Бюллетень новых поступлений за ноябрь 2012 года

Background: 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. Methods: An interview study was carried out where final semester students from programmes for the medical, nursing and specialist nursing in primary health care professions were asked to discuss the pharmacological aspects of two written case descriptions of the kind they would meet in their everyday work. The study focused on the communication they envisaged taking place on the concerns the patients were voicing, in terms of two features: how communication would take place and what would be the content of the communication. A phenomenographic research approach was used. Results: The results are presented as outcome spaces, sets of categories that describe the variation of ways in which the students voiced their understanding of communication in the two case descriptions and showed the qualitatively distinct ways in which the features of communication were experienced. Conclusions: The results offer a base of understanding the students perspectives on communication that they will take with them into their professional lives. We indicate that there is room for strengthening communication skills in the field of pharmacology, integrating them into programmes of education, by more widely implementing a problem-based, a case-oriented or role-playing pedagogy where final year students work across specialisations and there is a deliberate effort to evoke and assess advanced conceptions and skills.Funding Agencies|Department of Pedagogical; County Council Ostergotland [LIO-198671]; Mellon Foundation at the Faculty of Humanities, University of the Witwatersrand, South Africa</p

Soluble guanylate cyclase mediates the relaxation of healthy and inflamed bladder smooth muscle by aqueous nitric oxide

Introduction: Due to its chemical properties, functional responses to nitric oxide (NO) are often difficult to examine. In the present study, we established a method to produce NO in an aqueous solution and validated its capacity to evoke functional responses in isolated rat bladders. Furthermore, we compared the NO responses to the commonly used NO donor sodium nitroprusside (SNP). We also investigated the impact of ongoing inflammation on the involvement of soluble guanylate cyclase (sGC) dependent signaling in NO relaxation.Methods: A setup to produce an aqueous NO solution was established, allowing the production of an aqueous solution containing a calculated NO concentration of 2 mM. Sixty male Sprague-Dawley rats received either no treatment (controls) or cyclophosphamide (CYP; 100 mg*kg−1 i.p., 60 h prior to the experiment) to induce experimental cystitis. Bladder strip preparations were mounted in organ baths and studied at basal tension or pre-contracted with methacholine (3 μM). Aqueous NO solution (40–400 μL; 2 mM corresponding to 4–40 μM) or SNP (1–1,000 μM) was added cumulatively in increasing concentrations. Relaxation to aqueous NO was also studied in the presence of the sGC inhibitor ODQ (0.25–25 μM). The expression of sGC was investigated by immunohistochemical analysis.Results: The NO solution caused functional relaxations in both controls and inflamed bladder preparations. NO-induced relaxations were significantly greater in inflamed bladder strips at basal tension, whereas no differences were seen in methacholine pre-contracted strips. In the presence of the sGC inhibitor ODQ in a high concentration, the NO-evoked relaxations were abolished in both control and inflamed preparations. At a lower concentration of ODQ, only NO relaxations in inflamed preparations were attenuated. Immunohistochemical analysis showed that sGC was expressed in the detrusor and mucosa, with a significantly lower expression in the inflamed detrusor.Conclusion: In the present study, we found that aqueous NO solution induces relaxation of the rat detrusor by activating soluble guanylate cyclase in both control and inflamed bladder strips. Induction of inflammation conceivably leads to decreased sGC expression in the detrusor, which may explain the different susceptibility towards inhibition of sGC in inflamed versus control tissue. The use of an aqueous NO solution should be further considered as a valuable complement to the pharmacological tools currently used

Defining and unpacking the core concepts of pharmacology : A global initiative

The authors acknowledge the contribution of the expert group members who contributed their expertise to the study and Professor Martin Kingsbury for his invaluable guidance on concept mapping.Peer reviewe

Unveiling the Angiotensin-(1–7) Actions on the Urinary Bladder in Female Rats

Angiotensin-(1–7) is a peptide produced by different pathways, and regardless of the route, the angiotensin-converting enzyme 2 (ACE-2) is involved in one of the steps of its synthesis. Angiotensin-(1–7) binds to Mas receptors localized in different cells throughout the body. Whether angiotensin-(1–7) exerts any action in the urinary bladder (UB) is still unknown. We investigated the effects of intravenous and topical (in situ) administration of angiotensin-(1–7) on intravesical pressure (IP) and cardiovascular variables. In addition, the Mas receptors and ACE-2 gene and protein expression were analyzed in the UB. Adult female Wistar rats were anesthetized with 2% isoflurane in 100% O2 and submitted to the catheterization of the femoral artery and vein for mean arterial pressure (MAP) and heart rate (HR) recordings, and infusion of drugs, respectively. The renal blood flow was acquired using a Doppler flow probe placed around the left renal artery and the renal conductance (RC) was calculated as a ratio of Doppler shift (kHz) and MAP. The cannulation of the UB was performed for IP recording. We observed that angiotensin-(1–7) either administered intravenously [115.8 ± 28.6% angiotensin-(1–7) vs. −2.9 ± 1.3% saline] or topically [147.4 ± 18.9% angiotensin-(1–7) vs. 3.2 ± 2.8% saline] onto the UB evoked a significant (p &lt; 0.05) increase in IP compared to saline and yielded no changes in MAP, HR, and RC. The marked response of angiotensin-(1–7) on the UB was also investigated using quantitative real-time polymerase chain reaction and western blotting assay, which demonstrated the mRNA and protein expression of Mas receptors in the bladder, respectively. ACE-2 mRNA and protein expression was also observed in the bladder. Therefore, the findings demonstrate that angiotensin-(1–7) acts in the UB to increase the IP and suggest that this peptide can be also locally synthesized in the UB

Identifying the core concepts of pharmacology education : a global initiative

Background and Purpose: In recent decades, a focus on the most critical and fundamental concepts has proven highly advantageous to students and educators in many science disciplines. Pharmacology, unlike microbiology, biochemistry or physiology, lacks a consensus list of such core concepts . Experimental approach: We sought to develop a research-based, globally relevant list of core concepts that all students completing a foundational pharmacology course should master. This two-part project consisted of exploratory and refinement phases. The exploratory phase involved empirical data mining of the introductory sections of five key textbooks, in parallel with an online survey of over 200 pharmacology educators from 17 countries across six continents. The refinement phase involved three Delphi rounds involving 24 experts from 15 countries across six continents. Key Results: The exploratory phase resulted in a consolidated list of 74 candidate core concepts. In the refinement phase, the expert group produced a consensus list of 25 core concepts of pharmacology. Conclusion and Implications: This list will allow pharmacology educators everywhere to focus their efforts on the conceptual knowledge perceived to matter most by experts within the discipline. Next steps for this project include defining and unpacking each core concept and developing resources to help pharmacology educators globally teach and assess these concepts within their educational contexts

Purinergic effects in the rat urinary bladder. Functional studies of cyclophosphamide treatment on afferent and efferent mechanisms

Pathological conditions in the lower urinary tract are common and have a great impact on the quality of life for the patients suffering from such disorders. In this thesis cyclophosphamide (CYP)-induced cystitis, a well-established rat model of inflammatory bladder diseases such as bladder pain syndrome/interstitial cystitis (BPS/IC), has been employed to study the role of purinergic transmission in the normal and inflamed state. The main focus was to characterize purinergic functional contractile and relaxatory parameters, studied in vitro, in vivo and in situ, for which the latter a novel method was developed and validated. The P2X1 purinoceptor was, in concordance with previous studies, found to be the major contractile subtype, whereas P2Y purinoceptor(s) with different sensitivities to the purinergic agonists ADP/ATP and UDP/UTP were shown to be relaxatory. Furthermore, the adenosine P1A2B purinoceptor was demonstrated to play a functional relaxatory role. Using the novel in situ experimental setup presented in this thesis it was concluded that stretch-evoked contralateral contractions, mediated by afferent nerve fibers, were increased during cystitis. This was in contrast to most other contractile studies, in which the response in the inflamed bladder was generally decreased. This enlargement to stretch stimulus was found to be due to both cholinergic and purinergic factors, of which the latter were more pronounced at lower stimulation intensities. Since the purinoceptors are often mentioned in the context of inflammation, studies were also conducted to investigate the role of purinergic, as well as of cholinergic and nitrergic, blockade in the development of cystitis. It was concluded that blockade of the P1A1 purinoceptor or inhibition of nitric oxide synthase can alleviate the change in contractile function to CYP-induced bladder inflammation, which was confirmed by the study of several inflammatory findings common in cystitis. Taken together, the purinergic transmission is altered during cystitis, and the changes are likely predominantly on the afferent side of the micturition reflex arc. The novel in situ setup can be modified and used to study various afferent factors, without interfering with the contractility of the bladder. Future therapeutic drugs targeting purinoceptors on afferent neurons may provide a valuable addition to the currently used medicines. The fact that blockade of purinoceptors at the same time may have a beneficial impact on the inflammation itself may prove to be useful in the treatment of inflammatory conditions in the lower urinary tract