Mechanisms contributing to the enhanced respiratory burst of neutrophils observed in periodontitis

The aim of this thesis is to investigate possible mechanisms that may contribute to neutrophil hyperactivity and hyper-reactivity. One possibility is the presence of a neutrophil priming factors within the peripheral circulation of periodontitis patients. To examine this possibility differentiated HL-60 cells and primary neutrophils were studied in the presence and absence of plasma from periodontitis patients. In independent experiments, plasma was depleted of IL-8, GM-CSF, interferon-a, immunoglobulins and albumin. This work demonstrated that plasma factors such as IL-8, GM-CSF, and interferon-a present during periodontitis may contribute towards the reported hyperactive neutrophil phenotype. Furthermore, this work demonstrated that products from Pg may regulate neutrophil accumulation at infected periodontal sites by promoting gingipain-dependent modification of IL-8-77 into a more biologically active chemokine. To elucidate whether the oxidatively stressed environment that neutrophils are exposed to in periodontitis could influence hyperactivity and hyper-reactivity, neutrophils were depleted of glutathione. This work showed that during oxidative stress, where cellular redox-levels have been altered, neutrophils exhibit an increased respiratory burst. In conclusion, this work highlights the multiple mechanisms that may contribute to neutrophil hyperactivity and hyperreactivity including gingipain-modulated activity of IL-8 variants, the effect of host factors such as IL-8, GM-CSF, interferon-a on neutrophils priming and activation, and the shift of neutrophil GSH:GSSG ratio in favour of a more oxidised environment as observed in periodontitis.

Thin film bearings with phase change of lubricant

The possible evaporation of lubricant in fluid film bearings has been investigated theoretically and by experiment using a radial flow hydrostatic bearing supplied with liquid refrigerant R114. Good correlation between measured and theoretical values was obtained using a bespoke computational fluid dynamic model in which the flow was assumed to be laminar and adiabatic. The effects of viscous dissipation and vapour generation within the fluid film are fully accounted for by applying a fourth order Runge-Kutta routine to satisfy the radial and filmwise transverse constraints of momentum, energy and mass conservation. The results indicate that the radial velocity profile remains parabolic while the flow remains in the liquid phase and that the radial rate of enthalpy generation is then constant across the film at a given radius. The results also show that evaporation will commence at a radial location determined by geometry and flow conditions and in fluid layers adjacent to the solid boundaries. Evaporation is shown to progress in the radial direction and the load carrying capacity of such a bearing is reduced significantly. Expressions for the viscosity of the liquid/vapour mixture found in the literature survey have not been tested against experimental data. A new formulation is proposed in which the suitable choice of a characteristic constant yields close representation to any of these expressions. Operating constraints imposed by the design of the experimental apparatus limited the extent of the surface over which evaporation could be obtained, and prevented clear identification of the most suitable relationship for the viscosity of the liquid/vapour mixture. The theoretical model was extended to examine the development of two phase flow in a rotating shaft face seal of uniform thickness. Previous theoretical analyses have been based on the assumption that the radial velocity profile of the flow is always parabolic, and that the tangential component of velocity varies linearly from the value at the rotating surface, to zero at the stationary surface. The computational fluid dynamic analysis shows that viscous shear and dissipation in the fluid adjacent to the rotating surface leads to developing evaporation with a consequent reduction in tangential shear forces. The tangential velocity profile is predicted to decay rapidly through the film, exhibiting a profile entirely different to that assumed by previous investigators. Progressive evaporation takes place close to the moving wall and does not occur completely at a single radial location, as has been claimed in earlier work.

Activation of the neutrophil respiratory burst by plasma from periodontitis patients is mediated by pro-inflammatory cytokines

Aim: To determine the effect of periodontitis patients' plasma on the neutrophil oxidative burst and the role of albumin, immunoglobulins (Igs) and cytokines. Materials and Methods: Plasma was collected from chronic periodontitis patients (n=11) and periodontally healthy controls (n=11) and used with/without depletion of albumin and Ig or antibody neutralization of IL-8, GM-CSF or IFN-a to prime/stimulate peripheral blood neutrophils, isolated from healthy volunteers. The respiratory burst was measured by lucigenin-dependent chemiluminescence. Plasma cytokine levels were determined by ELISA. Results: Plasmas from patients were significantly more effective in both directly stimulating neutrophil superoxide production and priming for subsequent formyl-met-leu-phe (fMLP)-stimulated superoxide production than plasmas from healthy controls (p<0.05). This difference was maintained after depletion of albumin and Ig. Plasma from patients contained higher mean levels of IL-8, GM-CSF and IFN-a. Individual neutralizing antibodies against IL-8, GM-CSF or IFN-a inhibited the direct stimulatory effect of patients' plasma, whereas the ability to prime for fMLP-stimulated superoxide production was only inhibited by neutralization of IFN-a. The stimulating and priming effects of control plasma were unaffected by antibody neutralization. Conclusions: This study demonstrates that plasma cytokines may have a role in inducing the hyperactive (IL-8, GM-CSF, IFN-a) and hyper-reactive (IFN-a) neutrophil phenotype seen in periodontitis patients.

Oxidative and inflammatory status in Type 2 diabetes patients with periodontitis

Aim: To determine the impact of periodontitis on oxidative/inflammatory status and diabetes control in Type 2 diabetes. Materials and Methods: A comparative study of 20 Type 2 diabetes patients with periodontitis [body mass index (BMI) 31+5], 20-age/gender-matched, non-periodontitis Type 2 diabetes controls (BMI 29+6) and 20 non-diabetes periodontitis controls (BMI 25+4) had periodontal examinations and fasting blood samples collected. Oxidative stress was determined by plasma small molecule antioxidant capacity (pSMAC) and protein carbonyl levels; inflammatory status by total/differential leucocytes, fibrinogen and high sensitivity C-reactive protein (hsCRP); diabetes status by fasting glucose, HbA1c, lipid profile, insulin resistance and secretion. Statistical analysis was performed using SPSS. Results: pSMAC was lower (p=0.03) and protein carbonyls higher (p=0.007) in Type 2 diabetes patients with periodontitis compared with those without periodontitis. Periodontitis was associated with significantly higher HbA1c (p=0.002) and fasting glucose levels (p=0.04) and with lower ß-cell function (HOMA-ß; p=0.01) in diabetes patients. Periodontitis had little effect on inflammatory markers or lipid profiles, but Type 2 diabetes patients with periodontitis had higher levels of hsCRP than those without diabetes (p=0.004) and the lowest levels of HDL-cholesterol of all groups. Conclusion: Periodontitis is associated with increased oxidative stress and compromised glycaemic control in Type 2 diabetes patients.

Ophthalmic lenses availability:the guide to spectacle lenses, coatings and tints available in the United Kingdom

The guide to spectacle lenses and coatings and tints available in the UK. The Ophthalmic Lenses Availability Guide aims to collate information from lens manufacturers in the UK enabling practitioners to rapidly locate lenses suitable for your patients. Twenty lens and coating manufacturers are represented in the Guide which consists of three sections; the availability index, manufacturer's data and lens data files. In the 2008 edition, the availability index has been updated; arranging lenses by type and then in ascending order of refractive index. Additionally, for progressive power lenses, the corridor length or fitting height is included allowing the practitioner to more rapidly identify a lens which meets the fitting requirements of a selected frame. Further technical information is provided for a selected by going to the appropriate page number in the manufacturer’s section. The lens data files contain additional information on the optical properties of materials, tints and coatings and a summary list of hidden markings on progressive power lenses enabling the practitioner to identify the lens a patient is currently wearing.

New business formation in a rapidly growing economy: The Irish experience

The extraordinary growth of the Irish economy since the mid-1990s - the 'Celtic Tiger' - has attracted a great deal of interest, commentary and research. Indeed, many countries look to Ireland as an economic development role model, and it has been suggested that Ireland might provide key lessons for other EU members as they seek to achieve the objectives set out in the Lisbon Agenda. Much of the discussion of Ireland's growth has focused on its possible triggers: the long term consequences of the late 1980s fiscal stabilisation; EU structural funds; education; wage moderation; and devaluation of the Irish punt. The industrial policy perspective has highlighted the importance of inflows of foreign direct investment, but a notable absence from the discourse on the 'Celtic Tiger' has been any mention of the role of new business venture creation and entrepreneurship. In this paper we use unpublished Irish VAT data for the years 1988 to 2004 to provide the first detailed look at national trends in business birth and death rates in Ireland over the 'take-off' period. We also use sub-national VAT data to shed light on spatial trends in new venture creation. Our overall conclusions are that new business formation made no detectable contribution to the acceleration of Ireland's growth in the late 1990s, although we do find evidence of spatial convergence in per capita business stocks.

Progressive structural analysis for dynamic recognition of on-line handwritten mathematical expressions

Structural analysis in handwritten mathematical expressions focuses on interpreting the recognized symbols using geometrical information such as relative sizes and positions of the symbols. Most existing approaches rely on hand-crafted grammar rules to identify semantic relationships among the recognized mathematical symbols. They could easily fail when writing errors occurred. Moreover, they assume the availability of the whole mathematical expression before being able to analyze the semantic information of the expression. To tackle these problems, we propose a progressive structural analysis (PSA) approach for dynamic recognition of handwritten mathematical expressions. The proposed PSA approach is able to provide analysis result immediately after each written input symbol. This has an advantage that users are able to detect any recognition errors immediately and correct only the mis-recognized symbols rather than the whole expression. Experiments conducted on 57 most commonly used mathematical expressions have shown that the PSA approach is able to achieve very good performance results.

Towards a web-based progressive handwriting recognition environment for mathematical problem solving

The emergence of pen-based mobile devices such as PDAs and tablet PCs provides a new way to input mathematical expressions to computer by using handwriting which is much more natural and efficient for entering mathematics. This paper proposes a web-based handwriting mathematics system, called WebMath, for supporting mathematical problem solving. The proposed WebMath system is based on client-server architecture. It comprises four major components: a standard web server, handwriting mathematical expression editor, computation engine and web browser with Ajax-based communicator. The handwriting mathematical expression editor adopts a progressive recognition approach for dynamic recognition of handwritten mathematical expressions. The computation engine supports mathematical functions such as algebraic simplification and factorization, and integration and differentiation. The web browser provides a user-friendly interface for accessing the system using advanced Ajax-based communication. In this paper, we describe the different components of the WebMath system and its performance analysis.

New business formation in a rapidly growing economy:the Irish experience

The extraordinary growth of the Irish economy since the mid-1990s—the ‘Celtic Tiger’—has attracted a great deal of interest, commentary and research. Indeed, many countries look to Ireland as an economic development role model, and it has been suggested that Ireland might provide key lessons for other EU members as they seek to achieve the objectives set out in the Lisbon Agenda. Much of the discussion of Ireland’s growth has focused on its possible triggers: the long-term consequences of the late 1980s fiscal stabilisation, EU structural funds, education, wage moderation and devaluation of the Irish punt. The industrial policy perspective has highlighted the importance of inflows of foreign direct investment, but a notable absence from the discourse on the ‘Celtic Tiger’ has been any mention of the role of new business venture creation and entrepreneurship. In this paper we use unpublished Irish VAT data for the years 1988–2004 to provide the first detailed look at national trends in business birth and death rates in Ireland over the ‘take-off’ period. We also use sub-national VAT data to shed light on spatial trends in new venture creation. Our overall conclusions are that new business formation made no detectable contribution to the acceleration of Ireland’s growth in the late 1990s, although we do find evidence of spatial convergence in per capita business stocks.

Off-farm labour supply and labour markets in rapidly changing circumstances:Bulgaria during transition

This study examines off-farm labor supply in the rapidly changing conditions of Bulgaria during the 1990s. In doing so, we make use of three different waves of the Bulgarian Integrated Household Survey, each reflecting remarkably different environmental conditions. The results suggest that standard theories of off-farm labor supply provide little guidance in situations characterized by chronic excess supply in the off-farm labor market and/or rapidly changing circumstances. In particular, the results show (1) that off-farm employment throughout the transition was predominantly determined by demand rather than by supply, and (2) that the magnitude and statistical significance of the various determinants are very sensitive to changing environmental conditions. As such, the results can be extremely relevant for both theory and policy for the many countries which may still need to go through privatization and painful restructuring as a result of financial crises and globalization.

Spatial patterns of the tau pathology in progressive supranuclear palsy

Progressive supranuclear palsy (PSP) is characterized neuropathologically by neuronal loss, gliosis, and the presence of tau-immunoreactive neuronal and glial cell inclusions affecting subcortical and some cortical regions. The objectives of this study were to determine (1) the spatial patterns of the tau-immunoreactive pathology, viz., neurofibrillary tangles (NFT), oligodendroglial inclusions (GI), tufted astrocytes (TA), and Alzheimer's disease-type neuritic plaques (NP) in PSP and (2) to investigate the spatial correlations between the histological features. Post-mortem material of cortical and subcortical regions of eight PSP cases was studied. Spatial pattern analysis was applied to the NFT, GI, TA, NP, abnormally enlarged neurons (EN), surviving neurons, and glial cells. NFT, GI, and TA were distributed either at random or in regularly distributed clusters. The EN and NP were mainly randomly distributed. Clustering of NFT and EN was more frequent in the cortex and subcortical regions, respectively. Variations in NFT density were not spatially correlated with the densities of either GI or TA, but were positively correlated with the densities of EN and surviving neurons in some regions. (1) NFT were the most widespread tau-immunoreactive pathology in PSP being distributed randomly in subcortical regions and in regular clusters in cortical regions, (2) GI and TA were more localized and exhibited a regular pattern of clustering in subcortical regions, and (3) neuronal and glial cell pathologies were not spatially correlated. © 2012 Springer-Verlag.

Sulforaphane restores cellular glutathione levels and reduces chronic periodontitis neutrophil hyperactivity in vitro

The production of high levels of reactive oxygen species by neutrophils is associated with the local and systemic destructive phenotype found in the chronic inflammatory disease periodontitis. In the present study, we investigated the ability of sulforaphane (SFN) to restore cellular glutathione levels and reduce the hyperactivity of circulating neutrophils associated with chronic periodontitis. Using differentiated HL60 cells as a neutrophil model, here we show that generation of extracellular O2 . - by the nicotinamide adenine dinucleotide (NADPH) oxidase complex is increased by intracellular glutathione depletion. This may be attributed to the upregulation of thiol regulated acid sphingomyelinase driven lipid raft formation. Intracellular glutathione was also lower in primary neutrophils from periodontitis patients and, consistent with our previous findings, patients neutrophils were hyper-reactive to stimuli. The activity of nuclear factor erythroid-2-related factor 2 (Nrf2), a master regulator of the antioxidant response, is impaired in circulating neutrophils from chronic periodontitis patients. Although patients' neutrophils exhibit a low reduced glutathione (GSH)/oxidised glutathione (GSSG) ratio and a higher total Nrf2 level, the DNA-binding activity of nuclear Nrf2 remained unchanged relative to healthy controls and had reduced expression of glutamate cysteine ligase catalytic (GCLC), and modifier (GCLM) subunit mRNAs, compared to periodontally healthy subjects neutrophils. Pre-treatment with SFN increased expression of GCLC and GCM, improved intracellular GSH/GSSG ratios and reduced agonist-activated extracellular O2 . - production in both dHL60 and primary neutrophils from patients with periodontitis and controls. These findings suggest that a deficiency in Nrf2-dependent pathways may underpin susceptibility to hyper-reactivity in circulating primary neutrophils during chronic periodontitis. © 2013 Dias et al.

White matter pathology in progressive supranuclear palsy (PSP):a quantitative study of 8 cases

Aims: To quantify white matterpathology in progressive supranuclear palsy (PSP). Material: Histological sections of white matter of 8 PSP and 8 control cases \Method: Densities and spatial patterns of vacuolation, glial cell nuclei, and glial inclusions (GI) were measured in 8cortical and subcortical fiber tracts. Results: No GI wereobserved in control fiber tracts. Densities of vacuoles and glial cell nuclei were greater in PSP than in controls. In PSP, density of vacuoles was greatest in the alveus, frontopontine fibers (FPF), and central tegmental tract (CTT), and densities of glial cell nuclei were greater in cortical than subcortical regions.The highest densities of GI were observed in the basal ganglia, FPF, cerebellum, andsuperior frontal gyrus (SFG). Vacuoles, glialcells and GI were distributed randomly, uniformly,in regularly distributed clusters, or in large clusters across fiber tracts. GI wermore frequently distributed in regular clusters than the vacuoles and glial cell nuclei.Vacuoles, glial cell nuclei, and GI were not spatially correlated. Conclusions: The data suggest significant degeneration of white matter in PSP, vacuolation being related to neuronal loss in adjacent gray matterregions,GI the result of abnormal tau released from damaged axons, and gliosis a responseto these changes. © 2013.

Margetinggeschichte:Die Genese einer modernen Sozialtechnik, Hartmut Berghoff

Book revew: Marketinggeschichte: die Genese einer modernen Sozialtechnik [Marketing history: The genesis of a modern social technique], edited by Hartmut Berghoff, Frankfurt/Main, Campus Verlag, 2007, 409 pp., illus., [euro]30.00 (paperback), ISBN 978-3-593-38323-1. This edited volume is the result of a workshop at Göttingen University in 2006 and combines a number of different approaches to the research into the history of marketing in Germany's economy and society. The majority of contributions loosely focus around the occurrence of a ‘marketing revolution’ in the 1970s, which ties in with interpretations of the Americanisation of German business. This revolution replaced the indigenous German idea of Absatzwirtschaft (the economics of sales) with the American-influenced idea of Marketing, which was less functionally oriented and more strategic, and which aimed to connect processes within the firm in order to allow a greater focus on the consumer. The entire volume is framed by Hartmut Berghoff's substantial and informative introduction, which introduces a number of actors and trends beyond the content of the volume. Throughout the various contributions, authors provide explanations of the timing and nature of marketing revolutions. Alexander Engel identifies an earlier revolution in the marketing of dyes, which undergoes major change with the emergence of chemical dyes. While the natural dyestuff had been a commodity, with producers removed from consumers via a global network of traders, chemical dyes were products and were branded at an early stage. This was a fundamental change in the nature of production and sales. As Roman Rossfeld shows in his contribution on the Swiss chocolate industry (which focuses almost exclusively on Suchard), even companies that produced non-essential consumer goods which had always required some measure of labelling grappled for years with the need to develop fewer and higher impact brands, as well as an efficient sales operation. A good example for the classical ‘marketing revolution’ of the 1970s is the German automobile industry. Ingo Köhler convincingly argues that the crisis situation of German car manufacturers – the change from a seller's to a buyer's market, appreciation of the German mark which undermines exports, the oil crises coupled with higher inflation and greater frugality of consumers and the emergence of new competitors – lead companies to refocus from production to the demands of the consumer. While he highlights the role of Ford in responding most rapidly to these problems, he does not address whether the multinational was potentially transferring American knowledge to the German market. Similarly, Paul Erker illustrates that a marketing revolution in transport and logistics happened much later, because the market remained highly regulated until the 1980s. Both Paul Erker and Uwe Spiekermann in their contribution, present comparisons of two different sectors or companies (the tire manufacturer Continental and the logistics company Dachser, and agriculture and trade, respectively). In both cases, however, it remains unclear why these examples were chosen for comparison, as both seem to have little in common and are not always effectively used to demonstrate differences. The weakest section of the book is the development of marketing as an academic discipline. The attempt at sketching the phases in the evolution of marketing as an academic discipline by Ursula Hansen and Matthias Bode opens with an undergraduate-level explanation on the methodology of historical periodisation that seems extraneous. Considerably stronger is the section on the wider societal impact of marketing, and Anja Kruke shows how the new techniques of opinion research was accepted by politics and business – surprisingly more readily by politicians than their commercial counterparts. In terms of contemporary personalities, Hans Domizlaff emerges as one fascinating figure of German marketing history, which several contributors refer to and whose career as the German cigarette manufacturer Reemtsma is critically analysed by Tino Jacobs. Domizlaff was Germany's own ‘marketing guru’, whose successful campaigns led to the wide-ranging reception of his ideas about the nature of good branding and marketing. These are variously described as intuitive, elitist, and sachlich, a German concept of a sober, fact-based, and ‘no frills’ approach. Domizlaff did not believe in market research. Rather, he saw the genius of the individual advertiser as key to intuitively ascertaining the people's moods, wishes, and desires. This seems to have made him peculiarly suited to the tastes of the German middle class, according to Thomas Mergel's contribution on the nature of political marketing in the republic. Especially in politics, any form of hard sales tactics were severely frowned upon and considered to demean the citizen as incapable of making an informed choice, a mentality that he dates back to the traditions of nineteenth-century liberalism. Part of this disdain of ‘selling politics like toothpaste’ was also founded on the highly effective use of branding by the National Socialists, who identified their party through the use of an increasingly standardised image of Adolf Hitler and the swastika. Alexander Schug extends on previous research that criticised the simplistic notion of Hitler's charisma as the only explanation of the popular success and distances his approach from those who see it in terms of propaganda and demagogy. He argues that the NSDAP used the tools of advertising and branding precisely because they had to introduce their new ideology into a political marketplace dominated by more established parties. In this they were undoubtedly successful, more so than they intended: as bakers sold swastika cookies and butchers formed Führer heads out of lard, the NSDAP sought to regain control over the now effectively iconic images that constituted their brand, which was in danger of being trivialised and devalued. Key to understanding the history of marketing in Germany is on the one hand the exchange of ideas with the United States, and on the other the impact of national-socialist policies, and the question whether they were a force of modernisation or retardation. The general argument in the volume appears to favour the latter explanation. In the 1930s, some of the leading marketing experts emigrated to the USA, leaving German academia and business isolated. The aftermath of the Second World War left a country that needed to increase production to satisfy consumer demand, and there was little interest in advanced sales techniques. Although the Nazis were progressive in applying new marketing methods to their political campaign, this retarded the adoption of sales techniques in politics for a long time. Germany saw the development of idiosyncratic approaches by people like Domizlaff in the 1930s and 1940s, when it lost some leading thinkers, and only engaged with American marketing conceptions in the 1960s and 1970s, when consumers eventually became more important than producers.

The prevalence and phenotype of activated microglia/macrophages within the spinal cord of the hyperostotic mouse (twy/twy) changes in response to chronic progressive spinalcord compression:implications for human cervical compressive myelopathy

Background:Cervical compressive myelopathy, e.g. due to spondylosis or ossification of the posterior longitudinal ligament is a common cause of spinal cord dysfunction. Although human pathological studies have reported neuronal loss and demyelination in the chronically compressed spinal cord, little is known about the mechanisms involved. In particular, the neuroinflammatory processes that are thought to underlie the condition are poorly understood. The present study assessed the localized prevalence of activated M1 and M2 microglia/macrophages in twy/twy mice that develop spontaneous cervical spinal cord compression, as a model of human disease.Methods:Inflammatory cells and cytokines were assessed in compressed lesions of the spinal cords in 12-, 18- and 24-weeks old twy/twy mice by immunohistochemical, immunoblot and flow cytometric analysis. Computed tomography and standard histology confirmed a progressive spinal cord compression through the spontaneously development of an impinging calcified mass.Results:The prevalence of CD11b-positive cells, in the compressed spinal cord increased over time with a concurrent decrease in neurons. The CD11b-positive cell population was initially formed of arginase-1- and CD206-positive M2 microglia/macrophages, which later shifted towards iNOS- and CD16/32-positive M1 microglia/macrophages. There was a transient increase in levels of T helper 2 (Th2) cytokines at 18 weeks, whereas levels of Th1 cytokines as well as brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF) and macrophage antigen (Mac) -2 progressively increased.Conclusions:Spinal cord compression was associated with a temporal M2 microglia/macrophage response, which may act as a possible repair or neuroprotective mechanism. However, the persistence of the neural insult also associated with persistent expression of Th1 cytokines and increased prevalence of activated M1 microglia/macrophages, which may lead to neuronal loss and demyelination despite the presence of neurotrophic factors. This understanding of the aetiopathology of chronic spinal cord compression is of importance in the development of new treatment targets in human disease. © 2013 Hirai et al.