactions and time on all analytes. Regression models examined associations between serum and faecal zinc concentrations and GGT activity. Low spore numbers indicated low Pithomyces chartarum challenge. Serum zinc levels were significantly higher in the IVP than in the CP group [p < 0.0001] and varied by time [p < 0.001] and positively associated with faecal zinc concentration [p < 0.001]. Copper treatment did not affect serum zinc [p = 0.82] or faecal zinc [p = 0.92] concentrations. Liver copper concentrations did not differ between zinc treatment groups on Day −7 [p = 0.6] or Day 56 [p = 0.95]. Only the CP/no copper group had no increase in liver copper concentrations.     

Metabolism of Saponins From Narthecium Ossifragum - a Plant Implicated in the Aetiology of Alveld,a Hepatogenous Photosensitization of Sheep

One sheep was dosed over 4 consecutive days with 2.1 kg of leaves and flower stems of Narthecium ossifragum before it was killed. Sarsasapogenin and smilagenin glycosides, in the ratio 9:1, were the dominant saponins present in the dosed plant material. GC-MS analyses of the free and conjugated sapogenin content of samples recovered from the sheep identified three distinct regions of metabolic activity. In the first metabolic region, in the rumen and omasum, the ingested plant saponins were hydrolysed to the parent sapogenins, before being oxidized at C-3 and reduced to give the epi analogues of the ingested sapogenins. The second metabolic region consisted of the duodenum, jejunum, the liver and associated ducts. Sapogenins appear to be absorbed in the jejunum and may be transported via the portal vein to the liver, where 3-OH-5-H sapogenins (epismilagenin and episarsasapogenin), but not 3-OH-5-H sapogenins (smilagenin and sarsasapogenin), are conjugated and excreted into the bile as episarsasapogenin and epismilagenin conjugates in the ratio 4:1. In the third metabolic region, in the caecum and the colon, the epi-sapogenin conjugates were hydrolysed to free epi-sapogenins. The absence of free and/or conjugated sapogenins in urine, collected 24 h after dosing commenced, indicates that saponins and their metabolites are not likely to be implicated in the kidney disease occurring in ruminants ingesting N. ossifragum.     

Aldrin epoxidase and 7-ethoxyresorufin-O-deethylase (EROD) activity in livers from lambs of three different breeds of Norwegian sheep

The concentration of aldrin epoxidase was significantly greater in the livers of Norwegian Pelt lambs than in those of Rygja lambs but did not differ significantly between either of these two breeds and Spael lambs. Conversely, although there was no detectable EROD activity in the livers of many of the lambs in all three breeds, the median activity was greater in the livers of Rygja lambs than was the case for Spael lambs.Abbreviations EDTA ethylenediaminetetraacetic acid - EROD 7-ethoxyresorufin-O-deethylase - GST glutathioneS-transferase     

An attempt to reproduce crystal-associated cholangitis in lambs in experimental dosing of sarsasapogenin or diosgenin alone and in combination with sporidesmin

No liver damage occurred in a group of 21 lambs dosed intraruminally with up to 9 g of sarsasapogenin or diosgenin daily for 10 consecutive days. In contrast, seven out of 15 lambs dosed with 0.1 mg of sporidesmin/kg liveweight in combination with sarsasapogenin and three out of six lambs dosed with sporidesmin in combination with diosgenin developed liver lesions. These were typical of those induced by sporidesmin. One lamb dosed with sporidesmin in combination with 9 g of diosgenin developed a crystal-associated cholangitis typical of Panicurn intoxication and alveld. No sapogenins were detected in urine by gas chromatography-mass spectrometry. The results suggest that orally administered sarsasapogenin and diosgenin are either not hepatotoxic per se or are too poorly absorbed to elicit a toxic response. The results provide only weak evidence that sporidesmin may be involved in the aetiology of Panicurn intoxication.     

Accumulation of Sapogenin Conjugates and Histological Changes in the Liver and Kidneys of Lambs Suffering from Alveld,a Hepatogenous Photosensitization Disease of Sheep Grazing Narthecium ossifragum

Sixteen lambs exhibiting hepatogenous photosensitization (alveld) after grazing pasture containing Narthecium ossifragum and seven nonphotosensitized lambs grazing the same pastures were studied. All the alveld-affected lambs revealed liver damage dominated by single cell necrosis, portal fibroplasia and bile duct proliferation. Crystalloid clefts were demonstrated in the bile ducts of two and in the hepatocytes and Kupffer cells of nine photosensitized lambs. Plasma bilirubin concentration was severely increased in ten of the cases of alveld whereas the activity of aspartate aminotransferase was moderately to severely increased in seven cases. The activity of glutamate dehydrogenase was moderately elevated in one of the photosensitized lambs. The main histopathological findings in the kidneys from the alveld-affected lambs were dilated tubules, often with eosinophilic material in the tubular lumina. Regenerative changes were seen in a large proportion of the renal sections. Elevated plasma concentrations of urea and creatinine, and the renal histopathological changes, suggested that the photosensitized lambs had been through a phase of renal injury. Analysis of the free and conjugated sapogenin content in liver tissue and bile was performed by gas chromatography–mass spectrometry. There were significantly higher concentrations of conjugated episapogenins in both the liver and bile in the alveld-affected lambs than in the nonphotosensitized lambs.     

Detailed genetic analysis of feeding behaviour in Romane lambs and links with residual feed intake

Breeding strategies based on feed efficiency are now implemented in most animal species using residual feed intake (RFI) criteria. Although relevant, the correlated responses of feeding behaviour traits resulting from such selection on RFI are poorly documented. We report the estimated feeding behaviour at three time levels (visit, meal and day) and genetic parameters between the feeding behaviour traits and their links with RFI and its components. Feed intake, feeding duration at three time levels (per visit, meal and day), feeding rate, number of visits and time‐between‐visits were estimated for 951 Romane lambs fed via automatic concentrate feeders. Heritability estimates of feeding behaviour traits ranged from 0.19 to 0.54 with higher estimates for the day level than the visit level. Daily feed intake was not genetically linked to feed intake at the visit level, whereas feeding duration between visit and day levels was moderately correlated (R_g = +0.41 ± 0.12). RFI was not significantly correlated with feeding rate, but was positively linked to feed intake and feeding duration at the day level (+0.73 ± 0.09 and +0.41 ± 0.13, respectively) and negatively at the visit level (?0.33 ± 0.14 and ?0.22 ± 0.17, respectively). Selecting animals with lower RFI values might modify their feeding behaviour by increasing feed intake and feeding duration at the visit level but decrease the number of visits per day (+0.51 ± 0.14).     

细粒棘球蚴感染羊肝脏包囊纤维化形成的病理形态学观察

为了探讨细粒棘球蚴感染羊肝脏包囊纤维化形成的病理学过程,本研究通过病理组织学、细胞化学和超微形态学的诊断方法,对羊感染细粒棘球蚴后肝脏的病理组织学变化,以及肝组织纤维化和包囊形成过程进行病理学观察。结果显示:原头蚴感染肝组织后病变沿感染组织的血管周围产生,相继出现肝细胞萎缩、变性、坏死;同时病变组织血管壁出现纤维组织分解、血管管壁出芽,增生出的纤维组织伸向周围炎症区域,血管管腔及炎区大量嗜酸性粒细胞浸润,增生的胶原纤维沿残存的肝细胞周围围绕病变组织,最终形成包囊壁。该研究结果为进一步阐释细粒棘球蚴感染羊肝脏包囊纤维化形成的病理机制奠定了坚实的基础。     

锌、铜对实验性钼中毒绵羊肝脏、肾脏中钼含量的影响

小尾寒羊20只,随机分为5组,分别口服钼、铜和锌(mg/kg),Ⅰ组30mg/kg钼、Ⅱ组30mg/kg钼+15mg/kg铜、Ⅲ组30mg/kg钼+15mg/kg锌、Ⅳ组30mg/kg钼+15mg/kg铜+15mg/kg锌,Ⅴ组去离子水。试验90d期满,采取肝脏和肾脏,硫酸-高氯酸消化,原子吸收法测定钼、锌、铜含量,结果显示,Ⅰ组肝脏钼含量与第Ⅱ、Ⅲ、Ⅳ、Ⅴ组差异极显著(P<0.01),Ⅱ、Ⅲ组与Ⅳ、Ⅴ组差异极显著(P<0.01);Ⅳ组肝脏铜含量与Ⅰ、Ⅲ、Ⅴ组差异极显著(P<0.01),与Ⅱ组差异显著(P<0.05),Ⅱ组肝铜含量与Ⅰ、Ⅲ、Ⅴ组差异极显著(P<0.01);组间肝脏锌含量均差异极显著(P<0.01)。Ⅰ、Ⅲ组肾钼含量显著高于Ⅱ、Ⅳ、Ⅴ组(P<0.01);Ⅱ与Ⅳ、Ⅴ组差异极显著(P<0.01);肾铜含量Ⅲ组与Ⅰ组差异极显著(P<0.01);Ⅱ、Ⅲ、Ⅳ组与Ⅰ、Ⅴ组差异极显著(P<0.01);各组肾脏锌含量差异均极显著(P<0.01)。结果表明,30mg的钼可使肝脏钼含量显著增加(P<0.01),锌、铜含量降低。锌对肝脏钼有很好的颉抗作用,铜、锌有效地降低了钼在组织中的蓄积。     

Temporal changes in the populations of immune cells at the site of experimental Dermatophilus congolensis infection in mice and sheep

Abstract The temporal patterns of dermal immune cell influx were compared in mice and sheep, species reputedly resistant and susceptible, respectively, to infection with Dermatophilus congolensis. In both species, the response involved early mast cell degranulation, vasodilatation and an influx of dendritic cells which accumulated and apparently differentiated beneath the infected epidermis. A concomitant dermal invasion by neutrophils and T and B lymphocytes led to epidermal infiltration, particularly by neutrophils and thence to the formation of the surface scab. Hypertrophy of the epidermis also indicates keratinocyte involvement in the host response. The duration of the response, however, was considerably shorter in the mouse (about 5 days) and B cells' were the predominant lymphocyte under and adjacent to the lesion. During the more protracted response in the sheep (> 21 days), T cells, including T19 antigen +γδ T cells, outnumbered B cells. Résumé— Des modifications dans les populations des cellules immunes dans le derme sont comparées chez la souris et le mouton, espèces respectivement résistantes et sensibles à Dermatophilus congolensis. Dans ces deux espèces, la réponse fait intervenir d'abord la dégranulation des mastocytes, la vasodilatation et l'arrivée de cellules dendritiques qui s'accumulent et se différencient apparemment sous l'épiderme infecté. Une invasion concomittente dermique par des neutrophiles, des lymphocytes T et B est observée et aboutit à l'infiltration épidermique, particulièrement par les neutrophiles et pour cette raison, à la formation de croûtes superficielles. L'hypertrophie de l'épiderme indique aussi l'implication du kératinocyte dans la réponse de l'hôte. Cependant, la durée de cette réponse, est bien plus courte chez la souris (environ 5 jours) et les lymphocytes B sont les lymphocytes prédominants, sous-jacents à la lésion. Chez le mouton, la réponse est prolongée (plus de 21 jours) et les lymphocytes T, incluant les lymphocytes CD 19 et γδ surpassent en nombre les lymphocytes B. [Sasiak, A.B., Lloyd, D.H., McEwan Jenkinson, D., Kitson, S., Elder, H. Y. Temporal changes in the populations of immune cells at the site of experimental Dermatophilus congolensis infection in mice and sheep (Particularités de la population cellulaire immunitaire aux sites d'infections expérimentales à Dermatophilus congolensis chez la souris et le mouton). Veterinary Dermatology 1996; 7 : 59–66.] ResumeAn Se compararon los patrones temporales de llegada de células inmunitarias en el ratón y en la oveja, especies consideradas resistentes y susceptibles, respectivamente a la infección por Dermatophilus congolensis. En ambas especies la respuesta implicó degranulación temprana de mastocitos, vasodilatación y llegada de células dendríticas que se acumulaban y aparentemente diferenciaban bajo la epidermis infectada. La invasión dérmica concomitante por netrófilos y linfocitos T y B llevó a una infiltración epidérmica, especialmente por neutrófilos y consecuentemente a la formación de una costra superficial. La hipertrofi de la epidermis también indica la implicación de queratinocitos en la respuesta del huésped. Sin embargo, la duración de la respuesta fue considerablemente más corta en el ratón (unos 5 dias) y los linfocitos B fueron la célula predominante en la zona adyacente a la lesión y debajo de ella. Durante la respuesta más prolongada en la oveja (> 21 días), las células T, incluyendo el antigeno T19, células T γδ, superaban en número las células B. [Sasiak, A.B., Lloyd, D.H., McEwan Jenkinson, D., Kitson, S., Elder, H. Y. Temporal changes in the populations of immune cells at the site of experimental Dermatophilus congolensis infection in mice and sheep (Alteraciones temporales en las poblaciones de celulas inmunitarias en zonas cutaneas de infeccion experimental por Dermatophilus congolensis en raton y en la oveja). Veterinary Dermatology 1996; 7 : 59–66.] Zusammenfassung— Die temporären Muster des Influx dermaler Immunzellen wurden bei Maus und Schaf verglichen, Tierarten, die angeblich resistent und empfänglich speziell für die Infektion mit Dermatophilus congolensis sind. Bei beiden Spezies bezog die Reaktion eine frühe Mastzelldegranulation ein, weiterhin Vasodilatation und einen Influx dendritischer Zellen, die sich unter der infizierten Epidermis anhäuften und offensichtlich differenzierten. Eine begleitende Invasion der Dermis durch Neutrophile, T- und B-Lymphozyten führte zu einer epidermalen Infiltration, besonders durch Neutrophile und von dort an zur Bildung von Oberflächenschorf. Die Hypertrophic der Epidermis zeigt außerdem eine Beteiligung der Keratinozyten bei der Antwort des Wirtstieres. Die Dauer der Reaktion jedoch war bei der Maus beträchtlich kürzer (etwa 5 Tage) und die B-Zellen waren die vorherrschenden Lymphozyten unter und angrenzend an die Läsion. Während der mehr protrahierten Reaktion beim Schaf (> 21 Tage) übertrafen die T-Zellen einschließlich T19-Antigen und gamma-delta-T-Zellen die Anzahl der B-Zellen. [Sasiak, A. B., Lloyd, D. H., McEwan Jenkinson, Kitson, S., Elder, H. Y. Temporal chnges in the populations of immune cells at the site of experimental Dermatophilus congolensis infection in mice and sheep (Temporäre Veränderungen in den Populationen von Immunzellen an der Stelle experimenteller Infektionen mit Dermatophilus congolensis bei Maus und Schaf). Veterinary Dermatology 1996; 7 : 59–66.]     

Comparison of the histological changes in the dog after treatment with the progestins medroxyprogesterone acetate and proligestone

Abstract

Administration of progestins in the dog may result in overproduction of growth hormone, suppression of the hypothalamic‐pituitary‐adrenocortical axis, and insulin resistance. In this paper we present a comparison of the histological findings in control dogs and dogs treated with either medroxyprogesterone acetate (MPA) or proligestone (PROL).

Depot preparations of MPA or PROL were administered (SC) at 3‐week intervals in two groups of seven ovariohysterectomized beagle dogs, after which three dogs of each group were killed. After a 6‐month period without hormone treatment during which recovery was studied, the remaining dogs received five additional injections at the same interval and were subsequently killed. Tissue samples of four intact female beagle dogs served as controls.

Progestin treatment resulted in atrophy of the adrenal cortex. In both MPA‐ and PROL‐treated dogs, the thickness of the combined zona fasciculata and reticularis was significantly smaller than in control animals. In the mammary glands of progestin‐treated dogs there were well developed alveoli and normal ducts adjacent to foci of hyperplastic ductular epithelium. Five dogs in each treatment group had developed benign mammary tumours which varied from simple tubular and papillary adenomas to benign complex and mixed tumours, whereas no mammary tumours were observed in the control animals. In each treatment group, steroid‐induced hepatopathy was observed in the liver of three dogs. Vacuolation of the cells of the islets of Langerhans and the epithelium of the intercalated ducts was present in two dogs of each treatment group and was only observed after the second series of progestin administrations. Incidental findings included chronic pyelonephritis, aspecific dermatitis, and mucinous dysplasia of the gall bladder. No abnormalities were found in sections of spleen, lung, brain, or pituitary gland.

There were no significant differences in the frequencies of the various abnormalities between MPA‐ and PROL‐treated dogs. Our findings correspond with the clinical and biochemical results after treatment of dogs with MPA and PROL. The high incidence of mammary tumours might be associated with our recent finding that in the dog progestins induce ectopic production of growth hormone in the mammary gland. The dog might be a good model for further studies on hormonally induced breast cancers.     

Growth response to increasing doses of microencapsulated vitamin B12 and related changes in tissue vitamin B12 concentrations in cobalt-de cient lambs

AIM: To investigate growth responses of cobalt-deficient lambs to increasing doses of microencapsulated vitamin B₁₂, and to measure associated changes in serum and liver vitamin B₁₂ concentrations over 243 days.

METHODS: From a flock grazing pastures that had low cobalt (Co) levels (about 0.06 mg Co/kg dry matter), 4-6-week-old lambs (n=137) were assigned to four groups and received either no treatment or a subcutaneous injection of 3.0, 4.5 or 6.0 mg of microencapsulated vitamin B₁₂ on Day 1. At approximately monthly intervals, all lambs were weighed and blood samples were collected from a selection (n=10) of monitor animals, up to Day 243. Liver biopsies were also carried out on the monitor lambs (n=8) on Days 1, 124 and 215.

RESULTS: The vitamin B₁₂-treated lambs grew significantly faster (p<0.001) than untreated animals. Liveweights after 243 days were 28, 45, 45 and 47 kg for the untreated, 3.0, 4.5 and 6.0 mg vitamin B₁₂-treated lambs, respectively. Of the initial group of untreated lambs, 68% had to be removed before the end of the trial because of substantial weight loss, but none of the treated animals were similarly afflicted. Serum vitamin B₁₂ concentrations increased in all vitamin B₁₂-treated lambs, reaching a peak at Day 25, and those of the 4.5 and 6.0 mg vitamin B₁₂-treated lambs remained significantly higher (except at Day 124) than the untreated lambs to Day 187. However, at Day 124, but not Day 215, the liver vitamin B₁₂ concentrations of treated lambs were two to three times higher than those of controls.

CONCLUSIONS: The growth rates of Co-deficient lambs were markedly improved by injection of 3.0, 4.5 or 6.0 mg of microencapsulated vitamin B₁₂, and liveweights were maintained for at least 243 days. Serum vitamin B₁₂ concentrations were related to this growth response; concentrations of <220 pmol vitamin B₁₂/l were associated with a 95% probability that lambs were Co-deficient and would thus respond to Co/vitamin B₁₂ supplementation. Based on these data, the current New Zealand reference criteria for Co deficiency should be reviewed.

CLINICAL SIGNIFICANCE: An injection of 3 mg microencapsulated vitamin B₁₂2 given to lambs at tailing will treat Co deficiency and will increase and maintain liveweights in a flock for up to 8 months.