Drug Release from Lipogels According to Gelling Conditions and Mechanical Treatment

The release rate of a drug dissolved in the liquid phase of lipogels may be greatly affected by the type and concentration of gelling agent and by processing conditions and mechanical treatment of the ointment. These differences in release rate are reduced after application of mechanical stress comparable with the strain exerted on the ointment during application to the skin. Therefore, changes in the concentration of gelling agents used to achieve suitable consistency and manufacturing and packing processes that meet industrial and marketing requirements do not appear to exert a practical influence on drug availability after application to the skin.     

INFORMATION LITERACY IN A RESEARCHER'S LEARNING LIFE: THE SEVEN AGES OF RESEARCH

This article uses data from research conducted in the course of writing a book on the needs, wants and characteristics of researchers to examine how researchers view themselves and the research process. As a result of this, the Seven Ages of Research model was developed which categorises a researcher's learning life into a series of discrete stages. The article explores learning needs relevant to each age in the learning life and links them to the development of information literacy. The authors explore the polarisation that exists between what researchers think research is about and what they believe the library can offer them, and suggest that information literacy needs to be seen as involving a change in understanding of, and attitude to, the world of information, as well as the nature of those information needs. Finally, they explore the librarian's role in an e-environment which has changed the way researchers work and identify some of the challenges facing library and information services professionals in the future in supporting researchers throughout their learning lives.     

The seafood supply chain from a fraudulent perspective

Food fraud is an intentional act for economic gain. It poses a risk to food integrity, the economy, public health and consumers’ ethics. Seafood is one commodity which has endured extensive fraudulent activity owing to its increasing consumer demand, resource limitations, high value and complex supply chains. It is essential that these fraudulent opportunities are revealed, the risk is evaluated and countermeasures for mitigation are assigned. This can be achieved through mapping of the seafood supply chains and identifying the vulnerability analysis critical control points (VACCP), which can be exposed, infiltrated and exploited for fraudulent activity. This research systematically maps the seafood supply chain for three key commodities: finfish, shellfish and crustaceans in the United Kingdom. Each chain is comprised of multiple stakeholders across numerous countries producing a diverse range of products distributed globally. For each supply chain the prospect of fraud, with reference to species substitution, fishery substitution, illegal, unreported and unregulated substitution, species adulteration, chain of custody abuse, catch method fraud, undeclared product extension, modern day slavery and animal welfare, has been identified and evaluated. This mapping of the fraudulent opportunities within the supply chains provides a foundation to rank known and emerging risks and to develop a proactive mitigation plan which assigns control measures and responsibility where vulnerabilities exist. Further intelligence gathering and management of VACCPs of the seafood supply chains may deter currently unknown or unexposed fraudulent opportunities.     

Serenoa repens and Urtica dioica Fixed Combination: In-Vitro Validation of a Therapy for Benign Prostatic Hyperplasia (BPH)

Benign prostatic hyperplasia (BPH) is an age-related chronic disorder, characterized by the hyperproliferation of prostatic epithelial and stromal cells, which drives prostate enlargement. Since BPH aetiology and progression have been associated with the persistence of an inflammatory stimulus, induced both by Nuclear Factor-kappa B (NF-κB) activation and reactive oxygen species (ROS) production, the inhibition of these pathways could result in a good tool for its clinical treatment. This study aimed to evaluate the antioxidant and anti-inflammatory activity of a combined formulation of Serenoa repens and Urtica dioica (SR/UD) in an in vitro human model of BPH. The results confirmed both the antioxidant and the anti-inflammatory effects of SR/UD. In fact, SR/UD simultaneously reduced ROS production, NF-κB translocation inside the nucleus, and, consequently, interleukin 6 (IL-6) and interleukin 8 (IL-8) production. Furthermore, the effect of SR/UD was also tested in a human androgen-independent prostate cell model, PC3. SR/UD did not show any significant antioxidant and anti-inflammatory effect, but was able to reduce NF-κB translocation. Taken together, these results suggested a promising role of SR/UD in BPH and BPH-linked disorder prevention.     

Nanofriction behavior of cluster-assembled carbon films

We have characterized the frictional properties of nanostructured carbon films grown by supersonic cluster beam deposition via an atomic force-friction force microscope (AFM-FFM). The experimental data are discussed on the basis of a modified Amonton's law for friction, stating a linear dependence of friction on load plus an adhesive offset accounting for a finite friction force in the limit of null total applied load. Molecular dynamics simulations of the interaction of the AFM tip with the nanostructured carbon confirm the validity of the friction model used for this system. Experimental results show that the friction coefficient is not influenced by the nanostructure of the films nor by the relative humidity. On the other hand the adhesion coefficient depends on these parameters.     

Effect of gelling conditions and mechanical treatment on drug availability from a lipogel

This study has been conducted to determine whether the rheological differences depending on gelling and treatment conditions could have an influence on drug availability. Lipogels with constant composition were obtained by gelling olive oil with monodiglycerides at rest, under stirring, and milled after gelling. The considerable differences in rheological characteristics produced significant differences on in vitro drug release tests, whereas a lesser influence was observed on in vitro simulated absorption test. The rheological differences appeared not to influence in vivo drug availability. Also, rheological differences owing to the concentration of the gelling agent showed no significant influence on in vivo availability.     

Interactive Paper as a Mobile Client for a Multi-channel Web Information System

We describe how interactive paper can be used together with a multi-channel web information system to build a platform for experimenting with multi-modal context-aware mobile information services. As an application, we present a tourist guide for visitors to an international festival that was developed to investigate alternative modes of information delivery and interaction in mobile environments. The guide is based around a set of interactive paper documents—an event brochure, map and bookmark. The brochure and map are augmented with digital services by using a digital pen to activate links and a text-to-speech engine for information delivery. The digital pen is also used for data capture of event ratings and reviews. The bookmark provides access to advanced searches and ticket reservations. We describe the architecture and operation of the system, highlighting the challenges of extending a web information system to support both the generation of the paper documents and the interaction from these documents, alongside more traditional access channels. Finally, we discuss the range of context-aware interactions that is supported by our platform.     

Diet Prevents Social Stress-Induced Maladaptive Neurobehavioural and Gut Microbiota Changes in a Histamine-Dependent Manner

Exposure to repeated social stress may cause maladaptive emotional reactions that can be reduced by healthy nutritional supplementation. Histaminergic neurotransmission has a central role in orchestrating specific behavioural responses depending on the homeostatic state of a subject, but it remains to be established if it participates in the protective effects against the insults of chronic stress afforded by a healthy diet. By using C57BL/6J male mice that do not synthesize histamine (Hdc^−/−) and their wild type (Hdc^+/+) congeners we evaluated if the histaminergic system participates in the protective action of a diet enriched with polyunsaturated fatty acids and vitamin A on the deleterious effect of chronic stress. Behavioural tests across domains relevant to cognition and anxiety were performed. Hippocampal synaptic plasticity, cytokine expression, hippocampal fatty acids, oxylipins and microbiota composition were also assessed. Chronic stress induced social avoidance, poor recognition memory, affected hippocampal long-term potentiation, changed the microbiota profile, brain cytokines, fatty acid and oxylipins composition of both Hdc^−/− and Hdc^+/+ mice. Dietary enrichment counteracted stress-induced deficits only in Hdc^+/+ mice as histamine deficiency prevented almost all the diet-related beneficial effects. Interpretation: Our results reveal a previously unexplored and novel role for brain histamine as a mediator of many favorable effects of the enriched diet. These data present long-reaching perspectives in the field of nutritional neuropsychopharmacology.     

Discovery of an Allosteric Ligand Binding Site in SMYD3 Lysine Methyltransferase

SMYD3 is a multifunctional epigenetic enzyme with lysine methyltransferase activity and various interaction partners. It is implicated in the pathophysiology of cancers but with an unclear mechanism. To discover tool compounds for clarifying its biochemistry and potential as a therapeutic target, a set of drug-like compounds was screened in a biosensor-based competition assay. Diperodon was identified as an allosteric ligand; its R and S enantiomers were isolated, and their affinities to SMYD3 were determined (K_D=42 and 84 μM, respectively). Co-crystallization revealed that both enantiomers bind to a previously unidentified allosteric site in the C-terminal protein binding domain, consistent with its weak inhibitory effect. No competition between diperodon and HSP90 (a known SMYD3 interaction partner) was observed although SMYD3–HSP90 binding was confirmed (K_D=13 μM). Diperodon clearly represents a novel starting point for the design of tool compounds interacting with a druggable allosteric site, suitable for the exploration of noncatalytic SMYD3 functions and therapeutics with new mechanisms of action.