ABSTRACT
INTRODUCTION: Plastic surgery is an important specialty that involves widespread medical knowledge, some of which is taught in undergraduate curricula. The General Medical Council provides a well-defined plastic surgery curriculum for postgraduate training. However, there is no consensus on the provision for undergraduates in this specialty, potentially giving rise to a deficit in undergraduate medical education and a suboptimal basis for plastic surgery postgraduate training. Our aim was to identify the gap in undergraduate plastic surgery teaching and to understand student perceptions of the specialty as well as any trialled interventions. METHODS: A prospectively registered systematic review was conducted following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The MEDLINE®, Embase™, PubMed® and Google Scholar™ databases were searched for literature relating to undergraduate exposure to plastic surgery and relevant teaching interventions. Ten studies were included in this review, categorised into three main themes: exposure during medical school, determining factors and perceptions for pursuing a plastic surgery career, and teaching interventions. RESULTS: Surveys assessing medical student perceptions indicate a significant deficit in exposure to plastic surgery in the undergraduate curriculum. Medical students' interest in the specialty is affected by multiple factors, including the amount of surgical exposure in medical school. Interventions to address the deficit mostly involve one-day courses. CONCLUSIONS: Although the literature is currently limited, studies are needed to effectively assess the outcomes of plastic surgery teaching methods in undergraduate training. Moreover, there is a need for consensus around the provision of undergraduate teaching in plastic surgery. This should be reflected in the latest undergraduate curricula in medical education.
ABSTRACT
A novel series of 4-piperidinopyridines and 4-piperidinopyrimidines showed potent and selective inhibition of rat 2,3-oxidosqualene cyclase-lanosterol synthase (OSC) (e.g. 26 IC(50) rat = 398 +/- 25 nM, human = 112 +/- 25 nM) and gave selective oral inhibition of rat cholesterol biosynthesis (26 ED(80) = 1.2 +/- 0.3 mg/kg, n = 5; HMGCoA reductase inhibitor simvastatin ED(80) = 1.2 +/- 0.3 mg/kg, n = 5). The piperidinopyrimidine OSC inhibitors have a significantly lower pK(a) than the corresponding pyridine or the previously reported quinuclidine OSC inhibitor series. This indicates that other novel OSC inhibitors may be found in analogues of this series across a broader pK(a) range (6.0-9.0). These series may yield novel hypocholesterolemic agents for the treatment of cardiovascular disease.
Subject(s)
Anticholesteremic Agents/chemical synthesis , Enzyme Inhibitors/chemical synthesis , Intramolecular Transferases/antagonists & inhibitors , Piperazines/chemical synthesis , Piperidines/chemical synthesis , Pyridines/chemical synthesis , Pyrimidines/chemical synthesis , Administration, Oral , Animals , Anticholesteremic Agents/chemistry , Anticholesteremic Agents/pharmacology , Cholesterol/biosynthesis , Chromatography, High Pressure Liquid , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/pharmacology , Female , In Vitro Techniques , Microsomes/drug effects , Microsomes/enzymology , Piperazines/chemistry , Piperazines/pharmacology , Piperidines/chemistry , Piperidines/pharmacology , Pyridines/chemistry , Pyridines/pharmacology , Pyrimidines/chemistry , Pyrimidines/pharmacology , Rats , Structure-Activity RelationshipABSTRACT
Novel 3-substituted quinuclidine inhibitors of cholesterol biosynthesis are reported. Compounds were optimized against oxidosqualene cyclase-lanosterol synthase (OSC) inhibition in vivo, rather than by the conventional optimization of structure-activity relationship information based on in vitro OSC inhibition. Thus, examination of HPLC lipid profiles from orally dosed rats showed cholesterol biosynthetic intermediates and whether cholesterol levels were reduced. A new substituted quinuclidine pharmacophore 18a-c was rapidly found for the inhibition of OSC, and the most promising inhibitors were validated by the confirmation of potent OSC inhibition. Compound 16 gave an IC50 value of 83 +/- 11 nM for human and an IC50 value of 124 +/- 14 nM, for rat, coupled with oral and selective inhibition of cholesterol biosynthesis derived from OSC inhibition (rat, ED50 = 1.3 +/- 0.7 mg/kg, n = 5; marmoset, 15 mg/kg dose, n = 3, caused complete inhibition). These 3-substituted quinuclidines, which were derived from a quinuclidine series previously known to inhibit cholesterol biosynthesis at the squalene synthase step, may afford a novel series of hypocholesterolemic agents acting by the inhibition of OSC.
