Preadmission use of selective serotonin reuptake inhibitors and short-term mortality in diabetic patients hospitalized due to stroke.

BACKGROUND: Patients with diabetes have an increased risk of stroke with a poor prognosis. Moreover, diabetic patients are at increased risk of depression and therefore likely to use selective serotonin reuptake inhibitors (SSRIs). We examined whether preadmission SSRI use was associated with increased mortality in diabetic patients hospitalized due to stroke. METHODS: Population-based medical databases were used to identify all first-time stroke-related hospitalizations and subsequent mortality in diabetic patients in Denmark between 2004 and 2012 (n = 12 620). Based on redeemed prescriptions, SSRI use was categorized as current (new or long term), former or nonuse, and absolute 30-day mortality and mortality rate ratios (MRRs) were computed using Cox regression controlling for confounding factors. RESULTS: Amongst SSRI nonusers, 30-day stroke mortality was 15.8% (10.4% for ischaemic stroke, 41.8% for intracerebral haemorrhage and 27.3% for subarachnoid haemorrhage). Amongst current SSRI users, 30-day stroke mortality was 23.3% (17.1% for ischaemic stroke, 50.7% for intracerebral haemorrhage and 28.6% for subarachnoid haemorrhage). Current SSRI use was associated with increased 30-day stroke mortality compared with nonuse [adjusted MRR 1.3, 95% confidence interval (CI) 1.1-1.5], with the highest risk observed amongst new users (MRR 1.5, 95% CI 1.2-1.8). Overall stroke mortality was driven by increased mortality due to ischaemic stroke, with adjusted MRRs of 1.3 (95% CI 1.1-1.7) for current users and 1.7 (95% CI 1.2-2.4) for new users. Propensity score-matched results were similar and robust across subgroups. CONCLUSION: In patients with diabetes, preadmission SSRI use was associated with increased mortality following ischaemic stroke, compared with nonuse.

Pharmacogenomics in cardiovascular disease: focus on aspirin and ADP receptor antagonists.

Antiplatelet agents like aspirin and adenosine diphosphate receptor antagonists are effective in reducing recurrent ischemic events. Considerable inter-individual variability in the platelet inhibition obtained with these drugs has initiated a search for explanatory mechanisms and ways to improve treatment. In recent years, numerous genetic polymorphisms have been linked with reduced platelet inhibition and lack of clinical efficacy of antiplatelet drugs, particularly clopidogrel and aspirin. Consequently, attempts to adjust antiplatelet treatment according to genotype have been made, but the clinical benefit has been modest in studies performed so far. The progress in genome science over the last decade and the declining cost of sequencing technologies hold the promise of enabling genetically tailored antiplatelet therapy. However, more evidence is needed to clarify which polymorphisms may serve as targets to improve treatment. The present review outlines the panel of polymorphisms affecting the benefit of aspirin and adenosine diphosphate receptor antagonists, including novel and ongoing studies evaluating whether genotyping may be beneficial in tailoring antiplatelet therapy.

First record of the dog snapper Lutjanus jocu in the Mediterranean Sea.

The capture of a single specimen of the dog snapper Lutjanus jocu from the Ligurian Sea (north-west Mediterranean Sea) in November 2005 is reported. This finding constitutes the first record of this species from the Mediterranean Sea.

Enhanced microvascular permeability of PMA-induced acute lung injury is not mediated by cyclooxygenase products.

Products of cyclooxygenase activity have been proposed to mediate the pulmonary hypertension and increased microvascular permeability associated with phorbol myristate acetate- (PMA) induced acute lung injury. Previously, we reported that thromboxane (Tx) does not mediate PMA-induced pulmonary hypertension in intact anesthetized dogs. In the present study, PMA was administered to isolated canine lungs perfused with autologous blood at constant flow to investigate a possible role for Tx in the PMA-induced increase in microvascular permeability. Changes in permeability were assessed by determining changes in the capillary filtration coefficient (Kfc). In lobes pretreated with papaverine to prevent PMA-induced increases in pulmonary vascular resistance, Kfc increased from a baseline value of 0.2 +/- 0.03 to 1.5 +/- 0.29 ml.min-1.cmH2O-1.100 g wet lobe wt-1 (P < 0.01) 30 min after PMA (5.8 x 10(-8) M, n = 10). Concomitantly, TxB2, the stable metabolite of TxA2, increased from 138 +/- 44 to 1,498 +/- 505 pg/ml (P < 0.05) in the blood. Both the selective Tx synthase inhibitor, OKY-046 (7 x 10(-4) M, n = 6), and the cyclooxygenase inhibitor, indomethacin (10(-4) M, n = 7), prevented the PMA-induced increase in TxB2, but neither compound attenuated the PMA-induced increase in Kfc. ONO-3708 (10(-6) M), a selective prostaglandin (PG) H2/TxA2 receptor antagonist, prevented the vasoconstriction resulting from administration of U-46619, a stable PGH2/TxA2 receptor agonist, but it did not prevent the PMA-induced increases in Kfc (n = 6).(ABSTRACT TRUNCATED AT 250 WORDS)

Bacteriophage structure.

The purpose of this review is to provide information of the role played by electron microscopy in respect of bacteriophage structure. This 40 years' "love story" between phages and microscopy was a valuable contribution to the progress of scientific knowledge in molecular biology. In spite of the rather drastic treatment required for electron microscopical analysis, it was possible to reveal the molecular organization and morphogenic pathway of many of the bacteriophages cited in this paper.

Physiological, morphological, and physicochemical characterization of a novel Escherichia coli bacteriophage, phage MM.

A double-stranded DNA containing, T even-like, Escherichia coli bacteriophage, called MM, has been isolated from the local sewage and purified by polyethylene glycol precipitation followed by banding on a cesium chloride three-step gradient. It yields a burst size of 75 particles per infected cell, and has an adsorption coefficient of 3.3 x 10(-10) cm3/min and a latent period of 45 min. Electron microscopy of phage MM reveals an isometric icosahedral head, 92 nm long and 81 nm wide, and a 112-nm-long contractile tail with six pairs of 40-nm-long fibers attached to its baseplate. Phage MM appears similar to E. coli phage T4 or Salmonella phage O1. The density of phage MM in cesium chloride is 1.515 g/ml, and its total mass is 144 MDa. Gel electrophoresis of purified MM capsids displays two major capsid proteins in approximately equimolar amounts and with apparent molecular masses of 38 and 15 kDa. Similarly, purified MM tails yield two major polypeptides with apparent molecular masses of 55 and 16 kDa, most likely representing the major tail sheath and tail tube polypeptides. Its double-stranded DNA has a G-C content of 50%, a length of 131 kilobases (kb), and a mass of 89 MDa.

Length and shape variants of the bacteriophage T4 head: mutations in the scaffolding core genes 68 and 22.

The shape and size of the bacteriophage T4 head are dependent on genes that determine the scaffolding core and the shell of the prohead. Mutants of the shell proteins affect mainly the head length. Two recently identified genes (genes 67 and 68) and one already known gene (gene 22), whose products are scaffold constituents, have been investigated. Different types of mutants were shown to strongly influence the proportion of aberrantly shaped particles. By model building, these shape variants could be represented as polyhedral bodies derived from icosahedra, through outgrowths along different polyhedral axes. The normal, prolate particle is obtained by elongation along a fivefold axis. The mutations of the three core genes (genes 67, 68, and 22) affect the width mainly by lateral outgrowths of the prolate particle, although small and large isometric particles are also found. Many of the aberrant particles are multitailed, suggesting a correlation between tail attachment sites and shape.

Head structure of bacteriophages T2 and T4.

The length-to-width ratios of bacteriophage T2 and T4 heads and stereometric angles specifying the prolate icosahedral T2 capsid were evaluated on electron micrographs recorded from samples prepared by a variety of methods. The copy numbers of the major capsid protein, gp23*, of T2 and T4 phages were compared by quantitative gel electrophoresis. Taken together, the resulting values are most compatible with triangulation numbers T = 13 and Q = 21 for both T2 and T4, thus confirming the previously proposed capsid architecture of T4 revealed by indirect measurements and thereby eliminating the repeatedly reported discrepancy between T2 and T4 in favor of a common Q number of 21 corresponding to 960 copies of gp23*.

The efficiency of immunolabel on Lowicryl sections compared to theoretical predictions.

The surface of thin sections of aldehyde-fixed biological material shows a specimen-related relief of 2-6 nm with Lowicryl. Epon sections are about three times smoother. The relief is the consequence of thin-sectioning being in reality a cleavage. Epitopes are supposed to be laid open (or set free) because cleavage follows the interfaces between protein and Lowicryl. We have developed a simple theory on this basis and have theoretically estimated the efficiency of on-section labeling and compared it with experimental data. For randomly dispersed proteins in cytoplasm, Lowicryl sections will yield significant label only when the concentration of the antigen is about 10 microM or more. The complex situation of more compact proteins, as represented by fibers, sheets, and biological membranes is discussed and the difficulty of significant calculations is explained. Pre-embedding labeling and melted cryosections should give 10-30 times more label. The possible reasons for the observed much smaller gain of not more than two to three times are discussed.

The wrapping phenomenon in air-dried and negatively stained preparations.

We demonstrate that the interface energies involved in the direct preparation of supramolecular structures onto supporting films leads very frequently to a smooth wrapping of the supporting film around approximately one third to one half of the structure. We conclude that in such cases the structure is more rigid than the supporting film; examples being ribosomes, small viruses and small glass fragments. Other structures are less rigid and become significantly flattened. Complete flattening is frequently observed with empty virus capsids. The sandwich technique, by which a specimen is placed between two supporting films, in general leads to increased flattening. Only in few cases (e.g. ribosomes) are biological particles rigid enough to resist flattening and become wrapped from both sides.

The molecular organization of beet necrotic yellow vein virus.

Isolates of beet necrotic yellow vein virus (BNYVV) contain rod-like virus particles of four different lengths. Using electron microscopy in combination with optical diffraction and digital image processing methods, we have determined their structural organization. All particles observe the same helical symmetry, according to which the coat protein molecules (Mr approximately 21,000) follow a single-stranded right-handed helix of pitch 2.6 nm. This helix has an axial repeat of four turns, involving 49 protein subunits. The different particle lengths are apparently dictated by the four RNA species which compose the segmented BNYVV genome, with four nucleotides protected by each coat protein subunit. The spatial arrangement of BNYVV RNA--49 residues per helical turn, pitch = 2.6 nm--is virtually identical to that of tobacco mosaic virus (TMV) RNA (49 residues per turn, pitch = 2.3 nm), although the helical packing of protein (49/3 subunits per turn) and RNA-to-protein stoichiometry (3 bases per subunit) of TMV are significantly different from those of BNYVV (49/4 subunits per turn and 4 bases per subunit, respectively).

Paracrystalline arrays of protein-synthesis elongation factor Tu. Comparison with polymerized actin.

Homogeneous protein synthesis elongation factor Tu from Escherichia coli forms aggregates at high concentrations of ammonium sulfate which have a filamentous appearance in the light microscope. Electron microscopy of negatively stained preparations shows that these aggregates are paracrystalline, including three different forms. On the basis of analyses by optical diffraction, this polymorphism can be explained in terms of three different tubular foldings of the same basic two-dimensional surface lattice. This can be compared with that underlying the structure of actin filaments, thus providing a crucial test of the putative relationship between the elongation factor and actin [Rosenbusch, J. P. et al. (1976) J. Supramol. Struct. 5, 391-396]. The differences between the surface lattices, in conjunction with the negative results of sensitive immunochemical tests for possible cross-reactivities between the two proteins, suggest that any such relationship is very remote.