The pharmacokinetics and metabolism of ivermectin in domestic animal species

The pharmacokinetic properties of drugs are closely related to their pharmacological efficacy. The kinetics of ivermectin are characterised, in general terms, by a slow absorption process, a broad distribution in the organism, low metabolism, and slow excretion. The kinetics vary according to the route of administration, formulation, animal species, body condition, age, and physiological status, all of which contribute to differences in drug efficacy. Characterisation of ivermectin kinetics can be used to predict and optimise the value of the parasiticide effects and to design programmes for parasite control. This article reviews the pharmacokinetics of ivermectin in several domestic animal species.     

菊苣酸对围产期放牧牦牛生长性能、血清生化指标及抗氧化能力的影响

试验旨在研究菊苣酸对放牧牦牛围产期生长性能、血清生化指标及抗氧化能力的影响。选择体况良好、体重接近(195～205kg)的围产期牦牛16头,随机分为2组,每组8头,对照组饲喂精料补充料+燕麦青干草,试验组饲喂精料补充料+燕麦青干草+0.15kg/d菊苣酸。试验期60d(从产前30d到产后30d),于产前第15天、产前第7天、分娩当天、产后第7天、产后第15天采集血液,进行相应指标的测定。结果显示:在产后第15天,试验组牦牛血清尿素氮(BUN)显著低于对照组(P<0.05);在分娩当天和产后第7天,试验组牦牛血清葡萄糖(GLU)含量、碱性磷酸酶(ALP)活性及总抗氧化能力(T-AOC)显著高于对照组(P<0.05),谷草转氨酶(AST)活性显著低于对照组(P<0.05);在分娩当天,试验组牦牛血清谷胱甘肽过氧化物酶(GSH-Px)、超氧化物岐化酶(SOD)活性显著高于对照组(P<0.05),血清丙二醛(MDA)含量显著低于对照组(P<0.05)。综合试验结果,添加菊苣酸能有效缓解围产期放牧牦牛氧化应激状态,提高其抗氧化能力。     

Screening of five drugs for efficacy against Babesia felis in experimentally infected cats

The efficacy of 5 drugs was tested against experimental Babesia felis infection in domestic cats. Two of the drugs, rifampicin and a sulphadiazine-trimethoprim combination, appeared to have an anti-parasitic effect, but were inferior to primaquine. The other 3 drugs, buparvaquone, enrofloxacin and danofloxacin, had no significant anti-babesial effect.     

Intravenous administration of levothyroxine for treatment of suspected myxedema coma complicated by severe hypothermia in a dog

A 7-year-old male English Coonhound with suspected myxedema coma complicated by severe hypothermia and metabolic abnormalities was treated with a combination of active external and core rewarming techniques, i.v. and oral administration of levothyroxine, supplemental oxygen, and administration of fluids (0.9% NaCl solution). Myxedema coma develops as a consequence of severe hypothyroidism and is characterized by a hypometabolic, stuporous state. Myxedema coma is associated with a high mortality rate, and most reported cases have involved Doberman Pinschers. Intravenous administration of levothyroxine can be used successfully in combination with oral administration to restore normal metabolic function and assist in warming and thermoregulation, although dosages should be conservative to avoid adverse cardiovascular effects.     

Modulation of peripheral markers of the serotoninergic system in healthy horses

To evaluate the changes in plasma and platelet serotonin (5-HT) as markers of the serotoninergic system in equines, 5-HT content was measured by high performance liquid chromatography (HPLC) in deproteinized plasma obtained from peripheral blood samples of 12 clinically healthy horses, before and after feeding. 5-HT was measured in platelet rich plasma (PRP) and in platelet poor plasma (PPP). 5-HT in platelets (p5-HT) was obtained by subtracting free 5-HT in PPP (f5-HT) from 5-HT in PRP. After food ingestion, significant increases in p5-HT and f5-HT (p < 0.001), and no changes in the f5-HT/p5-HT ratio were recorded. Increase in the total circulating 5-HT might account both for initiating peristaltic activity and for increasing the f5-HT levels. Augmented 5-HT uptake by platelets could reflect the hypothetical increased activity of the serotoninergic neurons. Besides showing the feasibility to obtain f5-HT and p5-HT through HPLC determination of 5-HT in PRP and PPP equine plasma, these findings are consistent with the postulation that 5-HT is released from enterochromaffin cells following a mechanical and chemical stimulation.     

<Emphasis Type="Italic">Streptococcus uberis</Emphasis>-specific T cells are present in mammary gland secretions of cows and can be activated to kill <Emphasis Type="Italic">S. uberis</Emphasis>

The presence, phenotype and function of Streptococcus uberis-specific T cells in the mammary gland secretion (MGS) and blood of cows exposed to S. uberis were assessed. MGS T cells in the udder were purified and incubated with autologous blood monocytes as antigen-presenting cells (APC). Most cows, irrespective of prior S. uberis infection status and lactation status, were shown to have S. uberis-specific T cells both in MGS and in the blood. When cells from a subgroup of cows were studied, it was found that the S. uberis-specific T cells produced high levels of interferon-gamma (IFN-γ), but low levels of interleukin-10 (IL-10). A high percentage of responding T cells were of the CD8 ⁺ memory (CD45RO) subset. T cells from the MGS specific for S. uberis were propagated from animals during the drying off period and expanded in vitro using interleukin-2 (IL-2) and S. uberis antigens. This led to the accumulation of T cells of the CD8 ⁺ subset bearing memory cell markers (CD45A ⁻ , CD45RO ⁺ ), which released high levels of IFN-γ. Four of the five T cell lines derived from the MGS of three animals had substantial direct killing activity towards S. uberis in vitro. It is concluded that there is an emergence of S. uberis-specific bactericidal T cells in the MGS of cows after infection or environmental exposure to S. uberis. Vaccines aimed at activating and expanding this T cell population in the mammary glands of cattle may offer an avenue for the prevention of mastitis caused by S. uberis.     

Ki-67 and minichromosome maintenance-7 (MCM7) expression in canine pituitary corticotroph adenomas

Pituitary-dependent hyperadrenocorticism (PDH) caused by pituitary corticotroph adenoma is a common endocrine disorder in dogs. The ratio between pituitary height and the area of the brain (P/B) has been used to evaluate the pituitary size. A P/B ratio > 0.31 indicates an enlarged pituitary, whereas a P/B ratio ≤ 0.31 indicates a nonenlarged pituitary. The aim of this study was to investigate the expression of proliferation markers Ki-67 and minichromosome maintenance-7 (MCM7) in canine corticotroph adenomas in enlarged and in nonenlarged pituitaries and to evaluate their relation with the size of canine pituitary corticotroph adenomas. Ki-67 and MCM7 expression in ACTH-positive tumor cells was determined by dual-labeling immunohistochemistry in resected corticotroph adenomas from 15 dogs with PDH. The mean ± SD Ki-67 labeling index (LI) was 0.55% ± 0.59% in corticotroph adenomas with nonenlarged pituitaries and 1.6% ± 0.6% in adenomas with enlarged pituitaries. The MCM7 LI in corticotroph adenomas with nonenlarged pituitaries and in adenomas with enlarged pituitaries was 2.9% ± 2.2% and 10.9% ± 3.7%, respectively. The Ki-67 LI and MCM7 LI were significantly greater in the adenomas with enlarged pituitaries than in the adenomas with nonenlarged pituitaries (P < 0.01 and P < 0.01, respectively). The MCM7 LI was significantly greater than the Ki-67 LI in adenomas (P < 0.01). The Ki-67 LI was positively correlated with the MCM7 LI (r = 0.820, P < 0.01), and the P/B ratio was positively correlated with the Ki-67 LI (r = 0.560, P = 0.03) and the MCM7 LI (r = 0.854, P < 0.01). In conclusion, canine corticotroph adenomas in enlarged pituitaries show greater proliferation potential than do adenomas in nonenlarged pituitaries. MCM7 expression was significantly greater than Ki-67 expression in canine pituitary corticotroph adenomas. Thus, MCM7 may be superior to Ki-67 as a proliferation marker in pituitary tumors.     

Influence of condensed tannin on intake, digestibility, and efficiency of protein utilization in beef steers fed high concentrate diet

This trial was conducted to evaluate if the effect of condensed tannin (CT) is associated with a true protein source on intake, ruminal and total digestibility, ruminal digestion rate, protein efficiency, and microbial efficiency in beef steers fed high concentrate diet (87% of DM). Four Bos indicus steers (407 ± 12 kg of BW) fitted with rumen cannula were assigned to a 4 × 4 Latin square design, arranged in a 2 × 2 factorial arrangement. Treatments consisted of either inclusion (0.4% of DM) or exclusion of condensed tannin (CT) from quebracho extract (76% of CT) with or without the use of soybean meal (SBM) as source of true protein. The level of inclusion was calculated to provide a daily intake of 1 g/10 kg of BW of CT. Intake of DM and nutrients was not affected (P > 0.10) by CT inclusion. However, there was an effect (P < 0.10) of CT inclusion on ether extract digestibility. An interaction (P < 0.10) was observed between CT and SBM on ruminal digestibility and digestion rate of crude protein (CP): when mixed with soybean meal, CT decreased the ruminal digestibility and, consequently, reduced the digestion rate of CP. Intake of CP increased (P < 0.10) with the inclusion of SBM. No differences in DM passage rate were observed (P > 0.10) among treatments. Effects of the interaction (P < 0.10) between CT and SBM were observed on flux of rumen undegradable protein (RUP), metabolizable protein (MP), and on the ratio MP:CP. In the presence of soybean meal, the addition of CT increased (P < 0.10) the flux of RUP and MP, and improved the ratio MP:CP. The yield of microbial protein on the abomasum and the microbial efficiency did not differ among treatments (P > 0.10). There was no difference (P > 0.10) on the pH, VFA, and ruminal ammonia (N-NH₃) with the addition of condensed tannin. The N-NH₃ increased and the ruminal pH decreased with the inclusion of soybean meal (P < 0.10). The utilization of condensed tannin as an additive in beef cattle diets with high level of concentrate and soybean meal as a source of true protein implies positive effects on crude protein utilization, decreasing digestion rate and ruminal digestibility of crude protein and consequently increasing the levels of metabolizable protein, with no changes in the ruminal fermentation parameters.