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.     

Use of a graft of demineralized bone matrix along with TGF-β1 leads to an early bone repair in dogs

Tibia fractures are common in small animal practice. Over the past decade, improvements to animal internal fracture fixation have been developed. TGF-β1 has been shown to be crucial in the development, induction and repair of bone. In present study, we investigate the effect of local application of a graft demineralized bone matrix (DBM) along with TGF-β1 in a model of open osteotomy induced experimentally in dogs. Tibia fracture was brought about by using an open osteotomy model in young male dogs. Fracture repair was evaluated by a histological and biochemical analysis. Collagen content, proteolytic activity and urokinase-type plasminogen activator (uPA) expression were analyzed at the end of the study. Radiographic analysis, alkaline phosphatase and hematological evaluation were performed weekly. At the fifth week, there was an improvement and restoration of bone architecture in animals treated with a graft containing TGF-β1 (5 ng/ml) compared with the control and graft groups, as was evidenced by the presence of an early formation of wide callus and bone regeneration. In addition, local application of TGF-β1 led to an increase in collagen and proteolytic activity. More immunopositive osteoclast and mesenchymal cells were found in bone tissue from animals treated with TGF-β1 as compared with the control group. No changes in alkaline phosphatase, hematological and clinical parameters were observed. This study shows that the combined use of DBM along with TGF-β1 is able to improve and accelerate the bone repair.     

A recombinant-based ELISA evaluating the efficacy of netobimin and albendazole in ruminants with naturally acquired fascioliasis

The therapeutic efficacy of albendazole and netobimin in ruminants with naturally occurring fascioliasis was investigated using a recombinant-based ELISA. The variation in the IgG response against a 2.9-kDa recombinant protein (FhrAPS), termed efficacy index (EI) 1, and the egg-output changes, termed EI 2, were used to evaluate drug efficacy.The values of EI 1 ranged between 0% and 50% in sheep, and between 0% and 30% in cattle after treatment with albendazole and netobimin. Similar EI 2 values were observed in sheep receiving albendazole or netobimin, but the highest values were found in cattle treated with netobimin. The significant reduction in the IgG response to FhrAPS found in this study shows promise in terms of developing alternative methods for evaluating the efficacy of chemotherapy against Fasciola hepatica in grazing ruminants.     

Culture system and long-term storage of culture media in the in vitro production of bovine embryos

The optimum culture system for in vitro matured and fertilised oocytes still remains to be clarified. Culture media (CM) for mammalian embryos are routinely prepared fresh for use and preserved under refrigeration during one or two weeks. The purposes of this work were (1) to compare the efficiency of a synthetic oviduct fluid (SOF) with two different bovine serum albumin (BSA) concentrations (3 and 8 g/L) for the in vitro production of bovine blastocysts, (2) to test the effect of timing on adding fetal calf serum (FCS) to the SOF, and (3) to evaluate the effects on bovine embryo development of freezing and lyophilisation as procedures for preserving the SOF. Supplementation of SOF with 3 g/L BSA increased Day-7 blastocyst expansion rates (18.3 ± 1.6 vs. 14.4 ± 0.7; P < 0.05), although no differences in hatching rates were found. Addition of FCS to SOFaa (SOF with amino acids) medium supplemented with sodium citrate (SOFaaci) at 48 and at 72 h post-insemination (PI) allowed obtaining higher Day-6 embryo development rates than when FCS was added at 18 or 96 h PI (Day-6 morulae + blastocyst rate: 30.0 ± 1.1, 40.8 ± 1.1, 43.9 ± 2.3 and 39.3 ± 0.5 for FCS addition at 18, 48, 72 and 96 h, respectively). Hatching rates were significantly improved when serum was added at 72 h PI. Finally, both refrigeration and lyophilisation appeared as useful cryopreservation procedures for SOFaaci, although a significant loss of its ability to support embryo development, compared to the control fresh culture medium, was observed.     

Complex polysaccharide inclusions in the skeletal muscle of stranded cetaceans

Skeletal muscle samples were examined post-mortem in 148 cetaceans over a 12-year period. Histological analysis included haematoxylin and eosin (HE) and periodic acid-Schiff (PAS) staining with and without diastase digestion. In addition, histological muscle sections were immunostained for ubiquitin and fast and slow heavy-chain myosin isoforms. PAS-positive, diastase-resistant inclusions were detected in 26 animals from 11 different species. Older cetaceans were preferentially affected. These intrafibre inclusions varied from large aggregates to multiple coarse granules and were typically associated with type II fibres. All diastase-resistant inclusions were positive for ubiquitin. These features resembled those inclusions described as complex polysaccharide in horses. Based on these histological findings and the ubiquitin staining pattern, a morphological diagnosis of complex polysaccharide storage myopathy is proposed.     

The Effect of Supplementation with Fresh Browse of Ziziphus mauritiana or Combretum aculeatum on Feed Intake,Nitrogen Utilization and Growth of Grazing Range Sheep

The influence of 0, 60 or 120 min access to a grove of either Ziziphus mauritiana (Ziziphus) or Combretum aculeatum (Combretum) on forage intake and on the digestibility, growth and excretion of nutrients was determined using 40 Oudah rams grazing for 7 h/day on poor-quality dry season pasture in the Sahel. The effects of browse species and browsing duration (0, 30, 60 or 120 min) on the ruminal ammonia content were also evaluated using 8 mature fistulated rams. Ziziphus increased both total digestible organic matter and total dry matter intakes per (kg live weight)^0.75 without decreasing herbage intake, whereas 60 or 120 min access to Combretum reduced herbage intake by 6.3% and 4.2%, respectively. The digestibility of the diet decreased (p<0.05) with the duration of access to the groves. Despite the provision of more nitrogen (N) than in the control diet, ruminal NH₃-N decreased 24 h after browsing commenced. The reduced live weight gain of sheep browsing Combretum may indicate more deleterious compounds in Combretum than in Ziziphus. Ziziphus appears to have more potential than Combretum to increase sheep production in low-input crop/livestock systems.     

Study on the inductive factors of hypobiosis of Ostertagia ostertagi in cattle

Two experiments were carried out to determine the causes producing the Ostertagia ostertagi hypobiosis phenomenon in cattle. In the first experiment, the effect of time on third-stage larvae in the environment was studied during a 2-year period. Three experimental paddocks contaminated with O. ostertagi eggs at different times of the year were used, and the levels of hypobiosis were recorded by using 'indicator' and 'tracer' calves. The results suggest that time as such is not a hypobiosis-inductive factor. The second experiment was conducted under laboratory conditions, where the effects of temperature and light on infective larvae were studied. Infective larvae were subjected to different conditions of temperature and light during 6 weeks, and then inoculated to parasite-naive calves, which were slaughtered after 4 weeks. Percentages of hypobiotic larvae in these calves varied from 3.5 to 94.8%, depending on the different storage conditions the larvae underwent before inoculation. Results suggest that increasing temperature and increasing time of light exposure simulating spring conditions would be the factors which act upon third-stage larvae inducing them to a later hypobiotic stage in the host.