Pharmacy practice in a European perspective

In 1992 European pharmacy organisations joined in the EuroPtharm forum. This network has for the last two decades focused on development of pharmacy practice. Today 30 associations from 22 countries are members of the Forum.peer-reviewe

Vanillin formation from ferulic acid in <em>Vanilla planifolia</em> is catalysed by a single enzyme

Vanillin is a popular and valuable flavour compound. It is the key constituent of the natural vanilla flavour obtained from cured vanilla pods. Here we show that a single hydratase/lyase type enzyme designated vanillin synthase (VpVAN) catalyses direct conversion of ferulic acid and its glucoside into vanillin and its glucoside, respectively. The enzyme shows high sequence similarity to cysteine proteinases and is specific to the substitution pattern at the aromatic ring and does not metabolize caffeic acid and p-coumaric acid as demonstrated by coupled transcription/translation assays. VpVAN localizes to the inner part of the vanilla pod and high transcript levels are found in single cells located a few cell layers from the inner epidermis. Transient expression of VpVAN in tobacco and stable expression in barley in combination with the action of endogenous alcohol dehydrogenases and UDP-glucosyltransferases result in vanillyl alcohol glucoside formation from endogenous ferulic acid. A gene encoding an enzyme showing 71% sequence identity to VpVAN was identified in another vanillin-producing plant species Glechoma hederacea and was also shown to be a vanillin synthase as demonstrated by transient expression in tobacco. (Résumé d'auteur

Fifteen new risk loci for coronary artery disease highlight arterial-wall-specific mechanisms

Coronary artery disease (CAD) is a leading cause of morbidity and mortality worldwide. Although 58 genomic regions have been associated with CAD thus far, most of the heritability is unexplained, indicating that additional susceptibility loci await identification. An efficient discovery strategy may be larger-scale evaluation of promising associations suggested by genome-wide association studies (GWAS). Hence, we genotyped 56,309 participants using a targeted gene array derived from earlier GWAS results and performed meta-analysis of results with 194,427 participants previously genotyped, totaling 88,192 CAD cases and 162,544 controls. We identified 25 new SNP-CAD associations (P &lt; 5 × 10(-8), in fixed-effects meta-analysis) from 15 genomic regions, including SNPs in or near genes involved in cellular adhesion, leukocyte migration and atherosclerosis (PECAM1, rs1867624), coagulation and inflammation (PROCR, rs867186 (p.Ser219Gly)) and vascular smooth muscle cell differentiation (LMOD1, rs2820315). Correlation of these regions with cell-type-specific gene expression and plasma protein levels sheds light on potential disease mechanisms

Geochemical Development of Proterozoic Granites in the SW Baltic Shield

The plutonic rocks in the Western Segment of the Southwestern Swedish Gneiss Complex show a distinct geochemical evolution. The 1.6 Ga Åmål granitoids and Slottsbron migmatites are a quartz dioritic to granodioritic, calc-alkaline rock suite with smooth, but somewhat fractionated, REE and other trace-element patterns. The younger microcline granites of the 1.5 Ga and 1.3 Ga generations are evolved rocks having fractionated REE patterns with deep negative Eu anomalies. The 1.5 Ga granites vary from calc-alkalic, metaluminous granodiorites to evolved alkali-calcic peraluminous leucogranites. The REE and other trace-element patterns are less evolved than those of the 1.3 Ga rocks. The 1.3 Ga granites are the most evolved intrusions in the area. Granites with a bimodal geochemical character occur. All rocks can be ascribed to one of three types: i. The HUS1 type is homogeneous, alkali-calcic with high SiO2 content and is often leucocratic. ii. The SS2 type has a large geochemical variation, but shows regular inter-element relationships. It is alkali-calcic and has the most evolved REE patterns. iii. In the TYP3 type, calc-alkaline compositions are common. They are the least evolved rocks of this generation. The differences within the 1.3 Ga generation itself are partly due to a variety of source rocks, but also to different melting conditions. The chemical variation suggests that the SS2 type formed at deeper levels than the HUS1 and 1.5 Ga granites. The degree of melting was probably also higher than for the two latter types. The TYP3 rocks are likely to have formed at shallow levels, but with a higher degree of melting than the HUS1 rocks. A model based on isotopic, major- and trace-element data is consistent the theory that rocks similar to the Åmål granitoids are the source rock for the HUS1 type but not for the SS2 type. The epsilonNd(1.3) values for one of the HUS1-type rocks are, however, outside the known range of the time integrated epsilonNd(1.3) for the Åmål granitoids and could have a more primitive origin. Rocks from the Eastern Segment differ from those of the WS. The 1.7 Ga Mårdaklev granite has an evolved appearance similar to the HUS1 type, but no coeval rocks in the WS have this characteristic. The compositions of the 1.4 TTK intrusions vary between monzonite and granite - a trend not found in the Western Segment. The differences in geochemical character reflect differences in geological settings. The TTK intrusions of the Eastern Segment are interpreted to have formed at deep levels in a thicker and more evolved continental crust than the roughly coeval granites in the Western segment. The calc-alkaline character of the 1.6 Ga generation rocks suggests a less evolved, subduction related setting. The younger granites are derived from ensialic crust and variations in composition are interpreted to reflect different source rocks and different levels of magma generation. This investigation supports earlier suggestions that the evolutions of the Eastern and Western Segments were separate before Sveconorwegian time

ASSESSMENT OF THE COMMUNITY PHARMACY PRACTICE IN THE REPUBLIC OF MACEDONIA- BUILDING PLATFORM FOR IMPLEMENTATION OF GOOD PHARMACY PRACTICE

The objective of the study was to evaluate the actual status of the community pharmacy practice and quality of services and to identify the gaps and barriers to implement the best pharmacy practice and care. Cross-sectional descriptive survey was conducted for the pharmacies/pharmacists where pre-coded multiple choice closed questions were used with response format: activity fully applied, partially applied, applicable or not applicable. Set of 155 indicators was developed covering five essential components: pharmacy structure and practice; patient safety; manufacture practice; staff workflow and competences and quality assurance. The actual score was 64 out of 100. Pharmacy services related to manufacture practice and quality assurance were identified as the areas of highest priority for improvement, followed by the services related to patient safety. Priorities for intervention by key stakeholders (national authorities, academia, professional associations and pharmacists) and recommendations for introducing new and improving the existing roles of the pharmacists were defined. Key words: community pharmacy practice, services, standards, Republic of Macedoni

DNA Damage and DNA Damage Responses in THP-1 Monocytes after Exposure to Spores of either Stachybotrys chartarum or Aspergillus versicolor or to T-2 toxin

We have characterized cell death in THP-1 cells after exposure to heat-treated spores from satratoxin G–producing Stachybotrys chartarum isolate IBT 9631, atranone-producing S. chartarum isolate IBT 9634, and sterigmatocystin-producing Aspergillus versicolor isolate IBT 3781, as well as the trichothecenes T-2 and satratoxin G. Spores induced cell death within 3–6 h, with Stachybotrys appearing most potent. IBT 9631 induced both apoptosis and necrosis, while IBT 9634 and IBT 3781 induced mostly necrosis. T-2 toxin and satratoxin G caused mainly apoptosis. Comet assay ± formamidopyrimidine DNA glycosylase showed that only the spore exposures induced early (3h) oxidative DNA damage. Likewise, only the spores increased the formation of reactive oxygen species (ROS), suggesting that spores as particles may induce ROS formation and oxidative DNA damage. Increased Ataxia Telangiectasia Mutated (ATM) phosphorylation, indicating DNA damage, was observed after all exposures. The DNA damage response induced by IBT 9631 as well as satratoxin G was characterized by rapid (15 min) activation of p38 and H2AX. The p38 inhibitor SB 202190 reduced IBT 9631–induced H2AX activation. Both IBT 9631 and T-2 induced activation of Chk2 and H2AX after 3 h. The ATM inhibitor KU 55933, as well as transfection of cells with ATM siRNA, reduced this activation, suggesting a partial role for ATM as upstream activator for Chk2 and H2AX. In conclusion, activation of Chk2 and H2AX correlated with spore- and toxin-induced apoptosis. For IBT 9631 and satratoxin G, additional factors may be involved in triggering apoptosis, most notably p38 activation