144 research outputs found

    The Hazards of Monitoring Ecosystem Ocean Health in the Gulf of Mexico: A Mexican Perspective

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    Ecological services provided by the Gulf of Mexico constitute vital assets for the socioeconomic development of the USA, Mexico, and Cuba. This ecosystem houses vast biodiversity and significant fossil fuel reserves. However, its ecological stability and resilience have been jeopardized by anthropogenic disturbances. Massive oil spills (Ixtoc-I, 1979; Deepwater Horizon, 2010) caused severe environmental injuries and unveiled the vulnerability of coastal and deep-sea habitats. Baseline and monitoring studies are actions implemented by the Gulf stakeholders to cope with such disturbances. The 3-year monitoring program implemented by Mexico in 2010 to assess the environmental damage caused by the Deepwater Horizon (DWH) event confirmed the void of knowledge on the complexity of physical and biological processes susceptible of being altered by oil spills. Between the pelagic and benthic compartments, the latter proved to be a better option in establishing the baseline concentration and trends of oil compounds. Surficial sediments exhibited an increasing concentration trend of PAH, AH, and trace metals throughout the 3-year monitoring. The macroinfauna and selected biomarkers experienced interannual variability attributed to critical hydrocarbon and trace metal thresholds. Sediment toxicity bioassays added support to the distribution and potential sources of oil contaminants dispersed from the northern gulf toward Mexican waters

    Pharmacological and partial biochemical characterization of Bmaj-9 isolated from Bothrops marajoensis snake venom

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    Bmaj-9, a basic PLA2 (13679.33 Da), was isolated from Bothrops marajoensis snake venom through only one chromatographic step in reversed phase HPLC on ¼-Bondapak C-18 column. The amino acid composition showed that Bmaj-9 had a high content of Lys, His, and Arg, typical of a basic PLA2. The sequence of Bmaj-9 contains 124 amino acid residues with a pI value of 8.55, such as DLWQWGQMIL KETGKLPFSY YTAYGCYCGW GGRGGKPKAD TDRCCFVHDC, revealing a high homology with Asp49 PLA2 from other snake venoms. It also exhibited a pronounced phospholipase A2 activity when compared with crude venom. In chick biventer cervicis preparations, the time for 50% and 100% neuromuscular paralysis was respectively (in minutes): 110 ± 10 (1 µg/mL); 40 ± 6 and 90 ± 2 (5 µg/mL); 30 ± 3 and 70 ± 5 (10 µg/mL); 42 ± 1 and 60 ± 2 (20 µg/mL), with no effect on the contractures elicited by either exogenous ACh (110 µM) or KCl (20 mM). Bmaj-9 (10 µg/mL) neither interfered with the muscular response to direct electrical stimulation in curarized preparations nor significantly altered the release of CK at 0, 15, 30 and 60 minutes incubations (27.4 ± 5, 74.2 ± 8, 161.0 ± 21 and 353.0 ± 47, respectively). The histological analysis showed that, even causing blockade at the maximum dosage (5 µg/mL), the toxin does not induce significant morphological alterations such as necrosis or infiltration of inflammatory cells. These results identified Bmaj-9 as a new member of the basic Asp49 PLA2 family able to interact with the motor nerve terminal membrane, thereby inducing a presynaptic neuromuscular blockade181627

    Biochemical, Pharmacological, And Structural Characterization Of New Basic Pla2 Bbil-tx From Bothriopsis Bilineata Snake Venom

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    Bbil-TX, a PLA2, was purified from Bothriopsis bilineata snake venom after only one chromatographic step using RP-HPLC on μ7u-Bondapak C-18 column. A molecular mass of 14243.8 Da was confirmed by Q-Tof Ultima API ESI/MS (TOF MS mode) mass spectrometry. The partial protein sequence obtained was then submitted to BLASTp, with the search restricted to PLA2 from snakes and shows high identity values when compared to other PLA2s. PLA 2 activity was presented in the presence of a synthetic substrate and showed a minimum sigmoidal behavior, reaching its maximal activity at pH 8.0 and 25-37°C. Maximum PLA2 activity required Ca 2+ and in the presence of Cd2+, Zn2+, Mn 2+, and Mg2+ it was reduced in the presence or absence of Ca2+. Crotapotin from Crotalus durissus cascavella rattlesnake venom and antihemorrhagic factor DA2-II from Didelphis albiventris opossum sera under optimal conditions significantly inhibit the enzymatic activity. Bbil-TX induces myonecrosis in mice. The fraction does not show a significant cytotoxic activity in myotubes and myoblasts (C2C12). The inflammatory events induced in the serum of mice by Bbil-TX isolated from Bothriopsis bilineata snake venom were investigated. An increase in vascular permeability and in the levels of TNF-a, IL-6, and IL-1 was was induced. Since Bbil-TX exerts a stronger proinflammatory effect, the phospholipid hydrolysis may be relevant for these phenomena. © 2013 Victor Corasolla Carregari et al.2013McDiarmid, R.W., Campbell, J.A., Touré, T., (1999) Snake Species of the World: A Taxonomic and Geographic Reference, 1Barros, S.F., Friedlanskaia, I., Petricevich, V.L., Kipnis, T.L., Local inflammation, lethality and cytokine release in mice injected with Bothrops atrox venom (1998) Mediators of Inflammation, 7 (5), pp. 339-346Petricevich, V.L., Cytokine and nitric oxide production following severe envenomation (2004) Current Drug Targets: Inflammation and Allergy, 3 (3), pp. 325-332. , DOI 10.2174/1568010043343642Harris, J.B., Cullen, M.J., Muscle necrosis caused by snake venoms and toxins (1990) Electron Microscopy Reviews, 3 (2), pp. 183-211. , 2-s2.0-0025583295Dennis, E.A., Divesity of group tupes, regulation, and function oh phopholipase A 2 (1994) The Journal of Biological Chemistry, 269, pp. 13057-11306Bowton, D.L., Seeds, M.C., Fasano, M.B., Goldsmith, B., Bass, D.A., Phospholipase A2 and arachidonate increase in bronchoalveolar lavage fluid after inhaled antigen challenge in asthmatics (1997) American Journal of Respiratory and Critical Care Medicine, 155 (2), pp. 421-425Stadel, J.M., Hoyle, K., Naclerio, R.M., Roshak, A., Chilton, F.H., Characterization of phospholipase A2 from human nasal lavage (1994) American Journal of Respiratory Cell and Molecular Biology, 11 (1), pp. 108-113. , 2-s2.0-0028471889Vadas, P., Elevated plasma phospholipase A2 levels: Correlation with the hemodynamic and pulmonary changes in gram-negative septic shock (1984) Journal of Laboratory and Clinical Medicine, 104 (6), pp. 873-881Schroder, T., Kivilaakso, E., Kinnunen, P.K.J., Lempinen, M., Serum phospholipase A2 in human acute pancreatitis (1980) Scandinavian Journal of Gastroenterology, 15 (5), pp. 633-636Nakae, H., Endo, S., Inada, K., Yamashita, H., Yamada, Y., Takakuwa, T., Kasai, T., Uchida, K., Plasma concentrations of type II phospholipase A2, cytokines and eicosanoids in patients with burns (1995) Burns, 21 (6), pp. 422-426. , 2-s2.0-0029120333 10.1016/0305-4179(95)00022-4Vadas, P., Pruzanski, W., Role of secretory phospholipases A2 in the pathobiology of disease (1986) Laboratory Investigation, 55 (4), pp. 391-404Stefanski, E., Pruzanski, W., Sternby, B., Vadas, P., Purification of a soluble phospholipase A2 from synovial fluid in rheumatoid arthritis (1986) Journal of Biochemistry, 100 (5), pp. 1297-1303. , 2-s2.0-0022814387Seilhamer, J.J., Pruzanski, W., Vadas, P., Plant, S., Miller, J.A., Kloss, J., Johnson, L.K., Cloning and recombinant expression of phospholipase A2 present in rheumatoid arthritic synovial fluid (1989) Journal of Biological Chemistry, 264 (10), pp. 5335-5338Holzer, M., Mackessy, S.P., An aqueous endpoint assay of snake venom phospholipase A2 (1996) Toxicon, 34 (10), pp. 1149-1155. , DOI 10.1016/0041-0101(96)00057-8, PII S0041010196000578Schagger, H., Von Jagow, G., Tricine-sodium dodecyl sulfate-polyacrylamide gel electrophoresis for the separation of proteins in the range from 1 to 100 kDa (1987) Analytical Biochemistry, 166 (2), pp. 368-379. , DOI 10.1016/0003-2697(87)90587-2Heinrikson, R.L., Meredith, S.C., Amino acid analysis by reverse-phase high-performance liquid chromatography: Precolumn derivatization with phenylisothiocyanate (1984) Analytical Biochemistry, 136 (1), pp. 65-74. , 2-s2.0-0021312893Schumacher, J.H., O'Garra, A., Shrader, B., Van Kimmenade, A., Bond, M.W., Mosmann, T.R., Coffman, R.L., The characterization of four monoclonal antibodies specific for mouse IL-5 and development of mouse and human IL-5 enzyme-linked immunosorbent (1988) Journal of Immunology, 141 (5), pp. 1576-1581. , 2-s2.0-0023693868Ruff, M.R., Gifford, G.E., Purification and physico-chemical characterization of rabbit tumor necrosis factor (1980) Journal of Immunology, 125 (4), pp. 1671-1677Damico, D.C.S., Lilla, S., De Nucci, G., Ponce-Soto, L.A., Winck, F.V., Novello, J.C., Marangoni, S., Biochemical and enzymatic characterization of two basic Asp49 phospholipase A2 isoforms from Lachesis muta muta (Surucucu) venom (2005) Biochimica et Biophysica Acta - General Subjects, 1726 (1), pp. 75-86. , DOI 10.1016/j.bbagen.2005.05.022, PII S0304416505001777Ponce-Soto, L.A., Barros, J.C., Marangoni, S., Hernandez, S., Dal Belo, C.A., Corrado, A.P., Hyslop, S., Rodrigues-Simioni, L., Neuromuscular activity of BaTX, a presynaptic basic PLA2 isolated from Bothrops alternatus snake venom (2009) Comparative Biochemistry and Physiology C, 150 (2), pp. 291-297. , 2-s2.0-67649486833 10.1016/j.cbpc.2009.05.007Ponce-Soto, L.A., Bonfim, V.L., Rodrigues-Simioni, L., Novello, J.C., Marangoni, S., Determination of primary structure of two isoforms 6-1 and 6-2 PLA 2 D49 from Bothrops jararacussu snake venom and neurotoxic characterization using in vitro neuromuscular preparation (2006) Protein Journal, 25 (2), pp. 147-155. , DOI 10.1007/s10930-006-0006-4Ponce-Soto, L.A., Lomonte, B., Gutierrez, J.M., Rodrigues-Simioni, L., Novello, J.C., Marangoni, S., Structural and functional properties of BaTX, a new Lys49 phospholipase A2 homologue isolated from the venom of the snake Bothrops alternatus (2007) Biochimica et Biophysica Acta - General Subjects, 1770 (4), pp. 585-593. , DOI 10.1016/j.bbagen.2006.11.015, PII S0304416506003655Bonfim, V.L., Toyama, M.H., Novello, J.C., Hyslop, S., Oliveira, C.R.B., Rodrigues-Simioni, L., Marangoni, S., Isolation and enzymatic characterization of a basic phospholipase A 2 from Bothrops jararacussu snake venom (2001) Protein Journal, 20 (3), pp. 239-245. , 2-s2.0-52549108470Ponce-Soto, L.A., Martins-De-Souza, D., Marangoni, S., Neurotoxic, myotoxic and cytolytic activities of the new basic PLA 2 isoforms BmjeTX-I and BmjeTX-II isolated from the Bothrops marajoensis (marajó lancehead) snake venom (2010) Protein Journal, 29 (2), pp. 103-113. , 2-s2.0-77953250412 10.1007/s10930-010-9229-5Garcia-Denegri, M.E., Acosta, O.C., Huancahuire-Vega, S., Martins-De-Souza, D., Marangoni, S., Maruñak, S.L., Teibler, G.P., Ponce-Soto, L.A., Isolation and functional characterization of a new acidic PLA2 Ba SpII RP4 of the Bothrops alternatus snake venom from Argentina (2010) Toxicon, 56 (1), pp. 64-74. , 2-s2.0-77952545896 10.1016/j.toxicon.2010.02.031Gutierrez, J.M., Lomonte, B., (2003) Efectos Locales en El Envenenamiento Ofídico en America Latina Cap. 32 Efectos Locales en El Envenenamiento Ofídico en America Latina - Animais Pessonhentos No Brasil: Biologia, , São Paulo, Brazil Sarvier Clínica e Terapêutica dos AcidentesBurke, J.E., Dennis, E.A., Phospholipase A2 biochemistry (2009) Cardiovascular Drugs and Therapy, 23 (1), pp. 49-59. , 2-s2.0-58549086523 10.1007/s10557-008-6132-9Lomonte, B., Angulo, Y., Sasa, M., Gutiérrez, J.M., The phospholipase A2 homologues of snake venoms: Biological activities and their possible adaptive roles (2009) Protein and Peptide Letters, 16 (8), pp. 860-876. , 2-s2.0-68849126695 10.2174/092986609788923356Kini, R.M., Excitement ahead: Structure, function and mechanism of snake venom phospholipase A2 enzymes (2003) Toxicon, 42 (8), pp. 827-840. , DOI 10.1016/j.toxicon.2003.11.002Scott, D.L., Otwinowski, Z., Gelb, M.H., Sigler, P.B., Crystal structure of bee-venom phospholipase A2 in a complex with a transition-state analogue (1990) Science, 250 (4987), pp. 1563-1566Doley, R., Kini, R.M., Protein complexes in snake venom (2009) Cellular and Molecular Life Sciences, 66 (17), pp. 2851-2871. , 2-s2.0-68949212896 10.1007/s00018-009-0050-2Breithaupt, H., Enzymatic characteristics of crotalus phospholipase A2 and the crotoxin complex (1976) Toxicon, 14, pp. 221-233Rigden, D.J., Hwa, L.W., Marangoni, S., Toyama, M.H., Polikarpov, I., The structure of the D49 phospholipase A2 piratoxin III from Bothrops pirajai reveals unprecedented structural displacement of the calcium-binding loop: Possible relationship to cooperative substrate binding (2003) Acta Crystallographica Section D: Biological Crystallography, 59 (2), pp. 255-262. , DOI 10.1107/S0907444902021467Beghini, D.G., Toyama, M.H., Hyslop, S., Sodek, L.C., Novello, Marangoni, S., Enzymatic characterization of a novel phospholipase A2 from Crotalus durissus cascavella rattlesnake (maracambóia) venom (2000) Journal of Protein Chemistry, 19 (8), pp. 679-684. , DOI 10.1023/A:1007152303179Kini, R.M., Kini, R.M., Phospholipase A2 a complex multifunctional protein puzzle (1997) Enzymes: Structure, Function and Mechanism, pp. 1-28. , Chichester, UK John Wiley & SonsRomero-Vargas, F.F., Ponce-Soto, L.A., Martins-De-Souza, D., Marangoni, S., Biological and biochemical characterization of two new PLA2 isoforms Cdc-9 and Cdc-10 from Crotalus durissus cumanensis snake venom (2010) Comparative Biochemistry and Physiology C, 151 (1), pp. 66-74. , 2-s2.0-71649092384 10.1016/j.cbpc.2009.08.011Calgarotto, A.K., Damico, D.C.S., Ponce-Soto, L.A., Baldasso, P.A., Da Silva, S.L., Souza, G.H.M.F., Eberlin, M.N., Marangoni, S., Biological and biochemical characterization of new basic phospholipase A2 BmTX-I isolated from Bothrops moojeni snake venom (2008) Toxicon, 51 (8), pp. 1509-1519. , 2-s2.0-44649169648 10.1016/j.toxicon.2008.03.030Damico, D.C.S., Bueno, L.G.F., Rodrigues-Simioni, L., Marangoni, S., Da Cruz-Hofling, M.A., Novello, J.C., Functional characterization of a basic D49 phospholipase A2 (LmTX-I) from the venom of the snake Lachesis muta muta (bushmaster) (2006) Toxicon, 47 (7), pp. 759-765. , DOI 10.1016/j.toxicon.2006.02.007, PII S0041010106000894Landucci, E.C.T., Toyama, M., Marangoni, S., Oliveira, B., Cirino, G., Antunes, E., De Nucci, G., Effect of crotapotin and heparin on the rat paw oedema induced by different secretory phospholipases A2 (2000) Toxicon, 38 (2), pp. 199-208. , DOI 10.1016/S0041-0101(99)00143-9, PII S0041010199001439Gutierrez, J.M., Ownby, C.L., Skeletal muscle degeneration induced by venom phospholipases A 2: Insights into the mechanisms of local and systemic myotoxicity (2003) Toxicon, 42 (8), pp. 915-931. , DOI 10.1016/j.toxicon.2003.11.005Montecucco, C., Gutiérrez, J.M., Lomonte, B., Cellular pathology induced by snake venom phospholipase A2 myotoxins and neurotoxins: Common aspects of their mechanisms of action (2008) Cellular and Molecular Life Sciences, 65 (18), pp. 2897-2912. , 2-s2.0-52549092961 10.1007/s00018-008-8113-3Diaz, C., Leon, G., Rucavado, A., Rojas, N., Schroit, A.J., Gutierrez, J.M., Modulation of the susceptibility of human erythrocytes to snake venom myotoxic phospholipases A2: Role of negatively charged phospholipids as potential membrane binding sites (2001) Archives of Biochemistry and Biophysics, 391 (1), pp. 56-64. , DOI 10.1006/abbi.2001.2386Angulo, Y., Lomonte, B., Differential susceptibility of C2C12 myoblasts and myotubes to group II phospholipase A2 myotoxins from crotalid snake venoms (2005) Cell Biochemistry and Function, 23 (5), pp. 307-313. , DOI 10.1002/cbf.1208Gutierrez, J.M., Lomonte, B., Chaves, F., Pharmacological activities of a toxic phospholipase A isolated from the venom of the snake Bothrops asper (1986) Comparative Biochemistry and Physiology - C Pharmacology Toxicology and Endocrinology, 84 (1), pp. 159-164Gutiérrez, J.M., Ponce-Soto, L.A., Marangoni, S., Lomonte, B., Systemic and local myotoxicity induced by snake venom group II phospholipases A2: Comparison between crotoxin, crotoxin B and a Lys49 PLA2 homologue (2008) Toxicon, 51 (1), pp. 80-92. , 2-s2.0-38049077979 10.1016/j.toxicon.2007.08.007Ponce-Soto, L.A., Martins-De-Souza, D., Marangoni, S., Neurotoxic, myotoxic and cytolytic activities of the new basic PLA 2 isoforms BmjeTX-I and BmjeTX-II isolated from the Bothrops marajoensis (marajó lancehead) snake venom (2010) Protein Journal, 29 (2), pp. 103-113. , 2-s2.0-77953250412 10.1007/s10930-010-9229-5Majunatha Kini, R., Evans, H.J., A model to explain the pharmacological effects of snake venom phospholipases A2 (1989) Toxicon, 27 (6), pp. 613-635. , DOI 10.1016/0041-0101(89)90013-5Križaj, I., Ammodytoxin: A window into understanding presynaptic toxicity of secreted phospholipases A2 and more (2011) Toxicon, 58 (3), pp. 219-229. , 2-s2.0-79960943439 10.1016/j.toxicon.2011.06.009Landucci, E.C.T., Castro, R.C., Pereira, M.F., Cintra, A.C.O., Giglio, J.R., Marangoni, S., Oliveira, B., De Nucci, G., Mast cell degranulation induced by two phospholipase A2 homologues: Dissociation between enzymatic and biological activities (1998) European Journal of Pharmacology, 343 (2-3), pp. 257-263. , DOI 10.1016/S0014-2999(97)01546-X, PII S001429999701546XChaves, F., Leon, G., Alvarado, V.H., Gutierrez, J.M., Pharmacological modulation of edema induced by Lys-49 and Asp-49 myotoxic phospholipases A2 isolated from the venom of the snake Bothrops asper (terciopelo) (1998) Toxicon, 36 (12), pp. 1861-1869. , DOI 10.1016/S0041-0101(98)00107-X, PII S004101019800107XChacur, M., Picolo, G., Gutierrez, J.M., Teixeira, C.F.P., Cury, Y., Pharmacological modulation of hyperalgesia induced by Bothrops asper (terciopelo) snake venom (2001) Toxicon, 39 (8), pp. 1173-1181. , DOI 10.1016/S0041-0101(00)00254-3, PII S0041010100002543De Faria, L., Antunes, E., Bon, C., Lobo De Araujo, A., Pharmacological characterization of the rat paw edema induced by Bothrops lanceolatus (Fer de lance) venom (2001) Toxicon, 39 (6), pp. 825-830. , DOI 10.1016/S0041-0101(00)00213-0, PII S0041010100002130Carneiro, A.S., Ribeiro, O.G., De Franco, M., Cabrera, W.H.K., Vorraro, F., Siqueira, M., Ibanez, O.M., Starobinas, N., Local inflammatory reaction induced by Bothrops jararaca venom differs in mice selected for acute inflammatory response (2002) Toxicon, 40 (11), pp. 1571-1579. , DOI 10.1016/S0041-0101(02)00174-5, PII S0041010102001745Kanashiro, M.M., De Escocard, R.C.M., Petretski, J.H., Prates, M.V., Alves, E.W., Machado, O.L.T., Da Silva, W.D., Kipnis, T.L., Biochemical and biological properties of phospholipases A2 from Bothrops atrox snake venom (2002) Biochemical Pharmacology, 64 (7), pp. 1179-1186. , DOI 10.1016/S0006-2952(02)01288-1, PII S0006295202012881Teixeira, C.F.P., Landucci, E.C.T., Antunes, E., Chacur, M., Cury, Y., Inflammatory effects of snake venom myotoxic phospholipases A2 (2003) Toxicon, 42 (8), pp. 947-962. , DOI 10.1016/j.toxicon.2003.11.006Suwa, T., Hogg, J.C., English, D., Van Eeden, S.F., Interleukin-6 induces demargination of intravascular neutrophils and shortens their transit in marrow (2000) American Journal of Physiology - Heart and Circulatory Physiology, 279 (6), pp. H2954-H2960Van Snick, J., Interleukin-6: An overview (1990) Annual Review of Immunology, 8, pp. 253-278Crowl, R.M., Stoller, T.J., Conroy, R.R., Stoner, C.R., Induction of phospholipase A2 gene expression in human hepatoma cells by mediators of the acute phase response (1991) Journal of Biological Chemistry, 266 (4), pp. 2647-2651Suwa, T., Hogg, J.C., Quinlan, K.B., Van Eeden, S.F., The effect of interleukin-6 on L-selectin levels on polymorphonuclear leukocytes (2002) American Journal of Physiology, 283 (3), pp. H879-H884. , 2-s2.0-0036354115Schalkwijk, C., Pfeilschifter, J., Marki, F., Van Den Bosch, H., Interleukin-1 β, tumor necrosis factor and forskolin stimulate the synthesis and secretion of group II phospholipase A2 in rat mesangial cells (1991) Biochemical and Biophysical Research Communications, 174 (1), pp. 268-275. , 2-s2.0-0025976153 10.1016/0006-291X(91)90515-

    The Int7G24A variant of transforming growth factor-beta receptor type I is a risk factor for colorectal cancer in the male Spanish population: a case-control study

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    Background: The Int7G24A variant of transforming growth factor-beta receptor type I (TGFBR1) has been shown to increase the risk for kidney, ovarian, bladder, lung and breast cancers. Its role in colorectal cancer (CRC) has not been established. The aims of this study were to assess the association of TGFBR1*Int7G24A variant with CRC occurrence, patient age, gender, tumour location and stage. Methods: We performed a case-control study with 504 cases of sporadic CRC; and 504 non-cancerous age, gender and ethnically matched controls. Genotyping analysis was performed using allelic discrimination assay by real time PCR. Results: The Int7G24A variant was associated with increased CRC incidence in an additive model of inheritance (P for trend = 0.005). No significant differences were found between Int7G24A genotypes and tumour location or stage. Interestingly, the association of the Int7G24A variant with CRC risk was significant in men (odds ratio 4.10 with 95% confidence intervals 1.41-11.85 for homozygous individuals; P for trend = 0.00023), but not in women. We also observed an increase in susceptibility to CRC for individuals aged less than 70 years. Conclusion: Our data suggest that the Int7G24A variant represents a risk factor for CRC in the male Spanish population.Research supported in part by grants from the Generalitat Valenciana in Spain (AP106/06) and the Biomedical Research Foundation from the Hospital of Elche, Spain (FIBElx-02/2007). T.M-B is recipient of a fellowship from the Spanish Society of Medical Oncology (SEOM)

    A transcriptomic analysis of gene expression in the venom gland of the snake Bothrops alternatus (urutu)

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    <p>Abstract</p> <p>Background</p> <p>The genus <it>Bothrops </it>is widespread throughout Central and South America and is the principal cause of snakebite in these regions. Transcriptomic and proteomic studies have examined the venom composition of several species in this genus, but many others remain to be studied. In this work, we used a transcriptomic approach to examine the venom gland genes of <it>Bothrops alternatus</it>, a clinically important species found in southeastern and southern Brazil, Uruguay, northern Argentina and eastern Paraguay.</p> <p>Results</p> <p>A cDNA library of 5,350 expressed sequence tags (ESTs) was produced and assembled into 838 contigs and 4512 singletons. BLAST searches of relevant databases showed 30% hits and 70% no-hits, with toxin-related transcripts accounting for 23% and 78% of the total transcripts and hits, respectively. Gene ontology analysis identified non-toxin genes related to general metabolism, transcription and translation, processing and sorting, (polypeptide) degradation, structural functions and cell regulation. The major groups of toxin transcripts identified were metalloproteinases (81%), bradykinin-potentiating peptides/C-type natriuretic peptides (8.8%), phospholipases A<sub>2 </sub>(5.6%), serine proteinases (1.9%) and C-type lectins (1.5%). Metalloproteinases were almost exclusively type PIII proteins, with few type PII and no type PI proteins. Phospholipases A<sub>2 </sub>were essentially acidic; no basic PLA<sub>2 </sub>were detected. Minor toxin transcripts were related to L-amino acid oxidase, cysteine-rich secretory proteins, dipeptidylpeptidase IV, hyaluronidase, three-finger toxins and ohanin. Two non-toxic proteins, thioredoxin and double-specificity phosphatase Dusp6, showed high sequence identity to similar proteins from other snakes. In addition to the above features, single-nucleotide polymorphisms, microsatellites, transposable elements and inverted repeats that could contribute to toxin diversity were observed.</p> <p>Conclusions</p> <p><it>Bothrops alternatus </it>venom gland contains the major toxin classes described for other <it>Bothrops </it>venoms based on trancriptomic and proteomic studies. The predominance of type PIII metalloproteinases agrees with the well-known hemorrhagic activity of this venom, whereas the lower content of serine proteases and C-type lectins could contribute to less marked coagulopathy following envenoming by this species. The lack of basic PLA<sub>2 </sub>agrees with the lower myotoxicity of this venom compared to other <it>Bothrops </it>species with these toxins. Together, these results contribute to our understanding of the physiopathology of envenoming by this species.</p

    Elective Cancer Surgery in COVID-19-Free Surgical Pathways During the SARS-CoV-2 Pandemic: An International, Multicenter, Comparative Cohort Study.

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    PURPOSE: As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19-free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS: This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19-free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS: Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19-free surgical pathways. Patients who underwent surgery within COVID-19-free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19-free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score-matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19-free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION: Within available resources, dedicated COVID-19-free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

    Elective cancer surgery in COVID-19-free surgical pathways during the SARS-CoV-2 pandemic: An international, multicenter, comparative cohort study

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    PURPOSE As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19–free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19–free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19–free surgical pathways. Patients who underwent surgery within COVID-19–free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19–free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score–matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19–free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION Within available resources, dedicated COVID-19–free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

    Association between convalescent plasma treatment and mortality in COVID-19: a collaborative systematic review and meta-analysis of randomized clinical trials.

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    Funder: laura and john arnold foundationBACKGROUND: Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, https://doi.org/10.17605/OSF.IO/GEHFX ). METHODS: In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung-Knapp-Sidik-Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. RESULTS: A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis. CONCLUSIONS: Convalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care

    The Global Alliance for Infections in Surgery : defining a model for antimicrobial stewardship-results from an international cross-sectional survey

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    Background: Antimicrobial Stewardship Programs (ASPs) have been promoted to optimize antimicrobial usage and patient outcomes, and to reduce the emergence of antimicrobial-resistant organisms. However, the best strategies for an ASP are not definitively established and are likely to vary based on local culture, policy, and routine clinical practice, and probably limited resources in middle-income countries. The aim of this study is to evaluate structures and resources of antimicrobial stewardship teams (ASTs) in surgical departments from different regions of the world. Methods: A cross-sectional web-based survey was conducted in 2016 on 173 physicians who participated in the AGORA (Antimicrobials: A Global Alliance for Optimizing their Rational Use in Intra-Abdominal Infections) project and on 658 international experts in the fields of ASPs, infection control, and infections in surgery. Results: The response rate was 19.4%. One hundred fifty-six (98.7%) participants stated their hospital had a multidisciplinary AST. The median number of physicians working inside the team was five [interquartile range 4-6]. An infectious disease specialist, a microbiologist and an infection control specialist were, respectively, present in 80.1, 76.3, and 67.9% of the ASTs. A surgeon was a component in 59.0% of cases and was significantly more likely to be present in university hospitals (89.5%, p <0.05) compared to community teaching (83.3%) and community hospitals (66.7%). Protocols for pre-operative prophylaxis and for antimicrobial treatment of surgical infections were respectively implemented in 96.2 and 82.3% of the hospitals. The majority of the surgical departments implemented both persuasive and restrictive interventions (72.8%). The most common types of interventions in surgical departments were dissemination of educational materials (62.5%), expert approval (61.0%), audit and feedback (55.1%), educational outreach (53.7%), and compulsory order forms (51.5%). Conclusion: The survey showed a heterogeneous organization of ASPs worldwide, demonstrating the necessity of a multidisciplinary and collaborative approach in the battle against antimicrobial resistance in surgical infections, and the importance of educational efforts towards this goal.Peer reviewe
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