Role of thiamine status in sulphur induced polioencephalomalacia in sheep.

The effects of excess dietary sulphur were studied in sheep supplemented and unsupplemented with thiamine. The diets contained either 0.19 per cent sulphur (LS) or 0.63 per cent sulphur (HS) in combinations with 14 mg kg-1 thiamine (LB1) or 243 mg kg-1 thiamine (HB1). A total of 56 two-month-old lambs were used. Groups consisting of nine, nine, 22 and 16 lambs were fed LS-LB1, LS-HB1, HS-LB1 and HS-HB1 diets, respectively for 14 weeks. Out of 22 lambs fed the HS-LB1 diet, seven lambs developed neurological signs between the third and eighth week of the trial. Two of these lambs died, three that were in extremis were euthanased, and two recovered completely. All clinically affected animals had extensive malacic lesions in the cerebral cortex, midbrain and brainstem. None of the lambs from the LS groups or HS-HB1 group developed clinical signs. Several clinically normal lambs from the HS-LB1 group had necrotic lesions in their brains at gross and microscopic examination. Supplementation with dietary thiamine prevented development of clinical signs, but did not totally prevent development of microscopic brain lesions. Brain thiamine concentration, transketolase activity and thiamine pyrophosphate (TPP) effect were not different (P greater than 0.05) among groups. There was a strong effect (P less than 0.0001) of dietary thiamine supplementation on blood thiamine concentration and TPP effect. Blood thiamine concentration was higher whereas TPP effect was lower in the thiamine supplemented sheep. Blood and tissue thiamine concentrations in sheep exposed to high dietary sulphur did not indicate either systemic or local thiamine deficiency per se. Increased TPP effect in sheep fed the HS-LB1 diet indicated mild to moderate metabolic thiamine deficiency. Thiamine inadequacy may be an effect of an increased requirement for thiamine in animals exposed to excess dietary sulphur.     

Influence of various feeding conditions, the migrating myoelectric complex and cholinergic drugs on antral slow waves in sheep.

The presented study was designed to elucidate whether the cholinergic mechanisms control ovine antral slow waves in various physiological conditions, including feeding and various phases of migrating myoelectric complex (MMC). The investigations were carried out on six adult sheep of Polish Merino breed with seven bipolar electrodes surgically implanted onto the antral and small intestinal wall. In the course of chronic experiments, the myoelectric activity was recorded from these regions using the multichannel electroencephalograph. Experiments were performed on 48 h fasted and non-fasted animals. During some of these experiments, sheep were fed with standard fodder. During control experiments 0.15 M NaCl was slowly administered i.v. through the indwelling catheter and during other experiment, hexamethonium bromide (2.0 and 5.0 mg/kg). atropine sulfate (0.02; 0.1; 0.5 and 1.5 mg/kg) and pirenzepine dihydrochloride (0.02; 0.5 and 2.0 mg/kg) were administered i.v. during phase 1-2a or 2b MMC. The drugs were also given in combinations. The recordings were analysed and the antral slow wave amplitudes and frequencies were calculated. Unlike the slow wave amplitude, either feeding or the anticholinergic drugs significantly increased slow wave frequency, especially when the given procedure was started during phase 2b MMC. The most pronounced effects were observed after hexamethonium given alone or in combinations. Thus, the cholinergic system modulates antral slow wave frequency in sheep.     

Sulfur-induced polioencephalomalacia in sheep: some biochemical changes.

The effect of high dietary sulfur (S) supplementation on blood thiamine (B1) concentration, biochemical indices of liver, muscle and kidney damage and selected plasma electrolytes was studied in six sheep. Three of these sheep received an additional 230 mg thiamine/kg diet (Group 2). After approximately 2.5-3 weeks on this diet, all three sheep in the non-B1-supplemented group (Group 1) showed loss of appetite and developed mild neurological signs: depression, intermittent signs of excitation and head pressing. Increases in blood B1 concentration and plasma creatine kinase (CK) and aspartate aminotransferase (AST) were observed during this time in all affected animals. Clinical signs lasted only for two to five days. Sheep in group 2 were clinically normal throughout the experiment, but all of these animals also had elevated blood B1 concentrations and plasma CK activity at the 3 wk sampling. Plasma magnesium concentrations of group 1 sheep were elevated at the 2.5-3 wk and 6 wk samplings but they declined significantly (p less than 0.05) to low normal levels thereafter. Magnesium concentrations of group 2 sheep were low at the beginning but progressively increased during the course of the experiment. At necropsy, brain lesions suggestive of polioencephalomalacia (PEM) were observed in all sheep but were most marked in group 1. It is speculated that PEM may be caused by a direct toxic effect of S, S metabolites or B1 antimetabolites in the brain rather than by an in vivo B1 deficiency per se.     

Evaluation of edetate and thiamine for treatment of experimentally induced environmental lead poisoning in cattle.

Twenty mature Holstein cows were randomized into 5 treatment groups. Cows of groups 2 to 5 were given 2 mg of elemental Pb/kg of body weight for 28 days. Clinical signs of plumbism were scored, and blood for Pb, progesterone, and hematologic analyses was collected weekly. Cows also were examined weekly for anomalous ovarian cycles. Starting on study day 28, cows in group 3 were treated once daily with 2 mg of thiamine HCl/kg (IM) for 13 days, cows in group 4 were treated twice daily with 62 mg of Na2,Ca-EDTA/kg (IV) for 4 days, and cows in group 5 were given thiamine (dosage regimen the same as for group 3) plus Na2,Ca-EDTA (dosage regimen the same as for group 4). On study days 96 through 139, cows were slaughtered in a commercial abattoir and samples of blood, skeletal muscles, bones, liver, and kidneys were collected and assayed for Pb concentration. Thiamine was not effective in reducing blood Pb concentration, and treatment with Na2,Ca-EDTA and thiamine plus Na2,Ca-EDTA was effective in reducing the concentration of Pb in blood. However, treatment with thiamine was more effective than treatment with Na2,Ca-EDTA or thiamine plus Na2,Ca-EDTA in inducing remission of clinical signs of plumbism. The concentration of Pb in blood was significantly (P less than 0.05) correlated to the concentration of Pb in liver, kidneys, skeletal muscles, and bones. Significant (P less than 0.05) relationship existed between number of days from Pb exposure to slaughter and concentration of Pb in blood, liver, and skeletal muscles. Exposure to Pb did not significantly alter CBC values.(ABSTRACT TRUNCATED AT 250 WORDS)     

Emory milkvetch (Astragalus emoryanus var emoryanus) poisoning in chicks, sheep, and cattle.

A severe outbreak of Emory milkvetch poisoning in cattle and sheep occurred near Roswell, New Mexico, in the spring of 1975. Mortality averaged 2% to 3% and morbidity averaged 15% to 20%. Emory milkvetch collected from the infested area contained miserotoxin measured as 5 to 9 mg of NO2/g of plant (dry weight). Chicks fed extracts of Emory milkvetch showed toxic signs when fed one dose as 300 mg of NO2/kg of body weight, and died within 5 to 8 hours when fed milkvetch as 400 mg of NO2/kg. A sheep fed Emory milkvetch for 7 days in the form of 38 mg of NO2/kg/day developed signs of nitro poisoning on the 7th day. Cattle were poisoned or died when fed Emory milkvetch as 12 to 20 mg of NO2/ig for several days. The toxic signs observed in the field and under experimental conditions were similar.     

Neurological dysfunction in dogs following attenuation of congenital extrahepatic portosystemic shunts

Eleven of 89 dogs (12 per cent) developed neurological signs within six days of surgical attenuation of a congenital extrahepatic portosystemic shunt. Neurological signs were not associated with hepatic encephalopathy or hypoglycaemia. Signs varied in severity from non-progressive ataxia (three dogs) to generalised motor seizures (four dogs), progressing to status epilepticus (three dogs). In a further four cases, ataxia and disorientation were treated vigorously with anticonvulsant medication, presumably preventing the development of seizures. Two dogs that developed status epilepticus died or were eventually euthanased. All other animals survived, although some had persistent neurological deficits. Postligation neurological complications were not prevented by gradual shunt attenuation. Prophylactic treatment with phenobarbitone (5 to 10 mg/kg preoperatively, followed by 3 to 5 mg/kg every 12 hours for three weeks) did not significantly reduce the incidence of neurological sequelae (2/31 [6 per cent] dogs with phenobarbitone vs 9/58 [16 per cent] without phenobarbitone; P = 0.2). However, no animal receiving phenobarbitone experienced generalised motor seizures or status epilepticus. In conclusion, these observations suggest that postligation neurological syndrome comprises a spectrum of neurological signs of variable severity. Perioperative treatment with phenobarbitone may not reduce the risk of neurological sequelae, but may reduce their severity.     

Comparative pharmacokinetics of febantel and its metabolites in sheep and cattle

The pharmacokinetics of febantel and its main metabolites were studied in cattle and sheep. Seven ewes and 4 heifers were given febantel orally in a single dose of 7.5 mg/kg, 25 mg/kg, or 45 mg/kg of body weight. Plasma concentrations vs time of febantel and individual metabolites were determined by high-performance liquid chromatography analysis. Intestinal absorption of febantel was faster and biotransformations were more active in sheep than in cattle.     

Metronidazole neurotoxicosis in two cats

Two cats were presented for neurological dysfunction from suspected metronidazole toxicity. One cat was receiving 111 mg/kg body weight per day of metronidazole for 9 weeks. After 9 weeks, the dose was increased to 222 mg/kg body weight per day, and 2 days later the cat began to experience progressive neurological signs that culminated in generalized seizures. The second cat was receiving metronidazole at a total dose of 58 mg/kg body weight per day for 6 months. This cat experienced acute onset of ataxia and alteration in mentation. Laboratory evaluations in both cases were without significant findings. The neurological signs in both cats resolved within days of initiating supportive therapy and withdrawal of the drug. This report describes the two cases and discusses the etiology of metronidazole neurotoxicosis.     

Electroencephalogram and evoked potentials in naturally occurring scrapie in sheep

Electroencephalogram (EEG), brain stem auditory-evoked potential, and flash visual-evoked potential recordings were taken from healthy sheep and from 3 sheep with scrapie, a CNS slow virus infection. The EEG changes included semi-periodic, polyphasic, high-voltage sharp waves (bilaterally synchronous and symmetric in all channels), and a cyclic alternating pattern consisting of a high-voltage low-frequency phase, followed by a low-voltage high-frequency phase. The high-voltage phase occurred with increased arousal, and the low-voltage phase occurred with decreased arousal. Myoclonic jerks were coincident with EEG sharp waves in one sheep with scrapie. Several spontaneous focal seizures were observed. Wave-form amplitudes were greatly reduced in the brain stem auditory-evoked potential and flash visual-evoked potential; degree of reduction did not always correlate with disease severity. The EEG and evoked potential changes were seen in an exposed sheep that had not yet developed clinical signs of scrapie.     

Effect of a single dose of ponazuril on neural infection and clinical disease in Sarcocystis neurona-challenged interferon-gamma knockout mice

Interferon gamma-knockout mice were challenged with 5000 Sarcocystis neurona sporocysts acquired from a naturally infected opossum. Ponazuril was administered once, by gavage, at day 1, 3, 7, 10, or 14 post-infection (pi). Ponazuril was given at either 20 or 200mg/kg. Mice that survived to day 30 pi were euthanized. Severity of CNS infection was quantified as schizont density in the cerebellum. Unchallenged mice in treatment and non-treatment groups remained free of disease and gained weight throughout the experiment. All challenged mice, regardless of treatment, developed histologic evidence of CNS infection even though clinical signs were prevented in some groups. The greatest treatment benefits were seen in mice given 200mg/kg ponazuril between days 4 and 14 pi. Weight gain over the course of the experiment occurred only in mice that were given 200mg/kg ponazuril on day 7 or 10 pi. With the exception of groups given 200mg/kg ponazuril on day 7 or 14 pi, mice in groups that got sporocysts developed abnormal neurologic signs. No deaths before day 30 pi occurred in mice given ponazuril at 20mg/kg on day 7 pi or 200mg/kg on day 1, 7, 10, or 14 pi. This effect was not significant. Mice given 200mg/kg on day 7 pi had significantly fewer cerebellar schizonts than did those of the control group that was not given ponazuril. These results indicate that single-dose administration of ponazuril for prevention of CNS infection is partially protective when given between days 4 and 14 pi.     

Failure of oral zinc therapy to alleviate Bacteroides nodosus infections in cattle and sheep

Cattle and sheep with Bacteroides nodosus infection were treated orally with both high (65 mg Zn/kg and 82 mg Zn/kg) and low (1 mg Zn/kg and 8.6 mg Zn/kg) doses of zinc sulphate respectively. The lower dose rates administered weekly for one month, in the case of cattle, or daily for 2 weeks, in the case of sheep, had no effect either on serum zinc levels or the prevalence or severity of infection in treated animals. High dose rates of zinc (approximately 2.5 g Zn per head per day) were required to elevate serum levels above those normally present in both cattle and sheep. Even these dose rates continued daily for about 2 weeks had no beneficial effect on B. nodosus infection in either species.     

Blood thiamine levels in normal cattle and sheep at pasture

Analysis of whole blood samples from 174 cattle and, 174 sheep from 3 geographical regions of New Zealand over a 10 month period showed a mean (range) thiamine level of 122 nmol/l (71-237 nmol/l) for cattle and 118 nmol/l (67-227 nmol/l) for sheep. Regional and seasonal differences were noted with levels tending to rise over the summer period. A reference range of 75-185 nmol/l is proposed for both cattle and sheep to cover these variations. Levels below 50 nmol/l are considered indicative of deficiency.     

Dietary phosphorus for beef cows

Hereford heifers (48 initially) were individually fed variable amounts of dietary phosphorus (P) from weaning through their 8th gestation. During phase I, 2 groups (24 cows each) were given 20.6 to 38.1 g of P/day and 6.0 to 12.1 g of P/day (increasing as animals grew). During phase II (the 4th gestation), half of the animals from each group were maintained with the same respective diets, and the other half were given 5.1 to 6.6 g of P/day. Within 6 months, animals given 5.1 to 6.6 g of P/day gradually developed signs of P deficiency. Clinical signs of deficiency and lesions included general unthriftiness, body weight loss, reduced feed consumption, reluctance to move, abnormal stance, spontaneous bone fractures, and finally, impaired reproductive performance. Cows given 7.8 to 8.9 g of P/day in diet 2 during phase II did not develop discernible clinical signs of P deficiency. Cows that were given 5.1 to 6.6 g of P/day apparently regained their health and reproductive capability when fed 11.7 to 12.6 or 17.1 to 20.5 g of P/day. The data indicate that bones serve as an effective storage source of P and support and buffer body needs until there is serious depletion of skeletal P. These results indicate that common recommendations for dietary P, such as those outlined by the National Research Council (17.5 g of P/day over the entire year for cows weighing 450 kg), exceed the basic requirements for beef cattle; 12 g of P/day is adequate for 450-kg beef cows.     

Effect of levamisole on lymphocyte blastogenesis and neutrophil function in dexamethasone-treated cattle

Levamisole was evaluated at 6 dose levels for its ability to prevent the dexamethasone-induced suppression of in vitro lymphocyte blastogenesis or neutrophil function in cattle. Dexamethasone (0.4 mg/kg of body weight, IM) and levamisole hydrochloride (0.5, 1.0, 2.0, 4.0, or 8.0 mg/kg orally) were administered to groups of 4 cattle daily for 3 days. Another group of 4 cattle were given the 3-day dexamethasone treatment and 6.0 mg/kg of levamisole (the recommended anthelmintic dose) was given only once on the 1st day that dexamethasone was given. Results obtained from the dexamethasone-levamisole-treated cattle were compared with results obtained from cattle that were given only dexamethasone. Levamisole had no apparent consistent ability to enhance lymphocyte blastogenic responsiveness (to the mitogens phytohemagglutinin, concanavalin A, or pokeweed mitogen or in a 1-way mixed lymphocyte reaction) or to enhance neutrophil function (random migration, nitroblue tetrazolium reduction, iodination, or antibody-dependent cell-mediated cytotoxicity) in dexamethasone-treated cattle.     

Blood thiamine levels in normal cattle and sheep at pasture

Analysis of whole blood samples from 174 cattle and 174 sheep from 3 geographical regions of New Zealand over a 10 month period showed a mean (range) thiamine level of 122 nmol/l (71–237 nmol/l) for cattle and 118 nmol/l (67–227 nmol/l) for sheep. Regional and seasonal differences were noted with levels tending to rise over the summer period. A reference range of 75–185 nmol/l is proposed for both cattle and sheep to cover these variations. Levels below 50 nmol/l are considered indicative of deficiency.     

Clinical pharmacology of polymyxin B, colistin and colistimethate in young dairy calves

The in vitro sensitivity of 592 Gram-negative bacteria isolated from cattle against polymyxin B was determined by the agar plate dilution method. The minimal inhibitory concentration of polymyxin B for all but ten of the isolates was ≤ 2.0 μg/ml and 75% of the isolates were inhibited at 1.0 μg of polymyxin B/ml or less. Intramuscular injections of polymyxin B, colistin and colistimethate (CMS) were given to veal calves once daily for 3 days. Mean peak serum drug concentrations were observed within 0.5–1 h after treatment and were between 2.7 and 4.7 μg/ml when polymyxin B and colistin were administered at a dose rate of 2.5 mg/kg/day, and between 5.3 and 7.5 μg/ml at dose rate of 5.0 mg/kg/day. When CMS was given at 5.0 mg/kg/day mean peak drug concentration was 14.1 μg/ml. The elimination half-life ( t _1/2) of polymyxin B and colistin was 4–5 h but was approximately 2 h for CMS. Kidney function tests, using the double isotope single-injection method, were performed before and after the course of antibiotic treatment. No changes were detected in the glomerular filtration rate (GFR) or the effective renal plasma flow (ERPF) and blood urea levels were not raised following treatment. Several calves treated with the higher doses of polymyxin B and colistin exhibited transient ataxia and apathy 2–4 h after treatment but clinical signs suggesting interference with neurological function were not observed after an equivalent dose of CMS was administered.     

Evaluation of the respiratory elimination kinetics of selenium after oral administration in sheep

OBJECTIVE: To evaluate the respiratory excretion and elimination kinetics of organic and inorganic selenium after oral administration in sheep. ANIMALS: 38 crossbred sheep. PROCEDURES: Selenium was administered PO to sheep as a single dose of 0, 1, 2, 3, or 4 mg/kg as sodium selenite or selenomethionine. Expired air was collected and analyzed from all sheep at 4, 8, and 16 hours after administration. RESULTS: Clinical signs consistent with selenium intoxication were seen in treatment groups given sodium selenite but not in treatment groups given the equivalent amount of selenium as selenomethionine. However, a distinct garlic-like odor was evident in the breath of all sheep receiving 2 to 4 mg of selenium/kg. The intensity of odor in the breath did not correlate with clinical signs in affected animals receiving sodium selenite treatment. CONCLUSIONS AND CLINICAL RELEVANCE: The concentration of selenium in expired air was greater in sheep receiving selenium as selenomethionine than sodium selenite. The concentration of selenium in expired air from sheep receiving high doses of selenium (3 and 4 mg of selenium/kg) was larger and selenium was expired for a longer duration than the concentration of selenium in expired air from sheep receiving low doses of selenium (1 and 2 mg of selenium/kg).     

Increased tolerance to annual ryegrass toxicity in sheep given a supplement of cobalt

SUMMARY To determine whether oral cobalt supplements could modify the clinical onset of annual ryegrass toxicity, groups (n = 5) of sheep were dosed orally with 0, 4 or 16 mg cobalt/day. After 3 weeks on this treatment, toxic ryegrass seed was added to their feed to provide 0, 0.15 and 0.30 mg corynetoxins/kg body weight, daily. Sheep receiving cobalt ingested 30% more toxin than did unsupplemented sheep before clinical signs developed (P = 0.03). There was no significant difference between groups receiving 4 and 16 mg cobalt. The results showed that cobalt delayed, but did not prevent, the onset of clinical signs of annual ryegrass toxicity.     

Transient enhancement of the serum antibody response to Brucella abortus strain 19 in cattle treated with levamisole

Two experiments were done on 57 steers. These cattle were allotted to 8 groups (4 groups/experiment) and vaccinated with 1 to 3 X 10(9) colony-forming units of Brucella abortus strain 19. Cattle in 3 of the 4 groups/experiment were given 6 mg of levamisole/kg, subcutaneously, either at the time of vaccination (day 0), 7 days later, or at both times. Serum antibody titers to B abortus were measured sequentially for 28 days in experiment 1 and for 56 days in experiment 2, using the card test, Rivanol test, complement-fixation test, fluorometric immunoassay, and an enzyme-linked immunosorbent assay. In general, the highest mean antibody titers, as determined by all serologic tests, occurred in steers treated with levamisole at 7 days after vaccination or in those treated at the time of vaccination and 7 days later. By the card test on day 56, there was a significantly (P less than 0.05) greater number of seropositive cattle among those given levamisole 7 days after seropositive cattle among those given strain 19 alone. Simultaneous administration of strain 19 and levamisole did not alter antibody responses to B abortus.     

Repeated oral administration of coumaphos in sheep: interactions of coumaphos with bishydroxycoumarin, trichlorfon, and phenobarbital sodium.

Interactions between treatments with coumaphos, bishydroxycoumarin (an anticoagulane), trichlorfon (an organophosphorous compound), and phenobarbital sodium (an inducer of microsomal enzymes) were investigated in sheep. A daily dose of 2 mg of coumaphos/kg of body weight for 6 days did not affect the plasma enzymes or the antiprothrombinemic effect of bishydroxy-coumarin in wethers. The treatment of ewes with an intravenous (IV) injection of trichlorfon, insufficient to produce significant inhibition of erythrocyte acetylcholinesterase (AChE) activity, appeared to produce additive effects with those produced by subsequent treatment with 4 mg of coumaphos/kg/day. In ewes given 40 mg of phenobarbital sodium/kg for 5 days intraperitoneally (IP), the anticholinesterase effect of 4 mg of coumaphos/kg was significantly reduced and signs of toxicity were not present. Treatment with daily doses of 2 mg of coumaphos/kg for 6 days did not modify the anticholinesterase effect of a 2nd series of treatments given 6 weeks later.