Avandia (TM) - From molecule to market for type 2 diabetes.

Type 2 diabetes is a disease fast approaching epidemic proportions throughout the world. From insulin sensitizers to PPARg agonists, the lecture will outline the successful medicinal chem. and biol. strategy underpinning the discovery and selection of Avandia, an innovative new medicine for this disease.

In vitro testing of Advanced JAX (TM) Bone Void Filler System: species differences in the response of bone marrow stromal cells to beta tri-calcium phosphate and carboxymethylcellulose gel

The Advanced JAX (TM) Bone Void Filler System (AJBVFS) is a novel bone graft material manufactured by Smith and Nephew Orthopaedics Ltd. and comprises beta tri-calcium phosphate granules with carboxymethylcellulose (CMC) gel as a handling agent. This study investigated the potential, in vitro, of the AJBVFS to function as a delivery system for cell therapy to enhance healing of bone defects. The attachment of rabbit bone marrow stromal cells (rbBMSCs), human BMSCs (hBMSCs) and human bone-derived cells (hBDCs) to JAX (TM) granules and the effect of CMC gel on cell proliferation and differentiation were investigated. There were slight species differences in the number and morphology of cells attached on the JAX (TM) granules with less rbBMSC attachment than human. All cells tolerated the presence of CMC gel and a reduction in cell number was only seen after longer exposure to higher gel concentrations. Low concentrations of CMC gel enhanced proliferation, alkaline phosphatase (ALP) expression and ALP activity in human cells but had no effect on rbBMSC. This study suggests that AJBVFS is an appropriate scaffold for the delivery of osteogenic cells and the addition of CMC gel as a handling agent promotes osteogenic proliferation and differentiation and is therefore likely to encourage bone healing.

Characterisation of the photocatalyst Pilkington Activ (TM): a reference film photocatalyst?

Pilkington Glass Activ(TM) represents a possible suitable successor to P25 TiO2, especially as a benchmark photocatalyst film for comparing other photocatalyst or PSH self-cleaning films. Activ(TM) is a glass product with a clear, colourless, effectively invisible, photocatalytic coating of titania that also exhibits PSH. Although not as active as a film of P25 TiO2, Activ(TM) vastly superior mechanical stability, very reproducible activity and widespread commercial availability makes it highly attractive as a reference photocatalytic film. The photocatalytic and photo-induced superhydrophilitic (PSH) properties of Activ(TM) are studied in some detail and the results reported. Thus, the kinetics of stearic acid destruction (a 104 electron process) are zero order over the stearic acid range 4-129 monolayers and exhibit formal quantum efficiencies (FQE) of 0.7 X 10(-5) and 10.2 x 10(-5) molecules per photon when irradiated with light of 365 +/- 20 and 254 nm, respectively; the latter appears also to be the quantum yield for Activ(TM) at 254 nm. The kinetics of stearic acid destruction exhibit Langmuir-Hinshelwood-like saturation type kinetics as a function of oxygen partial pressure, with no destruction occurring in the absence of oxygen and the rate of destruction appearing the same in air and oxygen atmospheres. Further kinetic work revealed a Langmuir adsorption type constant for oxygen of 0.45 +/- 0.16 kPa(-1) and an activation energy of 19 +/- 1 Kj mol(-1). A study of the PSH properties of Activ(TM) reveals a high water contact angle (67) before ultra-bandgap irradiation reduced to 0degrees after prolonged irradiation. The kinetics of PSH are similar to those reported by others for sol-gel films using a low level of UV light. The kinetics of contact angle recovery in the dark appear monophasic and different to the biphasic kinetics reported recently by others for sol-gel films [J. Phys. Chem. B 107 (2003) 1028]. Overall, Activ(TM) appears a very suitable reference material for semiconductor film photocatalysis. (C) 2003 Elsevier Science B.V All rights reserved.

The effects of hexetidine (Oraldene (TM)) on the adherence of Candida albicans to human buccal epithelial cells in vitro and ex vivo and on in vitro morphogenesis

Purpose. This study reports the effects of hexetidine (Oraldene(TM)) on two virulence attributes of Candida albicans, namely, in vitro and ex vivo adherence of yeast cells to buccal epithelial cells (BEG) and in vitro morphogenesis.

PRELIMINARY INVESTIGATIONS CONCERNING THE ANTI-ADHERENCE PROPERTIES OF POLYHEXAMETHYLENEBIGUANIDE (VANTOCIL IB(TM))

The effect of polyhexamethylenebiguanide (PHMB) on adherence of Candida albicans blastospores to human buccal epithelial cells (BEG) was examined in vitro. Treatments of either blastospores or BEC with PHMB (50 and 1000 mu g ml(-1)) significantly reduced the number of adherent blastospores per BEC and increased the number of BEC devoid of blastospores.