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- Aronsson, Patrik, 1983, et al.
(författare)
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Cyclophosphamide-induced alterations of the micturition reflex in a novel in situ urinary bladder model in the anesthetized rat
- 2015
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Ingår i: Neurourology and Urodynamics. - : Wiley. - 0733-2467. ; 34:4, s. 375-380
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Cyclophosphamide-induced cystitis alterations have been reported to occur both at efferent and afferent level in the micturition reflex arc. In particular, the stretching of the bladder wall causing urothelial release of ATP has been proposed as one of the pivotal mechanisms causing these alterations. To evaluate functional changes at efferent and afferent levels of the micturition reflex following cyclophosphamide treatment we have applied a novel in situ half bladder rat model. Methods: Male Sprague-Dawley rats were treated with either saline or cyclophosphamide (100mg/kg), and stretch-, electric-, methacholine-, and ATP-induced responses were thereafter measured at 60-72hr postinjection under pentobarbitone anesthesia. In the novel in situ half bladder model, the urinary bladder was prepared via a midline incision, where the two halves were separated all the way to the urethra as previously described. Results: Following bladder stretch of 30-80mN, of the half that was not used for tension measurement, the cyclophosphamide-treated animals evoked significant two- to threefold larger contractile responses as compared to saline-treated control animals. A sensitization of the afferent arm was shown in cyclophosphamide-treated animals, since afferent stimulation evoked similar responses as in control animals despite that the efferent pelvic nerve stimulation displayed a lower contraction-frequency relationship in cyclophosphamide-treated animals. Atropine reduced the stretch(reflex)-evoked contraction by up to 50% in control and 75-80% in cyclophosphamide-treated rats. Subsequent addition of PPADS further reduced the contractions. Conclusion: The micturition reflex response is increased following cyclophosphamide-induced cystitis, as compared to control. The likely cause is sensitization at mechanosensor level in the micturition arc, which overrides the decrement of the efferent cholinergic effects. © 2014 Wiley Periodicals, Inc.
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- Aronsson, Patrik, 1983, et al.
(författare)
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Patterns in Swedish pharmacy students' performance and attitudes towards their education
- 2019
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Ingår i: Currents in Pharmacy Teaching and Learning. - : Elsevier BV. - 1877-1297 .- 1877-1300. ; 11:5, s. 433-449
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: For some time, our faculty have expressed concerns regarding an apparent decrease in pharmacy students' academic productivity and performance. This study aimed to elucidate present conditions and suggest suitable interventions to improve the pharmacy program. Methods: Student cohorts starting the pharmacy program from 2009 to 2014 were followed with respect to performance in two courses (earlier and later). The students were segmented by entry qualifications, age, gender, etc. Eight students were further interviewed about their attitudes regarding their education. Results and conclusions: Achievement in the earlier course fell sharply over time, despite basically unchanged entry grade levels, increasing the workload for both teachers and students. This decrease was greater for male students. In the later course, the overall achievement level was higher, possibly due to less successful students dropping out. Subgrouping of students revealed differences in study achievement depending on age, gender, study program entrance qualifications, and admission “ranking”. In the interviews, students frequently stressed that connections to their future profession should be clearer and appear earlier in the program. Furthermore, students claimed that lectures with many attendees prevent peer learning and suggested that smaller groups be formed to foster cooperation and unity within the program. Remaining within their original cohort was viewed as very important by most students.
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| 18. |
- Aronsson, Patrik, 1983, et al.
(författare)
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The understanding of core pharmacological concepts among health care students in their final semester
- 2015
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Ingår i: BMC Medical Education. - : Springer Science and Business Media LLC. - 1472-6920. ; 15 (1)
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Background: The overall aim of the study was to explore health care students ́ understanding of core concepts in pharmacology. Method: An interview study was conducted among twelve students in their final semester of the medical program (n = 4), the nursing program (n = 4), and the specialist nursing program in primary health care (n = 4) from two Swedish universities. The participants were individually presented with two pharmacological clinically relevant written patient cases, which they were to analyze and propose a solution to. Participants were allowed to use the Swedish national drug formulary. Immediately thereafter the students were interviewed about their assessments. The interviews were audio-recorded and transcribed verbatim. A thematic analysis was used to identify units of meaning in each interview. The units were organized into three clusters: pharmacodynamics, pharmacokinetics, and drug interactions. Subsequent procedure consisted of scoring the quality of students ́ understanding of core concepts. Non-parametric statistics were employed. Results: The study participants were in general able to define pharmacological concepts, but showed less ability to discuss the meaning of the concepts in depth and to implement these in a clinical context. The participants found it easier to grasp concepts related to pharmacodynamics than pharmacokinetics and drug interactions. Conclusion: These results indicate that education aiming to prepare future health care professionals for understanding of more complex pharmacological reasoning and decision-making needs to be more focused and effective.
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- da Silva, Luiz A, et al.
(författare)
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Unravelling the intravenous and in situ vasopressin effects on the urinary bladder in anesthetized female rats: More than one vasopressin receptor subtype involved?
- 2018
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Ingår i: European journal of pharmacology. - : Elsevier BV. - 1879-0712 .- 0014-2999. ; 834, s. 109-117
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Tidskriftsartikel (refereegranskat)abstract
- Urinary bladder dysfunctions show high prevalence in women. We focused to investigate the intravenous and in situ (topic) vasopressin effects on the bladder and also to characterize the vasopressin receptor subtypes in the bladder. Adult female Wistar rats anesthetized with isoflurane underwent to the cannulation of the femoral artery and vein, and also urinary bladder for mean arterial pressure, heart rate and intravesical pressure (IP) recordings, respectively. Doppler flow probe was placed around the renal artery for blood flow measurement. After baseline recordings, intravenous injection of saline or vasopressin at different doses (0.25, 0.5, 1.0ng/ml/kg of b.w.); or 0.1ml of saline or 0.1ml of vasopressin at different doses (0.25, 0.5, 1.0ng/ml) was randomly dropped on the bladder. In another group of rats, the UB was harvest for gene expression by qPCR and also for protein expression by Western blotting of the vasopressin receptor subtypes. We observed that either intravenous or in situ vasopressin evoked a huge increase in the IP in a dose-dependent manner compared to saline, whilst no differences were observed in the cardiovascular parameters. The genes and the protein expression of V1a, V1b and V2 vasopressin receptors subtypes were found in the bladder. Intravenous injection of V1a or V2 receptor antagonist evoked a huge fall in IP and 30min later, i.v or in situ vasopressin evoked responses on IP were significantly attenuated. Therefore, intravenous or in situ vasopressin increases the IP due to binding in V1a or V2 receptors localized in the bladder.
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| 21. |
- Mitra, Reinika, et al.
(författare)
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Local Change in Urinary Bladder Contractility Following CNS Dopamine Denervation in the 6-OHDA Rat Model of Parkinson's Disease
- 2015
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Ingår i: Journal of Parkinsons Disease. - : IOS Press. - 1877-7171 .- 1877-718X. ; 5:2, s. 301-311
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Tidskriftsartikel (refereegranskat)abstract
- Background: Urinary problems, including urinary frequency, urgency, and nocturia are some of the non-motor symptoms that correlate most with poor quality of life in Parkinson's disease. However, the mechanism behind these symptoms is poorly understood, in particular regarding peripheral bladder pathophysiology following dopamine degeneration. Objective: In this study, we compared the contractile responsiveness of urinary bladder from the 6-OHDA unilateral rat model of Parkinson's disease with that of normal untreated animals. Methods: The contractility of the urinary detrusor muscle was evaluated in bladder strip preparations using electrical field stimulation, and muscarinic and purinoceptor stimulations in an vitro organ bath setup. Results: Our data show that the overall contractile response following electrical field stimulation was significantly higher (43% at maximum contraction by 20-40 Hz stimulation) in the 6-OHDA-lesioned rats as compared to control animals. This increase was associated with a significant increase in the cholinergic contractile response, where the muscarinic agonist methacholine produced a 44% (at 10(-4) Mconcentration) higher response in the 6-OHDA-treated rats as compared to controls with a significant left-shift of the dose response. This indicates an altered sensitivity of the muscarinic receptor system following the specific central 6-OHDA-induced dopamine depletion. In addition a 36% larger contraction of strips from the 6-OHDA animals was also observed with purinoceptor activation using the agonist ATP (5x10(-3) M) during atropine treatment. Conclusions: Our data shows that it is not only the central dopamine control of the micturition reflex that is altered in Parkinson's disease, but also the local contractile function of the urinary bladder. The current study draws attention to a mechanism of urinary dysfunction in Parkinson's disease that has previously not been described.
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- Stenqvist, Johanna, et al.
(författare)
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Effects of caveolae depletion and urothelial denudation on purinergic and cholinergic signaling in healthy and cyclophosphamide-induced cystitis in the rat bladder.
- 2018
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Ingår i: Autonomic neuroscience : basic & clinical. - : Elsevier BV. - 1872-7484. ; 213, s. 60-70
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Tidskriftsartikel (refereegranskat)abstract
- Cholesterol rich membrane invaginations, caveolae, have important roles in various cellular activities, one of them being signal transduction. This signaling pathway seems to be affected during various bladder disorders and the current study aimed to elucidate the plausible involvement of caveolae mediated signal transduction during cyclophosphamide induced cystitis. Furthermore, the urothelial cholinergic part of ATP-evoked contractions and its possible link to caveolae were investigated. Cholinergic, as well as purinergic, contractile responses in rat urinary bladders were examined using a classic organ bath set-up with full-thickness strip preparations or a whole bladder model that enabled luminal administration of substances. Furthermore, sub groups with and without urothelium were examined. The expression of caveolin-1 was also tested using western blot and immunofluorescence. Caveolae cholesterol depletion by methyl-β-cyclodextrin entailed a significant decrease of ATP-evoked bladder contractility. Interestingly, after muscarinic blockade the ATP induced contractions were significantly reduced in the same manner. Furthermore, this atropine-sensitive part of ATP-evoked responses was absent in denuded as well as inflamed bladders. A tendency towards a reduced expression of caveolin-1 was observed in rats with experimental cystitis. The cholinergic part of ATP-induced contractile responses seemed to be affected by urothelium denudation as well as caveolae depletion. Removing one of these structures nullifies the effect of the other, suggesting an important interaction between the urothelium and the caveolar structures. These effects are absent in inflamed animals and might be one pathophysiological aspect behind BPS/IC.
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| 27. |
- Stenqvist, Johanna, et al.
(författare)
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Urothelial acetylcholine involvement in ATP-induced contractile responses of the rat urinary bladder
- 2017
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Ingår i: European Journal of Pharmacology. - : Elsevier BV. - 0014-2999. ; 809, s. 253-260
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Tidskriftsartikel (refereegranskat)abstract
- Both acetylcholine and adenosine 5'-triphosphate (ATP) are released from the urothelium. In in vivo experiments ATP has been shown to evoke contractile responses that are significantly reduced by atropine. Currently, we aimed to examine the cholinergic part of the ATP-evoked contractile response of normal and inflamed (cyclophosphamide-treated rats) bladders. A whole bladder preparation that enabled drug administration either outside or inside the urinary bladder was used. The responses were examined in bladders from control and cyclophosphamide-treated rats that were either intact or urothelium-denuded. The expression of choline acetyltransferase and carnitine acetyltransferase were examined by Western blotting of normal and inflamed bladders. Methacholine evoked larger contractions when administered to the outside of the bladder in comparison to instillation. For ATP, an opposite trend emerged. While atropine substantially reduced the ATP-induced responses at internal administration (7.4 +/- 1.1 and 3.7 +/- 0.9 mN at 10-3 M; n=13; P < 0.001), it had no effect when administered outside the bladder. The removal of the urothelium caused a similar reduction of the responses to internal administration of ATP as caused by atropine. In cyclophosphamide-treated rats, neither atropine nor urothelium-denudation had any effect on the ATP-evoked responses. No changes in the expressions of the acetylcholine synthesising enzymes were observed. The current study shows that ATP induces a release of urothelial acetylcholine that contributes to the purinergic contractile response in the rat urinary bladder. This atropine-sensitive part of the purinergic contractile response is absent in the inflamed bladder. This may be one pathological mechanism involved in bladder dysfunction.
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| 28. |
- Winder, Michael, 1980, et al.
(författare)
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Autonomic Receptor-mediated Regulation of Production and Release of Nitric Oxide in Normal and Malignant Human Urothelial Cells
- 2017
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Ingår i: Basic & Clinical Pharmacology & Toxicology. - : Wiley. - 1742-7835. ; 121:4, s. 257-265
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Tidskriftsartikel (refereegranskat)abstract
- In the urinary bladder, the main source of NO seems to be the urothelium and the underlying suburothelium. In this study, we aimed to characterize how receptors in the human urothelium regulate the production and release of NO. For this, we cultured two human urothelial cell lines - the normal immortalized cell line UROtsa and the malignant cell line T24. These were treated with an array of agonists and antagonists with affinity for adrenergic, muscarinic and purinergic receptors. The production of NO and expression of nitric oxide synthase (NOS) was studied by immunocytochemistry and Western blotting. The amount of released NO was measured indirectly by detecting nitrite using amperometry and a Griess reaction kit. The results showed that NO, endothelial NOS and inducible NOS were predominantly produced and expressed in the close vicinity of the nucleus in untreated human urothelial cells. Upon treatment with a beta-adrenoceptor agonist, but not any of the other agonists or antagonists, the pattern of NO production changed, showing a more even production throughout the cytosol. The pattern of expression of endothelial NOS changed in a similar way upon dobutamine treatment. The release of nitrite, as a measurement of NO, increased after treatment with dobutamine from 0.31 +/- 0.029 to 1.97 +/- 0.18nmol and 0.80 +/- 0.12 to 3.27 +/- 0.24nmol in UROtsa and T24, respectively. In conclusion, our results show that the expression of NOS and production of NO as well as the release of NO from human urothelial cells is regulated by beta-adrenoceptor activation.
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- Zetterqvist, Ann, 1957, et al.
(författare)
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On the pedagogy of pharmacological communication: a study of final semester health science students.
- 2015
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Ingår i: BMC medical education. - : Springer Science and Business Media LLC. - 1472-6920. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- There is a need to improve design in educational programmes for the health sciences in general and in pharmacology specifically. The objective of this study was to investigate and problematize pharmacological communication in educational programmes for the health sciences.
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