| 1. |
- Adolfsson, Per I, et al.
(författare)
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Zinc Induces a Bell-shaped Proliferative Dose-response Effect in Cultured Smooth Muscle Cells From Benign Prostatic Hyperplasia.
- 2015
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Ingår i: Urology. - : Elsevier BV. - 0090-4295 .- 1527-9995. ; 85:3, s. 704.e15-704.e19
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To investigate the effects of zinc (Zn(2+)) concentrations on cultured benign prostatic hyperplasia (BPH) smooth muscle cell (SMC) proliferation.METHODS: The effects of Zn(2+) were studied in primary cultures of human BPH SMC, stimulated with either 10-μM lysophosphatidic acid (LPA) or LPA in combination with 100-nM testosterone. Deoxyribonucleic acid replication and protein synthesis using [(3)H]-thymidine and [(35)S]-methionine incorporation were measured. Furthermore, studies were performed to evaluate if Zn(2+) could potentiate the inhibitory effect of phosphodiesterase-5 blockers, on BPH SMC proliferation.RESULTS: Zn(2+) generated a bell-shaped concentration response, both regarding deoxyribonucleic acid replication and protein synthesis in cultured BPH SMC. Below a threshold value (approximately 200 μM), a significant mitogenic effect was seen, whereas higher concentrations inhibited SMC proliferation after stimulation with LPA. This effect was even more pronounced after stimulation of LPA in combination with testosterone. Moreover, phosphodiesterase-5 inhibitors, that is, sildenafil blocked LPA-stimulated BPH SMC proliferation. This antiproliferative effect, was significantly potentiated by coincubation with Zn(2+) in an additative manner.CONCLUSION: The bell-shaped concentration response of Zn(2+) on cultured BPH SMC proliferation suggests that changes in prostate Zn(2+) concentrations, during aging, diet, or inflammatory conditions, may be of importance in the pathogenesis of BPH.
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| 2. |
- Agardh, Carl-David, et al.
(författare)
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Influence of treatment with diethylstilbestrol for carcinoma of prostate on platelet aggregation and plasma lipoproteins
- 1986
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Ingår i: Urology. - : Elsevier BV. - 1527-9995 .- 0090-4295. ; 28:6, s. 469-471
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Tidskriftsartikel (refereegranskat)abstract
- Treatment of prostatic carcinoma with estrogens is accompanied by an increased risk for thromboembolic and cardiovascular complications. The underlying mechanisms are still unknown. Patients treated with diethylstilbestrol (DES) were compared with patients given no estrogen treatment regarding factors (platelet aggregation in vitro and plasma lipoproteins) that have been suggested to contribute to increased thrombogenesis and cardiovascular risk. The results do not show any increase in in vitro platelet aggregation in patients treated with DES compared with those given no treatment. This indicates that hyperaggregability does not contribute to the increased incidence in thromboembolic events seen in DES-treated patients. This is in contrast to the increased platelet aggregation previously described in patients treated with polyestradiolphosphate + etinylestradiol. The changes in plasma lipoproteins observed during DES-treatment are generally considered beneficial from an atherogenic point of view and do not appear to cause the elevated incidence of cardiovascular disease in these patients.
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| 6. |
- Andersson, Karl-Erik
(författare)
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Bladder activation: afferent mechanisms.
- 2002
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Ingår i: Urology. - 1527-9995. ; 59:5 Suppl 1, s. 43-50
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Tidskriftsartikel (refereegranskat)abstract
- The major function of the lower urinary tract is to store and periodically evacuate urine from the bladder. This requires coordination of the smooth muscles of the bladder and urethra, and of the striated muscles of the outflow region and pelvic floor by a complex neural control system. Lumbosacral afferent fibers (pelvic afferents), but also afferents in the hypogastric and pudendal nerves, are of major importance for the regulation of the mechanisms for continence and micturition. In the bladder, afferent nerves have been identified suburothelially as well as in the detrusor muscle. Suburothelially, they form a plexus that lies immediately beneath the epithelial lining. This plexus is particularly dense in the bladder neck and the trigone. The most important afferents for the micturition process are myelinated Adelta-fibers and unmyelinated C-fibers. Immunocytochemical and tracing studies have revealed that numerous peptides, including substance P, calcitonin gene-related peptide, vasoactive intestinal polypeptide, enkephalins, and cholecystokinin are localized either alone, or in combination, in afferent pathways of the bladder and urethra. The receptors on these nerves include: vanilloid receptors, purinoceptors, tachykinin, and prostanoid receptors. Extracellular adenosine triphosphate (ATP) has been found to mediate excitation of small-diameter sensory neurons via P2X3 receptors, and it has been proposed that in the bladder, distention causes release of ATP from the urothelium. ATP, in turn, can activate P2X3 receptors on suburothelial afferent nerve terminals to evoke a neural discharge. However, it is most likely that a cascade of inhibitory and stimulatory transmitters/mediators, as well as ATP, are involved in the transduction mechanisms underlying the activation of afferent fibers during bladder filling.
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| 7. |
- Andersson, Karl-Erik
(författare)
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Introduction
- 2003
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Ingår i: Urology. - 1527-9995. ; 62:5 Suppl 2, s. 1-2
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Tidskriftsartikel (refereegranskat)
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| 8. |
- Andersson, Karl-Erik
(författare)
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New pharmacologic targets for the treatment of the overactive bladder: an update.
- 2004
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Ingår i: Urology. - : Elsevier BV. - 1527-9995 .- 0090-4295. ; 63:3 Suppl 1, s. 32-41
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Tidskriftsartikel (refereegranskat)abstract
- Although currently available antimuscarinic agents are the standard of care for overactive bladder (OAB), they are limited by certain side effects, particularly dry mouth and constipation. Research aimed at discovering new therapies for OAB has resulted in the identification of some promising drugs. Investigations of pharmacologic targets in the central nervous system (CNS) have yielded encouraging results with several agents, including tramadol and gabapentin. Further investigation may show that drugs acting at serotonergic and noradrenergic CNS sites are clinically useful as therapies for OAB. Some peripherally acting drugs, such as resiniferatoxin and botulinum toxin, have already been proved to be of clinical value. However, development of other agents that block afferent or efferent nerve impulses in the bladder through activity at vanilloid, purinergic, or opioid-like receptor sites may result in clinically useful drugs.
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| 9. |
- Andersson, Karl-Erik, et al.
(författare)
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Pharmacologic perspective on the physiology of the lower urinary tract
- 2002
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Ingår i: Urology. - : Elsevier. - 0090-4295 .- 1527-9995. ; 60:5 Suppl 1, s. 13-20
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Tidskriftsartikel (refereegranskat)abstract
- Myogenic activity, distention of the detrusor, and signals from the urothelium may initiate voiding. In the bladder, afferent nerves have been identified not only in the detrusor, but also suburothelially, where they form a plexus that lies immediately beneath the epithelial lining. Extracellular adenosine triphosphate (ATP) has been found to mediate excitation of small-diameter sensory neurons via P2X3 receptors, and it has been shown that bladder distention causes release of ATP from the urothelium. In turn, ATP can activate P2X3 receptors on suburothelial afferent nerve terminals to evoke a neural discharge. However, most probably, not only ATP but also a cascade of inhibitory and stimulatory transmitters and mediators are involved in the transduction mechanisms underlying the activation of afferent fibers during bladder filling. These mechanisms may be targets for future drugs. The central nervous control of micturition involves many transmitter systems, which may be suitable targets for pharmacologic intervention. gamma-Aminobutyric acid, dopamine, enkephalin, serotonin, and noradrenaline receptors and mechanisms are known to influence micturition, and potentially, drugs that affect these systems could be developed for clinical use. However, a selective action on the lower urinary tract may be difficult to obtain. Most drugs currently used for treatment of detrusor overactivity have a peripheral site of action, mainly the efferent (cholinergic) neurotransmission and/or the detrusor muscle itself. In the normal bladder, muscarinic receptor stimulation produces the main part of detrusor contraction, but evidence is accumulating that in disease states, such as neurogenic bladders, outflow obstruction, idiopathic detrusor instability, and interstitial cystitis, as well as in the aging bladder, a noncholinergic activation via purinergic receptors may occur. If this component of activation is responsible not only for part of the bladder contractions, but also for the symptoms of the overactive bladder, it should be considered an important target for therapeutic interventions.
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| 10. |
- Andersson, Karl-Erik
(författare)
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Storage and voiding symptoms: pathophysiologic aspects.
- 2003
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Ingår i: Urology. - : Elsevier BV. - 1527-9995 .- 0090-4295. ; 62:5 Suppl 2, s. 3-10
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Tidskriftsartikel (refereegranskat)abstract
- Lower urinary tract symptoms (LUTS) can be categorized as storage, voiding, and postmicturition symptoms. Although often associated with benign prostatic hyperplasia (BPH), they may also occur in women. This observation, the beneficial effects of a-adrenoceptor (AR) antagonists in men with BPH and LUTS, and the frail correlation between LUTS, and prostatic enlargement and/or outflow obstruction have focused interest on the role of extraprostatic alpha-ARs in the pathogenesis of LUTS. It has been suggested that an upregulation of contraction-mediating alpha-ARs and a downregulation of relaxation-mediating beta-ARs can contribute to LUTS generation. However, recent investigations on human bladder tissue could not confirm such a change. Antimuscarinic agents are effective for treatment of the overactive bladder, which is characterized by urge, frequency, urge incontinence, and nocturia (ie, LUTS). This suggests that muscarinic receptors are involved in the pathogenesis of LUTS, and there is recent evidence implicating purinergic receptors. Structural changes in the bladder, such as smooth muscle hypertrophy and connective tissue infiltration, are associated with detrusor overactivity in about 50% to 66% of patients with BPH. However, it is unclear whether this is caused by bladder outlet obstruction because the symptoms may remain in up to 33% of the patients after surgical removal of the obstruction. When outflow obstruction is reversed in rats, there is a subset (20%) that continues to have overactive voiding, despite a reversal of the bladder hypertrophy, suggesting that changes within the central nervous system may be a contributing factor. LUTS can be caused by many, often overlapping, pathophysiologic mechanisms, which may contribute to individual variation in response to treatment.
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