Modern adjunctive pharmacotherapy of myocardial infarction

During acute myocardial infarction (MI), aspirin, beta-adrenergic antagonists and oral angiotensin converting enzyme (ACE) inhibitors should be used as an adjunct to reperfusion therapy. Medications upon discharge from the hospital should include aspirin and a beta-blocker. An ACE inhibitor should also be prescribed unless the ejection fraction is > 45%. Particular indications for an ACE inhibitor are an anterior MI, congestive heart failure, ejection fraction < 45% and mitral regurgitation. beta-blockers, when given to patients treated with ACE inhibitors, appear to produce an additional benefit compared with an ACE inhibitor alone. Based on the Scandinavian Simvastatin Survival Study (4S), Cholesterol and Recurrent Events (CARE) and Long-Term Intervention with Pravastatin in Ischemic Disease (LIPID) trials, a statin should also be given to subjects with low density lipoprotein (LDL)-cholesterol levels above 125 mg/dl, independent of total cholesterol levels. Therapy should be administered in an attempt to reduce the LDL-cholesterol level to 90-100 mg/dl (2.3-2.6 mM/l). In patients with normal or low levels on initial evaluation, screening for lipid abnormalities should be deferred for 2 months since acute phase responses and passive hepatic congestion can cause spuriously normal levels. Calcium channel blockers, nitrates, lidocaine, anti-arrhythmic drugs and i.v. magnesium should not be administered routinely after acute MI and their use should be restricted to selected settings.     

Human myeloid alpha 3-fucosyltransferase is involved in the expression of the sialyl-Lewis(x) determinant, a ligand for E- and P-selectin

The sialyl-Lex determinant (NeuAc alpha 2-->3Gal beta 1-->4[Fuc alpha- 1-->3]GlcNAc) has been identified as a major ligand in the selectin- mediated adhesion of neutrophils and monocytes to activated endothelium or platelets. This carbohydrate epitope is formed by the sequential action of alpha 3-sialyltransferase and alpha 3-fucosyltransferase on N- acetyllactosamine (Gal beta 1-->4GlcNAc) disaccharide termini of glycoconjugates. We have addressed the role of the human myeloid alpha 3-fucosyltransferase in the expression of this epitope at the leucocyte surface by determining its activity in human-mouse leukemic cell hybrids (WEGLI), normal human granulocytes and chronic myeloid leukemia (CML) cells using sialylated and desialylated glycoproteins and oligosaccharides as acceptor substrates. In contrast to what has been reported for the myeloid-type enzyme, we found that the alpha 3- fucosyltransferase of the cells studied can use sialylated acceptors be it that the activity is several times lower than with asialo- substrates. Characterization of the product obtained with a sialylated oligosaccharide indicated that the enzyme can catalyze the formation of the sialyl-Le(x) structure. Flow cytometry of the WEGLI cells using a sialyl-Le(x)-specific monoclonal antibody (MoAb) showed that these cells indeed express sialyl-Lex at their surface, provided that they contain human chromosome 11. Earlier the presence of this chromosome had been correlated with the expression of alpha 3-fucosyltransferase activity. In addition to sialyl-Le(x), WEGLI cells containing chromosome 11 showed high-expression levels of related structures recognized by antibodies VIM-2 and VIM-8, suggesting that fucose addition can occur at both distal and proximal GlcNAc residues in poly- N-acetyl-lactosaminoglycan sequences. Based on the human chromosome contents it could be ruled out that the alpha 3-fucosyltransferase of WEGLI cells is a Lewis-type alpha 3/4- or plasma-type alpha 3- fucosyltransferase, the genes of which have been mapped to chromosome 19. It is concluded that the enzyme studied is of the myeloid-type and indeed is involved in the synthesis of sialyl-Le(x) (and also VIM-2 and VIM-8 structures) in leukocytes provided that its expression is at a sufficiently high level.     

Depletion of antral gastrin after food in rats.

The results of these studies indicate that in fasting rats, there is an abrupt and prolonged rise in circulating gastrin after feeding. This increase in serum gastrin is accompanied by an early (five minutes) diminution in antral gastrin which is followed by slightly higher and more variable antral gastrin values. These findings suggest that feeding triggers the release of gastrin with early depletion of antral gastrin and that, subsequently, gastrin syhthesis and release interact cyclically to maintain antral and serum concentrations of gastrin. Antral, fundic, and duodenal gastrin values in rats are similar to those reported in dogs and cats. The jejunum of the rat contains little, if any, gastrin.     

Sponsorship and fund-raising in New Zealand schools: implications for health

OBJECTIVE: To examine school participation in sponsorship, incentive and fundraising initiatives and to describe feedback about potential health implications and possible solutions from key stakeholders in the health and education sectors. METHODS: All secondary/area schools and 15% of primary/intermediate schools were randomly selected from six geographical regions of New Zealand. School principals completed a self-report questionnaire. Survey findings were summarised in a discussion document and forwarded to 53 key stakeholders for comment. RESULTS: Most schools reported participation in sponsorship, incentive and fundraising initiatives (83% of primary/intermediate and 85% of secondary/area schools). Some partnerships delivered positive health messages to students, but others were linked with products or activities potentially deleterious to health. Examples of the latter included provision of foods high in fat and sugar to students and funding from organisations whose profits were generated from gambling and alcohol sales. Key stakeholder concerns included the undermining of classroom health education and perceptions that schools were endorsing product consumption. Suggestions to address these concerns included increasing co-ordination and awareness, alternative sources of funding, and policy guidelines or legislation. CONCLUSIONS: Most schools were involved in some sort of sponsorship, incentive and fundraising initiatives, some of which had the potential to have a negative impact on the health of students. IMPLICATIONS: There is an urgent need for co-operation between the health and education sectors to ensure that these funding partnerships do not compromise student health.