Antifungal Activity of LL-37 and Truncated Mimetics

Background: Candida albicans is a commensal organism and a constituent of the normal oral flora. Cell concentrations of 1x102 cells/ml and below are indicative of commensal colonisation in the oral cavity, above this level C. albicans can become an opportunistic pathogen; it is the most prevalent human fungal pathogen and a causal agent of the oral infection, candidiasis. The capacity of C. albicans to cause infection arises from its ability to exist in a biofilm ecosystem. Mature C. albicans biofilms display a high level of resistance to antifungals and the need for other therapeutic options has become paramount. Objectives: The objectives of the current study were to determine the antifungal activity of LL-37 (a member of the human cathelicidin family) and two truncated peptide mimetics against C. albicans in both planktonic and biofilm form. Methods: Radial diffusion assays were used to obtain the minimum inhibitory concentration (MIC) of LL-37 and the truncated mimetics KE-18 and KR-12 against planktonic C. albicans. A 96 well microtitre plate assay was employed to study the effects of the peptides on early candida biofilm formation (up to 24 hours) compared with the antifungal drug fluconazole. Biofilm quantification was achieved using the crystal violet assay. Results: MIC values obtained: LL-37 >250µg/ml; KE-18 51µg/ml; and KR-12 11µg/ml. LL-37 significantly reduced the quantity of biofilm formed by C.albicans at both the 4 h and 24 h timepoints (p <0.0001). KE-18 showed significant biofilm reduction over 4 h and 24 h (p=0.0002, p=0.013 respectively), KR-12 showed significant reduction at the 24 h time point only (p=0.0256). Conclusions: Results suggest that LL-37 has the ability to disrupt early biofilm formation of C. albicans with its potency of action similar with that of fluconazole.

The Agent-Rule-Class Framework for Multi-Agent Systems

Multi-agent systems have become increasingly mature, but their appearance does not make the traditional OO approach obsolete. On the contrary, OO methodologies can benefit from the principles and tools designed for agent systems. The Agent-Rule-Class (ARC) framework is proposed as an approach that builds agents upon traditional OO system components and makes use of business rules to dictate agent behaviour with the aid of OO components. By modelling agent knowledge in business rules, the proposed paradigm provides a straightforward means to develop agent-oriented systems based on the existing object-oriented systems and offers features that are otherwise difficult to achieve in the original OO systems. The main outcome of using ARC is the achievement of adaptivity. The framework is supported by a tool that ensures agents implement up-to-date requirements from business people, reflecting desired current behaviour, without the need for frequent system rebuilds. ARC is illustrated with a rail track example.

A flexible bandwidth resource provisioning system with agent-enhanced SLA negotiation

Paper describes an effcicient approach for provisioning of network resources based on SLAs and a range of negotiating agents. The work arose from direct collboration with Fujitsu research and invlolved a worldwide press reslease of their agent brokering system which was based on this; also, a plenary address: A.Marshall (QUB) & A.Campbell (Columbia, USA) at 4th IFIP/IEEE International conference on Management of Multimedia Networks and Services' 2001 (MMNS'01). ISSN: 0926-6801

Org 25969 (sugammadex), a selective relaxant binding agent for antagonism of prolonged rocuronium-induced neuromuscular block

Background. Org 25969 is a cyclodextrin compound designed to reverse a rocuronium-induced neuromuscular block. The aim of this study was to explore the efficacy, dose-response relation and safety of Org 25969 for reversal of a prolonged rocuronium-induced neuromuscular block. Methods. Thirty anaesthetised adult patients received rocuronium 0.6mg kg as an initial dose followed by increments to maintain a deep block at level of