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  • 1.
    Aus, Gunnar
    et al.
    Department of Urology, Sahlgrens University Hospital, 413 45, Göteborg, Sweden.
    Nordenskjöld, Kerstin
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Robinson, David
    Department of Surgery, Höglandssjukhuset, Eksjö, Sweden.
    Rosell, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Varenhorst, Eberhard
    Department of Urology and Surgery, Vrinnevisjukhuset, Norrköping, Sweden.
    Prognostic Factors and Survival in Node-Positive (N1) Prostate Cancer: A Prospective Study Based on Data from a Swedish Population-Based Cohort2003In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 43, no 6, p. 627-631Article in journal (Refereed)
    Abstract [en]

    Objective: At presentation of prostate cancer, patients with proven lymph node metastasis (N1) are comparatively rare. It is difficult to give prognostic information based on the present literature. The aim of this study was to evaluate the impact of known risk factors in patients with pelvic node involvement and without distant metastasis.

    Methods: From the population-based, prospective prostate cancer tumour registry of the South–East Region in Sweden, we collected data on all 181 patients with N1, M0 prostate cancer diagnosed from January 1987 to October 2000 with a follow-up to December 2001. Mean follow-up was 62 months. Pre-operative risk factors as age, T-category, serum PSA, tumour grade and also primary treatment given was correlated to the outcome.

    Results: Median age at diagnosis was 65 years. Cancer-specific survival was highly variable with 5-year survival of 72%, a median of 8 years and the projected 13-year figure was 31%. T-category, age, PSA or treatment did not affect the outcome while poorly differentiated tumours had a tendency towards lower cancer-specific survival (p=0.0523) when compared to well and moderately differentiated tumours.

    Conclusions: This population-based cohort of prostate cancer patients with pelvic node involvement treated principally with non-curative intent had a median cancer-specific survival of 8 years. Preoperatively known risk factors seem to have but a modest impact on the prognosis for patients in this stage of the disease.

  • 2.
    Castiglione, Fabio
    et al.
    San Raffaele University, Italy .
    Bergamini, Alice
    San Raffaele University, Italy .
    Bettiga, Arianna
    San Raffaele University, Italy .
    Bivalacqua, Trinity J.
    Johns Hopkins University, MD, USA .
    Benigni, Fabio
    San Raffaele University, Italy .
    Strittmatter, Frank
    Munich University, Germany.
    Gandaglia, Giorgio
    San Raffaele University, Italy .
    Rigatti, Patrizio
    San Raffaele University, Italy .
    Montorsi, Francesco
    San Raffaele University, Italy .
    Hedlund, Petter
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Pharmacology.
    Perioperative Betamethasone Treatment Reduces Signs of Bladder Dysfunction in a Rat Model for Neurapraxia in Female Urogenital Surgery2012In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 62, no 6, p. 1076-1085Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Information on autonomic neurapraxia in female urogenital surgery is scarce, and a model to study it is not available.

    OBJECTIVE:

    To develop a model to study the impact of autonomic neurapraxia on bladder function in female rats, as well as to assess the effects of corticosteroid therapy on the recovery of bladder function in this model.

    DESIGN, SETTING, AND PARTICIPANTS:

    Female Sprague-Dawley rats were subjected to bilateral pelvic nerve crush (PNC) and perioperatively treated with betamethasone or vehicle. Bladder function and morphology of bladder tissue were evaluated and compared with sham-operated rats.

    OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:

    Western blot, immunohistochemistry, organ bath experiments, and cystometry.

    RESULTS AND LIMITATIONS:

    Sham-operated rats exhibited regular micturitions without nonvoiding contractions (NVCs). Crush of all nerve branches of the pelvic plexus or PNC resulted in overflow incontinence and/or NVCs. Betamethasone treatment improved recovery of regular micturitions (87.5% compared with 27% for vehicle; p<0.05), reduced lowest bladder pressure (8 ± 2 cm H(2)O compared with 21 ± 5 cm H(2)O for vehicle; p<0.05), and reduced the amplitude of NVCs but had no effect on NVC frequency in PNC rats. Compared with vehicle, betamethasone-treated PNC rats had less CD68 (a macrophage marker) in the pelvic plexus and bladder tissue. Isolated bladder from betamethasone-treated PNC rats exhibited better nerve-induced contractions, contained more cholinergic and sensory nerves, and expressed lower amounts of collagen III than bladder tissue from vehicle-treated rats.

    CONCLUSIONS:

    PNC causes autonomic neurapraxia and functional and morphologic changes of isolated bladder tissue that can be recorded as bladder dysfunction during awake cystometry in female rats. Perioperative systemic betamethasone treatment reduced macrophage contents of the pelvic plexus and bladder, partially counteracted changes in the bladder tissue, and had protective effects on micturition function.

  • 3.
    Castiglione, Fabio
    et al.
    University of Leuven, Belgium; IRCCS Osped San Raffaele, Italy.
    Dewulf, Karel
    University of Leuven, Belgium.
    Hakim, Lukman
    University of Leuven, Belgium; Airlangga University, Indonesia.
    Weyne, Emmanuel
    University of Leuven, Belgium.
    Montorsi, Francesco
    IRCCS Osped San Raffaele, Italy.
    Russo, Andrea
    IRCCS Osped San Raffaele, Italy.
    Boeri, Luca
    IRCCS Osped San Raffaele, Italy.
    Bivalacqua, Trinity J.
    Johns Hopkins Medical Institute, MD 21205 USA.
    De Ridder, Dirk
    University of Leuven, Belgium.
    Joniau, Steven
    University of Leuven, Belgium.
    Albersen, Maarten
    University of Leuven, Belgium.
    Hedlund, Petter
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology. Lund University, Sweden.
    Adipose-derived Stem Cells Counteract Urethral Stricture Formation in Rats2016In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 70, no 6, p. 1032-1041Article in journal (Refereed)
    Abstract [en]

    Background: A medical treatment for urethral stricture (US) is not yet available. Objective: To evaluate if local injection of human adipose tissue-derived stem cells (hADSC) prevents urethral fibrosis in a rat model of US. Design, setting, and participants: Male rats were divided into three groups: sham, US, and hADSC (n = 12 each). Sham rats received a vehicle injection in the urethral wall. US and hADSCs were incised and injected with the fibrosis-inducer transforming growth factor-beta 1 in the urethral wall. Intervention: One day later, hADSCs were injected in the urethral wall of hADSC rats whereas sham and US rats were injected with the vehicle. After 4 wk, the rats underwent cystometries and tissues were then harvested for functional and molecular analyses. Outcome measurements and statistical analysis: Cystometry, microultrasound, histochemistry, organ bath studies, reverse transcription polymerase chain reaction, and western blot. Results and limitations: US rats exhibited 49-51% shorter micturition intervals, 35-51% smaller micturition volumes and bladder capacity, 33-62% higher threshold pressures and flow pressures, and 35-37% lower bladder filling compliance compared with hADSC-treated rats and sham rats (p amp;lt; 0.05). By ultrasound, US rats had hyperechogenic and thick urethral walls with narrowed lumen compared with sham rats, whereas hADSC rats displayed less extensive urethral changes. Isolated detrusor from US rats exhibited 34-55% smaller contractions than detrusor from sham rats (p amp;lt; 0.05). Corresponding values were 11-35% for isolated detrusors from hADSC rats. Collagen and elastin protein expression were increased in the penile urethras of US rats compared with sham and hADSC groups (p amp;lt; 0.05). Endothelial and inducible nitric oxide synthase expressions were higher (p amp;lt; 0.05) in the hADSC group. Compared with US rats, hADSC rats demonstrated decreased expression of several fibrosis-related genes. Administration of hADSCs was performed at an early stage of US development, which we consider a limitation of the study. Conclusions: Local injection of hADSCs prevents stricture formation and urodynamic complications in a new rat model for US. Patient summary: Stem cell therapy is effective for preventing urethral stricture in an experimental setting. (C) 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  • 4.
    Castiglione, Fabio
    et al.
    University of Vita Salute San Raffaele, Milan, Italy .
    Hedlund, Petter
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Pharmacology.
    Van der Aa, Frank
    Katholieke University of Leuven, Belgium .
    Bivalacqua, Trinity J.
    Johns Hopkins Medical Institute, Baltimore, MD, USA.
    Rigatti, Patrizio
    University of Vita Salute San Raffaele, Milan, Italy .
    Van Poppel, Hein
    Katholieke University of Leuven, Belgium .
    Montorsi, Francesco
    University of Vita Salute San Raffaele, Milan, Italy .
    De Ridder, Dirk
    Katholieke University of Leuven, Belgium .
    Albersen, Maarten
    University of Vita Salute San Raffaele, Milan, Italy .
    Intratunical Injection of Human Adipose Tissue-derived Stem Cells Prevents Fibrosis and Is Associated with Improved Erectile Function in a Rat Model of Peyronies Disease2013In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 63, no 3, p. 551-560Article in journal (Refereed)
    Abstract [en]

    Background: Peyronies disease (PD) is a connective tissue disorder of the tunica albuginea (TA). Currently, no gold standard has been developed for the treatment of the disease in its active phase. less thanbrgreater than less thanbrgreater thanObjective: To test the effects of a local injection of adipose tissue-derived stem cells (ADSCs) in the active phase of a rat model of PD on the subsequent development of fibrosis and elastosis of the TA and underlying erectile tissue. less thanbrgreater than less thanbrgreater thanDesign, setting, and participants: A total of 27 male 12-wk-old Sprague-Dawley rats were divided in three equal groups and underwent injection of vehicle (sham), 50-mu g transforming growth factor (TGF)-beta 1 in a 50-mu l vehicle in either a PD or a PD plus ADSC group in the dorsal aspect of the TA. less thanbrgreater than less thanbrgreater thanIntervention: The sham and PD groups were treated 1 d after TGF-beta 1 injection with intralesional treatment of vehicle, and the PD plus ADSC group received 1 million human-labeled ADSCs in the 50-mu l vehicle. Five weeks after treatment, six rats per group underwent erectile function measurement. Following euthanasia, penises were harvested for histology and Western blot. less thanbrgreater than less thanbrgreater thanOutcome measurements and statistical analysis: The ratio of intracavernous pressure to mean arterial pressure (ICP/MAP) upon cavernous nerve stimulation, elastin, and collagen III protein expression and histomorphometric analysis of the penis. Statistical analysis was performed by analysis of variance followed by the Tukey-Kramer test for post hoc comparisons or the Mann-Whitney test when applicable. less thanbrgreater than less thanbrgreater thanResults and limitations: Erectile function significantly improved after ADSC treatment (ICP/MAP 0.37 in PD vs 0.59 in PD plus ADSC at 5-V stimulation; p = 0.03). PD animals developed areas of fibrosis and elastosis with a significant upregulation of collagen III and elastin protein expression. These fibrotic changes were prevented by ADSC treatment. less thanbrgreater than less thanbrgreater thanConclusions: This study is the first to test stem cell therapy in an animal model of PD. Injection of ADSCs into the TA during the active phase of PD prevents the formation of fibrosis and elastosis in the TA and corpus cavernosum.

  • 5.
    Castiglione, Fabio
    et al.
    University of Vita Salute San Raffaele, Milan, Italy .
    Hedlund, Petter
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Pharmacology.
    Van der Aa, Frank
    Katholieke University of Leuven, Belgium .
    Bivalacqua, Trinity J.
    Johns Hopkins Medical Institute, MD USA .
    Rigatti, Patrizio
    University of Vita Salute San Raffaele, Italy .
    Van Poppel, Hein
    Katholieke University of Leuven, Belgium .
    Montorsi, Francesco
    University of Vita Salute San Raffaele, Milan, Italy .
    De Ridder, Dirk
    Katholieke University of Leuven, Belgium .
    Albersen, Maarten
    University of Vita Salute San Raffaele, Milan, Italy .
    Reply from Authors re: Ching-Shwun Lin, Tom F. Lue. Adipose-derived Stem Cells for the Treatment of Peyronie's Disease? Eur Urol 2013;63:561–2: Xenogeneic Adipose Stem Cell Treatment in a Rat Model of Peyronie's Disease2013In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 63, no 3, p. 563-564Article in journal (Other academic)
  • 6.
    Dizeyi, N
    et al.
    Department of Urology, Malmö University Hospital, Lund University, Malmö, Sweden.
    Bjartell, A
    Department of Urology, Malmö University Hospital, Lund University, Malmö, Sweden.
    Hedlund, Petter
    Department of Clinical Pharmacology, Malmö University Hospital, Lund University, Malmö, Sweden.
    Taskén, K A
    Oslo Urological University Clinic, Aker University Hospital, Faculty Division Aker University Hospital, University of Oslo, Oslo, Norwaytal, Faculty Division Aker University Hospital, University of Oslo.
    Gadaleanu, V
    Department of Pathology, Malmö University Hospital, Lund University, Malmö, Sweden.
    Abrahamsson, P-A
    Department of Urology, Malmö University Hospital, Lund University, Malmö, Sweden.
    Expression of serotonin receptors 2B and 4 in human prostate cancer tissue and effects of their antagonists on prostate cancer cell lines.2005In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 47, no 6, p. 895-900Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Overexpression of receptors to neuroendocrine (NE) cell products has been suggested to contribute to development of hormone-refractory prostate cancer (HRPC). In this study, we evaluated the expression of 5-HTR2B and 5-HTR4 in HRPC, and the effects of their antagonist on PC cell line growth.

    METHODS: Proteins and mRNA expression was determined by immunohistochemistry, western blot and RT-PCR. Growth inhibition of PC cell lines was determined in vitro using ELISA-BrdU proliferation assay and cell cycle was evaluated by flow cytometry.

    RESULTS: Immunostaining of 5-HTR2B was observed in low-grade and high-grade tumours, PIN and BPH cells, and in vascular endothelial cells, whereas 5-HTR4 was found predominantly in high-grade tumours. This result was confirmed by western blot analysis. At the mRNA level, 5-HTR4 mRNA was expressed in DU145 and LNCaP cells. Antagonists to both receptor subtypes inhibited proliferation of PC cells in a dose-dependent manner.

    CONCLUSIONS: The present result indicate that 5-HTRs are present at various tumour stages and that antagonists to these receptors can inhibit the proliferative activity of androgen-independent PC cell lines.

  • 7.
    Duchek, Milos
    et al.
    Umea Univ, Dept Surg and Perioperat Sci Urol and Androl, Umea, Sweden.
    Johansson, Robert
    Umea Univ Hosp, Ctr Oncol, S-90185 Umea, Sweden.
    Jahnson, Staffan
    Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Urology in Östergötland.
    Mestad, Oddvar
    Stavanger Univ Hosp, Surg Clin, Dept Urol, Stavanger, Norway.
    Hellstrom, Pekka
    Univ Cent Hosp, Dept Urol, Oulu, Finland.
    Hellsten, Sverker
    Univ Hosp, Dept Urol, Malmo, Sweden.
    Malmstrom, Per-Uno
    Univ Uppsala Hosp, Dept Urol, S-75185 Uppsala, Sweden.
    Bacillus Calmette-Guerin Is Superior to a Combination of Epirubicin and Interferon-alpha 2b in the Intravesical Treatment of Patients with Stage T1 Urinary Bladder Cancer. A Prospective, Randomized, Nordic Study2010In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 57, no 1, p. 25-31Article in journal (Refereed)
    Abstract [en]

    Background: Bacillus Calmette-Guerin (BCG) instillation is regarded as the most effective bladder-sparing treatment for patients with high-grade T1 tumours and carcinoma in situ (CIS). The major problem with this therapy is the side-effects, making maintenance therapy difficult, even impossible, in a proportion of patients. Thus, alternative schedules and drugs have been proposed. Objective: To compare BCG to the combination of epirubicin and interferon-alpha 2b as adjuvant therapy of T1 tumours. Design, setting, and participants: This is a Nordic multicenter, prospective, randomised trial in patients with primary T1 G2-G3 bladder cancer. Initial transurethral resection (TUR) was followed by a second-look resection. Patients were randomised to receive either regimen, given as induction for 6 wk followed by maintenance therapy for 2 yr. Measurements: The drugs were compared with respect to time to recurrence and progression. Also, side-effects were documented. Results and limitations: A total of 250 patients were randomised. At the primary end point, 62% were disease free in the combination arm as opposed to 73% in the BCG arm (p = 0.065). At 24 mo, there was a significant difference in favour of the BCG-treated patients (p = 0.012) regarding recurrence, although there was no difference regarding progression. The subgroup analysis showed that the superiority of BCG was mainly in those with concomitant CIS. In a multivariate analysis of association with recurrence/progression status, significant variables for outcome were type of drug, tumour size, multiplicity, status at second-look resection, and grade. A corresponding analysis was performed separately in the two treatment arms. Tumour size was the only significant variable for BCG-treated patients, while multiplicity, status at second-look resection, and grade were significant for patients treated with the combination. Conclusions: For prophylaxis of recurrence, BCG was more effective than the combination. There were no differences regarding progression and adverse events between the two treatments.

  • 8.
    Frisk, Jessica
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Östergötland.
    Spetz, Anna-Clara
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Gynecology and Obstetrics in Linköping.
    Hjertberg, Hans
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Urology in Östergötland.
    Petersson, Bill
    Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Urology in Östergötland.
    Hammar, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Gynecology and Obstetrics in Linköping.
    Two Modes of Acupuncture as a Treatment for Hot Flushes in Men with Prostate Cancer—A Prospective Multicenter Study with Long-Term Follow-Up2009In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 55, no 1, p. 156-163Article in journal (Refereed)
    Abstract [en]

    Background: Hot flushes are common and distressing among men with castrational treatment for prostate cancer. Of the few treatments, most have side effects.

    Objective: Assess changes in hot flushes of electrostimulated (EA) and traditional acupuncture (TA).

    Design, Setting, and Participants: Thirty-one men with hot flushes due to prostate cancer treatment were recruited from three urological departments in Sweden, from 2001 to 2004.

    Intervention: Thirty-one men were randomized to EA (4 electrostimulated needle points) or TA (12 needle points) weekly for 12 wk.

    Measurements: Primary outcome: number of and distress from hot flushes in 24h and change in “hot flush score.” Secondary outcome: change in 24-h urine excretion of CGRP (calcitonin gene–related peptide).

    Results and Limitations: Twenty-nine men completed the treatment. Hot flushes per 24h decreased significantly, from a median of 7.6 (interquartile range [IQR], 6.0–12.3) at baseline in the EA group to 4.1 (IQR, 2.0–6.5) (p=0.012) after 12 wk, and from 5.7 (IQR, 5.1–9.5) in the TA group to 3.4 (IQR1.8–6.3) (p=0.001). Distress by flushes decreased from 8.2 (IQR, 6.5–10.7) in the EA group to 3.3 (IQR, 0.3–8.1) (p=0.003), and from 7.6 (IQR, 4.7–8.3) to 3.4 (IQR, 2.0–5.6) (p=0.001) in the TA group after 12 wk, (78% and 73% reduction in “hot flush score,” respectively). The effect lasted up to 9 mo after treatment ended. CGRP did not change significantly. Few, minor side effects were reported.

    Limitations: small number of patients; no placebo control, instead a small group controlled for 6 wk pretreatment.

    Conclusions: EA and TA lowered number of and distress from hot flushes. The hot flush score decreased 78% and 73%, respectively, in line with or better than medical regimens for these symptoms. Acupuncture should be considered an alternative treatment for these symptoms, but further evaluation is needed, preferably with a non- or placebo-treated control group.

  • 9.
    Gratzke, Christian
    et al.
    Department of Clinical and Experimental Pharmacology, Lund University, Lund, Sweden.
    Streng, Tomi
    Department of Pharmacology, Turku University, Turku, Finland.
    Stief, Christian G.
    Department of Urology, Ludwig-Maximilians-University, Munich, Germany.
    Downs, Thomas R.
    Women's Health, Procter & Gamble Health Care, Cincinnati, OH, USA.
    Alroy, Iris
    Pharmos Limited, Rehovot, Israel.
    Rosenbaum, Jan S
    Women's Health, Procter & Gamble Health Care, Cincinnati, OH, USA.
    Andersson, Karl-Erik
    Wake Forest Institute for Regenerative Medicine, Winston-Salem, NC, USA.
    Hedlund, Petter
    Department of Clinical and Experimental Pharmacology, Lund University, Lund, Sweden.
    Effects of cannabinor, a novel selective cannabinoid 2 receptor agonist, on bladder function in normal rats2010In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 57, no 6, p. 1093-1100Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Cannabinoid (CB) receptors may be involved in the control of bladder function; the role of CB receptor subtypes in micturition has not been established.

    OBJECTIVES: Our aim was to evaluate the effects of cannabinor, a novel CB2 receptor agonist, on rat bladder function.

    DESIGN, SETTING, AND PARTICIPANTS: Sprague Dawley rats were used. Distribution of CB2 receptors in sensory and cholinergic nerves of the detrusor was studied. Selectivity of cannabinor for human and rat CB receptors was evaluated. Effects of cannabinor on rat detrusor and micturition were investigated.

    MEASUREMENTS: Immunohistochemistry, radioligand binding, tritium outflow assays, organ bath studies of isolated bladder tissue, and cystometry in awake rats were used.

    RESULTS AND LIMITATIONS: CB2 receptor immunoreactivity was expressed in the urothelium and in sensory and cholinergic bladder nerves. Cannabinor exhibited similar binding at human and rat CB2 receptors and a 321-fold functional selectivity for the CB2 receptor versus the CB1 receptor. Cannabinor had no effect on isolated detrusor muscle function. In vivo, cannabinor 3.0mg/kg increased micturition intervals and volumes by 52% (p<0.05) and 96% (p<0.01), respectively, and increased threshold and flow pressures by 73% (p<0.01) and 49% (p<0.001), respectively. Cannabinor 0.3 or 1.0mg/kg or vehicle did not affect urodynamic parameters.

    CONCLUSIONS: Considering that CB2 receptors are localized on sensory nerves and on the urothelium and that cannabinor had effects on "afferent" urodynamic parameters, peripheral CB2 receptors may be involved in sensory functions of rat micturition. Effects of cannabinor on cholinergic nerve activity in normal bladder tissue appear to be limited.

  • 10.
    Hedlund, Petter
    Linköping University, Department of Medical and Health Sciences, Pharmacology. Linköping University, Faculty of Health Sciences.
    Editorial Comment on Characteristics of Spontaneous Activity in the Bladder Trigone: in EUROPEAN UROLOGY, vol 56, issue 2, pg 354.2009In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 56, no 2, p. 354-354Article in journal (Other academic)
    Abstract [en]

    n/a

  • 11.
    Hedlund, Petter
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology. IRCCS Osped San Raffaele, Italy.
    Editorial Material: Everyday Cold Exposure and Urgency in Translation in EUROPEAN UROLOGY2015In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 68, no 4, p. 662-663Article in journal (Other academic)
    Abstract [en]

    n/a

  • 12. Henningsohn, L
    et al.
    Wijkstrom, H
    Steven, K
    Pedersen, J
    Ahlstrand, Christer
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Urology . Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Urology in Östergötland.
    Aus, G
    Kallestrup, EB
    Bergmark, K
    Onelov, E
    Steineck, G
    Relative importance of sources of symptom-induced distress in urinary bladder cancer survivors2003In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 43, no 6, p. 651-662Article in journal (Refereed)
    Abstract [en]

    Objective: The influence of specific symptoms on emotions and social activities in the individual patient vanes. Little is known about this variation in urinary bladder cancer survivors (in other words, about the relative importance of sources of symptom-induced distress). Methods: We attempted to enrol 404 surgical patients treated with cystectomy and a conduit or reservoir in four Swedish towns (Stockholm, Orebro, Jonkoping, Linkoping), 101 surgical patients treated with cystectomy and orthotopic neobladder at the Herlev Hospital in Copenhagen, Denmark, and 71 patients treated with radical radiotherapy for bladder cancer, as well as 581 men and women controls in Stockholm and Copenhagen. An anonymous postal questionnaire was used to collect the information. Results: A total of 503 out of 576 (87%) treated patients and 422 out of 581 (73%) controls participated but 59 patients were excluded. The primary source of self-assessed distress among cystectomised patients was compromised sexual function, reduced intercourse frequency caused great distress in 19% of the conduit patients, 20% of the reservoir patients and 19% of the bladder substitute patients. The primary source of self-assessed distress in patients treated with radical radiotherapy was symptoms from the bowel, 17% reported great distress due to diarrhoea, 16% due to abdominal pain, 14% due to defecation urgency and 14% due to faecal leakage. The highest proportion of subjects being distressed was 93% (substantial: 43%, moderate: 29% and little: 21%) for treated upper or lower urinary retention (indwelling catheter or nephrostomy). Conclusion: The distress caused by a specific symptom varies considerably and the prevalence of symptoms causing great distress differs between treatments in bladder cancer survivors. It is possible that patient care and clinical research can be made more effective by focusing on important sources of symptom-induced distress. (C) 2003 Elsevier Science B.V. All rights reserved.

  • 13. Hofner, C
    et al.
    DeRiejke, Claes
    Folkestad, Bengt
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Urology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Urology in Östergötland.
    Speakman, MJ
    Tamsulosin 0,4 mg once daily: effect on sexual function in patients with lower urinary tract symptoms suggestive of benign prostatic obstruction.1999In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 36, p. 335-341Article in journal (Refereed)
  • 14.
    Jancke, Georg
    et al.
    Skåne Univ Hosp, Sweden; Lund Univ, Sweden.
    Aljabery, Firas
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland. Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Gudjonsson, Sigurdur
    Landspitali Univ Hosp, Iceland.
    Hosseini, Abolfazl
    Karolinska Univ Hosp, Sweden.
    Sorenby, Anne
    Skane Univ Hosp, Sweden; Lund Univ, Sweden.
    Wiklund, Peter
    Karolinska Univ Hosp, Sweden.
    Liedberg, Fredrik
    Skane Univ Hosp, Sweden; Lund Univ, Sweden.
    Port-site Metastases After Robot-assisted Radical Cystectomy: Is There a Publication Bias?2018In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 73, no 4, p. 641-642Article in journal (Other academic)
    Abstract [en]

    n/a

  • 15.
    Jancke, Georg
    et al.
    Skane Univ Hosp, Sweden; Lund Univ, Sweden.
    Aljabery, Firas
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Gudjonsson, Sigurdur
    Landspitali Univ Hosp, Iceland.
    Sorenby, Anne
    Skane Univ Hosp, Sweden; Lund Univ, Sweden.
    Liedberg, Fredrik
    Skane Univ Hosp, Sweden; Lund Univ, Sweden.
    Reply to Francesco Montorsi and Giorgio Gandaglias Letter to the Editor re: Georg Jancke, Firas Aljabery, Sigurdur Gudjonsson, et al. Port-site Metastases After Robot-assisted Radical Cystectomy: Is There a Publication Bias?2019In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 75, no 2, p. E32-E33Article in journal (Other academic)
    Abstract [en]

    n/a

  • 16.
    Krantz, David
    et al.
    Karolinska Inst, Sweden.
    Hartana, Ciputra Adijaya
    Karolinska Inst, Sweden.
    Winerdal, Malin E.
    Karolinska Inst, Sweden.
    Johansson, Markus
    Sundsvall Hosp, Sweden; Umea Univ, Sweden.
    Alamdari, Farhood
    Vastmanland Hosp, Sweden.
    Jakubczyk, Tomasz
    Ryhov Cty Hosp, Sweden.
    Huge, Ylva
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Aljabery, Firas
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Palmqvist, Karin
    Umea Univ, Sweden; Ostersund Cty Hosp, Sweden.
    Zirakzadeh, A. Ali
    Karolinska Inst, Sweden; Umea Univ, Sweden.
    Holmstrom, Benny
    Akad Univ Hosp, Sweden.
    Riklund, Katrine
    Umea Univ, Sweden.
    Sherif, Amir
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Umea univ, Sweden.
    Winqvist, Ola
    Karolinska Inst, Sweden.
    Neoadjuvant Chemotherapy Reinforces Antitumour T cell Response in Urothelial Urinary Bladder Cancer2018In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 74, no 6, p. 688-692Article in journal (Refereed)
    Abstract [en]

    Evidence indicates that neoadjuvant chemotherapy (NAC) may promote antitumour immune responses by activating T cells. The tumour-draining sentinel node (SN) is a key site to study tumour-specific T cell activation, being the primary immunological barrier against the tumour. In this prospective study, we set out to elucidate the effects of NAC on T cell subsets in the SNs of patients with muscle-invasive urothelial bladder cancer. We found that CD8(+) effector T (Teff) cell exhaustion was reduced after NAC treatment, while cytotoxicity was increased. Additionally, in complete responders (CR patients), these cells were functionally committed effectors, as displayed by epigenetic analysis. In CD4(+) Teffs, NAC treatment was associated with increased clonal expansion of tumour-specific SN-derived cells, as demonstrated by a specific cell reactivity assay. In contrast, we observed an attenuating effect of NAC on regulatory T cells (Tregs) with a dose-dependent decrease in Treg frequency and reduced effector molecule expression in the remaining Tregs. In addition, multicolour flow cytometry analysis revealed that CR patients had higher Teff to activated Treg ratio, promoting antitumoural T cell activation. These results suggest that NAC reinforces the antitumour immune response by activating the effector arm of the T cell compartment and diminishing the influence of suppressive Tregs. Patient summary: In this report, we analysed the effect of chemotherapy on immune cell subsets of 40 patients with advanced bladder cancer. We found that chemotherapy has a positive effect on immune effector T cells, whereas an opposite, diminishing effect was observed for immune-suppressive regulatory T cells. We conclude that chemotherapy reinforces the antitumour immune response in bladder cancer patients. (C) 2018 Published by Elsevier B.V. on behalf of European Association of Urology.

  • 17.
    Pettersson, Bill
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Urology . Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Urology in Östergötland.
    Varenhorst, Eberhard
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Urology . Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Urology in Östergötland.
    Petas, A.
    Department of Urology, Helsinki University Central Hospital, Helsinki, Finland.
    Sandow, J.
    Sanofi-Aventis Pharma, Hoechst Industry Park, Frankfurt, Germany.
    Duration of Testosterone Suppression after a 9.45 mg Implant of the GnRH-Analogue Buserelin in Patients with Localised Carcinoma of the Prostate. A 12-Month Follow-up Study2006In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 50, no 3, p. 483-489Article in journal (Refereed)
    Abstract [en]

    Objectives: (1) To determine the duration of androgen deprivation after a single buserelin implant 9.45 mg in the neoadjuvant setting in combination with curative radiation therapy of carcinoma of the prostate, and (2) to evaluate the time to recovery of gonadal function, and the incidence and duration of hypogonadal symptoms. Methods: We prospectively evaluated 21 men with carcinoma of the prostate who received one implant of 9.45 mg buserelin subcutaneously. Release of buserelin, changes in serum testosterone concentration, hot flushing and sexual function over a 12-month study period were recorded. Results: Testosterone was suppressed below the castration limit (0.58 ng/ml = 2 nmol/l) for 224 days (range, 139-309). The mean time to first return of testosterone above the castration limit was 246 days (range, 168-344), 50% of pre-treatment value was reached after 285 days (range, 218-370). The prevalence of hot flushing was 19 of 21 patients (90%) at 12 weeks. At the end of the study period, serum testosterone had reached 80% (range, 33%-166%) of pre-treatment concentration, sexual interest was present in 52%, erection was possible in 60%, and hot flushing remained in 24%. Conclusion: A single injection of 3-month buserelin implant 9.45 mg suppresses serum testosterone below the castration limit for at least 6 months. Testosterone secretion recovers by 8-12 months. Hypogonadal symptoms decreased with the restoration of serum testosterone secretion. These data are clinically relevant regarding the dose schedule for buserelin and the patient information provided. © 2006 European Association of Urology.

  • 18.
    Sandblom, Gabriel
    et al.
    Department of Surgery, Uppsala Akademiska Hospital, Akademiska Sjukhuset, Uppsala, Sweden.
    Varenhorst, Eberhard
    Linköping University, Department of Biomedicine and Surgery, Urology. Linköping University, Faculty of Health Sciences.
    Löfman, Owe
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Rosell, Johan
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Carlsson, Per
    Linköping University, Department of Department of Health and Society, Center for Medical Technology Assessment. Linköping University, Faculty of Health Sciences.
    Clinical consequences of screening for prostate cancer: 15 Years follow-up of a randomised controlled trial in Sweden2004In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 46, no 6, p. 717-723Article in journal (Refereed)
    Abstract [en]

    Objective:

    To test the feasibility of a population-based prostate cancer screening programme in general practice and explore the outcome after a 15-year follow-up period.

    Methods:

    From the total population of men aged 50–69 years in Norrköping (n = 9026) every sixth man (n = 1494) was randomly selected to be screened for prostate cancer every third year over a 12-year period. The remaining 7532 men were treated as controls. In 1987 and 1990 only digital rectal examination (DRE) was performed, in1993 and 1996 DRE was combined with a test for Prostate-Specific Antigen (PSA). TNM categories, grade of malignancy, management and cause of death were recorded in the South-East Region Prostate Cancer Register.

    Results:

    There were 85 (5.7%) cancers detected in the screened group (SG), 42 of these in the interval between screenings, and 292 (3.8%) in the unscreened group (UG). In the SG 48 (56.5%) of the tumours and in the UG 78 (26.7%) were localised at diagnosis (p < 0.001). In the SG 21 (25%) and in the UG 41 (14%) received curative treatment. There was no significant difference in total or prostate cancer-specific survival between the groups.

    Conclusions:

    Although PSA had not been introduced in the clinical practice at the start of the study, we were still able to show that it is possible to perform a long-term population-based randomised controlled study with standardised management and that screening in general practice is an efficient way of detecting prostate cancer whilst it is localised. Complete data on stage, treatment and mortality for both groups was obtained from a validated cancer register, which is a fundamental prerequisite when assessing screening programmes.

  • 19.
    Sennfält, Karin
    et al.
    Linköping University, Department of Department of Health and Society, Center for Medical Technology Assessment. Linköping University, Faculty of Health Sciences.
    Carlsson, Per
    Linköping University, Department of Department of Health and Society, Center for Medical Technology Assessment. Linköping University, Faculty of Health Sciences.
    Varenhorst, Eberhard
    Linköping University, Department of Biomedicine and Surgery, Urology. Linköping University, Faculty of Health Sciences.
    Diffusion and Economic Consequences of Health Technologies in Prostate Cancer Care in Sweden, 1991-20022006In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 49, no 6, p. 1028-1034Article in journal (Refereed)
    Abstract [en]

       Objective

    To describe the diffusion of six main health technologies used for management of prostate cancer, to estimate the economic consequences of technological changes, and to explore factors behind the diffusion.

    Methods

    Data describing the diffusion 1991–2002 were obtained from population-based databases. Costs were obtained from Linköping University Hospital and Apoteket AB. Factors affecting the diffusion of the technologies were explored.

    Results

    Utilization of technologies with a curative and/or palliative aim has increased over time, except for surgical castration. PSA-tests are used increasingly. The total cost of the study technologies has increased from 20 million euros in 1991 to 65 million euros in 2002. Classification of radical prostatectomy revealed a profile associated with a slow/limited diffusion, while classification of PSA-tests revealed a profile associated with a rapid/extensive diffusion.

    Conclusions

    Several technological changes in the management of prostate cancer have occurred without proven benefits and have contributed to increased costs. There are other factors, besides scientific evidence, that have an impact on the diffusion. Consequently, activities aimed at facilitating an appropriate diffusion of new technologies are needed. The analytical framework used here may be helpful in identifying technologies that are likely to experience inappropriate diffusion and therefore need particular attention.

  • 20.
    Streng, T.
    et al.
    Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Turku, Finland, Department of Clinical Chemistry and Pharmacology, Lund University Hospital, Lund, Sweden.
    Axelsson, H.E.
    Department of Clinical Chemistry and Pharmacology, Lund University Hospital, Lund, Sweden.
    Hedlund, Petter
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Andersson, D.A.
    Wolfson Centre for Age-Related Diseases, King's College London, London, United Kingdom.
    Jordt, S.-E.
    Department of Pharmacology, Yale University School of Medicine, New Haven, CT, United States.
    Bevan, S.
    Wolfson Centre for Age-Related Diseases, King's College London, London, United Kingdom.
    Andersson, K.-E.
    Department of Clinical Chemistry and Pharmacology, Lund University Hospital, Lund, Sweden, Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, Medical Center Boulevard, Winston Salem, NC, United States.
    Hogestatt, E.D.
    Högestätt, E.D., Department of Clinical Chemistry and Pharmacology, Lund University Hospital, Lund, Sweden.
    Zygmunt, P.M.
    Department of Clinical Chemistry and Pharmacology, Lund University Hospital, Lund, Sweden.
    Distribution and Function of the Hydrogen Sulfide-Sensitive TRPA1 Ion Channel in Rat Urinary Bladder2008In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 53, no 2, p. 391-400Article in journal (Refereed)
    Abstract [en]

    Objectives: To investigate the distribution of the transient receptor potential (TRP) A1 ion channel in the rat urinary bladder, and to study the effects of hydrogen sulfide (H2S) and known TRPA1 activators on micturition in conscious rats and on heterologously expressed ion channels. Methods: The expression of TRPA1 in urinary bladder was studied with fluorescence immunohistochemistry and real-time PCR in female Sprague-Dawley rats. Cystometric investigations were performed in conscious animals subjected to intravesical administration of sodium hydrogen sulfide (NaHS, donor of H2S), allyl isothiocyanate (AI), and cinnamaldehyde (CA). Fluorometric calcium imaging was used to study the effect of NaHS on human and mouse TRPA1 expressed in CHO cells. Results: TRPA1 immunoreactivity was found on unmyelinated nerve fibres within the urothelium, suburothelial space, and muscle layer as well as around blood vessels throughout the bladder. All TRPA1 immunoreactive nerves fibres also expressed TRPV1 immunoreactivity and vice versa. TRPA1 was also detected in urothelial cells at both transcriptional and protein levels. AI increased micturition frequency and reduced voiding volume. CA and NaHS produced similar changes in urodynamic parameters after disruption of the urothelial barrier with protamine sulfate. NaHS also induced calcium responses in TRPA1-expressing CHO cells, but not in untransfected cells. Conclusions: The expression of TRPA1 on C-fibre bladder afferents and urothelial cells together with the finding that intravesical TRPA1 activators initiate detrusor overactivity indicate that TRPA1 may have a role in sensory transduction in this organ. The study also highlights H2S as a TRPA1 activator potentially involved in inflammatory bladder disease. © 2007.

  • 21.
    Strittmatter, F.
    et al.
    Munich University, Germany.
    Gandaglia, G.
    San Raffaele University, Milan, Italy.
    Benigni, F.
    San Raffaele University, Milan, Italy.
    Bettiga, A.
    San Raffaele University, Milan, Italy.
    Rigatti, P.
    San Raffaele University, Milan, Italy.
    Montorsi, F.
    San Raffaele University, Milan, Italy.
    Gratzke, C.
    Munich University, Germany.
    Stief, C.
    Munich University, Germany.
    Colciago, G.
    San Raffaele University, Milan, Italy.
    Hedlund, Petter
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Pharmacology. San Raffaele University, Milan, Italy.
    Expression of fatty acid amide hydrolase (FAAH) in human, mouse, and rat urinary bladder and effects of FAAH inhibition on bladder function in awake rats2012In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 61, no 1, p. 98-106Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Cannabinoid receptor (CB)-mediated functions may be involved in the regulation of bladder function, but information on endocannabinoid signals during micturition is scarce.

    OBJECTIVE:

    Investigate the expression of the endocannabinoid-degrading enzyme fatty acid amide hydrolase (FAAH) in human, rat, and mouse bladders and study the effects of inhibition of FAAH during urodynamics in awake rats.

    DESIGN, SETTING, AND PARTICIPANTS:

    Bladder tissue from humans, mice, and rats was used for measurements. Female Sprague-Dawley rats were administered the FAAH inhibitor oleoyl ethyl amide (OEtA) or vehicle intravenously (IV) or intravesically (IVES) with or without rimonabant (CB1 antagonist) or SR144528 (CB2 antagonist).

    MEASUREMENTS:

    Real-time transcriptase-polymerase chain reaction, Western blot, immunohistochemistry, and cystometry in awake rats.

    RESULTS AND LIMITATIONS:

    Messenger RNA and protein for FAAH was expressed in the mucosa of human, mouse, and rat urinary bladders. Immunoreactivities for FAAH and CB2 were codistributed in rat and human urothelium. IV OEtA (0.3mg/kg) to rats increased intercontraction intervals (ICIs), micturition volume (MV), bladder capacity (BC), and threshold pressure (TP) by 17±1%, 16±1%, 17±1%, and 19±5%, respectively (all p<0.05 vs baseline). IVES OEtA (1 and 10mg/l) in rats dose-dependently increased (p<0.05 vs baseline) ICI (19±2% and 35±5%), MV (15±3% and 32±4%), BC (16±2% and 34±4%), and TP (15±1%, 21±3%). SR144528 (IVES 5mg/l) abolished all effects of OEtA, whereas rimonabant only counteracted effects of OEtA on TP.

    CONCLUSIONS:

    Bladder mucosa of all species expressed FAAH. Rat and human urothelium coexpressed FAAH and CB2. The FAAH inhibitor OEtA altered urodynamic parameters that reflect sensory functions of micturition in rats. Suggesting a role for the endocannabinoid system in bladder mechanoafferent functions of rats, effects of IVES OEtA were abolished by an IVES CB2 antagonist and partly counteracted by an IVES CB1 antagonist.

     

     

  • 22. Tyrrell, CJ
    et al.
    Altwein, JE
    Klippel, F
    Jurincic-Winkler, C
    Varenhorst, Eberhard
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Urology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Urology in Östergötland.
    Lunglmayr, G
    Boccardo, F
    Holdaway, IM
    Haefliger, J-M
    Jordaan, JP
    Comparison of an LH-RH analogue (Goeserelin acetate, ´Zoladex´) with combined androgen blockade in advanced prostate cancer: Final survival results of an internaitonal multicentre randomized-trial.2000In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 37, p. 205-211Article in journal (Refereed)
  • 23.
    Uckert, S
    et al.
    annover Medical School.
    Oelke, M
    University of Amsterdam.
    Stief, CG
    Ludwig-Maximilians-University.
    Andersson, KE
    Lund University Hospital.
    Jonas, U
    Hannover Medical School.
    Hedlund, Petter
    Lund University Hospital.
    Immunohistochemical distribution of cAMP- and cGMP-phosphodiesterase (PDE) isoenzymes in the human prostate2006In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 49, no 4, p. 740-745Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: With the introduction of sildenafil citrate (Viagra), the concept of phosphodiesterase (PDE) inhibition has gained tremendous interest in the field of urology. Cyclic nucleotide second messengers cGMP and cAMP have been assumed to be involved in the control of the normal function of the prostate. The aim of the present study was to evaluate by means of immunohistochemistry the expression and distribution of some cAMP- and cGMP-PDE isoenzymes in the prostate.

    MATERIAL & METHODS: Cryostat sections (10 microM) of formaldehyde-fixated tissue segments excised from the transition zone of human prostates were incubated with primary antibodies directed against the PDE isoenzymes 3, 4, 5, and 11. Then, sections were exposed to either fluorescein isothiocyanate- (FITC) or Texas Red- (TR) labeled secondary antibodies and visualization was commenced by means of laser fluorescence microscopy.

    RESULTS: TR-immunofluorescence indicating the presence of PDE4 (cAMP-PDE) was abundantly observed in the fibromuscular stroma as well as in glandular structures of the transition zone. In contrast to the distribution of PDE4, immunoactivity indicating PDE5 (cGMP-PDE) and 11 (dual substrate PDE) was mainly observed in glandular and subglandular areas. No immunostaining for PDE3 (cGMP-inhibited PDE) was detected.

    CONCLUSION: Our results confirm the presence of PDE isoenzymes 4, 5 and 11 in the transition zone of the human prostate and present evidence that these isoenzymes are not evenly distributed. These findings are in support of the hypothesis that there might be a rationale for the use of PDE inhibitors in the pharmacotherapy of BPH and LUTS.

  • 24.
    Ueckert, Stefan
    et al.
    Hannover Medical School.
    Hedlund, Petter
    Lund University Hospital.
    Andersson, Karl-Erik
    Lund University Hospital.
    Truss, Michael C.
    Hannover Medical School.
    Jonas, Udo
    Hannover Medical School.
    Stief, Christian G.
    Ludwig-Maximilians-University.
    Update on phosphodiesterase (PDE) isoenzymes as pharmacologic targets in urology: Present and future2006In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 50, no 6, p. 1194-1207Article, review/survey (Refereed)
  • 25.
    Waldkirch, Eginhard S.
    et al.
    Hannover Medical School.
    Uckert, Stefan
    Hannover Medical School.
    Langnaese, Kristina
    Otto-von-Guericke-University.
    Richter, Karin
    Otto-von-Guericke-University.
    Jonas, Udo
    Hannover Medical School.
    Wolf, Gerald
    Otto-von-Guericke-University.
    Andersson, Karl-Erik
    Lund University Hospital.
    Stief, Christian G.
    Ludwig-Maximilians-University.
    Hedlund, Petter
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Immunohistochemical distribution of cyclic GMP-dependent protein kinase-1 in human prostate tissue2007In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 52, no 2, p. 495-501Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Phosphodiesterase 5 (PDE5) inhibitors improve smooth muscle relaxation and therefore are considered for pharmacotherapy of benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS). Cyclic guanosine monophosphate (cGMP)-dependent protein kinase-1 (cGKI) has been identified as one of the downstream targets for cGMP. The aim of the present study was to evaluate, by means of immunohistochemistry and Western blot analysis, the expression and localization of cGKI isoforms in relation to smooth muscle alpha-actin and cGMP in the human prostate.

    METHODS: Cryostat sections of tissue segments excised from the transition zone of human prostates from 11 patients (aged 54-68 yr) were incubated with primary antibodies directed against smooth muscle alpha-actin, cGMP, cGKI, cGKIalpha, and cGKIbeta. Visualization of double-labelled immunofluorescent staining was achieved by laser microscopy. Western blot analysis was performed to confirm the expression of cGKI isoforms.

    RESULTS: Immunoreactivities specific for cGKI, cGKIalpha, and cGKIbeta were observed in the smooth musculature of the transition zone. Double-staining revealed the colocalization of smooth muscle alpha-actin, cGMP, and cGKI isoforms in smooth muscle cells of the fibromuscular stroma. The expression of cGKI isoforms was confirmed by Western blot analysis.

    CONCLUSIONS: Our results confirm the presence of cGKI isoforms alpha and beta in the transition zone of human prostate tissue. In addition, the colocalization of alpha-actin, cGMP, and cGKI isoforms provides further evidence for a significant role of the nitric oxide/cGMP pathway in the regulation of smooth muscle contractility in human prostate tissue and therefore could provide additional targets for pharmacotherapy of BPH and LUTS.

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