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.     

Validity of skin testing for diagnosis of food allergy in dogs.

One hundred suspected allergic dogs were skin-tested with 9 food extracts, in addition to other inhalant and insect allergens. Forty-eight of the dogs had +2 or greater intradermal reactions to 1 or more food extracts at concentration of 1,000 protein nitrogen units/ml. Thirty of the food extract-positive dogs were fed a restrictive hypoallergenic diet. Of these 30 dogs, 3 improved, then allergy signs worsened when they were challenge-exposed with the original diet. Fifty-two dogs did not have skin test reactivity to any of the 9 food extracts. Of these 52 dogs, 35 were fed a restrictive diet. Six improved, then allergy signs worsened when dogs were challenge-exposed with the original diet. Skin-testing with selected allergenic food extracts was not useful in identifying food-sensitive dogs.     

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.     

Effects of various steroid milieus or physiological states on sexual behavior of Holstein cows.

Two experiments were conducted to determine how steroid milieus and pregnancy affect sexual behavior. Experiment 1 was arranged as a Latin square with five ovariectomized cows and five steroid milieus: no steroid (N); progesterone (P4); estradiol benzoate (EB); P4 + EB; and P4 followed by EB (P4:EB). Progesterone was administered via pessary (2 g of P4) for 5 d and EB was injected (1 mg i.m.) on the day before a test day. On a test day, cows were exposed for four 30-min periods, twice each with a tied or a loose estrual test cow (prepared using P4:EB). Sexual behaviors recorded were attempted mounts, successful mounts, front mounts, stands, head butts, chin rests, and vulvar sniffs. Cows exhibited more (P less than .05) sexual behavior during periods with the loose estrual test cow than with the tied estrual test cow. Cows receiving P4 alone ranked lowest among treatments for each behavior, whereas cows receiving EB or P4:EB ranked highest or second-highest. Progesterone prevented stands in cows given P4 + EB, but these cows displayed mounting behaviors similar to those of cows given EB and P4:EB. Cows given P4 + EB were similar to those given N for most behaviors. In Exp. 2, 118 intact, lactating cows were observed in groups of four or five for mounting of estrual test cows during 24, 30-min observation periods on 8 d over 2 yr. The design was an incomplete block with physiological state, parity, estradiol, progesterone, and a calculated estrogen:progesterone ratio included in the model. Each block included one or two cows at 23 +/- .8 d after insemination, divided retrospectively into one pregnant and two non-pregnant groups (low [less than 1 ng/mL] vs high progesterone), and other cows at 89 +/- 1.0, 152 +/- 1.2, and 234 +/- 1.7 d of gestation (six physiological groups). Most cows were observed once, but 27 cows were included twice during 2 yr. Only 60% of the 118 cows made attempted or successful mounts even though estrual test cows were always receptive. Physiological state was not associated with amount of mounting because very active (greater than or equal to five attempts) and inactive cows were represented in all physiological groups. The estrogen:progesterone ratio on test day accounted for small, but significant, variation in mounting behavior. For cows observed on two different days, correlations between successive observations were .46 for attempted mounts, .78 for successful mounts, and .71 for total mounts.(ABSTRACT TRUNCATED AT 400 WORDS)