Oral bioavailability and pharmacokinetic characteristics of ketoprofen enantiomers after oral and intravenous administration in Asian elephants (Elephas maximus)

OBJECTIVE: To assess oral bioavailability (F) and pharmacokinetic characteristics of the R- and S-enantiomers of ketoprofen administered IV and orally to captive Asian elephants (Elephas maximus). ANIMALS: 5 adult Asian elephants. PROCEDURE: Elephants received single treatments of racemic ketoprofen at a dose of 2.2 mg/kg, administered IV and orally, in a complete crossover design. Blood samples were collected at intervals during the 24 hours following treatment. At least 4 weeks elapsed between drug administrations. Samples were analyzed for R- and S-ketoprofen with a validated liquid chromatography-mass spectroscopic assay. Pharmacokinetic parameters were determined by use of noncompartmental analysis. RESULTS: The enantiomers of ketoprofen were absorbed well after oral administration, with median F of 101% for R-ketoprofen and 85% for S-ketoprofen. Harmonic mean half-life ranged from 3.8 to 5.5 hours, depending on route of administration and enantiomer. The area under the concentration-time curve, mean residence time, apparent volume of distribution, plasma clearance, and maximum plasma concentration values were all significantly different between the 2 enantiomers for both routes of administration. CONCLUSIONS AND CLINICAL RELEVANCE: Ketoprofen has a long terminal half-life and complete absorption in this species. Based on the pharmacokinetic data, a dosage of ketoprofen of 1 mg/kg every 48 hours to 2 mg/kg every 24 hours, PO or IV, is recommended for use in Asian elephants, although the safety and efficacy of ketoprofen during long-term administration in elephants have not been determined.     

PNEUMOCOELOM ASSOCIATED WITH SERRATOSPICULUM AMACULATA IN A BALD EAGLE

Serratospiculum amaculata Nemutodes were identified radiographically in the air sacs of an eagle which developed acute respiratory distress several days after treatment for severe head trauma. The nematodes were found at necropsy within the air sacs and lungs. One of the nematodes was found protruding through a hole in the lung. Although this parasite was reported in a falcon which died post operatively this is the first report of death in an eagle related to the presence of this parasite and is also the first time the parasite itself has been observed in a raptor antemortem.     

Six novel gammaherpesviruses of Afrotheria provide insight into the early divergence of the Gammaherpesvirinae

The Afrotheria represent an early branching of placental mammals. Only two herpesviruses from Afrotheria have been previously identified, and the genus Proboscivirus in the subfamily Betaherpesvirinae has been proposed for them. Six novel gammaherpesviruses were identified in four species in the superorder Afrotheria by detection and analysis of their DNA polymerase genes. Elephantid herpesvirus 3 (ElHV3) and Elephantid herpesvirus 4 (ElHV4) were identified from conjunctival swabs from Asian elephants (Elephas maximus). ElHV3 was also found in a vaginal swab from one elephant with vaginitis. Elephantid herpesvirus 5 (ElHV5) was identified from vaginal swabs of two Asian elephants with vaginal plaques. Elephantid herpesvirus 6 was discovered in a conjunctival swab from an African elephant (Loxodonta africana). Procavid herpesvirus 1 (PrHV1) was found in spleen and conjunctival swabs of rock hyrax (Procavia capensis). Trichechid herpesvirus 1 (TrHV1) was identified from skin and buffy coats of Florida manatees (Trichechus manatus latirostris). ElHV3 and ElHV4 form a distinct cluster, and ElHV5, ElHV6, TrHV1, and PrHV1 form a second cluster. These viruses may have codiverged with their host species. Phylogenetic analysis of these novel herpesviruses suggests that two separate groups of gammaherpesviruses may have codiverged with the Afrotheria.     

Evaluation of a multiple-antigen enzyme-linked immunosorbent assay for detection of Mycobacterium tuberculosis infection in captive elephants.

Mycobacterium tuberculosis has become an important agent of disease in the captive elephant population of the United States, although current detection methods appear to be inadequate for effective disease management. This investigation sought to validate a multiple-antigen enzyme-linked immunosorbent assay (ELISA) for screening of M. tuberculosis infection in captive elephants and to document the elephant's serologic response over time using a cross-sectional observational study design. Serum samples were collected from 51 Asian elephants (Elephas maximus) and 26 African elephants (Loxodonta africana) from 16 zoos and circuses throughout the United States. Infection status of each animal was determined by mycobacterial culture of trunk washes. Reactivity of each serum sample against six antigens was determined, and the linear combination of antigens that accurately predicted the infection status of the greatest number of animals was determined by discriminant analysis. The resulting classification functions were used to calculate the percentage of animals that were correctly classified (i.e., specificity and sensitivity). Of the 77 elephants sampled, 47 fit the criteria for inclusion in discriminant analysis. Of these, seven Asian elephants were considered infected; 25 Asian elephants and 15 African elephants were considered noninfected. The remaining elephants had been exposed to one or more infected animals. The specificity and sensitivity of the multiple-antigen ELISA were both 100% (91.9-100% and 54.4-100%, respectively) with 95% confidence intervals. Mycobacterium bovis culture filtrate showed the highest individual antigen specificity (95%; 83.0-100%) and sensitivity (100%; 54.4-100%). Serum samples from 34 elephants were analyzed over time by the response to the culture filtrate antigen; four of these elephants were culture positive and had been used to calculate the discriminant function. Limitations such as sample size, compromised ability to ascertain each animal's true infection status, and absence of known-infected African elephants suggest that much additional research needs to be conducted regarding the use of this ELISA. However, the results indicate that this multiple-antigen ELISA would be a valuable screening test for detecting M. tuberculosis infection in elephant herds.     

Vaccination of Egyptian fruit bats (Rousettus aegyptiacus) with monovalent inactivated rabies vaccine.

Twenty-six captive, adult Egyptian fruit bats (Rousettus aegyptiacus) were tested for the presence of rabies virus neutralizing antibodies (RVNA) using a rapid fluorescent focus inhibition test before and after vaccination. The bats were randomly assigned into three treatment groups: group A (n = 10) bats each received one 0.1-ml dose of monovalent inactivated rabies vaccine, group B (n = 10) bats each received two 0.1-ml doses of vaccine given 30 days apart, and group C (n = 6) bats remained unvaccinated. Plasma was collected from all bats before vaccination and on days 14, 30, 60, and 360. All bats were seronegative before vaccination, and all unvaccinated animals remained negative throughout the study. Rabies virus neutralization titers remained above 0.5 IU/ml from day 30 through day 360 for both vaccinated groups. Group B had significantly higher titers on day 60. This study demonstrated a measurable humoral immune response after vaccination with an inactivated rabies vaccine, with two doses producing a higher level of RVNA. This study confirms the feasibility of a rabies vaccination program for Egyptian fruit bats.     

Effect of Zn binding to phytate and humic substances on its uptake by wheat (Triticum durum L.) as affected by carbonates and Fe oxides

Although complexation with soil organic matter may improve zinc (Zn) bioavailability to plants, the effect of Zn sorbent surface on the use of complexed Zn by plants remains unknown. The objective of this research was to elucidate how Zn complexation with humic substances (HS) and phytate affects the uptake of Zn by wheat plants depending on the main sorbent surface in growth media, i.e., carbonates and Fe oxides. To this end, two pot experiments were performed, one using Fe oxide-coated siliceous as the siliceous growth medium sand and the other using a mixture of calcareous sand and siliceous sand as the calcareous growth medium. Each experiment involved three Zn sources, Zn-HS complex, Zn phytate, and ZnSO₄. All sources were applied with surface irrigation at two Zn rates (0.25 and 2 mg kg^-1 growth medium). The Zn-HS complex significantly increased Zn uptake by plants in both media, relative to the other two Zn sources, but no significant difference was observed between Zn phytate and ZnSO₄. In the calcareous medium, Zn-HS complex and Zn phytate resulted in significantly higher dry biomass yields of wheat than ZnSO₄. In the siliceous medium, spike and shoot dry biomass yields with Zn-HS complex at the low rate and Zn phytate at both rates were not significantly different from those with ZnSO₄ at the high rate. After harvest, approximately 50% of the Zn applied as Zn-HS complex remained extractable by diethylenetriaminepentaacetic acid (DTPA), while this proportion was less than 20% for the other Zn sources. Thus, Zn-HS complex and Zn phytate are sources of available Zn for plants, and they are more effective than ZnSO₄ in increasing plant growth, particularly when carbonates are the main Zn sorbent surface.     

The determination of total phosphorus improves the accuracy of the bicarbonate extraction as an availability index

The efficient use of phosphorus (P) in agriculture should rely on accurate soil P tests (SPT). Organic P contributes to P supply to plants; however, it is not usually taken into account in assessing P fertilizer requirements. We hypothesized that there would be an increased accuracy of bicarbonate extraction as SPT in predicting P uptake by plants if total P (TP) in this soil extract is taken into account. We conducted a soil P depletion experiment with 36 soils involving four consecutive crops in pots. Molybdate‐reactive P (MRP) and total P were determined in extracts centrifuged at 19,000 g (Bic‐MRP_C and Bic‐TP_C) or not (Bic‐MRP and Bic‐TP). MRP in extracts explained <47% of the variance in the cumulative P uptake, while total P (centrifuged at 19,000 g or not) provided the most accurate estimation of P uptake (59% with Bic‐TP) and threshold values for fertilizer response (R² = 0.58 with Bic‐TPc). When soils were separated in two groups according to their Ca carbonate equivalent to clay ratio, the variance in the cumulative P uptake explained by Bic‐MRP was above 63%, and that explained by Bic‐TP was above 73%. This separation also enabled more realistic estimation of the threshold values for fertilizer response. It can be concluded that the use of total P instead of MRP in bicarbonate extraction was promising in terms of improving its accuracy in assessing P fertilizer requirements.     

Results of vaccination of Asian elephants (Elephas maximus) with monovalent inactivated rabies vaccine

OBJECTIVE: To evaluate the humoral immune response of Asian elephants to a primary IM vaccination with either 1 or 2 doses of a commercially available inactivated rabies virus vaccine and evaluate the anamnestic response to a 1-dose booster vaccination. ANIMALS: 16 captive Asian elephants. PROCEDURES: Elephants with no known prior rabies vaccinations were assigned into 2 treatment groups of 8 elephants; 1 group received 1 dose of vaccine, and the other group received 2 doses of vaccine 9 days apart. All elephants received one or two 4-mL IM injections of a monovalent inactivated rabies virus vaccine. Blood was collected prior to vaccination (day 0) and on days 9, 35, 112, and 344. All elephants received 1 booster dose of vaccine on day 344, and a final blood sample was taken 40 days later (day 384). Serum was tested for rabies virus-neutralizing antibodies by use of the rapid fluorescent focus inhibition test. RESULTS: All elephants were seronegative prior to vaccination. There were significant differences in the rabies geometric mean titers between the 2 elephant groups at days 35, 112, and 202. Both groups had a strong anamnestic response 40 days after the booster given at day 344. CONCLUSIONS AND CLINICAL RELEVANCE: Results confirmed the ability of Asian elephants to develop a humoral immune response after vaccination with a commercially available monovalent inactivated rabies virus vaccine and the feasibility of instituting a rabies virus vaccination program for elephants that are in frequent contact with humans. A 2-dose series of rabies virus vaccine should provide an adequate antibody response in elephants, and annual boosters should maintain the antibody response in this species.