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  • 1.
    Andersson, Karl-Erik
    et al.
    Wake Forest University, Winston Salem, North Carolina.
    Uckert, Stefan
    Hannover Medical School.
    Stief, Christian
    Ludwig-Maximilian University, Munich.
    Hedlund, Petter
    Linköpings universitet, Institutionen för medicin och hälsa, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Phosphodiesterases (PDEs) and PDE inhibitors for treatment of LUTS2007Ingår i: Neurourology and Urodynamics, ISSN 0733-2467, E-ISSN 1520-6777, Vol. 26, nr 6, s. 928-933Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Lower urinary tract (LUT) smooth muscle can be relaxed by drugs that increase intracellular concentrations of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). Both of these substances are degraded by phosphodiesterases (PDEs), which play a central role in the regulation of smooth muscle tone. The distribution and functional significance of PDE enzymes vary in different tissues of the LUT. Targeting specific PDE isoenzymes should thus allow organ selectivity. PDE 4 and 5 appear to predominate in the prostate, PDE 1 and 4 are thought to influence detrusor smooth muscle function, and PDE 5 may be functionally important in the urethra and vasculature. Studies on the use of PDE inhibitors to treat various LUT symptoms (LUTS), have yielded favorable results. Thus, positive effects of the PDE 5 inhibitors sildenafil and tadalafil on symptoms and quality of life in men with LUTS, erectile dysfunction, and BPH have also been demonstrated. These effects may be due to effects on cGMP signaling and/or modification of afferent input from bladder, urethral, and prostate tissue. This review gives an update on the distribution of PDEs in structures relevant for LUT function, and discusses how inhibition of these enzymes can contribute to beneficial effects on LUTS. Information for the review was obtained from searches of the PubMed database, and from the authors' files.

  • 2.
    Ask, Per
    et al.
    Linköpings universitet, Institutionen för medicinsk teknik, Fysiologisk mätteknik. Linköpings universitet, Tekniska högskolan.
    Enberg, Anders
    Öberg, Åke
    Spånberg, Anders
    A SHORT-TIME-DELAY URINARY FLOWMETER1985Ingår i: Neurourology and Urodynamics, ISSN 0733-2467, E-ISSN 1520-6777, Vol. 4, nr 3, s. 247-256Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A urinary flowmeter has been designed, using a quickly rotating disc and a balance principle. The flowmeter has a fast and accurate response to changing flows. The time delay of the flowmeter is less than about 0.25 s. The improved accuracy in recording urinary flow using the presented flowmeter should make it possible to extract more information from the detrusor pressure and urinary flow relations, relevant for assessing lower urinary tract function.

  • 3.
    Ask, Per
    et al.
    Linköpings universitet, Institutionen för medicinsk teknik, Fysiologisk mätteknik. Linköpings universitet, Tekniska högskolan.
    Hök, Bertil
    PRESSURE MEASUREMENT TECHNIQUES IN URODYNAMIC INVESTIGATIONS1990Ingår i: Neurourology and Urodynamics, ISSN 0733-2467, E-ISSN 1520-6777, Vol. 9, nr 1, s. 1-15Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    It is apparent that the use of accurate pressure measurement techniques is essential for the outcome of urodynamic investigations. The aim of this paper is to estimate the demands on urodynamic pressure measurements and to review the properties of various techniques used. For the infused catheter technique, the dynamic properties are very much dependent on the complicance of the infusion system. With optimal infusion, the bandwidth and the pressure rise rate seem to be sufficient for most applications. Intraluminal microtransducers have a high bandwidth, but a certain fiber optic transducer cannot accurately measure mechanical pressure in the collapsed urethra. The principal differences in measuring hydrostatic pressure between the infused catheter technique and microtransducers should be observed. Flexion artefacts are a problem when measuring urethral pressure profiles. Newly developed transducers may offer a solution to this problem.

  • 4.
    Chen, Hui
    et al.
    Guangzhou Med Univ, Peoples R China; Jinan Univ, Peoples R China.
    Zeng, Jianwen
    Guangzhou Med Univ, Peoples R China.
    Zeng, Peng
    Guangzhou Med Univ, Peoples R China.
    Jiang, Chonghe
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Guangzhou Med Univ, Peoples R China.
    Xie, Keji
    Guangzhou First Peoples Hosp, Peoples R China.
    Lindström, Sivert
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Repeat periods of electrical stimulation prolong the modulation of the micturition reflex in the rat2018Ingår i: Neurourology and Urodynamics, ISSN 0733-2467, E-ISSN 1520-6777, Vol. 37, nr 8, s. 2480-2486Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    AimsMethodsThe aim of this study was to determine if the duration of the micturition reflex modulation could be prolonged by repeated periods of afferent stimulation in the decorticated rat. Eighteen female Sprague-Dawley rats were used for the study, 10 for intravesical electrical stimulation (IVES), and 8 for Ano-genital pudendal afferents stimulation. Repeated constant flow cystometries were performed with body-warm saline (0.06-0.1mL/min) at about 10min interval. The selected afferents were stimulated continuously for 5min at maximal intensity. The same stimulation was repeated six times with a pause of 5min between the stimulations. The mean threshold volume of cystometries performed during one hour before and each hour after the stimulation were compared. ResultsConclusionsAfter six periods of IVES, the micturition threshold volume decreased to its lowest value (62% of control) during the first hour and remained at 80% 4h later (n=10, Pamp;lt;0.01). Ano-genital afferent stimulation produced a corresponding increase in the micturition threshold volume. The long-lasting poststimulation effect was again observed for more than 5h. During the first hour the mean threshold volume increased to 211% of controls and it remained at about this level for the entire observation period (n=8, Pamp;lt;0.01). Repeated short periods of stimulation prolonged the modulatory effect well beyond the stimulation period. The findings provide experimental evidence supporting the clinical application of IVES and ano-genital stimulation for treatment of neurogenic urinary bladder dysfunction.

  • 5.
    Fuellhase, Claudius
    et al.
    University of Rostock, Germany; University of Munich, Germany.
    Schreiber, Andrea
    University of Munich, Germany; University of Munich, Germany.
    Giese, Armin
    University of Munich, Germany.
    Schmidt, Michael
    University of Munich, Germany.
    Montorsi, Francesco
    University of Milan, Italy; University of Vita San Raffaele, Italy.
    Gratzke, Christian
    University of Munich, Germany.
    La Croce, Giovanni
    University of Milan, Italy; Lund University, Sweden.
    Castiglione, Fabio
    University of Vita San Raffaele, Italy; Lund University, Sweden.
    Stief, Christian
    University of Munich, Germany.
    Hedlund, Petter
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk farmakologi. University of Milan, Italy.
    Spinal neuronal cannabinoid receptors mediate urodynamic effects of systemic fatty acid amide hydrolase (FAAH) inhibition in rats2016Ingår i: Neurourology and Urodynamics, ISSN 0733-2467, E-ISSN 1520-6777, Vol. 35, nr 4, s. 464-470Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    AimsTo test if urodynamic effects from systemic Fatty Acid Amide Hydrolase (FAAH) inhibition involve sacral spinal cannabinoid type 1 (CB1) or type 2 (CB2) receptors. MethodsMale rats with or without partial urethral obstruction were used for cystometry or immunohistochemistry. Urodynamic effects of intravenous (IV) 0.3mg/kg Oleoyl Ethyl Amide (OEtA; FAAH inhibitor), and intrathecal (IT) 5g rimonabant (CB1 antagonist) or 5g SR144528 (CB2 antagonist) were studied in awake rats. ResultsAfter administration of rimonabant or SR144528, non-obstructed rats with normal bladder function developed bladder overactivity (BO), which was counteracted by OEtA. OEtA also counteracted BO in obstructed rats. SR144528 did not affect bladder function in obstructed rats but counteracted the urodynamic effects of OEtA. Surprisingly, rimonabant (and AM251, another CB1 antagonist) reduced BO in obstructed rats, whereafter OEtA produced no additional urodynamic effects. CB1 expression increased in the sacral spinal cord of obstructed rats whereas no changes were observed for CB2 or FAAH. ConclusionsUrodynamic effects of systemic FAAH inhibition involve activities at spinal neuronal CB1 and CB2 receptors in normal and obstructed rats. Endogenous spinal CB receptor ligands seem to regulate normal micturition and BO. Altered spinal CB receptor functions may be involved in the pathogenesis of obstruction-induced BO. Neurourol. Urodynam. 35:464-470, 2016. (c) 2015 Wiley Periodicals, Inc.

  • 6.
    Gandaglia, G.
    et al.
    San Raffaele Scientific Institute, Milan, Italy.
    Strittmatter, F.
    Lund University, Sweden.
    La Croce, G.
    San Raffaele Scientific Institute, Milan, Italy.
    Benigni, F.
    San Raffaele Scientific Institute, Milan, Italy.
    Bettiga, A.
    San Raffaele Scientific Institute, Milan, Italy.
    Castiglione, F.
    San Raffaele Scientific Institute, Milan, Italy.
    Moschini, M.
    San Raffaele Scientific Institute, Milan, Italy.
    Mistretta, F.
    San Raffaele Scientific Institute, Milan, Italy.
    Gratzke, C.
    Munich University, Germany.
    Montorsi, F.
    San Raffaele Scientific Institute, Milan, Italy.
    Stief, C.
    Munich University, Germany.
    Hedlund, Petter
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk farmakologi.
    The fatty acid amide hydrolase inhibitor oleoyl ethyl amide counteracts bladder overactivity in female rats2014Ingår i: Neurourology and Urodynamics, ISSN 0733-2467, E-ISSN 1520-6777, Vol. 33, nr 8, s. 1251-1258Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    AIMS:

    To study micturition and bladder overactivity in female rats after chronic treatment with the fatty acid amide hydrolase (FAAH) inhibitor oleoyl ethyl amide (OEtA).

    METHODS:

    Sprague-Dawley rats received daily subcutaneous injections of OEtA (0.3 mg/kg), or vehicle for 2 weeks. Cystometries, organ bath studies, Western blot, and immunofluorescence were then used. Expressions of FAAH, cannabinoid 1 and 2 receptors (CB1 and CB2), mitogen-activated protein kinase (MAPK), vesicular acetyl choline-transporter protein (VAChT), and calcitonin gene-related peptide (CGRP) were evaluated.

    RESULTS:

    At baseline, OEtA-treated rats had higher values (P < 0.05) of micturition intervals (MI) and volumes (MV), bladder capacity (BC), threshold pressure, and flow pressure than vehicle controls. Intravesical PGE2 reduced MI, MV, and BC, and increased basal pressure and the area under the curve in all rats. However, these urodynamic parameters were altered less by intravesical PGE2 in OEtA-treated rats (P < 0.05 vs. vehicle controls). Compared to vehicle controls, detrusor from OEtA-treated rats had larger contractions to carbachol at 10-0.1 µM, but no difference in Emax was recorded. FAAH, CB1, CB2, VAChT, or CGRP was similarly expressed in bladders from all rats. In separate experiments, intravesical OEtA increased mucosal expression of phosphorylated MAPK.

    CONCLUSIONS:

    Chronic FAAH inhibition altered sensory urodynamic parameters and reduced bladder overactivity. Even if it cannot be excluded that OEtA may act on central nervous sensory pathways to contribute to these effects, the presence of FAAH and CB receptors in the bladder and activation of intracellular signals for CB receptors by intravesical OEtA suggest a local role for FAAH in micturition control. Neurourol. Urodynam

  • 7.
    Gladh, Gunilla
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Effect of thoughtful preparation on the catheterization of children undergoing investigative studies2003Ingår i: Neurourology and Urodynamics, ISSN 0733-2467, E-ISSN 1520-6777, Vol. 22, nr 1, s. 58-61Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aims:

    To evaluate an anesthetic sedation free method of transurethral catheterization in children.

    Methods:

    The child and his or her parents are thoroughly prepared for the procedure by means of written and oral child-adapted information and practical instructions. To evaluate this routine, a simple questionnaire was given to 115 consecutive children undergoing transurethral catheterization.

    Results:

    The questionnaire was returned by 99 children (86%). Most children and parents (95) found the preparation“good”or“very good”and tolerated the catheterization procedure well. Only six children reported the catheterization to be“very painful”(without requiring that the procedure was terminated). Complications, such as urgency, smarting pain during voidings, or both, after withdrawal of the catheter, occurred in 12 children and urinary tract infections in 3. Unexpectedly, girls were affected more often than boys.

    Conclusions:

    Careful preparation of children and their parents allows the great majority of diagnostic studies that require urethral catheterization to be accomplished without anesthesia. Neurourol. Urodynam. 22:58–61, 2003. © 2003 Wiley-Liss, Inc.

  • 8.
    Gladh, Gunilla
    et al.
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Mattsson, Sven
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Lindström, Sivert
    Linköpings universitet, Institutionen för biomedicin och kirurgi. Linköpings universitet, Hälsouniversitetet.
    Intravesical electrical stimulation in the treatment of micturition dysfunction in children2003Ingår i: Neurourology and Urodynamics, ISSN 0733-2467, E-ISSN 1520-6777, Vol. 22, nr 3, s. 233-242Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aims To evaluate the results of intravesical electrical stimulation (IVES) in an open prospective study to treat underactive detrusor in children. The treatment was offered as an alternative to clean intermittent catheterization (CIC).

    Methods Forty-four children were included, 21 girls and 3 boys (6–16 years, md 10) with idiopathic, 9 girls and 11 boys (4–18 years; md 13) with neurogenic underactive detrusor. IVES was given by a catheter electrode in the bladder (cathode) with the anode attached to the suprapubic abdominal skin. Continuous stimulation at 20 or 25 Hz was delivered by battery powered stimulators giving unipolar square-wave pulses (0,2 or 0,7 ms). Stimulation intensity was adjusted individually according to the acceptance of the child (12–64 mA). IVES was initially given at the clinic but 18 children had additional treatment at home. Effect of treatment was monitored by micturiton/incontinence diary, reports of bladder sensation, recordings of urinary flow, residual volume and frequency of urinary tract infections.

    Results The IVES-treatment was completed by 39/44 children. Long term normalization of the voiding (md 2,5 years follow up) was obtained for 20/24 children with idiopathic problems (83%) and 8/20 with neurogenic problems (40%). Another four had much improved bladder function. The neurogenic group required more stimulation sessions than the idiopathic group. Of those on CIC, 11/15 who completed IVES could discontinue the catheterization. The frequency of urinary tract infections and incontinence decreased significantly (P < 0.01).

    Conclusions It is concluded that IVES is a promising method to treat the underactive detrusor in children.

  • 9.
    Gladh, Gunilla
    et al.
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Persson, D.
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Mattsson, Sven
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Lindström, Sivert
    Linköpings universitet, Institutionen för biomedicin och kirurgi. Linköpings universitet, Hälsouniversitetet.
    Voiding pattern in healthy newborns2000Ingår i: Neurourology and Urodynamics, ISSN 0733-2467, E-ISSN 1520-6777, Vol. 19, nr 2, s. 177-184Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A 4-hour observation period has been used in infants to investigate suspected bladder dysfunction. The aim of the present study was to extend the usefulness of this protocol by establishing reference values for voiding frequency, intervals, volumes, and residual urine in healthy newborns. The study included 51 healthy newborns, 26 girls and 25 boys, aged 3 to 14 days. During a 4-hour period, all micturitions and residuals were recorded as well as feeding, sleeping, crying, and defecations. The observation was completed with the child undressed to observe the urinary stream during one void. Different provocation tests were tried to induce urinary leakage. All newborns voided with a stream, about once per hour, with a median volume of 23 mL. For each voiding parameter, there was a large inter- and intra-individual variability. Double voidings were common as well as sizable residual volumes. The diuresis was about six times higher than in healthy school children. The healthy newborns did not leak during provocation tests such as manual compression of the bladder.

  • 10.
    Hedlund, Petter
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk farmakologi.
    Cannabinoids and the Endocannabinoid System in Lower Urinary Tract Function and Dysfunction2014Ingår i: Neurourology and Urodynamics, ISSN 0733-2467, E-ISSN 1520-6777, Vol. 33, nr 1, s. 46-53Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    AimsTo review knowledge on cannabinoids and the endocannabinoid system in lower urinary tract function and dysfunction. MethodsReview of MEDLINE using defined search terms, and manual analysis. Articles published in English were included. Results and DiscussionComponents of the endocannabinoid systemcannabinoid (CB) receptor types 1 and 2, anandamide, and fatty acid amide hydrolase (FAAH), which degrades anandamide and related fatty-acid amideshave been located to lower urinary tract tissues of mice, rats, monkeys, and humans. Studies have located CB receptors in urothelium and sensory nerves and FAAH in the urothelium. CB receptor- and FAAH-related activities have also been reported in the lumbosacral spinal cord. Data on supraspinal CB functions in relation to micturition are lacking. Cannabinoids are reported to reduce sensory activity of isolated tissues, cause antihyperalgesia in animal studies of bladder inflammation, affect urodynamics parameters reflecting sensory functions in animals models, and appear to have effects on storage symptoms in humans. FAAH inhibitors have affected sensory bladder functions and reduced bladder overactivity in rat models. Cannabinoids may modify nerve-mediated functions of isolated lower urinary tract tissues. ConclusionsEvidence suggests components of the endocannabinoid system are involved in regulation of bladder function, possibly at several levels of the micturition pathway. It is unclear if either CB receptor has a dominant role in modification of sensory signals or if differences exist at peripheral and central nervous sites. Amplification of endocannabinoid activity by FAAH inhibitors may be an attractive drug target in specific pathways involved in LUTS.

  • 11.
    Jiang, Chong-He
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Modulation of the micturition reflex pathway by intravesical electrical stimulation: An experimental study in the rat1998Ingår i: Neurourology and Urodynamics, ISSN 0733-2467, E-ISSN 1520-6777, Vol. 17, nr 5, s. 543-554Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Intravesical electrical stimulation (IVES) is used clinically to improve bladder evacuation in patients with inadequate micturition contractions. The procedure involves field stimulation of A bladder mechanoreceptor afferents resulting in a prolonged enhancement of the micturition reflex. The aim of the present experimental study in the rat was to identify the site for this neuromodulation, whether it was due to sensitization of bladder mechanoreceptors, to enhancement of transmission in the central micturition reflex pathway, or to improved effectiveness of the peripheral motor system of the bladder. The experiments were performed on female rats, anesthetized by -chloralose. Multi-unit afferent or efferent activity was recorded from bladder pelvic nerve branches during repeated cystometries before and after IVES. The specific antagonist CPPene was used to block central glutaminergic receptors of NMDA type. Micturition threshold volume decreased significantly after IVES. The afferent threshold volume, peak response, and pressure sensitivity were unchanged as were the peak efferent activity and bladder contractility. There was no efferent activity until just before the micturition contraction. The IVES-induced decrease in micturition threshold was blocked by prior administration of the NMDA (N-methyl-D-aspartic acid) antagonist CPPene (3-(2-carboxypiperazin-4-yl)-1-propenyl-1-phosphonic acid). The findings indicate that the IVES-induced modulation of the micturition reflex is due to an enhanced excitatory synaptic transmission in the central micturition reflex pathway. The observed modulation may account for the clinical beneficial effect of IVES treatment.

  • 12.
    Lee, Tack
    et al.
    Lund University Hospital.
    Andersson, Karl-Erik
    Wake Forest University, Winston Salem, North Carolina.
    Streng, Torni
    Lund University Hospital.
    Hedlund, Petter
    Linköpings universitet, Institutionen för medicin och hälsa, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Simultaneous registration of intraabdominal and intravesical pressures during cystometry in conscious rats-effects of bladder outlet obstruction and intravesical PGE(2)2008Ingår i: Neurourology and Urodynamics, ISSN 0733-2467, E-ISSN 1520-6777, Vol. 27, nr 1, s. 88-95Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    AIMS: A method was developed and evaluated to simultaneously register intraabdominal pressure (IAP) and intravesical pressure (IVP) during cystometry in conscious rats. In addition, IAP and IVP were recorded in rats with experimental detrusor overactivity (DO).

    METHODS: Sprague Dawley rats (n = 24) were used. Six female rats were subjected to partial bladder outlet obstruction for 2 weeks. A catheter was implanted into the bladder to record the IVP, and a balloon-fitted catheter was positioned in the abdominal cavity to record the IAP. PGE(2) was given intravesically to induce DO. Detrusor pressure (DP) was defined as the IVP corrected for IAP.

    RESULTS: Recorded as increases in IAP, all rats of both sexes exhibited abdominal straining during every void. In controls, a maximal IAP of 6.0 +/- 1.4 cmH(2)O (range 3-15 cmH(2)O) was registered (n = 12) at the time of the flow pressure (FP). Intravesical administration of PGE(2) or BOO did not affect the IAP at basal pressure, FP or micturition pressure. Changes in IAP due to movement or non-voiding-related straining were subtracted from IVP to generate DP and to visualize DO after BOO or intravesical PGE(2).

    CONCLUSIONS: The conscious rat uses abdominal straining during voiding, and maximal IAP is recorded at the onset of urinary flow. Simultaneous registration of IAP and IVP during the micturition cycle in conscious rats is a convenient method for accurate quantification of pressures inside the bladder and for studying "true" DO without interference from movement artifacts

  • 13.
    Li, Longkun
    et al.
    Third Military Medical University, Chongqing.
    Jiang, Chonghe
    Medical College of Hunan Normal University.
    Hao, Ping
    Third Military Medical University, Chongqing.
    Li, Weibing
    Third Military Medical University, Chongqing.
    Fan, Lixin
    Third Military Medical University, Chongqing.
    Zhou, Zhansong
    Third Military Medical University, Chongqing.
    Song, Bo
    Third Military Medical University, Chongqing.
    Changes in T-type calcium channel and its subtypes in overactive detrusor of the rats with partial bladder outflow obstruction2007Ingår i: Neurourology and Urodynamics, ISSN 0733-2467, E-ISSN 1520-6777, Vol. 26, nr 6, s. 870-878Artikel i tidskrift (Refereegranskat)
    Abstract [en]

       AimsTo investigate the activity of the T-type calcium channel (TCC) and the expression of its subtypes in overactive detrusor (OD) myocytes in rats after partial bladder outflow obstruction (PBOO).MethodsThirteen male Wistar rats with OD after PBOO (OD group) and eight sham-operated rats (control group) were studied. The two groups were compared regarding the expression of TCC subtype genes by reverse transcription-polymerase chain reaction (RT-PCR) and the TCC kinetics and cell action potential by whole-cell patch-clamp.ResultsThe time course and density of the current were significantly higher in the OD cells than those in the control detrusor. Whole-cell patch-clamp analysis showed that the activation of TCCs in detrusor myocytes in the OD group was faster than the control group, but inactivation was almost the same in both groups, suggesting a significant enhancement of the Ca2+ window current in the OD group. Patch-clamp recording of action potentials in the OD cells indicated an increase in excitability and a decrease in the repolarization interval. RT-PCR assay showed an abnormal expression of 1G subtype in the OD cells.ConclusionsTCCs could be one of the crucial factors for the abnormal excitation in OD cells. The development of OD after PBOO presumably relates to the increase in TCC current in the bladder cells, the enhancement of the Ca2+ window current for Ca2+ inflow, the prolongation of the intracellular calcium oscillations, and the acceleration of the cell depolarization.

  • 14. Schäfer, Werner
    et al.
    Abrams, Paul
    Liao, Limin
    Mattiasson, Anders
    Pesce, Francesco
    Spångberg, Anders
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Urologi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Urologiska kliniken i Östergötland.
    Sterling, Arthur
    Zinner, Norman
    van Kerrebroeck, Philip
    Good urodynamic practices: Uroflowmetry, filling cystometry, and pressure-flow studies2002Ingår i: Neurourology and Urodynamics, ISSN 0733-2467, E-ISSN 1520-6777, Vol. 21, s. 261-274Artikel i tidskrift (Refereegranskat)
  • 15.
    Semerdzhiev, Y
    et al.
    Lund University Hospital.
    Frederiksen, H
    Lund University Hospital.
    Hedlund, Petter
    Lund University Hospital.
    Davidsson, T
    Lund University Hospital.
    Mansson, W
    Lund University Hospital.
    Uvelius, B
    Lund University Hospital.
    Cystometric and in vitro muscle studies of cystoplastic appendiceal segments in the rat2006Ingår i: Neurourology and Urodynamics, ISSN 0733-2467, E-ISSN 1520-6777, Vol. 25, nr 3, s. 259-267Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    AIMS: The functional integration of the smooth muscle of enterocystoplasties into the detrusor muscle was investigated in an awake-rat cystometry model and in vitro.

    METHODS: The upper fourth of the bladder was removed, and a detubularized appendiceal segment (7 x 7 mm), with preserved vasculature, was incorporated into the bladder. After 1 or 3 months, a catheter was fixed to the top of the bladders. After a 3-day recovery, cystometries were performed. In separate experiments, agonist and nerve-induced responses were evaluated on isolated bladder strips.

    RESULTS: Cystometries revealed reduced basal pressure and micturition pressure in enterocystoplasty (ECP) bladders. Bladder capacity and micturition volume were increased. Threshold pressure (pressure immediately before micturition) was significantly lower at 1 month, but not at 3 months. Bladder compliance was significantly higher in the operated at 1 month but not at 3 months. Threshold tension did not differ between control and corresponding operated groups. Residual urine was significantly higher in the operated groups. ECP strips showed increased maximal contractions to nerve stimulation, to levels similar to those of detrusor strips. Maximal responses to carbachol increased to levels between those of intestine and detrusor. The inhibitory effect of scopolamine on nerve induced contractions increased to levels similar to those for detrusor. Purinergic activation had no effect on intestinal or ECP strips, but contracted detrusor muscle.

    CONCLUSIONS: The smooth muscle of the bowel segment in rat ECP bladders underwent a partial change in the response to nerve stimulation from that of intestine towards that of detrusor. The cystometry experiments suggested a partial functional integration of the ECP segment into the detrusor.

  • 16. Språngberg, Anders
    et al.
    TERIO, Heikki
    Ask, Per
    Linköpings universitet, Institutionen för medicinsk teknik, Fysiologisk mätteknik. Linköpings universitet, Tekniska högskolan.
    ENGBERG, Anders
    Griffiths, Derek
    PRESSURE-FLOW STUDIES PREOPERATIVELY AND POSTOPERATIVELY IN PATIENTS WITH BENIGN PROSTATIC HYPERTROPHY - ESTIMATION OF THE URETHRAL PRESSURE-FLOW RELATION AND URETHRAL ELASTICITY1991Ingår i: Neurourology and Urodynamics, ISSN 0733-2467, E-ISSN 1520-6777, Vol. 10, nr 2, s. 139-167Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Pressure/flow studies were performed in 28 men with benign prostatic hypertrophy. Twenty-three of the men were also studied postoperatively. Urethral function during micturition was quantified by the urethral pressure/flow relation, P(det) = P(mo) + L(m) Q(m), where P(det) is detrusor pressure, P(mo) is minimal opening pressure, Q is flow rate, and m and L(m) are parameters. Using this method to quantify urethral function, three urodynamically different types of obstruction can be defined. In the first of these, P(mo) is elevated corresponding to Schafer’s compressive obstruction. The second is a constrictive type of obstruction in which m greater-than-or-equal-to 4/3 and L(m) is elevated and the third is a low-compliant type of obstruction in which m less-than-or-equal-to 1 and L(m) is elevated. The two latter types of obstruction may be combined with a compressive obstruction. The preoperative pressure/flow relations were mostly characterized by a very high P(mo), a moderately elevated L(m), and a low m. Thus the majority of patients had a combination of compressive and low-compliant obstruction. Postoperatively, micturitions were much improved and the pressure/flow relations often had an even lower P(mo) than normal, a normal L(m), and a high m. From the pressure/flow relations, the elasticity of the flow-controlling zone can be estimated and described by the urethral pressure/area relation, p(A) = P(mo) + K(n) A(n), where p(A) is the intrinsic urethral pressure, A is the cross-sectional area of the flow-controlling zone and K(n) and n are parameters describing the distensibility of the flow-controlling zone. Preoperatively, the flow-controlling zone had a low distensibility. The shape of the curve suggested that the urethra could have been distended further by higher pressure. Postoperatively, the urethra was distended to larger cross-sectional areas, but in many cases the shape of the curve suggested that distension was restricted by fibrosis. Median and range values for the model parameters as well as discriminating limits between the preoperative micturitions and micturitions in elderly men without voiding problems are presented. The exponent m is not perfectly reproducible but tends to be the same if a person performs several micturitions. The residual sum of squares is often increased more than 100% if an exponent m value other than the optimal one is used for curve fitting. Results when the micturitions were analysed with Schafer’s model and classified using the maximum flow/pressure at maximum flow diagram recommended by the International Continence Society are also shown.

  • 17. Spånberg, Anders
    et al.
    Terio, Hikki
    Ask, Per
    Linköpings universitet, Institutionen för medicinsk teknik, Fysiologisk mätteknik. Linköpings universitet, Tekniska högskolan.
    PRESSURE-FLOW STUDIES IN ELDERLY MEN WITHOUT VOIDING PROBLEMS - ESTIMATION OF THE URETHRAL PRESSURE-FLOW RELATION AND URETHRAL ELASTICITY1990Ingår i: Neurourology and Urodynamics, ISSN 0733-2467, E-ISSN 1520-6777, Vol. 9, nr 2, s. 123-138Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The flow in the urethra is controlled by an elastic constriction, the flow-controlling zone. The distensibility of this zone is described by the pressure/area relation, which gives the static pressure as a function of the cross-sectional area at the flow-controlling zone. The pressure/area relation can be calculated from the pressure/flow relation, which is estimated from the pressure/flow plot obtained at a urodynamic examination. In this study the urethral pressure/flow and pressure/area relations were estimated for 21 randomly selected men (62–75 years old) without voiding problems.

    Nineteen of 21 persons in this group had pressure/flow relations with a low slope. This corresponds to a low slope in the pressure/area relation indicating high distensibility of the flow-controlling zone, which for 18 persons was estimated to be distended to areas larger than 10 mm2 during micturition. Twenty persons had a minimal urethral opening pressure below 55 cm H2O. The estimated pressure/area relation was linear in 59% of the micturitions, indicating that the flow-controlling zone could have been distended to a larger cross-sectional area, if the bladder had achieved a higher pressure. The 10th–90th percentiles for maximum flow and detrusor pressure at maximum flow were 7.2–24.3 ml/s and 24–76 cm H2O, respectively. Four persons had low flow and low pressure, indicating diminished detrusor contractility with age. Twenty-four percent of the persons had unstable bladder contractions with a pressure rise < 15cm H2O and 19% with a pressure rise < 15cm H2O.

  • 18. Spånberg, Anders
    et al.
    Terio, Hikki
    Enberg, Anders
    Ask, Per
    Linköpings universitet, Institutionen för medicinsk teknik, Fysiologisk mätteknik. Linköpings universitet, Tekniska högskolan.
    QUANTIFICATION OF URETHRAL FUNCTION BASED ON GRIFFITHS MODEL OF FLOW THROUGH ELASTIC TUBES1989Ingår i: Neurourology and Urodynamics, ISSN 0733-2467, E-ISSN 1520-6777, Vol. 8, nr 1, s. 29-52Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Griffiths' model of flow-through elastic tubes makes it possible to relate the elastic properties of the flow-controlling zone to the pressure/flow relation of the urethra. In this work the pressure function p(A) = Pmo + Kn An, where A is cross-sectional area, Pmo the minimal opening pressure, and Kn and n parameters describing urethral distensibility, describes the elastic properties of the flow-controlling zone. By curve-fitting in the pressure/flow plot, the three parameters pmo, Kn, and n can be estimated analytically. Using this model it is possible to identify three different biomechanical changes that may cause obstruction. First, pmo may be elevated. Second, the urethra can be distended to a certain area only, corresponding to high values of Kn and n. Third, the urethra can be distended but a higher-than-normal pressure increase above Pmo is needed, Kn is high, and n is low. With this model it is possible to quantify urethral function for both scientific and clinical purposes.

  • 19.
    Spångberg, Anders
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Urologi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Urologiska kliniken i Östergötland.
    Variability of pressure-flow studies in men with lower urinary tract symptoms - Editorial Comment2000Ingår i: Neurourology and Urodynamics, ISSN 0733-2467, E-ISSN 1520-6777, Vol. 19, nr 6, s. 653-656Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Abstract Not Available

  • 20.
    Weinhold, Philipp
    et al.
    Department of Urology, LMU, Munich,Germany; Department of Clinical and Experimental Pharmacology, Lund, Sweden.
    Hennenberg, Martin
    Department of Urology, LMU, Munich,Germany.
    Strittmatter, Frank
    Department of Urology, LMU, Munich,Germany.
    Stief, Christian G
    Department of Urology, LMU, Munich,Germany.
    Gratzke, Christian
    Department of Urology, LMU, Munich,Germany.
    Hedlund, Petter
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk farmakologi. Department of Clinical and Experimental Pharmacology, Lund, Sweden.
    Transient receptor potential a1 (TRPA1) agonists inhibit contractions of the isolated human ureter.2018Ingår i: Neurourology and Urodynamics, ISSN 0733-2467, E-ISSN 1520-6777, Vol. 37, nr 2, s. 600-608Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    AIMS: Mechanoafferent and peristaltic mechanisms of the human ureter involve transient receptor potential V1 (TRPV1)- and purinoceptor-mediated functions. Hydrogen sulphide, an endogenous TRPA1 ligand, is linked to inhibitory neurotransmission of the pig ureter. No information is available on TRPA1 activity in the human ureter. We therefore examined the distribution and function of TRPA1 in the human ureter.

    METHODS: Expression of TRPA1 in human ureter tissue was studied by Western blot and immunofluorescence. The TRPA1 distribution was compared to TRPV1, calcitonin gene related peptide (CGRP), tyrosine hydroxylase (TH), and vimentin. Effects of the TRPA1 agonists allyl isothiocyanate (AI), cinnamaldehyde (CA), sodium hydrogen sulfide (NaHS), and capsaicin (TRPV1 agonist) on human ureter preparations were studied in organ baths.

    RESULTS: By Western blot, bands were detected at the expected molecular weight for TRPA1. TRPA1- and TRPV1-immunoreactivities were located on CGRP-positive nerves, but not on TH-positive nerves. TRPA1 was also located in vimentin-positive interstitial cells. In functional experiments, neither of the TRPA1-agonists (1-100 μM) had any direct effects on ureter tension (baseline/potassium-induced contractions). However, CA, AI, NaHS, and capsaicin (10 μM) decreased (P < 0.01-0.05) tetrodotoxin-sensitive electrically induced (2,4,8,16,32 Hz) contractions. Inhibitory activities were 50-61% (CA), 30-56% (AI), 30-40% (NaHS), and 37-67% (Capsaicin).

    CONCLUSIONS: In the human ureter, TRPA1 is located to sensory nerves and interstitial cells. TRPA1 agonists inhibited electrically induced contractions but had no direct effect on smooth muscle tension of the human ureter. A role for TRPA1 in modulating neurotransmission and possibly peristalsis of the human ureter is proposed.

  • 21.
    Zeng, Jianwen
    et al.
    Jinan University.
    Xie, Keji
    Guangzhou City Peoples Hospital 1.
    Jiang, Chonghe
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Mo, Jianfeng
    Jinan University.
    Lindström, Sivert
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Bladder mechanoreceptor changes after artificial bladder outlet obstruction in the anesthetized rat2012Ingår i: Neurourology and Urodynamics, ISSN 0733-2467, E-ISSN 1520-6777, Vol. 31, nr 1, s. 178-184Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aims Experimental animal models of bladder outlet obstruction (BOO) have reproduced several features of BOO in man, i.e., detrusor hypertrophy, instability, frequency, and residual urine. This study was focused on the mechanisms underlying the development of residual urine in patient with benign prostatic hyperplasia (BPH) by examining changes in tension sensitivity of bladder mechanoreceptors in rat model. Methods: Female adult Sprague-Dawley rats including 12 BOO and 17 sham operated rats were used in this study. Cystometrograms together with the bladder afferent activity were recorded. Tension sensitivity of the afferents was determined by plotting the normalized afferent response against the contraction evoked bladder pressure at different volumes. Degree of obstruction was assessed by the wet weight of the bladder at the end of the experiment. Results: The bladder weight, maximal bladder capacity, micturition threshold volume, peak contraction force, and volume at peak contraction force were all significantly increased in obstructed animals. The threshold volume for afferent activation was increased ( mean 0.60 ml compared to 0.15 ml in controls; P andlt; 0.001), positively correlated with the bladder weight ( r 0.74). The tension sensitivity of the bladder mechanoreceptors and the slope of their normalized pressure-response functions were significantly lower at the comparable volumes in the obstructed animals. Conclusions: Rats with BOO had bladder mechanoreceptors with higher threshold volumes and lower tension sensitivity. Such changes would result in a weaker afferent drive of the micturition reflex. Similar changes may contribute to the development of residual urine and retention in patients with BOO. Neurourol. Urodynam. 31: 178-184, 2012. (C) 2011 Wiley Periodicals, Inc.

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