Retinal and systemic vascular function in health and disease: the effect of smoking and coronary artery disease

The purpose of the following studies was to explore the effect of systemic vascular and endothelial dysfunction upon the ocular circulation and functionality of the retina. There are 6 principal sections to the present work. Retinal vessel activity in smokers and non-smokers: the principal findings of this work were: chronic smoking affects retinal vessel motion at baseline and during stimulation with flickering light; chronic smoking leads to a vaso-constrictory shift in retinal arteriolar reactivity to flicker; retinal arteriolar elasticity is decreased in chronic smokers. The effect of acute smoking on retinal vessel dynamics in smokers and non-smokers: the principal finding of this work was that retinal reactivity in chronic smokers is blunted when exposed to clicker light provocation immediately after smoking one cigarette. Ocular blood flow in coronary artery disease: The principal findings of this work were: retrobulbar and retinal blood flow is preserved in CAD patients, despite a change pulse wave transmission; arterial retinal response to flickering light provocation is significantly delayed in CAD patients; retinal venular diameters are significantly dilated in CAD patients. Autonomic nervous system function and peripheral circulation in CAD: The principal findings in this work were: CAD patients demonstrate a sympathetic overdrive during a 24 period; a delay in peripheral vascular reactivity (nail-fold capillaries) as observed in patients suffering from CAD could be caused by either arteriosclerotic changes of the vascular walls or due to systemic haemodynamic changes. Visual function in CAD: The principal findings in this work were: overall visual function in CAD patients is preserved, despite a decrease in contrast sensitivity; applying a filtering technique selecting those with greater coefficient of variance which in turn represents a decrease in reliability, some patients appear to have an impaired visual function as assessed using FDT visual field evaluation. Multiple functional, structural and biochemical vascular endothelial dysfunctions in patients suffering from CAD: relationships and possible implications: The principal findings of this work were: BMI significantly correlated with vWF (a marker of endothelial function) in CAD patients. Retinal vascular reactivity showed a significant correlation with peripheral reactivity parameters in controls which lacked in the CAD group and could reflect a loss in vascular endothelial integrity; visual field parameters as assessed by frequency doubling technology were strongly related with systemic vascular elasticity (ambulatory arterial stiffness index) in controls but not CAD patients.

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.

New insights into the etiology of preeclampsia:identification of key elusive factors for the vascular complications

The incidence of preeclampsia is reduced by a third in smokers, but not in snuff users. Soluble Flt-1 (sFlt-1) and soluble endoglin (sEng) are increased prior to the clinical onset of preeclampsia. Animals exposed to high circulating levels of sFlt-1 and sEng elicit severe preeclampsia-like symptoms. Smokers have reduced circulating sFlt-1 and cigarette smoke extract decreases sFlt-1 release from placental villous explants. An anti-inflammatory enzyme, heme oxygenase-1 (HO-1) and its metabolite carbon monoxide (CO), inhibit sFlt-1 and sEng release. Women with preeclampsia exhale less CO than women with normal pregnancies and HO expression decreases as the severity of preeclampsia increases. In contrast, sFlt-1 levels increase with increasing severity. More importantly, chorionic villous sampling from women at eleven weeks gestation shows that HO-1 mRNA expression is decreased in women who go on to develop preeclampsia. Collectively, these facts provide compelling evidence to support the proposition that the pathogenesis of preeclampsia is largely due to loss of HO activity. This results in an increase in inflammation and excessive elevation of the two key anti-angiogenic factors responsible for the clinical signs of preeclampsia. These findings provide strong evidence for a protective role of HO-1 in pregnancy and identify HO as a target for the treatment of preeclampsia. The cardiovascular drugs, statins, stimulate HO-1 expression and inhibit sFlt-1 release in vivo and in vitro, thus, they have the potential to ameliorate early onset preeclampsia. The StAmP trial is underway to address this and if positive, its outcome will lead to the very first therapeutic intervention to prolong affected pregnancies.

Using an in vitro human airway model to study the toxic effects of components of e-cigarettes

Cigarette smoke is a complex mixture of more than 4000 hazardous chemicals including the carcinogenic benzopyrenes. Nicotine, the most potent component of tobacco, is responsible for the addictive nature of cigarettes and is a major component of e-cigarette cartridges. Our study aims to investigate the toxicity of nicotine with special emphasis on the replacement of animals. Furthermore, we intend to study the effect of nicotine, cigarette smoke and e-cigarette vapours on human airways. In our current work, the BEAS 2B human bronchial epithelial cell line was used to analyse the effect of nicotine in isolation, on cell viability. Concentrations of nicotine from 1.1µM to 75µM were added to 5x105 cells per well in a 96 well plate and incubated for 24 hours. Cell titre blue results showed that all the nicotine treated cells were more metabolically active than the control wells (cells alone). These data indicate that, under these conditions, nicotine does not affect cell viability and in fact, suggests that there is a stimulatory effect of nicotine on metabolism. We are now furthering this finding by investigating the pro-inflammatory response of these cells to nicotine by measuring cytokine secretion via ELISA. Further work includes analysing nicotine exposure at different time points and on other epithelial cells lines like Calu-3.

Nicotine exposure reduces cell viability but induces anti-inflammatory effects in human cystic fibrosis bronchial epithelial cells

Background: Mouse models of cystic fibrosis (CF) fail to truly represent the respiratory pathology. We have consequently developed human airways cell culture models to address this. The impact of cigarette smoke within the CF population is well documented, with exposure being known to worsen lung function. As nicotine is often perceived to be a less harmful component of tobacco smoke, this research aimed to identify its effects upon viability and inflammatory responses of CF (IB3-1) and CF phenotype corrected (C38) bronchial epithelial cells. Methods: IB3-1 and C38 cell lines were exposed to increasing concentrations of nicotine (0.55-75μM) for 24 hours. Cell viability was assessed via Cell Titre Blue and the inflammatory response with IL-6 and IL-8 ELISA. Results: CF cells were more sensitive; nicotine significantly (P<0.05) reduced cell viability at all concentrations tested, but failed to have a marked effect on C38 viability. Whilst nicotine induced anti-inflammatory effects in CF cells with a significant reduction in IL-6 and IL-8 release, it had no effect on chemokine release by C38 cells. Conclusion: CF cells may be more vulnerable to inhaled toxicants than non-CF cells. As mice lack a number of human nicotinic receptor subunits and fail to mimic the characteristic pathology of CF, these data emphasise the importance of employing relevant human cell lines to study a human-specific disease.