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- Hedlund, H., et al.
(författare)
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Pharmacotherapy in erectile dysfunction agents for self-injection programs and alternative application models
- 1996
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Ingår i: Scandinavian Journal of Urology and Nephrology, Supplementum. - 0300-8886 .- 1651-2537. ; 179, s. 129-38
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Forskningsöversikt (refereegranskat)abstract
- Previously, men with erectile dysfunction (ED) were frequently treated with penile prosthesis implants or considered to have psychogenic impotence. Since the reports by Virag and Brindley in 1932 and 1983, pharmacotherapy, by self-injection programs has become a new therapeutic concept for impotent men. In clinical practice, this application model has been generally accepted as the "golden standard" in the treatment of ED. Papaverine was first used as monotherapy, but because of side-effects such as prolonged erection, priapism, and fibrosis of the corpus cavernosum, single use of the drug was abandoned. Instead, papaverine was introduced in mixtures, e.g. together with alpha adrenoceptor-blockers as phentolamine, and/or prostaglandin E1 (PGE1) in these "cocktails", the dose of papaverine is reduced to 10-15 mg compared to the high doses (80-120 mg) that were used initially. By having two or more drugs in the mixture, a facilitating cascade effect as probably obtained. PGE1 is the only drug that has been approved by the FDA and is today registered in more than 50 countries. Other combination therapies such as vasoactive intestinal polypeptide+ phentolamine, or calcitonin gene-related peptide+ PGE1, have been suggested as suitable alternatives for intracavernosal injection. Transdermal and intraurethral application models may be considered in selected patients. Recently, oral administration of a phosphodiesterase inhibitor (UK-92.480) was reported to improve penile erection in patients with psychogenic impotence. Further clinical results from controlled trials will probably explain if this new oral drug will compete with PGE1 or other agents in self-injection programs.
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- Hedlund, Petter, et al.
(författare)
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Pituitary adenylate cyclase-activating polypeptide, helospectin, and vasoactive intestinal polypeptide in human corpus cavernosum
- 1995
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Ingår i: British Journal of Pharmacology. - 0007-1188 .- 1476-5381. ; 116:4, s. 2258-2266
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Tidskriftsartikel (refereegranskat)abstract
- 1. The distribution and effects of pituitary adenylate cyclase-activating polypeptide (PACAP-27 and -38), helospectin (Hel-1 and Hel-2), and vasoactive intestinal polypeptide (VIP), were investigated in isolated preparations of human corpus cavernosum (CC). 2. Immunohistochemistry revealed coinciding profiles of nerve structures that showed immunoreactivities for VIP and PACAP, and VIP and Hel. Confocal microscopy showed the co-existence of VIP- and PACAP-immunoreactivities, and VIP- and Hel-immunoreactivities in most (90%) varicose nerve structures. 3. As determined by radioimmunoassay, the amounts of VIP, PACAP-27, and PACAP-38 in the preparations were 61.7 +/- 11.6, 0.1 +/- 0.05, and 3.7 +/- 0.5 pmol g-1 wet weight of tissue (pmol g-1 wet wt.), respectively. In tissue from patients with diabetes, the content of VIP was lower (13.7 +/- 0.5 pmol g-1 wet wt.), whereas that of PACAP (-27 and -38) was unchanged. 4. Cyclic nucleotide levels were determined in preparations exposed to PACAP-27, PACAP-38, Hel-1, Hel-2, and VIP. All the peptides, but Hel-2, significantly increased the concentrations of cyclic AMP, whereas the levels of cyclic GMP were unchanged. 5. The peptides concentration-dependently relaxed noradrenaline-contracted preparations. The order of potency was VIP > PACAP 27 > Hel-1 > Hel-2 > PACAP-38. 6. Hel-1, VIP and PACAP-27 effectively counteracted electrically induced contractions. At 10(-6) M, the highest peptide concentration used, the inhibitory effects obtained reached 96 +/- 3%, 87 +/- 6%, and 80 +/- 3%, respectively. 7. The results suggest that PACAP and Hel-1 are co-localized with VIP in nerve structures within the human cavernous tissue, and that the peptides are effective relaxants of CC preparations in vitro. The role of the investigated peptides for penile erection remains to be established.
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- Bergman, B, et al.
(författare)
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An intraindividual clinical comparison of 2 metal-ceramic systems.
- 1999
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Ingår i: International Journal of Prosthodontics. - 0893-2174 .- 1139-9791. ; 12:5, s. 444-7
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: It has been questioned whether the surface and color of the ceramic and the metal-ceramic bond strength of a titanium-ceramic system are comparable to those of a conventional noble alloy-ceramic system. It was therefore the aim of this study to carry out an intraindividual clinical comparison between crowns fabricated according to the Procera system (titanium copings veneered with a low-fusing ceramic) and noble-alloy copings veneered with a medium-fusing ceramic. MATERIALS AND METHODS: Twenty-one crown pairs were fabricated for eighteen patients; three of the patients were each provided with two crown pairs. After 2 years nineteen crown pairs in sixteen patients could be compared. Clinical examinations were performed by two calibrated dentists who are long experienced in prosthetic dentistry. The crowns were rated according to the California Dental Association system. In addition, Bleeding Index and Margin Index were evaluated. RESULTS: After 2 years the quality of surface and color of the ceramic material seemed to have deteriorated more in titanium-ceramic crowns than in conventional metal-ceramic crowns, although the difference was not statistically significant. Regarding anatomic form, margin integrity, Bleeding Index, and Margin Index the differences between the two crown systems were small. CONCLUSION: The low-fusing ceramics have been subject to improvements during the last few years. Their bond strength to titanium seems to be comparable to that of conventional metal-ceramic systems. However, in the long run one problem may be the surface and color stability of low-fusing ceramics. To make extended long-term comparisons between the two metal-ceramic systems possible the present patient material will be followed for a longer period than the current 2 years.
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- Connell, H., et al.
(författare)
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Bacterial attachment to uro-epithelial cells : mechanisms and consequences.
- 1997
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Ingår i: Advances in dental research. - : SAGE Publications. - 0895-9374 .- 1544-0737. ; 11:1, s. 50-58
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Forskningsöversikt (refereegranskat)abstract
- Microbial attachment to mucosal surfaces is a first step in mucosal infection. Specific interactions between microbial surface ligands and host receptors influence the distribution of microbes in their sites of infection. Adhesion has often been regarded as a sufficient end point, explaining tissue tropism and bacterial persistence at mucosal sites. Adherence, however, is also a virulence factor through which microbes gain access to host tissues, upset the integrity of the mucosal barrier, and cause disease. The induction of mucosal inflammation is one aspect of this process. Bacterial attachment to mucosal surfaces activates the production of pro-inflammatory cytokines that cause both local and systemic inflammation. Epithelial cells are one source of these cytokines. The binding of fimbrial lectins to epithelial cell receptors triggers transmembrane signaling events that upregulate cytokine-specific mRNA and increase cytokine secretion. P fimbriae that bind the globoseries of glycolipids cause the release of ceramides and activation of the ceramide signaling pathway which contributes to the IL-6 response. Spread of cytokines and other pro-inflammatory mediators from the local site contributes to the symptoms and signs of infection.
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