Advances in Medical and Surgical Engineering integrates the knowledge and experience of experts from academia and practicing surgeons working with patients. The cutting-edge progress in medical technology applications is making the traditional line between engineering and medical science ever thinner. This is an excellent resource for biomedical engineers working in industry and academia on developing medical technologies. It covers challenges in the application of technology in the clinic with views from an editorial team that is highly experienced in engineering, biomaterials, surgical practice, biomedical science and technology, and that has a proven track record of publishing applied biomedical science and technology. For medical practitioners, this book covers advances in technology in their domain. For students, this book identifies the opportunities of research based on the reviews of utilization of current technologies. The content in this book can also be of interest to policymakers, research funding agencies, and libraries, that are contributing to development of medical technologies. Key Features Covers circulatory support, aortic valve implantation and microvascular antestmosis Explores arthroplasty of both the knee and the shoulder Includes tribology of materials, laser treatment and machining of biomaterials Readership Graduate students, researchers, or engineers who work in the interdisciplinary field of biomedical engineering

Since their discovery in 1991, carbon nanotubes (CNTs) have emerged as material structures with numerous potential applications with a number of products already in the market place. An exciting application, which is emerging, is the use of carbon nanotubes for drug delivery. In this chapter, we focus on the functionalization, mechanism of cellular update, and using carbon nanotubes for delivery of anticancer drugs.

Photocatalytic degradation of methyl orange (MO) in water was examined using TiO2 nanopowders under solar irradiation. These photocatalysts were successfully synthesized by hydrolysis of titanium tetra chloride (TiCl4) in the temperature range of 70-95 °C and calcined at higher temperatures of between 400 and 900 °C. The samples prepared were characterized using x-ray powder diffraction, scanning electron microscope (SEM) and Fourier transform infrared spectrophotometer (FTIR). UV-Vis spectrometer was used for analyzing the concentration of MO in solution at different time intervals during the photodegradation experiment. Parameters affecting the photodegradation rate such as catalyst crystallinity, concentration of the catalyst, MO concentration, and pH of the solution have been investigated. The results indicate that TiO2 nanopowder was antase at low calcination temperatures in the range of 400-500 °C. The sample calcined at 600 °C is composed of both anatase and rutile phase. Further increase in the temperature enhanced the intensities of diffraction peaks of the rutile phase. The size of the crystallites for all the samples prepared were found to be in the 6-13 nm range and from SEM micrographs it was in the range of 19-43 nm. The mixture of both phases exhibited a higher photoactivity in comparison with pure anatase or rutile catalysts.

There are increasing demands for higher levels of data assurance in higher education. This paper explores some of the drivers for this trend, and then explains what stakeholders mean by the concept of data assurance, since this has not been well defined previously. The paper captures insights from existing literature, stakeholders, auditors, and the university case experience of the authors to produce a logical model of data assurance. The model seeks to make the best use of scarce resources to deliver the stakeholders' assurance expectations, reducing redundancy and minimising the risks of omission. A logical and layered approach to the problem best delivers these outcomes. The paper concludes with a consideration of implementation issues, and demonstrates how traditional differences between academics and administrators in this difficult area may be addressed. While the paper is located in the English context, the principles will have wider applicability under other regulatory regimes.

A better understanding of protein adsorption onto surfaces of materials is required to control biocompatibility and bioactivity. Diamond-like carbon (DLC) is known to have excellent biocompatibility. Various samples of a-C:H and silicon-doped a-C:H thin films (Si-DLC) were deposited onto silicon substrates using plasma-enhanced chemical vapour deposition (PECVD). Subsequently, the adsorption of the simplest amino acid glycine onto the surfaces of the thin films was investigated to elucidate the mechanisms involved in protein adhesion. The physicochemical characteristics of the surfaces, before and after adsorption of glycine, were investigated using Raman spectroscopy and atomic force microscopy (AFM). The Raman study highlighted a slight decrease in the I D/I G ratio with increasing the silicon dopant levels. Following exposure to glycine solutions, the presence of bands at ~1735 and ~1200 cm−1 indicates that the adsorption of glycine onto the surfaces has taken place. Glycine was bound to the surfaces via both deprotonated carboxyl and protonated amino groups whilst, as the silicon content in the DLC film increased the adsorption of glycine decreased. AFM analysis showed that the surface roughness increased following exposure to glycine. These results show that at low silicon doping the adsorption of the amino acid was enhanced whilst increased doping levels led to a reduced adsorption compared to undoped DLC. Therefore, doping of DLC may provide an approach to control the protein adsorption.

Microbial pathogens with resistance to conventional drugs are a problem of global proportions and may be viral such as HIV, bacterial as in the case of MRSA or eukaryotic as seen with the malarial parasite Plasmodium falciparum. In response, photodynamic antimicrobial chemotherapy (PACT) has been developed, which is the delivery of a non-toxic photosensitiser (PS) to the site of a microbial infection. When taken up by the pathogen, illumination of the PS by light at an appropriate wavelength can lead to inactivation of the pathogen through the production of highly reactive free radical species, which induce oxidative damage to lipid, proteins and DNA / RNA, and / or adduct formation between the PS and these microbial biomolecules. Here the photochemical and photophysical steps underlying PS antimicrobial action along with the desirable electronic and physiochemical properties of PS are briefly reviewed. The therapeutic uses of PS are then illustrated with reference to a number that have featured in recent patents, including: The induction of endogenous PS by aminolevulinic acid; phenothiazinium based PS, which are the most studied of PACT agents, psoralens and organorhodium complexes.

Abstract: Atherosclerotic coronary heart disease and other forms of cardiovascular disease (CVD) are the major cause of mortality in type II diabetes (T2DM) as well as a major contributor to morbidity and lifetime costs. The purpose of this article is the identification of the biochemical parameters in plasma, which may serve as predisposition factors to CVD in T2DM patients of different ages. The variability of hyperglycemia, dyslipidemia, and inflammation with age progression was also studied for comparison. Four different diabetic groups allocated on the basis of the subjects' age (Group A: 15–25 years old; Group B: 26–40 years old; Group C: 40–60 years old; Group D: 60–80 years old) and consisting of 10 patients each, in parallel with 10 healthy controls matched for age, sex, and ethnic origin were screened for glucose, insulin, lipid profile (total cholesterol, triglycerides, LDL, and HDL), and inflammatory mediators (CRP, IL-6, and TNF-α). Significant differences were observed among the expressions of biochemical markers among different age groups. Hyperglycemia showed no variability with age whereas dyslipidemia correlated positively with age progression, as well as obesity, low physical activity, and family history of heart disease or diabetes. Marked inflammation was prominent only in Groups C and D. This article indicates that different biochemical parameters may be used for the assessment of CVD risk in T2DM patients of variable age.

It is known that there is a high occurrence of rare codons at the start of coding region. Here it is shown that although the remainder of the gene is likely to contain a relatively low number of rare codons, rare and non-rare codons do not form a random sequence. It is apparent that throughout the coding region there is a higher than expected number of rare codon clusters. For example once a rare codon has occurred there is a greater chance than expected of the next six codons containing another rare codon. This non-random distribution implies that rare codons may have an as yet unidentified biological role.

The replacement of hydrogen with deuterium is frequently used in conjunction with neutron diffraction to investigate peptide-membrane interaction. This isotopic substitution in an amino acid residue radically changes the neutron scatter pattern of the peptide, thereby allowing its localisation within the bilayer with the aid of derived Fourier maps. Nonetheless, this technique relies on the generally held assumption that normal and isotopically enriched protein species do not differ significantly in structure or biological activity. Recently, this assumption has been questioned and here, diffraction data from studies on a membrane interactive peptide clearly challenge the reliability of this assumption.

The ability of phenothiazinium-based photosensitizers to induce photodamage to Escherichia coli membranes is investigated. Phenothiazinium-based photosensitizers were found to be somewhat lipophilic (log P>0.7) and to induce surface-pressure changes (3-12 mN m(-1)) in lipid monolayers mimetic of bacterial membranes, implying that these molecules are able to penetrate biological membranes. Under dark and light conditions (3.15 J cm(-1) for 30 min), phenothiazinium-based photosensitizers were incubated with E. coli cells. These cells showed levels of dark bacteriolysis that ranged between 6% and 13%, with light conditions leading to no significant increase in these levels. Gas chromatography-based analyses showed such incubations to produce no significant changes in the levels of C(16) and C(18) fatty acid chain saturation found in E. coli whole lipid-extracts. It is concluded that the phenothiazinium-based photosensitizers studied may not use E. coli membranes as their primary photodynamic target, but may inflict photodamage on cytoplasmic targets, possibly DNA.

PhBPs show selectivity for tumour and microbial cells, which appears to be based on electrostatic interactions between the positive charge generally carried by these molecules and the negative charge found on the outer surface of these target cells. In some cases, a site of action for photoactivated PhBPs is the outer membrane/envelope of the target cell. Such action can involve the modification of membrane lipid and/or lipopolysaccharide, and the inactivation of essential proteins and enzymes, with these effects usually leading to cell lysis and death. However, more often, PhBPs are internalised by target cells, promoted by a variety of factors, including low pH and enzymatic reduction, and upon photoactivation, internalised, PhBPs are able to inflict damage on a number of intracellular targets. In tumour cells, PhBPs can photodamage DNA and the membranes of organelles, thereby inducing necrosis and/or apoptosis. In bacterial cells, whilst DNA is generally a primary target of PhBPs, these compounds can exhibit multiple sites of action within a given cell and show different sites of action between different bacterial species. This variable targeting makes PhBPs attractive propositions as alternatives to conventional antibiotics in that the emergence of bacterial strains with acquired resistance to these compounds appears to be highly unlikely.

m-calpain is a calcium-dependent heterodimeric protease implicated in a number of pathological conditions. The activation of m-calpain appears to be modulated by membrane interaction, which has been predicted to involve oblique-orientated alpha-helix formation by a GTAMRILGGVI segment located in domain V of the protein's small subunit. Here, we have investigated this prediction. Fourier transform infrared conformational analysis showed that VP1, a peptide homolog of this segment, exhibited alpha-helicity of approximately 45% in the presence of dimyristoylphosphatidylcholine/dimyristoylphosphatidylserine (DMPS) vesicles. The level of helicity was unaffected over a 1- to 8-mM concentration range and did not alter when the anionic lipid composition of these vesicles was varied between 1% and 10% DMPS. Similar levels of alpha-helicity were observed in trifluoroethanol and the peptide appeared to adopt alpha-helical structure at an air/water interface with a molecular area of 164 A(2) at the monolayer collapse pressure. VP1 was found to penetrate dimyristoylphosphatidylcholine/DMPS monolayers, and at an initial surface pressure of 30 mN m(-1), the peptide induced surface pressure changes in these monolayers that correlated strongly with their anionic lipid content (maximal at 4 mN m(-1) in the presence of 10% DMPS). Neutron diffraction studies showed VP1 to be localized at the hydrophobic core of model palmitoyloleylphosphatidylcholine/palmitoyloleylphosphatidylserine (10:1 molar ratio) bilayer structures and, in combination, these results are consistent with the oblique membrane penetration predicted for the peptide. It would also appear that although not needed for structural stabilization anionic lipid was required for membrane penetration.

To facilitate microbial membrane invasion, amphiphilic alpha-helical antimicrobial peptides (alpha-AMPs) show a spatial segregation of hydrophobic and hydrophilic residues about the alpha-helical long axis. Here we discuss potential mechanisms by which these peptides are able to disrupt membrane structure and the structural characteristics, which are required for function.

Globally, cataract accounts for the majority of cases of treatable blindness and the lens opacification associated with cataract is primarily due to the insolubilisation of crystallins, proteins essential for the transparency of the lens. Recent studies have suggested that a major cause of this insolubilisation may be the unregulated proteolysis of crystallins by calpains. These are intracellular cysteine proteases whose activation requires the presence of Ca2+ and elevated levels of lens Ca2+ is a condition strongly associated with cataract. Calpain 2 appears to be the major calpain involved in animal cataractogenesis and the strongest candidate of the calpains for a role in human cataractogenesis but despite intensive study, the mechanism(s) underlying activation of the enzyme both in cataractogenesis and normal lens function are unclear. Recently, the high-resolution structure of calpain 2 was recently solved and a structural basis for the Ca2+-dependence of the enzyme's activity has been putatively established. Other recent studies have suggested that membrane interaction(s) may play a role in lowering the Ca2+-requirements of calpain 2 activation and most recently, strongly supporting this suggestion, several lipid interactive regions in the enzyme have been identified. Here, we review progress in understanding of the role played by calpain 2 in cataractogenesis and the possible use of inhibitors of the enzyme as anti-cataract agents.

Oblique orientated alpha-helices are highly specialised protein structural elements that penetrate membranes at a shallow angle and are used to promote membrane destabilisation by a number of protein classes. Here, the use of extended hydrophobic moment methodology shows that the amphibian extrudates, aurein 1.2 and citropin 1.1, may use oblique orientated alpha-helices in their antimicrobial action and that such use may be shared by other antimicrobial peptides. This appears to be the first systematic analysis of these peptides for the possession of oblique orientated alpha-helical structure.

The open reading frame 4 (ORF 4) gene product of barley yellow dwarf virus (BYDV) may act as a movement protein (MP) by assisting the transport of viral genomic RNA across the nuclear envelope (NE) of host plant cells. To investigate interactions between BYDV MP and the NE, wild-type and mutant open reading frame (ORF 4)-green fluorescent protein (GFP) fusion cistrons were expressed in insect cells. A fusion protein expressed by the wild-type ORF 4-GFP cistron associated with the NE and caused protrusions from its surface. The fusion protein expressed by the mutant ORF 4-GFP cistron lacked a putative amphiphilic alpha-helix at its N-terminus and although associating with the NE, showed decreased levels of protrusions. A peptide homologue of this putative alpha-helix induced an increase of 7 degrees C in the phase transition temperature of dimyrystoyl phosphatidylserine (DMPS) membranes, accompanied by a decrease in membrane fluidity, but exhibited no significant interaction with either dimyristoyl phosphatidylcholine (DMPC) or dimyristoyl phosphatidylethanolamine (DMPE) membranes. These results strongly support the view that BYDV MP may interact with the NE to help transport viral genomic RNA into the nuclear compartment. This function of BYDV MP appears to involve protrusions on the surface of the NE and may require the presence of an N-terminal amphiphilic alpha-helix, which is speculated to destabilize membranes, thereby assisting the entry of BYDV-GAV into the nuclear compartment.

Background: There is an urgent need for effective cancer treatments and increasingly, photo-dynamic therapy (PDT) is being used to fulfil this need as it offers a number of advantages over traditional cancer treatments. Here, the potential of a series of phenothiazinium-based photo-sensitisers (PhBPs) as PDT agents is tested.Methods: PhBPs were incubated with EMT-6 tumour cells and erythrocytes respectively under dark and light conditions (3.15J cm(-2) over 30 min). "Comet assay" and haemolytic assay were then used to assess cellular photo-damage induced by these PhBPs. Additionally, in vitro assays were used to determine light adsorption characteristics, singlet oxygen yields (Phi(Delta PhBP)) and lipophilicity (log P) of these PhBPs.Results: "Comet assay" showed EMT-6 incubation with PhBPs under light conditions to produce DNA "tails", which were circa 35 mu m long, indicating the presence of DNA photo-damage. Corresponding incubations under dark conditions led to no such damage. The majority of the PhBPs tested possessed significant singlet oxygen yields (Phi(Delta PhBP) > 0.7), suggesting the general use of type II mechanisms for photosensitization, and were generally lipophilic (log P > 0). Incubation of erythrocytes with these PhBPs in the dark produced between 6% and 19% haemolysis. These levels were generally unaffected by illumination except in the case of DMMB, which showed haemolytic levels increasing from 11% to 61%.Conclusions: It is suggested that DNA may be the primary target for the photodynamic anti-tumour activity of the PhBPs tested with the exception of DMMB, which may potentially also target tumour cell membranes. (C) 2004 Elsevier B.V. All rights reserved.