Electrophysiological effects of 5-hydroxytryptamine on isolated human atrial myocytes, and the influence of chronic beta-adrenoceptor blockade

<b>1.</b> 5-Hydroxytryptamine (5-HT) has been postulated to play a proarrhythmic role in the human atria via stimulation of 5-HT<sub>4</sub> receptors. <b>2.</b> The aims of this study were to examine the effects of 5-HT on the L-type Ca<sup>2+</sup> current (<i>I</i><sub>CaL</sub>) action potential duration (APD), the effective refractory period (ERP) and arrhythmic activity in human atrial cells, and to assess the effects of prior treatment with β-adrenoceptor antagonists. <b>3.</b> Isolated myocytes, from the right atrial appendage of 27 consenting patients undergoing cardiac surgery who were in sinus rhythm, were studied using the whole-cell perforated patch-clamp technique at 37ºC. <b>4.</b> 5-HT (1 n-10 μM) caused a concentration-dependent increase in <i>I</i><sub>CaL</sub>, which was potentiated in cells from β-blocked (maximum response to 5-HT, E<sub>max</sub>=299±12% increase above control) compared to non-β-blocked patients (E<sub>max</sub>=220±6%, P<0.05), but with no change in either the potency (log EC<sub>50</sub>: -7.09±0.07 vs -7.26±0.06) or Hill coefficient (<i>n</i><sub>H</sub>: 1.5±0.6 vs 1.5±0.3) of the 5-HT concentration-response curve. <b>5.</b> 5-HT (10 μM) produced a greater increase in the APD at 50% repolarisation (APD50) in cells from β-blocked patients (of 37±10 ms, i.e. 589±197%) vs non-β-blocked patients (of 10±4 ms, i.e. 157±54%; P<0.05). Both the APD<sub>90</sub> and the ERP were unaffected by 5-HT. <b>6.</b> Arrhythmic activity was observed in response to 5-HT in five of 17 cells (29%) studied from β-blocked, compared to zero of 16 cells from the non-β-blocked patients (P<0.05). <b>7.</b> In summary, the 5-HT-induced increase in calcium current was associated with a prolonged early plateau phase of repolarisation, but not late repolarisation or refractoriness, and the enhancement of these effects by chronic β-adrenoceptor blockade was associated with arrhythmic potential

Dynamics of social class contempt in contemporary British television comedy

This is the author's accepted manuscript. The final published article is available from the link below. Copyright @ 2010 Taylor & Francis.British television comedy has often ridiculed the complexities and characteristics of social class structures and identities. In recent years, poor white socially marginalised groups, now popularly referred to as “chavs”, have become a prevalent comedy target. One of the most popular and controversial television “comedy chavs” is Little Britain's fictional teenage single mother, Vicky Pollard. This article examines the representation of Vicky Pollard in light of contemporary widespread abuse of the white working class. Highlighting the polysemic and ambivalent nature of Vicky Pollard's representation, the article argues that whilst Little Britain's characterisation of Vicky Pollard largely contributes to contemporary widespread demonisation of the working class, there are moments within Little Britain when a more sympathetic tone towards the poor working class may be read, and where chav identities are used to ridicule the pretensions, superficiality, and falsity of middle-class identities. The article concludes that television comedy has been, and continues to be, a significant vehicle through which serious concerns, anxieties, and questions about social class and class identities are discursively constructed and contested

Improving Productivity in Mixed-Species Plantations

Mixed species plantations are often promoted as being environmentally preferable to monocultures, but are rarely considered operationally viable by commercial forest growers. Despite many publications documenting benefits demonstrated in research studies, and despite continuing calls from a wide range of advocates for mixed-species plantations, polyculture remains the exception rather than the rule in industrial plantation forestry. The following observations are drawn from a recent workshop: - innovative experiment designs and analytical techniques are available to examine species interactions; - despite the enthusiasm for polycultures, relatively few robust experiments have been established, and even fewer have been maintained long enough to allow rotation-length consequences to be evaluated; - commercial polyculture plantations are even more scarce than experiments, and rarely offer data to support publication of financial analyses; - small landholders appear to be the main innovators in establishing and demonstrating polyculture plantations. To provide the evidence to encourage industrial uptake of polyculture plantations, there is a need for - a co-ordinated series of long-term trials, well replicated in time and space, using a standardised design with several treatments (species composition) and comparable species; - operational-scale demonstration plantings that gather ecological, financial and social data as well as the conventional production data

‘The Invisible Chain by Which All Are Bound to Each Other’: Civil Defence Magazines and the Development of Community During the Second World War

This article uses local collaboratively produced civil defence magazines to examine how community spirit was developed and represented within the civil defence services during the Second World War. It highlights the range of functions which the magazines performed, as well as the strategies employed by civil defence communities to manage their emotions in order to keep morale high and distract personnel from the fear and boredom experienced while on duty. The article also discusses silences in the magazines — especially around the experience of air raids — and argues that this too reflects group emotional management strategies. The significance of local social groups in developing narratives about civil defence and their workplace communities is demonstrated, and the article shows how personnel were able to engage with and refashion dominant cultural narratives of the ‘people’s war’ in order to assert their own status within the war effort

Varicella-Zoster viruses associated with post-herpetic neuralgia induce sodium current density increases in the ND7-23 Nav-1.8 neuroblastoma cell line

Post-herpetic neuralgia (PHN) is the most significant complication of herpes zoster caused by reactivation of latent Varicella-Zoster virus (VZV). We undertook a heterologous infection in vitro study to determine whether PHN-associated VZV isolates induce changes in sodium ion channel currents known to be associated with neuropathic pain. Twenty VZV isolates were studied blind from 11 PHN and 9 non-PHN subjects. Viruses were propagated in the MeWo cell line from which cell-free virus was harvested and applied to the ND7/23-Nav1.8 rat DRG x mouse neuroblastoma hybrid cell line which showed constitutive expression of the exogenous Nav 1.8, and endogenous expression of Nav 1.6 and Nav 1.7 genes all encoding sodium ion channels the dysregulation of which is associated with a range of neuropathic pain syndromes. After 72 hrs all three classes of VZV gene transcripts were detected in the absence of infectious virus. Single cell sodium ion channel recording was performed after 72 hr by voltage-clamping. PHN-associated VZV significantly increased sodium current amplitude in the cell line when compared with non-PHN VZV, wild-type (Dumas) or vaccine VZV strains ((POka, Merck and GSK). These sodium current increases were unaffected by acyclovir pre-treatment but were abolished by exposure to Tetrodotoxin (TTX) which blocks the TTX-sensitive fast Nav 1.6 and Nav 1.7 channels but not the TTX-resistant slow Nav 1.8 channel. PHN-associated VZV sodium current increases were therefore mediated in part by the Nav 1.6 and Nav 1.7 sodium ion channels. An additional observation was a modest increase in message levels of both Nav1.6 and Nav1.7 mRNA but not Nav 1.8 in PHN virally infected cells

BBC2 and world cinema

© Edinburgh University Press. This article examines the origins of BBC2's reputation as a purveyor of films from around the world, exploring the significance and impact of the strand World Cinema (1965-74) and assessing the range and diversity of its offer. Foreign-language titles had been broadcast by the Corporation since before the Second World War, due partly to their ready availability at a time when Hollywood films were 'off limits', given the hostility of American (and British) film companies towards the new rival medium of television. During this early period, however, these continental films were not popular, undoubtedly due to the fact that subtitles were very difficult to read on small, low-definition television screens. BBC2, with its commitment to minority tastes and interests and its use of both the higher-definition 625-line UHF system and colour, was perfectly placed to revive and foster interest in world cinema. For those who urged broadcasters to adopt and maintain an enlightened film policy, World Cinema became exemplary, as a rare exception to the general rules in early television of editing for content or length, block buying (the practice of buying the rights to a mixed package of films in order to acquire certain gems) and haphazard scheduling. For a generation of cinephiles, World Cinema was a formative and educative experience. Particular attention is paid here to the first five years of World Cinema, which saw the strand give attention to a variety of 'New Waves' and relay experiences from behind the Iron Curtain and further afield