Investigational agents that protect pancreatic islet β-cells from failure

Type 2 diabetes is associated with insulin resistance and reduced insulin secretion, which results in hyperglycaemia. This can then lead to diabetic complications such as retinopathy, neuropathy, nephropathy and cardiovascular disease. Although insulin resistance may be present earlier in the progression of the disease, it is now generally accepted that it is the deterioration in insulin-secretory function that leads to hyperglycaemia. This reduction in insulin secretion in Type 2 diabetes is due to both islet β-cell dysfunction and death. Therefore, interventions that maintain the normal function and protect the pancreatic islet β-cells from death are crucial in the treatment of Type 2 diabetes so that plasma glucose levels may be maintained within the normal range. Recently, a number of compounds have been shown to protect β-cells from failure. This review examines the evidence that the existing therapies for Type 2 diabetes that were developed to lower plasma glucose (metformin) or improve insulin sensitivity (thiazolidinediones) may also have islet-protective function. Newer emerging therapeutic agents that are designed to increase the levels of glucagon-like peptide-1 not only stimulate insulin secretion but also appear to increase islet β-cell mass. Evidence will also be presented that the future of drug therapy designed to prevent β-cell failure should target the formation of advanced glycation end products and alleviate oxidative and endoplasmic reticulum stress.

Nurse-led titration of angiotensin converting enzyme inhibitors, beta-adrenergic blocking agents and angiotensin receptor blockers for patients with left ventricular systolic dysfunction

This is the protocol for a review and there is no abstract. The objectives are as follows:

To assess the effects of nurse-led titration of ACEIs, beta-adrenergic blocking agents and ARBs in patients with left ventricular systolic dysfunction in terms of safety and patient outcomes.

Aptamers as theranostic agents: modifications, serum stability and functionalisation

Aptamers, and the selection process known as Systematic Evolution of Ligands by Exponential Enrichment (SELEX) used to generate them, were first described more than twenty years ago. Since then, there have been numerous modifications to the selectionprocedures. This review discusses the use of modified bases as a means of enhancing serum stability and producing effective therapeutic tools, as well as functionalising these nucleic acids to be used as potential diagnostic agents.

Localization and tracking of agents for close range applications

This research investigates the state estimation problem in close-range involving multiple targets using Doppler Radar. As the main theme is based on measurements with linear sensor arrays, optimal sensor arrangements are studied for two most popular measurement technologies: Angle-of-Arrival and range based localization systems.

Development of microfluidic-based analytical methodology for studying the effects of chemotherapy agents on cancer tissue

Whilst a multitude of techniques have been employed to study the biology of tumour tissue and its response to chemotherapeutic reagents, most current methodologies do not capture the sophistication of the in vivo environment. Microfluidics however offers the ability to maintain and interrogate primary tissue samples in an environment with biomimetic flow characteristics. In this study head and neck squamous cell carcinoma (HNSCC) tumour biopsies have been used to investigate the performance of a microfluidic device for generating clinically-useful information. The response of fresh and cryogenically-frozen primary HNSCC or metastatic lymph node samples to chemotherapy drugs (cisplatin, 5-flurouracil or docetaxel), alone and in combination, were monitored for both proliferation (water-soluble tetrazolium salt metabolism) and cell death biomarker release (lactate dehydrogenase, LDH) “off-chip”. The frozen tissue showed no significant difference in terms of either proliferation or LDH release in comparison with the matched fresh samples. Administration of all drugs caused cell death, in a dose-response manner, with the combination showing the greatest amount of cytotoxicity particularly at days 8 and 9; correlating well with published clinical data. The system described here offers an innovative method for studying the tumour microenvironment in vitro and, through incorporation of relevant analytical modules, provides the basis of a pre-clinical device that can be used to define personalised treatment regimens.

Direct processing of clinically relevant large volume samples for the detection of sexually transmitted infectious agents from urine on a microfluidic device

Urine is a preferred specimen for nucleic acid-based detection of sexually transmitted infections (STIs) but represents a challenge for microfluidic devices due to low analyte concentrations. We present an extraction methodology enabling rapid on-chip nucleic acid purification directly from clinically relevant sample volumes up to 1 ml and subsequent PCR amplification detection.

Modelling interplay in normative social systems: towards a heuristics formalism of agents and networks

The need for guiding model formulation of normative social systems in support of a digital ecosystem is introduced. Normative social systems improve the understanding of computational social processes in simulation and experimentation, and provide support for digital ecosystem developments. However, a successful simulation requires the appropriate implementation of a conceptual model. It is proposed that an heuristic formalism of agents, networks and environments, complements the conventional creative approach to model formulation by guiding the formulation of conceptual models via abstract components and facilitate interface with other components in a digital environment.