Determinants Of Blood Lead Levels In An Adult Population From A Mining Area In Brazil

During the last fifty years the Ribeira river valley, Brazil, had been under the influence of the full activity of a huge lead refinery and mining along the riverside. The plant completely stopped all kind of industrial activities at the end of 1995, and part of the worker population and their families still remain living nearby in small communities. The objective of the present study was to assess the determinants of blood lead levels (BLL) in these mining areas, where residual environmental contamination from the past industrial activity still remains. Blood samples of 350 adults aged 15 to 70, residing in areas around the mine and the refinery were collected. A questionnaire was given in order to gather information on food habits, current and former residential places, occupational activities, among other variables. Blood lead concentrations were analysed by graphite furnace atomic absorption spectrometry using Zeeman background correction. Logistic regression analysis was conducted to examine the independent contribution of selected variables in predicting BLL in those subjects. The following variables showed significant association with high BLL: residential area close to the lead refinery, former dwelling at the refinery village, male gender, smoking habits, and consume of fruits from home back yard.107I127130Berglund, M., Pedersen, N.L., Bjorkman, L., Vahter, M., (1999) Environ Res, 80, pp. 222-230Brody, D.J., Pirkle, J.L., Kramer, R.A., Flegal, K.M., Matte, T.D., Gunter, E.W., Paschal, D.C., (1994) JAMA, 27, pp. 277-283Hense, H.W., Filipiak, B., Novak, L., Stoeppler, M., (1992) Int J Epidem, 21Jakubowski, M., Trzcinka-Ochocka, M., Razniewska, G., Christensen, J.M., Starek, A., (1996) Int Arch Occup Environ Health, 68, pp. 193-198Kristal-Boneh, E., Froom, P., Yerushalmi, N., Ashkanazi, R., Pardo, A., Shine, R., Ribak, J., (1998) Am J Ind Med, 34, pp. 512-516Leroyer, A., Hemon, D., Nisse, C., Bazerques, J., Salomez, J.L., Haguenoer, (2001) Sci Total Environ, 267, pp. 87-99Liou, S.H., Wu, T.N., Chiang, H.C., Yang, G.Y., Yang, T., Wu, Y.Q., Lai, J.S., Chang, P.Y., (1996) Sci Total Environ, 180, pp. 211-219Mahaffey, K.R., (1995) Environ Health Perspect, 103, pp. 191-196Muldoon, S.B., Cauley, J.A., Kuller, L.H., Scott, S., Rohay, J., (1994) Am J Epidemiol, 139, pp. 599-608Ooi, P.L., Goh, K.T., Heng, B.H., Sam, C.T., Kong, K.H., Rajan, U., (1991) Rev Environ Health, 9, pp. 2017-2213Paoliello, M.M.B., Gutierrez, P.R., Turini, C.A., Matsuo, T., Mezzaroba, L., Barbosa, D.S., Alvarenga, A.L.P., Lobo, B., (2001) Pan Am J Public Health, 9, pp. 315-319Probst-Hensch, N., Braun-Fahrlaender, C., Bodenmann, A., Ackermann-Liebrich, U., (1993) Soz Praventivmed, 38, pp. 43-50Yang, J.S., Kang, S.K., Park, I.J., Rhee, K.Y., Moon, Y.H., Sohn, D.H., (1996) Int Arch Occup Environ Health, 68, pp. 199-20

Inclusion Complex Of S(-) Bupivacaine And 2-hydroxypropyl- β-cyclodextrin: Study Of Morphology And Cytotoxicity

Local anesthetics (LA) belong to a class of pharmacological compounds that attenuate or eliminate pain by binding to the sodium channel of excitable membranes, blocking the influx of sodium ions and the propagation of the nerve impulse. S (-) bupivacaine (S(-) bvc) is a local anesthetic of amino-amide type, widely used in surgery and obstetrics for sustained peripheral and central nerve blockade. This article focuses on the characterization of an inclusion complex of S(-) bvc in 2-hydroxypropyl-β-cyclodextrin (HP-β-CD). Differential scanning calorimetry, scanning electron microscopy and X-Ray diffraction analysis showed structural changes in the complex. In preliminary toxicity studies, the cell viability tests revealed that the inclusion complex decreased the toxic effect (p<0.001) produced by S(-) bvc. These results suggest that the S(-) bvc:HP-β-CD inclusion complex represents a promising agent for the treatment of regional pain.273207212Araújo, D.R., Cereda, C.M., Brunetto, G.B., Pinto, L.M.A., Santana, M.H., de Paula, E., Encapsulation of mepivacaine prolongs the analgesia provided by sciatic nerve blockade in mice (2004) Can J Anaesth, 51, pp. 566-572Araújo, D.R., Fraceto, L.F., Braga, A.F.A., de Paula, E., Drug-delivery systems for racemic bupivacaine (S50-R50) and bupivacaine enantiomeric mixture (S75-R25):cyclodextrins complexation effects on sciatic nerve blockade in mice (2005) Rev Bras Anestesiol, 55, pp. 316-328Araújo, D.R., Moraes, C.M., Fraceto, L.F., Braga, A.F.A., de Paula, E., Cyclodextrin-bupivacaine enantiomeric mixture (S75-R25) inclusion complex and intrathecal anesthesia in rats (2006) Rev Bras Anestesiol, 56, pp. 495-506Bibby, D., Davies, N.M., Tueker, I.G., Mechanisms by which cyclodextrins modify drug release from polymeric drug delivery systems (2000) Int J Pharm, 197, pp. 1-11Covino, B.G., Vassalo, H.G., (1976) Local anesthetics: Mechanisms of action and clinical use, , New York: Grune and Stratton;, 255pFoster, R.H., Markham, A., Levobupivacaine. A review of its pharmacology and use as a local anaesthetic (2000) Drugs, 59, pp. 551-579Grant, G.J., Bansinath, M., Liposomal delivery systems for local anesthetics (2001) Reg Anesth Pain Med, 26, pp. 61-63Gristwood, R.W., Cardiac and CNS toxicity of levobupivacaine: Strengths of evidence for advantage over bupivacaine (2002) Drug Saf, 25, pp. 153-163Hirayama, F., Uekama, K., Cyclodextrin-based controlled drug release system (1999) Adv Drug Deliv Rev, 36, pp. 125-141Huang, Y.F., Pryor, M.E., Mather, L.E., Veering, B.T., Cardiovascular and central nervous system effects of intravenous S-bupivacaine and bupivacaine in sheep (1998) Anesth Analg, 86, pp. 797-804Jong, R.H., (1994) Local anesthetics, , Springfield: CC. Thomas;, 325pKohata, S., Jyodi, K., Ohyoshi, A., Thermal decomposition of cyclodextrins (α -, β-, γ, and modified β-CyD) and of metal-(β-CyD) complex in the solid phase (1993) Thermochim Acta, 217, pp. 187-198Loftsson, T., Brewster, M.E., Pharmaceutical application of Cyclodextrin. 1. Drug solubilization and stabilization (1996) J Pharm Sci, 85, pp. 1017-1025Loukas, Y.L., Vraka, V., Gregoriadis, G., Novel non-acidic formulations of haloperidol complexed with beta-cyclodextrin derivatives (1997) J Pharm Biomed Anal, 16, pp. 263-268Mather, L.E., McCall, P., McNicol, P.L., Bupivacaine enantiomer pharmacokinetics after intercostal neural blockade in liver transplant patients (1995) Anesth Analg, 80, pp. 328-335Michaud, M., Icart, S., Determination of the substitution of hydroxypropylbetadex using fourier transform infrared spectrophotometry (2001) PharmEuropa, 13, pp. 714-716Naidu, N.B., Chowdary, K.P.R., Murthy, K.V.R., Satyanarayana, V., Hayman, A.R., Becket, G., Physicochemical characterization and dissolution properties of meloxicam-cyclodextrin binary systems (2004) J Pharm Biomed Anal, 35, pp. 75-86Pinto, L.M.A., Fraceto, L.F., Santana, M.H.A., Pertinhez, T.A., Oyama, S., de Paula, E., Physico-chemical characterization of benzocaine-β-cyclodextrin inclusion complexes (2005) J Pharm Biomed Anal, 39, pp. 956-963Ren, X., Xue, Y., Liu, J., Zhang, K., Zheng, J., Lou, G., Gou, C., Shen, J., A novel cyclodextrin-deri ved tellurium compound with glutathione peroxidase (2002) Chembiochem, 3, pp. 363-365Rose, J.S., Neal, J.M., Kopacz, D.J., Extended-duration analgesia: Update on microspheres and liposomes (2005) Reg Anesth Pain Med, 30, pp. 275-285Strichartz, G.R., Ritchie, J.M., (1987) Local anesthetics: Handbook of experimental pharmacology, , Berlin: Springer-Verlag;, 445pThompson, D.O., Cyclodextrin-enabling excipients: Their present and future use in pharmaceuticals (1997) Crit Rev Ther Drug Carrier Syst, 14, pp. 1-10

Spallation reactions. A successful interplay between modeling and applications

The spallation reactions are a type of nuclear reaction which occur in space by interaction of the cosmic rays with interstellar bodies. The first spallation reactions induced with an accelerator took place in 1947 at the Berkeley cyclotron (University of California) with 200 MeV deuterons and 400 MeV alpha beams. They highlighted the multiple emission of neutrons and charged particles and the production of a large number of residual nuclei far different from the target nuclei. The same year R. Serber describes the reaction in two steps: a first and fast one with high-energy particle emission leading to an excited remnant nucleus, and a second one, much slower, the de-excitation of the remnant. In 2010 IAEA organized a worskhop to present the results of the most widely used spallation codes within a benchmark of spallation models. If one of the goals was to understand the deficiencies, if any, in each code, one remarkable outcome points out the overall high-quality level of some models and so the great improvements achieved since Serber. Particle transport codes can then rely on such spallation models to treat the reactions between a light particle and an atomic nucleus with energies spanning from few tens of MeV up to some GeV. An overview of the spallation reactions modeling is presented in order to point out the incomparable contribution of models based on basic physics to numerous applications where such reactions occur. Validations or benchmarks, which are necessary steps in the improvement process, are also addressed, as well as the potential future domains of development. Spallation reactions modeling is a representative case of continuous studies aiming at understanding a reaction mechanism and which end up in a powerful tool.Comment: 59 pages, 54 figures, Revie

Immunophenotype of gastric tumors unveils a pleiotropic role of regulatory T cells in tumor development

Simple SummaryThe role of regulatory T cells (Tregs) in gastric cancer (GC) is still controversial and poorly understood. GC patients have increased numbers of Tregs in peripheral blood and among tumor infiltrating lymphocytes; however, their prognostic value depends on specific tumor features (e.g., tumor location and/or microsatellite instability status). We found that Tregs might induce membrane expression of IL2R alpha in intestinal-type GC cells, which associates with MAPK signaling pathway activation and spheroid growth. Moreover, Tregs accumulate at early steps of intestinal-type GCs progression, when tumors are starting to grow through the stomach wall, and do not present vascular and perineural invasion. Our findings suggest a novel non-immunosuppressive role of Treg cells in intestinal-type GC, which may unlock novel therapeutic immuno-oncology strategies for intestinal-type GC or other tumors with similar immune context.Gastric cancer (GC) patients display increased regulatory T cell (Tregs) numbers in peripheral blood and among tumor-infiltrating lymphocytes. Nevertheless, the role of Tregs in GC progression remains controversial. Here, we sought to explore the impact of Tregs in GCs with distinct histology, and whether Tregs can directly influence tumor cell behavior and GC development. We performed a comprehensive immunophenotyping of 82 human GC cases, through an integrated analysis of multispectral immunofluorescence detection of T cells markers and patient clinicopathological data. Moreover, we developed 3D in vitro co-cultures with Tregs and tumor cells that were followed by high-throughput and light-sheet imaging, and their biological features studied with conventional/imaging flow cytometry and Western blotting. We showed that Tregs located at the tumor nest were frequent in intestinal-type GCs but did not associate with increased levels of effector T cells. Our in vitro results suggested that Tregs preferentially infiltrated intestinal-type GC spheroids, induced the expression of IL2R alpha and activation of MAPK signaling pathway in tumor cells, and promoted spheroid growth. Accumulation of Tregs in intestinal-type GCs was increased at early stages of the stomach wall invasion and in the absence of vascular and perineural invasion. In this study, we proposed a non-immunosuppressive mechanism through which Tregs might directly modulate GC cells and thereby promote tumor growth. Our findings hold insightful implications for therapeutic strategies targeting intestinal-type GCs and other tumors with similar immune context.MTG4Molecular tumour pathology - and tumour genetic

Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in √s = 7 TeV pp collisions with the ATLAS detector

A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fb−1 of proton–proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results

Simulating rewetting events in intermittent rivers and ephemeral streams: A global analysis of leached nutrients and organic matter

Climate change and human pressures are changing the global distribution and the ex‐ tent of intermittent rivers and ephemeral streams (IRES), which comprise half of the global river network area. IRES are characterized by periods of flow cessation, during which channel substrates accumulate and undergo physico‐chemical changes (precon‐ ditioning), and periods of flow resumption, when these substrates are rewetted and release pulses of dissolved nutrients and organic matter (OM). However, there are no estimates of the amounts and quality of leached substances, nor is there information on the underlying environmental constraints operating at the global scale. We experi‐ mentally simulated, under standard laboratory conditions, rewetting of leaves, river‐ bed sediments, and epilithic biofilms collected during the dry phase across 205 IRES from five major climate zones. We determined the amounts and qualitative character‐ istics of the leached nutrients and OM, and estimated their areal fluxes from riverbeds. In addition, we evaluated the variance in leachate characteristics in relation to selected environmental variables and substrate characteristics. We found that sediments, due to their large quantities within riverbeds, contribute most to the overall flux of dis‐ solved substances during rewetting events (56%–98%), and that flux rates distinctly differ among climate zones. Dissolved organic carbon, phenolics, and nitrate contrib‐ uted most to the areal fluxes. The largest amounts of leached substances were found in the continental climate zone, coinciding with the lowest potential bioavailability of the leached OM. The opposite pattern was found in the arid zone. Environmental vari‐ ables expected to be modified under climate change (i.e. potential evapotranspiration, aridity, dry period duration, land use) were correlated with the amount of leached sub‐ stances, with the strongest relationship found for sediments. These results show that the role of IRES should be accounted for in global biogeochemical cycles, especially because prevalence of IRES will increase due to increasing severity of drying event

The comparative responsiveness of Hospital Universitario Princesa Index and other composite indices for assessing rheumatoid arthritis activity

Objective To evaluate the responsiveness in terms of correlation of the Hospital Universitario La Princesa Index (HUPI) comparatively to the traditional composite indices used to assess disease activity in rheumatoid arthritis (RA), and to compare the performance of HUPI-based response criteria with that of the EULAR response criteria. Methods Secondary data analysis from the following studies: ACT-RAY (clinical trial), PROAR (early RA cohort) and EMECAR (pre-biologic era long term RA cohort). Responsiveness was evaluated by: 1) comparing change from baseline (Delta) of HUPI with Delta in other scores by calculating correlation coefficients; 2) calculating standardised effect sizes. The accuracy of response by HUPI and by EULAR criteria was analyzed using linear regressions in which the dependent variable was change in global assessment by physician (Delta GDA-Phy). Results Delta HUPI correlation with change in all other indices ranged from 0.387 to 0.791); HUPI's standardized effect size was larger than those from the other indices in each database used. In ACT-RAY, depending on visit, between 65 and 80% of patients were equally classified by HUPI and EULAR response criteria. However, HUPI criteria were slightly more stringent, with higher percentage of patients classified as non-responder, especially at early visits. HUPI response criteria showed a slightly higher accuracy than EULAR response criteria when using Delta GDA-Phy as gold standard. Conclusion HUPI shows good responsiveness in terms of correlation in each studied scenario (clinical trial, early RA cohort, and established RA cohort). Response criteria by HUPI seem more stringent than EULAR''s

Gluons and the quark sea at high energies: distributions, polarization, tomography

This report is based on a ten-week program on "Gluons and the quark sea at high-energies", which took place at the Institute for Nuclear Theory in Seattle in Fall 2010. The principal aim of the program was to develop and sharpen the science case for an Electron-Ion Collider (EIC), a facility that will be able to collide electrons and positrons with polarized protons and with light to heavy nuclei at high energies, offering unprecedented possibilities for in-depth studies of quantum chromodynamics. This report is organized around four major themes: i) the spin and flavor structure of the proton, ii) three-dimensional structure of nucleons and nuclei in momentum and configuration space, iii) QCD matter in nuclei, and iv) Electroweak physics and the search for physics beyond the Standard Model. Beginning with an executive summary, the report contains tables of key measurements, chapter overviews for each of the major scientific themes, and detailed individual contributions on various aspects of the scientific opportunities presented by an EIC.Comment: 547 pages, A report on the joint BNL/INT/Jlab program on the science case for an Electron-Ion Collider, September 13 to November 19, 2010, Institute for Nuclear Theory, Seattle; v2 with minor changes, matches printed versio