In vivo and ex vivo assessment of the interaction between ivermectin and danofloxacin in sheep

The impact of an efflux pump-related interaction between ivermectin and danofloxacin on their intestinal transport (ex vivo) and disposition kinetics (in vivo) was assessed. Eighteen male Corriedale sheep were randomly assigned to one of three groups. Animals in Group A received 0.2mg/kg ivermectin by SC injection, those in Group B were given 6 mg/kg danofloxacin SC on two occasions 48 h apart and those in Group C were treated with both compounds at the same rates. Plasma concentrations of ivermectin and danofloxacin were measured by HPLC using fluorescence detection. Ex vivo intestinal drug transport activity was measured by the use of the Ussing chamber technique. Plasma concentrations of ivermectin in the first 6 days after injection tended to be higher in Group C than Group A. Contemporaneous treatment with ivermectin significantly increased systemic exposure to danofloxacin (AUC values were 32-35% higher) and prolonged the elimination half-life of danofloxacin (40-52% longer). Ex vivo, incubation with ivermectin significantly decreased the efflux transport of rhodamine 123, a P-glycoprotein substrate, in sheep intestine, but no significant effect of danofloxacin on transport activity was observed. Evaluation of the interaction of danofloxacin with the breast cancer resistance protein (BCRP) showed that pantoprazole and ivermectin significantly decreased danofloxacin secretion in the rat intestine. Thus, the ivermectin-induced reduction of danofloxacin efflux transport observed in this study may involve BCRP activity but the involvement of P-glycoprotein cannot be ruled out.     

Production of eosinophil chemoattractant activity by ovine gastrointestinal nematodes

Eosinophilia is a well documented feature of helminth infections but the precise nature of the interaction between parasite and eosinophil remains an enigma. This paper describes experiments demonstrating that ruminant gastrointestinal trichostrongyles produce potent chemoattractant activity for ovine bone marrow-derived eosinophils in vitro. This activity was initially identified as a constituent of whole worm extracts of third and fourth larval (L3, L4), and adult stages of Teladorsagia circumcincta, and adult Haemonchus contortus. Similar activity was detected in excretory/secretory (E/S) material derived from live T. circumcincta L3. Subsequently, by adapting the assay technique to incorporate live worms directly into the system, it was shown that L3 of both T. circumcincta and H. contortus produced eosinophil chemoattractant activity. In contrast, neither whole worm extracts, or E/S preparations from mixed stages of the free-living nematode Caenorhabditis elegans contained eosinophil chemoattractant activity, and there was no evidence of chemoattractant production by live C. elegans. The results described are challenging to the traditional dogma that eosinophils are host-protective effector cells, and raise the intriguing possibility that ovine nematodes actively encourage recruitment of eosinophils. Local eosinophil-mediated mucosal damage, comparable to that seen in the asthmatic lung, may then provide a permissive local microenvironment for the parasite. Moreover, if they prove important for pathogenicity, nematode chemoattractants could offer future potential as novel therapeutic targets.     

Feeding value of pastures for ruminants

Perennial ryegrass is the primary forage component of ruminant diets in New Zealand. It is persistent and palatable, and immature ryegrass has a high nutritive value (NV). However, seedhead development substantially lowers its feeding value (FV) as fibre concentration increases, the rate and extent of digestibility decreases, and voluntary intake declines. Ryegrass pastures are susceptible to accumulation of endophytic and saprophytic fungi in dead material at the base of the sward, especially when mature and laxly grazed. Feeding forage legumes to ruminants grazing grass-dominant pastures will improve animal performance and lessen the reliance on a single species to meet all nutritional requirements. The FV of forage is a function of intake and NV, measured by chemical analyses and animal feeding trials. Performance of individual animals grazing forages is usually limited by energy intake because structural fibre can slow digestion and clearance from the rumen and because of competition between individuals for available feed. The use of metabolisable energy (ME) content of forage to signify FV can give a reasonable indication of animal performance, but it should be used in conjunction with chemical analyses to improve the accuracy of predictions. The relationship between FV, pasture production, animal performance and profitability is complex. The importance of skilled management to maintain pasture quality and optimise animal performance under inconsistent climatic conditions should not be underestimated. Acceptable animal performance with minimal veterinary intervention requires good nutrition, but the genetic potential of livestock in New Zealand cannot be met solely by grazing pasture, especially when a high utilisation of pasture is required to maintain quality and profitability. Producers are responding to industry demands to reduce the seasonality in supply of milk and meat by changing lambing and calving dates, and extending lactation length in dairy cows. Social changes include adoption of once-daily milking in the dairy industry. Some changes have necessitated increased use of supplements and others can be met by feeding forages with a higher FV than ryegrass, all of which require an improved knowledge of feed quality. This information is available through rapid and inexpensive near infrared spectroscopy (NIRS) analysis, enabling animal nutritional needs to be balanced by appropriate nutrient supply. It is essential that producers continue to improve animal welfare, limit excessive use of fertilisers and meet the demands of overseas consumers. Good nutrition, with an increased use of legumes and other forages to complement ryegrass pastures, will enable these objectives to be achieved.     

Assessing Knowledge Production for Agrosilvopastoral Systems in South America

In recent decades agroforestry has undergone significant development in Latin America. South America generates the most scientific research on the topic in the region. We conducted a comprehensive review and analysis of knowledge production for South American agroforestry that includes livestock grazing, known as agrosilvopastoralism (AS), examining how different sociopolitical factors such as sources of funding, institutional priorities, and international cooperation can bias the direction and objectives of scientific research. We assessed the major attributes of scientific publications on the topic (25 articles per country; overall n = 210) and the potential factors underlying the processes of research and development in the region. The tree component was the most studied, while the livestock component received less attention. Studies were mainly focused on the production of goods and services (monetary or nonmonetary approaches), except in Brazil, where conservation was the major study objective. Stakeholders were involved in more than half of the studies (60%), and they were mostly ranchers and local producers. More than half (70%) of the studies offered recommendations based on their results, and such recommendations were mostly concerned with the management of agrosilvopastoral system components. In general, studies were led just as often by local as foreign first authors and coauthored by more than three people as part of interinstitutional working groups. Brazil, Argentina, Colombia, and Chile had more frequent cooperation among institutions and countries but mainly used their own funding. In contrast, Bolivia, Ecuador, and Peru had almost 100% of their studies supported by foreign countries (North America and Europe). Countries with greater internal funding of research generated more long-term studies. Besides this, two clear trends were detected: 1) conservation and social aspects were mainly supported by sources from external countries led by foreign principal investigators, and 2) production issues were supported from sources within countries and supported high levels of cooperation among institutions.