Advanced glycation endproduct modified basement membrane attenuates endothelin-1 induced [Ca2+]i signalling and contraction in retinal microvascular pericytes

PURPOSE: To assess the effects of advanced glycation endproduct (AGE) modification of vascular basement membrane (BM) on endothelin-1 (Et-1) induced intracellular [Ca2+] ([Ca2+]i) homeostasis and contraction in retinal microvascular pericytes (RMP). METHODS: RMPs were isolated from bovine retinal capillaries and propagated on AGE modified BM extract (AGE-BM) or non-modified native BM. Cytosolic Ca2+ was estimated using fura-2 microfluorimetry and cellular contraction determined by measurement of planimetric cell surface area. ETA receptor mRNA and protein expression was assessed by real time RT-PCR and western blotting, respectively. RESULTS: Exogenous endothelin-1 (Et-1) evoked rises in [Ca2+]i and contraction in RMPs were found to be mediated entirely through ETA receptor (ETAR) activation. Both peak and plateau phases of the Et-1 induced [Ca2+]i response and contraction were impaired in RMPs propagated on AGE modified BM. ETAR mRNA expression remained unchanged in RMPs exposed to native or AGE-BM, but protein expression for ETAR (66 kDa) was lower in the AGE exposed cells. CONCLUSIONS: These results suggest that substrate derived AGE crosslinks can influence RMP physiology by mechanisms which include disruption of ETA receptor signalling. AGE modification of vascular BMs may contribute to the retinal hemodynamic abnormalities observed during diabetes.

Breast cancer following augmentation mammoplasty - a review of its impact on prognosis and management

The incidence of breast cancer in women with implants is increasing and will continue to do so for the foreseeable future due to the marked increase in breast implant insertion in recent years. Undoubtedly many of these women will wish to know whether the presence of implants worsens the prognosis of their breast cancer. Furthermore, the clinical management of such patients may be difficult, as aesthetic results are likely to be a major concern for women who have already undergone cosmetic surgery to the breast. There is no consensus on surgical approach to this scenario. This article reviews the literature on the prognosis of breast cancer patients with a history of augmentation mammoplasty and examines the available data regarding their surgical treatment. (c) 2007 Published by Elsevier Ltd on behalf of British Association of Plastic, Reconstructive and Aesthetic Surgeons.

Assisted standing for Duchenne muscular dystrophy

This is the protocol for a review and there is no abstract. The objectives are as follows: To assess the effects of standing devices and orthoses on musculoskeletal impairments (such as pain, contracture, scoliosis development and bone density) in people with DMD, and secondarily to determine their effect on quality of life, participation in activities, and patient experience.