Ruminant Self-Medication Against Gastrointestinal Nematodes: Evidence, Mechanism, and Origins

Gastrointestinal helminths challenge ruminants in ways that reduce their fitness. In turn, ruminants have evolved physiological and behavioral adaptations that counteract this challenge. Ruminants display anorexia and avoidance behaviors, which tend to reduce the incidence of parasitism. In addition, ruminants appear to learn to self-medicate against gastrointestinal parasites by increasing consumption of plant secondary compounds with antiparasitic actions. This selective feeding improves health and fitness. Here, we review the evidence for self-medication in ruminants, propose a hypothesis to explain self-medicative behaviors (based on post-ingestive consequences), and discuss mechanisms (e.g., enhanced neophilia, social transmission) that may underlie the ontogeny and spread of self-medicative behaviors in social groups. A better understanding of the mechanisms that underlie and trigger self-medication in parasitized animals will help scientists devise innovative and more sustainable management strategies for improving ruminant health and well-being

Structure Analysis of Entamoeba histolytica DNMT2 (EhMeth)

In eukaryotes, DNA methylation is an important epigenetic modification that is generally involved in gene regulation. Methyltransferases (MTases) of the DNMT2 family have been shown to have a dual substrate specificity acting on DNA as well as on three specific tRNAs (tRNAAsp, tRNAVal, tRNAGly). Entamoeba histolytica is a major human pathogen, and expresses a single DNA MTase (EhMeth) that belongs to the DNMT2 family and shows high homology to the human enzyme as well as to the bacterial DNA MTase M.HhaI. The molecular basis for the recognition of the substrate tRNAs and discrimination of non-cognate tRNAs is unknown. Here we present the crystal structure of the cytosine-5-methyltransferase EhMeth at a resolution of 2.15 Å, in complex with its reaction product S-adenosyl-L-homocysteine, revealing all parts of a DNMT2 MTase, including the active site loop. Mobility shift assays show that in vitro the full length tRNA is required for stable complex formation with EhMeth

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age  6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score  652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

Host Behaviour, Environment and Ability to Self-Medicate

Herbivores form preferences for substances that raise fitness such as nutritious foods and avoid those substances, which lower fitness such as plant secondary compounds (PSC). Nevertheless, some PSC at certain concentrations have the potential to raise fitness as they act against infective diseases such as parasitism. The objective of the present review is to assess whether parasitized farm animals are able to manifest self-medicative behaviors. The ability of herbivores to self-select these medicinal plant compounds emerges from the inherent adaptive nature of behavioral responses in living organisms. In order to manifest self-medication animals should experience discomfort caused by a certain illness and also relief associated with the mitigation of sickness brought about by the ingestion of a medicinal plant. Observational and controlled studies suggest such conditions, as well as self-medicative behaviors occur not only in wild but also in domestic herbivores. Self-medicative behaviors may allow individuals seek medicinal plant products when infected by parasites, even at times when the manager is not aware of the existence of parasitism in the flock. Self-medication may also allow for proper nutrition as animals offered choices will consume PSC-containing plants as well as nutritious and safe forages. Management programs should be geared at enhancing in herbivores the likelihood of the association medicine-relief from sickness and at favoring the transmission of self-medicative behavior across generations

Ruminant self-medication against gastrointestinal nematodes: evidence, mechanism, and origins☆

Gastrointestinal helminths challenge ruminants in ways that reduce their fitness. In turn, ruminants have evolved physiological and behavioral adaptations that counteract this challenge. Ruminants display anorexia and avoidance behaviors, which tend to reduce the incidence of parasitism. In addition, ruminants appear to learn to self-medicate against gastrointestinal parasites by increasing consumption of plant secondary compounds with antiparasitic actions. This selective feeding improves health and fitness. Here, we review the evidence for self-medication in ruminants, propose a hypothesis to explain self-medicative behaviors (based on post-ingestive consequences), and discuss mechanisms (e.g., enhanced neophilia, social transmission) that may underlie the ontogeny and spread of self-medicative behaviors in social groups. A better understanding of the mechanisms that underlie and trigger self-medication in parasitized animals will help scientists devise innovative and more sustainable management strategies for improving ruminant health and well-being

Polyethylene Glycol Affects Goats\u27 Feeding Behavior in a Tannin-Rich Environment

High concentrations of condensed tannins in browse impair brush clearing by goats. We studied the effect of polyethylene glycol (PEG, MW 4000), a polymer that binds condensed tannins, on the feeding behavior of Damascus goats (Capra hircas) on a range dominated by tannin-rich lentisk (Pistacia lentiscus L.). This was done with or without a nutritious alternative to browse (alfalfa hay) available at pasture. In phase 1, no hay was provided to goats; in phase 2, hay was distributed daily in the field. In both phases, 6 goats had free access to PEG while at pasture, while 6 goats that grazed separately on another paddock did not. All goats received each night an allowance of concentrate (400 g day-1 of 40% ground corn grain, 40% ground barley, 17% soybean meal and 3% of a mineral-vitamin premix, and contained as fed 16% crude protein (CP) and 2.66 Mcal kg-1 of Metabolizable Energy). The 2 groups of goats alternated daily between paddocks. Goats supplemented with PEG spent more time browsing lentisk than goats in the control group (73 and 41%, respectively, P \u3c 0.0001). Goats in the control group spent more time foraging on dry grasses than their PEG-fed counterparts (28 and 12%, respectively, P \u3c 0.0001). Goats from the PEG group gained body weight at a higher rate than controls. The daily intake of PEG was 450 g, with an intake rate of 1.2 g sec-1. Supplemental alfalfa hay substituted partly for dry grasses in goats\u27 diets, but did not modify the percent of time goats in either treatment spent browsing lentisk. Our data suggest that PEG has the potential to increase intake of tannin-rich species, even where alternative fodder of better nutritional quality is present. However, self-feeding of PEG may not be the best way to provide PEG because goats may ingest more PEG than needed to annul the aversive effects of tannins on food intake

Long-term Trade-Offs Among Herbage Growth, Animal Production, and Supplementary Feeding in Heavily Grazed Mediterranean Grassland

A 17-yr grazing trial was conducted in the eastern Galilee of Israel to quantify trade-offs among the responses of pasture and livestock productivity, duration of grazing, amount of supplementary feed, and profitability to higher stocking density during the growing season of a Mediterranean grassland. Treatments included two stocking densities and two grazing protocols. The stocking densities throughout the grazing period were 0.55 animal unit (AU)·ha-1, which is common in this region, and 1.1 AU·ha-1, which is considered high. The grazing protocols were continuous grazing throughout the grazing season and split-paddock grazing in which the herd grazed one subpaddock from the onset of grazing until the pasture was depleted, after which the herd was moved to the second ungrazed subpaddock. Under both protocols, heavier stocking density reduced standing biomass of the whole paddock at the end of the growing season by 43% and grazing duration during the subsequent dry season by 38% but increased the daily consumption of supplementary feed and the weaned live-weight production per unit area. Under continuous grazing the high stocking density of 1.1 AU·ha-1 was maintained throughout the grazing season for 17 consecutive yr with no detectable effect on productivity of the pasture, typical to the resilience of Mediterranean grasslands that have been grazed for thousands of years. The lower pasture biomass production was compensated by higher weaned calf production. At the current local prices, the heavier stocking density was close to the economically optimal stocking density for the pasture in the region. It is concluded that on Mediterranean grassland intensive use of the pasture with high stocking density during the growing season can be economically feasible in those cases where the feed requirement of the herd can be maintained throughout the growing season. © 2015 Society for Range Management. Published by Elsevier Inc. All rights reserved.The Rangeland Ecology & Management archives are made available by the Society for Range Management and the University of Arizona Libraries. Contact [email protected] for further information