Browsing by Author "Plane, Frances"
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Item Repurposing of the PDE5 inhibitor sildenafil for treatment of persistent pulmonary hypertension in neonates(2021) Poitras, Erika L.; Gust, Stephen L.; Kerr, Paul; Plane, FrancesNitric oxide (NO), an important endogenous signaling molecule released from vascular endothelial cells and nerves, activates the enzyme soluble guanylate cyclase to catalyze the production of cyclic guanosine monophosphate (cGMP) from guanosine triphosphate. cGMP, in turn, activates protein kinase G to phosphorylate a range of effector proteins in smooth muscle cells that reduce intracellular Ca2+ levels to inhibit both contractility and proliferation. The enzyme phosphodiesterase type 5 (PDE5) curtails the actions of cGMP by hydrolyzing it into inactive 5’-GMP. Small molecule PDE5 inhibitors (PDE5is), such as sildenafil, prolong the availability of cGMP and therefore, enhance NO-mediated signaling. PDE5is are the first-line treatment for erectile dysfunction but are also now approved for the treatment of pulmonary arterial hypertension (PAH) in adults. Persistent pulmonary hypertension in neonates (PPHN) is currently treated with inhaled NO, but this is an expensive option and around 1/3 of newborns are unresponsive, resulting in the need for alternative approaches. Here the development, chemistry and pharmacology of PDE5is, the use of sildenafil for erectile dysfunction and PAH, are summarized and then current evidence for the utility of further repurposing of sildenafil, as a treatment for PPHN, is critically reviewed.Item Vasoconstrictor stimulus determines the functional contribution of myoendothelial feedback to mesenteric arterial tone(2018) Wei, Ran; Lunn, S. E.; Tam, R.; Gust, Stephen L.; Classen, B.; Kerr, Paul; Plane, FrancesThe last few decades have witnessed a dramatic rise in the use of surveillance, particularly in organizational life (Anteby & Chan, 2018). Primary forms of surveillance, such as the supervisor’s gaze, are being augmented by sophisticated devices capable of tracking more than employees’ work habits: public and private affairs, past and present choices, opinions and attitudes are increasingly recorded, retained, and used to predict or shape future behavior. The technologies of surveillance, elaborate in their subtlety, inexpensiveness, and accessibility, coupled with the proliferation of individual devices (e.g., cell phones), are decentralizing a strategic tool previously the exclusive domain of the managerial elite. Hence, a vision of what the future of leadership holds must grapple with the increased surveillance leaders will face by those inside and outside of the organization. The ascendancy and proliferation of surveillance have significant implications for leadership. In this brief paper, we identify and discuss two core implications: first, surveillance systems will alter the criteria discriminating between future leaders—i.e., leader emergence will increasingly rest on individuals’ knowledge of what surveillance systems capture as well as their performative capacity to enact behaviors suited for those systems. Second, the effectiveness of leaders within a time of heightened surveillance will place a premium on the forbearance and flexibility of leaders to work with one another within an organizational field.