Solid phase extraction for removal of matrix effects in lipophilic marine toxin analysis by liquid chromatography-tandem mass spectrometry

The potential of solid phase extraction (SPE) clean-up has been assessed to reduce matrix effects (signal suppression or enhancement) in the liquid chromatography-tandem mass spectrometry (LC¿MS/MS) analysis of lipophilic marine toxins. A large array of ion-exchange, silica-based, and mixed-function SPE sorbents was tested. Polymeric sorbents were found to retain most of the toxins. Optimization experiments were carried out to maximize recoveries and the effectiveness of the clean-up. In LC¿MS/MS analysis, the observed matrix effects can depend on the chromatographic conditions used, therefore, two different HPLC methods were tested, using either an acidic or an alkaline mobile phase. The recovery of the optimized SPE protocol was around 90% for all toxins studied and no break-through was observed. The matrix effects were determined by comparing signal response from toxins spiked in crude and SPE-cleaned extracts with those derived from toxins prepared in methanol. In crude extracts, all toxins suffered from matrix effects, although in varying amounts. The most serious effects were observed for okadaic acid (OA) and pectenotoxin-2 (PTX2) in the positive electrospray ionization mode (ESI+). SPE clean-up on polymeric sorbents in combination with the alkaline LC method resulted in a substantial reduction of matrix effects to less than 15% (apparent recovery between 85 and 115%) for OA, yessotoxin (YTX) in ESI¿ and azaspiracid-1 (AZA1), PTX2, 13-desmethyl spirolides C (SPX1), and gymnodimine (GYM) in ESI+. In combination with the acidic LC method, the matrix effects after SPE were also reduced but nevertheless approximately 30% of the matrix effects remained for PTX2, SPX1, and GYM in ESI+. It was concluded that SPE of methanolic shellfish extracts can be very useful for reduction of matrix effects. However, the type of LC and MS methods used is also of great importance. SPE on polymeric sorbents in combination with LC under alkaline conditions was found the most effective method

Hormonal crises following receptor radionuclide therapy with the radiolabeled somatostatin analogue [177Lu-DOTA0,Tyr3]octreotate

textabstractIntroduction: Receptor radionuclide therapy is a promising treatment modality for patients with neuroendocrine tumors for whom alternative treatments are limited. The aim of this study was to investigate the incidence of hormonal crises after therapy with the radiolabeled somatostatin analogue [177Lu-DOTA0,Tyr3]octreotate (177Lu-octreotate). Materials and methods: All177Lu- octreotate treatments between January 2000 and January 2007 were investigated. Four hundred seventy-six patients with gastroenteropancreatic neuroendocrine tumors and three patients with metastatic pheochromocytoma were included for analysis. Results: Four hundred seventy-nine patients received a total of 1,693 administrations of177Lu-octreotate. Six of 479 patients (1%) developed severe symptoms because of massive release of bioactive substances after the first cycle of177Lu-octreotate. One patient had a metastatic hormone-producing small intestinal carcinoid; two patients had metastatic, hormone-producing bronchial carcinoids; two patients had vasoactive intestinal polypeptide-producing pancreatic endocrine tumors (VIPomas); and one patient had a metastatic pheochromocytoma. With adequate treatment, all patients eventually recovered. Conclusion: Hormonal crises after177Lu- octreotate therapy occur in 1% of patients. Generally,177Lu- octreotate therapy is well tolerated

PPARα Deficiency in Inflammatory Cells Suppresses Tumor Growth

Inflammation in the tumor bed can either promote or inhibit tumor growth. Peroxisome proliferator-activated receptor (PPAR)α is a central transcriptional suppressor of inflammation, and may therefore modulate tumor growth. Here we show that PPARα deficiency in the host leads to overt inflammation that suppresses angiogenesis via excess production of the endogenous angiogenesis inhibitor thrombospondin-1 and prevents tumor growth. Bone marrow transplantation and granulocyte depletion show that PPARα expressing granulocytes are necessary for tumor growth. Neutralization of thrombospondin-1 restores tumor growth in PPARα-deficient mice. These findings suggest that the absence of PPARα activity renders inflammatory infiltrates tumor suppressive and, thus, may provide a target for inhibiting tumor growth by modulating stromal processes, such as angiogenesis

Valid Orderings of Real Hyperplane Arrangements

Given a real finite hyperplane arrangement $$\mathcal {A}$$ A and a point $$p$$ p not on any of the hyperplanes, we define an arrangement $$\mathrm {vo}(\mathcal {A},p)$$ vo ( A , p ) , called the valid order arrangement, whose regions correspond to the different orders in which a line through $$p$$ p can cross the hyperplanes in $$\mathcal {A}$$ A . If $$\mathcal {A}$$ A is the set of affine spans of the facets of a convex polytope $$\mathcal {P}$$ P and $$p$$ p lies in the interior of $$\mathcal {P}$$ P , then the valid orderings with respect to $$p$$ p are just the line shellings of $$\mathcal {P}$$ P where the shelling line contains $$p$$ p . When $$p$$ p is sufficiently generic, the intersection lattice of $$\mathrm {vo}(\mathcal {A},p)$$ vo ( A , p ) is the Dilworth truncation of the semicone of $$\mathcal {A}$$ A . Various applications and examples are given. For instance, we determine the maximum number of line shellings of a $$d$$ d -polytope with $$m$$ m facets when the shelling line contains a fixed point $$p$$ p . If $$\mathcal {P}$$ P is the order polytope of a poset, then the sets of facets visible from a point involve a generalization of chromatic polynomials related to list colorings

A middle Eocene carbon cycle conundrum

The Middle Eocene Climatic Optimum (MECO) was an approximately 500,000-year-long episode of widespread ocean–atmosphere warming about 40 million years ago, superimposed on a long-term middle Eocene cooling trend. It was marked by a rise in atmospheric CO2 concentrations, biotic changes and prolonged carbonate dissolution in the deep ocean. However, based on carbon cycle theory, a rise in atmospheric CO2 and warming should have enhanced continental weathering on timescales of the MECO. This should have in turn increased ocean carbonate mineral saturation state and carbonate burial in deep-sea sediments, rather than the recorded dissolution. We explore several scenarios using a carbon cycle model in an attempt to reconcile the data with theory, but these simulations confirm the problem. The model only produces critical MECO features when we invoke a sea-level rise, which redistributes carbonate burial from deep oceans to continental shelves and decreases shelf sediment weathering. Sufficient field data to assess this scenario is currently lacking. We call for an integrated approach to unravel Earth system dynamics during carbon cycle variations that are of intermediate timescales (several hundreds of thousands of years), such as the MECO

The Use of Bright and Dark Types of Humour is Rooted in the Brain

The ways in which humour can be used are related to the manifold interpersonal functions humour can serve, some of which are positive, and some negative. In the present study, phasic changes in the functional coupling of prefrontal and posterior cortex (EEG coherence) during other people's auditory displays of happy and sad mood were recorded to predict people's typical use of humour in social interactions. Greater use of benevolent humour, the intentions of which are in keeping with the characteristics of "laughing-with" humour, was associated with greater decreases of prefrontal-posterior coupling during the processing of happy laughter. More loose prefrontal-posterior coupling indicates loosening of control of the prefrontal cortex over the incoming perceptual information, thereby opening up the perceptual gate and allowing the brain to become more affected by the social-emotional signals. Greater use of humour styles linked to malicious intentions of "laughing-at" humour was associated with responses indicating a wider opened perceptual gate during the processing of other people's crying. The findings are consistent with the idea that typical humour styles develop in line with the rewarding values of their outcomes (e.g., interaction partners are happy or hurt), which in turn are defined through the individuals' latent interpersonal goals