Diclofenac Hypersensitivity: Antibody Responses to the Parent Drug and Relevant Metabolites

Background: Hypersensitivity reactions against nonsteroidal antiinflammatory drugs (NSAIDs) like diclofenac (DF) can manifest as Type I-like allergic reactions including systemic anaphylaxis. However, except for isolated case studies experimental evidence for an IgE-mediated pathomechanism of DF hypersensitivity is lacking. In this study we aimed to investigate the possible involvement of drug-and/or metabolite-specific antibodies in selective DF hypersensitivity. Methodology/Principal Findings: DF, an organochemically synthesized linkage variant, and five major Phase I metabolites were covalently coupled to carrier proteins. Drug conjugates were analyzed for coupling degree and capacity to crosslink receptor-bound IgE antibodies from drug-sensitized mice. With these conjugates, the presence of hapten-specific IgE antibodies was investigated in patients' samples by ELISA, mediator release assay, and basophil activation test. Production of sulfidoleukotrienes by drug conjugates was determined in PBMCs from DF-hypersensitive patients. All conjugates were shown to carry more than two haptens per carrier molecule. Immunization of mice with drug conjugates induced drug-specific IgE antibodies capable of triggering mediator release. Therefore, the conjugates are suitable tools for detection of drug-specific antibodies and for determination of their anaphylactic activity. Fifty-nine patients were enrolled and categorized as hypersensitive either selectively to DF or to multiple NSAIDs. In none of the patients' samples evidence for drug/metabolite-specific IgE in serum or bound to allergic effector cells was found. In contrast, a small group of patients (8/59, 14%) displayed drug/metabolite-specific IgG. Conclusions/Significance: We found no evidence for an IgE-mediated effector mechanism based on haptenation of protein carriers in DF-hypersensitive patients. Furthermore, a potential involvement of the most relevant metabolites in DF hypersensitivity reactions could be excluded

The Pleistocene cinder cones surrounding Volcán Colima, Mexico re-visited: eruption ages and volumes, oxidation states, and sulfur content

Located at the volcanic front in the western Mexican arc, in the Colima Rift, is the active Volcán Colima, which lies on the southern end of the massive (∼450 km 3 ) Colima-Nevado volcanic complex. Along the margins of this andesitic volcanic complex, is a group of 11 scoria cones and associated lavas, which have been dated by the 40 Ar/ 39 Ar method. Nine scoria cones erupted ∼1.3 km 3 of alkaline magma (basanite, leucite-basanite, minette) between 450 and 60 ka, with >99% between 240 and 60 ka. Two additional cones (both the oldest and calc-alkaline) erupted <0.003 km 3 of basalt (0.5 Ma) and <0.003 km 3 of basaltic andesite (1.2 Ma), respectively. Cone and lava volumes were estimated with the aid of digital elevation models (DEMs). The eruption rate for these scoria cones and their associated lavas over the last 1.2 Myr is ∼1.2 km 3 /Myr, which is more than 400 times smaller than that from the andesitic Colima-Nevado edifice. In addition to these alkaline Colima cones, two other potassic basalts erupted at the volcanic front, but ∼200 km to the ESE (near the historically active Volcán Jorullo), and were dated at 1.06 and 0.10 Ma. These potassic suites reflect the tendency in the west-central Mexican arc for magmas close to the volcanic front to be enriched in K 2 O relative to those farther from the trench.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47809/1/445_2005_Article_15.pd

Rise dynamics and relative ash distrubution in vulcanian eruption plumes at Santiaguito Volcano, Guatemala, revealed using an ultraviolet imaging camera

Santiaguito Volcano, Guatemala, regularly produces small vulcanian eruption plumes which rise to heights of up to 2 km. A combined study using a novel UV camera coupled with classical analysis of the fluid dynamics of finite-volume buoyant releases (thermals) has been used to develop a detection algorithm for ground-based volcanic ash monitoring. Analysis of plume rise dynamics shows that vulcanian eruption plumes at Santiaguito behave as axisymmetric buoyant thermals, and this behaviour is consistent with eruption of volcanic gas and particle mixtures whose initial momentum is dissipated by flow through a porous capping layer. The UV imager has been adapted to detect relative ash burdens through the use of a single filter, centred on 307 nm, an edge detection and background fitting procedure and normalising to a simple theoretical model. The method provides the capability to observe and measure the internal structure of the plume, and processes occurring during plume rise, including concentration of ash over time into the thermal \u27head\u27, increased ash at the plume edges during early formation of the thermal and dilution at the top of the plume head as entrainment occurs. Copyright 2008 by the American Geophysical Union

Stable runoff and weathering fluxes into the oceans over Quaternary climate cycles

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