Hobson’s choice? Constraints on accessing spaces of creative production

Successful creative production is often documented to occur in urban areas that are more likely to be diverse, a source of human capital and the site of dense interactions. These accounts chart how, historically, creative industries have clustered in areas where space was once cheap in the city centre fringe and inner city areas, often leading to the development of a creative milieu, and thereby stimulating further creative production. Historical accounts of the development of creative areas demonstrate the crucial role of accessible low-cost business premises. This article reports on the findings of a case study that investigated the location decisions of firms in selected creative industry sectors in Greater Manchester. The study found that, while creative activity remains highly concentrated in the city centre, creative space there is being squeezed and some creative production is decentralizing in order to access cheaper premises. The article argues that the location choices of creative industry firms are being constrained by the extensive city centre regeneration, with the most vulnerable firms, notably the smallest and youngest, facing a Hobson’s choice of being able to access low-cost premises only in the periphery. This disrupts the delicate balance needed to sustain production and begs the broader question as to how the creative economy fits into the existing urban fabric, alongside the competing demands placed on space within a transforming industrial conurbation

Combined aerobic and resistance exercise training decreases peripheral but not central artery wall thickness in subjects with type 2 diabetes

Objective Little is known about the impact of exercise training on conduit artery wall thickness in type 2 diabetes. We examined the local and systemic impact of exercise training on superficial femoral (SFA), brachial (BA), and carotid artery (CA) wall thickness in type 2 diabetes patients and controls. Methods Twenty patients with type 2 diabetes and 10 age- and sex-matched controls performed an 8-week training study involving lower limb-based combined aerobic and resistance exercise training. We examined the SFA to study the local effect of exercise, and also the systemic impact of lower limb-based exercise training on peripheral (i.e. BA) and central (i.e. CA) arteries. Wall thickness (WT), diameter and wall:lumen(W:L)-ratios were examined using automated edge detection of ultrasound images. Results Exercise training did not alter SFA or CA diameter in type 2 diabetes or controls (all P > 0.05). BA diameter was increased after training in type 2 diabetes, but not in controls. Exercise training decreased WT and W:L ratio in the SFA and BA, but not in CA in type 2 diabetes. Training did not alter WT or W:L ratio in controls (P > 0.05). Conclusion Lower limb-dominant exercise training causes remodelling of peripheral arteries, supplying active and inactive vascular beds, but not central arteries in type 2 diabetes

Inhibitors of 20-hydroxyeicosatetraenoic acid reduce renal vasoconstrictor responsiveness. J Pharmacol Exp Ther 307: 223–229

ABSTRACT 20-Hydroxyeicosatetraenoic acid (20-HETE) is a cytochrome P450-derived constrictor eicosanoid produced by the preglomerular vasculature where it contributes to regulation of tone. Removal of the tonic inhibitory influence of nitric oxide (NO) has been reported to increase renal 20-HETE release. Because inhibition of NO synthesis enhances responses to vasoconstrictor agents, we examined a contribution for increased 20-HETE generation. In the rat kidney perfused with Krebs' buffer, responses to U46619 (9,11-dideoxy-9␣,11␣-methanoepoxy PGF 2␣ ), a thromboxane A 2 mimetic, were compared before and after 50 M L-nitroarginine (L-NA) to inhibit NO synthase. L-NA raised perfusion pressure (PP) from 79 Ϯ 3 to 190 Ϯ 7 mm Hg and enhanced constrictor responsiveness to U46619. U46619 (10, 30, 100, and 300 ng) increased PP by 7 Ϯ 1, 17 Ϯ 2, 50 Ϯ 7, and 67 Ϯ 7 mm Hg, respectively, before L-NA and 15 Ϯ 1, 37 Ϯ 7, 68 Ϯ 10, and 85 Ϯ 11 mm Hg, respectively, after L-NA, which did not increase 20-HETE efflux from the kidney. Nonetheless, an inhibitor of -hydroxylase, dibromododecencyl methylsulfonimide (DDMS), which reduced 20-HETE release, normalized the enhanced responsiveness to U46619. When PP was elevated with phenylephrine, vasoconstrictor responses to U46619 were similarly enhanced, an effect that was also prevented by DDMS. DDMS and an antagonist of 20-HETE, 20-HEDE [20-hydroxyeicosa-6(Z),15(Z)-dienoic acid], also reduced vasoconstrictor responses to U46619 in the absence of elevation of PP. Because 20-HETE inhibits K ϩ channels, we examined the effects of K ϩ channel inhibitors on vasoconstrictor responses and showed that both tetraethylammonium (TEA) and charybdotoxin enhanced renal vasoconstrictor responses to U46619. However, the inhibitory effects of 20-HEDE on vasoconstrictor responses remained after treatment with TEA. These results support a role for 20-HETE vasoconstrictor responses but suggest an action independent of K ϩ channels