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.     

Hematochezia attributable to cranial mesenteric arterial aneurysm with connecting tracts to cecum and ileum in a horse

A cranial mesenteric arterial aneurysm with fistulous tracts to the cecum and ileum was discovered in a Missouri Fox Trotter stallion. The principal clinical sign was hematochezia, observed at 7- and 10-day intervals. The lesion may have been attributable to arteritis caused by fourth-stage larvae of Strongylus vulgaris.     

Evaluation of a serological test system for the diagnosis of natural Echinococcus granulosus infection in dogs using E. granulosus protoscolex and oncosphere antigens

Serum antibody responses in feral or domesticated dogs naturally infected with Echinococcus granulosus or/and other common helminths were examined in an enzyme-linked immunosorbent assay (ELISA) using antigens prepared from E. granulosus protoscoleces or oncospheres. The ELISA using the protoscolex antigen was optimised with serums from experimental dogs monospecifically infected with E. granulosus or other helminth parasites, and helminth-free dogs. Anti-protoscolex antibody was detected in 16 of 22 (72.7%) serums from feral dogs with E. granulosus burdens ranging from 300 to 302,600 worms per dog. Seven serums from feral dogs which did not harbour E. granulosus at autopsy but which originated from an endemic hydatid region were tested using protoscolex antigen, and 1 serum gave a positive reaction. One hundred and two serums from dogs known never to have been infected with E. granulosus all gave negative reactions to protoscolex antigen. The sensitivity of the ELISA test proved to be superior to that which has been achieved by arecoline purging as a method of diagnosis for E. granulosus infection in dogs. For use of the assay in hydatid control or eradication campaigns, its sensitivity can be increased by choosing a lower absorbance discrimination value above which serums are regarded as having positive reactions. However, this does introduce positive reactions of some serums from dogs infected with helminths other than E. granulosus. In further development of the assay, use of defined recombinant antigens may improve both sensitivity and specificity.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Sarcoid granuloma-like lesions in the lungs of broiler chicks.

Sarcoid granuloma-like lesions were observed in the lungs of two broiler chicks showing depressed growth. Multinucleated giant cells in the lesions often contained foreign bodies comprising amorphous and laminated material. These were morphologically similar to Schaumann bodies found in human sarcoidosis. This is the first report of sarcoid granuloma-like lesions and Schaumann body-like material in chickens.