George Olivier

Osteoconductive phosphoserine-modified poly(ε-lysine) dendrons: synthesis, titanium oxide surface functionalization and response of osteoblast-like cell lines

The lack of direct bonding between the surface of an implant and the mineralized bony tissue is among the main causes of aseptic loosening in titanium-based implants. Surface etching and ceramic coatings have led to improved osteointegration, but their clinical performance is still limited either by partial bonding or by coating delamination. In this work, a solid-phase synthesis method has been optimized to produce poly(ε-lysine) dendrons, the outermost branching generation of which is functionalized by phosphoserine (PS), a known catalyst of the biomineralization process. The dendrons were deposited onto etched titanium oxide surfaces as a near-to-monolayer film able to induce the formation of a homogeneous calcium phosphate phase in a simulated body fluid over 3 days. The dendron films also stimulated MG63 and SAOS-2 osteoblast-like cells to proliferate at a rate significantly higher than etched titanium, with SAOS-2 also showing a higher degree of differentiation over 14 days. PS-tethered dendron films were not affected by various sterilization methods and UV treatment appeared to improve the cell substrate potential of these films, thus suggesting their potential as a surface functionalization method for bone implants.

Development and use of standardised data collection tools to support and inform musculoskeletal practice

Clinicians all over the world are increasingly being faced with the need to demonstrate and account for the way in which clinical services are delivered and the quality of the delivery. It is also imperative to develop a comprehensive profile of who is accessing these services, who benefits from these services; how much these services cost in terms of clinicians time, the use of other healthcare resources and the effectiveness of interventions utilised in relation to quality outcomes. Clinicians are themselves keen to have mechanisms to identify what approaches are being utilised in their own practice setting, how they work best and how they can be improved from a professional development perspective. They are also anxious to improve their skills based on informed reflective practice and identify gaps in their knowledge and skills. This masterclass identifies how standardised data collection (SDC) tools can be utilised in practice to gather the information required in a robust, agreed and accessible way. It summarises a method of SDC tool development and gives some examples of how SDC has been implemented in physiotherapy National Health Services and in physiotherapy private practice in the United Kingdom. The global relevance is that increasingly all physiotherapy services are being held and will be accountable for the quality and equity of care. In addition clinicians can find it useful to have benchmarks with which to compare their own and their departmental performance in terms of clinical activities and outcomes.

Synthesis of 153N-6 analogues and structure-function analysis at murine melanocortin-1 (MC1) receptors.

153N-6 (H-[Met5,Pro6,D-Phe7,D-Trp9,Phe10]-MSH(5-13)) has emerged as the most potent antagonist of alpha-MSH activity on Xenopus laevis melanophores, from a library of 32 360 peptides based on alpha-MSH(5-13) [22]. A recent report has confirmed our observation that 153N-6 also binds to mammalian melanocortin receptors. Here we report the receptor-binding affinities and biologic activities of 153N-6 and 17 selected alpha-MSH analogues at the native MCI receptor expressed by murine B16 melanoma cells. Our intention is to determine the structural requirements for agonism and competitive antagonism of melanocortin activity at the MC1-R and to discover more potent antagonists. 153N-6 was able to inhibit the action of native alpha-MSH and the potent synthetic agonist, [Nle4,D-Phe7]alpha-MSH, at the murine MC1-R. However, the Ki of 153N-6 was 439 times higher than that of alpha-MSH and 4475 times higher than that of [Nle4,D-Phe7]alpha-MSH; too high to allow 153N-6 to be considered as a practical antagonist for use in vivo (Ki of 153N-6 = 9.0 X 10(-6) M). Because Met4 is an important component of alpha-MSH binding at the MC1-R, we investigated alpha-MSH(1-13) and alpha-MSH(4-13) analogues to produce compounds with higher MC1-R-binding affinity than 153N-6. The binding affinity of 153N-6 was not significantly different from alpha-MSH(5-13), but it was 232 times lower than alpha-MSH(4-13). Coupling of H-Nle (as an isosteric replacement for Met) or acetyl-Nle to the N-terminus of 153N-6 raised the binding affinity by a factor of 46, but this and all full-length alpha-MSH analogues with Met or Nle in position 4 were full agonists of the MC1-R. A full-length alpha-MSH(1-13) derivative of 153N-6 with Ala4 did not exhibit significantly greater binding affinity than 153N-6 and appeared to be a partial agonist at the MC1-R in the cAMP assay. These data suggest that Met4 is an important determinant of the intrinsic efficacy of melanocortins as well as their binding affinity at the MCI-R. Pro6 and Phe10 (with respect to alpha-MSH) were found to be the most influential substitutions that determined the antagonist activity of 153N-6.

Assessment of biological activity of novel peptide analogues of angiotensin IV

Objectives  Angiotensin IV (Ang IV) is a metabolite of angiotensin II which acts on specific AT4 receptors identified as the enzyme insulin regulated aminopeptidase (IRAP). The transduction process of these receptors is unresolved, but Ang IV inhibits the aminopeptidase activity. Ang IV improves cognition in animal models thus there is a desire to develop metabolically stable analogues for further development.

Enhancing Quality in the M.Pharm Degree Programme: Optimisation of the Personal Tutor System

Personal tutoring (PT) systems operating in Higher education (HE) generally aim to offer support, information and advice to students concerning many areas in their university life, both the pedagogical and the personal. This article considers the methodologies and perceptions of a PT system for 4-year Master of Pharmacy (M.Pharm) undergraduate students within the School of Pharmacy and Biomolecular Sciences at the University of Brighton. The 2000/2001 Level 1 and Level 2 M.Pharm cohorts were surveyed with respect to their perceptions of the personal tutor system. These perceptions are reported in this work. The majority of students made zero or one visits to their assigned personal tutor each academic year. Overall positive student perceptions concerning the effectiveness of the PT system is reported, with most students reporting that they found their allocated personal tutor helpful. Most students stated that they felt able to request a change of personal tutor under any circumstances without fear of any negative consequence, a key attribute of the system. Students described the PT system as a means of listening to personal problems, to review status of academic progress and to act as an initial point of contact between the students and the University. Yet the students did not acknowledge some of its key functions. The PT was not described as a means to discuss learning and assessment strategies, deploy information on course and exam regulations and help in choosing modules (as well as assistance in gaining access to support services). The results of this study provide us with a framework by which the current system may be improved. Results suggest that its focus now must be on enhancing staff dedication to the provision of a quality service, training support to staff in the skills of PT, instituting a minimum number of PT sessions-per-academic year and broadening student knowledge of the multi-dimensional role of the personal tutor. It is also concluded that the one-size-fits-all model does not fit all and that a flexible model for tutoring is more likely to satisfy the requirements of the student body as a whole.

Enhancing learning and teaching quality: Intranet hierarchy optimisation and application of stereochemical molecular representations

This article deals with the ongoing use and development of Intranet-based technologies within the School of Pharmacy and Biomolecular Sciences, University of Brighton. The course used as a test model is the M.Pharm. degree, a 4-year course with approximately 120 students per level. The student subjects of this study are the then Level 2 students. In this article we examine the continued optimisation of a School Intranet learning resource with regard to optimisation of the hierarchical structure. In response to a requirement previously identified, this work then focuses on the use of manipulatable molecular representations to enhance the learning and teaching of stereochemistry.