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Supplemental Material, supplementary_v3_gout_(1)_revised_Elaine-updated for Effectiveness of Statins as Primary Prevention in People With Gout: A Population-Based Cohort Study by Maria Garcia-Gil, Marc Comas-Cufí, Rafel Ramos, Ruth Martí, Lia Alves-Cabratosa, Dídac Parramon, Daniel Prieto-Alhambra, Jose Miguel Baena-Díez, Betlem Salvador-González, Roberto Elosua, Irene R. Dégano, Jaume Marrugat and María Grau in Journal of Cardiovascular Pharmacology and Therapeutics

An increasing flow of evidences collected on elementary forms of learning processes in selected animal models evidentiates some mechanisms which can represent the basic cellular principles underlying plastic changes: 1. 5HT and second messengers of nucleotide type (like cAMP) have a pivotal role in the learning process. 2. In almost all short-term learning processes the modifications are subserved by a mechanism of protein phosphorylation. 3. In various animal models the modulation of K+ and Ca2+ channels is the molecular mechanism for learning. Experiments performed in sensory T neuron of the leech indicate that the modulation of Na+/K+ electrogenic pump is one of the fundamental mechanism for learning. 4. In long-term plastic changes, the most important finding is that newly synthesized proteins are formed. 5. In addition to what has been observed in the Aplysia model, where changes in synaptic efficacy represent the basic principles of memory storage, in the leech it has been demonstrated that a molecular machinery present in a single neuron can adapt the activity of the cell to environmental stimuli.

The activation of rat basophilic leukemia cells for histamine release is accompanied by Ca2+ influx and arachidonic acid release. IgE receptor but not A23187 ionophore stimulation of these cells also resulted in phosphoinositide breakdown. In these experiments, the culture of these cells with dexamethasone inhibited IgE- and ionophore-mediated histamine release. The concentration for 50% of maximal inhibition was 12 nM, and prolonged exposure to the drug was required, with maximal effect observed in 8 to 15 hr. The inhibitory effect of dexamethasone was reversible (t1/2 for recovery was 16 hr). Dexamethasone blocked the IgE-mediated 45Ca2+ influx and the release of [14C]-arachidonic acid (IC50 of 1 nM and 10 nM respectively). Dexamethasone inhibited the IgE receptor-mediated phosphoinositide breakdown (IC50 of 5 nM). It also decreased arachidonic acid release after A23187 stimulation demonstrating an effect on phospholipase A2. Therefore, exposure of the cells to dexamethasone results in the inhibition of both phospholipase A2 and phospholipase C pathways of arachidonic acid generation.

The bridging of IgE receptors on rat basophilic leukemia cells (RBL-2H3) results in a number of biochemical events that accompany histamine secretion. Prominent among these is the release of arachidonic acid from cellular phospholipids, which could be due to the activation of phospholipase enzymes. In the present experiments we studied the intracellular activation of phospholipase A2 (PLA2) during histamine release. RBL-2H3 cells were stimulated through the IgE receptor, and the homogenates were prepared and tested for phospholipase A2 activity on 1-stearoyl-2-[14C]arachidonyl-sn-3-phosphatidylcholine. The amount of activity in the homogenates was dependent on the concentration of secretagogue used to activate the cells. Under optimal conditions there was a 1.86 +/- 0.12-fold (mean +/- SEM, N = 44) increase in the activity found in homogenates of stimulated cells. Activity was present in homogenates prepared 30 sec after cell activation, was optimal between 5 and 10 min, and decreased later. In time course experiments the PLA2 activation preceded histamine release. The activation of the enzyme in the cell occurred in the presence of 10 microM EGTA in the extracellular medium, which completely inhibited release of arachidonic acid and histamine. However, the activity of the enzyme required Ca2+. The PLA2 activity in the homogenates and the extent of cell stimulation for histamine release were maximal at the same concentration of antigen, and both were blocked by the addition of a monovalent hapten. The enzyme in the homogenates was capable of cleaving arachidonic acid from different phospholipids. The production of lysophospholipids could play a critical role in histamine release from cells. These results demonstrate the activation of PLA2 enzyme in cellular homogenates during the secretory process.

Triggering of rat basophilic leukemia cells for histamine secretion is accompanied by arachidonic acid release. We studied the source of this arachidonic acid released after IgE or calcium ionophore A23187 stimulation. The 48-hr culture of the cells with [14C]arachidonic acid resulted in labeling of the phospholipids to constant specific activity. After IgE stimulation, 8.8% of the cellular [14C]arachidonate was released; this was predominantly from phosphatidylinositol (PI)/phosphatidylserine (PS) (66.3%), less from phosphatidylethanolamine (PE) (25.9%), and minimally from phosphatidylcholine (PC). In contrast, after ionophore stimulation the cells released 16.4% of cellular [14C]arachidonate, most of this was from PE (55.4%) followed by about equal amounts from PS/PI and PC (24% and 20%, respectively). Therefore, the source of the released arachidonic acid depends on the stimulus. In contrast, the results are different when the cells are cultured for only 2 hr with [14C]arachidonic acid. The label in phospholipids was in PC (44%), PE (38%), and PI/PS (20%); the stimulation of the cells with IgE or ionophore resulted in the release of the [14C]arachidonate from PC (81% and 96%, respectively). This suggests the presence of several pools of phospholipids that are labeled at different rates and have variable proximity and/or accessibility to the phospholipase(s) enzyme(s) activated during cell secretion.

The economic and environmental impact of shallow gas in marine sediments has led to an increase in the number of studies of this subject over the last twenty years. Shallow gas in marine sediments is mainly composed of methane that can be generated by biogenic or thermogenic processes (Flodgate and Judd, 1992), although most shallow gas is biogenic in origin. Gas accumulates in marine sediments worldwide, mainly associated with muddy sediments rich in organic matter (Hovland and Judd, 1988). Acoustic methods are a very useful tool for detecting them due to the masking effect on the seismic records caused by the presence of free gas in sediments. The Galician Rías Baixas are ancient fluvial valleys affected by seasonal upwelling events that make them highly productive. Also, the oceanographic conditions and morphology of the Ría de Vigo favor the sedimentation of muddy sediment along its axis, making it a propitious environment for the generation of biogenic gas in the sedimentary infill. The main objectives of the present thesis are (1) to reinterpret the seismic records of the ria in order to determine the stratigraphic context in which methane accumulations take place, and (2) to study gas accumulations and seepages in seismic records and to perform a geochemical and sedimentological characterization of the sediment containing the gas. The study of the location of the gas accumulations and seepage inside the stratigraphic context of the Ría de Vigo, the methane concentrations in sediment and the methane fluxes to the water column further our knowledge of the methane budget in the ria. Ministerio de Ciencia e Innovación | Ref. CTM2009-13926- C02-01