Pharmacy Education and Training in Ireland. The PHARMINE survey of European higher education institutions delivering pharmacy education & training - Ireland, 2010.

Pharmacy education is provided for in Ireland by three Higher Education Institutions; The Royal College of Surgeons in Ireland (RCSI), University of Dublin, Trinity College (TCD), and University College Cork (UCC). TCD was the sole provider of the undergraduate programme from 1977 until 2002 when the School of Pharmacy RCSI opened. The Schools educate approximately 150 students per annum. Applications to study pharmacy are far in excess of the places available as demand is high, and the profession is therefore fortunate to attract students of high calibre. There have been a number of recent developments which have transformed the landscape of pharmacye ducation and training in Ireland. The Bologna declaration, for instance, prompted curriculum reform in the Schools with RCSI completely reforming in 2005 to be fully compliant. One of the main drivers for development has been the Pharmacy Act 2007, which conferred responsibility ont he Pharmaceutical Society of Ireland (PSI), the pharmacy regulator, for overseeing education, training and lifelong learning in pharmacy. The PSI recently commissioned The Review of Pharmacy Education and Accreditation (PEARs) Project, a Review of International CPD Models, a review of competency frameworks and a baseline survey of standards in practice. These are intended to inform undergraduate curriculum development and a strategy for lifelong learning. The primary recommendation of the PEARs report(http://www.pharmaceuticalsociety.ie/Education/upload/File/Accreditation/PEARs_Project_Report.pdf) is that “the current 4+1 model of pharmacy education to first registration should be replaced by a five year fully integrated programme of education, training and assessment as the basis for application for registration as a pharmacist.” This report will instigate major curriculum reform in the Higher Education Institutions imminently. The Review of International CPD Models(http://www.pharmaceuticalsociety.ie/News/upload/File/Publications/PSI_International_Review_of CPD_Models.pdf ) set forth a vision for continuing professional development provision that will be implemented by 2014, as mandated by the Pharmacy Act 2007. The PSI also prioritised reform of the pre‐registration year – the year of training between the undergraduatep rogramme and registration. The National Pharmacy Internship Programme, a globally unique programme, was developed on behalf of the PSI by the School of Pharmacy of the Royal College of Surgeons in Ireland. Successful completion of the programme results in the award of a Masters of Pharmacy (M.Pharm) and entitlement to apply for registration as a pharmacist in Ireland and for subsequent free movement within the EU/EEA under the Professional Qualification Directive (2005/36/EC). The programme is a 12 month, full‐time, blended‐learning programme, attracting 90 European Credit Transfer and Accumulation System (ECTS) credits on completion. The basis for the curriculum is a competency framework that describes the knowledge, skills and attitudes required of a newly registered pharmacist, consistent with international norms. It is envisaged that improvements in the education and training of pharmacists will allow for significante enhancements to be made to the delivery of pharmacy services that capable of being benchmarked against the best internationally.</p

Besting Vitamin E: Sidechain Substitution is Key to the Reactivity of Naphthyridinol Antioxidants in Lipid Bilayers

A series of naphthyridinol analogs of α-tocopherol (α-TOH, right) with varying sidechain substitution was synthesized to determine how systematic changes in the lipophilicity of these potent antioxidants impact their radical-trapping activities in lipid bilayers, regenerability by water-soluble reductants, and binding to human tocopherol transport protein (TTP). The activities of the naphthyridinols were assayed in phosphatidylcholine unilamellar liposomes using a recently developed high-throughput assay that employs a boron dipyrromethene conjugate of α-TOH (H₂B-PMHC) that undergoes fluorescence enhancement upon oxidation. The naphthyridinols afforded a dose-dependent protection of H₂B-PMHC consistent with unprecedented peroxyl radical-trapping activity in lipid bilayers. While sidechain length and/or branching had no effect on their apparent reactivity, it dramatically impacted reaction stoichiometry, with more lipophilic compounds trapping two peroxyl radicals and more hydrophilic compounds trapping significantly less than one. It is suggested that the less lipophilic compounds autoxidize rapidly in the aqueous phase and that preferential partitioning of the more lipophilic compounds to the bilayer protects them from autoxidation. The cooperativity of a lipophilic naphthyridinol with water-soluble reducing agents was also studied in liposomes using H₂B-PMHC and revealed superior regenerability by each of ascorbate, <i>N</i>-acetylcysteine, and urate when compared to α-TOH. Binding assays with human TTP, a key determinant of the bioavailability of the tocopherols, reveal that the naphthyiridinols can be very good ligands for the protein. In fact, naphthyridinols with sidechains of eight or more carbons had affinities for TTP which were similar to, and in one case 10-fold better than, α-TOH

Hypotension-induced changes in pial arteriolar diameters.

<p>Internal diameters of pial arterioles (ID, µm) during decrease in systemic mean arterial blood pressure (mmHg), <b>A</b>: in 4–5 month-old normotensive rats (WKY, empty circles) and hypertensive vehicle-treated rats (SHR, full triangles); and <b>B</b>: in hypertensive rats treated for 10 days with telmisartan (TELMI, 2 mg/kg per day, empty squares) or candesartan cilexetil (CANDE, 10 mg/kg per day, full squares). n = 4–8 per group, m±sem.</p

Levels of PPAR-gamma and eNOS expression and glutathione content in brain microvessels.

<p>PPAR-gamma and eNOS mRNA expression in brain microvessels and glutathione (GSH) content of brain microvessels of 4–5 month-old SHR that where vehicle-treated (SHR) or treated for 10 days with candesartan cilexetil (CANDE, 10 mg/kg per day), pioglitazone (PIO, 2.5 mg/kg per day) or both (CANDE+PIO, 10+2.5 mg/kg per day), or telmisartan (TELMI, 2 mg/kg per day).</p><p>n = 6–15, m±sem, Bonferroni post-test: $: p<0.05 <i>vs</i> CANDE.</p><p>t-tests for TELMI:</p>!<p>p<0.05 <i>vs</i> SHR,</p>£<p>: p<0.05 <i>vs</i> CANDE,</p>¥<p>: p<0.05 <i>vs</i> CANDE+PIO.</p

Tocopherol Activity Correlates with Its Location in a Membrane: A New Perspective on the Antioxidant Vitamin E

We show evidence of an antioxidant mechanism for vitamin E which correlates strongly with its physical location in a model lipid bilayer. These data address the overlooked problem of the physical distance between the vitamin’s reducing hydrogen and lipid acyl chain radicals. Our combined data from neutron diffraction, NMR, and UV spectroscopy experiments all suggest that reduction of reactive oxygen species and lipid radicals occurs specifically at the membrane’s hydrophobic–hydrophilic interface. The latter is possible when the acyl chain “snorkels” to the interface from the hydrocarbon matrix. Moreover, not all model lipids are equal in this regard, as indicated by the small differences in vitamin’s location. The present result is a clear example of the importance of lipid diversity in controlling the dynamic structural properties of biological membranes. Importantly, our results suggest that measurements of aToc oxidation kinetics, and its products, should be revisited by taking into consideration the physical properties of the membrane in which the vitamin resides

Structure and vasoactivity of pial arterioles.

<p>Passive internal diameter (passive ID, µm) and wall thickness at the arteriolar pressure range of 30–35 mmHg (WT_30–35, µm) and slope of the elastic modulus <i>versus</i> stress (E_T), responses of pial arterioles to serotonin and ADP (percentage of change in baseline ID) of 4–5 month-old SHR that where vehicle-treated (SHR) or treated for 10 days with candesartan cilexetil (CANDE, 10 mg/kg per day), pioglitazone (PIO, 2.5 mg/kg per day) or both (CANDE+PIO, 10+2.5 mg/kg per day), or telmisartan (TELMI, 2 mg/kg per day).</p><p>n = 6–15, m±sem, Bonferroni post-test:</p>*<p>p<0.05 <i>vs</i> SHR,</p>†<p>p<0.05 <i>vs</i> PIO,</p>$<p>: p<0.05 <i>vs</i> CANDE.</p><p>t-tests for TELMI: ! p<0.05 vs SHR, £: p < 0.05 vs CANDE, ¥: p < 0.05 vs CANDE+PIO.</p

Blood pressure and baseline pial arteriolar diameters.

<p><b>A:</b> Systemic mean arterial blood pressure (mmHg), <b>B:</b> mean intra-arteriolar blood pressure (mmHg) and <b>C:</b> baseline internal diameter of pial arterioles (ID, µm) in 4–5 month-old SHR that where vehicle-treated (SHR, full bars) or treated for 10 days with candesartan cilexetil (CANDE, 10 mg/kg per day, left-sloping hatched bars), pioglitazone (PIO, 2.5 mg/kg per day, right-sloping hatched bars) or both (CANDE+PIO, 10+2.5 mg/kg per day, double-sloping hatched bars), or telmisartan (TELMI, 2 mg/kg per day, horizontal hatched bars); m±sem. p values for two-way ANOVA: - A: mean arterial blood pressure (n = 13–18) p_interaction 0.051, p_cande<1.10⁻⁴, p_pio 0.180 - B: mean intra-arteriolar blood pressure (n = 10–12) p_interaction 0.456, p_cande<1.10⁻⁴, p_pio 0.389 – C: ID (n = 12–13) p_interaction 0.017, p_cande<1.10⁻⁴, p_pio 0.107 Bonferroni post-test: * p<0.05 <i>vs</i> SHR, † p<0.05 <i>vs</i> PIO, $: p<0.05 <i>vs</i> CANDE t-tests for TELMI: * p<0.05 <i>vs</i> SHR,$: p<0.05 <i>vs</i> CANDE.</p

Levels of PPAR-gamma and eNOS mRNA expression.

<p><b>A:</b> PPAR-gamma and <b>B:</b> eNOS mRNA expression in brain microvessels of 4–5 month-old normotensive rats (WKY, empty bars), hypertensive rats that where vehicle-treated (SHR, full bars) or treated for 10 days with telmisartan (TELMI, 2 mg/kg per day, horizontal hatched bars) or candesartan cilexetil (CANDE, 10 mg/kg per day, left-sloping hatched bars). n = 4–5, m±sem; 1-way ANOVA; Newman-Keuls *: p<0.05 <i>vs</i> WKY, $: p<0.05 <i>vs</i> CANDE.</p

Vasoreactivity of pial arterioles to Ang II.

<p>Vasoactive response of pial arterioles (percentage of change in baseline ID) to suffusion of Ang II (10⁻⁶ M) in 4–5 month-old SHR that where vehicle-treated (SHR, full bars) or treated for 10 days with candesartan cilexetil (CANDE, 10 mg/kg per day, left-sloping hatched bars), pioglitazone (PIO, 2.5 mg/kg per day, right-sloping hatched bars) or both (CANDE+PIO, 10+2.5 mg/kg per day, double-sloping hatched bars), or telmisartan (TELMI, 2 mg/kg per day, horizontal hatched bars) ; m±sem. p values for two-way ANOVA (n = 7–9) p_interaction 0.018, p_cande 0.012, p_pio 0.009 Bonferroni post-test: * p<0.05 <i>vs</i> SHR, † p<0.05 <i>vs</i> PIO, $: p<0.05 <i>vs</i> CANDE t-tests for TELMI: * p<0.05 <i>vs</i> SHR, † p<0.05 <i>vs</i> PIO,$: p<0.05 <i>vs</i> CANDE.</p

Early morphant malformations.

<p>Images of embryo development from 6–18 hpf demonstrating early effects of TTP knockdown (right panel) compared to an injected control animal at the same age (left panel). Embryos from each MO injection type remain constant through 11 hpf. Beginning at 12 hpf, malformations are noticeable in the rostral region of the TRN embryo. These initial malformations occur in the head at the time the developing eye (marked) becomes distinguishable. The malformations in TRN embryos are more pronounced at later stages of development (16 and 18 hpf), while somite formation continues unabated. Images are frames from a time-lapse video (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0047402#pone.0047402.s005" target="_blank">Videos S1</a> and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0047402#pone.0047402.s005" target="_blank">S2</a>).</p