{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T18:44:11Z","timestamp":1780339451300,"version":"3.54.1"},"reference-count":144,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2020,3,6]],"date-time":"2020-03-06T00:00:00Z","timestamp":1583452800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["401270\/2014-0"],"award-info":[{"award-number":["401270\/2014-0"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["306338\/2014-2"],"award-info":[{"award-number":["306338\/2014-2"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["408633\/2018-2"],"award-info":[{"award-number":["408633\/2018-2"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["303868\/2016-3"],"award-info":[{"award-number":["303868\/2016-3"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["15\/13765-0"],"award-info":[{"award-number":["15\/13765-0"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["15\/18868-2"],"award-info":[{"award-number":["15\/18868-2"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004612","name":"Funda\u00e7\u00e3o Arauc\u00e1ria","doi-asserted-by":"publisher","award":["057\/2017"],"award-info":[{"award-number":["057\/2017"]}],"id":[{"id":"10.13039\/501100004612","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008224","name":"Funda\u00e7\u00e3o da Universidade Federal do Paran\u00e1","doi-asserted-by":"publisher","award":["04\/2018"],"award-info":[{"award-number":["04\/2018"]}],"id":[{"id":"10.13039\/501100008224","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Spiders of the genus Loxosceles, popularly known as Brown spiders, are considered a serious public health issue, especially in regions of hot or temperate climates, such as parts of North and South America. Although the venoms of these arachnids are complex in molecular composition, often containing proteins with distinct biochemical characteristics, the literature has primarily described a family of toxins, the Phospholipases-D (PLDs), which are highly conserved in all Loxosceles species. PLDs trigger most of the major clinical symptoms of loxoscelism i.e., dermonecrosis, thrombocytopenia, hemolysis, and acute renal failure. The key role played by PLDs in the symptomatology of loxoscelism was first described 40 years ago, when researches purified a hemolytic toxin that cleaved sphingomyelin and generated choline, and was referred to as a Sphingomyelinase-D, which was subsequently changed to Phospholipase-D when it was demonstrated that the enzyme also cleaved other cellular phospholipids. In this review, we present the information gleaned over the last 40 years about PLDs from Loxosceles venoms especially with regard to the production and characterization of recombinant isoforms. The history of obtaining these toxins is discussed, as well as their molecular organization and mechanisms of interaction with their substrates. We will address cellular biology aspects of these toxins and how they can be used in the development of drugs to address inflammatory processes and loxoscelism. Present and future aspects of loxoscelism diagnosis will be discussed, as well as their biotechnological applications and actions expected for the future in this field.<\/jats:p>","DOI":"10.3390\/toxins12030164","type":"journal-article","created":{"date-parts":[[2020,3,6]],"date-time":"2020-03-06T09:26:41Z","timestamp":1583486801000},"page":"164","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":59,"title":["Forty Years of the Description of Brown Spider Venom Phospholipases-D"],"prefix":"10.3390","volume":"12","author":[{"given":"Luiza Helena","family":"Gremski","sequence":"first","affiliation":[{"name":"Departamento de Biologia Celular, Universidade Federal do Paran\u00e1 (UFPR), Curitiba 81531-980, PR, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanna C\u00e2mara","family":"da Justa","sequence":"additional","affiliation":[{"name":"Departamento de Biologia Celular, Universidade Federal do Paran\u00e1 (UFPR), Curitiba 81531-980, PR, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tha\u00eds Pereira","family":"da Silva","sequence":"additional","affiliation":[{"name":"Departamento de Biologia Celular, Universidade Federal do Paran\u00e1 (UFPR), Curitiba 81531-980, PR, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nayanne Louise Costacurta","family":"Polli","sequence":"additional","affiliation":[{"name":"Departamento de Biologia Celular, Universidade Federal do Paran\u00e1 (UFPR), Curitiba 81531-980, PR, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno C\u00e9sar","family":"Antunes","sequence":"additional","affiliation":[{"name":"Departamento de Biologia Celular, Universidade Federal do Paran\u00e1 (UFPR), Curitiba 81531-980, PR, Brazil"},{"name":"Centro de Produ\u00e7\u00e3o e Pesquisa de Imunobiol\u00f3gicos (CPPI), Piraquara 83302-200, PR, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo\u00e3o Carlos","family":"Minozzo","sequence":"additional","affiliation":[{"name":"Centro de Produ\u00e7\u00e3o e Pesquisa de Imunobiol\u00f3gicos (CPPI), Piraquara 83302-200, PR, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Carolina Martins","family":"Wille","sequence":"additional","affiliation":[{"name":"Departamento de Biologia Estrutural, Molecular e Gen\u00e9tica, Universidade Estadual de Ponta Grossa, Ponta Grossa 84030-900, PR, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7967-6307","authenticated-orcid":false,"given":"Andrea","family":"Senff-Ribeiro","sequence":"additional","affiliation":[{"name":"Departamento de Biologia Celular, Universidade Federal do Paran\u00e1 (UFPR), Curitiba 81531-980, PR, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2460-1145","authenticated-orcid":false,"given":"Raghuvir Krishnaswamy","family":"Arni","sequence":"additional","affiliation":[{"name":"Centro Multiusu\u00e1rio de Inova\u00e7\u00e3o Biomolecular, Departamento de F\u00edsica, Universidade Estadual Paulista (UNESP), S\u00e3o Jos\u00e9 do Rio Preto 15054-000, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvio Sanches","family":"Veiga","sequence":"additional","affiliation":[{"name":"Departamento de Biologia Celular, Universidade Federal do Paran\u00e1 (UFPR), Curitiba 81531-980, PR, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,3,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/S0041-0101(03)00127-2","article-title":"Hematological cell findings in bone marrow and peripheral blood of rabbits after experimental acute exposure to Loxosceles intermedia (brown spider) venom","volume":"42","author":"Hashimoto","year":"2003","journal-title":"Toxicon"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1016\/j.toxicon.2004.07.012","article-title":"Brown spiders and loxoscelism","volume":"44","author":"Mangili","year":"2004","journal-title":"Toxicon"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1016\/j.annemergmed.2004.08.028","article-title":"Loxoscelism: Old obstacles, new directions","volume":"44","author":"Hogan","year":"2004","journal-title":"Ann. Emerg. Med."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Barceloux, D.G. (2008). Medical Toxicology of Natural Substances: Foods, Fungi, Medicinal Herbs, Plants, and Venomous Animals, John Wiley & Sons.","DOI":"10.1002\/9780470330319"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.toxicon.2014.02.023","article-title":"Recent advances in the understanding of brown spider venoms: From the biology of spiders to the molecular mechanisms of toxins","volume":"83","author":"Gremski","year":"2014","journal-title":"Toxicon"},{"key":"ref_6","first-page":"1","article-title":"Highlights in the knowledge of brown spider toxins","volume":"23","author":"Wille","year":"2017","journal-title":"J. Venom. Anim. Toxins Incl. Trop. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1067\/mjd.2001.112385","article-title":"Necrotic arachnidism","volume":"44","author":"Sams","year":"2001","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2403","DOI":"10.1039\/c004118a","article-title":"A novel expression profile of the Loxosceles intermedia spider venomous gland revealed by transcriptome analysis","volume":"6","author":"Gremski","year":"2010","journal-title":"Mol. Biosyst."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Fernandes-Pedrosa, M., de, F., Junqueira-de-Azevedo, I.D.L.M., Gon\u00e7alves-de-Andrade, R.M., Kobashi, L.S., Almeida, D.D., Ho, P.L., and Tambourgi, D.V. (2008). Transcriptome analysis of Loxosceles laeta (Araneae, Sicariidae) spider venomous gland using expressed sequence tags. BMC Genomics, 9.","DOI":"10.1186\/1471-2164-9-279"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.toxicon.2016.08.002","article-title":"Description of Loxtox protein family and identification of a new group of Phospholipases D from Loxosceles similis venom gland","volume":"120","author":"Dantas","year":"2016","journal-title":"Toxicon"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Segura-Ram\u00edrez, P.J., and Silva J\u00fanior, P.I. (2018). Loxosceles gaucho spider venom: An untapped source of antimicrobial agents. Toxins, 10.","DOI":"10.3390\/toxins10120522"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.toxicon.2012.04.350","article-title":"Sphingomyelinase D in sicariid spider venom is a potent insecticidal toxin","volume":"60","author":"Kerins","year":"2012","journal-title":"Toxicon"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1016\/j.biochi.2006.02.008","article-title":"Molecular cloning and functional characterization of two isoforms of dermonecrotic toxin from Loxosceles intermedia (Brown spider) venom gland","volume":"88","author":"Pigozzo","year":"2006","journal-title":"Biochimie"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.biochi.2006.12.002","article-title":"Two novel dermonecrotic toxins LiRecDT4 and LiRecDT5 from Brown spider (Loxosceles intermedia) venom: From cloning to functional characterization","volume":"89","author":"Pigozzo","year":"2007","journal-title":"Biochimie"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1162","DOI":"10.1016\/j.toxicon.2007.08.001","article-title":"Biological and structural comparison of recombinant phospholipase D toxins from Loxosceles intermedia (brown spider) venom","volume":"50","author":"Ribeiro","year":"2007","journal-title":"Toxicon"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2479","DOI":"10.1002\/jcb.24594","article-title":"Brown spider phospholipase-D containing a conservative mutation (D233E) in the catalytic site: Identification and functional characterization","volume":"114","author":"Vuitika","year":"2013","journal-title":"J. Cell. Biochem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1046\/j.1365-2613.2002.00241.x","article-title":"Histopathological findings in rabbits after experimental acute exposure to the Loxosceles intermedia (brown spider) venom","volume":"83","author":"Ospedal","year":"2002","journal-title":"Int. J. Exp. Pathol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1016\/j.toxicon.2009.02.013","article-title":"SMase II, a new sphingomyelinase D from Loxosceles laeta venom gland: Molecular cloning, expression, function and structural analysis","volume":"53","author":"de","year":"2009","journal-title":"Toxicon"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2947","DOI":"10.1093\/bioinformatics\/btm404","article-title":"Clustal W and Clustal X version 2.0","volume":"23","author":"Larkin","year":"2007","journal-title":"Bioinformatics"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1097\/00000441-199210000-00008","article-title":"Loxoscelism","volume":"304","author":"Futrell","year":"1992","journal-title":"Am. J. Med. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1126\/science.126.3263.73.a","article-title":"Probable cause of necrotic spider bite in the Midwest","volume":"126","author":"Atkins","year":"1957","journal-title":"Science"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"165","DOI":"10.4269\/ajtmh.1958.7.165","article-title":"Necrotic arachnidism","volume":"7","author":"Atkins","year":"1958","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/0003-9861(78)90046-2","article-title":"Red blood cell lysis induced by the venom of the brown recluse spider. The role of sphingomyelinase D","volume":"187","author":"Forrester","year":"1978","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1016\/0304-4165(81)90128-8","article-title":"Platelet aggregation and sphingomyelinase D activity of a purified toxin from the venom of loxosceles reclusa","volume":"678","author":"Kurpiewski","year":"1981","journal-title":"BBA-Gen. Subj."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1016\/0041-0101(90)90095-O","article-title":"Serum amyloid P component: Its role in platelet activation stimulated by sphingomyelinase D purified from the venom of the brown recluse spider (Loxosceles reclusa)","volume":"28","author":"Gates","year":"1990","journal-title":"Toxicon"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2167","DOI":"10.1002\/pmic.200401096","article-title":"Proteome analysis of brown spider venom: Identification of loxnecrogin isoforms in Loxosceles gaucho venom","volume":"5","author":"Machado","year":"2005","journal-title":"Proteomics"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1042\/BJ20050043","article-title":"Brown recluse spider (Loxosceles reclusa) venom phospholipase D (PLD) generates lysophosphatidic acid (LPA)","volume":"391","author":"Lee","year":"2006","journal-title":"Biochem. J."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.bbalip.2010.11.005","article-title":"Phospholipase-D activity and inflammatory response induced by brown spider dermonecrotic toxin: Endothelial cell membrane phospholipids as targets for toxicity","volume":"1811","author":"Chaim","year":"2011","journal-title":"Biochim. Biophys. Acta Mol. Cell Biol. Lipids"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2529","DOI":"10.1002\/jcb.23177","article-title":"The relationship between calcium and the metabolism of plasma membrane phospholipids in hemolysis induced by brown spider venom phospholipase-D toxin","volume":"112","author":"Souza","year":"2011","journal-title":"J. Cell. Biochem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"10994","DOI":"10.1074\/jbc.M115.636951","article-title":"Variable substrate preference among phospholipase D toxins from sicariid spiders","volume":"290","author":"Lajoie","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1016\/j.toxicon.2007.07.001","article-title":"The Loxtox protein family in Loxosceles intermedia (Mello-Leit\u00e3o) venom","volume":"50","author":"Kalapothakis","year":"2007","journal-title":"Toxicon"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1016\/j.toxicon.2004.11.011","article-title":"Sphingomyelinase D from venoms of Loxosceles spiders: Evolutionary insights from cDNA sequences and gene structure","volume":"45","author":"Binford","year":"2005","journal-title":"Toxicon"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1016\/j.ympev.2008.08.003","article-title":"Phylogenetic relationships of Loxosceles and Sicarius spiders are consistent with Western Gondwanan vicariance","volume":"49","author":"Binford","year":"2008","journal-title":"Mol. Phylogenet. Evol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1093\/molbev\/msn274","article-title":"Molecular evolution, functional variation, and proposed nomenclature of the gene family that includes sphingomyelinase D in sicariid spider venoms","volume":"26","author":"Binford","year":"2009","journal-title":"Mol. Biol. Evol."},{"key":"ref_35","first-page":"291","article-title":"Hemotoxic effect of Loxosceles reclusus venom: In vivo and in vitro studies","volume":"64","author":"Denny","year":"1964","journal-title":"J. Lab. Clin. Med."},{"key":"ref_36","first-page":"276","article-title":"Utilization of mammalian cell cultures in spider venom studies","volume":"133","author":"Morgan","year":"1965","journal-title":"Bact. Proc."},{"key":"ref_37","first-page":"90","article-title":"The role of polymorphonuclear leukocytes in the lesion caused by the venom of the brown spider, Loxosceles reclusa","volume":"22","author":"Smith","year":"1970","journal-title":"Lab. Investig."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1016\/0041-0101(77)90120-9","article-title":"Action of venom from the brown recluse spider (Loxosceles reclusa) on human neutrophils","volume":"15","author":"Majeski","year":"1977","journal-title":"Toxicon"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1432","DOI":"10.3181\/00379727-131-34124","article-title":"An inhibitor of complement in the venom of the brown recluse spider, Loxosceles reclusa","volume":"131","author":"Kniker","year":"1969","journal-title":"Proc. Soc. Exp. Biol. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1172\/JCI117379","article-title":"The necrotic venom of the brown recluse spider induces dysregulated endothelial cell-dependent neutrophil activation. Differential induction of GM-CSF, IL-8, and E-selectin expression","volume":"94","author":"Patel","year":"1994","journal-title":"J. Clin. Investig."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/0041-0101(92)90873-4","article-title":"Dermonecrotic and lethal components of Loxosceles gaucho spider venom","volume":"30","author":"Barbaro","year":"1992","journal-title":"Toxicon"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"4459","DOI":"10.4049\/jimmunol.155.9.4459","article-title":"Incorporation of a 35-Kilodalton Purified Protein from Loxosceles intermedia Spider Venom Transforms Human Erythrocytes into Activators of Autologous Complement Alternative Pathway","volume":"155","author":"Tambourgi","year":"1995","journal-title":"J. Immunol."},{"key":"ref_43","first-page":"1491","article-title":"Identification and neutralization of biological activities in the venoms of Loxosceles spiders","volume":"29","author":"Barbaro","year":"1996","journal-title":"Braz. J. Med. Biol. Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1006\/bbrc.1998.9474","article-title":"Sphingomyelinases in the venom of the spider Loxosceles intermedia are responsible for both dermonecrosis and complement-dependent hemolysis","volume":"251","author":"Tambourgi","year":"1998","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.1016\/S0041-0101(02)00201-5","article-title":"Molecular cloning, expression and immunological properties of LiD1, a protein from the dermonecrotic family of Loxosceles intermedia spider venom","volume":"40","author":"Kalapothakis","year":"2002","journal-title":"Toxicon"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1016\/S0006-291X(02)02521-4","article-title":"Molecular cloning and expression of a functional dermonecrotic and haemolytic factor from Loxosceles laeta venom","volume":"298","author":"Ramos","year":"2002","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.taap.2005.05.015","article-title":"Brown spider dermonecrotic toxin directly induces nephrotoxicity","volume":"211","author":"Chaim","year":"2006","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.bbagen.2007.11.007","article-title":"Identification, cloning and functional characterization of a novel dermonecrotic toxin (phospholipase D) from brown spider (Loxosceles intermedia) venom","volume":"1780","author":"Appel","year":"2008","journal-title":"Biochim. Biophys. Acta Gen. Subj."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.toxicon.2013.01.027","article-title":"Modulation of membrane phospholipids, the cytosolic calcium influx and cell proliferation following treatment of B16-F10 cells with recombinant phospholipase-D from Loxosceles intermedia (brown spider) venom","volume":"67","author":"Wille","year":"2013","journal-title":"Toxicon"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2086","DOI":"10.1016\/j.vaccine.2014.02.012","article-title":"Generation and molecular characterization of a monoclonal antibody reactive with conserved epitope in sphingomyelinases D from Loxosceles spider venoms","volume":"32","author":"Felicori","year":"2014","journal-title":"Vaccine"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.toxicon.2006.04.010","article-title":"North and South American Loxosceles spiders: Development of a polyvalent antivenom with recombinant sphingomyelinases D as antigens","volume":"48","author":"Olvera","year":"2006","journal-title":"Toxicon"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1002\/jbt.20399","article-title":"Two new phospholipase D isoforms of Loxosceles laeta: Cloning, heterologous expression, functional characterization, and potential biotechnological application","volume":"25","author":"Cortes","year":"2011","journal-title":"J. Biochem. Mol. Toxicol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1773","DOI":"10.1016\/j.biochi.2013.06.002","article-title":"Cloning, expression and characterization of a phospholipase D from Loxosceles gaucho venom gland","volume":"95","author":"Caporrino","year":"2013","journal-title":"Biochimie"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1016\/j.molimm.2004.03.027","article-title":"Molecular cloning, expression, function and immunoreactivities of members of a gene family of sphingomyelinases from Loxosceles venom glands","volume":"41","author":"Tambourgi","year":"2004","journal-title":"Mol. Immunol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/j.toxicon.2006.06.019","article-title":"Functional characterization and epitope analysis of a recombinant dermonecrotic protein from Loxosceles intermedia spider","volume":"48","author":"Felicori","year":"2006","journal-title":"Toxicon"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1016\/j.toxicon.2009.09.019","article-title":"A protective immune response against lethal, dermonecrotic and hemorrhagic effects of Loxosceles intermedia venom elicited by a 27-residue peptide","volume":"55","author":"Felicori","year":"2010","journal-title":"Toxicon"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1426","DOI":"10.1016\/j.toxicon.2010.08.008","article-title":"Cardiotoxic effects of Loxosceles intermedia spider venom and the recombinant venom toxin rLiD1","volume":"56","author":"Felicori","year":"2010","journal-title":"Toxicon"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Rojas, J.M., Ar\u00e1n-Sekul, T., Cort\u00e9s, E., Jald\u00edn, R., Ordenes, K., Orrego, P.R., Gonz\u00e1lez, J., Araya, J.E., and Catal\u00e1n, A. (2017). Phospholipase d from loxosceles laeta spider venom induces IL-6, IL-8, CXCL1\/GRO-\u03b1, and CCL2\/MCP-1 production in human skin fibroblasts and stimulates monocytes migration. Toxins, 9.","DOI":"10.3390\/toxins9040125"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1722","DOI":"10.1016\/j.biochi.2008.07.011","article-title":"Nephrotoxicity caused by brown spider venom phospholipase-D (dermonecrotic toxin) depends on catalytic activity","volume":"90","author":"Kusma","year":"2008","journal-title":"Biochimie"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"3828","DOI":"10.1016\/j.vaccine.2016.05.039","article-title":"Protective antibodies against a sphingomyelinase D from Loxosceles intermedia spider venom elicited in mice with different genetic background","volume":"34","author":"Oliveira","year":"2016","journal-title":"Vaccine"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"970","DOI":"10.1016\/j.bbalip.2016.05.009","article-title":"Active site mapping of Loxosceles phospholipases D: Biochemical and biological features","volume":"1861","author":"Vuitika","year":"2016","journal-title":"Biochim. Biophys. Acta Mol. Cell Biol. Lipids"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"13658","DOI":"10.1074\/jbc.M412437200","article-title":"Structural basis for metal ion coordination and the catalytic mechanism of sphingomyelinases D","volume":"280","author":"Murakami","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1016\/j.bbrc.2011.05.053","article-title":"Structure of a novel class II phospholipase D: Catalytic cleft is modified by a disulphide bridge","volume":"409","author":"Ullah","year":"2011","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1418","DOI":"10.1107\/S2053230X14019207","article-title":"Crystallization and preliminary X-ray diffraction analysis of a novel sphingomyelinase D from Loxosceles gaucho venom","volume":"70","author":"Ullah","year":"2014","journal-title":"Acta Crystallogr. Sect. F Struct. Biol. Commun."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1016\/j.ijbiomac.2017.09.081","article-title":"Spider\u2019s venom phospholipases D: A structural review","volume":"107","author":"Masood","year":"2018","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1016\/j.toxicon.2005.12.005","article-title":"Kinetic and mechanistic characterization of the Sphingomyelinases D from Loxosceles intermedia spider venom","volume":"47","author":"Andrade","year":"2006","journal-title":"Toxicon"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1371\/journal.pone.0072372","article-title":"Phospholipase D Toxins of Brown Spider Venom Convert Lysophosphatidylcholine and Sphingomyelin to Cyclic Phosphates","volume":"8","author":"Lajoie","year":"2013","journal-title":"PLoS ONE"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.toxicon.2014.01.011","article-title":"Tryptophan and aspartic acid residues present in the glycerophosphoryl diester phosphodiesterase (GDPD) domain of the Loxosceles laeta phospholipase D are essential for substrate recognition","volume":"81","author":"Araya","year":"2014","journal-title":"Toxicon"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"14863","DOI":"10.1074\/jbc.M113.466532","article-title":"The cation-\u03c0 box is a specific phosphatidylcholine membrane targeting motif","volume":"288","author":"Cheng","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"7087","DOI":"10.1074\/jbc.M116.769273","article-title":"Crystal structure of the human alkaline sphingomyelinase provides insights into substrate recognition","volume":"292","author":"Gorelik","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1023\/A:1023470829671","article-title":"Purification and Characterization of Loxnecrogin, a Dermonecrotic Toxin from Loxosceles gaucho Brown Spider Venom","volume":"22","author":"Cunha","year":"2003","journal-title":"J. Protein Chem."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/S1096-4959(03)00045-9","article-title":"The phylogenetic distribution of sphingomyelinase D activity in venoms of Haplogyne spiders","volume":"135","author":"Binford","year":"2003","journal-title":"Comp. Biochem. Physiol. B Biochem. Mol. Biol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1177\/002215540405200404","article-title":"Experimental Evidence for a Direct Cytotoxicity of Loxosceles intermedia (Brown Spider) Venom in Renal Tissue","volume":"52","author":"Luciano","year":"2004","journal-title":"J. Histochem. Cytochem."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/j.toxicon.2004.12.002","article-title":"Analysis of the toxic potential of venom from Loxosceles adelaida, a Brazilian brown spider from karstic areas","volume":"45","author":"Pretel","year":"2005","journal-title":"Toxicon"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1016\/j.toxicon.2005.09.002","article-title":"Characterization of the venom from the Brazilian Brown Spider Loxosceles similis Moenkhaus, 1898 (Araneae, Sicariidae)","volume":"46","author":"Silvestre","year":"2005","journal-title":"Toxicon"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"933","DOI":"10.2174\/092986609788923383","article-title":"Brown recluse spider venom: Proteomic analysis and proposal of a putative mechanism of action","volume":"16","author":"Dias","year":"2009","journal-title":"Protein Pept. Lett."},{"key":"ref_77","first-page":"1","article-title":"A multi-protease, multi-dissociation, bottom-up-to-top-down proteomic view of the Loxosceles intermedia venom","volume":"4","author":"Bednaski","year":"2017","journal-title":"Sci. Data"},{"key":"ref_78","first-page":"1060","article-title":"New insights on the role of ceramide 1-phosphate in inflammation","volume":"1831","author":"Gangoiti","year":"2013","journal-title":"Biochim. Biophys. Acta Mol. Cell Biol. Lipids"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1038\/nature13475","article-title":"Sphingolipid metabolites in inflammatory disease","volume":"510","author":"MacEyka","year":"2014","journal-title":"Nature"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1264","DOI":"10.1038\/sj.jid.5700644","article-title":"Upregulation of IL-6, IL-8, CXCL1, and CXCL2 dominates gene expression in human fibroblast cells exposed to Loxosceles reclusa sphingomyelinase D: Insights into spider venom dermonecrosis [2]","volume":"127","author":"Dragulev","year":"2007","journal-title":"J. Investig. Dermatol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1682","DOI":"10.1038\/jid.2013.40","article-title":"Lysophosphatidic acid mediates the release of cytokines and chemokines by human fibroblasts treated with loxosceles spider venom","volume":"133","author":"Horta","year":"2013","journal-title":"J. Investig. Dermatol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1002\/jcb.22148","article-title":"Identification of a direct hemolytic effect dependent on the catalytic activity induced by phospholipase-D (dermonecrotic toxin) from brown spider venom","volume":"107","author":"Chaim","year":"2009","journal-title":"J. Cell. Biochem."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Stock, R.P., Brewer, J., Wagner, K., Ramos-Cerrillo, B., Duelund, L., Jernsh\u00f8j, K.D., Olsen, L.F., and Bagatolli, L.A. (2012). Sphingomyelinase D activity in model membranes: Structural effects of in situ generation of ceramide-1-phosphate. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0036003"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"e31","DOI":"10.1016\/j.jemermed.2009.08.055","article-title":"Suspected brown recluse envenomation: A case report and review of different treatment modalities","volume":"41","author":"Andersen","year":"2011","journal-title":"J. Emerg. Med."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"2039","DOI":"10.1016\/S0140-6736(10)62230-1","article-title":"Spider bite","volume":"378","author":"Isbister","year":"2011","journal-title":"Lancet"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1111\/j.1553-2712.2001.tb02107.x","article-title":"Direct Correlation between Diffusion of Loxosceles recluse venom and extent of dermal inflammation","volume":"8","author":"Gomez","year":"2001","journal-title":"Acad. Emerg. Med."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1016\/j.toxicon.2009.01.033","article-title":"Analysis of therapeutic benefits of antivenin at different time intervals after experimental envenomation in rabbits by venom of the brown spider (Loxosceles intermedia)","volume":"53","author":"Pauli","year":"2009","journal-title":"Toxicon"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"2065","DOI":"10.1007\/s00204-019-02476-9","article-title":"Neurotoxicity of Micrurus lemniscatus lemniscatus (South American coralsnake) venom in vertebrate neuromuscular preparations in vitro and neutralization by antivenom","volume":"93","author":"Floriano","year":"2019","journal-title":"Arch. Toxicol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/0041-0101(94)90027-2","article-title":"Antigenic cross-reactivity of venoms from medically important Loxosceles (araneae) species in Brazil","volume":"32","author":"Barbaro","year":"1994","journal-title":"Toxicon"},{"key":"ref_90","first-page":"193","article-title":"A reduced immunization scheme to obtain an experimental anti-Loxosceles laeta (\u201cViolinist spider\u201d) venom","volume":"11","author":"Litwin","year":"2002","journal-title":"J. Nat. Toxins"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1016\/S0041-0101(01)00085-X","article-title":"Neutralization of dermonecrotic and lethal activities and differences among 32-35 kDa toxins of medically important Loxosceles spider venoms in Brazil revealed by monoclonal antibodies","volume":"39","author":"Guilherme","year":"2001","journal-title":"Toxicon"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1016\/S0041-0101(97)00083-4","article-title":"Detection and characterization of metalloproteinases with gelatinolytic, fibronectinolytic and fibrinogenolytic activities in Brown spider (Loxosceles intermedia) venom","volume":"36","author":"Feitosa","year":"1998","journal-title":"Toxicon"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1042\/BJ20070363","article-title":"Identification, cloning, expression and functional characterization of an astacin-like metalloprotease toxin from Loxosceles intermedia (brown spider) venom","volume":"406","author":"Wille","year":"2007","journal-title":"Biochem. J."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.biochi.2009.10.003","article-title":"Astacin-like metalloproteases are a gene family of toxins present in the venom of different species of the brown spider (genus Loxosceles)","volume":"92","author":"Gremski","year":"2010","journal-title":"Biochimie"},{"key":"ref_95","first-page":"1081","article-title":"Loxosceles Astacin-Like Proteases (LALPs), an Astacin Metalloprotease Family from the Brown Spider Venom","volume":"Voume 1","author":"Gremski","year":"2013","journal-title":"Handbook of Proteolytic Enzymes"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.biocel.2011.10.013","article-title":"Molecular cloning, heterologous expression and functional characterization of a novel translationally-controlled tumor protein (TCTP) family member from Loxosceles intermedia (brown spider) venom","volume":"44","author":"Sade","year":"2012","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.toxicon.2015.09.041","article-title":"Brown spider (Loxosceles genus) venom toxins: Evaluation of biological conservation by immune cross-reactivity","volume":"108","author":"Buch","year":"2015","journal-title":"Toxicon"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1016\/j.toxicon.2004.12.009","article-title":"Enzymatic characterization, antigenic cross-reactivity and neutralization of dermonecrotic activity of five Loxosceles spider venoms of medical importance in the Americas","volume":"45","author":"Barbaro","year":"2005","journal-title":"Toxicon"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1016\/j.toxicon.2006.11.024","article-title":"Hyaluronidases in Loxosceles intermedia (Brown spider) venom are endo-\u03b2-N-acetyl-d-hexosaminidases hydrolases","volume":"49","author":"Chaim","year":"2007","journal-title":"Toxicon"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1371\/journal.pntd.0002206","article-title":"A Novel Hyaluronidase from Brown Spider (Loxosceles intermedia) Venom (Dietrich\u2019s Hyaluronidase): From Cloning to Functional Characterization","volume":"7","author":"Ferrer","year":"2013","journal-title":"PLoS Negl. Trop. Dis."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"768","DOI":"10.2174\/1389203716666150505231625","article-title":"Structural Insights into Substrate Binding of Brown Spider Venom Class II Phospholipases D","volume":"16","author":"Coronado","year":"2015","journal-title":"Curr. Protein Pept. Sci."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"2053","DOI":"10.1002\/jcb.25781","article-title":"Bacterial and Arachnid Sphingomyelinases D: Comparison of Biophysical and Pathological Activities","volume":"118","author":"Mariutti","year":"2017","journal-title":"J. Cell. Biochem."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1111\/j.1476-4431.2009.00440.x","article-title":"Brown recluse spider (Loxosceles reclusa) envenomation in small animals","volume":"19","author":"Pace","year":"2009","journal-title":"J. Vet. Emerg. Crit. Care"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"4201","DOI":"10.1016\/j.vaccine.2009.04.038","article-title":"An in vivo protective response against toxic effects of the dermonecrotic protein from Loxosceles intermedia spider venom elicited by synthetic epitopes","volume":"27","author":"Felicori","year":"2009","journal-title":"Vaccine"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"7992","DOI":"10.1016\/j.vaccine.2011.08.065","article-title":"Protection against the toxic effects of Loxosceles intermedia spider venom elicited by mimotope peptides","volume":"29","author":"Felicori","year":"2011","journal-title":"Vaccine"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.toxicon.2013.07.007","article-title":"Synthetic peptides for invitro evaluation of the neutralizing potency of Loxosceles antivenoms","volume":"73","author":"Ramada","year":"2013","journal-title":"Toxicon"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"653","DOI":"10.3389\/fimmu.2018.00653","article-title":"Recombinant protein containing B-cell epitopes of different Loxosceles spider toxins generates neutralizing antibodies in immunized rabbits","volume":"9","author":"Lima","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Berm\u00fadez-M\u00e9ndez, E., Fuglsang-Madsen, A., F\u00f8ns, S., Lomonte, B., Guti\u00e9rrez, J.M., and Laustsen, A.H. (2018). Innovative immunization strategies for antivenom development. Toxins, 10.","DOI":"10.3390\/toxins10110452"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1266","DOI":"10.1038\/sj.jid.5700745","article-title":"Upregulation of cytokine expression in fibroblasts exposed to Loxosceles sphingomyelinase D: What is the trigger?","volume":"127","author":"Stortelers","year":"2007","journal-title":"J. Investig. Dermatol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"20555","DOI":"10.1074\/jbc.R400013200","article-title":"Lysophospholipid G protein-coupled receptors","volume":"279","author":"Anliker","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"4605","DOI":"10.1242\/jcs.02637","article-title":"Sphingosine 1-phosphate and ceramide 1-phosphate: Expanding roles in cell signaling","volume":"118","author":"Chalfant","year":"2005","journal-title":"J. Cell Sci."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1038\/nrm2329","article-title":"Principles of bioactive lipid signalling: Lessons from sphingolipids","volume":"9","author":"Hannun","year":"2008","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1002\/jcb.25678","article-title":"Potential Implications for Designing Drugs Against the Brown Spider Venom Phospholipase-D","volume":"118","author":"Caruso","year":"2017","journal-title":"J. Cell. Biochem."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1410","DOI":"10.1038\/sj.jid.5700688","article-title":"Tetracycline protects against dermonecrosis induced by Loxosceles spider venom","volume":"127","author":"Okamoto","year":"2007","journal-title":"J. Investig. Dermatol."},{"key":"ref_115","doi-asserted-by":"crossref","unstructured":"Okamoto, C.K., van den Berg, C.W., Masashi, M., Gon\u00e7alves-de-Andrade, R.M., and Tambourgi, D.V. (2017). Tetracycline reduces kidney damage induced by loxosceles spider venom. Toxins, 9.","DOI":"10.3390\/toxins9030090"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1590\/0037-8682-0390-2016","article-title":"Infrared thermography to diagnose and manage venomous animal bites and stings","volume":"50","author":"Brioschi","year":"2017","journal-title":"Rev. Soc. Bras. Med. Trop."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"2104","DOI":"10.1093\/clinchem\/39.10.2104","article-title":"Passive hemagglutination inhibition test for diagnosis of brown recluse spider bite envenomation","volume":"39","author":"Barrett","year":"1993","journal-title":"Clin. Chem."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1016\/S0041-0101(97)00159-1","article-title":"ELISA for the detection of venom antigens in experimental and clinical envenoming by Loxosceles intermedia spiders","volume":"36","author":"Zanetti","year":"1998","journal-title":"Toxicon"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1053\/ajem.2000.9272","article-title":"Detection of Loxosceles venom in lesional hair shafts and skin: Application of a specific immunoassay to identify dermonecrotic arachnidism","volume":"18","author":"Miller","year":"2000","journal-title":"Am. J. Emerg. Med."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1067\/mem.2002.122914","article-title":"A new assay for the detection of Loxosceles species (brown recluse) spider venom","volume":"39","author":"Gomez","year":"2002","journal-title":"Ann. Emerg. Med."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1067\/mem.2002.123551","article-title":"Detection of Loxosceles species venom in dermal lesions: A comparison of 4 venom recovery methods","volume":"39","author":"Krywko","year":"2002","journal-title":"Ann. Emerg. Med."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1016\/j.jaad.2006.04.065","article-title":"Diagnosis of loxoscelism in a child confirmed with an enzyme-linked immunosorbent assay and noninvasive tissue sampling","volume":"55","author":"Stoecker","year":"2006","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"11","DOI":"10.5070\/D30TH242G0","article-title":"Diagnosis of loxoscelism in two Turkish patients confirmed with an enzyme-linked immunosorbent assay (ELISA) and non-invasive tissue sampling","volume":"13","author":"Akdeniz","year":"2007","journal-title":"Dermatol. Online J."},{"key":"ref_124","first-page":"425","article-title":"Systemic loxoscelism confirmation by bite-site skin surface: ELISA","volume":"106","author":"Stoecker","year":"2009","journal-title":"Mo. Med."},{"key":"ref_125","first-page":"216","article-title":"Duration of Loxosceles reclusa venom detection by ELISA from swabs","volume":"22","author":"McGlasson","year":"2009","journal-title":"Clin. Lab. Sci."},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"Dias-Lopes, C., Paiva, A.L., Guerra-Duarte, C., Molina, F., and Felicori, L. (2018). Venomous arachnid diagnostic assays, lessons from past attempts. Toxins, 10.","DOI":"10.3390\/toxins10090365"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/s40409-018-0155-x","article-title":"Heterophilic antibodies in sera from individuals without loxoscelism cross-react with phospholipase D from the venom of Loxosceles and Sicarius spiders","volume":"24","author":"Rojas","year":"2018","journal-title":"J. Venom. Anim. Toxins Incl. Trop. Dis."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.imlet.2016.03.001","article-title":"Immunodetection of the \u201cbrown\u201d spider (Loxosceles intermedia) dermonecrotoxin with an scFv-alkaline phosphatase fusion protein","volume":"173","author":"Jiacomini","year":"2016","journal-title":"Immunol. Lett."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/S0041-0101(99)00155-5","article-title":"Structural and ultrastructural description of the venom gland of Loxosceles intermedia (brown spider)","volume":"38","author":"Franco","year":"2000","journal-title":"Toxicon"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/0717-6287-47-2","article-title":"First report of in vitro selection of RNA aptamers targeted to recombinant Loxosceles laeta spider toxins","volume":"47","author":"Sapag","year":"2014","journal-title":"Biol. Res."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1016\/j.toxicon.2005.02.016","article-title":"Practical applications of snake venom toxins in haemostasis","volume":"45","author":"Marsh","year":"2005","journal-title":"Toxicon"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"559","DOI":"10.7326\/0003-4819-143-8-200510180-00006","article-title":"Exenatide versus insulin glargine in patients with suboptimally controlled type 2 diabetes: A randomized trial","volume":"143","author":"Heine","year":"2005","journal-title":"Ann. Intern. Med."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"3030","DOI":"10.1007\/s00018-006-6315-0","article-title":"Snake venom components and their applications in biomedicine","volume":"63","author":"Koh","year":"2006","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/j.neuropharm.2007.05.002","article-title":"Venom therapy in multiple sclerosis","volume":"53","author":"Mirshafiey","year":"2007","journal-title":"Neuropharmacology"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"1569","DOI":"10.1016\/S0140-6736(10)60354-6","article-title":"Ziconotide for treatment of severe chronic pain","volume":"375","author":"Schmidtko","year":"2010","journal-title":"Lancet"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"309","DOI":"10.3390\/toxins3030309","article-title":"Brown spider (Loxosceles genus) venom toxins: Tools for biological purposes","volume":"3","author":"Chaim","year":"2011","journal-title":"Toxins"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"3041","DOI":"10.2174\/0929867043363947","article-title":"Potassium Channel Blockade by the Sea Anemone Toxin ShK for the Treatment of Multiple Sclerosis and Other Autoimmune Diseases","volume":"11","author":"Norton","year":"2012","journal-title":"Curr. Med. Chem."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1046\/j.1365-2567.2002.01483.x","article-title":"Mechanism of induction of complement susceptibility of erythrocytes by spider and bacterial sphingomyelinases","volume":"107","author":"Tambourgi","year":"2002","journal-title":"Immunology"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"6598","DOI":"10.1158\/1078-0432.CCR-06-1721","article-title":"Of spiders and crabs: The emergence of lysophospholipids and their metabolic pathways as targets for therapy in cancer","volume":"12","author":"Murph","year":"2006","journal-title":"Clin. Cancer Res."},{"key":"ref_140","first-page":"805","article-title":"Phospholipase D and its essential role in cancer","volume":"40","author":"Cho","year":"2017","journal-title":"Mol. Cells"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1007\/s10555-011-9319-7","article-title":"Autotaxin and LPA receptor signaling in cancer","volume":"30","author":"Houben","year":"2011","journal-title":"Cancer Metastasis Rev."},{"key":"ref_142","unstructured":"(2020, February 10). World Spider Catalog (2020). World Spider Catalog. Version 21.0. Natural History Museum Bern. Available online: http:\/\/wsc.nmbe.ch."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1097\/SMJ.0b013e3181a0abb3","article-title":"The distribution of brown recluse spiders in the southeastern quadrant of the United States in relation to loxoscelism diagnoses","volume":"102","author":"Vetter","year":"2009","journal-title":"South. Med. J."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/s40409-015-0028-5","article-title":"Arachnids of medical importance in Brazil: Main active compounds present in scorpion and spider venoms and tick saliva","volume":"21","author":"Cordeiro","year":"2015","journal-title":"J. Venom. Anim. Toxins Incl. Trop. Dis."}],"container-title":["Toxins"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6651\/12\/3\/164\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:04:44Z","timestamp":1760173484000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6651\/12\/3\/164"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3,6]]},"references-count":144,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2020,3]]}},"alternative-id":["toxins12030164"],"URL":"https:\/\/doi.org\/10.3390\/toxins12030164","relation":{},"ISSN":["2072-6651"],"issn-type":[{"value":"2072-6651","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,3,6]]}}}