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At least 73 records · Page 4Linked to original sources
PubMed1992

Sodium, calcium and exocytosis: confessions of calcified scientists.

Stimulated exocytotic secretion from nerve endings is initiated by an increase in intracellular free calcium concentration. We summarize here our latest findings regarding the temporal relationship between depolarization, elevation of [Ca2+]i and exocytosis in single vertebrate neuroendocrine nerve endings. In addition, we present surprising findings for a regulatory role of intracellular Na+ on exocytosis.

Animals↗
PubMed2001

Lead optimization in 12 months? True confessions of a chemistry team.

In 1998 GlaxoWellcome embarked upon a new enzyme-inhibitor programme. This programme featured an aggressive timeframe of seven years, from the start of medicinal chemistry through to drug launch. This period, dominated as it was by the constraints of the clinical programme, translated into a lead-optimization phase of no more than 12 months. In this article, we describe our attempts to meet this target, examining not only what we did and what worked, but also what didn't work and, most importantly, what we learnt as a result. At a time of considerable upheaval and challenge to the traditional model of drug discovery, we hope our experiences might stimulate interest, empathy and further discussion.

Journal Article↗
PubMed2005

Prospects and possible pitfalls of a preventive Polypill: confessions of a health promotion convert.

A proposal by Wald and Law (2003) for a single pill containing a statin, three half-dose antihypertensives, aspirin, and folic acid, met with a storm of controversy and seemed to have been relegated as much to the fanciful as to the accolades it might have deserved. The benefits such a Polypill could confer on people age 55+y were to reduce both cardiovascular and stroke events by 80% or more. Considering the daunting and, at best, slow process of changing the same risk factors through health promotion interventions on food policy, dietary and physical activity behaviors, and urban planning to make less prevalent the sedentary lifestyles developed over decades, the argument here is to view the Polypill as a harm reduction strategy that would complement health promotion, as Nicotine Replacement Therapy did for tobacco control, seat belts did for traffic injuries, and needle exchange programs did for secondary complications of injection drug use.

Aged↗