Teaching safe prescribing to medical students: perspectives in the UK.

Prescribing is a characteristic role of a medical practitioner. On graduating from medical school, students are presumed to have acquired the necessary pharmacology knowledge underpinning the therapeutics and developed their personal skills and behaviors in order to write a safe and effective prescription (The Four Ps). However, there are reports of errors in medical prescribing and dissatisfied feedback from recent graduates, which evidence potential flaws in the current training in the practice of prescribing.

A study to investigate the effectiveness of SimMan® as an adjunct in teaching preclinical skills to medical students.

Background: Following the GMC's report on Tomorrow's Doctors, greater emphasis has been placed on training in clinical skills, and the integration of clinical and basic sciences within the curriculum to promote the development of effective doctors. The use of simulation in the learning environment has the potential to support the development of clinical skills in preclinical medical students whilst in a 'safe' environment, but currently there is little evidence on its effectiveness.

Methods: Seventy nine year one medical students were divided into two groups.

Substance misuse teaching in undergraduate medical education.

Background: Over 12,000 hospital admissions in the UK result from substance misuse, therefore issues surrounding this need to be addressed early on in a doctor's training to facilitate their interaction with this client group. Currently, undergraduate medical education includes teaching substance misuse issues, yet how this is formally integrated into the curriculum remains unclear.

Methods: Semi-structured interviews with 17 key members of staff responsible for the whole or part of the undergraduate medical curriculum were conducted to identify the methods used to teach substance misuse.

Do students learn to be more conscientious at medical school?

Background: Professionalism in medical students is not only difficult to define but difficult to teach and measure. As negative behaviour in medical students is associated with post-graduate disciplinary action it would be useful to have a model whereby unprofessional behaviour at the undergraduate level can easily be identified to permit appropriate intervention. We have previously developed a scalar measure of conscientiousness, the Conscientiousness Index (CI), which positively correlates to estimates of professional behaviour in undergraduate medical students.

Modulation of gap-junction-dependent arterial relaxation by ascorbic acid.

Aims: To investigate whether ascorbic acid (AA) can influence endothelium-dependent relaxation by modulating the spread of endothelial hyperpolarization through the arterial wall via gap junctions.

Methods: Force development and membrane potential were monitored by myography and sharp electrode techniques in isolated rabbit iliac arteries.

Results: AA prevented the ability of the gap junction blocker 2-aminoethoxydiphenyl borate to inhibit endothelium-dependent relaxations and subintimal smooth muscle hyperpolarizations evoked by cyclopiazonic acid in the presence of nitric oxide (NO) synthase and cyclooxygenase blockade.

5-Methyltetrahydrofolate and tetrahydrobiopterin can modulate electrotonically mediated endothelium-dependent vascular relaxation.

We have investigated the ability of 5-methyltetrahydrofolate (5-MTHF) and tetrahydrobiopterin (BH(4)) to modulate nitric oxide (NO)-independent vascular relaxations that are mediated by the sequential spread of endothelial hyperpolarization through the wall of the rabbit iliac artery by means of myoendothelial and homocellular smooth muscle gap junctions. Relaxations and subintimal smooth muscle hyperpolarizations evoked by cyclopiazonic acid were depressed by the gap junction inhibitor 2-aminoethoxydiphenyl borate, whose effects were prevented by 5-MTHF and BH(4), but not by their oxidized forms folic acid and 7,8-dihydrobiopterin. Analogously, 5-MTHF and BH(4), but not folic acid or 7,8-dihydrobiopterin, attenuated the depression of subintimal hyperpolarization by a connexin-mimetic peptide targeted against Cx37 and Cx40 ((37,40)Gap 26) and the depression of subadventitial hyperpolarization by a peptide targeted against Cx43 ((43)Gap 26), thus reflecting the known differential expression of Cx37 and Cx40 in the endothelium and Cx43 in the media of the rabbit iliac artery.

Connexin-mimetic peptides dissociate electrotonic EDHF-type signalling via myoendothelial and smooth muscle gap junctions in the rabbit iliac artery.

Synthetic peptides corresponding to the Gap 26 and Gap 27 domains of the first and second extracellular loops of the major vascular connexins (Cx37, Cx40 and Cx43), designated as (43)Gap 26, (40)Gap 27, (37,40)Gap 26 and (37,43)Gap 27 according to Cx homology, were used to investigate the role of gap junctions in the spread of endothelial hyperpolarizations evoked by cyclopiazonic acid (CPA) through the wall of the rabbit iliac artery. Immunostaining and confocal microscopy demonstrated that gap junction plaques constructed from Cx37 and Cx40 were abundant in the endothelium, whereas Cx43 was the dominant Cx visualized in the media. None of the Cx-mimetic peptides affected endothelial hyperpolarizations evoked by CPA directly.

Enhanced inhibition of the EDHF phenomenon by a phenyl methoxyalaninyl phosphoramidate derivative of dideoxyadenosine.

In rabbit arteries endogenous production of cAMP facilitates electrotonic signalling via gap junctions, thus explaining the ability of P-site inhibitors of adenylyl cyclase to attenuate EDHF-type responses. In the present study, we show that a lipophilic phosphoramidate pronucleotide derivative of dideoxyadenosine, 2',3'-ddA-PMAPh, exhibits enhanced activity as an inhibitor of EDHF-type smooth muscle hyperpolarizations induced by acetylcholine (ACh) compared to the parent nucleoside 2',3'-ddA, and that the effects of both compounds can be reversed by the cAMP phosphodiesterase inhibitor IBMX. Neither 2',3'-ddA nor 2',3'-ddA-PMAPh depress ACh-evoked endothelial hyperpolarization directly.

The obligatory link: role of gap junctional communication in endothelium-dependent smooth muscle hyperpolarization.

Although an endothelium-derived hyperpolarizing factor (EDHF) has often been hypothesized to underpin vascular relaxations that are independent of nitric oxide (NO) and prostanoids, bioassay techniques have failed to confirm the existence of a freely transferable EDHF in a consistent fashion. Indeed, observations that inhibitors of direct cell-cell coupling such as connexin-mimetic peptides (e.g.

Distinct hyperpolarizing and relaxant roles for gap junctions and endothelium-derived H2O2 in NO-independent relaxations of rabbit arteries.

We have compared the contributions of gap junctional communication and chemical signaling via H2O2 to NO-independent relaxations evoked by the Ca2+ ionophore A23187 and acetylcholine (ACh) in rabbit ilio-femoral arteries. Immunostaining confirmed the presence of connexins (Cxs) 37 and 40 in the endothelium and Cxs 40 and 43 in smooth muscle. Maximal endothelium-dependent subintimal smooth muscle hyperpolarizations evoked by A23187 and ACh were equivalent (approximately 20 mV) and almost abolished by an inhibitory peptide combination targeted against Cxs 37, 40, and 43.

Essential role of Gap junctions in NO- and prostanoid-independent relaxations evoked by acetylcholine in rabbit intracerebral arteries.

Background And Purpose: Direct intercellular communication via gap junctions may play a central role in endothelium-dependent relaxations that are mediated by a conducted hyperpolarization and do not involve the synthesis of NO and prostanoids. In the present study, inhibitory peptides homologous to the Gap27 domain of the second extracellular loop of connexin37/connexin43 and connexin40, designated as 37,43Gap27 and 40Gap27, respectively, were used to evaluate the role of this mechanism in intracerebral arteries.

Methods: Isolated rings of rabbit middle cerebral artery were constricted by histamine (10 micromol/L) in the presence of N(G)-nitro-L-arginine methyl ester (300 micromol/L) and indomethacin (10 micromol/L).

cAMP facilitates EDHF-type relaxations in conduit arteries by enhancing electrotonic conduction via gap junctions.

We have investigated the role of cAMP in NO- and prostanoid-independent relaxations that are widely attributed to an endothelium-derived hyperpolarizing factor (EDHF). Under control conditions EDHF-type relaxations evoked by acetylcholine (ACh) in rabbit iliac arteries were transient, but in the presence of the cAMP phosphodiesterase inhibitor isobutylmethylxanthine (IBMX) or the cell permeant cAMP analog 8-bromo-cAMP, relaxations became sustained with their maxima potentiated approximately 2-fold. Relaxation was associated with transient approximately 1.

Gap junction-dependent and -independent EDHF-type relaxations may involve smooth muscle cAMP accumulation.

We have compared the mechanisms that contribute to endothelium-derived hyperpolarizing factor (EDHF)-type responses induced by ACh and the Ca(2+) ionophore A-23187 in the rabbit iliac artery. Relaxations to both agents were associated with ~1.5-fold elevations in smooth muscle cAMP levels and were attenuated by the adenylyl cyclase inhibitor 2',5'-dideoxyadenosine (DDA) and potentiated by the cAMP phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX).