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Silvio Sanches Veiga - One of the best experts on this subject based on the ideXlab platform.
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forty years of the description of brown spider venom phospholipases d
Toxins, 2020Co-Authors: Luiza Helena Gremski, Andrea Senffribeiro, Raghuvir K Arni, Hanna Câmara Da Justa, Thais Pereira Da Silva, Nayanne Louise Costacurta Polli, Bruno Cesar Antunes, Joao Carlos Minozzo, Ana Carolina Martins Wille, Silvio Sanches VeigaAbstract:Spiders of the genus Loxosceles, popularly known as Brown spiders, are considered a serious public health issue, especially in regions of hot or temperate climates, such as parts of North and South America. Although the venoms of these arachnids are complex in molecular composition, often containing proteins with distinct biochemical characteristics, the literature has primarily described a family of toxins, the Phospholipases-D (PLDs), which are highly conserved in all Loxosceles species. PLDs trigger most of the major clinical symptoms of Loxoscelism i.e., dermonecrosis, thrombocytopenia, hemolysis, and acute renal failure. The key role played by PLDs in the symptomatology of Loxoscelism was first described 40 years ago, when researches purified a hemolytic toxin that cleaved sphingomyelin and generated choline, and was referred to as a Sphingomyelinase-D, which was subsequently changed to Phospholipase-D when it was demonstrated that the enzyme also cleaved other cellular phospholipids. In this review, we present the information gleaned over the last 40 years about PLDs from Loxosceles venoms especially with regard to the production and characterization of recombinant isoforms. The history of obtaining these toxins is discussed, as well as their molecular organization and mechanisms of interaction with their substrates. We will address cellular biology aspects of these toxins and how they can be used in the development of drugs to address inflammatory processes and Loxoscelism. Present and future aspects of Loxoscelism diagnosis will be discussed, as well as their biotechnological applications and actions expected for the future in this field.
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brown spiders and Loxoscelism
Toxicon, 2004Co-Authors: Paulo Henrique Da Silva, Rafael Bertoni Da Silveira, Marcia Helena Appel, Oldemir C Mangili, Waldemiro Gremski, Silvio Sanches VeigaAbstract:Accidents caused by brown spiders (Loxosceles genus) are classically associated with dermonecrotic lesions and systemic manifestations including intravascular haemolysis, disseminated intravascular coagulation and acute renal failure. Systemic reactions occur in a minority of cases, but may be severe in some patients and occasionally fatal. The mechanisms by which Loxosceles venom exerts these noxious effects are currently under investigation. The venom contains several toxins, some of which have been well-characterised biochemically and biologically. The purpose of the present review is to describe some insights into Loxoscelism obtained over the last ten years. The biology and epidemiology of the brown spider, the histopathology of envenomation and the immunogenicity of Loxosceles venom are reviewed, as are the clinical features, diagnosis and therapy of brown spider bites. The identification and characterisation of some toxins and the mechanism of induction of local and systemic lesions caused by brown spider venom are also discussed. Finally, the biotechnological application of some venom toxins are covered.
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isolation and identification of clostridium perfringens in the venom and fangs of loxosceles intermedia brown spider enhancement of the dermonecrotic lesion in Loxoscelism
Toxicon, 2002Co-Authors: Cristina Leise Bastos Monteiro, Oldemir C Mangili, Waldemiro Gremski, Rosalia Rubel, Laura Lucia Cogo, Silvio Sanches VeigaAbstract:Loxoscelism or the envenoming by the brown spiders (Loxosceles genus spiders), may produce extensive dermonecrosis and hemorrhage at the bite site and, eventually, systemic reactions that may be lethal. Isolation and identification of many different bacteria, among them Clostridium perfringens, of great medical importance due to its involvement in dermonecrotizing and systemic conditions, was carried out from the venomous apparatus (fangs and venom) of spiders obtained directly from nature, through microbiological cultures in aerobic and anaerobic conditions. Working with Loxosceles intermedia venom (alone) and with the venom conjugated with Clostridium perfringens using rabbits as experimental models for dermonecrosis, allowed for the observation that venom and anaerobic bacteria conjugated resulted in a striking increase of the dermonecrotic picture when compared to venom alone, suggesting a role for Clostridium perfringens in the severe dermonecrotic picture of these patients and opening the possibility for the association of antibiotic therapy in treating Loxoscelism.
Denise V. Tambourgi - One of the best experts on this subject based on the ideXlab platform.
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Tetracycline Reduces Kidney Damage Induced by Loxosceles Spider Venom.
Toxins, 2017Co-Authors: Cinthya Kimori Okamoto, Carmen W. Van Den Berg, Rute M. Gonçalves-de-andrade, Mizuno Masashi, Denise V. TambourgiAbstract:Envenomation by Loxosceles spider can result in two clinical manifestations: cutaneous and systemic Loxoscelism, the latter of which includes renal failure. Although incidence of renal failure is low, it is the main cause of death, occurring mainly in children. The sphingomyelinase D (SMase D) is the main component in Loxosceles spider venom responsible for local and systemic manifestations. This study aimed to investigate the toxicity of L. intermedia venom and SMase D on kidney cells, using both In vitro and in vivo models, and the possible involvement of endogenous metalloproteinases (MMP). Results demonstrated that venom and SMase D are able to cause death of human kidney cells by apoptosis, concomitant with activation and secretion of extracellular matrix metalloproteases, MMP-2 and MMP-9. Furthermore, cell death and MMP synthesis and secretion can be prevented by tetracycline. In a mouse model of systemic Loxoscelism, Loxosceles venom-induced kidney failure was observed, which was abrogated by administration of tetracycline. These results indicate that MMPs may play an important role in Loxosceles venom-induced kidney injury and that tetracycline administration may be useful in the treatment of human systemic Loxoscelism.
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Microcirculation abnormalities provoked by Loxosceles spiders' envenomation
Toxicon : official journal of the International Society on Toxinology, 2015Co-Authors: Kátia Cristina De Oliveira-lima, Rute Maria Goncalves De Andrade, Priscila Hess Lopes, Carmen W. Van Den Berg, Sandra Helena Poliselli Farsky, Denise V. TambourgiAbstract:Loxoscelism is caused by envenomation by spiders from Loxosceles genus. Clinical symptoms only appear a few hours after envenomation and can evolve in local reactions, such as dermonecrosis, and systemic reactions, including intravascular haemolysis, intravascular coagulation and renal failure. Considering that alterations in the microcirculatory network are involved in the pathogenesis of different diseases, including the inflammatory process, the aim of this study was to investigate the action of venoms of males and females of Loxosceles intermedia and Loxosceles laeta on the microcirculatory network and examine the systemic production of inflammatory mediators in a murine model of Loxoscelism. We observed that during systemic envenomation, the alterations in the microcirculation include increase in the number of rolling cells, which was more intense in animals injected with female Loxosceles spider venoms. This positively correlated with increase in TNF-α and NO serum levels, induction of which was higher by female venoms when compared with male venoms. The increase of leukocytes rolling was not accompanied by increase of cell adhesion. The absence of leukocyte extravasation may explain why in mice, in contrast to humans, no cutaneous Loxoscelism occurs. Thus, targeting the neutrophil adhesion and extravasation in Loxosceles envenomed patients may prevent cutaneous pathology.
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variations in loxosceles spider venom composition and toxicity contribute to the severity of envenomation
Toxicon, 2005Co-Authors: Katia C Oliveira, Rute Maria Goncalves De Andrade, Roxane M F Piazza, Jorge M C Ferreira, C W Van Den Berg, Denise V. TambourgiAbstract:Envenomation by Loxosceles spiders causes two main clinical manifestations: cutaneous and systemic Loxoscelism. The factors contributing to the severity of Loxoscelism are not fully understood. We have analysed biochemical and toxicity variations in venom of L. laeta and L. intermedia, with the aim to find a correlation with the seriousness of Loxoscelism. Differences in expression of proteins, glycoproteins and sphingomyelinase activity were observed between venom from male and female spiders and between venom from the two species. These differences were reflected in the toxicity of the venoms including the capacity to induce complement-dependent haemolysis, dermonecrosis and lethality. Comparative analysis of gender and species, showed that these biological activities were more prominent in venom from female spiders, especially from L. laeta. Antiserum raised against venom from females L. laeta spiders had the highest efficacy in neutralizing venoms of males and females of both species. These results indicate that the severity of Loxoscelism depends, at least partially, on the species and sex of the spider and suggest that for accidents involving L. laeta an specific serum therapy is necessary. Furthermore, it emphasizes the efficacy of the antiserum produced against L. laeta female venom in neutralizing Loxosceles venoms from different species and gender.
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molecular cloning expression function and immunoreactivities of members of a gene family of sphingomyelinases from loxosceles venom glands
Molecular Immunology, 2004Co-Authors: Denise V. Tambourgi, Carmen W. Van Den Berg, Matheus Fernandes F Pedrosa, Rute M Goncalvesdeandrade, Matheus Ferracini, Danielle Paixaocavalcante, Paul B Morgan, N K RushmereAbstract:Loxoscelism is the clinical condition produced by the venom of spiders belonging to the genus Loxosceles, which can be observed as two well-defined clinical variants: cutaneous Loxoscelism and systemic or viscerocutaneous Loxoscelism. We have recently identified, purified and characterised the toxins (sphingomyelinases) from Loxosceles intermedia venom that are responsible for all the local (dermonecrosis) and systemic effects (complement dependent haemolysis) induced by whole venom. In the present study, we have cloned and expressed the two functional sphingomyelinases isoforms, P1 and P2, and shown that the recombinant proteins display all the functional characteristics of whole L. intermedia venom, e.g., dermonecrotic and complement-dependent hemolytic activities and ability of hydrolyzing sphingomyelin. We have also compared the cross-reactivities of antisera raised against the toxins from different Loxosceles species and show here that the cross-reactivity is high when toxins are from the same species (P1 and P2 from L. intermedia) but low when the toxins are from different species (L. intermedia versus L. laeta). These data suggest that in order to obtain a suitable comprehensive neutralizing antiserum using the recombinant toxin as an immunogen, a mixture of the recombinant toxins from the different species has to be used. The use of anti-recombinant toxin antisera may have clinical benefits to those individuals displaying acute loxoscelic lesions.
Olga Meiri Chaim - One of the best experts on this subject based on the ideXlab platform.
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tctp from loxosceles intermedia brown spider venom contributes to the allergic and inflammatory response of cutaneous Loxoscelism
Cells, 2019Co-Authors: Marianna Boiaferreira, Katia C Barbaro, Ana Carolina Martins Wille, Kamila G Moreno, Alana Basilio, Lucas P Da Silva, Larissa Vuitika, Bruna Da Silva Soley, Lucelia Donatti, Olga Meiri ChaimAbstract:LiTCTP is a toxin from the Translationally Controlled Tumor Protein (TCTP) family identified in Loxosceles brown spider venoms. These proteins are known as histamine-releasing factors (HRF). TCTPs participate in allergic and anaphylactic reactions, which suggest their potential role as therapeutic targets. The histaminergic effect of TCTP is related to its pro-inflammatory functions. An initial characterization of LiTCTP in animal models showed that this toxin can increase the microvascular permeability of skin vessels and induce paw edema in a dose-dependent manner. We evaluated the role of LiTCTP in vitro and in vivo in the inflammatory and allergic aspects that undergo the biological responses observed in Loxoscelism, the clinical condition after an accident with Loxosceles spiders. Our results showed LiTCTP recombinant toxin (LiRecTCTP) as an essential synergistic factor for the dermonecrotic toxin actions (LiRecDT1, known as the main toxin in the pathophysiology of Loxoscelism), revealing its contribution to the exacerbated inflammatory response clinically observed in envenomated patients.
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potential implications for designing drugs against the brown spider venom phospholipase d
Journal of Cellular Biochemistry, 2017Co-Authors: Daniele Chavesmoreira, Olga Meiri Chaim, Andrea Senffribeiro, Fabio Rogerio De Moraes, Icaro Putinhon Caruso, Anwar Ullah, Luciane Sussuchi Da Silva, Jorge Chahine, Raghuvir K ArniAbstract:Loxoscelism refers to the clinical symptoms that develop after brown spider bites. Brown spider venoms contain several phospholipase-D isoforms, which are the main toxins responsible for both the cutaneous and systemic effects of Loxoscelism. Understanding of the phospholipase-D catalytic mechanism is crucial for the development of specific treatment that could reverse the toxic effects caused by the spider bite. Based on enzymatic, biological, structural, and thermodynamic tests, we show some features suitable for designing drugs against Loxoscelism. Firstly, through molecular docking and molecular dynamics predictions, we found three different molecules (Suramin, Vu0155056, and Vu0359595) that were able to bind the enzyme's catalytic site and interact with catalytically important residues (His12 or His47) and with the Mg2+ co-factor. The binding promoted a decrease in the recombinant brown spider venom phospholipase-D (LiRecDT1) enzymatic activity. Furthermore, the presence of the inhibitors reduced the hemolytic, dermonecrotic, and inflammatory activities of the venom toxin in biological assays. Altogether, these results indicate the mode of action of three different LiRecDT1 inhibitors, which were able to prevent the venom toxic effects. This strengthen the idea of the importance of designing a specific drug to treat the serious clinical symptoms caused by the brown spider bite, a public health problem in several parts of the world, and until now without specific treatment. J. Cell. Biochem. 118: 726-738, 2017. © 2016 Wiley Periodicals, Inc.
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Loxosceles and Loxoscelism: Biology, Venom, Envenomation and Treatment
2015Co-Authors: Ceila Maria Sant’ana Malaque, Olga Meiri Chaim, Marlene Entres, Katia C BarbaroAbstract:Loxosceles spiders are not aggressive and have nocturnal habits. Accidents occur owing to the compression of the spiders against victims’ body parts. The envenomation can progress to cutaneous necrosis at the bite site and, less frequently, to intravascular hemolysis. Loxosceles venom is has many components, among them phospholipase D, which is responsible for inducing dermonecrosis and complementdependent hemolysis. The mechanism of action is very complex and multifactorial. Several treatments have been suggested for Loxoscelism particularly antivenom, corticosteroids, and dapsone. As the cutaneous lesions of Loxoscelism progress in a variety of forms and diagnosis is often relatively delayed, the assessment of treatment efficacy is compromised.
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two novel dermonecrotic toxins lirecdt4 and lirecdt5 from brown spider loxosceles intermedia venom from cloning to functional characterization
Biochimie, 2007Co-Authors: Rafael Bertoni Da Silveira, Olga Meiri Chaim, Marcia Helena Appel, Romine Bachmann Pigozzo, Dilza Trevisan Silva, Juliana L Dreyfuss, Leny Toma, Carl P Dietrich, Helena B NaderAbstract:Abstract Loxoscelism (the condition produced by the bite of brown spiders) has been reported worldwide, but especially in warmer regions. Clinical manifestations include skin necrosis with gravitational spreading while systemic Loxoscelism may include renal failure, hemolysis and thrombocytopenia. The venom contains several toxins, of which the best biochemically and biologically studied is the dermonecrotic toxin, a phospholipase-D. Purified toxin induces cutaneous and systemic Loxoscelism, especially necrotic lesions, hematological disturbances and renal failure. Herein, we describe cloning, heterologous expression and purification of two novel dermonecrotic toxins: LiRecDT4 and LiRecDT5. The recombinant proteins stably expressed in Escherichia coli cells were purified from culture supernatants in a single step using Ni2+-chelating chromatography producing soluble proteins of 34 kDa (LiRecDT4) and 37 kDa (LiRecDT5). Circular dichroism analysis evidenced correctly folding for toxins but differences in secondary structures. Both proteins were recognized by whole venom serum antibodies and by a specific antibody to dermonecrotic toxin. Also, recombinant toxins with phospholipase activity induced experimental skin lesions and caused a massive inflammatory response in rabbit skin dermis. Nevertheless, toxins displayed different effects upon platelet aggregation, increase in vascular permeability and not caused death in mice. These characteristics in combination with functional studies illustrates that a family of dermonecrotic toxins exists, and includes two novel members that are useful for future structural and functional studies. They will also be useful in biotechnological ends, for example, as inflammatory and platelet aggregating studies, as antigens for serum therapy source and for lipids biochemical research.
Donna Seger - One of the best experts on this subject based on the ideXlab platform.
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systemic Loxoscelism in the age of community acquired methicillin resistant staphylococcus aureus
Annals of Emergency Medicine, 2011Co-Authors: Karen M Rogers, Carrie R Klotz, Meg Jack, Donna SegerAbstract:The increase in cases of community-acquired methicillin-resistant Staphylococcus aureus (MRSA), as well as its isolation from the majority of skin and soft tissue abscesses in the emergency department, requires the emergency physician to consider this diagnosis in all skin or soft tissue infections. However, making the diagnosis of MRSA when the wound is actually a cutaneous lesion of a brown recluse spider bite may have untoward consequences. Furthermore, the clinical manifestations of systemic Loxoscelism may be misdiagnosed as a systemic staphylococcal infection. We present a patient with systemic Loxoscelism who was diagnosed with a systemic infection and received an unnecessary surgical procedure.
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hemolytic anemia following a presumptive brown recluse spider bite
Clinical Toxicology, 1994Co-Authors: Lindsay Murray, Donna SegerAbstract:AbstractThis case report describes a systemic reaction occurring in a 12-year-old female following presumed envenomation by a brown recluse spider (Loxosceles reclusa). The systemic reaction included self-limited hemolysis necessitating blood transfusion. The clinical course and management are described and compared with those of previously reported cases of systemic Loxoscelism.
Raghuvir K Arni - One of the best experts on this subject based on the ideXlab platform.
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forty years of the description of brown spider venom phospholipases d
Toxins, 2020Co-Authors: Luiza Helena Gremski, Andrea Senffribeiro, Raghuvir K Arni, Hanna Câmara Da Justa, Thais Pereira Da Silva, Nayanne Louise Costacurta Polli, Bruno Cesar Antunes, Joao Carlos Minozzo, Ana Carolina Martins Wille, Silvio Sanches VeigaAbstract:Spiders of the genus Loxosceles, popularly known as Brown spiders, are considered a serious public health issue, especially in regions of hot or temperate climates, such as parts of North and South America. Although the venoms of these arachnids are complex in molecular composition, often containing proteins with distinct biochemical characteristics, the literature has primarily described a family of toxins, the Phospholipases-D (PLDs), which are highly conserved in all Loxosceles species. PLDs trigger most of the major clinical symptoms of Loxoscelism i.e., dermonecrosis, thrombocytopenia, hemolysis, and acute renal failure. The key role played by PLDs in the symptomatology of Loxoscelism was first described 40 years ago, when researches purified a hemolytic toxin that cleaved sphingomyelin and generated choline, and was referred to as a Sphingomyelinase-D, which was subsequently changed to Phospholipase-D when it was demonstrated that the enzyme also cleaved other cellular phospholipids. In this review, we present the information gleaned over the last 40 years about PLDs from Loxosceles venoms especially with regard to the production and characterization of recombinant isoforms. The history of obtaining these toxins is discussed, as well as their molecular organization and mechanisms of interaction with their substrates. We will address cellular biology aspects of these toxins and how they can be used in the development of drugs to address inflammatory processes and Loxoscelism. Present and future aspects of Loxoscelism diagnosis will be discussed, as well as their biotechnological applications and actions expected for the future in this field.
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potential implications for designing drugs against the brown spider venom phospholipase d
Journal of Cellular Biochemistry, 2017Co-Authors: Daniele Chavesmoreira, Olga Meiri Chaim, Andrea Senffribeiro, Fabio Rogerio De Moraes, Icaro Putinhon Caruso, Anwar Ullah, Luciane Sussuchi Da Silva, Jorge Chahine, Raghuvir K ArniAbstract:Loxoscelism refers to the clinical symptoms that develop after brown spider bites. Brown spider venoms contain several phospholipase-D isoforms, which are the main toxins responsible for both the cutaneous and systemic effects of Loxoscelism. Understanding of the phospholipase-D catalytic mechanism is crucial for the development of specific treatment that could reverse the toxic effects caused by the spider bite. Based on enzymatic, biological, structural, and thermodynamic tests, we show some features suitable for designing drugs against Loxoscelism. Firstly, through molecular docking and molecular dynamics predictions, we found three different molecules (Suramin, Vu0155056, and Vu0359595) that were able to bind the enzyme's catalytic site and interact with catalytically important residues (His12 or His47) and with the Mg2+ co-factor. The binding promoted a decrease in the recombinant brown spider venom phospholipase-D (LiRecDT1) enzymatic activity. Furthermore, the presence of the inhibitors reduced the hemolytic, dermonecrotic, and inflammatory activities of the venom toxin in biological assays. Altogether, these results indicate the mode of action of three different LiRecDT1 inhibitors, which were able to prevent the venom toxic effects. This strengthen the idea of the importance of designing a specific drug to treat the serious clinical symptoms caused by the brown spider bite, a public health problem in several parts of the world, and until now without specific treatment. J. Cell. Biochem. 118: 726-738, 2017. © 2016 Wiley Periodicals, Inc.
