This page has only limited features, please log in for full access.

Dr. Ana Moura-Da-Silva
Laboratório de Imunopatologia, Instituto Butantan, São Paulo CEP 05503-900, Brazil

Basic Info


Research Keywords & Expertise

0 Hemostasis
0 Immunoassays
0 Antivenoms
0 Metalloproteinases
0 snake venoms

Fingerprints

Metalloproteinases
Antivenoms
snake venoms
Venom composition
Venom variability
Hemostasis

Honors and Awards

The user has no records in this section


Career Timeline

The user has no records in this section.


Short Biography

The user biography is not available.
Following
Followers
Co Authors
The list of users this user is following is empty.
Following: 0 users

Feed

Journal article
Published: 25 May 2021 in Toxicology Letters
Reads 0
Downloads 0

Is snake venom activity influenced by size? This is a long-standing question that can have important consequences for the treatment of snake envenomation. Ontogenetic shifts in venom composition are a well-documented characteristic of numerous snake species. Although snake venoms can cause a range of pathophysiological disturbances, establishing the coagulotoxic profiles related to such shifts is a justified approach because coagulotoxicity can be deadly, and its neutralisation is a challenge for current antivenom therapy. Thus, we aimed to assess the coagulotoxicity patterns on plasma and fibrinogen produced by B othrops jararacussu venoms from individuals of different sizes and sex, and the neutralisation potential of SAB (anti bothropic serum produced by Butantan Institute). The use of a metalloproteinase inhibitor (Prinomastat) and a serine proteinase inhibitor (AEBSF) enabled us to determine the toxin class responsible for the observed coagulopathy: activity on plasma was found to be metalloprotease driven, while the activity on fibrinogen is serine protease driven. To further explore differences in venom activity, the activation of Factor X and prothrombin as a function of snake size was also evaluated. All the venoms exhibited a potent procoagulant effect upon plasma and were less potent in their pseudo-procoagulant clotting effect upon fibrinogen. On human plasma, the venoms from smaller snakes produced more rapid clotting than the larger ones. In contrast, the venom activity on fibrinogen had no relation with size or sex. The difference in procoagulant potency was correlated with the bigger snakes being proportionally better neutralized by antivenom due to the lower levels of procoagulant toxins, than the smaller. Thus, while the antivenom ultimately neutralized the venoms, proportionally more would be needed for an equal mass of venom from a small snake than a large one. Similarly, the neutralisation by SAB of the pseudo-procoagulant clotting effects was also correlated with relative potency, with the smaller and bigger snakes being neutralized proportional to potency, but with no correlation to size. Thromboelastography (TEG) tests on human and toad plasma revealed that small snakes’ venoms acted quicker than large snakes’ venom on both plasmas, with the action upon amphibian plasma consistent with smaller snakes taking a larger proportion of anuran prey than adults. Altogether, the ontogenetic differences regarding coagulotoxic potency and corresponding impact upon relative antivenom neutralisation of snakes with different sizes were shown, underscoring the medical importance of investigating ontogenetic changes in order to provide data crucial for evidence-based design of clinical management strategies.

ACS Style

Caroline Fabri Bittencourt Rodrigues; Christina N. Zdenek; Lachlan A. Bourke; Lorenzo Seneci; Abhinandan Chowdhury; Luciana Aparecida Freitas-De-Sousa; Frederico de Alcantara Menezes; Ana Maria Moura-Da-Silva; Anita Mitico Tanaka-Azevedo; Bryan G. Fry. Clinical implications of ontogenetic differences in the coagulotoxic activity of Bothrops jararacussu venoms. Toxicology Letters 2021, 348, 59 -72.

AMA Style

Caroline Fabri Bittencourt Rodrigues, Christina N. Zdenek, Lachlan A. Bourke, Lorenzo Seneci, Abhinandan Chowdhury, Luciana Aparecida Freitas-De-Sousa, Frederico de Alcantara Menezes, Ana Maria Moura-Da-Silva, Anita Mitico Tanaka-Azevedo, Bryan G. Fry. Clinical implications of ontogenetic differences in the coagulotoxic activity of Bothrops jararacussu venoms. Toxicology Letters. 2021; 348 ():59-72.

Chicago/Turabian Style

Caroline Fabri Bittencourt Rodrigues; Christina N. Zdenek; Lachlan A. Bourke; Lorenzo Seneci; Abhinandan Chowdhury; Luciana Aparecida Freitas-De-Sousa; Frederico de Alcantara Menezes; Ana Maria Moura-Da-Silva; Anita Mitico Tanaka-Azevedo; Bryan G. Fry. 2021. "Clinical implications of ontogenetic differences in the coagulotoxic activity of Bothrops jararacussu venoms." Toxicology Letters 348, no. : 59-72.

Journal article
Published: 10 May 2021 in Proceedings of the National Academy of Sciences
Reads 0
Downloads 0

Venom is a key adaptive innovation in snakes, and how nonvenom genes were co-opted to become part of the toxin arsenal is a significant evolutionary question. While this process has been investigated through the phylogenetic reconstruction of toxin sequences, evidence provided by the genomic context of toxin genes remains less explored. To investigate the process of toxin recruitment, we sequenced the genome of Bothrops jararaca, a clinically relevant pitviper. In addition to producing a road map with canonical structures of genes encoding 12 toxin families, we inferred most of the ancestral genes for their loci. We found evidence that 1) snake venom metalloproteinases (SVMPs) and phospholipases A2 (PLA2) have expanded in genomic proximity to their nonvenomous ancestors; 2) serine proteinases arose by co-opting a local gene that also gave rise to lizard gilatoxins and then expanded; 3) the bradykinin-potentiating peptides originated from a C-type natriuretic peptide gene backbone; and 4) VEGF-F was co-opted from a PGF-like gene and not from VEGF-A. We evaluated two scenarios for the original recruitment of nontoxin genes for snake venom: 1) in locus ancestral gene duplication and 2) in locus ancestral gene direct co-option. The first explains the origins of two important toxins (SVMP and PLA2), while the second explains the emergence of a greater number of venom components. Overall, our results support the idea of a locally assembled venom arsenal in which the most clinically relevant toxin families expanded through posterior gene duplications, regardless of whether they originated by duplication or gene co-option.

ACS Style

Diego Dantas Almeida; Vincent Louis Viala; Pedro Gabriel Nachtigall; Michael Broe; H. Lisle Gibbs; Solange Maria De Toledo Serrano; Ana Maria Moura-Da-Silva; Paulo Lee Ho; Milton Yutaka Nishiyama-Jr; Inácio L. M. Junqueira-De-Azevedo. Tracking the recruitment and evolution of snake toxins using the evolutionary context provided by the Bothrops jararaca genome. Proceedings of the National Academy of Sciences 2021, 118, 1 .

AMA Style

Diego Dantas Almeida, Vincent Louis Viala, Pedro Gabriel Nachtigall, Michael Broe, H. Lisle Gibbs, Solange Maria De Toledo Serrano, Ana Maria Moura-Da-Silva, Paulo Lee Ho, Milton Yutaka Nishiyama-Jr, Inácio L. M. Junqueira-De-Azevedo. Tracking the recruitment and evolution of snake toxins using the evolutionary context provided by the Bothrops jararaca genome. Proceedings of the National Academy of Sciences. 2021; 118 (20):1.

Chicago/Turabian Style

Diego Dantas Almeida; Vincent Louis Viala; Pedro Gabriel Nachtigall; Michael Broe; H. Lisle Gibbs; Solange Maria De Toledo Serrano; Ana Maria Moura-Da-Silva; Paulo Lee Ho; Milton Yutaka Nishiyama-Jr; Inácio L. M. Junqueira-De-Azevedo. 2021. "Tracking the recruitment and evolution of snake toxins using the evolutionary context provided by the Bothrops jararaca genome." Proceedings of the National Academy of Sciences 118, no. 20: 1.

Journal article
Published: 19 April 2021 in Proceedings of the National Academy of Sciences
Reads 0
Downloads 0

The role of natural selection in the evolution of trait complexity can be characterized by testing hypothesized links between complex forms and their functions across species. Predatory venoms are composed of multiple proteins that collectively function to incapacitate prey. Venom complexity fluctuates over evolutionary timescales, with apparent increases and decreases in complexity, and yet the causes of this variation are unclear. We tested alternative hypotheses linking venom complexity and ecological sources of selection from diet in the largest clade of front-fanged venomous snakes in North America: the rattlesnakes, copperheads, cantils, and cottonmouths. We generated independent transcriptomic and proteomic measures of venom complexity and collated several natural history studies to quantify dietary variation. We then constructed genome-scale phylogenies for these snakes for comparative analyses. Strikingly, prey phylogenetic diversity was more strongly correlated to venom complexity than was overall prey species diversity, specifically implicating prey species’ divergence, rather than the number of lineages alone, in the evolution of complexity. Prey phylogenetic diversity further predicted transcriptomic complexity of three of the four largest gene families in viper venom, showing that complexity evolution is a concerted response among many independent gene families. We suggest that the phylogenetic diversity of prey measures functionally relevant divergence in the targets of venom, a claim supported by sequence diversity in the coagulation cascade targets of venom. Our results support the general concept that the diversity of species in an ecological community is more important than their overall number in determining evolutionary patterns in predator trait complexity.

ACS Style

Matthew L. Holding; Jason L. Strickland; Rhett M. Rautsaw; Erich P. Hofmann; Andrew J. Mason; Michael P. Hogan; Gunnar S. Nystrom; Schyler A. Ellsworth; Timothy J. Colston; Miguel Borja; Gamaliel Castañeda-Gaytán; Christoph I. Grünwald; Jason M. Jones; Luciana A. Freitas-De-Sousa; Vincent Louis Viala; Mark J. Margres; Erika Hingst-Zaher; Inácio L. M. Junqueira-De-Azevedo; Ana M. Moura-Da-Silva; Felipe G. Grazziotin; H. Lisle Gibbs; Darin R. Rokyta; Christopher L. Parkinson. Phylogenetically diverse diets favor more complex venoms in North American pitvipers. Proceedings of the National Academy of Sciences 2021, 118, 1 .

AMA Style

Matthew L. Holding, Jason L. Strickland, Rhett M. Rautsaw, Erich P. Hofmann, Andrew J. Mason, Michael P. Hogan, Gunnar S. Nystrom, Schyler A. Ellsworth, Timothy J. Colston, Miguel Borja, Gamaliel Castañeda-Gaytán, Christoph I. Grünwald, Jason M. Jones, Luciana A. Freitas-De-Sousa, Vincent Louis Viala, Mark J. Margres, Erika Hingst-Zaher, Inácio L. M. Junqueira-De-Azevedo, Ana M. Moura-Da-Silva, Felipe G. Grazziotin, H. Lisle Gibbs, Darin R. Rokyta, Christopher L. Parkinson. Phylogenetically diverse diets favor more complex venoms in North American pitvipers. Proceedings of the National Academy of Sciences. 2021; 118 (17):1.

Chicago/Turabian Style

Matthew L. Holding; Jason L. Strickland; Rhett M. Rautsaw; Erich P. Hofmann; Andrew J. Mason; Michael P. Hogan; Gunnar S. Nystrom; Schyler A. Ellsworth; Timothy J. Colston; Miguel Borja; Gamaliel Castañeda-Gaytán; Christoph I. Grünwald; Jason M. Jones; Luciana A. Freitas-De-Sousa; Vincent Louis Viala; Mark J. Margres; Erika Hingst-Zaher; Inácio L. M. Junqueira-De-Azevedo; Ana M. Moura-Da-Silva; Felipe G. Grazziotin; H. Lisle Gibbs; Darin R. Rokyta; Christopher L. Parkinson. 2021. "Phylogenetically diverse diets favor more complex venoms in North American pitvipers." Proceedings of the National Academy of Sciences 118, no. 17: 1.

Journal article
Published: 11 December 2020 in Toxins
Reads 0
Downloads 0

Ontogenetic changes in venom composition have been described in Bothrops snakes, but only a few studies have attempted to identify the targeted paralogues or the molecular mechanisms involved in modifications of gene expression during ontogeny. In this study, we decoded B. jararacussu venom gland transcripts from six specimens of varying sizes and analyzed the variability in the composition of independent venom proteomes from 19 individuals. We identified 125 distinct putative toxin transcripts, and of these, 73 were detected in venom proteomes and only 10 were involved in the ontogenetic changes. Ontogenetic variability was linearly related to snake size and did not correspond to the maturation of the reproductive stage. Changes in the transcriptome were highly predictive of changes in the venom proteome. The basic myotoxic phospholipases A2 (PLA2s) were the most abundant components in larger snakes, while in venoms from smaller snakes, PIII-class SVMPs were the major components. The snake venom metalloproteinases (SVMPs) identified corresponded to novel sequences and conferred higher pro-coagulant and hemorrhagic functions to the venom of small snakes. The mechanisms modulating venom variability are predominantly related to transcriptional events and may consist of an advantage of higher hematotoxicity and more efficient predatory function in the venom from small snakes.

ACS Style

Luciana A. Freitas-De-Sousa; Pedro G. Nachtigall; José A. Portes-Junior; Matthew L. Holding; Gunnar S. Nystrom; Schyler A. Ellsworth; Noranathan C. Guimarães; Emilly Tioyama; Flora Ortiz; Bruno R. Silva; Tobias S. Kunz; Inácio L. M. Junqueira-De-Azevedo; Felipe G. Grazziotin; Darin R. Rokyta; Ana M. Moura-Da-Silva. Size Matters: An Evaluation of the Molecular Basis of Ontogenetic Modifications in the Composition of Bothrops jararacussu Snake Venom. Toxins 2020, 12, 791 .

AMA Style

Luciana A. Freitas-De-Sousa, Pedro G. Nachtigall, José A. Portes-Junior, Matthew L. Holding, Gunnar S. Nystrom, Schyler A. Ellsworth, Noranathan C. Guimarães, Emilly Tioyama, Flora Ortiz, Bruno R. Silva, Tobias S. Kunz, Inácio L. M. Junqueira-De-Azevedo, Felipe G. Grazziotin, Darin R. Rokyta, Ana M. Moura-Da-Silva. Size Matters: An Evaluation of the Molecular Basis of Ontogenetic Modifications in the Composition of Bothrops jararacussu Snake Venom. Toxins. 2020; 12 (12):791.

Chicago/Turabian Style

Luciana A. Freitas-De-Sousa; Pedro G. Nachtigall; José A. Portes-Junior; Matthew L. Holding; Gunnar S. Nystrom; Schyler A. Ellsworth; Noranathan C. Guimarães; Emilly Tioyama; Flora Ortiz; Bruno R. Silva; Tobias S. Kunz; Inácio L. M. Junqueira-De-Azevedo; Felipe G. Grazziotin; Darin R. Rokyta; Ana M. Moura-Da-Silva. 2020. "Size Matters: An Evaluation of the Molecular Basis of Ontogenetic Modifications in the Composition of Bothrops jararacussu Snake Venom." Toxins 12, no. 12: 791.

Journal article
Published: 29 August 2020 in Toxins
Reads 0
Downloads 0

Bleeding is a common hemostatic disorder that occurs in Bothrops envenomations. We evaluated the changes in coagulation, fibrinolysis components, and platelets in Bothrops atrox envenomations with bleeding. This is an observational study with B. atrox snakebite patients (n = 100) treated in Manaus, Brazilian Amazon. Bleeding was recorded on admission and during hospitalization. We found that the platelet count in our patients presented a weak correlation to tissue factor, factor II, and plasminogen. Tissue factor presented weak correlation to factor V, II, D-dimer, plasminogen, alpha 2-antiplasmin, and moderate correlation to fibrinogen and fibrin/fibrinogen degradation product (FDP). Patients with systemic bleeding (n = 20) presented low levels of factor V, II, fibrinogen, plasminogen, and alpha 2-antiplasmin, and high levels of tissue factor and FDP compared to those without bleeding. Patients with only local bleeding (n = 41) and without bleeding showed similar levels of hemostatic factors. Thrombocytopenia was observed mainly in patients with systemic bleeding and increased levels of serum venom. No association was found between venom levels and systemic bleeding, or between venom levels and clinical severity of envenomation. This is the first report that shows the participation of the extrinsic coagulation pathway in the consumption coagulopathy of B. atrox envenomations with systemic bleeding due to tissue factor release.

ACS Style

Sâmella S. Oliveira; Eliane C. Alves; Alessandra S. Santos; Elizandra F. Nascimento; João T. Pereira; Iran M. Silva; Jacqueline A. G. Sachett; Lybia S. Sarraff; Luciana Freitas-De-Sousa; Mônica Colombini; Hedylamar O. Marques; Marcus V. G. Lacerda; Marco Sartim; Ana Moura-Da-Silva; Luiz L. Ferreira; Ida S. Sano-Martins; Wuelton M. Monteiro. Bleeding Disorders in Bothrops atrox Envenomations in the Brazilian Amazon: Participation of Hemostatic Factors and the Impact of Tissue Factor. Toxins 2020, 12, 554 .

AMA Style

Sâmella S. Oliveira, Eliane C. Alves, Alessandra S. Santos, Elizandra F. Nascimento, João T. Pereira, Iran M. Silva, Jacqueline A. G. Sachett, Lybia S. Sarraff, Luciana Freitas-De-Sousa, Mônica Colombini, Hedylamar O. Marques, Marcus V. G. Lacerda, Marco Sartim, Ana Moura-Da-Silva, Luiz L. Ferreira, Ida S. Sano-Martins, Wuelton M. Monteiro. Bleeding Disorders in Bothrops atrox Envenomations in the Brazilian Amazon: Participation of Hemostatic Factors and the Impact of Tissue Factor. Toxins. 2020; 12 (9):554.

Chicago/Turabian Style

Sâmella S. Oliveira; Eliane C. Alves; Alessandra S. Santos; Elizandra F. Nascimento; João T. Pereira; Iran M. Silva; Jacqueline A. G. Sachett; Lybia S. Sarraff; Luciana Freitas-De-Sousa; Mônica Colombini; Hedylamar O. Marques; Marcus V. G. Lacerda; Marco Sartim; Ana Moura-Da-Silva; Luiz L. Ferreira; Ida S. Sano-Martins; Wuelton M. Monteiro. 2020. "Bleeding Disorders in Bothrops atrox Envenomations in the Brazilian Amazon: Participation of Hemostatic Factors and the Impact of Tissue Factor." Toxins 12, no. 9: 554.

Journal article
Published: 22 August 2020 in Toxicology Letters
Reads 0
Downloads 0

Bothrops (lance-head pit vipers) venoms are rich in weaponised metalloprotease enzymes (SVMP). These toxic enzymes are structurally diverse and functionally versatile. Potent coagulotoxicity is particularly important for prey capture (via stroke-induction) and relevant to human clinical cases (due to consumption of clotting factors including the critical depletion of fibrinogen). In this study, three distinct isoforms of P-III class SVMPs (IC, IIB and IIC), isolated from Bothrops neuwiedi venom, were evaluated for their differential capacities to affect hemostasis of prey and human plasma. Furthermore, we tested the relative antivenom neutralisation of effects upon human plasma. The toxic enzymes displayed differential procoagulant potency between plasma types, and clinically relevant antivenom efficacy variations were observed. Of particular importance was the confirmation the antivenom performed better against prothrombin activating toxins than Factor X activating toxins, which is likely due to the greater prevalence of the former in the immunising venoms used for antivenom production. This is clinically relevant as the enzymes displayed differential potency in this regard, with one (IC) in particular being extremely potent in activating Factor X and thus was correspondingly poorly neutralised. This study broadens the current understanding about the adaptive role of the SVMPs, as well as highlights how the functional diversity of SVMP isoforms can influence clinical outcomes. Key Contribution: Our findings shed light upon the hemorrhagic and coagulotoxic effects of three SVMPs of the P-III class, as well as the coagulotoxic effects of SVMPs on human, avian and amphibian plasmas. Antivenom neutralised prothrombin-activating isoforms better than Factor X activating isoforms.

ACS Style

Leijiane F. Sousa; Juliana L. Bernardoni; Christina N. Zdenek; James Dobson; Francisco Coimbra; Amber Gillett; Mônica Lopes-Ferreira; A.M. Moura-Da-Silva; Bryan G. Fry. Differential coagulotoxicity of metalloprotease isoforms from Bothrops neuwiedi snake venom and consequent variations in antivenom efficacy. Toxicology Letters 2020, 333, 211 -221.

AMA Style

Leijiane F. Sousa, Juliana L. Bernardoni, Christina N. Zdenek, James Dobson, Francisco Coimbra, Amber Gillett, Mônica Lopes-Ferreira, A.M. Moura-Da-Silva, Bryan G. Fry. Differential coagulotoxicity of metalloprotease isoforms from Bothrops neuwiedi snake venom and consequent variations in antivenom efficacy. Toxicology Letters. 2020; 333 ():211-221.

Chicago/Turabian Style

Leijiane F. Sousa; Juliana L. Bernardoni; Christina N. Zdenek; James Dobson; Francisco Coimbra; Amber Gillett; Mônica Lopes-Ferreira; A.M. Moura-Da-Silva; Bryan G. Fry. 2020. "Differential coagulotoxicity of metalloprotease isoforms from Bothrops neuwiedi snake venom and consequent variations in antivenom efficacy." Toxicology Letters 333, no. : 211-221.

Research article
Published: 08 June 2020 in PLOS Neglected Tropical Diseases
Reads 0
Downloads 0

Snake venoms are complex mixtures of proteins with toxic activities, with many distinct isoforms, affecting different physiological targets, comprised in a few protein families. It is currently accepted that this diversity in venom composition is an adaptive advantage for venom efficacy on a wide range of prey. However, on the other side, variability on isoforms expression has implications in the clinics of human victims of snakebites and in the efficacy of antivenoms. B. atrox snakes are responsible for most of the human accidents in Brazilian Amazon and the type and abundance of protein families on their venoms present individual variability. Thus, in this study we attempted to correlate the individual venom proteome of the snake brought to the hospital by the patient seeking for medical assistance with the clinical signs observed in the same patient. Individual variability was confirmed in venoms of the 14 snakes selected for the study. The abundance of each protein family was quite similar among the venom samples, while the isoforms composition was highly variable. Considering the protein families, the SVMP group presented the best correlation with bleeding disorders and edema. Considering individual isoforms, some isoforms of venom metalloproteinase (SVMP), C-type lectin-like toxins (CTL) and snake venom serine proteinases (SVSP) presented expression levels that with statistically significant positive correlation to signs and symptoms presented by the patients as bleeding disorders, edema, ecchymosis and blister formation. However, some unexpected data were also observed as the correlation between a CTL, CRISP or LAAO isoforms with blister formation, still to be confirmed with a larger number of samples. Although this is still a small number of patient samples, we were able to indicate that venom composition modulates clinical manifestations of snakebites, to confirm at the bedside the prominent role of SVMPs and to include new possible toxin candidates for the development of toxin inhibitors or to improve antivenom selectiveness, important actions for the next generation treatments of snakebites.

ACS Style

Ana Maria Moura-Da-Silva; Jorge Carlos Contreras-Bernal; Sarah Natalie Cirilo Gimenes; Luciana Aparecida Freitas-De-Sousa; José Antonio Portes-Junior; Pedro Da Silva Peixoto; Leo Kei Iwai; Valéria Mourão De Moura; Pedro Ferreira Bisneto; Marcus Lacerda; Iran Mendonça Da Silva; Luiz Carlos De Lima Ferreira; Sâmella Silva De Oliveira; Fan Hui Wen; Jacqueline De Almeida Gonçalves Sachett; Wuelton M. Monteiro. The relationship between clinics and the venom of the causative Amazon pit viper (Bothrops atrox). PLOS Neglected Tropical Diseases 2020, 14, e0008299 .

AMA Style

Ana Maria Moura-Da-Silva, Jorge Carlos Contreras-Bernal, Sarah Natalie Cirilo Gimenes, Luciana Aparecida Freitas-De-Sousa, José Antonio Portes-Junior, Pedro Da Silva Peixoto, Leo Kei Iwai, Valéria Mourão De Moura, Pedro Ferreira Bisneto, Marcus Lacerda, Iran Mendonça Da Silva, Luiz Carlos De Lima Ferreira, Sâmella Silva De Oliveira, Fan Hui Wen, Jacqueline De Almeida Gonçalves Sachett, Wuelton M. Monteiro. The relationship between clinics and the venom of the causative Amazon pit viper (Bothrops atrox). PLOS Neglected Tropical Diseases. 2020; 14 (6):e0008299.

Chicago/Turabian Style

Ana Maria Moura-Da-Silva; Jorge Carlos Contreras-Bernal; Sarah Natalie Cirilo Gimenes; Luciana Aparecida Freitas-De-Sousa; José Antonio Portes-Junior; Pedro Da Silva Peixoto; Leo Kei Iwai; Valéria Mourão De Moura; Pedro Ferreira Bisneto; Marcus Lacerda; Iran Mendonça Da Silva; Luiz Carlos De Lima Ferreira; Sâmella Silva De Oliveira; Fan Hui Wen; Jacqueline De Almeida Gonçalves Sachett; Wuelton M. Monteiro. 2020. "The relationship between clinics and the venom of the causative Amazon pit viper (Bothrops atrox)." PLOS Neglected Tropical Diseases 14, no. 6: e0008299.

Journal article
Published: 03 May 2020 in Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology
Reads 0
Downloads 0

Snakebite is a common occurrence for pet cats and dogs worldwide and can be fatal. In Australia the eastern brown snake (Pseudonaja textilis) is responsible for an estimated 76% of reported snakebite cases to domestic pets nationally each year, with the primary pathology being venom-induced consumptive coagulopathy. While only 31% of dogs survive P. textilis bites without antivenom, cats are twice as likely to survive bites (66%). Even with antivenom treatment, cats have a significantly higher survival rate. The reason behind this disparity is unclear. Using a coagulation analyser (Stago STA R Max), we tested the relative procoagulant effects of P. textilis venom—as well as 10 additional procoagulant venoms found around the world—on cat and dog plasma in vitro, as well as on human plasma for comparison. All venoms acted faster upon dog plasma than cat or human, indicating that dogs would likely enter coagulopathic states sooner, and are thus more vulnerable to procoagulant snake venoms. The spontaneous clotting time (recalcified plasma with no venom added) was also substantially faster in dogs than in cats, suggesting that the naturally faster clotting blood of dogs predisposes them to being more vulnerable to procoagulant snake venoms. This is consistent with clinical records showing more rapid onset of symptoms and lethal effects in dogs than cats. Several behavioural differences between cats and dogs are also highly likely to disproportionately negatively affect prognosis in dogs. Thus, compared to cats, dogs require earlier snakebite first-aid and antivenom to prevent the onset of lethal venom effects.

ACS Style

Christina N. Zdenek; Joshua Llinas; James Dobson; Luke Allen; Nathan Dunstan; Leijiane de Sousa; Ana Maria Moura-Da-Silva; Bryan G. Fry. Pets in peril: The relative susceptibility of cats and dogs to procoagulant snake venoms. Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology 2020, 236, 108769 .

AMA Style

Christina N. Zdenek, Joshua Llinas, James Dobson, Luke Allen, Nathan Dunstan, Leijiane de Sousa, Ana Maria Moura-Da-Silva, Bryan G. Fry. Pets in peril: The relative susceptibility of cats and dogs to procoagulant snake venoms. Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology. 2020; 236 ():108769.

Chicago/Turabian Style

Christina N. Zdenek; Joshua Llinas; James Dobson; Luke Allen; Nathan Dunstan; Leijiane de Sousa; Ana Maria Moura-Da-Silva; Bryan G. Fry. 2020. "Pets in peril: The relative susceptibility of cats and dogs to procoagulant snake venoms." Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology 236, no. : 108769.

Journal article
Published: 23 April 2020 in Toxicon: X
Reads 0
Downloads 0

Bothrops atrox snakes are mostly endemic of the Amazon rainforest and is certainly the South American pit viper responsible for most of the snakebites in the region. The composition of B. atrox venom is significantly known and has been used to trace the relevance of the venom phenotype for snake biology and for the impacts in the clinics of human patients involved in accidents by B. atrox. However, in spite of the wide distribution and the great medical relevance of B. atrox snakes, B. atrox taxonomy is not fully resolved and the impacts of the lack of taxonomic resolution on the studies focused on venom or envenoming are currently unknown. B. atrox venom presents different degrees of compositional variability and is generally coagulotoxic, inducing systemic hematological disturbances and local tissue damage in snakebite patients. Antivenoms are the effective therapy for attenuating the clinical signs. This review brings a comprehensive discussion of the literature concerning B. atrox snakes encompassing from snake taxonomy, diet and venom composition, towards clinical aspects of snakebite patients and efficacy of the antivenoms. This discussion is highly supported by the contributions that venomics and antivenomics added for the advancement of knowledge of B. atrox snakes, their venoms and the treatment of accidents they evoke.

ACS Style

Wuelton Marcelo Monteiro; Jorge Carlos Contreras-Bernal; Pedro Ferreira Bisneto; Jacqueline Sachett; Iran Mendonça da Silva; Marcus Lacerda; Allyson Guimarães da Costa; Fernando Val; Lisele Brasileiro; Marco Aurélio Sartim; Sâmella Silva-De-Oliveira; Paulo Sérgio Bernarde; Igor Kaefer; Felipe Grazziotin; Fan Hui Wen; Ana Maria Moura-Da-Silva. Bothrops atrox, the most important snake involved in human envenomings in the amazon: How venomics contributes to the knowledge of snake biology and clinical toxinology. Toxicon: X 2020, 6, 100037 .

AMA Style

Wuelton Marcelo Monteiro, Jorge Carlos Contreras-Bernal, Pedro Ferreira Bisneto, Jacqueline Sachett, Iran Mendonça da Silva, Marcus Lacerda, Allyson Guimarães da Costa, Fernando Val, Lisele Brasileiro, Marco Aurélio Sartim, Sâmella Silva-De-Oliveira, Paulo Sérgio Bernarde, Igor Kaefer, Felipe Grazziotin, Fan Hui Wen, Ana Maria Moura-Da-Silva. Bothrops atrox, the most important snake involved in human envenomings in the amazon: How venomics contributes to the knowledge of snake biology and clinical toxinology. Toxicon: X. 2020; 6 ():100037.

Chicago/Turabian Style

Wuelton Marcelo Monteiro; Jorge Carlos Contreras-Bernal; Pedro Ferreira Bisneto; Jacqueline Sachett; Iran Mendonça da Silva; Marcus Lacerda; Allyson Guimarães da Costa; Fernando Val; Lisele Brasileiro; Marco Aurélio Sartim; Sâmella Silva-De-Oliveira; Paulo Sérgio Bernarde; Igor Kaefer; Felipe Grazziotin; Fan Hui Wen; Ana Maria Moura-Da-Silva. 2020. "Bothrops atrox, the most important snake involved in human envenomings in the amazon: How venomics contributes to the knowledge of snake biology and clinical toxinology." Toxicon: X 6, no. : 100037.

Health sciences
Published: 01 March 2020 in Acta Amazonica
Reads 0
Downloads 0

This study addresses the clinical and epidemiological aspects of envenoming cases resulting from snakebites treated at a hospital in Cruzeiro do Sul, in the upper Juruá River region, western Brazilian Amazonia. The specific identity of snakes that caused the envenomings was inferred (a) from the diagnosis of patient symptoms and signs upon hospital admission, (b) by enzyme immunoassay for detection of Bothrops atrox and Lachesis muta venom from serum samples taken from patients before antivenom therapy, or (c) by direct identification of the snake, when it was brought along to the hospital or photographed. There were 133 snakebites (76.2 cases per 100,000 inhabitants) registered during one year (July 2017 to June 2018). Most snakebites (88.7%) were caused by Bothrops spp., and the rest by non-venomous snakes or dry bites. Snakebites tended to occur more often during the rainy season, coinciding with the period of greater reproductive activity of the snakes and greater availability of their prey. In addition, the increase in the water level of rivers and lakes during the rainy season tends to concentrate snakes in dry places and, thus, to increase encounters with humans. Information campaigns on prevention and first aid, specially among the most vulnerable groups (indigenous people, farmers, and children and teenagers in rural areas), and the importance of using protective equipment (boots, leggings, leather gloves) in certain high risk activities (e.g. agriculture and extractivism in forests) are fundamental for the reduction of snakebite morbidity.

ACS Style

Ageane Mota Da Silva; Mônica Colombini; Ana Maria Moura-Da-Silva; Rodrigo Medeiros de Souza; Wuelton Marcelo Monteiro; Paulo Sérgio Bernarde. Epidemiological and clinical aspects of snakebites in the upper Juruá River region, western Brazilian Amazonia. Acta Amazonica 2020, 50, 90 -99.

AMA Style

Ageane Mota Da Silva, Mônica Colombini, Ana Maria Moura-Da-Silva, Rodrigo Medeiros de Souza, Wuelton Marcelo Monteiro, Paulo Sérgio Bernarde. Epidemiological and clinical aspects of snakebites in the upper Juruá River region, western Brazilian Amazonia. Acta Amazonica. 2020; 50 (1):90-99.

Chicago/Turabian Style

Ageane Mota Da Silva; Mônica Colombini; Ana Maria Moura-Da-Silva; Rodrigo Medeiros de Souza; Wuelton Marcelo Monteiro; Paulo Sérgio Bernarde. 2020. "Epidemiological and clinical aspects of snakebites in the upper Juruá River region, western Brazilian Amazonia." Acta Amazonica 50, no. 1: 90-99.

Journal article
Published: 02 February 2020 in Toxins
Reads 0
Downloads 0

Snake venom metalloproteinases (SVMPs) play an important role in local tissue damage of snakebite patients, mostly by hydrolysis of basement membrane (BM) components. We evaluated the proinflammatory activity of SVMPs Atroxlysin-Ia (ATXL) and Batroxrhagin (BATXH) from Bothrops atrox venom and their hydrolysis products of Matrigel. BALB/c mice were injected with SVMPs (2 μg), for assessment of paw edema and peritoneal leukocyte accumulation. Both SVMPs induced edema, representing an increase of ~70% of the paw size. Leukocyte infiltrates reached levels of 6 × 106 with ATXL and 5 × 106 with BATXH. TNF-α was identified in the supernatant of BATXH—or venom-stimulated MPAC cells. Incubation of Matrigel with the SVMPs generated fragments, including peptides from Laminin, identified by LC–MS/MS. The Matrigel hydrolysis peptides caused edema that increased 30% the paw size and promoted leukocyte accumulation (4–5 × 106) to the peritoneal cavity, significantly higher than Matrigel control peptides 1 and 4 h after injection. Our findings suggest that ATXL and BATXH are involved in the inflammatory reaction observed in B. atrox envenomings by direct action on inflammatory cells or by releasing proinflammatory peptides from BM proteins that may amplify the direct action of SVMPs through activation of endogenous signaling pathways.

ACS Style

Michelle Teixeira De Almeida; Luciana Aparecida Freitas-De-Sousa; Monica Colombini; Sarah Gimenes; Eduardo S. Kitano; Eliana L. Faquim-Mauro; Solange M. T. Serrano; Ana Maria Moura-Da-Silva. Inflammatory Reaction Induced by Two Metalloproteinases Isolated from Bothrops atrox Venom and by Fragments Generated from the Hydrolysis of Basement Membrane Components. Toxins 2020, 12, 96 .

AMA Style

Michelle Teixeira De Almeida, Luciana Aparecida Freitas-De-Sousa, Monica Colombini, Sarah Gimenes, Eduardo S. Kitano, Eliana L. Faquim-Mauro, Solange M. T. Serrano, Ana Maria Moura-Da-Silva. Inflammatory Reaction Induced by Two Metalloproteinases Isolated from Bothrops atrox Venom and by Fragments Generated from the Hydrolysis of Basement Membrane Components. Toxins. 2020; 12 (2):96.

Chicago/Turabian Style

Michelle Teixeira De Almeida; Luciana Aparecida Freitas-De-Sousa; Monica Colombini; Sarah Gimenes; Eduardo S. Kitano; Eliana L. Faquim-Mauro; Solange M. T. Serrano; Ana Maria Moura-Da-Silva. 2020. "Inflammatory Reaction Induced by Two Metalloproteinases Isolated from Bothrops atrox Venom and by Fragments Generated from the Hydrolysis of Basement Membrane Components." Toxins 12, no. 2: 96.

Journal article
Published: 16 October 2019 in Toxicon
Reads 0
Downloads 0

The Alto Juruá region, located in the extreme western part of the Brazilian Amazonia, possesses an indigenous and riverine population which is involved in agricultural and forest extraction activities, and is a region that stands out for its high incidence of snakebites. To assess the attitudes of the victims, the characteristics of the snakes and the circumstances of the snakebites which occurred in a region where human populations are highly exposed to snakes. The study was conducted at the Regional Hospital of Juruá in the Municipality of Cruzeiro do Sul (Acre), which regularly attends victims of snakebites in the Alto Juruá region. The snakes that caused the envenomations were identified from clinical and epidemiological diagnosis of the symptoms and signs that patients presented during hospital, and by enzyme immunoassay for venom detection using serum samples of the patients, or by identification of the snake responsible for the envenomation when it was taken to the hospital or photographed. People who suffered or witnessed the snakebite were interviewed to assess the circumstances of the bite, the attitude adopted after the accident and whether they recognized the species of snake that caused the envenomation. There were 133 cases of snakebite (76.24/100.000 inhabitants), mainly involving male individuals living in the rural area and who had a low level of education. The most affected groups were farmers (48%) and children and teenagers (39%). It was observed that 8.3% of them presented a history of recurrence for bites. The lower limbs were the most affected anatomical region (84%). The Bothrops atrox snake, mainly small specimens (mostly juveniles), was the main species involved in the envenomations (83.4%). Snakebites occurred mainly in forest areas, backyards of houses in rural areas and near to aquatic environments, during activities (walking, farming, extractivism, hunting). Most of the time, the snake was on the ground and the bite occurred because of the approximation of the individual, either by trampling or by approximation of a hand. Half of the victims performed some kind of inadequate first aid (not drinking water, use of tourniquet, incision at the site of the bite, use of black stone, drinking a compound “Específico Pessoa”). Snakebite is an important cause of morbidity in the Alto Juruá region. Bothrops bites are mostly caused by small-sized specimens, probably due to the greater abundance of B. atrox juveniles, and also because small snakes are more difficult for people to see. People are more often bitten on the lower limbs probably due to the size of B. atrox (small and medium) and because the snakes are usually on the ground in most situations. Many victims resort to ineffective actions that can cause complications and also delay serotherapy. A low level of education is a factor that may contribute to worse outcomes in snakebites since it is associated with a lack of knowledge of preventive and first aid measures.

ACS Style

Ageane Mota da Silva; Mônica Colombini; Ana Maria Moura-Da-Silva; Rodrigo Medeiros de Souza; Wuelton Marcelo Monteiro; Paulo Sérgio Bernarde. Ethno-knowledge and attitudes regarding snakebites in the Alto Juruá region, Western Brazilian Amazonia. Toxicon 2019, 171, 66 -77.

AMA Style

Ageane Mota da Silva, Mônica Colombini, Ana Maria Moura-Da-Silva, Rodrigo Medeiros de Souza, Wuelton Marcelo Monteiro, Paulo Sérgio Bernarde. Ethno-knowledge and attitudes regarding snakebites in the Alto Juruá region, Western Brazilian Amazonia. Toxicon. 2019; 171 ():66-77.

Chicago/Turabian Style

Ageane Mota da Silva; Mônica Colombini; Ana Maria Moura-Da-Silva; Rodrigo Medeiros de Souza; Wuelton Marcelo Monteiro; Paulo Sérgio Bernarde. 2019. "Ethno-knowledge and attitudes regarding snakebites in the Alto Juruá region, Western Brazilian Amazonia." Toxicon 171, no. : 66-77.

Journal article
Published: 06 August 2019 in Clinical Toxicology
Reads 0
Downloads 0

Introduction: Snake venom composition shows significant inter- and intra-species variation. In the case of the viperid species Bothrops atrox, responsible for the majority of snakebites in the Amazon region, geographical and ontogenetic variables affect venom composition, with ecological and medical implications. Previous studies had shown that venom from neonate and juvenile Bothrops specimens have a higher in vitro coagulant activity. The aim of this investigation was to assess the association of clinical outcomes, such as venom-induced coagulopathy and local complications, with B. atrox ontogenetic variables.Methods: This study explored the relationship between some clinical parameters in patients suffering envenomations by B. atrox in the Amazon and several morphometric parameters of the snake specimens causing the bites.Results: There were 248 specimens confirmed as agents of envenomation, mostly female snakes (70.5%) and classified as juveniles (62.7%). Patients bitten by neonates compared to adult snakes [OR = 2.70 (95%CI 1.15-6.37); p = .021] and by snakes with white tail tip [OR = 1.98 (95%CI 1.15-3.41); p = .013] were more likely to develop coagulopathy. Time from patient admission to the unclottable blood reversion was not affected by the snake gender (p = .214) or age (p = .254). Patients bitten by neonate (p = .024) or juvenile snakes (p < .0001) presented a lower frequency of moderate to severe edema, as compared to those bitten by adult snakes. In agreement with experimental observations, patients bitten by neonates and by snakes with a white tail tip were more likely to develop coagulopathy than those bitten by adult snakes. In contrast, envenomations by adult snakes were associated with a higher incidence of severe local edema.Conclusion: Despite these variations, no difference was observed in the time needed to recover blood clotting in these patients after Bothrops antivenom administration.

ACS Style

Jorge Carlos Contreras Bernal; Pedro Ferreira Bisneto; João Pedro Tavares Pereira; Hiochelson Najibe Dos Santos Ibiapina; Lybia Kássia Santos Sarraff; Cláudio Monteiro-Júnior; Handerson Da Silva Pereira; Bruno Santos; Valeria Mourão De Moura; Sâmella Silva De Oliveira; Marcus Lacerda; Vanderson Sampaio; Igor Kaefer; José María Gutiérrez; Paulo Sérgio Bernarde; Hui Wen Fan; Jacqueline Sachett; Ana Maria Moura-Da-Silva; Wuelton Marcelo Monteiro. “Bad things come in small packages”: predicting venom-induced coagulopathy in Bothrops atrox bites using snake ontogenetic parameters. Clinical Toxicology 2019, 58, 388 -396.

AMA Style

Jorge Carlos Contreras Bernal, Pedro Ferreira Bisneto, João Pedro Tavares Pereira, Hiochelson Najibe Dos Santos Ibiapina, Lybia Kássia Santos Sarraff, Cláudio Monteiro-Júnior, Handerson Da Silva Pereira, Bruno Santos, Valeria Mourão De Moura, Sâmella Silva De Oliveira, Marcus Lacerda, Vanderson Sampaio, Igor Kaefer, José María Gutiérrez, Paulo Sérgio Bernarde, Hui Wen Fan, Jacqueline Sachett, Ana Maria Moura-Da-Silva, Wuelton Marcelo Monteiro. “Bad things come in small packages”: predicting venom-induced coagulopathy in Bothrops atrox bites using snake ontogenetic parameters. Clinical Toxicology. 2019; 58 (5):388-396.

Chicago/Turabian Style

Jorge Carlos Contreras Bernal; Pedro Ferreira Bisneto; João Pedro Tavares Pereira; Hiochelson Najibe Dos Santos Ibiapina; Lybia Kássia Santos Sarraff; Cláudio Monteiro-Júnior; Handerson Da Silva Pereira; Bruno Santos; Valeria Mourão De Moura; Sâmella Silva De Oliveira; Marcus Lacerda; Vanderson Sampaio; Igor Kaefer; José María Gutiérrez; Paulo Sérgio Bernarde; Hui Wen Fan; Jacqueline Sachett; Ana Maria Moura-Da-Silva; Wuelton Marcelo Monteiro. 2019. "“Bad things come in small packages”: predicting venom-induced coagulopathy in Bothrops atrox bites using snake ontogenetic parameters." Clinical Toxicology 58, no. 5: 388-396.

Basic research
Published: 02 July 2019 in Clinical Toxicology
Reads 0
Downloads 0

Introduction: Bothrops atrox snakebites are a major public health problem in the Amazon region and also cause hemostatic disorders. In this study, we assessed the recovery from hemostatic disorders in Bothrops snakebite patients after being given antivenom therapy. Methods: This is a prospective study of Bothrops snakebite patients (n = 100) treated at the Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, Brazilian Amazon, between January 2016 and December 2017. Blood samples were taken for the measurement of venom concentrations, platelets, clotting time and factors of patients on admission, 12, 24 and 48 h after antivenom therapy, and taken again on discharge. The presence of systemic bleeding was recorded during the follow-up. Results: On admission, systemic bleeding was observed in 14% of the patients. Thrombocytopenia was noted in 10% of the patients. A total of 54% of the patients presented unclottable blood with low levels of fibrinogen and alpha 2-antiplasmin, and high levels of fibrin/fibrinogen degradation product (FDP) and D-dimers. Unclottable blood and systemic bleeding were overcome in most patients 12 h after the antivenom therapy. Three patients developed systemic bleeding 48 h after antivenom therapy. Levels of fibrinogen and alpha 2-antiplasmin, FDP and D-dimer returned to normal around 48 h after the treatment or on discharge. The frequency of thrombocytopenia with high mean platelet volume increased in the first 24 h after antivenom therapy, and decreased on discharge. Bothrops venom levels in patients decreased 12 h after antivenom therapy and were not correlated with coagulation and fibrinolytic parameters. There were no deaths. Conclusion: Laboratorial parameters of coagulopathy returned to normal values within 48 h after the antivenom therapy until discharge. A few patients still presented bleeding signs within 48 h after beginning antivenom therapy. However, the Brazilian antivenom was able to overcome the hemostatic disorders in these cases of envenomation.

ACS Style

Sâmella Silva De Oliveira; Eliane Campos Alves; Alessandra Dos Santos Santos; Elizandra Freitas Nascimento; João Pedro Tavares Pereira; Iran Mendonça Da Silva; Jacqueline Sachett; Hiochelson Najibe Dos Santos Ibiapina; Lybia Kássia Santos Sarraf; Jorge Carlos Contreras Bernal; Luciana Aparecida Freitas De Sousa; Mônica Colombini; Hedylamar Oliveira Marques; Marcus Vinicius Guimarães De Lacerda; Ana Maria Moura-Da-Silva; Hui Wen Fan; Luiz Carlos De Lima Ferreira; Ida Sigueko Sano Martins; Wuelton Marcelo Monteiro. Bothrops snakebites in the Amazon: recovery from hemostatic disorders after Brazilian antivenom therapy. Clinical Toxicology 2019, 58, 266 -274.

AMA Style

Sâmella Silva De Oliveira, Eliane Campos Alves, Alessandra Dos Santos Santos, Elizandra Freitas Nascimento, João Pedro Tavares Pereira, Iran Mendonça Da Silva, Jacqueline Sachett, Hiochelson Najibe Dos Santos Ibiapina, Lybia Kássia Santos Sarraf, Jorge Carlos Contreras Bernal, Luciana Aparecida Freitas De Sousa, Mônica Colombini, Hedylamar Oliveira Marques, Marcus Vinicius Guimarães De Lacerda, Ana Maria Moura-Da-Silva, Hui Wen Fan, Luiz Carlos De Lima Ferreira, Ida Sigueko Sano Martins, Wuelton Marcelo Monteiro. Bothrops snakebites in the Amazon: recovery from hemostatic disorders after Brazilian antivenom therapy. Clinical Toxicology. 2019; 58 (4):266-274.

Chicago/Turabian Style

Sâmella Silva De Oliveira; Eliane Campos Alves; Alessandra Dos Santos Santos; Elizandra Freitas Nascimento; João Pedro Tavares Pereira; Iran Mendonça Da Silva; Jacqueline Sachett; Hiochelson Najibe Dos Santos Ibiapina; Lybia Kássia Santos Sarraf; Jorge Carlos Contreras Bernal; Luciana Aparecida Freitas De Sousa; Mônica Colombini; Hedylamar Oliveira Marques; Marcus Vinicius Guimarães De Lacerda; Ana Maria Moura-Da-Silva; Hui Wen Fan; Luiz Carlos De Lima Ferreira; Ida Sigueko Sano Martins; Wuelton Marcelo Monteiro. 2019. "Bothrops snakebites in the Amazon: recovery from hemostatic disorders after Brazilian antivenom therapy." Clinical Toxicology 58, no. 4: 266-274.

Journal article
Published: 24 May 2019 in Toxins
Reads 0
Downloads 0

Variability in snake venom composition has been frequently reported and correlated to the adaptability of snakes to environmental conditions. Previous studies report plasticity for the venom phenotype. However, these observations are not conclusive, as the results were based on pooled venoms, which present high individual variability. Here we tested the hypothesis of plasticity by influence of confinement and single diet type in the venom composition of 13 adult specimens of Bothrops atrox snakes, maintained under captivity for more than three years. Individual variability in venom composition was observed in samples extracted just after the capture of the snakes. However, composition was conserved in venoms periodically extracted from nine specimens, which presented low variability restricted to the less abundant components. In a second group, composed of four snakes, drastic changes were observed in the venom samples extracted at different periods, mostly related to snake venom metalloproteinases (SVMPs), the core function toxins of B. atrox venom, which occurred approximately between 400 and 500 days in captivity. These data show plasticity in the venom phenotype during the lifetime of adult snakes maintained under captive conditions. Causes or functional consequences involved in the phenotype modification require further investigations.

ACS Style

Diana R. Amazonas; Luciana A. Freitas-De-Sousa; Daniele P. Orefice; Leijiane F. De Sousa; Melissa G. Martinez; Rosa H. V. Mourão; Hipócrates M. Chalkidis; Plínio B. Camargo; Ana M. Moura-Da-Silva. Evidence for Snake Venom Plasticity in a Long-Term Study with Individual Captive Bothrops atrox. Toxins 2019, 11, 294 .

AMA Style

Diana R. Amazonas, Luciana A. Freitas-De-Sousa, Daniele P. Orefice, Leijiane F. De Sousa, Melissa G. Martinez, Rosa H. V. Mourão, Hipócrates M. Chalkidis, Plínio B. Camargo, Ana M. Moura-Da-Silva. Evidence for Snake Venom Plasticity in a Long-Term Study with Individual Captive Bothrops atrox. Toxins. 2019; 11 (5):294.

Chicago/Turabian Style

Diana R. Amazonas; Luciana A. Freitas-De-Sousa; Daniele P. Orefice; Leijiane F. De Sousa; Melissa G. Martinez; Rosa H. V. Mourão; Hipócrates M. Chalkidis; Plínio B. Camargo; Ana M. Moura-Da-Silva. 2019. "Evidence for Snake Venom Plasticity in a Long-Term Study with Individual Captive Bothrops atrox." Toxins 11, no. 5: 294.

Original article
Published: 23 May 2019 in Inflammation
Reads 0
Downloads 0

Bothrops snakes cause around 80% of snakebites in Brazil, with muscle tissue damage as an important consequence, which may cause dysfunction on the affected limb. Bothropstoxin-I (BthTX-I) from Bothrops jararacussu is a K49-phospholipase A2, involved in the injury and envenomation’s inflammatory response. Immune system components act in the resolution of tissue damage and regeneration. Thus, macrophages exert a crucial role in the elimination of dead tissue and muscle repair. Here, we studied the cellular influx and presence of classical and alternative macrophages (M1 and M2) during muscle injury induced by BthTX-I and the regeneration process. BthTX-I elicited intense inflammatory response characterized by neutrophil migration, then increased influx of M1 macrophages followed by M2 population that declined, resulting in tissue regeneration. The high expressions of TNF-α and IL6 were changed by increased TGF-β expression after BthTX-I injection, coinciding with the iNOs and arginase expression and the peaks of M1 and M2 macrophages in muscle tissue. A coordinated sequence of PAX7, MyoD, and myogenin expression involved in muscle regenerative process appeared after BthTX-I injection. Together, these results demonstrate a direct correlation between the macrophage subsets, cytokine microenvironment, and the myogenesis process. This information may be useful for new envenomation and muscular dysfunction therapies.

ACS Style

Priscila Andrade Ranéia E Silva; Adriana Da Costa Neves; Cristiani Baldo Da Rocha; Ana Maria Moura-Da-Silva; Eliana L. Faquim-Mauro. Differential Macrophage Subsets in Muscle Damage Induced by a K49-PLA2 from Bothrops jararacussu Venom Modulate the Time Course of the Regeneration Process. Inflammation 2019, 42, 1542 -1554.

AMA Style

Priscila Andrade Ranéia E Silva, Adriana Da Costa Neves, Cristiani Baldo Da Rocha, Ana Maria Moura-Da-Silva, Eliana L. Faquim-Mauro. Differential Macrophage Subsets in Muscle Damage Induced by a K49-PLA2 from Bothrops jararacussu Venom Modulate the Time Course of the Regeneration Process. Inflammation. 2019; 42 (5):1542-1554.

Chicago/Turabian Style

Priscila Andrade Ranéia E Silva; Adriana Da Costa Neves; Cristiani Baldo Da Rocha; Ana Maria Moura-Da-Silva; Eliana L. Faquim-Mauro. 2019. "Differential Macrophage Subsets in Muscle Damage Induced by a K49-PLA2 from Bothrops jararacussu Venom Modulate the Time Course of the Regeneration Process." Inflammation 42, no. 5: 1542-1554.

Comparative study
Published: 13 April 2019 in Toxicon
Reads 0
Downloads 0

Variability in the composition of snake venoms occurs in different taxa and is usually correlated to snake fitness. Here, we compared B. atrox venoms from three different geographic regions across the Brazilian Amazon and found remarkable functional differences particularly between venoms from two populations separated by the Amazon River, in specimens born, raised and maintained under the same conditions at Instituto Butantan serpentary. Venom from Presidente Figueiredo snakes induced stronger dermonecrosis, but was less procoagulant and lethal to mice; these activities were correlated to the presence of a PI-class SVMP and absence of a SVSP in the venom, respectively. Venom from São Bento snakes was more hemorrhagic, killed mice more efficiently, but induced lower signs of dermonecrosis, which was correlated to the higher proportion of SVMPs and the absence of a PI-class SVMP isoform. Belterra snakes, a reference of wild snakes, presented venoms with intermediate phenotypes. Commercial Bothrops antivenom was effective in neutralizing all biological activities evaluated in this study, including dermonecrosis and pro-coagulant, which are relevant for human snakebite accidents by B. atrox. Functional differences correlated to snake fitness may also imply in different symptomatology for B. atrox snakebite patients and deserve special attention from clinical toxicologists.

ACS Style

Tiago H. Moretto Del-Rei; Leijiane F. Sousa; Marisa M.T. Rocha; Luciana A. Freitas-De-Sousa; Silvia R. Travaglia-Cardoso; Kathleen Grego; Sávio S. Sant'Anna; Hipócrates M. Chalkidis; Ana M. Moura-Da-Silva. Functional variability of Bothrops atrox venoms from three distinct areas across the Brazilian Amazon and consequences for human envenomings. Toxicon 2019, 164, 61 -70.

AMA Style

Tiago H. Moretto Del-Rei, Leijiane F. Sousa, Marisa M.T. Rocha, Luciana A. Freitas-De-Sousa, Silvia R. Travaglia-Cardoso, Kathleen Grego, Sávio S. Sant'Anna, Hipócrates M. Chalkidis, Ana M. Moura-Da-Silva. Functional variability of Bothrops atrox venoms from three distinct areas across the Brazilian Amazon and consequences for human envenomings. Toxicon. 2019; 164 ():61-70.

Chicago/Turabian Style

Tiago H. Moretto Del-Rei; Leijiane F. Sousa; Marisa M.T. Rocha; Luciana A. Freitas-De-Sousa; Silvia R. Travaglia-Cardoso; Kathleen Grego; Sávio S. Sant'Anna; Hipócrates M. Chalkidis; Ana M. Moura-Da-Silva. 2019. "Functional variability of Bothrops atrox venoms from three distinct areas across the Brazilian Amazon and consequences for human envenomings." Toxicon 164, no. : 61-70.

Journal article
Published: 22 February 2019 in Toxicon
Reads 0
Downloads 0

Human accidents with venomous snakes represent an overwhelming public health problem, mainly in rural populations of underdeveloped countries. Their high incidence and the severity of the accidents result in 81,000 to 138,000 deaths per year. The treatment is based on the administration of purified antibodies, produced by hyper immunization of animals to generate immunoglobulins (Igs), and then obtained by fractionating hyper immune plasma. The use of recombinant antibodies is an alternative to conventional treatment of snakebite envenoming, particularly the Fv fragment, named the single-chain variable fragment (scFv). We have produced recombinant single chain variable fragment scFv against the venom of the pit viper Bothrops asper at high levels expressed transiently and stably in transgenic plants and in vitro cultures that is reactive to BaP1 (a metalloproteinase from B. asper venom). The yield from stably transformed plants was significantly (p > 0.05) higher than the results in from transient expression. In addition, scFvBaP1 yields from systems derived from stable transformation were: transgenic callus 62 μg/g (± 2); biomass from cell suspension cultures 83 μg/g (± 0.2); culture medium from suspensions 71.75 mg/L (± 6.18). The activity of scFvBaP1 was confirmed by binding and neutralization of the fibrin degradation induced by BnP1 toxins from B. neuwiedi and by Atroxlysin Ia from B. atrox venoms. In the present work, we demonstrated the potential use of plant cells to produce scFvBaP1 to be used in the future as a biotechnological alternative to horse immunization protocols to produce anti-venoms to be used in human therapy against snakebites.

ACS Style

Marinna Gomes; Maria Alejandra Alvarez; Leonardo Ramos Quellis; Melina Laguia Becher; Juciane Maria De Andrade Castro; Jacy Gameiro; Maria Cristina Caporrino; Ana Maria Moura-Da-Silva; Marcelo De Oliveira Santos. Expression of an scFv antibody fragment in Nicotiana benthamiana and in vitro assessment of its neutralizing potential against the snake venom metalloproteinase BaP1 from Bothrops asper. Toxicon 2019, 160, 38 -46.

AMA Style

Marinna Gomes, Maria Alejandra Alvarez, Leonardo Ramos Quellis, Melina Laguia Becher, Juciane Maria De Andrade Castro, Jacy Gameiro, Maria Cristina Caporrino, Ana Maria Moura-Da-Silva, Marcelo De Oliveira Santos. Expression of an scFv antibody fragment in Nicotiana benthamiana and in vitro assessment of its neutralizing potential against the snake venom metalloproteinase BaP1 from Bothrops asper. Toxicon. 2019; 160 ():38-46.

Chicago/Turabian Style

Marinna Gomes; Maria Alejandra Alvarez; Leonardo Ramos Quellis; Melina Laguia Becher; Juciane Maria De Andrade Castro; Jacy Gameiro; Maria Cristina Caporrino; Ana Maria Moura-Da-Silva; Marcelo De Oliveira Santos. 2019. "Expression of an scFv antibody fragment in Nicotiana benthamiana and in vitro assessment of its neutralizing potential against the snake venom metalloproteinase BaP1 from Bothrops asper." Toxicon 160, no. : 38-46.

Journal article
Published: 12 February 2019 in Toxins
Reads 0
Downloads 0

Human accidents with spiders of the genus Loxosceles are an important health problem affecting thousands of people worldwide. Patients evolve to severe local injuries and, in many cases, to systemic disturbances as acute renal failure, in which cases antivenoms are considered to be the most effective treatment. However, for antivenom production, the extraction of the venom used in the immunization process is laborious and the yield is very low. Thus, many groups have been exploring the use of recombinant Loxosceles toxins, particularly phospholipases D (PLDs), to produce the antivenom. Nonetheless, some important venom activities are not neutralized by anti-PLD antibodies. Astacin-like metalloproteases (ALMPs) are the second most expressed toxin acting on the extracellular matrix, indicating the importance of its inclusion in the antigen’s formulation to provide a better antivenom. Here we show the construction of a hybrid recombinant immunogen, called LgRec1ALP1, composed of hydrophilic regions of the PLD and the ALMP toxins from Loxosceles gaucho. Although the LgRec1ALP1 was expressed as inclusion bodies, it resulted in good yields and it was effective to produce neutralizing antibodies in mice. The antiserum neutralized fibrinogenolytic, platelet aggregation and dermonecrotic activities elicited by L. gaucho, L. laeta, and L. intermedia venoms, indicating that the hybrid recombinant antigen may be a valuable source for the production of protective antibodies against Loxosceles ssp. venoms. In addition, the hybrid recombinant toxin approach may enrich and expand the alternative antigens for antisera production for other venoms.

ACS Style

Paula A. L. Calabria; Lhiri Hanna A. L. Shimokawa-Falcão; Monica Colombini; Ana M. Moura-Da-Silva; Katia C. Barbaro; Eliana L. Faquim-Mauro; Geraldo S. Magalhaes. Design and Production of a Recombinant Hybrid Toxin to Raise Protective Antibodies against Loxosceles Spider Venom. Toxins 2019, 11, 108 .

AMA Style

Paula A. L. Calabria, Lhiri Hanna A. L. Shimokawa-Falcão, Monica Colombini, Ana M. Moura-Da-Silva, Katia C. Barbaro, Eliana L. Faquim-Mauro, Geraldo S. Magalhaes. Design and Production of a Recombinant Hybrid Toxin to Raise Protective Antibodies against Loxosceles Spider Venom. Toxins. 2019; 11 (2):108.

Chicago/Turabian Style

Paula A. L. Calabria; Lhiri Hanna A. L. Shimokawa-Falcão; Monica Colombini; Ana M. Moura-Da-Silva; Katia C. Barbaro; Eliana L. Faquim-Mauro; Geraldo S. Magalhaes. 2019. "Design and Production of a Recombinant Hybrid Toxin to Raise Protective Antibodies against Loxosceles Spider Venom." Toxins 11, no. 2: 108.

Journal article
Published: 11 October 2018 in Toxins
Reads 0
Downloads 0

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. Bothrops atrox (common lancehead), responsible for majority of snakebites and related deaths within the Brazilian Amazon, is a highly adaptable and widely distributed species, whose venom variability has been related to several factors, including geographical distribution and habitat type. This study examined venoms from four B. atrox populations (Belterra and Santarém, PA; Pres. Figueiredo, AM and São Bento, MA), and two additional Bothrops species (B. jararaca and B. neuwiedi) from Southeastern region for their coagulotoxic effects upon different plasmas (human, amphibian, and avian). The results revealed inter– and intraspecific variations in coagulotoxicity, including distinct activities between the three plasmas, with variations in the latter two linked to ecological niche occupied by the snakes. Also examined were the correlated biochemical mechanisms of venom action. Significant variation in the relative reliance upon the cofactors calcium and phospholipid were revealed, and the relative dependency did not significantly correlate with potency. Relative levels of Factor X or prothrombin activating toxins correlated with prey type and prey escape potential. The antivenom was shown to perform better in neutralising prothrombin activation activity than neutralising Factor X activation activity. Thus, the data reveal new information regarding the evolutionary selection pressures shaping snake venom evolution, while also having significant implications for the treatment of the envenomed patient. These results are, therefore, an intersection between evolutionary biology and clinical medicine.

ACS Style

Leijiane F. Sousa; Christina N. Zdenek; James S. Dobson; Bianca Op Den Brouw; Francisco C. P. Coimbra; Amber Gillett; Tiago H. M. Del-Rei; Hipócrates De M. Chalkidis; Sávio Sant’Anna; Marisa M. Teixeira-Da-Rocha; Kathleen Grego; Silvia R. Travaglia Cardoso; Ana M. Moura Da Silva; Bryan G. Fry. Coagulotoxicity of Bothrops (Lancehead Pit-Vipers) Venoms from Brazil: Differential Biochemistry and Antivenom Efficacy Resulting from Prey-Driven Venom Variation. Toxins 2018, 10, 411 .

AMA Style

Leijiane F. Sousa, Christina N. Zdenek, James S. Dobson, Bianca Op Den Brouw, Francisco C. P. Coimbra, Amber Gillett, Tiago H. M. Del-Rei, Hipócrates De M. Chalkidis, Sávio Sant’Anna, Marisa M. Teixeira-Da-Rocha, Kathleen Grego, Silvia R. Travaglia Cardoso, Ana M. Moura Da Silva, Bryan G. Fry. Coagulotoxicity of Bothrops (Lancehead Pit-Vipers) Venoms from Brazil: Differential Biochemistry and Antivenom Efficacy Resulting from Prey-Driven Venom Variation. Toxins. 2018; 10 (10):411.

Chicago/Turabian Style

Leijiane F. Sousa; Christina N. Zdenek; James S. Dobson; Bianca Op Den Brouw; Francisco C. P. Coimbra; Amber Gillett; Tiago H. M. Del-Rei; Hipócrates De M. Chalkidis; Sávio Sant’Anna; Marisa M. Teixeira-Da-Rocha; Kathleen Grego; Silvia R. Travaglia Cardoso; Ana M. Moura Da Silva; Bryan G. Fry. 2018. "Coagulotoxicity of Bothrops (Lancehead Pit-Vipers) Venoms from Brazil: Differential Biochemistry and Antivenom Efficacy Resulting from Prey-Driven Venom Variation." Toxins 10, no. 10: 411.