Natural products for the treatment of urinary incontinence

This review summarises the material covered during a workshop entitled “Natural Products as Treatments for Urinary Incontinence” that was presented at the online ICS (Melbourne) annual conference held in 2021. The clinical and scientific evidence of the effectiveness of naturally sourced treatments such as traditional Chinese medicines, phytoestrogens and saw palmetto for lower urinary tract symptoms are discussed, and also the use of cranberry and D-mannose for the treatment of bacterial infections of the urinary tract. The workshop and this review finish with a look towards the future and a discussion of potential treatments to repair the barrier function of the urothelium, an action that may be useful in conditions such as interstitial cystitis/bladder pain syndrome

Age Related Differences in Responsiveness to Sildenafil and Tamsulosin are due to Myogenic Smooth Muscle Tone in the Human Prostate

Lower urinary tract symptoms (LUTS) due to Benign Prostatic Hyperplasia (BPH) are highly prevalent in older men, having a profound impact on patient quality of life. Current therapeutics for BPH/LUTS target neurogenic smooth muscle tone, but response is unpredictable and many patients fail to respond. Spontaneous myogenic tone is another component of smooth muscle contractility that is uncharacterized in human prostate. To better understand and improve the predictability of patient response, we defined myogenic contractility using human prostate specimens and examined the effect of existing therapeutics. We show that myogenic activity is present in the human prostate with the frequency of contractions in transition zone (TZ) specimens from BPH diagnosed patients approximately 160% greater than matched controls. α1-adrenoreceptor antagonists (Tamsulosin) and PDE5 inhibitors (Sildenafil) both significantly reduced myogenic contractile parameters, including frequency, with notable interpatient variability. Tamsulosin was more effective in older patients (R2 = 0.36, p < 0.01) and men with larger prostate volumes (R2 = 0.41, p < 0.05), while Sildenafil was more effective in younger men (R2 = 0.45, p < 0.05). As myogenic tone is significantly increased in BPH, therapeutics targeting this mechanism used with reference to patient characteristics could improve clinical outcomes and better predict patient response

Oxytocin receptor antagonists as a novel pharmacological agent for reducing smooth muscle tone in the human prostate

Pharmacotherapies for the treatment of Benign Prostatic Hyperplasia (BPH) are targeted at reducing cellular proliferation (static component) or reducing smooth muscle tone (dynamic component), but response is unpredictable and many patients fail to respond. An impediment to identifying novel pharmacotherapies is the incomplete understanding of paracrine signalling. Oxytocin has been highlighted as a potential paracrine mediator of BPH. To better understand oxytocin signalling, we investigated the effects of exogenous oxytocin on both stromal cell proliferation, and inherent spontaneous prostate contractions using primary models derived from human prostate tissue. We show that the Oxytocin Receptor (OXTR) is widely expressed in the human prostate, and co-localises to contractile cells within the prostate stroma. Exogenous oxytocin did not modulate prostatic fibroblast proliferation, but did significantly (p < 0.05) upregulate the frequency of spontaneous contractions in prostate tissue, indicating a role in generating smooth muscle tone. Application of atosiban, an OXTR antagonist, significantly (p < 0.05) reduced spontaneous contractions. Individual tissue responsiveness to both exogenous oxytocin (R2 = 0.697, p < 0.01) and atosiban (R2 = 0.472,p < 0.05) was greater in tissue collected from older men. Overall, our data suggest that oxytocin is a key regulator of inherent spontaneous prostate contractions, and targeting of the OXTR and associated downstream signalling is an attractive prospect in the development of novel BPH pharmacotherapies

Developing a Global Community of Practice for Pharmacy Workforce Resilience—Meet GRiT

From MDPI via Jisc Publications RouterHistory: accepted 2021-06-07, pub-electronic 2021-06-10Publication status: PublishedWorkforce resilience in pharmacy is required to ensure the practice, education, and administrative systems remain viable and sustainable over time and when facing challenges. Whether it is addressing burnout of pharmacists or students, or the structure and policies/procedures of employment and professional organizations, working to increase resilience across all individuals and sectors is essential to relieve pressure and promote better well-being, especially during the recent pandemic. The purpose of this article is to describe the development of a community of practice global group focused on development of resilience within the pharmacy workforce that is inclusive of students, pharmacy interns/preregistration and registered pharmacists. The steering group meets monthly and has representation of 24 members across eight countries. Members meet to discuss pertinent issues they are facing in practice, as well as to share and progress ideas on education, research, and practice initiatives. To date, members have collectively implemented resilience training in pharmacy education, researched burnout and resilience in both students and pharmacists, and facilitated international collaborations both within and outside core group members. Future activities will focus on strengthening the community of practice in order to harness the power of the collective

Developing a global community of practice for pharmacy workforce resilience— meet GRiT

Workforce resilience in pharmacy is required to ensure the practice, education, and administrative systems remain viable and sustainable over time and when facing challenges. Whether it is addressing burnout of pharmacists or students, or the structure and policies/procedures of employment and professional organizations, working to increase resilience across all individuals and sectors is essential to relieve pressure and promote better well-being, especially during the recent pandemic. The purpose of this article is to describe the development of a community of practice global group focused on development of resilience within the pharmacy workforce that is inclusive of students, pharmacy interns/preregistration and registered pharmacists. The steering group meets monthly and has representation of 24 members across eight countries. Members meet to discuss pertinent issues they are facing in practice, as well as to share and progress ideas on education, research, and practice initiatives. To date, members have collectively implemented resilience training in pharmacy education, researched burnout and resilience in both students and pharmacists, and facilitated international collaborations both within and outside core group members. Future activities will focus on strengthening the community of practice in order to harness the power of the collective

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

Extracellular Ca²⁺ entry and mobilization of inositol trisphosphate-dependent Ca²⁺ stores modulate histamine and electrical field stimulation induced contractions of the guinea-pig prostate

This investigation aimed to examine the source of Ca²⁺ mobilization that leads to the contractile response to either exogenously added histamine (1 μM–1 mM) or electrical field stimulation (10 Hz, 0.5 ms, 60 V). Removal of extracellular Ca²⁺ by removal of Ca²⁺ from the bathing medium reduced histamine (1 mM) induced responses by 34% and responses induced by electrical field stimulation by 94%. Similarly, blockade of L-type Ca²⁺ channels by nifedipine (1 μM) reduced histamine (1 mM) induced responses by 43% and responses induced by electrical field stimulation by 77%. Application of cyclopiazonic acid (CPA) (10 μM) to inhibit Ca²⁺ reuptake to the sarcoplasmic reticulum enhanced both histamine-induced and electrical field stimulation induced responses to a small degree, while the addition of the inosotol triphosphate (IP3) receptor antagonist, 2-aminophenoxyethane borane (2-APB) (100 μM) inhibited histamine induced responses by 70% and electrical field stimulation induced responses by 57%. Ryanodine (1 μM) did not affect contractile responses to either histamine or electrical field stimulation, either in the absence or presence of 2-APB (100 μM). During both histamine and electrical field stimulation induced contractions, prostate smooth muscle generates IP3 receptor mediated Ca²⁺ release in conjunction with Ca²⁺ entry from the extracellular environment. Ryanodine receptors on the other hand, appear not to play a role in this physiological mechanism