Pharmacological evaluation of a selective bradykinin B1 antagonist in a canine model of arthritis.

The effects of a selective bradykinin 1 receptor antagonist, compound A, were evaluated in a canine model of acute inflammatory model of arthritis. Despite detection of the B1 receptor in canine type B synoviocytes using a fluorescent ligand, oral administration of compound A (9 and 27 mg/kg) did not improve weight bearing of dogs injected intra-articularly with IL-1ß in a force plate analysis. Analysis of the synovial fluid of IL-1ß-treated dogs indicated high levels of bradykinin postchallenge. Excellent exposure, coupled with evidence of the presence of the B1 receptor during an acute inflammatory model of pain, indicates an inability of the receptor to mediate inflammatory pain in canines.

Pulmonary pharmacokinetics of tulathromycin in swine. Part 2: Intra-airways compartments.

The objective of this study was to assess the pharmacokinetics of tulathromycin in pulmonary and bronchial epithelial lining fluid (PELF and BELF) from pigs. Clinically healthy pigs were allocated to two groups of 36 animals each. All animals were treated with tulathromycin (2.5 mg/kg/i.m). Animals in group 2 were also challenged intratracheally with lipopolysaccharide from Escherichia coli 3 h prior to tulathromycin administration. Both PELF and BELF samples were harvested using bronchoalveolar lavage fluid and bronchial micro-sampling probes, respectively. Samples were taken for 17 days post-tulathromycin administration. No statistical differences in the concentration of tulathromycin were observed in PELF between groups. The concentration vs. time profile in BELF was evaluated only in Group 1. Tulathromycin distributed rapidly and extensively into the airway compartments. The time to maximal (Tmax ) concentration was 6 h postdrug administration in PELF but 72 h post-tulathromycin administration for BELF. In group 2, the Tmax was seen at 24 h post-tulathromycin administration. The area under the concentration time curve (h*ng/mL) was 522 000, 348 000 and 1 290 000 for PELFGroup-1 , PELFGroup-2 , and BELFGroup-1 , respectively. Tulathromycin not only distributed rapidly into intra-airway compartments at relatively high concentrations but also resided in the airway lining fluid for a long time (>4 days).

Pulmonary pharmacokinetics of tulathromycin in swine. Part I: Lung homogenate in healthy pigs and pigs challenged intratracheally with lipopolysaccharide of Escherichia coli.

The objective of the study was to assess the pharmacokinetics of tulathromycin in lung tissue homogenate (LT) and plasma from healthy and lipopolysaccharide (LPS)-challenged pigs. Clinically healthy pigs were allocated to two dosing groups of 36 animals each (group 1 and 2). All animals were treated with tulathromycin (2.5 mg/kg). Animals in group 2 were also challenged intratracheally with LPS from Escherichia coli (LPS-Ec) 3 h prior to tulathromycin administration. Blood and LT samples were collected from all animals during 17-day post-tulathromycin administration. For LT, one sample from the middle (ML) and caudal lobes (CL) was taken. The concentration of tulathromycin was significantly lower in the ML after the intratracheal administration of LPS-E. coli (P < 0.02). In healthy pigs and LPS-challenged animals, the distribution of the drug into the lungs was rapid and persisted at high levels for 17-day postadministration. The distribution of the drug within the lung seems to be homogenous, at least between the middle and caudal lobes within dosing groups. The concentration versus time profile of the drug and pharmacokinetic parameters in two different lung areas (middle and caudal lobe) were consistent within the groups. The clinical significance of these findings is unknown.

An acute reversible experimental model of pneumonia in pigs: time-related histological and clinical signs changes.

The objective of this study was to evaluate the long-term survival rates, clinical response, and lung gross and microscopic changes in pigs treated intratracheally with lipopolysaccharide of Escherichia coli 0111:B4 (LPS-Ec). Healthy pigs were randomly allocated to three groups: (i) no-LPS-Ec (n=1), (ii) LPS-Ec-T1 (1 mg/mL, 10 mL/pig) (n=7), and (iii) LPS-Ec-T2 (0.5 mg/mL, 10 mL/pig) (n=6). Two pigs from each dose group were euthanized at 24 (n=3 for T1), 48 and 144 h post-LPS-Ec challenge. LPS-Ec-treated animals showed macroscopic lesions in middle lobes of the lung. A reversible recruitment of macrophages and neutrophils was observed at 24, 48, and 144 h post-LPS-Ec challenge. The highest cellular infiltration level was observed at 24 h after challenge. The highest clinical scores were evident in both experimental dose levels within 3 and 5 h after LPS-Ec administration. Administration of LPS-Ec, under the conditions evaluated, can be used to induce a reproducible model of acute pulmonary inflammation in pigs.

Serological survey of Neospora caninum infection in dairy cattle herds in Aguascalientes, Mexico.

A serological survey for antibody activity to Neospora caninum was carried out in Aguascalientes, a state in the central part of Mexico. One-hundred and eighty-seven serum samples from 13 dairy herds were tested by the ELISA test. The herd prevalence was 100% and the overall prevalence was 59% (n=110). Seventy-six of 97 seropositive cows had previous records of abortion. There was a statistically significant difference between the groups (P<0.05). However, the odds ratio was 1.4, suggesting an association between abortion and seropositivity. Neosporosis in dairy cattle appears to be widespread in Mexico, warranting more epidemiological studies to determine the distribution of the causative protozoan.

Plasmodium chabaudi chabaudi: effect of low parasitemias on immunity in CB6F1 mice.

We examined the effect that low parasitemias have on the immune response of CB6F1 mice infected with Plasmodium chabaudi chabaudi AS. Ascending parasitemias were stopped by chloroquine treatment when they were between 1.6 and 9.4%. Mice that suffered low parasitemias developed good immunity to homologous reinfection but, contrary to what happened in mice that suffered full parasitemias, they did not develop immunity to heterologous reinfection with Plasmodium yoelii 17XL. Total IgG antiparasite antibody responses were similar in mice that suffered low or full parasitemia, both in primary infection and after reinfection. At the level of isotypes, IgM, IgG1, IgG2b, and IgG3 responses were similar in mice that suffered low or full parasitemias, but after reinfection, mice that suffered low parasitemias responded with higher levels of IgG2a than mice that suffered full parasitemias. Mice that suffered low parasitemias did not have splenomegaly but their immunity to homologous reinfection was diminished after splenectomy in a manner similar to that of splenectomized mice that suffered full parasitemia. CB6F1 mice can develop homologous immunity even if exposed to low parasitemias but cannot develop heterologous immunity unless exposed to high parasite loads.

Bovine anaplasmosis prevalence in northern Veracruz state, Mexico.

In order to learn more about the presence of bovine anaplasmosis in northern Veracruz state, México, paired blood and serum samples from 368 cattle were subjected to polymerase chain reaction (PCR) and complement-fixation test (CFt). The overall prevalence of Anaplasma marginale by PCR was 69.2% and seroprevalence by CFt 54.6%. Age-specific prevalence was calculated for each test. Sixty-eight percent of animals from 0 to 3 months of age already were infected (PCR-positive), compared to only 42.4% positive by serology. CFt results suggested that presence of antibody increases with age up to 18 to 36 months, decreasing thereafter. Presence of the rickettsia seems to follow the same early pattern but with a new increase in animals 36 months or older. Serology results provided a biased picture of the true prevalence of anaplasmosis. Calculated specificity and sensitivity (63.5% and 68.2%) for CFt using PCR values as true values, appear very low and unreliable. The data generated by DNA-based surveys seem more appropriate to help design and implement control or eradication programs for bovine anaplasmosis.