| 11. |
- Balakrishnan, N, et al.
(författare)
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Biocompatibility of nitinol and stainless steel in the bladder: An experimental study
- 2005
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Ingår i: Journal of Urology. - : Ovid Technologies (Wolters Kluwer Health). - 1527-3792 .- 0022-5347. ; 173:2, s. 647-650
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: We tested the biocompatibility of nitinol, a nickel titanium alloy, and stainless steel (SS) as bladder implant materials. Materials and Methods: Rats received a nitinol implant, an SS implant or were sham controls. Two, 3, 6 and 8 weeks following implantation 24-hour voiding behavior studies were per-formed to investigate bladder irritation. All animals were sacrificed 8 weeks after implantation and a sample of urine was aspirated for culture. The bladders were examined by light microscopy and scanning electron microscopy (SEM). Results: No visible encrustations or infections were noted in urine. Voiding frequency in the light period 6 weeks after implantation was significantly decreased in the 2 implant groups compared with sham controls. There were no other significant differences in frequency or mean volume per void in the light or dark periods at any time point. Light microscopy demonstrated similar implant tissue effects in all groups with little or no inflammation or fibrosis. Under SEM all implants showed a brittle, amorphous coating devoid of cells. The transition between the urothelium, mucosa and the rod was smoother for SS than for nitinol, suggesting an affinity of SS for mucosa. In all nitinol rods discontinuity was present between the mucosa and rod. Conclusions: Nitinol and SS do not cause more irritation than the effects of surgery alone and the 2 materials seem to be biocompatible in the bladder. Nitinol may be more inert than SS based on SEM results.
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| 12. |
- Boels, P J, et al.
(författare)
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Structure and mechanics of growing arterial microvessels from hypertrophied urinary bladder in the rat
- 1994
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Ingår i: Pflügers Archiv. - 0031-6768. ; 426:6, s. 506-515
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Tidskriftsartikel (refereegranskat)abstract
- Rat bladder hypertrophy, induced by a partial ligation of the urethra, was used to study the accompanying changes of microvascular smooth muscle mechanics, pharmacology and morphology. A segment of a microarterial vessel to the bladder was taken from a defined anatomical location and studied in a wire myograph in vitro at the length for maximal isometric force development (Lmax). After 10 days of ligation, bladder hypertrophy resulted in a microvascular growth response compared to non-operated controls which was characterized by (i) an increase of the calculated diameter at Lmax from 134 +/- 5 microns to 222 +/- 19 microns; (ii) an increase of the media thickness from 22.4 +/- 1.9 microns to 32.2 +2- 3.0 microns; (iii) an increase of the active tension from 1.42 +/- 0.28 mN/mm to 3.06 +/- 0.33 mN/mm; (iv) no change of the wall/lumen ratio (from 0.83 +/- 0.10 to 0.79 +/- 0.15). Normalized length/force relations (active, passive and total) did not differ significantly between microarteries from control and hypertrophic bladders. Microvascular smooth muscle growth was also associated with a decreased sensitivity to K(+)-induced depolarization and an increased sensitivity to alpha 1-adrenergic stimulation. No differences were noted regarding the Ca2+ sensitivity of force during K(+)-induced depolarization. The results suggest that microvascular growth (1) is immediately and positively influenced by the organ growth; (2) results in a functional resetting of the microvascular segments towards larger diameters without gross morphological or mechanical alterations; and (3) is accompanied by pharmacological alterations of the smooth muscle reactivity.
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| 13. |
- Chen, Y, et al.
(författare)
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Increase in insulin-like growth factor I in hypertrophying smooth muscle
- 1994
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Ingår i: American Journal of Physiology - Endocrinology and Metabolism. - 1522-1555. ; 266:2 Pt 1, s. 224-229
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Tidskriftsartikel (refereegranskat)abstract
- The present study focuses on the role of the insulin-like growth factor (IGF) system in the development of smooth muscle hypertrophy. Hypertrophy was initiated by partial ligation of portal vein or urethra in female Sprague-Dawley rats weighing approximately 220 g. Levels of mRNA were analyzed by solution hybridization. Seven days after ligation, the wet weight of the portal vein was increased about threefold and the concentration of IGF-I mRNA was increased fourfold. The bladder wet weight was increased twofold 3 days after ligation and fourfold 10 days after ligation. IGF-I mRNA in the bladder was elevated 3-fold after 3 days and 2.5-fold after 10 days, whereas IGF binding protein 2 mRNA was increased approximately 2-fold after 3 days and 5-fold after 10 days. IGF-I receptor mRNA in the hypertrophying bladder remained unchanged. Increased levels of IGF-I were demonstrated with immunohistochemistry in both hypertrophying portal vein and urinary bladder. The results show a specific increase in IGF-I mRNA as well as an increased IGF-I immunoreactivity during hypertrophy of smooth muscle, which suggests that the local IGF-system may play a role in smooth muscle hypertrophy.
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| 14. |
- Ekman, Mari, et al.
(författare)
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Association of muscarinic M(3) receptors and Kir6.1 with caveolae in human detrusor muscle.
- 2012
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Ingår i: European Journal of Pharmacology. - : Elsevier BV. - 1879-0712 .- 0014-2999. ; 683:1-3, s. 238-245
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Tidskriftsartikel (refereegranskat)abstract
- Caveolae are 50-100nm large membrane invaginations that play a role in cellular signaling. The aim of the present study was to assess whether muscarinic M(3) receptors and the K(ATP) channel subunit Kir6.1 are associated with human detrusor caveolae, and to pharmacologically assess the relevance of this organization for contractility. Detrusor strips were dissected and used in ultrastructural, biochemical and mechanical studies. Caveolae were manipulated by cholesterol desorption using mβcd (methyl-β-cyclodextrin). Mβcd disrupted caveolae and caused a cholesterol-dependent ~3-fold rightward shift of the concentration-response curve for the muscarinic receptor agonist carbachol. The effect of mβcd was inhibited by the K(ATP) blockers glibenclamide, repaglinide and PNU-37883, and it was mimicked by the K(ATP) activator levcromakalim. Immunoelectron microscopy showed muscarinic M(3) receptors and Kir6.1 to be enriched in caveolae. In conclusion, pharmacological K(ATP) channel inhibition antagonizes the effect of caveolae disruption on muscarinic contractility in the human detrusor, and the K(ATP) channel subunit Kir6.1 co-localizes with M(3) receptors in caveolae.
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| 15. |
- Ekman, Mari, et al.
(författare)
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HIF-mediated metabolic switching in bladder outlet obstruction mitigates the relaxing effect of mitochondrial inhibition.
- 2014
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Ingår i: Laboratory Investigation. - : Elsevier BV. - 1530-0307 .- 0023-6837. ; 94:5, s. 557-568
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Tidskriftsartikel (refereegranskat)abstract
- Prior work demonstrated increased levels of hypoxia-inducible factor-1α (HIF-1α) in the bladder following outlet obstruction, associated with bladder growth and fibrosis. Here we hypothesized that HIF induction in outlet obstruction also switches energetic support of contraction from mitochondrial respiration to glycolysis. To address this hypothesis, we created infravesical outlet obstruction in female Sprague-Dawley rats and examined HIF induction and transcriptional activation. HIF-1α increased after 6 weeks of outlet obstruction as assessed by western blotting and yet transcription factor-binding site analysis indicated HIF activation already at 10 days of obstruction. Accumulation HIF-2α and of Arnt2 proteins were found at 10 days, providing an explanation for the lack of correlation between HIF-1α protein and transcriptional activation. HIF signature targets, including Slc2a1, Tpi1, Eno1 and Ldha increased in obstructed compared with sham-operated bladders. The autophagy markers Bnip3 and LC3B-II were also increased at 6 week of obstruction, but electron microscopy did not support mitophagy. Mitochondria were, however, remodeled with increased expression of Cox4 compared with other markers. In keeping with a switch toward glycolytic support of contraction, we found that relaxation by the mitochondrial inhibitor cyanide was reduced in obstructed bladders. This was mimicked by organ culture with the HIF-inducer dimethyloxalylglycine, which also upregulated expression of Ldha. On the basis of these findings, we conclude that HIF activation in outlet obstruction involves mechanisms beyond the accumulation of HIF-1α protein and that it results in a switch of the energetic support of contraction to anaerobic glycolysis. This metabolic adaptation encompasses increased expression of glucose transporters and glycolytic enzymes combined with mitochondrial remodeling. Together, these changes uphold contractility when mitochondrial respiration is limited.Laboratory Investigation advance online publication, 3 March 2014; doi:10.1038/labinvest.2014.48.
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| 16. |
- Ekman, Mari, et al.
(författare)
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MicroRNAs in Bladder Outlet Obstruction: Relationship to Growth and Matrix Remodelling.
- 2016
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Ingår i: Basic & Clinical Pharmacology & Toxicology. - : Wiley. - 1742-7843 .- 1742-7835. ; 119:S3, s. 5-17
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Forskningsöversikt (refereegranskat)abstract
- The discovery of microRNAs (miRNAs), which are ~22 nucleotide RNAs that inhibit protein synthesis in a sequence-specific manner and are present in a range of species, has born hope of new therapeutic strategies. miRNAs play important roles in development "Development" of what??and disease, but they remain poorly studied in uropathologies beyond cancer. Here, we discuss biological functions of miRNAs in the lower urogenital tract. A special focus is on miRNAs that change in bladder outlet obstruction (BOO). This is a condition that affects nearly one third of all men over 60 years and that involves growth and fibrosis of the urinary bladder. Animal models of BOO, such as that in rat, have been developed and they feature a massive 6-fold bladder growth over 6 weeks. Using microarrays, we have charted the miRNAs that change during the time-course of this process and identified several with important modulatory roles. We discuss known and predicted functions of miR-1, miR-29, miR-30, miR-132/212, miR-204 and miR-221, all of which change in BOO. The majority of the miRNA-mediated influences in BOO are expected to favour growth. We also outline evidence that miR-29 represents a key effector molecule in a generic response to mechanical distension that is designed to counteract exaggerated organ deformation via effects on matrix deposition and stiffness. We conclude that miRNAs play important roles in bladder remodelling and growth and that they may be targeted pharmacologically to combat diseases of the lower urinary tract. This article is protected by copyright. All rights reserved.
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| 17. |
- Ekman, Mari, et al.
(författare)
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Mir-29 repression in bladder outlet obstruction contributes to matrix remodeling and altered stiffness.
- 2013
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:12
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Tidskriftsartikel (refereegranskat)abstract
- Recent work has uncovered a role of the microRNA (miRNA) miR-29 in remodeling of the extracellular matrix. Partial bladder outlet obstruction is a prevalent condition in older men with prostate enlargement that leads to matrix synthesis in the lower urinary tract and increases bladder stiffness. Here we tested the hypothesis that miR-29 is repressed in the bladder in outlet obstruction and that this has an impact on protein synthesis and matrix remodeling leading to increased bladder stiffness. c-Myc, NF-κB and SMAD3, all of which repress miR-29, were activated in the rat detrusor following partial bladder outlet obstruction but at different times. c-Myc and NF-κB activation occurred early after obstruction, and SMAD3 phosphorylation increased later, with a significant elevation at 6 weeks. c-Myc, NF-κB and SMAD3 activation, respectively, correlated with repression of miR-29b and miR-29c at 10 days of obstruction and with repression of miR-29c at 6 weeks. An mRNA microarray analysis showed that the reduction of miR-29 following outlet obstruction was associated with increased levels of miR-29 target mRNAs, including mRNAs for tropoelastin, the matricellular protein Sparc and collagen IV. Outlet obstruction increased protein levels of eight out of eight examined miR-29 targets, including tropoelastin and Sparc. Transfection of human bladder smooth muscle cells with antimiR-29c and miR-29c mimic caused reciprocal changes in target protein levels in vitro. Tamoxifen inducible and smooth muscle-specific deletion of Dicer in mice reduced miR-29 expression and increased tropoelastin and the thickness of the basal lamina surrounding smooth muscle cells in the bladder. It also increased detrusor stiffness independent of outlet obstruction. Taken together, our study supports a model where the combined repressive influences of c-Myc, NF-κB and SMAD3 reduce miR-29 in bladder outlet obstruction, and where the resulting drop in miR-29 contributes to matrix remodeling and altered passive mechanical properties of the detrusor.
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| 18. |
- Ekman, Mari, et al.
(författare)
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Neurite outgrowth in cultured mouse pelvic ganglia - Effects of neurotrophins and bladder tissue
- 2017
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Ingår i: Autonomic Neuroscience: Basic & Clinical. - : Elsevier BV. - 1566-0702. ; 205, s. 41-49
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Tidskriftsartikel (refereegranskat)abstract
- Neurotrophic factors regulate survival and growth of neurons. The urinary bladder is innervated via both sympathetic and parasympathetic neurons located in the major pelvic ganglion. The aim of the present study was to characterize the effects of the neurotrophins nerve growth factor (NGF), brain derived neurotrophic factor (BDNF) and neurotrophin 3 (NT-3) on the sprouting rate of sympathetic and parasympathetic neurites from the female mouse ganglion. The pelvic ganglion was dissected out and attached to a petri dish and cultured in vitro. All three factors (BDNF, NT-3 and NGF) stimulated neurite outgrowth of both sympathetic and parasympathetic neurites although BDNF and NT-3 had a higher stimulatory effect on parasympathetic ganglion cells. The neurotrophin receptors TrkA, TrkB and TrkC were all expressed in neurons of the ganglia. Co-culture of ganglia with urinary bladder tissue, but not diaphragm tissue, increased the sprouting rate of neurites. Active forms of BDNF and NT-3 were detected in urinary bladder tissue using western blotting whereas tissue from the diaphragm expressed NGF. Neurite outgrowth from the pelvic ganglion was inhibited by a TrkB receptor antagonist. We therefore suggest that the urinary bladder releases trophic factors, including BDNF and NT-3, which regulate neurite outgrowth via activation of neuronal Trk-receptors. These findings could influence future strategies for developing pharmaceuticals to improve re-innervation due to bladder pathologies.
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| 19. |
- Forsberg, Annika Mandahl, et al.
(författare)
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Open partial nephrectomy for renal cell cancer in a medium patient volume centre: Is high quality possible?
- 2010
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Ingår i: Scandinavian Journal of Urology and Nephrology. - : Informa UK Limited. - 1651-2065 .- 0036-5599. ; 44, s. 204-211
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Objective. To describe the surgical complication rate of open partial nephrectomy (OPN) in patients with renal tumours, and to report the oncological long-term outcome in unilateral renal cell cancer patients subjected to this procedure, from a medium patient volume urological centre. Material and methods. Data from all patients (n = 89) subjected to OPN for proven or suspected renal cell cancer during the period 1965-2007 were registered in a specifically designed database system. Tumour stage and size, surgical margin, histology, perioperative and postoperative complications were analysed in all patients. In addition, long-term follow-up outcomes in malignant unilateral tumours (n = 51) were analysed. Results. Seventy-four of the resected tumours were malignant. Six of these had a positive surgical margin; five from patients with multifocal or bilateral tumours and one from a patient with a solitary malignant cyst. Perioperative complications were registered in only one case (1%). Postoperative complications (within 30 days postoperatively) reached 18%. The long-term follow-up (mean 79 months, median 49 months, range 14 months to 26 years) in patients with unilateral malignant tumours, all staged T1-T2, revealed two systemic recurrences, both in patients with poor prognostic markers at the time of surgery, but no local recurrence. Conclusions. OPN has complication rates similar to open radical nephrectomy. Long-term tumour control in unilateral cases and with organ confined disease is excellent. The results demonstrate that carefully performed OPN at a medium-volume centre can achieve equal results to high-volume centres.
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| 20. |
- Frederiksen, Hans, et al.
(författare)
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Nerve distribution in rat urinary bladder after incorporation of acellular matrix graft or subtotal cystectomy.
- 2008
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Ingår i: Scandinavian Journal of Urology and Nephrology. - : Informa UK Limited. - 0036-5599 .- 1651-2065. ; 42:3, s. 205-212
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Tidskriftsartikel (refereegranskat)abstract
- Objective. In the treatment of reduced bladder capacity, matrix grafts have been used as a scaffold into which cell elements from the native bladder grow, eventually forming a new bladder segment. Functioning motor nerve endings in such segments in the rat have been demonstrated, although little is known about nerve distribution. We compare the pattern of nerve distribution in scaffold-augmented rat bladders with that in bladders regrown after subtotal cystectomy and that in control bladders. Material and methods. Female Sprague-Dawley rats were either subtotally cystectomized (n=7) or had a part of the bladder dome replaced by an acellular collagen (small intestinal submucosa) matrix graft (n=10). Fourteen age-matched, unoperated animals were used as controls. Two and a half to 10 months after surgery the bladders were stained for acetylcholinesterase and studied in wholemounts. Results. No ganglion neurons were observed in any of the bladders. On their ventral side the control bladders showed longitudinal nerve trunks, running in parallel along the longitudinally oriented muscle bundles, while on the lateral and dorsal aspects the nerves were thinner, more irregularly arranged and frequently branched. In the bladders regrown after subtotal cystectomy, the ventral nerves were seen running obliquely to the still longitudinally oriented muscle bundles, resembling the pattern of the normal bladder base; the pattern of the dorsolateral nerves was the same as that in the controls. In the matrix bladders, the muscle and nerve patterns in the native part were the same as those in controls. Muscle bundles were growing into the matrix, accompanied by nerves, which showed limited branching when entering the matrix, usually running in parallel to the muscle, but then branching within the matrix. Conclusions. The nerves in the matrix grafts and the regrown parts of the subtotally cystectomized bladders derive from preexisting nerves in the bladder. In neither case does the nerve trunk or muscle bundle arrangement fully attain the pattern found in normal bladders.
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