Evaluation of activated charcoal as treatment for Yellow tulp (Moraea pallida) poisoning in cattle.

The efficacy of activated charcoal as a treatment for cattle (n = 57) poisoned by Yellow tulp (Moraea pallida) was investigated. Treatment with activated charcoal resulted in full recovery, irrespective of the degree of posterior paresis, provided that this clinical sign did not develop within the first 12 hours after initial exposure to Yellow tulp-infested grazing. For instance, despite treatment, 1 of 7 cattle succumbed after manifesting mild posterior paresis 6 to 8 h after initial exposure and 3 of 3 treated cattle died after developing severe posterior paresis within 6 to 12 h.

Changes in sheep oesophageal diameter and function during Geigeria ornativa (vermeerbos) poisoning and subsequent recovery.

Changes in the oesophageal diameter and function together with changes in body weight, feed intake and the cardiac pulmonary flow index were investigated during experimentally induced poisoning with Geigeria ornativa and subsequent recovery. This was performed under varying conditions for individual sheep. Results showed an increase in the oesophageal diameter index (ODI) during vermeersiekte, accompanied with a decrease in oesophageal function (OF). Cessation of G. ornativa intake resulted in a considerable although incomplete recovery of the ODI. Recovery of the OF for the different sheep, however, varied between 0 and 100%. Detrimental changes in the oesophageal diameter and function were also measured in sheep receiving only subclinical doses of G. ornativa. Decreases in body weight and feed intake commenced 1 to 3 weeks before the onset of vermeersiekte, while indications of a decline in these 2 parameters were also noticed with ingestion of subclinical amounts of G. ornativa. An increase in the cardiac pulmonary flow index (CPFI) to a value indicating the onset of heart failure was found in 1 of the sheep showing clinical signs of vermeersiekte. The CPFI returned to normal after termination of G. ornativa intake.

A potential krimpsiekte vaccine.

Krimpsiekte, a chronic form of cardiac glycoside poisoning, is an important plant-induced intoxication of small stock in South Africa. It is caused by cumulative, neurotoxic bufadienolides, such as cotyledoside. A cotyledoside-bovine serum albumin conjugate was synthesized to immunize animals. The efficacy of the cotyledoside-conjugate in inducing an immunological response was ascertained in rabbits (n = 4) and sheep (n = 4) by determining cotyledoside antibody titres with an ELISA using cotyledoside-hen ovalbumin as antigen. The formation of anticotyledoside antibodies was induced in both rabbits and sheep following immunization with the cotyledoside-protein conjugate. Protection provided by the vaccine was demonstrated by challenging sheep (n = 4) with repeated, daily doses of cotyledoside (0.015 mg/kg) administered intravenously, commencing 45 days after the initial vaccination. One control animal died on Day 3 of the challenge period and the other was severely affected after administration of the third cotyledoside dose. The immunized ewes (n = 2) remained clinically unaffected and the challenge was suspended following six daily injections. Vaccination as a means of preventing krimpsiekte seems to be quite feasible and deserves further investigation.

The toxicity of Senecio inaequidens DC.

This study was designed to confirm the toxicity of a plant implicated in an outbreak of poisoning of stock in Frankfort, Free State Province, South Africa. Cows died acutely after being introduced into a camp, where an abundant, green shrublet was noted to be heavily grazed. This plant was subsequently identified as Senecio inaequidens DC. (Asteraceae) by the South African National Biodiversity Institute (SANBI). Extraction and chemical analyses for pyrrolizidine alkaloids (PAs) in Senecio inaequidens revealed the presence of 4 different compounds, namely retrorsine and senecionine (known to be hepatotoxic) and 2 unidentified compounds. The average total PA (free base plus N-oxide) concentration in plant parts of S. inaequidens collected at Frankfort during the outbreak was 0.81%, compared with the total alkaloid content in the dried, milled S. inaequidens plant material, collected 7 weeks after the outbreak, of only 0.18%. Male Sprague-Dawley rats (n = 4), aged 8-9 weeks, were dosed per os. Each rat received a different dose of the crude Senecio inaequidens extract, ranging from 0.049 mg/g body weight (b.w.) to 0.25 mg/g b.w. No clinical signs were observed in the rat receiving the lowest dose. Rats receiving higher doses showed depression, an unsteady gait, pilo-erection and jaundice, which was particularly noticeable in the ears. Clinical chemistry evaluation revealed an increase in the activities of ALP (except Rat 4), AST and GGT in all animals. Total serum bilirubin, creatinine and urea concentrations were also elevated. All rats had low serum globulin concentrations with an A/G ratio above 1.2. Post mortem examination of the rats revealed marked hepatic lesions. Histopathologically, these changes were characterised by necrosis (variable in extent) of the centrilobular and midzonal hepatocytes (but sparing the portal hepatocytes), with extensive haemorrhage and congestion. Proliferation of the bile ducts, fibrosis and oedema were also present. Ultrastructural changes in affected rats were characterised by margination of chromatin, the presence of numerous autolysosomes in necrotic hepatocytes, intramitochondrial woolly inclusions and changes in the endoplasmic reticulum. A sheep, also dosed with the crude extract, failed to exhibit clinical signs, clinical chemistry aberrations or macroscopic lesions; however, examination of the liver of this sheep revealed histopathological and ultrastructural changes similar, though milder, to those displayed by the rats. Pyrrolizidine alkaloids were extracted from the liver and kidneys of the rats and the sheep. In the case of the sheep, retrorsine was also detected in the lungs, urine and bile.

Experimental Albizia versicolor poisoning in sheep and its successful treatment with pyridoxine hydrochloride.

Five sheep developed severe nervous signs after being drenched with Albizia versicolor pod-material. Four of these sheep were treated with pyridoxine hydrochloride (a vitamin B6) when the symptoms of toxicity became life-threatening. All the treated sheep recovered dramatically and completely after treatment while the untreated one died 2 h after receiving pod-material. A therapeutic dose of 20-25 mg pyridoxine hydrochloride/kg body mass given twice with an 8 h interval is the recommended treatment regimen. The route of administration will depend on the severity of symptoms. Chemical pathology and post-mortem findings are discussed.

Continuous exposure to an aversive mixture as a means of maintaining aversion to vermeerbos (Geigeria ornativa O. Hoffm.) in the presence of non-averted sheep.

Continuous exposure to an aversive mixture was investigated as a means of maintaining aversion to vermeerbos in sheep subjected to the social influence of non-averted sheep. The use of an aversive mixture was based on a hypothesis that continuous exposure to an acceptable aversive mixture (containing both the aversive substance and the identification factors of vermeerbos mixed with maize meal) would tempt sheep to consume small quantities of the aversive mixture each day and that this would keep them averted to vermeerbos, despite the social influence of non-averted sheep. Persistent aversion to a vermeerbos-maize meal mixture (1:99 by mass) by sheep continuously exposed to such an aversive mixture, after an initial aversion conditioning with lithium chloride (LiCl, 160 mg/kg BM), was demonstrated. Aversion in adjacent controls not exposed to the aversive mixture only lasted for some time. A similar result was obtained when sheep were challenged for intake of a pure stand of established vermeerbos. Three sheep continuously exposed to an aversive mixture after an initial aversion conditioning totally refused grazing the vermeerbos during a 42-day trial, despite the social influence of three non-averted control sheep grazing vermeerbos on an adjacent site. These results were confirmed by a second replication the following year. Joint grazing for an hour a day by averted and non-averted sheep during the last seven days of this replication also resulted in total avoidance of vermeerbos by the averted animals, despite continued intake of vermeerbos by the control sheep

Effect of pavetamine on protein synthesis in rat tissue.

Pavetamine, the active principle of plants causing gousiekte in ruminants, was found in this study to be an inhibitor of protein synthesis in the rat heart. Sprague-Dawley rats were injected intra-peritoneally with 8-10 mg/kg pavetamine and the levels of protein synthesis in different organs determined utilizing L-[4-3H]phenylalanine incorporation. In contrast to the more than 23% inhibition found in heart tissue at 4, 24 and 48 h after administration of pavetamine, the effect on the kidney, liver, spleen, intestine and skeletal muscle was minimal or returned to pretreatment levels within 48 h. These results may offer an explanation for the clinical signs observed in ruminants with gousiekte, where the heart only is affected.

Clinical pathological changes in gousiekte, a plant-induced cardiotoxicosis of ruminants.

Twenty sheep were dosed with either Pachystigma pygmaeum or Fadogia homblei belonging to the Rubiaceae. The experimentally-induced cardiotoxicoses were monitored by various clinical pathological parameters and heart function tests. Elevated AST (aspartate transaminase) activity in the serum proved to be a more reliable indicator of cardiac damage in gousiekte than either LD (lactate dehydrogenase) or CK (creatine kinase). Persistent increases of AST activity were recorded from c. 14 days after commencement of dosing, and this activity sometimes peaked as late as 30 days after the dosing had ceased. Tachycardia and diminished heart function were registered only terminally. Lesions of gousiekte were present in all the sheep that were exposed to the plants. In a field outbreak of P. pygmaeum, where 60 out of 90 sheep died, 14 out of the 15 animals examined had increased AST levels compared with none of the 15 controls. These results indicated that increased enzyme levels can be of use to identify affected animals during latency in a natural outbreak of gousiekte.

Conditioned feed aversion as a means to prevent tulp (Homeria pallida) poisoning in cattle.

Conditioned feed aversion was investigated as a means to prevent tulp (Homeria pallida) poisoning in cattle on tulp-infested grazing. Aversion treatment with a combination of epoxyscillirosidin and lithium chloride together with a tulp-hexane extract, which served as identification factor for tulp, resulted in a significantly lower (P < 0.001) proportion of severe tulp poisoning. In a first trial where 21 averted and 21 non-averted control cattle were exposed to a tulp-infested grass pasture, only two of the averted cattle were severely poisoned compared to 13 of the non-averted control cattle. In a second trial, with cattle being exposed to a pure stand of tulp supplemented with maize residues, only two of 21 averted cattle were severely poisoned compared to 14 of 21 non-averted control cattle. Occurrence of mild tulp poisoning, however, did not differ much between averted and non-averted control cattle. The results show that conditioned feed aversion effectively restricted severe poisoning in cattle on tulp-infested grazing.

Neurotoxicity in calves induced by the plant, Nierembergia hippomanica Miers var. violacea Millán in South Africa.

The plant Nierembergia hippomanica var. violacea has been incriminated in field outbreaks of neurotoxicity in calves in the Free State Province. Hepatotoxicity and electrocardiogram (ECG) deviations were induced in a sheep dosed with 5 g/kg dried plant material on four consecutive days. A calf dosed with 2.5 g/kg dried plant material, on two consecutive days, did not show overt clinical changes. Voluntary ingestion of approximately 30 g/kg fresh flowering plants by a second calf resulted in nervous signs characterized by chewing motions, protrusion of the tongue, dysphagia, hypermetria, ataxia, paresis and lateral recumbency. Salivation, dehydration and cardiac irregularities completed the clinical picture. Clinical chemistry changes revealed muscle damage and increased serum urea and creatinine concentrations indicative of kidney involvement. This is the first confirmed outbreak of Nierembergia hippomanica var. violacea intoxication of stock in South Africa.

Isolation and characterization of and some observations on poisoning by bufadienolides from Cotyledon orbiculata L. var. orbiculata.

The approximate LD50 and cumulative effect of 4 bufadienolides, isolated from Cotyledon orbiculata, were determined in guinea-pigs. Two of the bufadienolides proved to be mildly cumulative. One of the mildly cumulative bufadienolides induced subacute intoxication with some signs of krimpsiekte when injected intravenously into a sheep over 13 days. In the sheep, the paralysis was accompanied by signs of malaise, such as electrocardiographic changes and ruminal stasis.

Galenia africana L. poisoning in sheep and goats: hepatic and cardiac changes.

Lesions in 4 field cases (3 sheep and 1 goat) of 'waterpens' or water belly, caused by the plant Galenia africana, are described. The clinical pathological and pathological findings in 7 sheep which were drenched with toxic plant material are also reported. Inappetence, ruminal stasis and apathy as well as tachycardia were noticed in some of the sheep towards the end of the dosing period. The most prominent clinical pathological change in the experimental animals was an increase in the activity of gamma-glutamyltransferase which in some animals occurred within days after commencement of dosing. This indicates liver involvement in the early stages of the intoxication, and at this stage no heart abnormalities were detected clinically, clinical pathologically or with cardiac function tests. Decrease in cardiac function were recorded in 2 sheep towards the end of the dosing period. Liver and heart lesions were present in all the animals. In some cases hepatic changes were mild and characterized by dilation of central veins and sinusoids and, less commonly, centrilobular fibrosis. More advanced lesions included centrilobular fibrosis and bridging between neighbouring lobules with adjacent areas of coagulative necrosis, lysis and ballooning degeneration of hepatocytes. Myocardial changes occurred in the free ventricular walls and interventricular septum and comprised hypertrophy of myocytes with consequent degeneration and necrosis and fibrosis. In cases of longer duration myocytes were diffusely atrophic with scattered groups of remaining hypertrophic fibres. The clinical pathological and pathological features suggest that G. africana is primarily hepatotoxic with myocardial involvement occurring only in the terminal stages of the intoxication.

Vermeersiekte caused by Geigeria burkei Harv. subsp. burkei var. hirtella merxm. in the northern province of South Africa.

The 1st field outbreak of vermeersiekte induced by Geigeria burkei Harv. subsp. burkei var. hirtella Merxm, is reported. It is also the first recorded outbreak of this disease in the arid sweet bushveld of the Northern Province of South Africa. The toxicosis was experimentally reproduced in a sheep following daily intraruminal administration of 2.5-5.0 g/kg dried, milled plant material for 18 consecutive days. Neither the sheep in the field outbreak nor the ewe in the experiment exhibited any signs of regurgitation of rumen contents (vermeersiekte). All developed only the stiff or paretic/paralytic forms of the disease. Serum activities of CK and GGT were slightly raised in clinically affected sheep (n = 11) during the field outbreak, and serum activities of AST, GLDH, GGT, LDH and CK increased in the ewe dosed with the plant material. Analysis of dried, milled Geigeria plant material confirms that this species is moderately nutritious.

Poisoning of wildlife in South Africa.

Over a period of 7 years the Toxicology Diagnostic Laboratory at the Onderstepoort Veterinary Institute investigated 370 suspected incidents of poisoning of wildlife. A diagnosis was made in 166 of the outbreaks. Synthetic organic pesticides were responsible for 82.5% of the poisonings. More than 90% of the poisonings were maliciously intended and monocrotophos was the chemical most often used. The data were derived from authenticated outbreaks of poisoning and indicate the chemicals most often incriminated in acute poisoning of wildlife. Of all wild animals, birds are the most frequent victims of poisoning. Uncommon toxicities such as ionophore, cardiac glycoside poisoning and chronic fluorosis are also described.