Mirabegron attenuates porcine ureteral contractility via α1-adrenoceptor antagonism

The β(3)-agonist mirabegron is thought to induce relaxation of the detrusor muscle, contributing to the improvement of overactive bladder symptoms. There has been recent interest in purposing mirabegron as a medical expulsive therapy drug to improve the passage of smaller kidney stones by relaxing the ureteral smooth muscles. The aim of this study was to determine the effects of mirabegron on the activity of the ureter. Additionally, we investigated the receptor and mechanisms through which mirabegron exerts these effects. In vitro agonist-induced responses of isolated porcine distal ureteral tissues were measured in the absence and presence of mirabegron in organ bath experiments. The responses were expressed as frequency, area under the curve and maximum amplitude. Mirabegron at concentrations of 100 nM and lower failed to suppress phenylephrine- or 5-HT-induced contractions in the porcine ureteral strip. Mirabegron at 1 μM and 10 μM produced a rightward shift of phenylephrine concentration–response curves in these tissues. This effect of mirabegron (10 μM) was not present in 5-HT concentration–response curves. The mirabegron effect on phenylephrine-induced contractions was also not abolished by β-adrenoceptor antagonist SR 59230A (10 μM), β-adrenoceptor antagonist propranolol (10 μM), α(2)-adrenoceptor antagonist yohimbine (30 nM), and nitric oxide synthase inhibitor l-NNA (10 μM). The present results show that mirabegron suppresses ureteral contractile responses in the porcine ureter via α(1)-adrenoceptor antagonism, since their effects were not present when the tissues were contracted with 5-HT. Furthermore, the inhibitory effects by mirabegron were not affected by β(3)-adrenoceptor antagonists

The use of non-intrusive user logging to capture engineering rationale, knowledge and intent during the product life cycle

Within the context of Life Cycle Engineering it is important that structured engineering information and knowledge are captured at all phases of the product life cycle for future reference. This is especially the case for long life cycle projects which see a large number of engineering decisions made at the early to mid-stages of a product's life cycle that are needed to inform engineering decisions later on in the process. A key aspect of technology management will be the capturing of knowledge through out the product life cycle. Numerous attempts have been made to apply knowledge capture techniques to formalise engineering decision rationale and processes; however, these tend to be associated with substantial overheads on the engineer and the company through cognitive process interruptions and additional costs/time. Indeed, when life cycle deadlines come closer these capturing techniques are abandoned due the need to produce a final solution. This paper describes work carried out for non-intrusively capturing and formalising product life cycle knowledge by demonstrating the automated capture of engineering processes/rationale using user logging via an immersive virtual reality system for cable harness design and assembly planning. Associated post-experimental analyses are described which demonstrate the formalisation of structured design processes and decision representations in the form of IDEF diagrams and structured engineering change information. Potential future research directions involving more thorough logging of users are also outlined

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