Imbalance between matrix metalloproteinases and tissue inhibitor of metalloproteinases in hypertensive vascular remodeling

Structural vascular changes in two-kidney, one-clip (2K-1C) hypertension may result from increased matrix metalloproteinase (MMP)-2 activity. MMP-2 activation is regulated by other MMPs, including transmembrane-MMPs, and by tissue inhibitors of MMPs (TIMPs). We have investigated the localization of MMP-2, -9, -14, and TIMPs 1-4 in hypertensive aortas and measured their levels by zymography/Western blotting and immunohistochemistry. Gelatinolytic activity was assayed in tissues by in situ zymography. Sham-operated and 2K-1C hypertensive rats were treated with doxycycline (or vehicle) for 8 weeks, and the systolic blood pressure was monitored weekly. Doxycycline attenuated 2K-1C hypertension (165 +/- 11.7 mmHg versus 213 +/- 7.9 mm Hg in hypertensive controls, P<0.01), and completely prevented increase in the thicknesses of the media and the intima in 2K-1C animals (P<0.01). Increased amounts of MMP-2, -9, and -14 were found in hypertensive aortas, as well as enhanced gelatinolytic activity. A gradient in the localization of MMP-2, -9, and -14 was found, with increased amounts detected in the intima, at sites with higher gelatinolytic activity. Doxycycline attenuated hypertension induced increases in all the 3 investigated MMPs in both the media and the intima (all P<0.05). but it did not change the amounts of TIMPs 1-4 (P>0.05). Therefore, an imbalance between increased amounts of MMPs at the tissue level without a corresponding increase in the quantities of TIMPs, particularly in the intima and inner media layers, appears to account for the increased proteolytic activity found in 2K-1C hypertension-induced maladaptive vascular remodeling. (C) 2009 Elsevier B.V. All rights reserved.

Smooth muscle cells of injured rat and rabbit arteries in culture: contractile and cytoskeletal proteins

The aim of this study is to determine whether subpopulations of smooth muscle cells (SMC). as distinguished by variations in contractile and cytoskeletal proteins, appear in the neointima at different times after vascular injury, and/or whether subpopulations develop during serial passaging of these cells. Rat aortae and rabbit carotid arteries were injured with a 2F Fogarty balloon catheter and cultures established from the resulting neointima and the media 2, 6, 12, 16 and 24 weeks later. Cultures were examined at passages 1-5 and subpopulations of SMC categorised by intensity of staining for each protein by immunohistochemistry. Two populations of SMC with different staining intensities ('+ +', '+') were observed for each of the following proteins: alpha -SM actin, SM-myosin, desmin and vimentin. Populations without these proteins were also found. Changes in the percentages of cells expressing these proteins were transitory, indicating that the populations were not limited to a particular tissue (neointima or media), time after injury or passage number. One exception was found in rabbit cultures where the number of desmin-expressing cells quickly decreased with both time after injury and time in culture. Subpopulations of SMC were found at all times after injury in the media and neointima of rat and rabbit arteries, and after multiple passage of these cells. There was no pattern of development of one population suggesting that either no subpopulation has a proliferative or migratory advantage over others, or that only one population exists: that is capable of diverse phenotypic changes. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.

'Suitable mothers': lesbian and single women and the 'unborn' in Australian parliamentary discourse

Throughout the latter months of 2000 and early 2001, the Australian public, media and parliament were engaged in a long and emotive debate about motherhood. This debate constructed the two main protagonists, the unborn 'child' and the potential mother, with a variety of different and often oppositional identities. The article looks at the way that these subject identities interacted during the debate, starting from the premise that policy making has unintended and unacknowledged material outcomes, and using governmentality as a tool through which to analyse and understand processes of identity manipulation and resistance within policy making. The recent debate concerning the right of lesbian and single women to access new reproductive technologies in Australia is used as a case study. Nominally the debate was about access to IVF technology; in reality, however, the debate was about the governing of women and, in particular, the governing of motherhood identities. The article focuses on the parliamentary debate over the drafting of legislation designed to stop lesbian and single women from accessing these technologies, particularly the utilization of the 'unborn' subject within these debates as a device to discipline the identity of 'mother'.

Historical and conceptual landscape of the character

This paper was developed with the intention of broadly demonstrating the complexity of the area known recently as character development, as a creative process methods and implementation. It searches the understanding of the character itself, its place in the narrative and its reception by the reader or target audience. It is a multidisciplinary tool that faces a multitude of challenges from an increasingly demanding public and with specific goals in mind, and yet it also gives us valuable insight over how we interact with one another and the world around us, teaching us how to transfer such knowledge into fiction promoting empathic bonds between the reader and the characters. The human tendency to create is limitless and as old as mankind itself, we create, recreate and reinterpret and then populate such tales with believable characters from who we learn, and experience events and tales that shape our very lives.