Clays have played an important role in medicine since the dawn of mankind and are still applied widely as active ingredients and/or excipients in pharmaceutical formulations. Due to their outstanding properties of large retention capacity, swelling and rheological properties, and relative low cost, they have been used widely as advanced carriers for the efficient delivery of drugs by modifying their release (rate and/or time), increasing the stability of the drug, improving the dissolution profile of a drug, or enhancing their intestinal permeability. In addition, recent studies have shed new light on the potential of clay minerals in the nanomedicine field due to their biocompatibility, beneficial effects of clay nanoparticles on cellular adhesion, proliferation, and differentiation. Use as active ingredients and excipients are exerted via the oral and topical administration pathways. Skin drug delivery represents an attractive alternative to the oral route, providing local and/or systemic drug delivery. Due to their complex structures, however, most drugs penetrate the human skin only with difficulty. Enormous efforts have been invested, therefore, in developing advanced drug delivery systems able to overcome the skin barrier. Most strategies require the use of singular materials with new properties. In particular, and on the basis of their inherent properties, clay minerals are ideal candidates for the development of intelligent skin drug delivery systems. In this article, the properties of clay materials and their use in the skin-addressed pharmaceutical field are reviewed. A brief introduction of skin physiology and biopharmaceutical features of penetration by a drug through the skin layers is also included and is designed to shed light on the optimum properties of ideal nanosystems for advanced skin drug delivery. Special attention is devoted to the pharmacological functions of clays and their biomedical applications in pelotherapy, wound healing, regenerative medicine, antimicrobial, and dermocosmetics.

The European Commission’s proposal to address antimicrobial resistance using transferable exclusivity vouchers (TEVs) is fundamentally flawed. European policymakers and regulators should consider alternatives, such as better funding for basic and clinical research, use of advance market commitments funded by a pay-or-play tax, or enacting an EU Fund for Antibiotic Development.

The objective of this study was to conduct a systematic review of the scientific literature evaluating the efficacy and comparative efficacy of antimicrobials (AMs) for the treatment of diarrhea in calves. Eligible studies were non- and randomized controlled trials evaluating an AM intervention against a positive and negative control, with at least one of the following outcomes: fecal consistency score, fever, dehydration, appetite, attitude, weight gain, and mortality. Four electronic databases were searched. Titles and abstracts (three reviewers) and full texts (two reviewers) were screened. A total of 2899 studies were retrieved; 11 studies met the inclusion criteria. The risk of bias was assessed. Most studies had incomplete reporting of trial design and results. Eight studies compared AMs to a negative control (placebo or no treatment). Among eligible studies, the most common outcomes reported were diarrhea severity (n = 6) and mortality (n = 6). Eligible studies evaluated very different interventions and outcomes; thus, a meta-analysis was not performed. The risk of bias assessment revealed concerns with reporting of key trial features, including disease and outcome definitions. Insufficient evidence is available in the scientific literature to assess the efficacy of AMs in treating calf diarrhea.

The welfare of farm animals is strongly influenced by the man-made environment. Welfare problems also arise from reduced homeostatic capacities in animals. Feed additives, used to promote growth or to prevent diseases can alter the animals' self-regulating capacities thus affecting their welfare. The EU regulates the use of these additives within specified groups of Directive 70/524/EEC. Although these feed additives can be regarded as prescription-free veterinary drugs, critical remarks on their desired and adverse effects have received little attention.

A survey of the available literature shows that about one-third of licensed feed additives alter adrenal function in vitro. Reports of the adverse effects of anticoccidial additives in vivo suggest they can be classified under three headings: (i) substances with a very narrow safety margin (the difference between the permitted dose and the dose with adverse effects) and often irreversible effects on growth and feed conversion; (ii) substances with a narrow safety margin and largely reversible effects; (iii) substances with an adequate safety margin. The growth promoters (including antibiotic growth promoters) can - on the basis of their adverse effects - be classified into two groups: (i) substances with a very narrow safety margin; and (ii) substances with an adequate safety margin.

On the one hand, animal welfare considerations require use of disease-preventing additives, but on the other hand, they also demand discontinuation of current practices. Judicious use of additives can add to animal welfare. However, their unlimited use to obscure defects in husbandry is detrimental to animal welfare. A major obstacle to the judicious use of feed additives, is the lack of published, unbiased information on their efficacy and safety for farm animals.

Bovine respiratory disease (BRD) is one of the most common indications for antimicrobial therapy in beef cattle production and research trials demonstrate that antibiotic therapy greatly improves clinical outcome for BRD. These trials also show that BRD treatment success rates are less than 100% and that there are opportunities to optimize antimicrobial prescribing and improve clinical outcomes if the underlying cause(s) of BRD treatment failures can be identified and addressed. As the etiology of BRD in an individual animal is frequently multi-factorial in nature; it is likely that BRD treatment failures also result from complex interactions between the drug, drug administrator, animal host, pathogens, and the environment. This review will focus specifically on the pharmacological aspects, specifically the interactions between the host and the drug and the drug and the drug administrator, of BRD treatment failures and the actions that veterinary practitioners can take to investigate and mitigate therapeutic failures in future cases.

Cette étude examine les approches réglementaires de dix pays : la France, le Danemark, l’Australie, le Canada, les États-Unis, la Russie, le Japon, le Brésil, la Chine et l’Inde, relativement à la réglementation des antimicrobiens aux trois points d’entrée principaux dans le processus agricole, soit dans le cadre de la médecine vétérinaire, de la production agricole et de la vente des produits agricoles. Pour être efficace, la réglementation doit tenir compte du contexte dans lequel elle s’inscrit. Cette étude tente donc de tirer des leçons des dix juridictions ci-haut à la lumière des réalités qui entourent l’utilisation d’antimicrobiens dans les processus agricoles.

The data presented in this research communication represent the first comprehensive report on the prevalence of udder pathogens and their resistance in Slovak dairy cattle breeds. A total of 633 milk samples from 42 herds were tested. The most frequently isolated pathogens were coagulase negative staphylococci CNS or non-aureus staphylococci (NAS) followed by Escherichia (E.) coli, Staphylococcus (S.) aureus, Streptococcus (Str.) uberis and Streptococcus (Str.) agalactiae. Generally, isolated pathogens showed common resistance to aminoglycosides (streptomycin, neomycin), which are the most commonly used antibiotics to treat mastitis in Slovakia.

Bedding material is an important requirement of floor-based poultry production systems to meet the health and welfare requirements. This substrate can be an organic material like wood or plant-based material or inorganic material like clay and sand and should generally be a good absorbant, easily available, comfortable and nontoxic to birds. Wood is an organic renewable resource having good humidity regulation and antimicrobial properties and its by-products are commonly used as poultry litter in many countries. For example, in France, wood-based bedding is used in 80% of turkey production. This litter has approximately 50% lower NH3 production compared to other materials like sand and hulls, and has multiple environment-friendly disposal options. Moreover, the birds grown on such litter show better health and welfare and they prefer to practice their natural behaviours on this material which is helpful for the amelioration of physiological status and reduction of locomotion injuries. Moreover, according to some studies, the birds show improvement in different performance parameters, for example, up to 5-7% improvement in daily weight gain, live body weight, feed conversion ratio (FCR) and survivability. These improvements may differ depending upon the production system and type of wood material used in experiments, still it can be concluded that wood-based bedding materials do not negatively affect the production potential of poultry. In addition, the antimicrobial potential of wood may help to counter the load of certain pathogens in environment of birds. This review describes the physiochemical properties of wood-based bedding materials and their role in production and welfare of poultry.

Antimicrobial use in pig farming is influenced by a range of risk factors, including herd characteristics, biosecurity level, farm performance, occurrence of clinical signs and vaccination scheme, as well as farmers’ attitudes and habits towards antimicrobial use. So far, the effect of these risk factors has been explored separately. Using an innovative method called multiblock partial least-squares regression, this study aimed to investigate, in a sample of 207 farrow-to-finish farms from Belgium, France, Germany and Sweden, the relative importance of the six above mentioned categories or ‘blocks’ of risk factors for antimicrobial use in pig production. Four country separate models were developed; they showed that all six blocks provided useful contribution to explaining antimicrobial use in at least one country. The occurrence of clinical signs, especially of respiratory and nervous diseases in fatteners, was one of the largest contributing blocks in all four countries, whereas the effect of the other blocks differed between countries. In terms of risk management, it suggests that a holistic and country-specific mitigation strategy is likely to be more effective. However, further research is needed to validate our findings in larger and more representative samples, as well as in other countries.

Antimicrobials are among the most prescribed drugs and their prescription increases with age, due to frailty and accrued risk factors for acquiring infections. Antimicrobial prescription in elderly patients must not only account for the risk of toxicity due to drug overexposure, but also of treatment failure or promotion of antimicrobial resistance due to under-dosage. This paper reviews the main antimicrobial, pharmacokinetic and pharmacodynamic variations induced by aging, comorbidities and polypharmacy, and how to take them into account to optimize antimicrobial prescription in elders.

Lactic acid bacteria (LAB) can be isolated from different sources such as milk and cheese, and the lipolytic, proteolytic and glycolytic enzymes of LAB are important in cheese preservation and in flavour production. Moreover, LAB produce several antimicrobial compounds which make these bacteria interesting for food biopreservation. These characteristics stimulate the search of new strains with technological potential. From 156 milk and cheese samples from cow, buffalo and goat, 815 isolates were obtained on selective agars for LAB. Pure cultures were evaluated for antimicrobial activities by agar antagonism tests and for proteolytic activity on milk proteins by cultivation on agar plates. The most proteolytic isolates were also tested by cultivation in skim milk followed by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) analysis of the fermented milk. Among the 815 tested isolates, three of them identified as Streptococcus uberis (strains FT86, FT126 and FT190) were bacteriocin producers, whereas four other ones identified as Weissella confusa FT424, W. hellenica FT476, Leuconostoc citreum FT671 and Lactobacillus plantarum FT723 showed high antifungal activity in preliminary assays. Complementary analyses showed that the most antifungal strain was L. plantarum FT723 that inhibited Penicillium expansum in modified MRS agar (De Man, Rogosa, Sharpe, without acetate) and fermented milk model, however no inhibition was observed against Yarrowia lipolytica. The proteolytic capacities of three highly proteolytic isolates identified as Enterococcus faecalis (strains FT132 and FT522) and Lactobacillus paracasei FT700 were confirmed by SDS–PAGE, as visualized by the digestion of caseins and whey proteins (β-lactoglobulin and α-lactalbumin). These results suggest potential applications of these isolates or their activities (proteolytic activity or production of antimicrobials) in dairy foods production.

The need for new drugs to treat microbial infections is pressing. The great progress made in the middle part of the twentieth Century was followed by a period of relative inactivity as the medical needs relating to infectious disease in the wealthier nations receded. Growing realisation that anti-infectives are needed in many parts of the world, to treat neglected diseases as well as to combat the burgeoning risk of resistance to existing drugs, has galvanised a new wave of research into anti-microbial drugs. The transfer of knowledge from the Pharmaceutical industry relating to the importance of understanding how to target drugs successfully within the body, and improved understanding of how pathogens interact with their hosts, is driving a series of new paradigms in anti-infective drug design. Here we provide an overview of those processes as an introduction to a series of articles from experts in this area that emerged from a meeting entitled “Emerging Paradigms in Anti-Infective Drug Design” held in London on the 17th and 18th September 2012. The symposium was organised jointly by British Society for Parasitology (BSP) and the Biological & Medicinal Chemistry sector of the Royal Society of Chemistry (RSC) and held at the London School of Hygiene & Tropical Medicine. The symposium set out to cover all aspects of the identification of new therapeutic modalities for the treatment of neglected and tropical diseases. We aimed to bring together leading scientists from all the disciplines working in this field and cover the pharmacology, medicinal chemistry and drug delivery of potential new medicines. Sessions were held on: “Target diseases and targets for drugs”, “Target based medicinal chemistry”, “Bioavailability and chemistry”, “Targeting intracellular microbes”, “Alternative approaches and models”, and “New anti-infectives – how do we get there?”

This symposium was organised by Simon Croft (LSHTM) and Mike Barrett (University of Glasgow) for the BSP, and David Alker (David Alker Associates) and Andrew Stachulski (University of Liverpool) for the Biological & Medicinal Chemistry sector of the RSC.

Antibiotics are one of the most important medical discoveries of the 20th century and will remain an essential tool for treating animal and human diseases in the 21st century. However, antibiotic resistance among bacterial pathogens and concerns over their extensive use in food animals has garnered global interest in limiting antibiotic use in animal agriculture. Yet, limiting the availability of medical interventions to prevent and control animal diseases on the farm will directly impact global food security and safety as well as animal and human health. Insufficient attention has been given to the scientific breakthroughs and novel technologies that provide alternatives to antibiotics. The objectives of the symposium ‘Alternatives to Antibiotics’ were to highlight promising research results and novel technologies that could potentially lead to alternatives to conventional antibiotics, and assess challenges associated with their commercialization, and provide actionable strategies to support development of alternative antimicrobials. The symposium focused on the latest scientific breakthroughs and technologies that could provide new options and alternative strategies for preventing and treating diseases of animals. Some of these new technologies have direct applications as medical interventions for human health, but the focus of the symposium was animal production, animal health and food safety during food-animal production. Five subject areas were explored in detail through scientific presentations and expert panel discussions, including: (1) alternatives to antibiotics, lessons from nature; (2) immune modulation approaches to enhance disease resistance and to treat animal diseases; (3) gut microbiome and immune development, health and diseases; (4) alternatives to antibiotics for animal production; and (5) regulatory pathways to enable the licensure of alternatives to antibiotics.

The mammalian intestine harbors a large and diverse community of micro-organisms, known as the intestinal microbiota. Recent developments in molecular profiling methods, mainly based on microbial 16S ribosomal RNA gene sequencing, have provided unprecedented insights into the make-up and diversity of intestinal microbial communities. Using these culture-independent analyses, gut microbiota of several mammals including laboratory rodents, have been revisited. The laboratory rat is one of the major species bred and kept for scientific research. Although this animal is bred in confined environments and subjected to procedures for satisfying health requirements that hamper natural colonization, some major features of mammalian gut microbiota are conserved. However, the gut microbiota varies according to the breeding conditions of the rats and this could impact reproducibility of the experimental models. Determining the non-pathogenic microbial community might be relevant in standards of quality control of laboratory animals. Molecular profiling techniques could be applied to document this information.

The present article reviews the historical and popular uses of garlic, its antioxidant, haematological, antimicrobial, hepatoprotective and antineoplastic properties and its potential toxicity (from sulfoxide). Garlic has been suggested to affect several cardiovascular risk factors. It has also been shown that garlic and its organic allyl sulfur components are effective inhibitors of the cancer process. Since garlic and its constituents can suppress carcinogen formation, bioactivation and tumour proliferation, it is imperative that biomarkers be established to identify which individuals might benefit most. Garlic powder, aged garlic and garlic oil have demonstrated antiplatelet and anticoagulant effects by interfering with cyclo-oxygenase-mediated thromboxane synthesis. Garlic has also been found to have synergistic effects against Helicobacter pylori with a proton pump inhibitor. The active compound allicin may affect atherosclerosis not only by acting as an antioxidant, but also by other mechanisms, such as lipoprotein modification and inhibition of LDL uptake and degradation by macrophages. Freshly prepared garlic homogenate protects against isoniazid+rifampicin-induced liver injury in experimental animal models. Several mechanisms are likely to account for this protection.

In the search for alternatives to banned in-feed antibiotics, a concept was developed based on studies with medium-chain fatty acid-containing triacylglycerols (MCTAG) and selected lipases for in situ generation of diacylglycerols, monoacylglycerols and medium-chain fatty acids (MCFA) in the stomach and proximal gut of piglets. MCFA are known to have strong antibacterial properties but can hardly be used as such because of their repellent odour and taste. Those problems could be overcome by the generation of MCFA in situ. The concept was tested in vitro and validated in vivo with gastric-cannulated piglets and under field conditions, including effects on zootechnical performance, with classical antibacterial growth promoters or organic acids acting as positive controls. Furthermore, the metabolic and dietary constraints on the nutritional and nutritive use of MCTAG and/or MCFA (for example, the effects on digestive physiology, gut flora, feed intake, performance, carcass composition) are reviewed. The role of natural preduodenal lipase activity, the presence of endogenous plant lipase activity in raw materials and the feasibility for exogenous lipase addition to the feed are discussed, in order to optimize the concept. The present review illustrates the similarity of the action of MCFA and commonly used antimicrobials on the flora (total flora, Gram-positive flora, Gram-negative flora, potential pathogens) and epithelial morphology and histology in the foregut. These observations are believed to be the basis for obtaining optimal growth performances. In addition, these naturally occurring antimicrobial agents have little or no human or animal toxicity and induce no problems of residues and cross-resistance induction. They are proposed as a valuable alternative to in-feed antibiotics, used for growth promotion, and even for the preventive and curative treatment of gastrointestinal diseases.

The immediate post-weaning period is often associated with gut malfunction and diarrhoea for young pigs. Administration of antimicrobials remains an effective way to control weaning diarrhoea but it remains unclear how they affect gut physiology and microbiology although this is a prerequisite for being able to devise better alternatives. Hence, for 7 d we treated pigs, weaned at 24 d of age, with a combination of amoxicillin (25 mg/kg feed and injection of 8·75 mg/kg body weight per 12 h) and ZnO (2·5 g/kg feed). The pigs treated with antimicrobials (n 11) showed no signs of gut malfunction at any time, whereas untreated weaned controls (n 11) developed clinical diarrhoea. The antimicrobial treatment resulted in a higher daily weight gain compared with weaned controls (101 v. − 44 g/d, P < 0·0001), whereas both groups had a similar degree of villous atrophy compared with unweaned 24-d-old controls (n 8; P < 0·05). The antimicrobial treatment gave a dramatic reduction in small intestinal microbial diversity, and specifically prevented tissue colonization with Escherichia coli compared with weaned controls. Further, the antimicrobial treatment improved amylase, trypsin and small intestinal aminopeptidase A and N activities (all P < 0·05). Specifically for the colon, the antimicrobial treatment was associated with reduced tissue weight ( − 23 %, P < 0·05), reduced concentration of SCFA (P < 0·05), and increased mucosal goblet cell area (P < 0·0001) compared with weaned controls. We conclude that the beneficial effects of antimicrobials are mediated not only through reduction in intestinal bacterial load, but also through a stimulation of protein digestive function and goblet cell density.

Feed additives are renamed as microfeedingstuffs. They are subdivided into nutrients, pronutrients, conditioners and prophylactics in order to specify their nature and scientific functions in nutrition, to improve their public image and to facilitate the standardization of their terminology and use in international regulations.