DOCSLIB.ORG

Development of Nanobodies Against Hemorrhagic and Myotoxic Components of Bothrops Atrox Snake Venom

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Development of Nanobodies Against Hemorrhagic and Myotoxic Components of Bothrops Atrox Snake Venom fimmu-11-00655 May 7, 2020 Time: 13:9 # 1 ORIGINAL RESEARCH published: 07 May 2020 doi: 10.3389/fimmu.2020.00655 Development of Nanobodies Against Hemorrhagic and Myotoxic Components of Bothrops atrox Snake Venom Henri Bailon Calderon1*, Verónica Olga Yaniro Coronel1,2, Omar Alberto Cáceres Rey1, Elizabeth Gaby Colque Alave1, Walter Jhon Leiva Duran1, Carlos Padilla Rojas1, Harrison Montejo Arevalo1, David García Neyra1, Marco Galarza Pérez1, César Bonilla3, Benigno Tintaya3, Giulia Ricciardi4, Natalia Smiejkowska4, Ema Romão4, Cécile Vincke4, Juan Lévano1, Mary Celys1, Bruno Lomonte5 and Serge Muyldermans4 Edited by: 1 Abdul Qader Abbady, Laboratorio de Referencia Nacional de Biotecnología y Biología Molecular, Centro Nacional de Salud Pública, Instituto 2 Atomic Energy Commission of Syria, Nacional de Salud, Lima, Peru, Laboratorio de Biología Molecular, Universidad Nacional Mayor de San Marcos, Lima, Peru, 3 4 Syria Centro Nacional de Producción de Biológicos (INS), Lima, Peru, Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium, 5 Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San Jose, Reviewed by: Costa Rica Wayne Robert Thomas, The University of Western Australia, Australia Snake envenoming is a globally neglected public health problem. Antivenoms produced Peter Timmerman, using animal hyperimmune plasma remain the standard therapy for snakebites. Although Pepscan, Netherlands effective against systemic effects, conventional antivenoms have limited efficacy against *Correspondence: Henri Bailon Calderon local tissue damage. In addition, potential hypersensitivity reactions, high costs for [email protected]; animal maintenance, and difficulties in obtaining batch-to-batch homogeneity are [email protected] some of the factors that have motivated the search for innovative and improved Specialty section: therapeutic products against such envenoming. In this study, we have developed a set of This article was submitted to nanobodies (recombinant single-domain antigen-binding fragments from camelid heavy Vaccines and Molecular Therapeutics, a section of the journal chain-only antibodies) against Bothrops atrox snake venom hemorrhagic and myotoxic Frontiers in Immunology components. An immune library was constructed after immunizing a Lama glama with Received: 03 December 2019 whole venom of B. atrox, from which nanobodies were selected by phage display Accepted: 23 March 2020 using partially purified hemorrhagic and myotoxic proteins. Biopanning selections Published: 07 May 2020 retrieved 18 and eight different nanobodies against the hemorrhagic and the myotoxic Citation: Bailon Calderon H, Yaniro proteins, respectively. In vivo assays in mice showed that five nanobodies inhibited the Coronel VO, Cáceres Rey OA, Colque hemorrhagic activity of the proteins; three neutralized the hemorrhagic activity of whole Alave EG, Leiva Duran WJ, Padilla Rojas C, Montejo Arevalo H, García B. atrox venom, while four nanobodies inhibited the myotoxic protein. A mixture of the Neyra D, Galarza Pérez M, Bonilla C, anti-hemorrhagic and anti-myotoxic nanobodies neutralized the local tissue hemorrhage Tintaya B, Ricciardi G, and myonecrosis induced by the whole venom, although the nanobody mixture failed Smiejkowska N, Romão E, Vincke C, Lévano J, Celys M, Lomonte B and to prevent the venom lethality. Nevertheless, our results demonstrate the efficacy and Muyldermans S (2020) Development usefulness of these nanobodies to neutralize important pathologies of the venom, of Nanobodies Against Hemorrhagic and Myotoxic Components highlighting their potential as innovative therapeutic agents against envenoming by B. of Bothrops atrox Snake Venom. atrox, a viperid species causing many casualties in South America. Front. Immunol. 11:655. doi: 10.3389/fimmu.2020.00655 Keywords: nanobodies, snake, venom, myotoxic, hemorrhagic, neutralization, Bothrops atrox, viperidae Frontiers in Immunology| www.frontiersin.org 1 May 2020| Volume 11| Article 655 fimmu-11-00655 May 7, 2020 Time: 13:9 # 2 Bailon Calderon et al. Nanobodies Against Bothrops atrox Venom INTRODUCTION levels in microorganisms, such as E. coli, thereby reducing the production cost. Snakebite envenoming is an important public health problem Bothrops atrox snake venom has been characterized in worldwide, especially in tropical and subtropical countries. previous studies (16) including proteomic analysis, which have Around the world, 5 million snakebites occur each year, affecting determined the predominant presence of metalloproteinases of mainly the rural populations and causing an estimated 100,000 the SVMP-I and SVMP-III classes in addition to other protein deaths (1). Victims that survive snake envenoming may suffer types, such as phospholipase A2 (PLA2) and PLA2-like homologs, from permanent physical sequelae, such as amputation of the serine proteinases, and disintegrins, among others (17). affected body parts, as well as psychological sequela, such SVMPs are relevant toxins of Bothrops spp. venoms since as depression, which can reduce their productive capacities many display a potent hemorrhagic effect, especially those of the and affect normal life. Moreover, most snake envenoming SVMP-III class (18, 19). On the other hand, basic PLA2 and accidents in developing countries occur in remote areas, often PLA2-like proteins induce a strong myotoxic effect leading to far away from health services, or where antivenoms are local necrosis (20, 21). Together, these two types of toxins are unavailable, which decreases the chances for effective treatment mainly responsible for the local tissue damage that may develop and lifesaving of the victims. in severe envenoming by Bothrops species (3). Venomous snakes around the world include the families Currently, there are few countries in Latin America that Viperidae, Elapidae, Atractaspididae, and Colubridae (2), the produce antivenoms. In Peru, the National Institute of Health former two being the most medically relevant. Within the produces a polyvalent antivenom in equines, which is the only Viperidae family, the genus Bothrops is responsible for the most effective treatment against snake bites. The antivenom is obtained snake envenoming in Central and South America, causing high after successive subcutaneous injection of equines every 8 days morbidity and mortality (3). with the venoms of several snake species. Blood is collected Antivenom administration is the only effective treatment for after a period of 3 months and plasma is processed to obtain snake envenoming. Currently, antivenom production is based the IgG fraction. on the immunization of equines or ovine with snake venoms It has been calculated that probably less than 30% of the total according to the species responsible for the accidents in a antibodies from an equine antivenom are effectively neutralizing region or country. the toxins of the venom (22). Moreover, among important Hyperimmune plasma is obtained and used for purification potential adverse effects of the antivenoms produced in equines of whole IgG antibodies (150 kDa) or for obtaining antibody are vasculitis, arthritis, and renal failure, which may originate fragments, such as F(ab’)2 (100 kDa) or Fab (50 kDa), for the from the formation of immunocomplexes between antivenom antivenom formulation (4). antibodies and the anti-horse antibodies that accumulate in blood Besides conventional antibodies, camelids and some shark vessels, joints, and glomeruli (22). species produce naturally a unique type of antibody that is There is an urgent need to reduce the costs and to increase composed of heavy chains only, referred to as heavy-chain- the efficiency of current antivenoms. In this context, many only antibodies (HCAbs) (5). The antigen recognition of researchers have proposed novel alternatives to the common these functional HCAbs is comprised in the variable region use of equine antibodies, such as recombinant antibodies from of their heavy chain [abbreviated as VHH and referred to human or camelid VHH (23). as Nanobody (Nb)]. In this study, we have constructed a camelid (Lama glama) Nanobodys are small proteins of approximately 15 kDa; immune VHH library to retrieve Nbs against B. atrox venom they are the smallest intact antigen-binding fragment (6) that using a phage display strategy. Several Nbs directed against retains the specificity and affinity of the original HCAb in hemorrhagic and myotoxic components were cloned and recognizing the antigen (7,8). The Nbs have promising potential recombinantly expressed in E. coli. Their ability to neutralize as therapeutic (9–11) and diagnostic tools (12). Their third hemorrhage and myotoxicity was screened in preincubation-type antigen-binding loop, or CDR3 (complementarity determining assays in mice, to reveal their potential as eventual therapeutic region), is longer than that of VH domains of conventional agents against snakebite envenoming, particularly against the antibodies, and this prolonged loop interacts preferentially with local tissue pathology induced by venom SVMPs and PLA2. cavities or concave surfaces, such as the active site of enzymes (13). While large clefts or grooves on the surface of antigens are less likely to interact with the flat surface of the paratope MATERIALS AND METHODS of classical antibodies, they are frequently observed to associate with the convex paratope formed mainly by the CDR3 of camelid Ethics Statement VHHs (14). Furthermore, the substitution of conserved large Experiments involving animals were carried
Load more

Recommended publications
  • Major Article Epidemiological Study of Snakebite Cases in Brazilian Western Amazonia
    Rev Soc Bras Med Trop 51(3):338-346, May-June, 2018 doi: 10.1590/0037-8682-0489-2017 Major Article Epidemiological study of snakebite cases in Brazilian Western Amazonia Katia Regina Pena Schesquini Roriz[1], Kayena Delaix Zaqueo[2],[3], Sulamita Silva Setubal[2], Tony Hiroshi Katsuragawa[4], Renato Roriz da Silva[1], Carla Freire Celedônio Fernandes[2],[4], Luiz Augusto Paiva Cardoso[5], Moreno Magalhães de Souza Rodrigues[2], Andreimar Martins Soares[2], Rodrigo Guerino Stábeli[1],[2] and Juliana Pavan Zuliani[1],[2] [1]. Departamento de Medicina, Universidade Federal de Rondônia, Porto Velho, RO, Brasil. [2]. Fundação Oswaldo Cruz-Rondônia, Porto Velho, RO, Brasil. [3]. Centro de Referência de Jaciara, Instituto Federal de Educação, Ciência e Tecnologia de Mato Grosso, Campus São Vicente, Jaciara, MT, Brasil. [4]. Centro de Pesquisa em Medicina Tropical, Porto Velho, RO, Brasil. [5]. Centro de Medicina Tropical de Rondônia, Porto Velho, RO, Brasil. Abstract Introduction: Brazil has the largest number of snakebite cases in South America, of which the large majority is concentrated in the Midwest and North. Methods: In this descriptive observational study, we assessed the epidemiological and clinical snakebite cases referred to the Centro de Medicina Tropical de Rondônia from September 2008 to September 2010. Results: We followed up 92 cases from admission until discharge, namely 81 (88%) men and 11 (12%) women, with a mean age of 37 years, and mainly from rural areas (91.3%). The snakebites occurred while performing work activities (63%) during the Amazon rainy season (78.3%). The vast majority of individuals presented from the Porto Velho microregion (84.7%).
    [Show full text]
  • Preclinical Testing of Peruvian Anti-Bothropic Anti-Venom Against Bothrops Andianus Snake Venom
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Toxicon 60 (2012) 1018–1021 Contents lists available at SciVerse ScienceDirect Toxicon journal homepage: www.elsevier.com/locate/toxicon Short communication Preclinical testing of Peruvian anti-bothropic anti-venom against Bothrops andianus snake venom Francisco S. Schneider a, Maria C. Starling a, Clara G. Duarte a, Ricardo Machado de Avila a, Evanguedes Kalapothakis a, Walter Silva Suarez b, Benigno Tintaya b, Karin Flores Garrido b, Silvia Seraylan Ormachea b, Armando Yarleque c, César Bonilla b, Carlos Chávez-Olórtegui a,* a Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antonio Carlos 6627, CP: 486, CEP: 31270-901, Belo Horizonte, Minas Gerais, Brazil b Instituto Nacional de Salud, Lima, Peru c Universidad Nacional Mayor de San Marcos, Lima, Peru article info abstract Article history: Bothrops andianus is a venomous snake found in the area of Machu Picchu (Peru). Its Received 3 April 2012 venom is not included in the antigenic pool used for production of the Peruvian anti- Received in revised form 20 June 2012 bothropic anti-venom. B. andianus venom can elicit many biological effects such as Accepted 28 June 2012 hemorrhage, hemolysis, proteolytic activity and lethality. The Peruvian anti-bothropic Available online 14 July 2012 anti-venom displays consistent cross-reactivity with B. andianus venom, by ELISA and Western Blotting and is also effective in neutralizing the venom’s toxic activities. Keywords: Ó 2012 Elsevier Ltd. Open access under the Elsevier OA license.
    [Show full text]
  • Cohabitation by Bothrops Asper (Garman 1883) and Leptodactylus Savagei (Heyer 2005)
    Herpetology Notes, volume 12: 969-970 (2019) (published online on 10 October 2019) Cohabitation by Bothrops asper (Garman 1883) and Leptodactylus savagei (Heyer 2005) Todd R. Lewis1 and Rowland Griffin2 Bothrops asper is one of the largest (up to 245 cm) log-pile habitat (approximately 50 x 70 x 100cm) during pit vipers in Central America (Hardy, 1994; Rojas day and night. Two adults (with distinguishable size et al., 1997; Campbell and Lamar, 2004). Its range and markings) appeared resident with multiple counts extends from northern Mexico to the Pacific Lowlands (>20). Adults of B. asper were identified individually of Ecuador. In Costa Rica it is found predominantly in by approximate size, markings, and position on the log- Atlantic Lowland Wet forests. Leptodactylus savagei, pile. The above two adults were encountered on multiple a large (up to 180 mm females: 170 mm males snout- occasions between November 2002 and December vent length [SVL]), nocturnal, ground-dwelling anuran, 2003 and both used the same single escape hole when is found in both Pacific and Atlantic rainforests from disturbed during the day. Honduras into Colombia (Heyer, 2005). Across their On 20 November 2002, two nights after first locating ranges, both species probably originated from old forest and observing the above two Bothrops asper, a large but now are also found in secondary forest, agricultural, (131mm SVL) adult Leptodactylus savagei was seen disturbed and human inhabited land (McCranie and less than 2m from two coiled pit vipers (23:00 PM local Wilson, 2002; Savage, 2002; Sasa et al., 2009). Such time). When disturbed, it retreated into the same hole the habitat adaptation is most likely aided by tolerance for a adult pit vipers previously escaped to in the daytime.
    [Show full text]
  • Coagulotoxicity of Bothrops (Lancehead Pit-Vipers) Venoms from Brazil: Differential Biochemistry and Antivenom Efficacy Resulting from Prey-Driven Venom Variation
    toxins Article Coagulotoxicity of Bothrops (Lancehead Pit-Vipers) Venoms from Brazil: Differential Biochemistry and Antivenom Efficacy Resulting from Prey-Driven Venom Variation Leijiane F. Sousa 1,2, Christina N. Zdenek 2 , James S. Dobson 2, Bianca op den Brouw 2 , Francisco Coimbra 2, Amber Gillett 3, Tiago H. M. Del-Rei 1, Hipócrates de M. Chalkidis 4, Sávio Sant’Anna 5, Marisa M. Teixeira-da-Rocha 5, Kathleen Grego 5, Silvia R. Travaglia Cardoso 6 , Ana M. Moura da Silva 1 and Bryan G. Fry 2,* 1 Laboratório de Imunopatologia, Instituto Butantan, São Paulo 05503-900, Brazil; [email protected] (L.F.S.); [email protected] (T.H.M.D.-R.); [email protected] (A.M.M.d.S.) 2 Venom Evolution Lab, School of Biological Sciences, University of Queensland, St. Lucia, QLD 4072, Australia; [email protected] (C.N.Z.); [email protected] (J.S.D.); [email protected] (B.o.d.B.); [email protected] (F.C.) 3 Fauna Vet Wildlife Consultancy, Glass House Mountains, QLD 4518, Australia; [email protected] 4 Laboratório de Pesquisas Zoológicas, Unama Centro Universitário da Amazônia, Pará 68035-110, Brazil; [email protected] 5 Laboratório de Herpetologia, Instituto Butantan, São Paulo 05503-900, Brazil; [email protected] (S.S.); [email protected] (M.M.T.-d.-R.); [email protected] (K.G.) 6 Museu Biológico, Insituto Butantan, São Paulo 05503-900, Brazil; [email protected] * Correspondence: [email protected] Received: 18 September 2018; Accepted: 8 October 2018; Published: 11 October 2018 Abstract: Lancehead pit-vipers (Bothrops genus) are an extremely diverse and medically important group responsible for the greatest number of snakebite envenomations and deaths in South America.
    [Show full text]
  • Reptiles and Amphibians of Lamanai Outpost Lodge, Belize
    Reptiles and Amphibians of the Lamanai Outpost Lodge, Orange Walk District, Belize Ryan L. Lynch, Mike Rochford, Laura A. Brandt and Frank J. Mazzotti University of Florida, Fort Lauderdale Research and Education Center; 3205 College Avenue; Fort Lauderdale, Florida 33314 All pictures taken by RLL: [email protected] and MR: [email protected] Vaillant’s Frog Rio Grande Leopard Frog Common Mexican Treefrog Rana vaillanti Rana berlandieri Smilisca baudinii Veined Treefrog Red Eyed Treefrog Stauffer’s Treefrog Phrynohyas venulosa Agalychnis callidryas Scinax staufferi White-lipped Frog Fringe-toed Foam Frog Fringe-toed Foam Frog Leptodactylus labialis Leptodactylus melanonotus Leptodactylus melanonotus 1 Reptiles and Amphibians of the Lamanai Outpost Lodge, Orange Walk District, Belize Ryan L. Lynch, Mike Rochford, Laura A. Brandt and Frank J. Mazzotti University of Florida, Fort Lauderdale Research and Education Center; 3205 College Avenue; Fort Lauderdale, Florida 33314 All pictures taken by RLL: [email protected] and MR: [email protected] Tungara Frog Marine Toad Gulf Coast Toad Physalaemus pustulosus Bufo marinus Bufo valliceps Sheep Toad House Gecko Dwarf Bark Gecko Hypopachus variolosus Hemidactylus frenatus Shaerodactylus millepunctatus Turnip-tailed Gecko Yucatan Banded Gecko Yucatan Banded Gecko Thecadactylus rapicaudus Coleonyx elegans Coleonyx elegans 2 Reptiles and Amphibians of the Lamanai Outpost Lodge, Orange Walk District, Belize Ryan L. Lynch, Mike Rochford, Laura A. Brandt and Frank J. Mazzotti University
    [Show full text]
  • Snake Venom from the Venezuelan C
    BOLETÍN DE MALARIOLOGÍA Y SALUD AMBIENTAL Agosto-Diciembre 2014, Vol. LIV (2): 138-149 Biochemical and biological characterisation of lancehead (Bothrops venezuelensis Sandner 1952) snake venom from the Venezuelan Central Coastal range Caracterización bioquímica y biológica del veneno de la serpiente "tigra mariposa" (Bothrops venezuelensis Sandner 1952) de la región central de la Cordillera de la Costa Venezolana Elda E. Sánchez1, María E. Girón2, Nestor L. Uzcátegui2, Belsy Guerrero3, Max Saucedo1, Esteban Cuevas1 & Alexis Rodríguez-Acosta2* RESUMEN SUMMARY Se aislaron fracciones del veneno de Bothrops Venom fractions isolated from Bothrops venezuelensis que demuestran ser un espectro abundante de venezuelensis were shown to contain a broad spectrum proteínas con actividades variadas (coagulante, hemorrágica, of proteins with varied activities. This study describes fibrinolítica, proteolítica y de función plaquetaria), para el venom fractions with coagulant, haemorrhagic, fibrinolytic, análisis de sus propiedades físico-químicas y biológicas, proteolytic and antiplatelet activities, and analyses their el veneno fue fraccionado por cromatografía de exclusión physico-chemical properties and biological activities via molecular, corrido en una electroforesis en gel y realizada molecular exclusion chromatography, gel electrophoresis una batería de ensayos biológicos. La DL50 del veneno and a bioassay battery. The LD50, determined by injecting de B. venezuelensis fue 6,39 mg/kg de peso corporal, fue intraperitoneally serial dilutions of B. venezuelensis determinada inyectando intraperitonealmente en ratones, venom into mice, was 6.39 mg/kg body weight. Twelve diluciones seriadas de veneno de B. venezuelensis. Se fractions were collected from B. venezuelensis venom colectaron doce fracciones a partir del veneno de B. using molecular exclusion chromatography. Of these, venezuelensis mediante cromatografía de exclusión molecular.
    [Show full text]
  • Neutralizing Capacity of a New Monovalent Anti-Bothrops Atrox Antivenom: Comparison with Two Commercial Antivenoms
    BrazilianNeutralizing Journal capacity of Medical of a new and antivenom Biological againstResearch Bothrops (1997) atrox30: 375-379 375 ISSN 0100-879X Neutralizing capacity of a new monovalent anti-Bothrops atrox antivenom: comparison with two commercial antivenoms R. Otero1, V. Núñez1, 1Proyecto de Ofidismo, Facultad de Medicina, J.M. Gutiérrez4, A. Robles4, 2Facultad de Química Farmacéutica, and R. Estrada4, R.G. Osorio2, 3Facultad de Medicina Veterinaria y de Zootecnia, G. Del-Valle3, R. Valderrama1 Universidad de Antioquia, A.A.1226, Medellín, Colombia and C.A. Giraldo1 4Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica Abstract Correspondence Three horse-derived antivenoms were tested for their ability to neu- Key words R. Otero tralize lethal, hemorrhagic, edema-forming, defibrinating and myotoxic • Bothrops atrox Proyecto de Ofidismo activities induced by the venom of Bothrops atrox from Antioquia and • Snake venom Facultad de Medicina Chocó (Colombia). The following antivenoms were used: a) polyva- • Antivenom Universidad de Antioquia lent (crotaline) antivenom produced by Instituto Clodomiro Picado • Neutralization A.A.1226, Medellín • (Costa Rica), b) monovalent antibothropic antivenom produced by Antioquia Colombia • Chocó Fax: 57-4-263-8282 Instituto Nacional de Salud-INS (Bogotá), and c) a new monovalent anti-B. atrox antivenom produced with the venom of B. atrox from Research supported by the Antioquia and Chocó. The three antivenoms neutralized all toxic Instituto Colombiano para el activities tested albeit with different potencies. The new monovalent Desarrollo de la Ciencia y la anti-B. atrox antivenom showed the highest neutralizing ability against Tecnología Francisco José de edema-forming and defibrinating effects of B.
    [Show full text]
  • Effect of Bothrops Alternatus Snake Venom on Macrophage Phagocytosis Er
    The Journal of Venomous Animals and Toxins including Tropical Diseases ISSN 1678-9199 | 2011 | volume 17 | issue 4 | pages 430-441 Effect of Bothrops alternatus snake venom on macrophage phagocytosis ER P and superoxide production: participation of protein kinase C A P Setubal SS (1), Pontes AS (1), Furtado JL (1), Kayano AM (1), Stábeli RG (1, 2), Zuliani JP (1, 2) RIGINAL O (1) Laboratory of Biochemistry and Biotechnology and Laboratory of Cell Culture and Monoclonal Antibodies, Tropical Pathology Research Institute (Ipepatro), Oswaldo Cruz Foundation (Fiocruz), Porto Velho, Rondônia State, Brazil; (2) Center of Biomolecules Applied to Medicine, Department of Medicine, Federal University of Rondônia (UNIR), Porto Velho, Rondônia State, Brazil. Abstract: Envenomations caused by different species ofBothrops snakes result in severe local tissue damage, hemorrhage, pain, myonecrosis, and inflammation with a significant leukocyte accumulation at the bite site. However, the activation state of leukocytes is still unclear. According to clinical cases and experimental work, the local effects observed in envenenomation by Bothrops alternatus are mainly the appearance of edema, hemorrhage, and necrosis. In this study we investigated the ability of Bothrops alternatus crude venom to induce macrophage activation. At 6 to 100 μg/mL, BaV is not toxic to thioglycollate-elicited macrophages; at 3 and 6 μg/mL, it did not interfere in macrophage adhesion or detachment. Moreover, at concentrations of 1.5, 3, and 6 μg/mL the venom induced an increase in phagocytosis via complement receptor one hour after incubation. Pharmacological treatment of thioglycollate-elicited macrophages with staurosporine, a protein kinase (PKC) inhibitor, abolished phagocytosis, suggesting that PKC may be involved in the increase of serum-opsonized zymosan phagocytosis induced by BaV.
    [Show full text]
  • Inflammatory Oedema Induced by Lachesis Muta Muta
    Toxicon 53 (2009) 69–77 Contents lists available at ScienceDirect Toxicon journal homepage: www.elsevier.com/locate/toxicon Inflammatory oedema induced by Lachesis muta muta (Surucucu) venom and LmTX-I in the rat paw and dorsal skin Tatiane Ferreira a, Enilton A. Camargo a, Maria Teresa C.P. Ribela c, Daniela C. Damico b, Se´rgio Marangoni b, Edson Antunes a, Gilberto De Nucci a, Elen C.T. Landucci a,b,* a Department of Pharmacology, Faculty of Medical Sciences (FCM), UNICAMP, PO Box 6111, 13084-971 Campinas, SP, Brazil b Department of Biochemistry, Institute of Biology (IB), UNICAMP, PO Box 6109, 13083-970 Campinas, SP, Brazil c Department of Application of Nuclear Techniques in Biological Sciences, IPEN/CNEN, Sa˜o Paulo, SP, Brazil article info abstract Article history: The ability of crude venom and a basic phospholipase A2 (LmTX-I) from Lachesis muta muta Received 7 June 2008 venom to increase the microvascular permeability in rat paw and skin was investigated. Received in revised form 12 October 2008 Crude venom or LmTX-I were injected subplantarly or intradermally and rat paw oedema Accepted 16 October 2008 and dorsal skin plasma extravasation were measured. Histamine release from rat perito- Available online 1 November 2008 neal mast cell was also assessed. Crude venom or LmTX-I induced dose-dependent rat paw oedema and dorsal skin plasma extravasation. Venom-induced plasma extravasation was Keywords: inhibited by the histamine H antagonist mepyramine (6 mg/kg), histamine/5-hydroxy- Snake venom 1 Vascular permeability triptamine antagonist cyproheptadine (2 mg/kg), cyclooxygenase inhibitor indomethacin Mast cells (5 mg/kg), nitric oxide synthesis inhibitor L-NAME (100 nmol/site), tachykinin NK1 Sensory fibres antagonist SR140333 (1 nmol/site) and bradykinin B2 receptor antagonist Icatibant Lachesis muta muta (0.6 mg/kg).
    [Show full text]
  • Candidatus Rickettsia Colombianensi in Ticks from Reptiles in Córdoba, Colombia
    Veterinary World, EISSN: 2231-0916 RESEARCH ARTICLE Available at www.veterinaryworld.org/Vol.13/September-2020/5.pdf Open Access Candidatus Rickettsia colombianensi in ticks from reptiles in Córdoba, Colombia Jorge Miranda1 , Lina Violet-Lozano1 , Samia Barrera1 , Salim Mattar1 , Santiago Monsalve-Buriticá2 , Juan Rodas3 and Verónica Contreras1 1. University of Córdoba, Institute of Tropical Biology Research, Córdoba, Colombia; 2. Corporación Universitaria Lasallista, Colombia; 3. University of Antioquia, Colombia, Colombia. Corresponding author: Jorge Miranda, e-mail: [email protected] Co-authors: LV: [email protected], SB: [email protected], SM: [email protected], SaM: [email protected], JR: [email protected], VC: [email protected] Received: 11-02-2020, Accepted: 09-07-2020, Published online: 03-09-2020 doi: www.doi.org/10.14202/vetworld.2020.1764-1770 How to cite this article: Miranda J, Violet-Lozano L, Barrera S, Mattar S, Monsalve-Buriticá S, Rodas J, Contreras V (2020) Candidatus Rickettsia colombianensi in ticks from reptiles in Córdoba, Colombia, Veterinary World, 13(9): 1764-1770. Abstract Background and Aim: Wildlife animals are reservoirs of a large number of microorganisms pathogenic to humans, and ticks could be responsible for the transmission of these pathogens. Rickettsia spp. are the most prevalent pathogens found in ticks. This study was conducted to detect Rickettsia spp. in ticks collected from free-living and illegally trafficked reptiles from the Department of Córdoba, Colombia. Materials and Methods: During the period from October 2011 to July 2014, ticks belonging to the family Ixodidae were collected, preserved in 96% ethanol, identified using taxonomic keys, and pooled (between 1 and 14 ticks) according to sex, stage, host, and collected place for subsequent DNA extraction.
    [Show full text]
  • Bothrops Leucurus (Serpentes, Viperidae) Preying on Micrurus Corallinus (Serpentes, Elapidae) and Blarinomys Breviceps (Mammalia, Cricetidae)
    BOL. MUS. BIOL. MELLO LEITÃO (N. SÉR.) 25:67-71. DEZEMBRO DE 2009 67 Bothrops leucurus (Serpentes, Viperidae) preying on Micrurus corallinus (Serpentes, Elapidae) and Blarinomys breviceps (Mammalia, Cricetidae) Valéria Fagundes1*, Leonardo A. Baião1, Lucas A. Vianna1, Clara S. Alvarenga1, Marianna X. Machado1 & Sílvia R. Lopes1 ABSTRACT: The pitviper genus Bothrops belongs to the subfamily Crotalinae and has currently about 45 species distributed in the Neotropical region, mainly in South America. This genus includes the white-tailed lancehead B. leucurus, which has a wide geographic distribution in northeastern Brazil. We recorded an unusual predation event based on the examination of stomach contents from one specimen of Bothrops leucurus collected in a pitfall trap on February 17, 2009, at the Reserva Biológica do Córrego do Veado, Espírito Santo, Brazil. The snake’s stomach was dissected and two prey items were found: one partially digested juvenile snake Micrurus corallinus (Elapidae) and one undigested rodent of the fossorial species Blarinomys breviceps (Cricetidae). Bothrops leucurus feeds on lizards, rodents and frogs, but here we report ophiophagy by this species for the first time. Key words: Atlantic Forest, Brazil, natural history, ophiophagy, predation. RESUMO: Bothrops leucurus (Serpentes, Viperidae) predando Micrurus corallinus (Serpentes, Elapidae) e Blarinomys breviceps (Mammalia, Cricetidae). O gênero de serpentes Bothrops pertence à família Crotalinae e possui cerca de 45 espécies distribuídas na região neotropical, principalmente na América do Sul. Uma dessas espécies é a jararaca-de-rabo-branco B. leucurus, que tem ampla distribuição geográfica no nordeste do Brasil. Registramos um evento raro de predação, baseado na análise do conteúdo estomacal de um exemplar de B.
    [Show full text]
  • Snakebite Dynamics in Colombia: Effects of Precipitation Seasonality on Incidence Angarita-Gerlein, D
    IBIO4299 INTERNATIONAL RESEARCH EXPERIENCE FOR STUDENTS IRES 2017 (HTTPS://MCMSC.ASU.EDU/IRES) 1 Snakebite Dynamics in Colombia: Effects of Precipitation Seasonality on Incidence Angarita-Gerlein, D. ∗, Bravo-Vega, CA.y, Cruz, C. z, Forero-Munoz,˜ NR. x, Navas-Zuloaga, MG.{ and Umana-Caro,˜ JD. k Departamento de Ingenier´ıa Biomedica,´ Universidad de los Andes. Bogota,´ Colombia Email: ∗[email protected], [email protected], [email protected], [email protected], {[email protected] [email protected] Abstract—Snakebite is a neglected tropical disease that repre- Bothrops, the reproductive cycle is related with rainy seasons sents a significant public health issue in Colombia, particularly and the population density of the snakes increases [8, 9, 10]. in rural areas. Studies in other countries have presented strong Furthermore, in Costa Rica it is known that this increase in evidence to support the hypothesis that snakebite and rainy seasons are related. We aim to evaluate whether there is a strong the populations of Bothrops asper may lead to an increase in correlation between precipitation and snakebite incidence in the incidence of snakebite, so envenomings and rainy seasons Colombia. Employing two datasets of monthly precipitation and are temporally correlated [11]. reported snakebite incidence from 2007 to 2013, we performed Now, this present study makes use of data reporting precip- cross-correlation analysis for 314 municipalities. Results showed itation and snakebite incidence in different municipalities of a significant correlation between precipitation and snakebite incidence in 49.36% of the municipalities. Colombia. The objective of this project is to determine if there is a strong correlation between precipitation and snakebite incidence in Colombia and evaluate its contribution to the I.
    [Show full text]