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- Bivalacqua, Trinity J., et al.
(författare)
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Dysregulation of cGMP-dependent protein kinase 1 (PKG-1) impairs erectile function in diabetic rats: influence of in vivo gene therapy of PKG1 alpha
- 2007
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Ingår i: BJU International. - 1464-4096 .- 1464-410X. ; 99:6, s. 1488-1494
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Tidskriftsartikel (refereegranskat)abstract
- To investigate the expression of cGMP-dependent protein kinase 1 (PKG1)alpha and PKG1 beta in the corpus cavernosum, and to evaluate the effect of adenoviral gene transfer of PKG1 alpha to the erectile compartment on erectile function in a rat model of diabetes. Diabetic (DM; induced by streptozotocin) male Sprague Dawley rats were transfected with adenoviruses (AdCMV beta gal or AdCMVPKG1 alpha, in 10 rats each) 2 months after the induction of DM. Intracavernosal pressure (ICP) during stimulation of the cavernosal nerve (CN) was assessed, and compared with mean arterial pressure (MAP). Erectile tissue was harvested for Western blot analysis, immunohistochemistry and total PKG activity. Ten age-matched rats without DM served as the control. Compared to controls, AdCMV beta gal-transfected DM rats had significantly lower peak ICP responses, ICP/MAP ratios, and filling rates during CN stimulation. In DM rats transfected with AdCMVPKG1 alpha, peak ICP, ICP/MAP ratios and filling rates were significantly better than in DM rats transfected with the reporter gene. As assessed by Western blot and immunohistochemistry, expression of PKG1 alpha and PKG1 beta was lower in corporal tissue from DM AdCMV beta gal-transfected rats than in controls. PKG1 alpha expression was improved after AdCMVPKG1 alpha gene therapy. Total PKG activity was lower in DM rat corporal tissue than in controls, and PKG1 alpha gene transfer significantly improved DM corporal PKG activity to a value greater than in the control. PKG1 alpha and PKG1 beta activities are reduced in the erectile tissue of the diabetic rat, and gene transfer of PKG1 alpha to the penis restored PKG activity and erectile function in vivo in diabetic rats. Gene therapy procedures targeting PKG1 alpha might be an interesting future therapeutic approach to overcome diabetic erectile dysfunction resistant to oral pharmacotherapy.
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| 2. |
- Jones, HRA, et al.
(författare)
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Status of the physics of substellar objects project
- 2005
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Ingår i: Astronomical Notes - Astronomische Nachrichten. - : Wiley. - 0004-6337. ; 326:10, s. 920-924
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Tidskriftsartikel (refereegranskat)abstract
- A full understanding of the properties of substellar objects is one of the major challenges facing astrophysics. Since their discovery in 1995, hundreds of brown dwarfs and extrasolar planets have been discovered. While these discoveries have enabled important comparisons with theory, observational progress has been much more rapid than the theoretical understanding of cool atmospheres. The reliable determination of mass, abundances, gravities and temperatures is not yet possible. The key problem is that substellar objects emit their observable radiation in the infrared region of the spectrum where our knowledge of atomic, molecular and line broadening data is poor. Here we report on the status of our PoSSO (Physics of SubStellar Objects) project. In order to understand brown dwarfs and extrasolar planets increasing more like those in our solar system, we are studying a wide range of processes. Here we give an update on the project and sketch an outline of atoms, molecules and processes requiring study.
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