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.     

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.     

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)     

Immunization of dogs with a Leishmania infantum-derived vaccine

A partially-purified extract of Leishmania infantum has been administered to healthy dogs. Post-immunization sera were found to neutralize the infectivity of L. infantum and to abate the development of L. major. Muramyl dipeptide and one of its derivates, murabutide, were the best adjuvants.     

Canine leishmaniasis. A review based on 95 cases in The Netherlands

The clinically relevant aspects of canine leishmaniasis are reviewed. Included are data from 92 dogs imported from the Mediterranean basin and at least 2 autochthonous cases. New aspects on pathogenesis are presented, including evidence that canine leishmaniasis is an immune complex disease. Therapy with meglumine antimonate (Glucantime) is evaluated. The hazards of imported canine leishmaniasis for public health are discussed.     

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.     

Otitis externa. A disease of multifactorial etiology

Dogs and cats with long-standing otitis externa pose a difficult diagnostic challenge for the veterinarian, because chronically affected ears usually have the same appearance regardless of the underlying cause(s). In patients with chronic otitis externa, the disease is often caused by different combinations of primary, predisposing, and perpetuating factors. The unique therapeutic needs of each patient may be determined by careful interpretation of historical and physical findings, which should be supported by ancillary diagnostic tests.     

Isoleucine requirement of broiler chicks as affected by the concentrations of leucine and valine in practical diets.

1. Chicks were fed on an isoleucine-deficient diet, with 6 added concentrations of isoleucine to determine their isoleucine requirement and an additional 6 treatments were devised to determine their isoleucine requirement when dietary leucine and valine contents were increased. 2. The diet deficient in isoleucine contained 5.6 g/kg isoleucine with leucine and valine contents of 20.1 and 10.3 g/kg, respectively. Supplementation with leucine and valine increased these to 24.7 and 12.6 g/kg, respectively. 3. The isoleucine requirement was not affected by dietary leucine and valine contents in a diet with 13.4 MJ of ME per kg. Analysis of variance and Least Significant Difference of means indicated an isoleucine requirement of 7.2 g/kg. Non-linear regression of the same data indicated an isoleucine requirement of 8.44 g/kg, based on weight gain, or 8.19 g/kg based on food efficiency. 4. Reasons for the failure to find an imbalancing effect of branched chain amino acids in practical diets are discussed.