Glycated haemoglobin in various pathological conditions: investigations based on a new, fully automated method

A new automated affinity chromatographic method for determining glycated haemoglobin (GHb) in dogs and cats was tested. The method appeared to be practical, quick and accurate. The reference range, calculated on the basis of 50 healthy dogs and 43 healthy cats, lay between 2·4 and 3·4 per cent in dogs and 2·0 and 2·9 per cent in cats. Concentrations were not influenced by age or gender. GHb levels obtained for 21 dogs and 18 cats with newly diagnosed diabetes mellitus were significantly higher than those of the control animals, ranging from 4·5 to 8·6 per cent (median 6·1) in dogs and from 2·7 to 6·0 per cent (median 3.8 per cent) in cats. The GHb levels in 31 normoglycaemic dogs with anaemia ranged from 2·3 to 4·3 per cent (median 3·3 per cent), and those of 22 normogiycaemic cats with anaemia from 2·6 to 3·9 per cent (median 3·2 per cent); both sets of levels were significantly elevated compared to control group values. GHb concentrations in animals with polycythaemia, azotaemia or liver disease showed no significant deviations from the control group; in individual cases they were slightly elevated compared to the reference range. The automated measuring method employed can be used to determine GHb in dogs and cats. Anaemic animals should generally be excluded from the GHb determination.     

The pathophysiology of ovine trypanosomosis: haematological and blood biochemical changes.

The course of Trypanosoma congolense infection in sheep was followed for 96 days. Infected animals developed fluctuating parasitaemia, macrocytic normochromic anaemia and leucocytosis which was principally a lymphocytosis. Following treatment with the trypanocidal drug, diminazene aceturate at 84 days after infection, the haematological values returned to normal within 12 days. Infected sheep developed hypocholesterolaemia and hypophospholipidaemia leading to a reduction in total serum lipids. This study has shown that sheep infected with T. congolense develop anaemia, the onset of which follows the first wave of parasitaemia. The changes in blood lipids observed in infected sheep appeared to be related to the intensity and duration of parasitaemia.     

DNA polymorphism of 5' flanking region of prolactin gene and its association with litter size in sheep

A single nucleotide polymorphism of 5' flanking region of the prolactin gene was investigated in both high prolificacy breeds (Small Tail Han and Hu sheep) and low prolificacy breeds (Dorset and Suffolk sheep) using polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP). The results indicated that two genotypes (AA and AB) were detected in Small Tail Han sheep (n   =   239), only one genotype (AA) was detected in Hu (n   =   40), Dorset (n   =   50) and Suffolk sheep (n   =   39). The mutant homozygous genotype (BB) was not detected in four sheep breeds. In Small Tail Han sheep (n   =   239), the frequency of genotypes AA and AB was 0.91 and 0.09, the frequency of the A and B alleles was 0.95 and 0.05, respectively. The fitness tests showed that the Small Tail Han sheep population was in Hardy–Weinberg equilibrium. Sequencing revealed a mutation (G→T) at the position 63 bp of the 5' flanking region of prolactin gene in AB genotype compared with AA genotype in Small Tail Han sheep. The Small Tail Han ewes with AB genotype had 0.83 (p < 0.05) lambs more than those with AA genotype. These results preliminarily showed that the prolactin locus is either a major gene that influences the high prolificacy in Small Tail Han sheep or is in close linkage with such a gene.     

Effects of supplementation on voluntary dry matter intake, growth and nutrient digestibility of the Fiji Fantastic sheep on a basal diet of Guinea grass (Panicum maximum)

Eighteen growing Fiji Fantastic (FF) sheep (nine ram lambs and nine ewe lambs), 5–6 months old, pre-experimental average body weight of 25.6 ± 0.82 kg were randomly divided into three groups of six and allotted to the treatments designated as A: Guinea grass (Panicum maximum); B: Guinea grass + concentrate mixture; and C: Guinea grass + crushed wheat grain in a completely randomized design experiment that lasted for 92 days. Total DM intake of sheep on forage + concentrate mixture were significantly higher (P < 0.001) than those on forage + crushed wheat grain and forage alone. Average daily gains (ADG) were 30, 75 and 42 g/day for forage, forage + concentrate mixture and forage + crushed wheat grain, respectively. ADG was significantly (P < 0.001) higher in sheep on forage + concentrate mixture. Daily protein intakes and BUN concentration were 3.59, 10.39 and 5.60 g/kg^0.75/day; and 6.0, 9.7 and 6.0 mmol/l for sheep on forage alone, forage + concentrate mixture and forage + crushed wheat grain, respectively. BUN and glucose concentrations at the post-experimental period were significantly (P < 0.001) higher in sheep on forage + concentrate mixture. DM, organic matter (OM), crude protein (CP), acid detergent lignin (ADL), hemicellulose and energy digestibility were significantly (P < 0.001) higher in sheep on the concentrate mixture while neutral detergent fibre (NDF) digestibility was significantly (P < 0.001) higher in sheep fed crushed wheat grain. Sheep on the concentrate mixture were also significantly (P < 0.002) higher in metabolizable energy intake (MEI). Sheep on concentrate mixture had higher organic matter (OM) and crude protein (CP) digestibility, high DMI and ADG. In conclusion this experiment has provided some relevant lacking information on the average DMI and ADG of the FF sheep and a concentrate mixture of 16.5% CP plus 19.0 MJ GE/kg BW seems ideal to meet the protein and energy requirements of the FF sheep for growth in the tropical environment of Fiji. Finally data obtained also demonstrated the influence of supplementary concentrate feeding on DMI and ADG of the FF sheep.     

Exploring the limitations of pathophysiological indicators used for targeted selective treatment in sheep experimentally infected with Haemonchus contortus

Identifying which sheep to treat as part of a Targeted Selective Treatment approach to gastro-intestinal nematode control relies entirely on the efficacy of the indicators. Indicators such as FAMACHA© (anaemia), DISCO (diarrhea) and reductions in weight gains were designed specifically to reflect those sheep experiencing symptomatic consequences of infection. Using the gastro-intestinal nematode Haemonchus contortus as a model species, this study explored the utility and sensitivity of these indicators under controlled experimental conditions on 63 adult sheep. The potential effect of sheep with different H. contortus resistance phenotypes on indicator efficacy was compared in three different phenotypes, i.e. high (Blackbelly females), medium (Blackbelly rams) and low resistance (Romane rams). The potential effect of the H. contortus isolate on indicator efficacy was also explored by using four different isolates, with varying anthelmintic resistance capacities, to infect the sheep. We limited the study to the first month of infection to evaluate the interest of these indicators as an early predictive means for controlling infection. The pathophysiological indicators FAMACHA© and DISCO do not reflect infection intensity based on Faecal Egg Counts, nor do reductions in weight gains. FAMACHA© was however a good indicator of anaemia with strong correlations to haematocrit. There was little agreement among the three indicators to identify the same animals in need of treatment and even combining them did not increase their predictive value of infection intensity or relative host damage from infection. The indicator sensitivity was influenced by the H. contortus isolate and sheep resistance phenotype in which they were tested. One isolate was poorly infective but induced high levels of anaemia (FAMACHA©) and diarrhea (DISCO) compared to the three others. The FAMACHA© and DISCO had higher values in the sheep group with a medium resistance phenotype (Blackbelly rams) indicating higher levels of damage compared to the high and low resistance phenotypes. We conclude that there is no ‘one size fits all’ approach to the use of indicators for Targeted Selective Treatment and the indicators should be calibrated to farm-specific conditions to increase their efficacy.     

Pathophysiology of ovine trypanosomiasis: ferrokinetics and erythrocyte survival studies.

The haematological changes, erythrokinetics and ferrokinetics of sheep were investigated after infection with Trypanosoma congolense. Following the detection of parasites in blood, the infected sheep developed macrocytic hypochromic anaemia. Studies with 51Cr-red cells, 125I-albumin and 59Fe as ferric citrate 11 weeks after infection revealed that infected sheep had significantly lower mean circulating red cell volumes but higher plasma and blood volumes than control sheep. The infected sheep also had enhanced erythropoietic activity as judged by significantly higher plasma iron turnover rates, faster disappearance of radio-labelled iron and higher iron incorporation rates than control sheep. The rate of disappearance of 51Cr-labelled red cells was greater in infected than in control sheep. It was concluded that the anaemia observed at this stage of infection was due to an increased rate of removal of red cells from the circulation coupled with haemodilution, with no evidence of dyshaemopoiesis.     

Haemonchus spp. in sheep farmed under resource-poor conditions in South Africa--effect on haematocrit,conjunctival mucous membrane colour and body condition

A longitudinal study was conducted on the differential faecal egg counts, haematocrits and body condition scores of sheep belonging to resource-poor farmers at Rust de Winter, Gauteng province, and Kraaipan, North West Province, South Africa. The animals were scored for level of anaemia using the FAMACHA method, an assay for the clinical evaluation of anaemia caused by Haemonchus spp. Periods of higher Haemonchus egg counts occurred from October to March for sheep at Rust de Winter and from September/October to February or April for sheep at Kraaipan. Lower haematocrit values were registered during these periods as was a higher incidence of anaemic conjunctival mucous membrane colour scores compared to the period April to September. No clear relationship between the faecal egg counts and the body condition scores was evident. Although wider application of the FAMACHA system in sheep raised by resource-poor farmers should be investigated, the present study indicates that this method may certainly prove to be a valuable worm control strategy for such livestock owners.     

Pathophysiology of ovine fascioliasis: The influence of dietary protein and iron on the erythrokinetics of sheep experimentally infected with Fasciola hepatica

Worm-free sheep were fed diets with a high or low protein and iron content and infected with 1,000 F. hepatica metacercariae. The adult fluke burdens of the sheep on each diet were similar, but animals on the poorer plane of nutrition developed an earlier and ultimately more severe anaemia and as a result had to be necropsied earlier. By measuring the attendant changes in blood volume and erythrokinetics, it was found that the underlying cause of the anaemia in all animals was a combination of haemodilution, intra-hepatic and biliary haemorrhage, and its earlier appearance and faster development in the poorer-fed group was a refelection of the earlier onset of these changes in association with a faster rate of fluke migration. The ultimate degree of anaemia was not related to the severity of biliary haemorrhage, but rather to the animals' erythropoietic capacity. This was substantially lower in the sheep maintained on the poorer diet, which unlike their better-fed counterparts, became iron deficient by virtue of their inability to replace from the diet iron lost in the faeces as a result of haemorrhage. It was concluded that this difference was primarily a reflection of the better appetite and hence iron intake of the supplemented sheep, but differences in the efficiency of dietary iron utilization, possibly related to protein intake, may also have been involved.In a further experiment involving sheep infected with 600 metacercariae, there was no evidence of haemodilution. When provided with a diet of high protein and iron content, these animals were able to maintain constant, albeit reduced PCV values in the face of substantial biliary haemorrhage. However, when switched to an inferior diet, the same degree of haemorrhage produced a sharp fall in PCV, suggesting that erythropoiesis was adversely affected by reduced protein and iron intake.     

Ontogenesis of the reticulum with special reference to neuroendocrine and glial cells: a comparative analysis of the merino sheep and iberian red deer

The present study was designed to compare the differences in the ontogenesis of the reticulum in sheep (domestic ruminant) and deer (wild ruminant). A total of 50 embryos and foetuses Merino sheep and 50 Iberian deer were used, from the first pre‐natal life until birth. The appearance of the reticulum from the primitive gastric tube was earlier in the sheep (22% gestation, 33 days) than in the deer (25% gestation, 66 days). In both cases, it displayed a primitive epithelium of a stratified, cylindrical, non‐ciliary type. At around 48% gestation in the sheep (72 days) and 36% (97 days) in the deer, the reticulum was configured of four clearly differentiated layers: mucosa (with epithelial layer and lamina propria), submucosa, tunica muscularis and serosa. The stratification of the epithelial layer was accompanied by modifications in its structure with the appearance of the primitive reticular ribs. The primary ribs began to be formed first in the deer, at 117 days of pre‐natal life (40% gestation) and later in the sheep (79 days, 53% gestation). The differentiation of the corneum papillae in the primary ribs coincided with the appearance of secondary reticular ribs. These structures began to be formed first in the deer, at 142 days of pre‐natal life (51% gestation) and later in the sheep (83 days, 55% gestation). The presence of neuroendocrine cells (non‐neuronal enolase‐positive cells) in the reticular mucosa was not detected until 97 days (36% gestation) in deer and 81 days (54% gestation) in sheep. The presence of glial cells (GFAP‐positive cells) occurred at around 142 days (51% gestation) in deer and at 112 days (75% gestation) in sheep. In conclusion, the presence of neuroendocrine and glial cells was detected in deer at earlier stages than sheep.     

Isolation and Culture of Ovine and Bubaline Small and Large Pre-antral Follicles: Effect of Cyclicity and Presence of a Dominant Follicle

Studies were conducted to examine the effects of the cyclicity and the presence of a dominant follicle (DF) in ovary on the recovery and in vitro growth of pre-antral follicles (PFs) in sheep and buffalo. Small pre-antral follicles (SPFs, 100–250 μm) and large pre-antral follicles (LPFs, 250–450 μm) were isolated from slaughterhouse ovaries in the breeding seasons by a mechanical and enzymatic method. The sheep and buffalo PFs were cultured in vitro for 6 and 15 days, respectively, and examined for their growth, survival and antrum formation rates and growth rates of oocytes in cultured pre-antral follicles. The follicles of the sheep and buffalo were recovered and cultured simultaneously within replicates. The recovery rates (number per ovary) of both SPFs and LPFs were significantly (p < 0.05) higher in cyclic ewes (SPFs: 22.0 ± 3.3 vs 12.1 ± 2.6 and LPFs: 16.0 ± 3.6 vs 9.2 ± 1.8) and buffaloes (SPFs: 9.2 ± 1.3 vs 4.1 ± 1.0 and LPFs: 10.3 ± 2.7 vs 5.4 ± 0.7) compared with those recovered from acyclic ones. Presence of a DF in ovary significantly (p < 0.05) reduced the recovery rates of LPFs in ewes (9.06 ± 2.7 vs 16.4 ± 3.8) but had no effect in buffalo. Cyclicity of animals or follicular dominance had no effects on in vitro growth, survival and antrum formation rates and growth rates of oocytes in cultured PFs of SPFs and LPFs in both sheep and buffalo. The in vitro growth, survival and antrum formation rates of LPFs and growth rates of oocytes in cultured LPFs were significantly (p < 0.05) higher than those observed in SPFs in both sheep and buffalo. The overall recovery and growth rates of the PFs were lower in buffaloes compared with ewes.     

Effects on animal performance and sward composition of mixed and sequential grazing of permanent pasture by cattle and sheep

Previous experiments have shown that mixed or conjoint grazing, when two or more animal species are grazed together, can lead to improved performance of one or more of the species and a higher total output per unit area. Sequential grazing systems, when different animal species graze an area in succession, also have the potential to improve productivity. This experiment directly compared these two approaches for integrating the grazing of cattle and sheep when pastured on improved permanent pasture. Four treatments were compared: 1) sheep only from May to October (S/S); 2) cattle only from May to July followed by sheep only from August to October (C/S); 3) cattle and sheep from May to July, sheep only for the rest of the growing season (C + S/S); and 4) cattle and sheep from May to October (C + S/C + S). Each treatment was replicated three times. From May until weaning at the end of July the plots were grazed by steers and ewes and lambs, and from weaning until October by steers and lambs. Sward heights were maintained at 6 cm using a “put and take” stocking system. Animal performance and sward composition data were collected during three growing seasons, 2001–2003. During the pre-weaning period lambs grazing plots which were grazed only by sheep had significantly poorer growth rates than those grazing plots where there was mixed grazing. Lambs grazing the sheep only plots also had lower liveweight gain during the post-weaning period, with the highest growth rates being recorded on the C + S/C + S treatment. Carrying capacity and total liveweight gain per unit area post-weaning were also consistently higher for the C + S/C + S treatment, while carrying capacity pre-weaning was highest for the C/S treatment. Measurements of clover content in the grazed horizon and botanical separation of material from quadrat cuts indicated that even under relatively controlled conditions choice of grazing system can influence sward composition. However, there was no clear link between any single sward change and the growth of the animals, indicating that the improved performance of cattle and sheep under mixed grazing is the result of a combination of factors, rather than a response to a particular sward parameter.     

Pharmacokinetics of ivermectin in sheep following pretreatment with Escherichia coli endotoxin

The comparative pharmacokinetics of ivermectin (IVM), between healthy and in Escherichia coli lipopolysaccharides (LPS) injected sheep, was investigated after an intravenous (IV) administration of a single dose of 0.2 mg/kg. Ten Suffolk Down sheep, 55 ± 3.3 kg, were distributed in two experimental groups: Group 1 (LPS): treated with three doses of 1 μg LPS/kg bw at ?24, ?16, and ?0.75 hr before IVM; group 2 (Control): treated with saline solution (SS). An IV dose of 0.2 mg IVM/kg was administered 45 min after the last injection of LPS or SS. Plasma concentrations of IVM were determined by liquid chromatography. Pharmacokinetic parameters were calculated based on non‐compartmental modeling. In healthy sheep, the values of the pharmacokinetic parameters were as follows: elimination half‐life (2.85 days), mean residence time (MRT) (2.27 days), area under the plasma concentration curve over time (AUC, 117.4 ng day^?1 ml^?1), volume of distribution (875.6 ml/kg), and clearance (187.1 ml/day). No statistically significant differences were observed when compared with the results obtained from the group of sheep treated with LPS. It is concluded that the acute inflammatory response (AIR) induced by the intravenous administration of E. coli LPS in adult sheep produced no changes in plasma concentrations or in the pharmacokinetic behavior of IVM, when it is administered intravenously at therapeutic doses.     

Strategic use of crutching and dicyclanil to protect unmulesed sheep against breech strike

Objective   To test strategies for the application of dicyclanil and mid-season crutching to maximise protection of unmulesed sheep against breech strike.
Procedure   Three hundred and eighty unmulesed Merino weaners were randomly allocated to four groups either left untreated or treated by different strategies with 50 g/L dicyclanil. Treatments included breech treatment alone and breech plus body treatment, with two application times, immediately after shearing and 6 weeks after crutching or shearing. To assess protection, larval implants with newly hatched Lucilia cuprina larvae were applied to 10 different sheep from each group at 3, 4, 5 and 6 months after crutching and shearing and assessed for the development of strike at 48 hours. The concentration of dicyclanil was measured in wool samples clipped from the breeches of the test sheep.
Results   All dicyclanil treatments gave significant reduction in strike in comparison to controls up until 4 months after crutching but protection in the sheep treated immediately after shearing had waned at 5 months. Treating at 6 weeks after crutching provided significant reduction ( P < 0.05) in strike for 6 months. Results for strike incidence immediately after shearing and concentration of dicyclanil in the breech wool also suggested improvements in protection by delaying treatment for 6 weeks.
Conclusion   In most environments it should be possible to protect unmulesed sheep against breech strike with a carefully planned integrated control program incorporating strategically timed crutching, shearing and dicyclanil application. Delaying treatment with dicyclanil to at least 6 weeks after shearing or crutching increased the protection provided in comparison to treatment immediately after shearing.     

Early Breeding and Pregnancy Diagnosis in Syrian Awassi Sheep Yearlings

Contents
Fifty-nine female yearlings of local Awassi sheep were randomly divided into two groups. Animals in group T (treated) were fitted with intravaginal sponges containing 60 mg of medroxyprogesterone acetate for 14 days followed by 400 IU of pregnant mare's serum gonadotrophin (PMSG) at sponge withdrawal, whereas group C (control) received no treatment. Oestrus rate was 92.7 and 11.2% for groups T and C, respectively. Lambing rate was 78 and 5.6% for groups T and C, respectively. Twinning rate was 31.3% in group T compared to zero in group C. Average birth weight for single born lambs (4.7 ± 0.6 kg) was significantly (p < 0.05) higher than twin born lambs (3.0 ± 0.5 kg) in group T. The average concentration of blood progesterone collected between days 17–19 after mating was 19.30 nmol/l and the accuracy of early pregnancy diagnosis was 100%. It was concluded that, it is possible to induce synchronized oestrus, and to increase the twinning rate in Syrian Awassi sheep yearlings outside the breeding season, using intravaginal sponges and PMSG. In addition, early pregnancy diagnosis could be successfully determined in female Awassi sheep yearlings between days 17–19 after mating.     

地果的光能利用特性及叶面积指数对土壤营养的响应

研究了地果Ficus tikoua的光能利用特点和地果叶面积指数对土壤营养的响应。结果表明:1)地果光饱和点为1 124 μmol/(m2·s),光补偿点接近0,因此地果具有较宽的光强适应范围;2)地果水分利用效率为1.45～15.8,在光合有效辐射达500 μmol/（m2·s）时达到最大;3)地果斑块的叶面积指数处于0.662.67 m2/m2,平均为1.51 m2/m2,与其它园林绿化植物相比较低;4)叶面积指数能对土壤营养中的水分和全N含量变化作出响应,对有机C、有机P、有机K的含量变化不敏感。     

Serological analysis of Chlamydophila abortus in Australian sheep and implications for the rejection of breeder sheep for export

Objective   To examine the incidence of positive results in a complement fixation test (CFT) and enzyme-linked immunosorbent assay (ELISA) for Chlamydophila abortus in Australian sheep and how this incidence differs with state of origin, age, sex, breed and property. To examine the consequences in relation to rejection of breeder sheep for export.
Design   Collection of blood samples from 891 sheep on 109 properties in southern Australia. All samples had a unique, coded property identification.
Procedure   The samples were tested using the Institut Pourquier Chlamydophila abortus antibody ELISA (rELISA) and a CFT. Residual maximum likelihood analyses of the sample to positive ratio of the corrected optical density for the rELISA and generalised linear mixed model analyses of the CFT outcomes were carried out.
Results   The sample to positive ratio of the corrected optical density values of the rELISA did not differ between sex, age, breed or state of origin, but differed greatly between properties. The CFT outcome did not differ between age, breed or state of origin, but differed greatly between properties and was more often positive with rams than with ewes.
Conclusion   Positive outcomes to C. abortus antibody tests are very common in Australia. Rams have a particularly high incidence of positive results with the CFT. Rejection of sheep and property consignments is likely to be very common with all tests and situations examined except for the CFT (at 1:32 dilution) in ewes.     

High‐milking sheep have a lower ovulation rate and tend to yield fewer embryos in response to superovulation and intrauterine artificial insemination

Antagonistic relationship between milk yield and reproduction is reported in several livestock species. This study aimed to investigate whether genetic merit for milk production in dairy sheep affects responses to superovulation, embryo yield and quality. A total of 21 cross‐bred Sarda x Lacaune ewes homogeneous for age, parity and stage of lactation were included. The ewes were stratified as high‐producing or low‐producing based on their genetic merit for milk production estimated by a pentatrait repeatability animal model. Oestrus was synchronized using an intravaginal progesterone pessary inserted on Day 0 and removed on Day 14. Superovulatory treatment consisted of 350 I.U. of porcine FSH administered in eight decreasing intramuscular doses every 12 hr with a total dose of 10 ml of solution starting 12 days after insertion of sponges. Laparoscopic artificial insemination (AI) was performed 48 hr after pessary removal. Surgical embryo recovery was performed at Day 8 after pessary removal. Correlation between breeding value for milk production and the number of corpora lutea (CL) was significantly different from zero (?0.49). High‐producing ewes had a lower number of CL than low‐producing counterparts (7.6 ± 2.50 vs 12.1 ± 5.16 respectively; p < .02). Furthermore, there was a tendency for high‐producing ewes to yield fewer embryos than low‐producing females (5.3 ± 3.46 vs 9.18 ± 5.11; p = .09). No differences were observed between ewes in both genetic groups with regard to the number of embryos of grades 1, 2 and 3. To our knowledge, this is the first report highlighting an antagonism between genetic merit for milk production and the ability to produce embryos in sheep. These results deserve to be considered in sheep breeding programmes.     

Paramphistomiasis in sheep

Extract

Paramphistome flukes are well known parasites of New Zealand cattle, and a study of their life cycle has been made by Jonathan. Records of the same parasite in sheep are rare, and the purpose of this note is to record the fact that the parasite does occur in sheep and that it has given rise to what is considered to be a pathogenic infestation in young ewes. The outbreak occurred in a flock of 250 ewes, of which 35 died showing symptoms of diarrhoea and anaemia.     

Effect of Eperythrozoon ovis on the lysis of sheep erythrocytes in the complement fixation test

When erythrocytes from sheep experimentally infected with Eperythrozoon ovis were used in the titration of reagents for a standardised complement fixation test, increased amounts of both haemolysin and complement were required for erythrocyte lysis compared with preinfection titrations. The haemolysin requirement increased by up to 125% at 55 days post-infection and complement requirement increased by up to 40% at 40 days post-infection. These changes appeared to correlate with the development of a macrocytic anaemia in affected sheep rather than E. ovis parasitaemia. The results emphasise the need to carefully monitor the haematological parameters of sheep used as sources of erythrocytes for the complement fixation test.     

Pharmacokinetics of monepantel and its sulfone metabolite, monepantel sulfone, after intravenous and oral administration in sheep

The pharmacokinetic properties of the developmental Amino-Acetonitrile Derivative (AAD), monepantel and its sulfone metabolite, monepantel sulfone were investigated in sheep following intravenous (i.v.) and oral administrations. The sulfone metabolite was rapidly formed and predominated over monepantel 4 h after dosing, irrespective of the route of administration. The steady-state volume of distribution, total body clearance and mean residence time of monepantel were 7.4 L/kg, 1.49 L/(kg·h) and 4.9 h, respectively and 31.2 L/kg, 0.28 L/(kg·h) and 111 h, respectively for monepantel sulfone. The overall bioavailability of monepantel was 31%, but it was demonstrated that approximately the same amount of monepantel sulfone was produced whether monepantel was given intravenously or orally ( AUC _(0–∞) oral/ AUC _(0–∞) i.v. of 94% for monepantel sulfone), making oral administration a very efficient route of administration for monepantel in terms of the amount of sulfone metabolite generated. Because monepantel sulfone is the main chemical entity present in sheep blood after monepantel administration and because it is also an active metabolite, its pharmacokinetic properties are of primary importance for the interpretation of future residue and efficacy studies. Overall, these pharmacokinetic data aid in the evaluation of monepantel as an oral anthelmintic in sheep.