| 1. |
- Andersson, Karl-Erik
(författare)
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Alpha-adrenoceptors and benign prostatic hyperplasia: basic principles for treatment with alpha-adrenoceptor antagonists.
- 2002
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Ingår i: World Journal of Urology. - : Springer Science and Business Media LLC. - 1433-8726 .- 0724-4983. ; 19:6, s. 390-396
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Tidskriftsartikel (refereegranskat)abstract
- The selective blockade of alpha1-adrenoceptors (ARs) is now a well-accepted and widely used treatment for patients presenting with lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) and bladder outlet obstruction. The sites of action of the currently used alpha1-AR antagonists when relieving LUTS have not yet been established, but it seems clear that effects on prostatic as well as non-prostatic tissues are important. Alpha1-ARs in the bladder, urethra, and vas deferens, on ganglia and nerve terminals, and in the central nervous system (CNS) may all influence LUTS and the clinical effects of alpha1-AR antagonists. The relevance of alpha1-AR subtype selectivity for the clinical usefulness of existing drug therapy has still not been clarified, but it cannot be dismissed that blockading both alpha1A- and alpha1D-ARs is necessary for optimal clinical effect. Despite the above uncertainties, there seems to be a consensus that clinically available alpha1-AR antagonists provide a safe, effective and generally well-tolerated therapy for patients with LUTS.
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| 2. |
- Andersson, Karl-Erik, et al.
(författare)
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Future drugs for the treatment of benign prostatic hyperplasia.
- 2002
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Ingår i: World Journal of Urology. - : Springer Science and Business Media LLC. - 1433-8726 .- 0724-4983. ; 19:6, s. 436-442
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Tidskriftsartikel (refereegranskat)abstract
- For at least a decade, no new drug principles have been added to the therapeutic armamentarium for the treatment of lower urinary tract symptoms (LUTS) associated with or suggestive of benign prostatic hyperplasia (BPH). Theoretically, there seem to be several possibilities to improve the current treatment, which is based mainly on alpha1-adrenoceptor (AR) antagonists, 5alpha-reductase inhibitors and phytotherapy. It cannot be dismissed that subtype selective alpha1-AR antagonists can further improve treatment, but convincing evidence is still lacking. Muscarinic receptor antagonists are currently evaluated in BPH patients, but their eventual place in therapy, as a single treatment or in combination with alpha1-AR antagonists, has to be established. Endothelin receptor antagonists, alone or together with alpha1-AR antagonists, seem to offer a new attractive approach; however, proof of concept studies are lacking. The L-arginine/NO/cGMP pathway awaits further exploration; nitric oxide (NO) donors or phosphodiesterase (PDE) inhibitors may be clinically useful. Purinoceptors are currently the focus of interest as treatment targets in the lower urinary tract and inhibitors of P2X3 (and P2X1) subtypes may offer new opportunities. If a treatment based on desensitising C-fibres in the bladder and urethra is effective, not only in neurogenic bladders, but also for treating LUTS, it would be a viable option. For new treatments of LUTS, targets within the central nervous system (CNS) may offer exciting opportunities.
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| 3. |
- Chapple, C, et al.
(författare)
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Tamsulosin: an overview
- 2002
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Ingår i: World Journal of Urology. - : Springer Science and Business Media LLC. - 1433-8726 .- 0724-4983. ; 19:6, s. 397-404
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Tidskriftsartikel (refereegranskat)abstract
- This article reviews the contemporary literature related to tamsulosin, which is now the most widely used alpha antagonist in treating benign prostatic hyperplasia. The primary emphasis of this article is on the clinical data that exist related to this agent. Currently, there are no adequate studies that effectively compare existing agents for the treatment of benign prostatic hyperplasia using a randomised, placebo-controlled design with adequate numbers and this needs to be addressed in future studies.
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| 4. |
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| 5. |
- Kristjansson, A, et al.
(författare)
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Renal function in the setting of urinary diversion
- 2004
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Ingår i: World Journal of Urology. - : Springer Science and Business Media LLC. - 1433-8726 .- 0724-4983. ; 22:3, s. 172-177
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Tidskriftsartikel (refereegranskat)abstract
- Incorporating bowel into the urinary tract sets the stage for a potentially dangerous situation for the upper part of this tract. Obstruction, reflux and chronic bacteriuria may develop, all of which can all be detrimental. Most reports on renal function have used IVP and serum creatinine only, methods which are inadequate for proper assessment. Long-term follow-up of patients with ileal conduit diversion reveals a high incidence of morphological and/or functional damage to the kidneys. Refluxing techniques for implanting the ureters have usually been employed. In patients with continent cutaneous diversion or orthotopic bladder substitution, some recent publications have shown rather well preserved glomerular filtration rates. Traditionally, antirefluxing ureteric implantation has been used in these patients. There is presently a trend towards refluxing anastomosis in this setting, providing a low pressure pouch has been constructed. However, pressure can be high in such pouches and bacteriuria is common. The consequences for the fate of the upper urinary tract is unknown and caution should be exercised in recommending such techniques. There is clearly a need for prospective randomized controlled studies on the issue of refluxing versus antirefluxing anastomosis in continent urinary reconstruction. Patients with continent or non-continent diversion should have lifelong follow-up with regard to the upper urinary tract.
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| 6. |
- Uckert, S, et al.
(författare)
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Interactions between cGMP- and cAMP-pathways are involved in the regulation of penile smooth muscle tone
- 2004
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Ingår i: World Journal of Urology. - : Springer Science and Business Media LLC. - 1433-8726 .- 0724-4983. ; 22:4, s. 261-266
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Tidskriftsartikel (refereegranskat)abstract
- Nitric oxide (NO)/cyclic GMP (cGMP)-mediated mechanisms have a pivotal function in reducing the tone of the penile smooth musculature during normal erectile responses. The cyclic AMP ( cAMP) signaling pathway is also involved in the adjustment of smooth muscle contractility, and suggestions for interactions between cGMP- and cAMP-mediated mechanisms have been presented. Using activators of the cGMP- or the cAMP-pathway, as well as inhibitors of protein kinase A (PKA; cAMP-dependent kinase) and protein kinase G (PKG; cGMP- dependent kinase), the present study was undertaken to further delineate the functional relation between these pathways in the penis. In addition, the distribution of PKA and some cAMP-binding phosphodiesterases (cAMP-PDEs) were investigated in human erectile tissue. Functional experiments were performed on isolated human corpus cavernosum (HCC). The effects of an inhibitor of the PKA, Rp-8CPT-cAMPS ( 10 muM), or the PKG, Rp-8-pCPT-cGMPS ( 10 muM), on relaxation induced by the cumulative administration of sodium nitroprusside ( SNP), forskolin, sildenafil or tadalafil (IC351) were studied in preparations of HCC precontracted with 1 muM norepinephrine ( NE). Using immunohistochemical procedures, the presence of immunoreactivity for cAMP-PDEs PDE3, PDE4, and PDE4A, as well as for PKA was investigated in specimens of HCC from which preparations were also used in the functional experiments. Forskolin, SNP, sildenafil, and IC 351 dose-dependently reversed NE-induced tension of isolated HCC preparations. The relaxing effects of SNP were significantly attenuated by Rp-8-pCPT-cGMPS, but not by Rp-8CPT-cAMPS. In contrast, relaxation induced by forskolin, sildenafil and tadalafil were significantly reversed by both Rp-8-pCPT-cGMPS and Rp-8CPT-cAMPS. Abundant immunoreactivity for PDE3 and PKA was observed in the corpus cavernosum smooth muscle cells. Immunoreactivity for PDE4 was also detected in the smooth musculature and in the cytoplasm of endothelial cells lining the cavernous sinusoids, as well as in nerve fibres interspersing the trabecular stroma. The present results support the hypothesis of interactions between cGMP- and cAMP-mediated signals in the HCC, and suggest that the effects of inhibitors of PDE5 on isolated erectile tissue may also partly or indirectly include actions of the cAMP second messenger system. The exact mechanism by which such an interaction occurs is not clear, but it may involve altered activity of the cGMP- inhibited PDE3 brought about by a change in the intracellular levels of cGMP by the inhibition of PDE5. This will in turn lead to increasing levels of cAMP, facilitating the interaction of cAMP with the PKA. The immunoreactivity specific for PDE3, PDE4, PDE4A and PKA registered in HCC section is also in support of an important role for the cAMP/PKA-system for penile smooth muscle function.
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