Development of a toxin-binding agent as a treatment for tunicaminyluracil toxicity: protection against tunicamycin poisoning of sheep

Objective To assess the ability of certain derivatives of beta-cyclodextrin to treat sheep affected by tunicaminyluracil toxicity, using tunicamycin poisoning as a model system.
Design Controlled treatment trial.
Animals One hundred and sixty Merino wethers were used in the studies.
Procedure Groups of sheep were experimentally poisoned with tunicamycin. Derivatives of beta-cyclodextrin, with or without magnesium sulphate and magnesium gluconate, were administered to treatment groups daily for 2 to 3 days. Treatment groups were compared with untreated groups in terms of survival.
Results A significant increase in survival was observed following treatment of tunicamycin-affected sheep with hydroxypropyl-beta-cyclodextrin (HPb -CD) and magnesium sulphate in solution (P < 0.05). In subsequent trials, formula tion of the cyclodextrin in the form of a magnesium gluconate gel suspension demonstrated significant protection (P < 0.01) and was equally as effective as the cyclodextrin in solution, but required half the frequency of administration, even when the treatment was not commenced until 24 h after the final toxin dose. Beta-cyclodextrin-epichlorohydrin copolymer also improved the survival rate. After toxin administration, the sheep lost significantly less weight if treatment with HPb -CD was commenced early (P < 0.001).
Conclusion Protection studies using these two beta-cyclodextrin derivatives suggest that they may be effective in increasing the survival of sheep poisoned by tunicamycin and warrant further testing in field outbreaks of annual ryegrass toxicity.     

Follicular,Oocyte and Embryo Features Related to Metabolic Status in Primiparous Lactating does Fed with High‐Fibre Rearing Diets

Fertility of primiparous lactating does in the early postpartum (pp) period is very low mainly due to pronounced deficient energy intake, influencing oocyte and embryo developmental competence. The hypothesis used in this work was that high‐lignin fibre diet supplied during the rearing period could increase feed intake and, consequently, improve the reproductive physiology and metabolic status of primiparous does in the early pp period. Diets with high‐lignin [HL: 15.8% dry matter (DM)] or standard‐lignin content (SL: 4.9% DM) were supplied until parturition time. No diet effects in serum oestradiol, progesterone concentrations and follicle categories were found in the histological study. Metaphase II rate of in vitro‐matured oocytes was significantly higher in the SL vs the HL group (p < 0.001). Cytoplasmically degenerated oocytes (in terms of abnormal distribution of cortical granules) and follicular atresia rate were significantly lower in the SL group than in the HL group (p < 0.05 and p < 0.005 respectively). In addition, HL‐fed does showed lower number of viable embryos and higher rate of retarded in vivo‐recovered embryos compared with the SL group (p < 0.05). Neither in vitro embryo development of viable embryos nor conception rate was significantly different between groups. Feed intake increased during the first pregnancy in the HL group (p < 0.05), but not during early lactation. Serum protein, non‐esterified fatty acid and leptin concentrations, as well as estimated body composition were similar in does fed with both diets. In conclusion, the enhancement of reproductive management by using highly lignified products in rearing diets does not seem to report physiological reproductive benefits affecting oocyte maturation rate and embryo viability in primiparous lactating does.     

Hydroureteronephrosis and fetal mummification secondary to uterine torsion in a Merino ewe

A 6 year old pluriparous Merino ewe was presented for investigation of a large intra-abdominal mass. Post-mortem examination revealed a 360° clockwise uterine torsion was present with a mummifying fetus. The torsion involved the left ureter resulting in a severe hydroureteronephrosis. Uterine torsion is uncommon in the ewe, occurring in less than 0.1% of pregnancies in one report (Mahmoud et al. Livest Res Rural Dev 2018;30), but cases are likely to be undiagnosed, particularly under the extensive management conditions typical of Australia. The chronicity of the condition in this ewe would support this statement. To the authors' knowledge this is the first reported case of hydroureteronephrosis secondary to uterine torsion in any species.     

Acute hindlimb paresis caused by extension of a peripheral nerve sheath tumour into the spinal canal of a horse

A 10-year-old Quarter Horse gelding presented for a large, slowly growing mass in the right thoracic region caudal to the withers (approximately at the level of thoracic vertebrae 10 to 16). The mass was surgically removed, the horse returned to normal riding activity, and no external regrowth was observed. Two years after surgery, the horse developed progressive signs of hindlimb weakness, ataxia and adopting a dog-sitting stance. Post-mortem examination confirmed spinal canal infiltration and spinal cord compression (at the level of the 12th thoracic vertebra) by a similar soft tissue sarcoma as diagnosed previously. Immunohistochemistry confirmed the tumour as a peripheral nerve sheath tumour (PNST) likely originating from the twelfth thoracic spinal nerve. This report demonstrates that with incomplete tumour resection, local recurrence and extension of a PNST into the central nervous system can occur even years after initial tumour removal. Immunohistochemistry to differentiate the type of soft tissue sarcoma in cases with close association to the nervous system may prove beneficial to anticipate this uncommon complication. Early surgical resection with adjunctive therapies should be considered in these cases.     

Using sodium molybdate to treat chronic copper toxicity in dairy cows: A practical approach

Abstract

CASE HISTORY: A Jersey herd of 350 cows and 70 heifers located in the Taranaki region of New Zealand ceased milking in June 2011. Ten cows died during the subsequent 14 days. For at least 9 months, the cows had received palm kernel expeller (PKE) and molasses supplements. Additional Cu supplementation was provided through the water system. Total Cu intake was calculated to be 400?mg/day/cow.

CLINICAL AND PATHOLOGICAL FINDINGS: Half of the cows died suddenly while others presented with anorexia, depression and ataxia, which progressed to recumbency and death after 1 to 3 days. Clinical signs were mild dehydration, cyanosis and firm faeces which were covered in dark blood. Mean concentrations of Cu in liver and kidney in three of the dead cows were 3,900 and 440?µmol/kg fresh weight (FW), respectively. Haemorrhages were observed throughout the alimentary tracts and in muscles, and there were ecchymotic haemorrhages on the epi- and endocardia. The livers were swollen and the gall bladder walls were inflamed.

DIAGNOSIS: High concentrations of Cu in the liver and kidney are characteristic findings of chronic Cu toxicity.

TREATMENT: The remaining herd was fed 200?mg Mo, as sodium molybdate, per cow per day and all Cu supplements were removed including those provided by the water supply. This reduced mean concentrations of Cu in liver from 3,100 to 1,320?µmol/kg FW within 26 days in the five live animals that were biopsied. There were no further deaths.

CLINICAL RELEVANCE: In dairy herds where excessive Cu intakes have resulted in high liver Cu concentrations and caused chronic Cu toxicity, the removal of all Cu supplements and provision of high intakes of Mo (200?mg/cow/day) can markedly reduce liver Cu stores within 4 weeks.     

Confirmation of resistance to ivermectin by Cooperia curticei in sheep

AIM: To investigate the occurrence of resistance to a full dose of oral ivermectin by Cooperia curticei in sheep.

METHODS: Twelve lambs on a sheep and cattle property in the North Island of New Zealand were randomly allocated to one of two equal-sized groups. One group was treated orally with a single dose of ivermectin at the manufacturer's recommended dose rate of 0.2 mg/kg, while the other remained as an untreated control. Worm counts were carried out post mortem on the abomasa and small intestines of all animals in both groups 7 days after treatment.

RESULTS: While treatment with ivermectin reduced the numbers of all other worm genera to almost zero, those of Ostertagia (= Telodorsagia) circumcincta and C. curticei were reduced by only 37% and 19%, respectively.

CONCLUSIONS: These results provide clear evidence of resistance to ivermectin by O. circumcincta and C. curticei. They also appear to represent the first record of macrocylic lactone (ML) resistance in C. curticei in sheep in New Zealand or elsewhere.     

In Vitro Development of Marmoset Monkey Oocytes by Pre-antral Follicle Culture

A technique for in vitro maturation of oocytes from small ovarian follicles of marmoset monkeys (Callithrix jacchus) has been developed. We employed a two‐step culture system for primary follicles (45–85 μm) and a one‐step culture technique for secondary follicles (>85 μm). The two‐step technique started with the culture of stromal tissue fragments for 2 days. Thereafter, mechanically isolated follicles were transferred to a culture system where they attached to the culture surface and grew for up to a further 12 days. Significant growth of the small follicles and their oocytes was only achieved with gonadotrophins in the medium. Oocytes with a mean diameter of 39 μm from follicles <85 μm reached a mean diameter of 90 μm by the end of the two‐step culture. After in vitro maturation, 19% of oocytes from these follicles had progressed to the germinal vesicle breakdown (GVBD). Follicles between 85 and 170 μm in diameter were isolated from the stroma and placed directly in the culture. Oocytes from these follicles had a mean diameter of 64 μm. The maximum size the oocytes reached in culture was related to the age of the females (pre‐pubertal females: 102 ± 1.3 μm; adults: 96 ± 1.4 μm). Twenty‐seven per cent of oocytes from pre‐pubertal ovaries achieved GVBD and nearly two‐thirds of these progressed to polar body stage. From adult ovaries, only 12% progressed to GVBD and one‐third of these to polar body stage. It is possible to develop mature oocytes in vitro from marmoset secondary pre‐antral follicles (>85 μm). From primary follicles, although near full size oocytes were developed, maturation capacity was incomplete.     

Intravenous anaesthesia using detomidine, ketamine and guaiphenesin for laparotomy in pregnant pony mares

Objective To characterize intravenous anaesthesia with detomidine, ketamine and guaiphenesin in pregnant ponies. Animals Twelve pony mares, at 260–320 days gestation undergoing abdominal surgery to implant fetal and maternal vascular catheters. Materials and methods Pre‐anaesthetic medication with intravenous (IV) acepromazine (30 µg kg^?1), butorphanol (20 µg kg^?1) and detomidine (10 µg kg^?1) preceded induction of anaesthesia with detomidine (10 µg kg^?1) and ketamine (2 mg kg^?1) IV Maternal arterial blood pressure was measured directly throughout anaesthesia and arterial blood samples were taken at 20‐minute intervals for measurement of blood gases and plasma concentrations of cortisol, glucose and lactate. Anaesthesia was maintained with an IV infusion of detomidine (0.04 mg mL^?1), ketamine (4 mg mL^?1) and guaiphenesin (100 mg mL^?1) (DKG) for 140 minutes. Oxygen was supplied by intermittent positive pressure ventilation (IPPV) adjusted to maintain PaCO₂ between 5.0 and 6.0 kPa (38 and 45 mm Hg), while PaO₂ was kept close to 20.0 kPa (150 mm Hg) by adding nitrous oxide. Simultaneous fetal and maternal blood samples were withdrawn at 90 minutes. Recovery quality was assessed. Results DKG was infused at 0.67 ± 0.17 mL kg^?1 hour^?1 for 1 hour then reduced, reaching 0.28 ± 0.14 mL kg^?1 hour^?1 at 140 minutes. Arterial blood gas values and pH remained within intended limits. During anaesthesia there was no change in heart rate, but arterial blood pressure decreased by 10%. Plasma glucose and lactate increased (10‐fold and 2‐fold, respectively) and cortisol decreased by 50% during anaesthesia. Fetal umbilical venous pH, PO₂ and PCO₂ were 7.34 ± 0.06, 5.8 ± 0.9 kPa (44 ± 7 mm Hg) and 6.7 ± 0.8 kPa (50 ± 6 mm Hg); and fetal arterial pH, PO₂ and PCO₂ were 7.29 ± 0.06, 4.0 ± 0.7 kPa (30 ± 5 mm Hg) and 7.8 ± 1.7 kPa (59 ± 13 mm Hg), respectively. Surgical conditions were good but four ponies required a single additional dose of ketamine. Ponies took 60 ± 28 minutes to stand and recovery was good. Conclusions and clinical relevance Anaesthesia produced with DKG was smooth while cardiovascular function in mare and fetus was well preserved. This indicates that DKG infusion is suitable for maintenance of anaesthesia in pregnant equidae.