Pyrrolizidine alkaloid-induced liver disease in horses: an early diagnosis

Nine adult horses were fed alfalfa hay cubes containing approximately 10% Senecio vulgaris until all horses had consumed approximately the same amount of toxic components of S vulgaris, pyrrolizidine alkaloids (PA). The amount of PA consumed was determined by the amount that induced clinical signs of PA toxicosis in 3 horses. The 6 other horses were given similar amounts per kilogram of body weight. An initial decrease of feed intake was observed when horses' diets were changed from alfalfa cubes to alfalfa/Senecio cubes, and feed intake was decreased further over 89 to 98 days. From 50 to 159 days, body weight decreased in all horses. Liver disease was induced in all 9 horses after they ate an average of 233 +/- 9.2 mg of PA/kg of body weight. Eight horses died or were euthanatized. Treatment with branched chain amino acids had no effect on mortality, but appeared to reduce neurologic problems. Clinical signs of PA-induced liver disease included ataxia, head pressing, and decreased feed intake. Other clinical signs of toxicosis were observed individual horses, but did not develop in most horses. Megalocytic hepatopathy developed. Liver abnormalities proceeded as PA was consumed and were severe in 8 of 9 horses before clinical signs of toxicosis appeared. Sulfobromophthalein sodium clearance did not decrease until PA-induced liver disease was advanced. Bile acid (BA) concentrations increased to greater than or equal to 50 mumol/L, in the 8 horses that died. One horse had hepatopathy and increased BA concentration, but survived. In this horse, BA concentration peaked at 33 mumol/L and then decreased.(ABSTRACT TRUNCATED AT 250 WORDS)     

Some pharmacokinetic data of aditoprim and trimethoprim in healthy and tick-borne fever infected dwarf goats

Aditoprim (AP) is a new dihydrofolate reductase inhibitor, which is structurally related to trimethoprim (TMP). The pharmacokinetics of AP (10 mg/kg) and TMP (20 mg/kg) were assessed in healthy dwarf goats. Therapeutic efficacy against rickettsial infections was tested in tick-borne fever (TBF) infected goats. The animals were given TMP (n = 5) or AP (n = 5) by i.v. injection, and subsequently the drugs were administered orally (same groups, similar doses). Finally, both groups were infected with TBF and the i.v. experiment was repeated. Plasma concentration-time curves for both drugs followed first-order two-compartment decay. For TMP, mean t1/2 beta +/- SEM (h) was 0.84 +/- 0.06 (i.v. control) and 0.90 +/- 0.06 (i.v. infected), respectively, whereas for AP values of 8.00 +/- 0.31 (i.v. control) and 10.28 +/- 0.67 (i.v. infected) were obtained (P less than 0.05). Mean Vd beta +/- SEM values (l/kg) were 3.84 +/- 0.27 (i.v. control) and 4.07 +/- 0.85 (i.v. infected) for TMP (NS) and 7.02 +/- 0.63 vs 9.29 +/- 0.21 (P less than 0.05) for AP. After i.v. injection, rumen fluid concentrations of AP were significantly (P less than 0.05) higher and more persistent than those of TMP. For AP, the plasma and rumen fluid concentrations at 3 h were 1.20 +/- 0.06 micrograms/ml and 0.85 +/- 0.17 microgram/ml, respectively. After oral administration of TMP, Cmax in plasma was 0.12 +/- 0.01 microgram/ml and the maximum was reached after 1.2 +/- 0.16 h; systemic bioavailability (F) was 10.3% (relative to AUC i.v.). Oral treatment with AP resulted in a Cmax value of 0.21 +/- 0.02 microgram/ml with Tmax of 22.5 +/- 1.65 h and a F value of 71%. Based on WBC, serum ALP and rectal temperature responses, it was concluded that both TMP and AP were inactive against Ehrlichia phagocytophila.     

In vitro Sendai viral replication in pulmonary macrophages from mice treated with 4-ipomeanol

The ability of pulmonary macrophages from female mice given 4-ipomeanol (4-IP) to support viral replication in vitro was examined. On posttreatment days 5, 7, and 9, greater numbers of macrophages were recovered in lavage fluid from lungs of mice given 4-IP, compared with those from controls. Pulmonary macrophages recovered in lavage fluid from control mice and from mice given 4-IP supported Sendai virus replication in vitro, and nearly all Sendai virus produced in pulmonary macrophages from both groups was in an infectious form. On posttreatment days 5 and 7, slightly greater absolute numbers of virions were produced in pulmonary macrophages recovered from mice given 4-IP.     

Effect of D-glucose on in vitro short-circuit current in neonatal calf jejunum and rabbit ileum

Thin sheets of mucosa from small intestine of neonatal calves were mounted in incubation chambers for in vitro studies. These mucosal sheets generated a potential difference (PD) of 2.05 +/- 0.02 mV (mean +/- SEM), short-circuit current (SCC) of 23.32 +/- 3.81 microA x cm2, and tissue resistance of 86.22 +/- 4.41 ohms x cm2 (n = 6). Ouabain in the serosal bathing solution caused a sharp decrease in the SCC (P less than 0.01) and PD (P less than 0.005), a decrease in tissue K content (P less than 0.05), and an increase in tissue Na content (P less than 0.05). The mucosa responded to D-glucose by an increase in PD (P less than 0.001) and SCC (P less than 0.001). In vitro methods used in the calf were validated in similar experiments on rabbit ileum.     

Verification of ineffectual activity of ivermectin against adult Onchocerca spp in the ligamentum nuchae of horses

Ivermectin paste formulation (200 micrograms/kg) was administered orally to 27 horses (13 Thoroughbreds and 14 of mixed breeding) to evaluate activity against adult Onchocerca spp in the ligamentum nuchae. Ages, known or estimated, of the horses ranged from 1 to 22 years. Single or multiple doses (1 to 5) of the drug were given to each horse. When multiple doses were administered, the intervals between treatments ranged from 7 to 92 days. At 27 to 171 days after initial treatment (single dose or first of multiple doses), the horses were killed. Some of the horses treated more than once were killed as soon as 7 days after the last treatment. At necropsy, Onchocerca spp were found in the ligamentum nuchae of 24 (89%) of the 27 horses. All of the specimens were pieces of worms, apparently adult, which appeared to be alive. The only noninfected horses were 2 to 3 years old. In 18 (75%) of the 24 infected horses, microfilariae, most being obviously viable, were found in the worm specimens or ligamentum nuchae.     

Epidemiology of ovine helminthiasis in Haryana,India

Tracer lambs were used to study the pasture contamination with infective stages of helminth parasites during one annual cycle in a subtropical climate. Post-mortem worm counts indicated that low infections with Haemonchus contortus occurred throughout the year except in June. However, twenty five or more H. contortus per lamb were recorded in January, April, May and August. Trichostrongylus colubriformis infection was detected throughout the year and 150 or more worms per lamb were recorded during January to May and in August. Anoplocephalids were recorded from the lambs throughout the year but had no seasonal pattern. Low infections with Oesophagostomum columbianum and Trichuris ovis were observed. The faecal egg counts from the permanent flock with whom the tracer lambs were grazed revealed heavy to mild worm burdens throughout the year. Coproculture indicated that H. contortus predominated from the second fortnight of May to December except in the second fortnight of July. Infection with T. colubriformis was more severe from January to the first fortnight of May and in the second fortnight of July. Negligible infections with O. columbianum, Bunostomum trigonocephalum, Gaigeria pachyscelis and Dictyocaulus filaria were also observed. Biohythergraphs prepared for H. contortus and T. colubriformis showed differences between observed and expected results. It is suggested that for realistic biohythergraphs related parameters in addition to rainfall and temperature should also be considered.     

The clinical pathology of heartwater. I. Haematology and blood chemistry

Clinical pathological studies were undertaken in 5 calves with experimentally-induced heartwater. The most important findings include a progressive anaemia which may be associated with bone marrow depression and fluctuations in the total and differential white cell count, of which an eosinopenia and a lymphocytosis were the most marked. A severe drop in serum protein, especially in the albumin levels, was observed in all 5 cases. This disease is probably associated with an increased capillary permeability, as the protein content of the pericardial fluid in 1 case that died, approximated that of the serum. The osmolality of the effused fluid was also higher than that of the blood. No significant changes in the serum electrolyte levels occurred, except for total calcium levels which tended to decrease to below normal during the acute stage of the disease. Marked increases in total bilirubin were recorded. This, however, was not associated with liver pathology or haemolysis and may possibly be ascribed to a fasting hyperbilirubinaemia. Darkening of plasma colour was associated with peak rises in total bilirubin. Increases in both blood urea and creatinine levels indicate interference with renal glomerular filtration during the acute stage of the disease.     

Immunological studies with liposome-bound corynetoxins

Attempts were made to raise antibodies against corynetoxins, a family of toxins responsible for annual ryegrass toxicity. The glycolipid nature of corynetoxins made them ideally suited for incorporation into the structure of small unilamellar liposomes. Sheep were injected with corynetoxin liposomes with and without adjuvants such as lipid A and muramyl dipeptide, and the sera tested for anti-corynetoxin antibody. Similarly, rabbits were injected with hydrolysed corynetoxin coupled to human IgG and keyhole limpet haemocyanin and with corynetoxin coupled to bovine serum albumin. These preparations were administered with complete Freund's adjuvant. The failure of any of these preparations to elicit an anti-corynetoxin antibody response in either sheep or rabbits is discussed.     

Biochemical analysis by SDS-PAGE and western blotting of the antigenic relationship between Leptospira and equine ocular tissues.

The antigenic relationship between Leptospira interrogans, equine cornea and lens was previously noted in our studies. Serum antibodies from horses inoculated with serovars wolffi, pomona, icterohaemorrhagiae, and tarassovi, were able to bind to five antigenic fractions from both cornea and lens, as demonstrated by immunoblotting. These antigens seem to be made up of protein and carbohydrates. After treatment with periodate for cleavage of glycoside ring structures, those fractions kept their condition of target for anti-Leptospira antibodies. Nevertheless, all fractions lost that condition after being subjected to peptide hydrolysis.