Experimental combined aflatoxin B1 and ochratoxin A intoxication in pigs

Twenty-one pigs weighing approximately 18 kg were placed in 7 groups of 3 and given diets containing respectively aflatoxin B1 alone at 0.375 and 0.0750 mg/kg, ochratoxin A alone at 1 and 2 mg/kg, 0.375 mg/kg of aflatoxin B1 plus 1 mg/kg of ochratoxin A and 0.750 mg/kg aflatoxin B1 and 2 mg/kg of ochratoxin A. The remaining group served as untreated control. At the respective dose levels, pigs receiving similar doses of ochratoxin A alone or in combination with aflatoxin B1, were similarly affected, the clinical effects of aflatoxin having been mostly obscured by those due to ochratoxin A. Mild degenerative hepatic changes typical of aflatoxicosis were observed in pigs fed this toxin alone or in combination with ochratoxin A. In kidneys of pigs fed diet containing 1 and 2 mg of ochratoxin A alone changes included interstitial fibrosis of the vortex and dystrophy and degeneration of the tubular epithelium. Similar lesions but less pronounced fibrosis were found in kidneys of pigs receiving both toxins. The respective lower dose levels of mycotoxins selected were judged to be about the no-effect levels for each dosed separately under the conditions of the trial. Such levels have been found not infrequently on mould affected grain and stock foods. The result highlights the difficulties that may be experienced in the recognition of such multimycotoxicoses as they are likely to occur in the field and indicate the need for toxicological analysis as well as pathological investigation in establishing a diagnosis.     

VITAMIN B12 AND COPPER SUPPLEMENTATION IN BEEF CALVES

SUMMARY Bodyweight responses to subcutaneous injections of vitamin B₁₂ and copper were investigated using Hereford calves in the southeast of South Australia, an area known to produce cobalt and copper deficient sheep. Calves were allocated to one of four groups: control; copper; vitamin B₁₂; copper plus vitamin B₁₂. Responses in bodyweight gain to vitamin B₁₂, and to copper were obtained during the trial of one year. The results of biochemical analysis of blood, hair and faeces from calves and of dam's milk are reported. It is concluded that calves raised on cobalt-deficient pastures will require cobalt or vitamin B₁₂ supplementation prior to weaning.     

Vitamin B12 responses to cobalt pellets in beef cows

Objective To assess the effectiveness of cobalt pellets in maintaining adequate vitamin B₁₂ in beef cows on pasture of low cobalt content.
Design A field experiment in a herd grazing cobalt deficient pasture.
Animals Mature Murray Grey cows.
Procedure Cows were given a single oral dose of 0, 1, 2 or 4 cobalt pellets (30 g pellets containing 30% by weight cobaltic oxide) with a selenium pellet and a grub screw. Samples of blood, liver, faeces and milk for chemical analyses were collected at intervals over a period of 2 years after treatment.
Results A single cobalt pellet raised liver vitamin B₁₂ concentration of cows above that of untreated cows for at least 28 weeks, and 2 or 4 pellets for 57 weeks. Plasma vitamin B₁₂ concentration was an unreliable indicator of the effectiveness of cobalt pellet therapy. Milk vitamin B₁₂ and faecal cobalt concentrations increased in response to cobalt pellet therapy.
Conclusion These studies show that one cobalt pellet will prevent vitamin B₁₂ inadequacy in beef cows for between 28 and 57 weeks; two or four pellets will prevent inadequacy for 57 to 75 weeks. Milk vitamin B₁₂ concentration may be a useful indicator of the effectiveness of cobalt pellets in increasing the vitamin B₁₂ supply in lactating cows.     

The effect of prostaglandin E1 on motility of the equine gut

Prostaglandin E1 was infused intravenously (25, 50 and 75 ng/kg/min) in three ponies. Changes in gastrointestinal mechanical and electrical activity were recorded from chronically implanted strain-gauge force transducers and electrodes. Dose-dependent responses were obtained: there were significant decreases in electrical spiking activity in the stomach, left large colon and small colon, with a corresponding decrease of activity in the left dorsal colon mechanogram. The small intestine was also affected, showing a decrease in both contraction rate and amplitude, which was more marked in the proximal jejunum than in the ileum. There was an association between these changes in gastrointestinal activity and the presence of discomfort and diminished gut sounds.     

The effect of xylazine on plasma thromboxane B2 concentration in sheep

α₂-adrenoceptor agonist drugs can cause respiratory changes leading to a short period of hypoxaemia in sheep. It has been suggested that this is due to transient platelet aggregation and pulmonary microembolism. If platelet aggregation were to follow platelet activation in response to the administration of α₂ agonists, plasma thromboxane levels would be expected to rise. This study was carried out to measure plasma thromboxane B₂ concentrations before and after the intravenous administration of the α₂-agonist drug xylazine at a dose of 0.1 mg/kg. It was found that the plasma thromboxane concentration rose by 320% and, furthermore, the rise was prevented by the prior administration of atipamezole hydrochloride (0.125 mg/kg), an α₂-adrenoceptor antagonist.     

Serum and red cell folate and serum vitamin B12 levels in horses

SUMMARY Vitamin B12 and folate concentrations were determined by radioimmunoassay in groups of horses in Queensland. Highest serum vitamin B¹² levels were found in supplemented performance horses. These, together with pastured horses that included pregnant and lactating mares, had significantly greater serum folate activity than permanently stabled animals. The range of red cell folate concentrations was much narrower in horses in training than from any other group. Red cell folate may be a better indicator of a horse's folate status than the serum folate value. Vitamin B¹² and folate concentrations were highest in spring and summer. Small intestinal dysfunction in 2 horses was not associated with vitamin B¹² or folate malabsorption. Serum folate levels returned to normal 24 h after intramuscular injections of 75 to 150 mg folic acid, whereas serum vitamin B¹² values remained elevated for at least one week following injections of 8 to 10 mg to non-supplemented horses.     

Sex-related responses to vitamin B12 and trace element supplementation in prime lambs

Bodyweight, plasma vitamin B12 and blood selenium concentrations were monitored in prime lambs given different forms of supplementation at 2 sites in separate years. At the first site treatment groups comprised control, vitamin B12 injection, selenium given orally and a combination of vitamin B12 and selenium. At the second site cobalt and selenium supplied in a glass bullet was compared with an untreated group. Significant sex-related responses were observed to treatment in terms of bodyweight and at site 2 in plasma vitamin B12 concentrations. A marked bodyweight response to glass bullet supplementation was observed in castrated male lambs but not in ewe lambs. These studies show that sex differences should be considered when investigating trace element deficiencies.     

Alpha-adrenoceptors in equine digital veins: Evidence for the presence of both alpha1 and alpha2-receptors mediating vasoconstriction

Rings of equine digital vein examined under conditions of isometric tension recording constricted to alpha-adrenoceptor agonists with an order of potency of 5-bromo-6-[2-imidazolin-2-yl-amino]-quinoxaline bitartrate (UK 14304) = noradrenaline > 6-Allyl-2-amino-5,6,7,8-tetrahydro-4H-thiazolo-(4,5-d) azepine (BHT-920) > phenylephrine > dopamine > methoxamine. The maximum force generated was greatest for the non-selective agonist noradrenaline and lowest for the alpha₂-selective agonist BHT-920 with the other agonists between these two extremes. Selective inactivation of alpha₁-adrenoceptors (achieved by treating yohimbine-protected tissues with phenoxybenzamine) reduced the maximum responses of all agonists, the EC₅₀ values of UK 14304, BHT-920 and noradrenaline and increased the EC₅₀ values of phenylephrine and methoxamine. Prazosin (30 n M ) had no inhibitory effect on responses to low concentrations of BHT-920 and UK 14304 and caused competitive inhibition of responses to phenylephrine and noradrenaline giving pK_b values of 8.49 ± 0.18 and 8.23 ± 0.14, respectively. Yohimbine (0.1 μ M ) caused significant competitive inhibition of responses to BHT-920 and noradrenaline with calculated pK_b values of 8.43 ± 0.11 for BHT-920 and 7.43 ± 0.31 for noradrenaline and non-competitive inhibition of responses to UK 14304. 2-[2-methoxy-1,4-benzodioxan-2-yl]-2-imidazoline (RX 821002; 10 n M ) caused competitive inhibition of responses to BHT-920 (pK_b 9.04 ± 0.27) and dopamine (pK_b 8.2 ± 0.2). These data indicate that equine digital veins possess both post-synaptic alpha₁ and alpha₂-adrenoceptors.     

Correlation between the pharmacokinetics of oxindanac and inhibition of serum thromboxane B2 in calves

The pharmacokinetics and pharmacodynamics of the non-steroidal antiinflammatory drug, oxindanac, were assessed simultaneously in calves after intravenous (i.v.) administration at dose rates of 0.5, 1, 2, 4 and 8 mg/kg. Plasma pharmacokinetic data were fitted to either two or three compartment open models. The elimination t ¹/₂ was constant in the dose range 0.5 to 4 mg/kg (20.2–22.8 h) and shorter at 8 mg/kg (14.7 h). The pharmacodynamics of oxindanac were assessed by its inhibition of serum TxB₂, an index of platelet cyclo-oxygenase activity. Plots of total plasma oxindanac concentration vs. inhibition of serum TxB₂ fitted in all cases a sigmoidal E_max equation. There were no significant differences in the estimates for ED ₅₀ (1.6-1.9 μg/ml), Hill constant (1.3-2.7) or Emax between the doses used in the in vivo studies or when blood was spiked with oxindanac in vitro. Plots of inhibition of serum TxB₂ vs. time were prepared from the pharmacokinetic model equations in each calf in combination with a single sigmoidal E_max plot generated in vitro. These data were not significantly different from the results produced in vivo. It is concluded that oxindanac causes reversible inhibition of platelet cyclo-oxygenase in calves. Its inhibition of serum TxB₂ can be predicted from total plasma drug concentration, as described by a multicompartmental model, and sigmoidal E_max enzyme kinetics. It was not necessary to take into account factors such as drug equilibration between plasma and its target site, free vs. total drug concentration or chirality. This simple model may be useful for predicting the pharmacodynamics of oxindanac in other species.     

Efficacy of avermectin B1a against microfilariae of Dirofilaria immitis

Avermectin B1a given at a dose level of 0.05 or 0.1 mg/kg of body weight caused rapid removal of Dirofilaria immitis microfilariae from the blood of dogs with heartworm infections. If the adult worms were also killed with an arsenical (melarsoprol), the removal of microfilariae was permanent.     

Studies of maternally-acquired antibodies in the foal to equine influenza A1 and A2, and equine rhinopneumonitis

Serum and colostrum were collected from 50 mares at parturition. Pre- and post-nursing serum samples were obtained from their foals. Bi-weekly serum samples were obtained from 25 of the foals for eight weeks. Hemagglutination-inhibiting (HAI) antibody titers to equine influenza viruses A₁ and A₂ (EIVA₁ and EIVA₂) and serum-neutralizing antibody titers to equine herpes virus 1 (EHV₁) were measured in serum and colostrum samples. IgG levels in serum and colostrum were determined.No antibody was detected in any foal's pre-nursing serum sample. Foal post-nursing antibody and IgG levels were equivalent to those measured in their dam's sera (EHVA₁ p=0.86; EHVA₂ p=0.54; EHV₁ p=0.91; IgG p=0.58). The half-life of maternally-acquired serum antibody in the foals was determined to be: EIVA₁=28.88 days (26.4 to 31.7 days); EIVA₂=29.1 days (26.7 to 32.1 days); EHV₁=31.0 days (28.1 to 34.8 days). Colostrum contained antibody and IgG at levels ranging from 2 to 8 times higher (4.3 average) than those detected in the mare's serum.     

Plasma concentrations of flunixin in the horse: its relationship to thromboxane B2 production

The effects of the intravenous (i.v.) administration of 1.1 mg/kg of flunixin meglumine on thromboxane B2 (TxB2) concentrations were studied in sedentary and 2-year-old horses in training. The baseline TxB2 serum concentrations generated during clotting were 2.89 +/- 0.81, 2.19 +/- 0.25 and 0.88 +/- 0.12 ng/ml for the 2-year-old Thoroughbreds in training, sedentary horses under 10 and over 10 years old, respectively. There was a significant difference in baseline TxB2 concentrations between older and younger horses (P less than 0.005). Significant reduction in TxB2 production from baseline were noted at 1 (P less than 0.01) and 4 h (P less than 0.01) but not at 8 h after flunixin administration. The percent reduction in serum TxB2 concentration at 1 h after the administration of flunixin was 68.6 +/- 7.3 and 45.2 +/- 6.8 for the training and sedentary horses, respectively; the differences were significant (P less than 0.04). Serum concentrations of TxB2 returned to baseline values by 12-16 h after flunixin administration. The results of this study indicate a difference in the TxB2 concentrations of older vs. younger horses and a difference in the suppression of TxB2 after the administration of flunixin in 2-year-old Thoroughbreds in training compared to sedentary horses. The results of this study suggest that the detection of low concentrations of flunixin in urine 24 h post-administration may not represent pharmacologic effective concentrations of flunixin in plasma.     

Efficacy of moxidectin and other anthelmintics against small strongyles in horses

Objective To compare the efficacy of moxidectin to ivermectin, oxibendazole and morantel against some gastrointestinal nematodes in horses.
Design Faecal egg count reduction after treatment.
Procedure A farm was selected where the population of small strongyles in horses was known to be resistant to oxibendazole. Horses were allocated to treatment groups based on faecal egg counts. After treatment, faecal samples were taken up to 109 days after treatment and faecal egg counts estimated. Faecal cultures were used to estimate the contribution of small and large strongyles to the faecal egg counts at each sampling.
Results Moxidectin (0.4 mg/kg) suppressed faecal egg counts for 109 days after treatment in most horses compared to 40 days with ivermectin (0.2 mg/kg), 13 days with morantel (9.4 mg/kg) and less than 13 days with oxibendazole (10 mg/kg). Most of the faecal egg count was attributable to small strongyles based on faecal culture, although Strongylus vulgaris was present in some samples in low numbers. Oxibendazole resistance in small strongyles was confirmed and a less than expected efficacy of morantel was also seen.
Conclusion Moxidectin was highly effective in reducing faecal egg counts after treatment for at least 12 weeks and up to 16 weeks in most horses. These horses were infected with a population of small strongyles known to be resistant to oxibendazole and possibly morantel. The duration of the reduction in faecal egg counts after treatment with moxidectin (0.4 mg/kg) was at least twice that of ivermectin (0.2 mg/kg) and greater than four times that for morantel and oxibendazole.     

Agreement of SpO2, SaO2 and ScO2 in anesthetized cynomolgus monkeys (Macaca fascicularis)

Objective To assess the agreement between three measurements of arterial oxygen saturation (SpO₂, SaO₂ and ScO₂) in anesthetized cynomolgus monkeys. Study Design Prospective study. Animals Eleven mature, male cynomolgus monkeys (Macaca fasicularis). Methods Monkeys were anesthetized with intramuscular ketamine followed by intravenous propofol. The trachea of each was intubated and the lungs ventilated. Arterial oxygen saturation was measured with a Nonin 8500 V pulse oximeter, using a lingual clip on the cheek. Arterial blood samples were taken from an indwelling catheter. Inspired oxygen concentration was varied from 12 to 20%, and 88 paired arterial blood samples and saturation measurements were taken. Arterial oxygen saturation in the blood samples was measured using a cooximeter. The saturation was also calculated from the arterial oxygen tension using the Adair equation. The results were compared using Bland and Altman's method. Results The pulse oximeter readings were 2.7% higher than that of the cooximeter, with a limit of agreement of ?3.9 to 9.3%. The pulse oximeter readings were 1.8% higher than the calculated saturation, with a limit of agreement of ?6.5% to 10.1%. The cooximeter readings were 0.9% lower than the calculated saturation, with a limit of agreement of ?5.6% to 3.8%. Conclusions The agreement between SpO₂ and other measurements of arterial oxygen saturation in this study is typical for this technique. The bias and limits of agreement are consistent with reports in other species. Clinical relevance The Nonin 8500 V is a useful pulse oximeter for clinical use in primates.     

Utilization of F1 information in estimating QTL effects in F2 crosses between outbred lines

Quantitative trait loci (QTL) analysis in designed experiments is investigated using a mixed model framework through the modification of segment mapping techniques. Allele effects are modelled in the F₁ generation allowing the estimation of additive substitution effects while accounting for QTL segregation within lines and differences in mean QTL effects between lines. The resulting approach is called F₁ segment mapping. Simulation is used to illustrate the method and its properties. F₁ segment mapping has advantages over F₂ segment mapping in the derivation of exact additive genetic covariances and in the computation time for variance component estimation.     

Neuronal-Visceral GM1 Gangliosidosis in Portuguese Water Dogs

Three female siblings in a litter of seven Portuguese Water dogs (PWDs) showed clinical signs of ataxia and/or lameness at 5 months of age. Signs of cerebellar dysfunction (intention tremors, ataxia, widebased stance, dysmetria, and/or nystagmus) and mild limb weakness developed rapidly. Results of hemograms (three dogs), blood chemistry profiles (two dogs), urinalyses (two dogs), electroencephalograms (two dogs), and radiographs of the limbs or pelvis (three dogs), vertebrae (two dogs), and skull (one dog) were unremarkable except for an absolute lymphocytosis in one dog. Routine cerebrospinal fluid (CSF) analyses were normal in all three dogs. However, the CSF creatine kinase concentration was elevated in the one dog in which it was measured. Mucopolysacchariduria was present in all three dogs. Due to the rapid progression of clinical signs and a poor prognosis, all three dogs were euthanatized between 6 and 7 months of age. Histopathologic and electron microscopic studies showed neuronal cytoplasmic inclusions, vacuolated hepatocytes, and vacuolated renal tubular epithelial cells, compatible with the diagnosis of a storage disease. Beta-galactosidase activities in leukocytes, serum, and brain homogenates were reduced when compared with that in normal dogs and the stored product was identified as GM1 ganglioside, confirming GM1 gangliosidosis.